recent research on clinical depression

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Researchers treat depression by reversing brain signals traveling the wrong way

A new study led by Stanford Medicine researchers is the first to reveal how magnetic stimulation treats severe depression: by correcting the abnormal flow of brain signals.

May 15, 2023 - By Nina Bai

Brain images from a patient with major depression before (left) and after treatment with Stanford neuromodulation therapy, which restores the normal timing of activity in the anterior cingulate cortex. Nolan Williams Lab

Powerful magnetic pulses applied to the scalp to stimulate the brain can bring fast relief to many severely depressed patients for whom standard treatments have failed. Yet it’s been a mystery exactly how transcranial magnetic stimulation, as the treatment is known, changes the brain to dissipate depression. Now, research led by Stanford Medicine scientists has found that the treatment works by reversing the direction of abnormal brain signals.

The findings also suggest that backward streams of neural activity between key areas of the brain could be used as a biomarker to help diagnose depression.

“The leading hypothesis has been that TMS could change the flow of neural activity in the brain,” said  Anish Mitra , MD, PhD, a postdoctoral fellow in psychiatry and behavioral sciences. “But to be honest, I was pretty skeptical. I wanted to test it.”

Mitra had just the tool to do it. As a graduate student at Washington University in Saint Louis, in the lab of Mark Raichle, MD, he developed a mathematical tool to analyze functional magnetic resonance imaging, or fMRI — commonly used to locate active areas in the brain. The new analysis used minute differences in timing between the activation of different areas to also reveal the direction of that activity.

In the new study , published May 15 in the  Proceedings of the National Academy of Sciences , Mitra and Raichle teamed up with  Nolan Williams , MD, associate professor of psychiatry and behavioral sciences, whose team has advanced the use of magnetic stimulation, personalized to each patient’s brain anatomy, to treat profound depression. The FDA-cleared treatment, known as  Stanford neuromodulation therapy , incorporates advanced imaging technologies to guide stimulation with high-dose patterns of magnetic pulses that can modify brain activity related to major depression. Compared with traditional TMS, which requires daily sessions over several weeks or months, SNT works on an accelerated timeline of 10 sessions each day for just five days.

“This was the perfect test to see if TMS has the ability to change the way that signals flow through the brain,” said Mitra, who is lead author of the study. “If this doesn’t do it, nothing will.”

Raichle and Williams are senior authors of the study. 

Anish Mitra

Timing is everything

The researchers recruited 33 patients who had been diagnosed with treatment-resistant major depressive disorder. Twenty-three received SNT treatment, and 10 received a sham treatment that mimicked SNT but without magnetic stimulation. They compared data from these patients with that of 85 healthy controls without depression.

When they analyzed fMRI data across the whole brain, one connection stood out. In the normal brain, the anterior insula, a region that integrates bodily sensations, sends signals to a region that governs emotions, the anterior cingulate cortex.

“You could think of it as the anterior cingulate cortex receiving this information about the body — like heart rate or temperature — and then deciding how to feel on the basis of all these signals,” Mitra said.

In three-quarters of the participants with depression, however, the typical flow of activity was reversed: The anterior cingulate cortex sent signals to the anterior insula. The more severe the depression, the higher the proportion of signals that traveled the wrong way.

“What we saw is that who’s the sender and who’s the receiver in the relationship seems to really matter in terms of whether someone is depressed,” Mitra said. 

“It’s almost as if you’d already decided how you were going to feel, and then everything you were sensing was filtered through that,” he said. “The mood has become primary.”

“That’s consistent with how a lot of psychiatrists see depression,” he added. “Even things that are quite joyful to a patient normally are suddenly not bringing them any pleasure.”

When depressed patients were treated with SNT, the flow of neural activity shifted to the normal direction within a week, coinciding with a lifting of their depression.

Those with the most severe depression — and the most misdirected brain signals — were the most likely to benefit from the treatment.

“We’re able to undo the spatio-temporal abnormality so that people’s brains look like those of normal, healthy controls,” Williams said.

Nolan Williams

A biomarker for depression

A challenge of treating depression has been the lack of insight into its biological mechanisms. If a patient has a fever, there are various tests — for a bacterial or viral infection, for example — that could determine the appropriate treatment. But for a patient with depression, there are no analogous tests.

“This is the first time in psychiatry where this particular change in biology — the flow of signals between these two brain regions — predicts the change in clinical symptoms,” Williams said.

Not everyone with depression has this abnormal flow of neural activity, and it may be rare in less severe cases of depression, Williams said, but it could serve as an important biomarker for triaging treatment for the disorder. “The fMRI data that allows precision treatment with SNT can be used both as a biomarker for depression and a method of personalized targeting to treat its underlying cause,” he said.

“When we get a person with severe depression, we can look for this biomarker to decide how likely they are to respond well to SNT treatment,” Mitra said.

“Behavioral conditions like depression have been difficult to capture with imaging because, unlike an obvious brain lesion, they deal with the subtlety of relationships between various parts of the brain,” said Raichle, who has studied brain imaging for more than four decades. “It’s incredibly promising that the technology now is approaching the complexity of the problems we’re trying to understand."

The researchers plan to replicate the study in a larger group of patients. They also hope others will adopt their analytic technique to uncover more clues about the direction of brain activity hidden in fMRI data. “As long as you have good clean fMRI data, you can study this property of the signals,” Mitra said.

The study was funded by a Brain and Behavior Research Foundation Young Investigator Award, the NIMH Biobehavioral Research Awards for Innovative New Scientists award (grant R01 5R01MH122754-02), Charles R. Schwab, the David and Amanda Chao Fund II, the Amy Roth PhD Fund, the Neuromodulation Research Fund, the Lehman Family, the Still Charitable Trust, the Marshall and Dee Ann Payne Fund, the Gordie Brookstone Fund, the Mellam Family Foundation, and the Baszucki Brain Research Fund.

About Stanford Medicine

Stanford Medicine is an integrated academic health system comprising the Stanford School of Medicine and adult and pediatric health care delivery systems. Together, they harness the full potential of biomedicine through collaborative research, education and clinical care for patients. For more information, please visit med.stanford.edu .

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Analysis: Depression is probably not caused by a chemical imbalance in the brain – new study

20 July 2022

Writing in The Conversation, Professor Joanna Moncrieff and Dr Mark Horowitz (both UCL Psychiatry) report on their new research showing no clear evidence that serotonin levels or serotonin activity are responsible for depression.

For three decades, people have been deluged with information suggesting that depression is caused by a “chemical imbalance” in the brain – namely an imbalance of a brain chemical called serotonin. However, our latest research review shows that the evidence does not support it.

Although first proposed in the 1960s, the serotonin theory of depression started to be widely promoted by the pharmaceutical industry in the 1990s in association with its efforts to market a new range of antidepressants, known as selective serotonin-reuptake inhibitors or SSRIs. The idea was also endorsed by official institutions such as the American Psychiatric Association, which still tells the public that “differences in certain chemicals in the brain may contribute to symptoms of depression”.

Countless doctors have repeated the message all over the world, in their private surgeries and in the media. People accepted what they were told. And many started taking antidepressants because they believed they had something wrong with their brain that required an antidepressant to put right. In the period of this marketing push, antidepressant use climbed dramatically, and they are now prescribed to one in six of the adult population in England, for example.

For a long time, certain academics, including some leading psychiatrists, have suggested that there is no satisfactory evidence to support the idea that depression is a result of abnormally low or inactive serotonin. Others continue to endorse the theory. Until now, however, there has been no comprehensive review of the research on serotonin and depression that could enable firm conclusions either way.

At first sight, the fact that SSRI-type antidepressants act on the serotonin system appears to support the serotonin theory of depression. SSRIs temporarily increase the availability of serotonin in the brain, but this does not necessarily imply that depression is caused by the opposite of this effect.

There are other explanations for antidepressants’ effects. In fact, drug trials show that antidepressants are barely distinguishable from a placebo (dummy pill) when it comes to treating depression. Also, antidepressants appear to have a generalised emotion-numbing effect which may influence people’s moods, although we do not know how this effect is produced or much about it.

There has been extensive research on the serotonin system since the 1990s, but it has not been collected systematically before. We conducted an “umbrella” review that involved systematically identifying and collating existing overviews of the evidence from each of the main areas of research into serotonin and depression. Although there have been systematic reviews of individual areas in the past, none have combined the evidence from all the different areas taking this approach.

One area of research we included was research comparing levels of serotonin and its breakdown products in the blood or brain fluid. Overall, this research did not show a difference between people with depression and those without depression.

Another area of research has focused on serotonin receptors, which are proteins on the ends of the nerves that serotonin links up with and which can transmit or inhibit serotonin’s effects. Research on the most commonly investigated serotonin receptor suggested either no difference between people with depression and people without depression, or that serotonin activity was actually increased in people with depression – the opposite of the serotonin theory’s prediction.

Research on the serotonin “transporter”, that is the protein which helps to terminate the effect of serotonin (this is the protein that SSRIs act on), also suggested that, if anything, there was increased serotonin activity in people with depression. However, these findings may be explained by the fact that many participants in these studies had used or were currently using antidepressants.

We also looked at research that explored whether depression can be induced in volunteers by artificially lowering levels of serotonin. Two systematic reviews from 2006 and 2007 and a sample of the ten most recent studies (at the time the current research was conducted) found that lowering serotonin did not produce depression in hundreds of healthy volunteers. One of the reviews showed very weak evidence of an effect in a small subgroup of people with a family history of depression, but this only involved 75 participants.

Very large studies involving tens of thousands of patients looked at gene variation, including the gene that has the instructions for making the serotonin transporter. They found no difference in the frequency of varieties of this gene between people with depression and healthy controls.

Although a famous early study found a relationship between the serotonin transporter gene and stressful life events, larger, more comprehensive studies suggest no such relationship exists. Stressful life events in themselves, however, exerted a strong effect on people’s subsequent risk of developing depression.

Some of the studies in our overview that included people who were taking or had previously taken antidepressants showed evidence that antidepressants may actually lower the concentration or activity of serotonin.

The serotonin theory of depression has been one of the most influential and extensively researched biological theories of the origins of depression. Our study shows that this view is not supported by scientific evidence. It also calls into question the basis for the use of antidepressants.

Most antidepressants now in use are presumed to act via their effects on serotonin. Some also affect the brain chemical noradrenaline. But experts agree that the evidence for the involvement of noradrenaline in depression is weaker than that for serotonin.

There is no other accepted pharmacological mechanism for how antidepressants might affect depression. If antidepressants exert their effects as placebos, or by numbing emotions, then it is not clear that they do more good than harm.

Although viewing depression as a biological disorder may seem like it would reduce stigma, in fact, research has shown the opposite, and also that people who believe their own depression is due to a chemical imbalance are more pessimistic about their chances of recovery.

It is important that people know that the idea that depression results from a “chemical imbalance” is hypothetical. And we do not understand what temporarily elevating serotonin or other biochemical changes produced by antidepressants do to the brain. We conclude that it is impossible to say that taking SSRI antidepressants is worthwhile, or even completely safe. People need all this information to make informed decisions about whether or not to take antidepressants.

This article originally appeared in  The Conversation on 20 July 2022.

• Article in  The Conversation
• Article in  The Conversation  (Spanish)
• Professor Joanna Moncrieff's academic profile
• Dr Mark Horowitz's academic profile
• UCL Division of Psychiatry
• UCL Faculty of Brain Sciences

Clinical Trials

Depression (major depressive disorder).

Displaying 61 studies

The purpose of this study is to evaluate the effectiveness of adjunctive lithium in the acute (2 weeks) and continuation phase (4 weeks) for maintenance of ketamine-associated remission.

The purpose of this study is to learn if measures of brain activity are different in children and adolescents with depression who are in different stages of treatment. This is important because it may identify a biological marker for depression that could one day be used to identify depressed children who would benefit from certain treatments (medications for example), or to monitor how well treatments are working. Brain activity measures(known as cortical excitability and inhibition) will be collected by Transcranial Magnetic Stimulation (TMS). TMS is a noninvasive (no surgery or implants) brain stimulation technology which can make parts of the ...

The purpose of this study is to ascertain the effects of the Authentic Connections intervention among nurse leaders who are mothers at Mayo Clinic Rochester in comparison to a control group. Outcomes that will be measured include: psychological distress, depression, self-compassion, parenting stress, burnout, and feasibility measures.

This is a double-blind, sham controlled, multi-center study to confirm the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) for the treatment of patients currently experiencing an episode of depression who have failed to respond to at least one (1) antidepressant medication. Patients will be randomly assigned to either active or sham therapy and will undergo daily treatments for a period of time. Following completion of blinded treatments, patients may be eligible for a course of open label treatments.

The purpose of this study is to evaluate the feasibility of developing a microbiome probe of depression and to evaluate the microbiome change in a preliminary analysis of treatment response (n=20) vs. non response (n=20) to the antidepressant citalopram. This study is a 12 week open trial that will enroll approximately 80 participants (anticipated 40 study completers with paired biomarker data) with an episode of major depression, Bipolar I or Bipolar II and 40 age- and sex-matched healthy controls.

Depression is common in patients with cancer. Current medications for depression, while effective, take several weeks to take effect. Ketamine has emerged as a drug with promise for cancer patients. In two reported cases, a single dose of ketamine induced rapid and moderately sustained symptom reduction in depression and anxiety with no adverse side effects. Benefit was seen in as little as 1 hour and sustained up to 30 days. This study is a randomized, double-blind, placebo-controlled investigation testing whether a single dose of ketamine improves depression and anxiety relative to placebo in patients with cancer.

This study is to learn how effective a night of no sleep, with or without light therapy, is for patients in an inpatient setting who are experiencing Major depression.

To evaluate the safety and efficacy of daily, active Neurostar® TMS (when compared with sham treatment) in adolescents meeting criteria for Major Depressive Disorder (MDD).

The purpose of this study is to evaluate and analyze the clinical data that is already being collected for clinical purposes to determine the long-term effects of the repeated use of subanaesthetic ketamine/esketamine for patients with depression.  We hypothesize that patients who have a greater number of infusions/treatments will be more likely to have increased side effects to the drug.  We would like to be able to also analyze data related to any other assessments that are implemented as part of the clinical practice in the future.

The primary purpose of this study is to compare outcomes of depressive symptoms (PHQ-9 and HAM-D) over 6 months following an eight-week program of SMART-D therapy + treatment as usual versus treatment as usual for patients with major depression in partial-to full-remission.

The purpose of this study is to systematically investigate the use of repetitive transcranial magnetic stimulation (rTMS) as an added treatment for patients who have depression that is not decreasing with standard care.

The purpose of this study is to measure, rank, and categorize the subject sample of depression, stress, resilience, and happiness scores using quantitive surgeys. This research aims to learn how a Three Good Things (3GT) journaling activity affects a subject's symptoms of stress, depression, reslieince, and happiness.  The data will allow the project team to gain an in-depth understanding of the impact of the use of resilience strategies from a patient's perspective. This project aims to review if there is a correlation between stress, depression, resiliency, and happiness scores to the use of Positive Psychology.

The purpose of this study is to explore the role of Cognitive Behavioral Therapy (CBT), a treatment for depression, on self-effectiveness (feeling empowered to accomplish a given task) and depression in persons with chronic pain and depression. Past research has shown that persons with chronic pain show improvement in self-efficacy and depression scores when they are using CBT. The Pain rehabilitation Center (PRC) at Mayo Clinic is adding CBT focused groups to better understand the role of CBT on self-efficacy and depression in persons with chronic pain and depression.

The primary purpose of this study is to evaluate the degree of statistical agreement between observed clinical outcomes (non-response/remission) after 8 weeks of treatment and the outcomes predicted by an Augmented Human Intelligence (AHI)-based clinical decision support tool after 2 weeks of follow up.

In this project the investigators will develop and pilot test a supervised, vigorous intensity exercise intervention for depressed female smokers. If the pilot intervention is successful, the investigators will have a blueprint for a large randomized controlled trial. The long term objective is to develop interventions for depressed women that will ultimately reduce their risk of tobacco-caused disease and mortality.

The purpose of this study is to assess the feasibility and acceptability of passive data collection with a smartphone in depressed patients and investigate how passive data gathered via technology platforms can generate transdiagnostic digital phenotypes that potentially inform the assessment and/or treatment outcome of major mood disorders. This study aims to assess self-reported, behavioral, cognitive, and physiological data gathered from smartphones and smart watches as compared to gold standard clinical measured in treatment seeking depressed patients.

The purpose of this study is to gather information regarding the use of rTMS as a treatment for depression in adolescents with Major Depressive Disorder. The investigators also hope to learn if measures of brain activity (cortical excitability and inhibition) collected with transcranial magnetic stimulation (TMS) can be used to identify which patients will benefit from certain types of rTMS treatment. 

This research proposal aims to better understand the neurobiology of depression in adolescents and how repetitive transcranial magnetic stimulation (rTMS) may therapeutically impact brain function and mood. This investigation also proposes the first study to examine the efficacy of rTMS maintenance therapy in adolescents who have met clinical criteria following acute rTMS treatment. The magnetic resonance (MR) spectroscopy pattern of rTMS response will be analyzed according to previously established protocols.

The overall goal of this investigator-initiated trial is to evaluate the impact of platform algorithm products designed to rapidly identify pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation on treatment outcome of depression in adolescents. This new technology may have the potential to optimize treatment selection by improving response, minimizing unfavorable adverse events / side effects and increasing treatment adherence

The purpose of this research study is to find out if the medication known as ketamine can help the symptoms of depression. This drug is approved by the Food and Drug Administration (FDA) but the investigators will use it for a non-FDA approved reason (depression).

The purpose of this study is to explore whether Medibio’s system can provide objective measures of response to standard medication treatment for unipolar depression and bipolar depression, and to see if the system can tell these two conditions apart.

Medibio’s system uses software to analyse a person’s heart rate, activity, and posture to provide objective measures of a person’s autonomic nervous system, sleep, and other daily patterns.

This research study aims to test the safety and effectiveness of repetitive transcranial magnetic stimulation (rTMS) on teens with depression. The study also seeks to understand how rTMS treatment affects the neurobiology of teens with depression.

The purpose of this study is to learn if measures of brain chemicals from a brain scan called Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) and brain activity (known as cortical excitability and inhibition) collected by Transcranial Magnetic Stimulation (TMS) are different in adolescents with depression who are in different stages of treatment. Researchers are conducting this study to learn more about how the brain works in adolescents with depression and without depression (healthy controls). This is important because it may identify a biological marker (a measure of how bad an illness is) for depression that could one day be used ...

The proposed study seeks to obtain preliminary signal of the tolerability and efficacy of transcranial direct current stimulation (tDCS) for depressive symptoms in a sample of adolescents with depression and epilepsy. Additionally, effects of tDCS will be assessed via electroencephalographic, cognitive, and psychosocial measures.

The purpose of this study is to contribute to our understanding of the relationships between social media use in adolescents and psychological development, psychiatric comorbidity, and physiological markers of stress. 

The overall goal of this investigator-initiated trial is to evaluate the treatment outcome of depression utilizing platform algorithm products that can allow rapid identification of pharmacokinetic (PK) and/or pharmacodynamic (PD) genomic variation. This new technology may have the potential to optimize treatment selection by improving response, minimizing unfavorable adverse events / side effects and increasing treatment adherence.

Quetiapine, a second generation antipsychotic, is only available as oral tablets. However, topical and rectal formulations have been produced in compounding pharmacies. There is no data available suggesting that topical or rectal formulations provide serum levels similar to oral medication. In the clinical setting, when oral administration of quetiapine is not possible (for example, when a patient is extremely ill physically or mentally or both), clinicians and pharmacists have collaborated in such cases and have at times had to administer quetiapine compounded in other dosage formulations such as rectal or topical formulations. Despite clinical effectiveness of these "other" formulations, there ...

The purposes of this study are to summarize clinician evaluations of the NNDC battery in the single clinic where the adult battery is currently being administered to adolescents, to determine patient and clinician level of interest in using the NNDC battery in clinics where the adult battery is not currently being administered to adolescent patients (n=14), to measure change in evaluation 3 months post-implementation for any sites that begin administering the NNDC battery to adolescents, and to generate potential new Child and Adolescent Mood Disorders Interest Group (CAMDIG) research protocols for future consideration.

Transcranial Magnetic Stimulation (TMS) is an increasingly accepted neurostimulation- based treatment for major depressive disorder. While there is a growing anecdotal database supporting its use in bipolar depression the investigators propose to collect open label efficacy and safety data in a small population of patients with clinically verified bipolar disorder.

The purpose of this study is to assess the effectiveness and safety of MYDAYIS® as an augmentation agent for bipolar depression.

The purpose of this study is to determine the baseline chronotype patterns (with Morningness-Eveningness Questionnaire (MEQ) ) among inpatients with Major depressive disorder and then compare the chronotype distribution with the control group.

The purpose of this study is to validate measures of depression, anxiety, traumatic stress, and factors related to these outcomes in medical patients, to develop a model for identifying persons with myocarditis who are at risk for depressive and anxiety disorders (clinically significant depressive and anxious symptoms), and for examining the effects of anxiety and depression on quality of life and health outcomes in respondents with myocarditis and caregivers.

This feasibility study aims to better understand the neurobiology of major depression and how ketamine may therapeutically impact brain function. This research may provide important insights into the mechanism of ketamine response, thus, potentially increasing the likelihood of successful treatment interventions and decrease the number of ineffective treatments and/or risk for serious side effects.

The purpose of this study is to analyze the prevalence of mood disorders in newly-diagnosed breast cancer patients with use of specific questionnaires, aimed to diagnose clinically significant depression and anxiety, at a rural community hospital.

The FLAME Study is a 16-week clinical trial to study treatment with lamotrigine or fluoxetine in bipolar I, II and bipolar schizoaffective depressed adults. The purpose of the trial is to have a better understanding of whether individuals with a particular gene type and other inherited biological markers will have a good response to fluoxetine or lamotrigine, or alternatively, would be more likely to have side effects to this medication.

People with COPD have a greater risk for symptoms of depression, anxiety, and fear of breathlessness. Those emotions are independently associated with lower physical activity, poorer quality of life, and higher hospitalization and exacerbations; all independent predictors of survival and costs. There is a lack of treatment options to be routinely used in primary clinics for patients with COPD. Systematic reviews suggest that interventions that promote an accepting mode of response, such as mindfulness, might be more appropriate and effective for managing psychological distress in COPD patients, especially breathing-related anxiety. Hypothesis: A home-based 8-week Mindfulness-Based Stress Reduction (MBSR) for COPD ...

This study aims to assess the level of anxiety and depression in children with epilepsy and compare to the level of anxiety and depression perceived by family by using validated, standardized measures as both comorbid conditions can significantly impact both quality of life and disease course.

The purpose of this study is to examine the effects of a health coaching intervention on the stress and burden of caregivers of patients awaiting heart or lung transplant.

Hypotheses:  Caregivers will have traits and behaviors pre-transplant that will predict caregiver readiness, quality of life, and transplant recipient outcomes. Specifically, thoracic pre-transplant caregivers report stress, symptoms of anxiety or depression, and perceive high caregiver burden. These factors may be amenable to pre-transplant intervention to improve overall patient and caregiver outcomes.

Aims, purpose, or objectives:  We will conduct a pilot trial to test whether caregivers of heart and lung transplant candidates ...

In an effort to understand the effects of evidence-based interventions on children and adolescents, the aims of this study are to 1) evaluate the feasibility of utilizing wearable devices to track health information (i.e., sleep, physical activity); 2) evaluate the effectiveness of evidence-based intervention components on emotional and interpersonal functioning, family engagement, and sleep and physical activity level outcomes.

The purpose of this study is to implement a facilitated peer support group for women that have experienced an unexpected birth process in the last 12 months. 

Data collected from the MEVOKED Study #1 (IRB#14-009159) showed wide variability in how participants engaged with and used the MEVOKED program. This study will obtain additional information on participants – in particular PHQ9 depression scores and medication use during their enrollment in the MEVOKED program will provide additional data to support the analysis of the MEVOKED Study #1 (IRB#14-009159).  

The goal of this proposed study is to examine the genetic signature of the validated proteomic signature (model) based on a panel of serum proteomic markers that discriminates different mood disorders.

The purpose of this research study is to compare the antidepressant effect of lithium versus placebo in adults receiving ketamine. Lithium is available commercially for depression; ketamine is available commercially and can help the symptoms of depression; however, it has not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has allowed the use of this drug in this research study.

The proposed study will examine sequential bilateral accelerated theta burst stimulation (aTBS). Three sessions are administered daily for 10 days (5 days per week). During each session continuous theta burst stimulation (cTBS) in which 1800 pulses are delivered continuously over 120 seconds to the right dorsolateral prefrontal cortex (RDPFC) is administered first, followed by iTBS in which 1800 pulses are delivered in 2 second bursts, repeated every 10 seconds for 570 seconds (1800 pulses) to the left dorsolateral prefrontal cortex (LDPFC). The theta burst stimulation (TBS) parameters were adopted from prior work, with 3-pulse 50 Hz bursts given ...

The purpose of this study is to study brain chemistry in depressed patients compared to healthy patients who are not depressed.

The purpose of this study is to:

• Increase screening of adolescents for symptoms of depression in primary care La Crosse, WI clinics using the PHQ9M screening tool.Screening to occur at all well child visits and all subsequent visits for adolescents with Depression on their problem list.Clinics to include Pediatrics, Family Medicine, Family Health, Center for Womens Health.
• Develop a clear care pathway for adolescents identified with clinically meaningful symptoms of depression through increased screening, referral and treatment options.  Pathway may include psychoeducational materials (multimedia options), intake paperwork and process for Department of Behavioral Health locally, and ...

This study will compare glutamate and other neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) in bipolar I and II patients currently depressed with age-matched healthy controls. The study will also compare 1H-MRS of bipolar I and II patients before and after taking a 12-week course of lamotrigine. This study requires 8 visits over a 12 week period. These visits need to occur at Mayo Clinic in Rochester, MN.

The overall goal is to better understand the underlying pathophysiology of mood disorders and bipolar disorders in particular. We aim to investigate whether the subclinical atherosclerotic and inflammatory markers differ between patients with bipolar disorder, major depressive disorder, and psychiatric non-mood disorders and healthy subjects.

The purpose of this study is to identify pre-operative emotional factors that may affect surgical outcomes and how a multidisciplinary approach may improve success after urologic surgery for voiding dysfunction. 

The investigators are doing this research study to find out if the Stress Management and Resiliency Training (SMART) therapy will help subjects with their major depression treatment.

The purpose of this study is to evaluate the impact of interventions on important CV biomarkers to provide valuable information on the mechanism linking depression and anxiety to cardiac prognosis resulting in improved quality of life and diagnosis.

Study hypothesis: Do serial low-dose ketamine infusions, followed by weekly maintenance infusions, increase the length of time depressive symptoms stay in remission and the length of time associated suicide risk is improved? Brief Summary: This open label clinical trial is intended to further clarify initial response to low-dose ketamine infusion with repeated dosing and maintenance treatment model. Primary outcomes will be reduction in depression severity and reduction of suicide risk along with duration of response.

The purpose of this research is to gather information from the child and parent with regards to the use of electronic treatment tools to treat those with a mental health illness.

The purpose of this study is to remotely use the Ellipsis Health (EH) voice analysis technology to record the speech patterns and content of individuals with a recent diagnosis of Coronavirus-19 (COVID-19) presenting to the post-COVID-19 clinic at Mayo Clinic, to validate its use as a tool to screen for major depressive disorder (MDD) and generalized anxiety disorder (GAD) against gold-standard questionnaires used in clinical practice namely the PHQ-9 and GAD-7

Primary Aim

            We aim to evaluate: 1) the correlation between patient-reported rectal bleeding and stool frequency and health-related quality of life focused on fatigue, depression and anxiety, and work productivity; and 2) the correlation between the severity of endoscopic inflammation and health-related quality of life focused on fatigue, depression and anxiety, and work productivity.

Secondary Aims

We also aim to evaluate the correlation between the combination of clinical/PRO and the severity of endoscopic inflammation and health-related quality of life focused on fatigue, depression and anxiety, and work productivity.

The purpose of this study is to evaluate the long-term impact of treatment with sertraline on aspects of cognitive, emotional and physical development and maturation at puberty, in pediatric subjects ages 6 to 16 years (inclusive) with a diagnosis of anxiety disorder, depressive disorder or obsessive compulsive disorder.

The purpose of this study is to see if there is a connection between bad experiences in the patient's childhood, either by the patient or the parent, and poor blood sugar control, obesity, poor blood lipid levels, and depression in patients with type 1 diabetes.

Physical activity plays an important role in reducing the adverse effects of cancer treatment. There are few studies using prehabilitation to improve peri-operative outcomes in patients undergoing cancer surgery. This study will pilot a program of structured activity for women undergoing neoadjuvant chemotherapy with the intent to improve their physical state prior to surgical intervention and thus improve outcomes.

It has been shown that patients with advanced ovarian cancer may suffer from high levels of cancer –specific distress, depression and anxiety. It has also been proposed that psychological resilience can favorably affect psychological and treatment-related outcomes in cancer ...

The purpose of this study is to measure the frequency and severity of posttraumatic stress symptoms, depressive symptoms, anxiety symptoms, and cognitive impairment following dismissal from the ICU and three months later. This study also seeks to identify which of the multiple ICUs at Mayo Clinic yields the highest incidence of post-intensive care syndrome so that a future study designed to provide a therapeutic intervention can be implemented in those areas with the greatest potential.

The purpose of this study is to compare the effectiveness of combination therapy with antidepressants (AD), fear avoidance rehabilitation (EFAR) AD+EFAR vs. each treatment alone to improve pain, self-reported function, depression, and anxiety in patients with chronic low back pain and high negative affect.

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Depression articles from across Nature Portfolio

Depression refers to a state of low mood that can be accompanied with loss of interest in activities that the individual normally perceived as pleasurable, altered appetite and sleep/wake balance. Its severe form, major depression is classified as a mood disorder.

Latest Research and Reviews

Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension

• Sanne Y. Smith-Apeldoorn
• Jolien K. E. Veraart
• Robert A. Schoevers

The impact of mental health on health-related quality of life in patients with NF2-related Schwannomatosis

• Anna Freier
• Anna C. Lawson McLean
• Johannes Kruse

Long-term outcomes of physical activity counseling in in-patients with major depressive disorder: results from the PACINPAT randomized controlled trial

• Jan-Niklas Kreppke
• Markus Gerber

Depressive symptoms and antidepressant use in relation to white blood cell count among postmenopausal women from the Women’s Health Initiative

• Hind A. Beydoun
• May A. Beydoun
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Discontinuation of psychotropic medication: a synthesis of evidence across medication classes

• Christiaan H. Vinkers
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Dorsal CA3 overactivation mediates witnessing stress-induced recognition memory deficits in adolescent male mice

• Tian-Mei Si

News and Comment

Reply to bisol: critical review and recommendations for enhancement of the article on novel neurosteroid therapeutics for postpartum depression.

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MMP8 and stress susceptibility

Increased levels of matrix metalloproteinase 8, expressed by circulating myeloid cells, may have a role in stress-induced changes in social behaviour in mice.

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Methodological concerns in umbrella review of serotonin and depression

• Andrew L. Smith
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Physical activity compensates affective downsides of daily life aloneness

Combining accelerometry, electronic diaries and neuroimaging, we found that physical activity is reproducibly linked to better wellbeing in people lacking social contact in everyday life, especially in people at neural and psychological risk of affective disorders.

Mental health inequality in young LGBT+ people demands early universal interventions

• Elizabeth Ingram
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• Gemma Lewis

Depression genetics goes global

• Shari Wiseman

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What is depression?

Depression (also known as major depression, major depressive disorder, or clinical depression) is a common but serious mood disorder. It causes severe symptoms that affect how a person feels, thinks, and handles daily activities, such as sleeping, eating, or working.

To be diagnosed with depression, the symptoms must be present for at least 2 weeks.

There are different types of depression, some of which develop due to specific circumstances.

• Major depression includes symptoms of depressed mood or loss of interest, most of the time for at least 2 weeks, that interfere with daily activities.
• Persistent depressive disorder (also called dysthymia or dysthymic disorder) consists of less severe symptoms of depression that last much longer, usually for at least 2 years.
• Perinatal depression is depression that occurs during or after pregnancy. Depression that begins during pregnancy is prenatal depression and depression that begins after the baby is born is postpartum depression.
• Seasonal affective disorder is depression that comes and goes with the seasons, with symptoms typically starting in the late fall and early winter and going away during the spring and summer.
• Depression with symptoms of psychosis is a severe form of depression in which a person experiences psychosis symptoms, such as delusions (disturbing, false fixed beliefs) or hallucinations (hearing or seeing things others do not hear or see).

People with  bipolar disorder  (formerly called manic depression or manic-depressive illness) also experience depressive episodes, during which they feel sad, indifferent, or hopeless, combined with a very low activity level. But a person with bipolar disorder also experiences manic (or less severe hypomanic) episodes, or unusually elevated moods, in which they might feel very happy, irritable, or “up,” with a marked increase in activity level.

Other types of depressive disorders found in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5)   include disruptive mood dysregulation disorder (diagnosed in children and adolescents) and premenstrual dysphoric disorder (that affects women around the time of their period).

Who gets depression?

Depression can affect people of all ages, races, ethnicities, and genders.

Women are diagnosed with depression more often than men, but men can also be depressed. Because men may be less likely to recognize, talk about, and seek help for their feelings or emotional problems, they are at greater risk of depression symptoms being undiagnosed or undertreated.

Studies also show higher rates of depression and an increased risk for the disorder among members of the LGBTQI+ community.

What are the signs and symptoms of depression?

If you have been experiencing some of the following signs and symptoms, most of the day, nearly every day, for at least 2 weeks, you may be experiencing depression:

• Persistent sad, anxious, or “empty” mood
• Feelings of hopelessness or pessimism
• Feelings of irritability, frustration, or restlessness
• Feelings of guilt, worthlessness, or helplessness
• Loss of interest or pleasure in hobbies and activities
• Decreased energy, fatigue, or feeling slowed down
• Difficulty concentrating, remembering, or making decisions
• Difficulty sleeping, waking early in the morning, or oversleeping
• Changes in appetite or unplanned weight changes
• Physical aches or pains, headaches, cramps, or digestive problems that do not have a clear physical cause and do not go away with treatment
• Thoughts of death or suicide or suicide attempts

Not everyone who is depressed experiences every one of these symptoms. Some people experience only a few symptoms, while others experience many symptoms. Symptoms associated with depression interfere with day-to-day functioning and cause significant distress for the person experiencing them.

Depression can also involve other changes in mood or behavior that include:

• Increased anger or irritability
• Feeling restless or on edge
• Becoming withdrawn, negative, or detached
• Increased engagement in high-risk activities
• Greater impulsivity
• Increased use of alcohol or drugs
• Isolating from family and friends
• Inability to meet the responsibilities of work and family or ignoring other important roles
• Problems with sexual desire and performance

Depression can look different in men and women. Although men, women, and people of all genders can feel depressed, how they express those symptoms and the behaviors they use to cope with them may differ. For example, some men (as well as women) may show symptoms other than sadness, instead seeming angry or irritable. And although increased use of alcohol or drugs can be a coping strategy for any person with depression, men may be more likely to use alcohol or drugs to help them cope.

In some cases, mental health symptoms appear as physical problems. For example, a racing heart, tightened chest, ongoing headaches, or digestive issues. Men are often more likely to see a health care provider about these physical symptoms than their emotional ones.

Because depression tends to make people think more negatively about themselves and the world, some people may also have thoughts of suicide or self-harm.

Several persistent symptoms, in addition to low mood, are required for a diagnosis of depression, but people with only a few symptoms may also benefit from treatment. The severity and frequency of symptoms and how long they last will vary depending on the person, the illness, and the stage of the illness.

If you experience signs or symptoms of depression and they persist or do not go away, talk to a health care provider. If you see signs or symptoms of depression in someone you know, encourage them to seek help from a mental health professional.

If you or someone you know is struggling or having thoughts of suicide, call or text the 988 Suicide and Crisis Lifeline   at 988 or chat at 988lifeline.org   . In life-threatening situations, call 911 .

What are the risk factors for depression?

Depression is one of the most common mental disorders in the United States . Research suggests that genetic, biological, environmental, and psychological factors play a role in depression.

Depression can happen at any age, but it often begins in adulthood. Depression is now recognized as occurring in children and adolescents, although children may express more irritability than sadness. Many chronic mood and anxiety disorders in adults begin as high levels of anxiety in childhood.

Depression, especially in midlife or older age, can co-occur with other serious medical illnesses, such as diabetes, cancer, heart disease, and Parkinson’s disease. These conditions are often worse when depression is present, and research suggests that people with depression and other medical illnesses tend to have more severe symptoms of both illnesses. The Centers for Disease Control and Prevention (CDC)  has also recognized that having certain mental disorders, including depression and schizophrenia, can make people more likely to get severely ill from COVID-19.

Sometimes a physical health problem, such as thyroid disease, or medications taken for a physical illness cause side effects that contribute to depression. A health care provider experienced in treating these complicated illnesses can help work out the best treatment strategy. Learn more about getting help and finding a health care provider .

Other risk factors for depression include:

• Personal or family history of depression
• Major negative life changes, trauma, or stress

How is depression treated?

Depression, even the most severe cases, can be treated. The earlier treatment begins, the more effective it is. Depression is usually treated with medication , psychotherapy , or a combination of the two.

Some people may experience treatment-resistant depression, which occurs when a person does not get better after trying at least two antidepressant medications. If treatments like medication and psychotherapy do not reduce depressive symptoms or the need for rapid relief from symptoms is urgent, brain stimulation therapy  may be an option to explore.

Quick tip : No two people are affected the same way by depression, and there is no "one-size-fits-all" treatment. Finding the treatment that works best for you may take trial and error.

Medications

Antidepressants are medications commonly used to treat depression. They work by changing how the brain produces or uses certain chemicals involved in mood or stress. You may need to try several different antidepressants before finding the one that improves your symptoms and has manageable side effects. A medication that has helped you or a close family member in the past will often be considered first.

Antidepressants take time—usually 4–8 weeks—to work, and problems with sleep, appetite, and concentration often improve before mood lifts. It is important to give a medication a chance to work before deciding whether it’s the right one for you.

New medications, such as intranasal esketamine , can have rapidly acting antidepressant effects, especially for people with treatment-resistant depression. Esketamine is a medication approved by the U.S. Food and Drug Administration (FDA)  for treatment-resistant depression. Delivered as a nasal spray in a doctor’s office, clinic, or hospital, it acts rapidly, typically within a couple of hours, to relieve depression symptoms. People who use esketamine will usually continue taking an oral antidepressant to maintain the improvement in their symptoms.

Another option for treatment-resistant depression is to take an antidepressant alongside a different type of medication that may make the antidepressant more effective, such as an antipsychotic or anticonvulsant medication. Further research is needed to identify the best role of these newer medications in routine practice.

If you begin taking an antidepressant, do not stop taking it without talking to a health care provider . Sometimes people taking antidepressants feel better and stop taking the medications on their own, and their depression symptoms return. When you and your health care provider have decided it is time to stop a medication, usually after a course of 9–12 months, the provider will help you slowly and safely decrease your dose. Abruptly stopping a medication can cause withdrawal symptoms.

Note : In some cases, children, teenagers, and young adults under 25 years may experience an increase in suicidal thoughts or behavior when taking antidepressants, especially in the first few weeks after starting or when the dose is changed. The FDA advises that patients of all ages taking antidepressants be watched closely, especially during the first few weeks of treatment.

If you are considering taking an antidepressant and are pregnant, planning to become pregnant, or breastfeeding, talk to a health care provider about any health risks to you or your unborn or nursing child and how to weigh those risks against the benefits of available treatment options.

To find the latest information about antidepressants, talk to a health care provider and visit the FDA website  .

Psychotherapies

Several types of psychotherapy (also called talk therapy or counseling) can help people with depression by teaching them new ways of thinking and behaving and how to change habits that contribute to depression. Evidence-based approaches to treating depression include cognitive-behavioral therapy (CBT) and interpersonal therapy (IPT). Learn more about psychotherapy .

The growth of telehealth for mental health services , which offers an alternative to in-person therapy, has made it easier and more convenient for people to access care in some cases. For people who may have been hesitant to look for mental health care in the past, telemental health services might be an easier first step than traditional mental health services.

Brain stimulation therapies

If medication or psychotherapy does not reduce symptoms of depression, brain stimulation therapy may be an option to explore. There are now several types of brain stimulation therapy, some of which have been authorized by the FDA to treat depression. Other brain stimulation therapies are experimental and still being investigated for treating mental disorders like depression.

Although brain stimulation therapies are less frequently used than medication and psychotherapy, they can play an important role in treating mental disorders in people who do not respond to other treatments. These therapies are used for most mental disorders only after medication and psychotherapy have been tried and usually continue to be used alongside these treatments.

Brain stimulation therapies act by activating or inhibiting the brain with electricity. The electricity is given directly through electrodes implanted in the brain or indirectly through electrodes placed on the scalp. The electricity can also be induced by applying magnetic fields to the head.

The brain stimulation therapies with the largest bodies of evidence include:

• Electroconvulsive therapy (ECT)
• Repetitive transcranial magnetic stimulation (rTMS)
• Vagus nerve stimulation (VNS)
• Magnetic seizure therapy (MST)
• Deep brain stimulation (DBS)

ECT and rTMS are the most widely used brain stimulation therapies, with ECT having the longest history of use. The other therapies are newer and, in some cases, still considered experimental. Other brain stimulation therapies may also hold promise for treating specific mental disorders.

ECT, rTMS, and VNS have authorization from the FDA to treat severe, treatment-resistant depression. They can be effective for people who have not been able to feel better with other treatments or for whom medications cannot be used safely and in severe cases where a rapid response is needed, such as when a person is catatonic, suicidal, or malnourished.

Whereas ECT involves using electricity to induce seizures, in rTMS, a magnet is used to activate the brain. Unlike ECT, in which stimulation is more generalized, in rTMS, the stimulation is targeted to a specific brain site. Both procedures are noninvasive and do not require surgery to perform. In contrast, VNS is usually a surgical procedure that involves implanting a device under the skin to activate the vagus nerve.

Additional types of brain stimulation therapy are being investigated for treating depression and other mental disorders. Learn more about these brain stimulation therapies . Talk to a health care provider and make sure you understand the potential benefits and risks before undergoing brain stimulation therapy.

Alternative treatments

The FDA has not approved any natural products for depression. Although research is ongoing, some people use natural products, including vitamin D and the herbal dietary supplement St. John’s wort, for depression. However, these products can come with risks. For instance, dietary supplements and natural products can limit the effectiveness of some medications or interact in dangerous or even life-threatening ways with them.

Do not use vitamin D, St. John’s wort, or other dietary supplements or natural products without talking to a health care provider. Rigorous studies must be conducted to test whether these and other natural products are safe and effective.

Daily morning light therapy is a common treatment choice for people with seasonal affective disorder. Light therapy devices are much brighter than ordinary indoor lighting and considered safe, except for people with certain eye diseases or taking medications that increase sensitivity to sunlight. As with all interventions for depression, evaluation, treatment, and follow-up by a health care provider are strongly recommended. Research into the potential role of light therapy in treating non-seasonal depression is ongoing.

How can I find help for depression?

If you think you may have depression, start by making an appointment to see a health care provider. This could be your primary care provider; a psychiatrist, psychologist, or social worker; or another provider who specializes in diagnosing and treating mental health conditions. Find  tips to help prepare for and get the most out of your visit and information about getting help .

Once you enter treatment, you should gradually start to feel better. Here are some other things you can do outside of treatment that may help you or a loved one during treatment for depression:

• Try to get physical activity. Just 30 minutes a day of walking can boost your mood.
• Try to maintain a regular bedtime and wake-up time.
• Eat regular, healthy meals.
• Break up large tasks into small ones; do what you can as you can. Decide what must get done and what can wait.
• Try to connect with people. Talk with people you trust about how you are feeling.
• Delay making important decisions, such as getting married or divorced, or changing jobs until you feel better. Discuss decisions with people who know you well.
• Avoid using alcohol, nicotine, or drugs, including medications not prescribed for you.

How can I find a clinical trial for depression?

Clinical trials are research studies that look at new ways to prevent, detect, or treat diseases and conditions, including depression. The goal of a clinical trial is to determine if a new test or treatment works and is safe. Although people may benefit from being part of a clinical trial, they should know that the primary purpose is to gain new scientific knowledge so that others can be better helped in the future.

Researchers at NIMH and around the country conduct many studies with patients with depression and healthy volunteers. We have new and better treatment options today because of what clinical trials have uncovered. Talk to a health care provider about clinical trials, their benefits and risks, and whether one is right for you.

To learn more or find a study, visit:

• Clinical Trials – Information for Participants : Information about clinical trials, why people might take part in a clinical trial, and what people might experience during a clinical trial
• Clinicaltrials.gov: Current Studies on Depression   : List of clinical trials funded by the National Institutes of Health (NIH) being conducted across the country
• Join a Study: Depression—Adults : List of studies currently recruiting adults with depression being conducted on the NIH campus in Bethesda, MD
• Join a Study: Depression—Children : List of studies currently recruiting children with depression being conducted on the NIH campus in Bethesda, MD
• Join a Study: Perimenopause-Related Mood Disorders : List of studies on perimenopause-related mood disorders being conducted on the NIH campus in Bethesda, MD
• Join a Study: Postpartum Depression : List of studies on postpartum depression being conducted on the NIH campus in Bethesda, MD

Where can I learn more about depression?

Free brochures and shareable resources.

• Chronic Illness and Mental Health: Recognizing and Treating Depression : This brochure provides information about depression for people living with chronic illnesses, including children and adolescents. It discusses signs and symptoms, risk factors, and treatment options.
• Depression : This brochure provides information about depression, including different types of depression, signs and symptoms, how it is diagnosed, treatment options, and how to find help for yourself or a loved one.
• Depression in Women: 4 Things to Know : This fact sheet provides information about depression in women including signs and symptoms, types of depression unique to women, treatment options, and how to find help.
• Perinatal Depression : This brochure provides information about perinatal depression, including how it differs from “baby blues,” causes, signs and symptoms, treatment options, and how to find help for yourself or a loved one.
• Seasonal Affective Disorder : This fact sheet provides information about seasonal affective disorder, including signs and symptoms, how it is diagnosed, causes, and treatment options.
• Seasonal Affective Disorder (SAD): More Than the Winter Blues : This infographic provides information about how to recognize the symptoms of seasonal affective disorder and what to do to get help.
• Teen Depression: More Than Just Moodiness : This fact sheet is for teens and young adults and provides information about how to recognize the symptoms of depression and what to do to get help.
• Digital Shareables on Depression : These digital resources, including graphics and messages, can be used to spread the word about depression and help promote depression awareness and education in your community.

Federal resources

• Depression   (MedlinePlus - also en español  )
• Moms’ Mental Health Matters: Depression and Anxiety Around Pregnancy   (National Institute of Child Health and Human Development)

Research and statistics

• Journal Articles   : This webpage provides articles and abstracts on depression from MEDLINE/PubMed (National Library of Medicine).
• Statistics: Major Depression : This webpage provides the statistics currently available on the prevalence and treatment of depression among people in the United States.
• Depression Mental Health Minute : Take a mental health minute to watch this video on depression.
• NIMH Experts Discuss the Menopause Transition and Depression : Learn about the signs and symptoms, treatments, and latest research on depression during menopause.
• NIMH Expert Discusses Seasonal Affective Disorder : Learn about the signs and symptoms, treatments, and latest research on seasonal affective disorder.
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Evolution and Emerging Trends in Depression Research From 2004 to 2019: A Literature Visualization Analysis

1 School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China

Xuemei Tian

2 School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China

Xianrui Wang

Associated data.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.

Depression has become a major threat to human health, and researchers around the world are actively engaged in research on depression. In order to promote closer research, the study of the global depression knowledge map is significant. This study aims to map the knowledge map of depression research and show the current research distribution, hotspots, frontiers, and trends in the field of depression research, providing researchers with worthwhile information and ideas. Based on the Web of Science core collection of depression research from 2004 to 2019, this study systematically analyzed the country, journal, category, author, institution, cited article, and keyword aspects using bibliometric and data visualization methods. A relationship network of depression research was established, highlighting the highly influential countries, journals, categories, authors, institutions, cited articles, and keywords in this research field. The study identifies great research potential in the field of depression, provides scientific guidance for researchers to find potential collaborations through collaboration networks and coexistence networks, and systematically and accurately presents the hotspots, frontiers, and shortcomings of depression research through the knowledge map of global research on depression with the help of information analysis and fusion methods, which provides valuable information for researchers and institutions to determine meaningful research directions.

Introduction

Health issues are becoming more and more important to people due to the continuous development of health care. The social pressures on people are becoming more and more pronounced in a social environment that is developing at an increasing rate. Prolonged exposure to stress can have a negative impact on brain development ( 1 ), and depression is one of the more typical disorders that accompany it. Stress will increase the incidence of depression ( 2 ), depression has become a common disease ( 3 ), endangering people's physical health. Depression is a debilitating mental illness with mood disorders, also known as major depression, clinical depression, or melancholia. In human studies of the disease, it has been found that depression accounts for a large proportion of the affected population. According to the latest data from the World Health Organization (WHO) statistics in 2019, there are more than 350 million people with depression worldwide, with an increase of about 18% in the last decade and an estimated lifetime prevalence of 15% ( 4 ), it is a major cause of global disability and disease burden ( 5 ), and depression has quietly become a disease that threatens hundreds of millions of people worldwide.

Along with the rise of science communication research, the quantification of science is also flourishing. As a combination of “data science” and modern science, bibliometrics takes advantage of the explosive growth of research output in the era of big data, and uses topics, authors, publications, keywords, references, citations, etc. as research targets to reveal the current status and impact of the discipline more accurately and scientifically. Whereas, there is not a wealth of bibliometric studies related to depression. Fusar-Poli et al. ( 6 ) used bibliometrics to systematically evaluate cross-diagnostic psychiatry. Hammarström et al. ( 7 ) used bibliometrics to analyze the scientific quality of gender-related explanatory models of depression in the medical database PubMed. Tran et al. ( 8 ) used the bibliometric analysis of research progress and effective interventions for depression in AIDS patients. Wang et al. ( 9 ) used bibliometric methods to analyze scientific studies on the comorbidity of pain and depression. Shi et al. ( 10 ) performed a bibliometric analysis of the top 100 cited articles on biomarkers in the field of depression. Dongping et al. ( 11 ) used bibliometric analysis of studies on the association between depression and gut flora. An Chunping et al. ( 12 ) analyzed the literature on acupuncture for depression included in PubMed based on bibliometrics. Yi and Xiaoli ( 13 ) used a bibliometric method to analyze the characteristics of the literature on the treatment of depression by Chinese medicine in the last 10 years. Zhou and Yan ( 14 ) used bibliometric method to analyze the distribution of scientific and technological achievements on depression in Peoples R China. Guaijuan ( 15 ) performed a bibliometric analysis of the interrelationship between psoriasis and depression. Econometric analysis of the relationship between vitamin D deficiency and depression was performed by Yunzhi et al. ( 16 ) and Shauni et al. ( 17 ) performed a bibliometric analysis of domestic and international research papers on depression-related genes from 2003 to 2007. A previous review of depression-related bibliometric studies revealed that there is no bibliometric analysis of global studies in the field of depression, including country network analysis, journal network analysis, category network analysis, author network analysis, institutional network analysis, literature co-citation analysis, keyword co-presentation analysis, and cluster analysis.

The aim of this study was to conduct a comprehensive and systematic literature-based data mining and metrics analysis of depression-related research. More specifically, this analysis focuses on cooperative network and co-presentation analysis, based on the 36,477 papers included in the Web of Science Core Collection database from 2004 to 2019, and provides an in-depth analysis of cooperative network, co-presentation network, and co-citation through modern metrics and data visualization methods. Through the mining of key data, the data correlation is further explored, and the results obtained can be used to scientifically and reasonably predict the depression-related information. This study aims to show the spatial and temporal distribution of research countries, journals, authors, and institutions in the field of depression in a more concise manner through a relational network. A deeper understanding of the internal structure of the research community will help researchers and institutions to establish more accurate and effective global collaborations, in line with the trend of human destiny and globalization. In addition, the study will allow for the timely identification of gaps in current research. A more targeted research direction will be established, a more complete picture of the new developments in the field of depression today will be obtained, and the research protocol will be informed for further adjustments. The results of these analyses will help researchers understand the evolution of this field of study. Overall, this paper uses literature data analysis to find research hotspots in the field of depression, analyze the knowledge structure within different studies, and provide a basis for predicting research frontiers. This study analyzed the literature in the field of depression using CiteSpace 5.8.R2 (64-bit) to analyze collaborative networks, including country network analysis, journal network analysis, category network analysis, researcher network analysis, and institutional network analysis using CiteSpace 5.8.R2 (64-bit). In addition, literature co-citation, keyword co-presentation, and cluster analysis of depression research hotspots were also performed. Thus, exploring the knowledge dimensions of the field, quantifying the research patterns in the field, and uncovering emerging trends in the field will help to obtain more accurate and complete information. The large amount of current research results related to depression will be presented more intuitively and accurately with the medium of information technology, and the scientific evaluation of research themes and trend prediction will be provided from a new perspective.

Data Sources

The data in this paper comes from the Web of Science (WoS) core collection. The time years were selected as 2004–2019. First, the literature was retrieved after entering “depression” using the title search method. A total of 73,829 articles, excluding “depression” as “suppression,” “decline,” “sunken,” “pothole,” “slump,” “low pressure,” “frustration.” The total number of articles with other meanings such as “depression” was 5,606, and the total number of valid articles related to depression was 68,223. Next, the title search method was used to search for studies related to “major depressive disorder” not “depression,” and a total of 8,070 articles were retrieved. For the two search strategies, a total of 76,293 records were collected. The relevant literature retrieved under the two methods were combined and exported in “plain text” file format. The exported records included: “full records and references cited.” CiteSpace processed the data to obtain 41,408 valid records, covering all depression-related research articles for the period 2004–2019, and used this as the basis for analysis.

Processing Tools

CiteSpace ( 18 ), developed by Chao-Mei Chen, a professor in the School of Information Science and Technology at Drexel University, is a Java-based program with powerful data visualization capabilities and is one of the most widely used knowledge mapping tools. The software version used in this study is CiteSpace 5.8.R2 (64-bit).

Methods of Analysis

This study uses bibliometrics and data visualization as analytical methods. First, the application of bibliometrics to the field of depression helped to identify established and emerging research clusters, demonstrating the value of research in this area. Second, data visualization provides multiple perspectives on the data, presenting correlations in a clearer “knowledge graph” that can reveal underestimated and overlooked trends, patterns, and differences ( 19 ). CiteSpace is mainly based on the “co-occurrence clustering idea,” which extracts the information units (keywords, authors, institutions, countries, journals, etc.) in the data by classification, and then further reconstructs the data in the information units to form networks based on different types and strengths of connections (e.g., keyword co-occurrence, author collaboration, etc.). The resulting networks include nodes and links, where the nodes represent the information units of the literature and the links represent the existence of connections (co-occurrence) between the nodes. Finally, the network is measured, statistically analyzed, and presented in a visual way. The analysis needs to focus on: the overall structure of the network, key nodes and paths. The key evaluation indicators in this study are: betweenness centrality, year, keyword frequency, and burst strength. Betweenness centrality (BC) is the number of times a node acts as the shortest bridge between two other nodes. The higher the number of times a node acts as an “intermediary,” the greater its betweenness centrality. Betweenness centrality is a measure of the importance of articles found and measured by nodes in the network by labeling the category (or authors, journals, institutions, etc.) with purple circles. There may be many shortest paths between two nodes in the network, and by counting all the shortest paths of any two nodes in the network, if many of the shortest paths pass through a node, then the node is considered to have high betweenness centrality. In CiteSpace, nodes with betweenness centrality over 0.1 are called critical nodes. Year, which represents the publication time of the article. Frequency, which represents the number of occurrences. Burst strength, an indicator used to measure articles with sudden rise or sudden decline in citations. Nodes with high burst strength usually represent a shift in a certain research area and need to be focused on, and the burst article points are indicated in red. The nodes and their sizes and colors are first analyzed initially, and further analyzed by betweenness centrality indicators for evaluation. Each node represents an article, and the larger the node, the greater the frequency of the keyword word and the greater the relevance to the topic. Similarly, the color of the node represents time: the warmer the color, the more recent the time; the colder the color, the older the era; the node with a purple outer ring is a node with high betweenness centrality; the color of each annual ring can determine the time distribution: the color of the annual ring represents the corresponding time, and the thickness of one annual ring is proportional to the number of articles within the corresponding time division; the dominant color can reflect the relative concentration of the emergence time; the node The appearance of red annual rings in the annual rings means hot spots, and the frequency of citations has been or is still increasing rapidly.

Large-Scale Assessment

Country analysis.

During the period 2004–2019, a total of 157 countries/territories have conducted research on depression, which is about 67.38% of 233 countries/territories worldwide. This shows that depression is receiving attention from many countries/regions around the world. Figure 1 shows the geographical distribution of published articles for 157 countries. The top 15 countries are ranked according to the number of articles published. Table 1 lists the top 15 countries with the highest number of publications in the field of depression worldwide from 2004 to 2019. These 15 countries include 4 Asian countries (Peoples R China, Japan, South Korea, Turkey), 2 North American countries (USA, Canada), 1 South American country (Brazil), 7 European countries (UK, Germany, Netherlands, Italy, France, Spain, Sweden), and 1 Oceania country (Australia).

Geographical distributions of publications, 2004–2019.

The top 15 productive countries.

TP, total publications; TP R (%), the ratio of the amount of the publications in the country to the publications in the word during 2004–2019; BC, betweenness centrality; TPA (million), total publications in all areas; TPA R (%), the ratio of the amount of publications in depression to publications in all areas .

Overall, the main distribution of these articles is in USA and some European countries, such as UK, Germany, Netherlands, Italy, France, Spain, and Sweden. This means that these countries are more interested and focused on research on depression compared to others. The total number of publications across all research areas in the Web of Science core collection is similar to the distribution of depression research areas, with the trend toward USA, UK, and Peoples R China as leading countries being unmistakable, and USA has been a leader in the field of depression, with far more articles published than any other country. It can also be seen that USA is the country with the highest betweenness centrality in the network of national collaborations analyzed in this paper. USA research in the field of depression is closely linked to global research, and is an important part of the global collaborative network for depression research. As of 2019, the total number of articles published in depression performance research in USA represents 27.13% of the total number of articles published in depression worldwide, which is ~4 times more than the second-place country, UK, which is far ahead of other countries. Peoples R China, as the third most published country, has a dominant number of articles, but its betweenness centrality is 0.01, reflecting the fact that Peoples R China has less collaborative research with other countries, so Peoples R China should strengthen its foreign collaborative research and actively establish global scientific research partnerships to seek development and generate breakthroughs in cooperation. The average percentage of scientific research on depression in each country is about 0.19%, also highlighting the urgent need to address depression as one of the global human health problems. The four Asian countries included in the top 15 countries are Peoples R China, Japan, South Korea, and Turkey, with Peoples R China ranking third with 6.72% of the total number of all articles counted. The distribution may be explained by the fact that Peoples R China is the largest developing country with a rapid development rate as the largest. Along with the steady rise in the country's economic power, people are creating economic benefits and their health is becoming a consumable commodity. The lifetime prevalence and duration of depression varies by country and region ( 2 ), but the high prevalence and persistence of depression worldwide confirms the increasing severity of the disease worldwide. The WHO estimates that more than 300 million people, or 4.4% of the world's population, suffer from depression ( 20 ), with the number of people suffering from depression increasing at a patient rate of 18.4% between 2005 and 2015. Depression, one of the most prevalent mental illnesses of our time, has caused both physical and psychological harm to many people, and it has become the leading cause of disability worldwide today, and in this context, there is increased interest and focus on research into depression. It is expected that a more comprehensive understanding of depression and finding ways to prevent and cope with the occurrence of this disease can help people get rid of the pain and shadow brought by depression, obtain a healthy and comfortable physical and mental environment and physical health, and make Chinese contributions to the cause of human health. Undoubtedly, the occurrence of depressive illnesses in the context of irreversible human social development has stimulated a vigorous scientific research environment on depression in Peoples R China and other developing countries and contributed to the improvement of research capacity in these countries. Moreover, from a different perspective, the geographical distribution of articles in this field also represents the fundamental position of the country in the overall scientific and academic research field.

Growth Trend Analysis

Figure 2 depicts the distribution of 38,433 articles from the top 10 countries in terms of the number of publications and the trend of growth during 2004–2019.

The distribution of publications in top 10 productive countries, 2004–2019. Source: author's calculation. National development classification criteria refer to “Human Development Report 2020” ( 21 ).

First, the number of articles published per year for the top 10 countries in terms of productivity was counted and then the white bar chart in Figure 2 was plotted, with the year as the horizontal coordinate and total publications as the vertical coordinate, showing the distribution of the productivity of articles in the field of depression per year. The total number of publications for the period 2004–2019 is 38,433. Based on the white bars and line graphs in Figure 2 , we can divide this time period into three growth periods. The number of publications in each growth period is calculated based on the number of publications per year. As can be seen from the figure, the period 2004–2019 can be divided into three main growth periods, namely 2004–2009, 2010–2012, and 2013–2019, the first growth period being from 2004 to 2009, the number of publications totaled 6,749, accounting for 23.97% of all publications; from 2010 to 2012, the number of publications totaled 8,236, accounting for 17.56% of all publications; and from 2013 to 2019, the number of publications totaled 22,473, accounting for 58.47% of all publications. Of these, 2006 was the first year of sharp growth with an annual growth rate of 19.97%, 2009 was the second year of sharp growth with an annual growth rate of 17.64%, and 2008 was the third year of sharp growth with an annual growth rate of 16.09%. In the last 5 years, 2019 has also shown a sharp growth trend with a growth rate of 14.34%. Notably, in 2010 and 2013, there was negative growth with the growth rate of −3.39 and −1.45%. In the last 10 years, depression research has become one of the most valuable areas of human research. It can also be noted that the number of publications in the field of depression in these 10 countries has been increasing year after year.

Second, the analysis is conducted from the perspective of national development, divided into developed and developing countries, as shown in the orange bar chart in Figure 2 , where the horizontal coordinate is year and the vertical coordinate is total publications, comparing the article productivity variability between developed and developing countries. The top 10 most productive countries in the field of depression globally include nine developed countries and one developing country, respectively. During the period 2004–2019, 34,631 papers were published in developed countries and 3,802 papers were published in developing countries, with developed countries accounting for 90.11% of the 38,433 articles and developing countries accounting for 9.89%, and the total number of publications in developed countries was about 9 times higher than that in developing countries. During the period 2004–2019, the number of publications in developed countries showed negative growth in 2 years (2010 and 2013) with growth rates of −3.39 and −1.45%, respectively. The rest of the years showed positive growth with growth rates of 1.52% (2005), 19.97 (2006), 8.11 (2007), 12.70 (2008), 17.64 (2009), 13.22 (2011), 10.17 (2012), 16.09 (2014), 10.46 (2015), 4.10 (2016), 1.59 (2017), 3.91 (2018), and 14.34 (2019), showing three periods of positive growth: 2004–2009, 2011–2012, and 2014–2019, with the highest growth rate of 19.97% in 2006. Recent years have also shown a higher growth trend, with a growth rate of 14.34% in 2019. It is worth noting that developing countries have been showing positive growth in the number of articles in the period 2004–2019, with annual growth rates of 81.25 (2005), 17.24 (2006), 35.29 (2007), 19.57 (2008), 65.45 (2009), 13.19 (2010), 29.13 (2011), 54.89 (2012), 12.14 (2013), 36.36 (2014), 14.92 (2015), 16.02 (2016), 10.24 (2017), 21.17 (2018), and 31.37 (2019), with the highest growth rate of 81.25% in 2005. In the field of depression research, developed countries are still the main force and occupy an important position.

Further, 10 countries with the highest productivity in the field of depression are compared, total publications in the vertical coordinate, and the colored scatter plot contains 10 colored dots, representing 10 different countries. On the one hand, the variability of the contributions of different countries in the same time frame can be compared horizontally. On the other hand, it is possible to compare vertically the variability of the growth of different countries over time. Among them, USA, with about 40.29% of the world's publications in the field of depression, has always been a leader in the field of depression with its rich research results. Peoples R China, as the only developing country, ranks 3rd in the top 10 countries with high production of research papers in the field of depression, and Peoples R China's research in the field of depression has shown a rapid growth trend, and by 2016, it has jumped to become the 2nd largest country in the world, with the number of published papers increasing year by year, which has a broad prospect and great potential for development.

Distribution of Periodicals

Table 2 lists the top 15 journals in order of number of journal co-citations. In the field of depression, the top 15 cited journals accounted for 19.06% of the total number of co-citations, nearly one in five of the total number of journal co-citations. In particular, the top 3 journals were ARCH GEN PSYCHIAT (ARCHIVES OF GENERAL PSYCHIATRY), J AFFECT DISORDERS (JOURNAL OF AFFECTIVE DISORDERS), and AM J PSYCHIAT (AMERICAN JOURNAL OF PSYCHIATRY), with co-citation counts of 20,499, 20,302, and 20,143, with co-citation rates of 2.09, 2.07, and 2.06%, respectively. The main research area of ARCH GEN PSYCHIAT is Psychiatry; the main research area of the journal J AFFECT DISORDERS is Neurosciences and Neurology, Psychiatry; AM J PSYCHIAT is the main research area of Psychiatry, and the three journals have “psychiatry” in common, making them the most frequently co-cited journals in the field of depression.

The top 15 co-cited journals.

TP, total publications; TP R (%), the ratio of the amount of the journal's publications to the total publications; BC, betweenness centrality .

Figure 3 shows the network relationship graph of the cited journals from 2004 to 2019. The figure takes g-index as the selection criteria, the scale factor k = 25 to include more nodes. Each node of the graph represents each journal, the node size represents the number of citation frequencies, the label size represents the size of the betweenness centrality of the journal in the network, and the links between journals represent the co-citation relationships. The journal co-citation map reflects the structure of the journals, indicating that there are links between journals and that the journals include similar research topics. These journals included research topics related to neuroscience, psychiatry, neurology, and psychology. The journal with betweenness centrality size in the top 1 was ARCH GEN PSYCHIAT, with betweenness centrality size of 0.07, and impact shadows of 14.48. ARCH GEN PSYCHIAT, has research themes of Psychiatry. In all, these journals in Figure 3 occupy an important position in the journal's co-citation network and have strong links with other journals.

Prominent journals involved in depression. The betweenness centrality of a node in the network measures the importance of the position of the node in the network. Two types of nodes may have high betweenness centrality scores: (1) Nodes that are highly connected to other nodes, (2) Nodes are positioned between different groups of nodes. The lines represent the link between two different nodes.

Distribution of Categories

Table 3 lists the 15 most popular categories in the field of depression research during the period 2004–2019. In general, the main disciplines involved are neuroscience, psychology, pharmacy, medicine, and health care, which are closely related to human life and health issues. Of these, psychiatry accounted for 20.78%, or about one-five, making it the most researched category. The study of depression focuses on neuroscience, reflecting the essential characteristics of depression as a category of mental illness and better reflecting the fact that depression is an important link in the human public health care. In addition, Table 3 shows that the category with the highest betweenness centrality is Neuroscience, followed by Public, Environment & Occupational Health, and then Pharmacology & Pharmacy, with betweenness centrality of 0.16, 0.13, and 0.11, respectively. It is found that the research categories of depression are also centered on disciplines such as neuroscience, public health and pharmacology, indicating that research on depression requires a high degree of integration of multidisciplinary knowledge and integration of information from various disciplines in order to have a more comprehensive and in-depth understanding of the depression.

The top 15 productive categories, 2004–2019.

TP, total publications; TP R (%), the ratio of the amount of the category's publications to the total publications; BC, betweenness centrality .

Figure 4 shows the nine categories with the betweenness centrality in the category research network, with Neuroscience being the node with the highest betweenness centrality in this network, meaning that Neuroscience is most strongly linked to all research categories in the field of depression research. Depression is a debilitating psychiatric disorder with mood disorders. It is worth noting that the development of depression not only has psychological effects on humans, but also triggers many somatic symptoms that have a bad impact on their daily work and life, giving rise to the second major mediating central point of research with public health as its theme. The somatization symptoms of depression often manifest as abnormalities in the cardiovascular system, and many studies have looked at the pathology of the cardiovascular system in the hope of finding factors that influence the onset of depression, mechanisms that trigger it or new ways to treat it. Thus, depression involves not only the nervous system, but also interacts with the human cardiovascular system, for example, and the complexity of depression dictates that the study of depression is an in-depth study based on complex systems.

Prominent categories involved in depression, 2004–2019. The betweenness centrality of a node in the network measures the importance of the position of the node in the network. Two types of nodes may have high betweenness centrality scores: (1) Nodes that are highly connected to other nodes, (2) Nodes are positioned between different groups of nodes. The lines represent the link between two different nodes.

Author Statistics

The results of the analysis showed that there were many researchers working in the field of depression over the past 16 years, and 63 of the authors published at least 30 articles related to depression. Table 4 lists the 15 authors with the highest number of articles published. It includes the rank of the number of articles published, author, country, number of articles published in depression-related studies, total number of articles included in Web of Science, total number of citations, average number of citations, and H-index. According to the statistics, seven of the top 15 authors are from USA, three from the Netherlands, one from Canada, one from Australia, one from New Zealand, one from Italy, and one from Germany. From this, it can be seen that these productive authors are from developed countries, thus it can be inferred that developed countries have a better research environment, more advanced research technology and more abundant research funding. The evaluation indicators in the author co-occurrence network are frequency, betweenness centrality and time of first appearance. The higher the frequency, i.e., the higher the number of collaborative publications, the more collaboration, the higher the information dissemination rate, the three authors with the highest frequency in this author co-occurrence network are MAURIZIO FAVA, BRENDA W. J. H. PENNINX, MADHUKAR H. TRIVEDI; the higher the betweenness centrality, i.e., the closer the relationship with other authors, the more collaboration, the higher the information dissemination rate, the three authors with the highest betweenness centrality are the three authors with the highest betweenness centrality are MICHAEL E. THASE, A. JOHN RUSH; the time of first appearance, i.e., the longer the influence generated by the author's research, the higher the information dissemination rate; in addition, the impact factor and citations can also reflect the information dissemination efficiency of the authors.

The top 15 authors in network of co-authorship, 2004–2019.

BC, betweenness centrality; TP, total publications; AP, publications in all areas; DP (%), the ratio of the publications about depression in 2004–2019 to the publications about all areas in all times; TC, total citation; CPP (%), citations per publication .

The timezone view ( Figure 5 ) in the author co-occurrence network clearly shows the updates and interactions of author collaborations, for example. All nodes are positioned in a two-dimensional coordinate with the horizontal axis of time, and according to the time of first posting, the nodes are set in different time zones, and their positions are sequentially upward with the time axis, showing a left-to-right, bottom-up knowledge evolution diagram. The time period 2004–2019 is divided into 16 time zones, one for each year, and each circle in the figure represents an author, and the time zone in which the circle appears is the year when the author first published an article in the data set of this study. The closer the color, the warmer the color, the closer the time, the colder the color, the older the era, the thickness of an annual circle, and the number of articles within the corresponding time division is proportional, the dominant color can reflect the relative concentration of the emergence time, the nodes appear in the annual circle of the red annual circle, that is, on behalf of the hot spot, the frequency of being cited was or is still increasing sharply. Nodes with purple outer circles are nodes with high betweenness centrality. The time zone view demonstrates the growth of author collaboration in the field, and it can be found from the graph that the number of author collaborations increases over time, and the frequency of publications in the author collaboration network is high; observe that the thickness of the warm annual rings in the graph is much greater than the thickness of the cold annual rings, which represents the increase of collaboration in time; there are many authors in all time zones, which indicates that there are many research collaborations and achievements in the field, and the field is in a period of collaborative prosperity. The linkage relationship between the sub-time-periods can be seen by the linkage relationship between the time periods, and it can be found from the figure that there are many linkages in the field in all time periods, which indicates that the author collaboration in the field of depression research is strong.

Timezone view of the author's co-existing network in depression, 2004–2019. The circle represents the author, the time zone in which the circle appears is the year in which the author first published in this study dataset, the radius of the circle represents the frequency of appearance, the color represents the different posting times, the lines represent the connections between authors, and the time zone diagram shows the evolution of author collaboration.

Institutional Statistics

Table 5 lists the top 15 research institutions in network of co-authors' institutions. These include 10 American research institutions, two Netherlands research institutions, one UK research institution, one Canadian research institution and one Australian research institution, all of which, according to the statistics, are from developed countries. Of these influential research institutions, 66.7% are from USA. Figure 6 shows the collaborative network with these influential research institutions as nodes. Kings Coll London (0.2), Univ Michigan (0.17), Univ Toronto (0.15), Stanford Univ (0.14), Univ Penn (0.14), Univ Pittsburgh (0.14), Univ Melbourne (0.12), Virginia Commonwealth Univ (0.12), Columbia Univ (0.1), Duke Univ (0.1), Massachusetts Gen Hosp (0.1), Vrije Univ Amsterdam (0.1), with betweenness centrality >0.1. Kings Coll London has a central place in this collaborative network and is influential in the field of depression research. Table 6 lists the 15 institutions with the strong burst strength. The top 3 institutions are all from USA. Univ Copenhagen, Univ Illinois, Harvard Med Sch, Boston Univ, Univ Adelaide, Heidelberg Univ, Univ New South Wales, and Icahn Sch Med Mt Sinai have had strong burst strength in recent years. It suggests that these institutions may have made a greater contribution to the field of depression over the course of this year and more attention could be paid to their research.

The top 15 institutions in network of co-authors' institutions, 2004–2019.

TP, total publications; BC, betweenness centrality .

Prominent institutions involved in depression, 2004–2019. The betweenness centrality of a node in the network measures the importance of the position of the node in the network. Two types of nodes may have high betweenness centrality scores: (1) Nodes that are highly connected to other nodes, (2) Nodes are positioned between different groups of nodes. The lines represent the link between two different nodes.

The top 15 institutions with the strongest citation bursts, 2004–2019.

Burst denote the citation burst strength; blue thin lines denote the whole period of 2004962019, which provide a useful means to trace the development of research focus; the location and length of red thick lines denote the start and end time during the whole period of the bursts and how long the burst lasts .

Summing up the above analysis, it can be seen that the research institutions in USA are at the center of the depression research field, are at the top of the world in terms of quantity and quality of research, and are showing continuous growth in vitality. Research institutions in USA, as pioneers among all research institutions, lead and drive the development of depression research and play an important role in cutting-edge research in the field of depression.

Article Citations

Table 7 lists the 16 articles that have been cited more than 1,000 times within the statistical range of this paper from 2004 to 2019. As can be seen from the table, the most cited article was written by Dowlati et al. from Canada and published in BIOLOGICAL PSYCHIATRY 2010, which was cited 2,556 times. In addition, 11 of these 16 highly cited articles were from the USA. Notably, two articles by Kroenke, K as first author appear in this list, ranked 7th and 11th, respectively. In addition, there are three articles from Canada, one article from Switzerland, and one article from the UK. And interestingly, all of these countries are developed countries. It can be reflected that developed countries have ample research experience and high quality of research in the field of depression research. On the other hand, it also reflects that depression is a key concern in developed countries. These highly cited articles provide useful information to many researchers and are of high academic and exploratory value.

The top 15 frequency cited articles, 2004–2019.

TP, total publications (citations) .

Research Hotspots Ang Frontiers

Keyword analysis.

The keyword analysis of depression yielded the 25 most frequent keywords in Table 8 and the keyword co-occurrence network in Figure 7 . Also, the data from this study were detected by burst, the 25 keywords with the strongest burst strength were obtained in Table 9 . These results bring out the popular and cutting-edge research directions in the field clearly.

Top 25 frequent keywords in the period of 2004–2019.

Count, number of times the article has been cited; BC, betweenness centrality .

Keyword co-occurrence network in depression, 2004–2019.

Top 25 keywords with strongest citation bursts in the period of 2004–2019.

Burst denote the citation burst strength; blue thin lines denote the whole period of 2004–2019, which provide a useful means to trace the development of research focus; the location and length of red thick lines denote the start and end time during the whole period of the bursts and how long the burst lasts .

The articles on depression during 2004–2019 were analyzed in 1-year time slices, and the top 25 keywords with the highest frequency of occurrence were selected from each slice to obtain the keyword network shown in Table 8 . The top 25 keywords with the highest frequencies were: symptom, disorder, major depression, prevalence, meta-analysis, anxiety, risk, scale, association, quality of life, health, risk factor, stress, validity, validation, mental health, women, double blind, brain, population, disease, impact, primary care, mood, and efficacy. High-frequency nodes respond to popular keywords and are an important basis for the field of depression research.

Figure 7 shows the co-occurrence network mapping of keywords regarding depression research. Each circle in the figure is a node representing a keyword, and the greater the betweenness centrality, the more critical the position of the node in the network. The top 10 keywords in terms of betweenness centrality are: symptom (0.6), major depression (0.28), prevalence (0.27), disorder (0.25), double blind (0.18), risk factor (0.12), stress (0.11), children (0.1), schizophrenia (0.1), and expression (0.1). Nodes with high betweenness centrality reflect that the keyword forms a co-occurrence relationship with multiple other keywords in the domain. A higher betweenness centrality indicates that it is more related to other keywords, and therefore, the node plays an important role in the study. Relatively speaking, these nodes represent the main research directions in the field of depression; they are also the key research directions in this period, and to a certain extent, represent the research hotspots in this period.

Burst detection was performed on the keywords, and the 25 keywords with the strongest strength were extracted, as shown in Table 9 . These keywords contain: fluoxetine, community, follow up, illness, psychiatric disorder, dementia, trial, placebo, disability, serotonin reuptake inhibitor, myocardial infarction, hospital anxiety, antidepressant treatment, late life depression, United States, epidemiology, major depression, model, severity, adolescent, people, prefrontal cortex, management, meta-analysis, and expression. The keywords that burst earlier include fluoxetine (2004), community (2004), follow up (2004), illness (2004), and psychiatric disorder (2004), are keywords that imply that researchers focused on themes early in the field of depression. As researchers continue to explore, the study of depression is changing day by day, and the keywords that have burst in recent years are people (2015), prefrontal cortex (2016), management (2016), meta-analysis (2017), and expression (2017). Reflecting the fact that depression research in recent years has mainly focused on human subjects, the focus has been on the characterization of populations with depression onset. The relationship between depression and the brain has aroused the curiosity of researchers, what exactly are the causes that trigger depression and what are the effects of depression for the manifestation of depression have caused a wide range of discussions in the research community, and the topics related to it have become the most popular studies and have been the focus of research in recent years. All of these research areas showed considerable growth, indicating that research into this area is gaining traction, suggesting that it is becoming a future research priority. The keywords with the strongest burst strength are fluoxetine (111.2), community (110.08), antidepressant treatment (94.28), severity (88.35), meta-analysis (86.42), people (85.33), and follow up (84.46). The rapid growth of research based on these keywords indicates that these topics are the most promising and interesting. The keywords that has been around the longest burst are follow up (2004–2013), model (2013–2019), hospital anxiety (2008–2013), severity (2014–2019), and psychiatric disorder (2004–2008), researchers have invested a lot of research time in these research directions, making many research results, and responding to the exploratory value and significance of research on these topics. At the same time, the longer duration of burst also proves that these research directions have research potential and important value.

Research Hotspots

Hotspots must mainly have the characteristics of high frequency, high betweenness centrality, strong burst, and time of emergence can be used as secondary evaluation indicators. The higher the number of occurrences, the higher the degree of popularity and attention. The higher betweenness centrality means the greater the influence and the higher the importance. Nodes with strong burst usually represent key shift nodes and need to be focused on. The time can be dynamically adjusted according to the target time horizon of the analysis. Thus, based on the results of statistical analysis, it is clear that the research hotspots in the field of depression can be divided into four main areas: etiology (external factors, internal factors), impact (quality of life, disease symptoms, co-morbid symptoms), treatment (interventions, drug development, care modalities), and assessment (population, size, symptoms, duration of disease, morbidity, mortality, effectiveness).

Risk factors for depression include a family history of depression, early life abuse and neglect, and female sexuality and recent life stressors. Physical illnesses also increase the risk of depression, particularly increasing the prevalence associated with metabolic (e.g., cardiovascular disease) and autoimmune disorders.

Research on the etiology of depression can be divided into internal and external factors. In recent years, researchers have increasingly focused on the impact of external factors on depression. Depression is influenced by environmental factors related to social issues, such as childhood experiences, social interactions, and lifestyles. Adverse childhood experiences are risk factors for depression and anxiety in adolescence ( 37 ) and are a common pathway to depression in adults ( 38 ). Poor interpersonal relationships with classmates, family, teachers, and friends increase the prevalence of depression in adolescents ( 39 ). Related studies assessed three important, specific indicators of the self-esteem domain: social confidence, academic ability, and appearance ( 40 ). The results suggest that these three dimensions of self-esteem are key risk factors for increased depressive symptoms in Chinese adolescents. The vulnerability model ( 41 ) suggests that low self-esteem is a causal risk factor for depression, and low self-esteem is thought to be one of the main causes of the onset and progression of depression, with individuals who exhibit low self-esteem being more likely to develop social anxiety and social withdrawal, and thus having a sense of isolation ( 42 ), which in turn leads to subsequent depression. Loneliness predicts depression in adolescents. Individuals with high levels of loneliness experience more stress and tension from psychological and physical sources in their daily lives, which, combined with insufficient care from society, can lead to depression ( 43 ). A mechanism of association exists between life events and mood disorders, with negative life events being directly associated with depressive symptoms ( 44 ). In a cross-sectional study conducted in Shanghai, the prevalence of depression was higher among people who worked longer hours, and daily lifestyle greatly influenced the prevalence of depression ( 45 ). A number of studies in recent years have presented a number of interesting ideas, and they suggest that depression is related to different environmental factors, such as temperature, sunlight hours, and air pollution. Environmental factors have been associated with suicidal behavior. Traffic noise is a variable that triggers depression and is associated with personality disorders such as depression ( 46 ). The harmful effects of air pollution on mental health, inhalation of air pollutants can trigger neuroinflammation and oxidative stress and induce dopaminergic neurotoxicity. A study showed that depression was associated with an increase in ambient fine particulate matter (PM2.5) ( 47 ).

Increased inflammation is a feature of many diseases and even systemic disorders, such as some autoimmune diseases [e.g., type 1 diabetes ( 48 ) or rheumatoid arthritis ( 49 )] and infectious diseases [e.g., hepatitis and sepsis ( 50 )], are associated with an inflammatory response and have been found to increase the risk of depression. A growing body of evidence supports a bidirectional association between depression and inflammatory processes, with stressors and pathogens leading to excessive or prolonged inflammatory responses when combined with predisposing factors (e.g., childhood adversity and modifying factors such as obesity). The resulting illnesses (e.g., pain, sleep disorders), depressive symptoms, and negative health (e.g., poor diet, sedentary lifestyle) may act as mediating pathways leading to inflammation and depression. In terms of mechanistic pathways, cytokines induce depression by affecting different mood-related processes. Elevated inflammatory signals can dysregulate the metabolism of neurotransmitters, damaging neurons, and thus altering neural activity in the brain. In addition cytokines can modulate depression by regulating hormone levels. Inflammation can have different effects on different populations depending on individual physiology, and even lower levels of inflammation may have a depressive effect on vulnerable individuals. This may be due to lower parasympathetic activity, poorer sensitivity to glucocorticoid inhibitory feedback, a greater response to social threat in the anterior oral cortex or amygdala and a smaller hippocampus. Indeed, these are all factors associated with major depression that can affect the sensitivity to the inhibitory consequences of inflammatory stimuli.

Depression triggers many somatization symptoms, which can manifest as insomnia, menopausal syndrome, cardiovascular problems, pain, and other somatic symptoms. There is a link between sleep deprivation and depression, with insomnia being a trigger and maintenance of depression, and more severe insomnia and chronic symptoms predicting more severe depression. Major depression is considered to be an independent risk factor for the development of coronary heart disease and a predictor of cardiovascular events ( 51 ). Patients with depression are extremely sensitive to pain and have increased pain perception ( 52 ) and is associated with an increased risk of suicide ( 53 , 54 ), and generally the symptoms of these pains are not relieved by medication.

Studies have shown that depression triggers an inflammatory response, promoting an increase in cytokines in response to stressors vs. pathogens. For example, mild depressive symptoms have been associated with an amplified and prolonged inflammatory response ( 55 , 56 ) following influenza vaccination in older adults and pregnant women. Among women who have recently given birth, those with a lifetime history of major depression have greater increases in both serum IL-6 and soluble IL-6 receptors after delivery than women without a history of depression ( 57 ). Pro-inflammatory agents, such as interferon-alpha (IFN-alpha), for specific somatization disorders [e.g., hepatitis C or malignant melanoma ( 58 , 59 )], although effective for somatic disorders, pro-inflammatory therapy often leads to psychiatric side effects. Up to 80% of patients treated with IFN-α have been reported to suffer from mild to moderate depressive symptoms.

Clinical trials have shown better antidepressant treatment with anti-inflammatory drugs compared to placebo, either as monotherapy ( 60 , 61 ) or as an add-on treatment ( 62 – 65 ) to antidepressants ( 66 , 67 ). However, findings like whether NSAIDs can be safely used in combination with antidepressants are controversial. Patients with depression often suffer from somatic co-morbidities, which must be included in the benefit/risk assessment. It is important to consider the type of medication, duration of treatment, and dose, and always balance the potential treatment effect with the risk of adverse events in individual patients. Depression, childhood adversity, stressors, and diet all affect the gut microbiota and promote gut permeability, another pathway that enhances the inflammatory response, and effective depression treatment may have profound effects on mood, inflammation, and health. Early in life gut flora colonization is associated with hypothalamic-pituitary-adrenal (HPA) axis activation and affects the enteric nervous system, which is associated with the risk of major depression, gut flora dysbiosis leads to the onset of TLR4-mediated inflammatory responses, and pro-inflammatory factors are closely associated with depression. Clinical studies have shown that in the gut flora of depressed patients, pro-inflammatory bacteria such as Enterobacteriaceae and Desulfovibrio are enriched, while short-chain fatty acid producing bacteria are reduced, and some of these bacterial taxa may transmit peripheral inflammation into the brain via the brain-gut axis ( 68 ). In addition, gut flora can affect the immune system by modulating neurotransmitters (5-hydroxytryptamine, gamma-aminobutyric acid, norepinephrine, etc.), which in turn can influence the development of depression ( 69 ). Therefore, antidepressant drugs targeting gut flora are a future research direction, and diet can have a significant impact on mood by regulating gut flora.

As the molecular basis of clinical depression remains unclear, and treatments and therapeutic effects are limited and associated with side effects, researchers have worked to discover new treatment modalities for depression. High-amplitude low-frequency musical impulse stimulation as an additional treatment modality seems to produce beneficial effects ( 70 ). Studies have found electroconvulsive therapy to be one of the most effective antidepressant treatment therapies ( 71 ). Physical exercise can promote molecular changes that lead to a shift from a chronic pro-inflammatory to an anti-inflammatory state in the peripheral and central nervous system ( 72 ). Aromatherapy is widely used in the treatment of central nervous system disorders ( 73 ). By activating the parasympathetic nervous system, qigong can be effective in reducing depression ( 74 ). The exploration of these new treatment modalities provides more reference options for the treatment of depression.

Large-scale assessments of depression have found that the probability of developing depression varies across populations. Depression affects some specific populations more significantly, for example: adolescents, mothers, and older adults. Depression is one of the disorders that predispose to adolescence, and depression is associated with an increased risk of suicide among college students ( 75 ). Many women develop depression after childbirth. Depression that develops after childbirth is one of the most common complications for women in the postpartum period ( 76 ). The health of children born to mothers who suffer from postpartum depression can also be adversely affected ( 77 ). Depression can cause many symptoms within the central nervous system, especially in the elderly population ( 78 ).

Furthermore, one of the most consistent findings of the association between inflammation and depression is the elevated levels of peripheral pro-inflammatory markers in depressed individuals, and peripheral pro-inflammatory marker levels can also be used as a basis for the assessment of depressed patients. Studies have shown that the following pro-inflammatory markers have been found to be at increased levels in depressed individuals: CRP ( 79 , 80 ), IL-6 ( 22 , 79 , 81 , 82 ), TNF–α, and interleukin-1 receptor antagonist (IL-1ra) ( 79 , 82 ), however, this association is not unidirectional and the subsequent development of depression also increases pro-inflammatory markers ( 82 , 83 ). These biomarkers are of great interest, and depressed patients with increased inflammatory markers may represent a relatively drug-resistant population.

Frontier Analysis

The exploration and analysis of frontier areas of depression were based on the results of the analysis of the previous section on keywords. According to the evaluation index and analysis idea of this study, the frontier research topics need to have the following four characteristics: low to medium frequency, strong burst, high betweenness centrality, and the research direction in recent years. Therefore, combining the results of keyword analysis and these characteristics, it can be found that the frontier research on depression also becomes clear.

Research on Depression Characterized by Psychosexual Disorders

Exploration of biological mechanisms based on depression-associated neurological disorders and analysis of depression from a neurological perspective have always been the focus of research. Activation of neuroinflammatory pathways may contribute to the development of depression ( 84 ). A research model based on the microbial-gut-brain axis facilitates the neurobiology of depression ( 85 ). Some probiotics positively affect the central nervous system due to modulation of neuroinflammation and thus may be able to modulate depression ( 86 ). The combination of environmental issues and the neurobiological study of depression opens new research directions ( 46 ).

Research on Relevant Models of Depression

How to develop a model that meets the purpose of the study determines the outcome of the study and has become the direction that researchers have been exploring in recent years. Martínez et al. ( 87 ) developed a predictive model to assess factors that modify the treatment pathway for postpartum depression. Nie et al. ( 88 ) extended the work on predictive modeling of treatment-resistant depression to establish a predictive model for treatment-resistant depression. Rational modeling methods and behavioral testing facilitate a more comprehensive exploration of depression, with richer studies and more scientifically valid findings.

Research and Characterization of the Depressed Patient Population

Current research on special groups and depression has received much attention. In a study of a group of children, 4% were found to suffer from depression ( 89 ). The diagnosis and treatment of mental health disorders is an important component of pediatric care. Second, some studies of populations with distinct characteristics have been based primarily on female populations. Maternal perinatal depression is also a common mental disorder with a prevalence of over 10% ( 90 ). In addition, geriatric depression is a chronic and specific disorder ( 91 ). Studies based on these populations highlight the characteristics of the disorder more directly than large-scale population explorations and are useful for conducting extended explorations from specific to generalized.

Somatic Comorbidities Associated With Depression

Depression often accompanies the onset and development of many other disorders, making the study of physical comorbidities associated with depression a new landing place for depression research. Depression is a complication of many neurological or psychopathological disorders. Depression is a common co-morbidity of glioblastoma multiforme ( 92 ). Depression is an important disorder associated with stroke ( 93 ). Chronic liver disease is associated with depression ( 94 ). The link between depressive and anxiety states and cancer has been well-documented ( 95 ). In conclusion, depression is associated with an increased risk of lung, oral, prostate, and skin cancers, an increased risk of cancer-specific death from lung, bladder, breast, colorectal, hematopoietic system, kidney, and prostate cancers, and an increased risk of all-cause mortality in lung cancer patients. The early detection and effective intervention of depression and its complications has public health and clinical implications.

Research on Mechanisms of Depression

Research based on the mechanisms of depression includes the study of disease pathogenesis, the study of drug action mechanisms, and the study of disease treatment mechanisms. Research on the pathogenesis of depression has focused more on the study of the hypothalamic-pituitary-adrenal axis. Social pressure can change the hypothalamic-pituitary-adrenal axis ( 96 ). Studies on the mechanism of action of drugs are mostly based on their effects on the central nervous system. The antidepressant effects of Tanshinone IIA are mediated by the ERK-CREB-BDNF pathway in the hippocampus of mice ( 97 ). Research on the mechanisms of depression treatment has also centered on the central nervous system. It has been shown that the vagus nerve can transmit signals to the brain that can lead to a reduction in depressive behavior ( 98 ).

In this study, based on the 2004–2019 time period, this wealth of data is effectively integrated through data analysis and processing to reproduce the research process in a particular field and to co-present global trends in homogenous fields while organizing past research.

Journals that have made outstanding contributions in this field include ARCH GEN PSYCHIAT, J AFFECT DISORDERS and AM J PSYCHIAT. PSYCHIATRY, NEUROSCIENCES & NEUROLOGY and CLINICAL NEUROLOGY are the three most popular categories. The three researchers with the highest number of articles were MAURIZIO FAVA (USA), BRENDA W. J. H. PENNINX (NETHERLANDS) and MADHUKAR H TRIVEDI (USA). Univ Pittsburgh (USA), Kings Coll London (UK) and Harvard Univ (USA) are three of the most productive and influential research institutions. A Meta-Analysis of Cytokines in Major Depression, Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice and Deep brain stimulation for treatment-resistant depression are key articles. Through keyword analysis, a distribution network centered on depression was formed. Although there are good trends in the research on depression, there are still many directions to be explored in depth. Some recommendations regarding depression are as follows.

(1) The prevention of depression can be considered by focusing on treating external factors and guiding the individual.

Faced with the rising incidence of depression worldwide and the difficulty of treating depression, researchers can think more about how to prevent the occurrence of depression. Depressed moods are often the result of stress, not only social pressures on the individual, but also environmental pressures in the developmental process, which in turn have an unhealthy relationship with the body and increase the likelihood of depression. The correlation between external factors and depression is less well-studied, but the control of external factors may be more effective in the short term than in the long term, and may be guided by self-adjustment to avoid major depressive disorder.

(2) The measurement and evaluation of the degree of depression should be developed in the direction of precision.

In the course of research, it has been found that the Depression Rating Scale is mostly used for the detection and evaluation of depression. This kind of assessment is more objective, but it still lacks accuracy, and the research on measurement techniques and methods is less, which is still at a low stage. Patients with depression usually have a variety of causes, conditions, and duration of illness that determine the degree of depression. Therefore, whether these scales can truly accurately measure depression in depressed patients needs further consideration. Accurate measurement is an important basis for evidence-based treatment of depression, and thus how to achieve accurate measurement of depression is a research direction that researchers can move toward.

Therefore, there is an urgent need for further research to address these issues.

A systematic analysis of research in the field of depression in this study concludes that the distribution of countries, journals, categories, authors, institutions, and citations may help researchers and research institutions to establish closer collaboration, develop appropriate publication plans, grasp research hotspots, identify valuable research ideas, understand current emerging research, and determine research directions. In addition, there are still some limitations that can be overcome in future work. First, due to the lack of author and address information in older published articles, it may not be possible to accurately calculate their collaboration; second, although the data scope of this paper is limited to the Web of Science, it can adequately meet our objectives.

Data Availability Statement

Author contributions.

HW conceived and designed the analysis, collected the data, performed the analysis, and wrote the paper. XT, XW, and YW conceived and designed the analysis. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China under Grant No. 81973495.

Conflict of Interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher's Note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

What are 7 signs of ‘high-functioning’ depression? A viral video explains.

High-functioning depression isn’t a clinical diagnosis, but the phrase can reflect a wide range of symptoms caused by depression.

Mental health counselor Jeffrey Meltzer sees clients nearly every day who suffer from “high-functioning” depression, so he decided to post a video about it on TikTok. He struck a nerve. The video now has more than 8 million views and more than 5,000 comments.

“This describes me to a tee,” one wrote.

“Does it go away at some point?” another replied.

“Can someone tell me how to fix it?” wrote a third.

@therapytothepoint 7 Signs of High Functioning Depression. #highfunctioningdepression #depressionawareness #depresedtiktok #feelinglow #depressed #functionaldepression #fyp #foryou #foryoupage ♬ Sad piano ballad (BGM / sad)(936782) - TrickSTAR MUSIC

Meltzer, who meets with clients in-person and virtually in Bradenton, Fla., said it’s not always obvious if someone suffers from depression. “There’s a myth” that somebody with depression can barely get out of bed in the morning, he said. “They can function, they can go to work, they can do all these things. But deep inside, they’re feeling really down, they’re feeling quite empty or lonely.”

The response to Meltzer’s video is “a huge signal about unmet mental health need,” said Jon Rottenberg , a psychology professor at the University of South Florida who has studied the course and prognosis of depression.

The term high-functioning depression “is really resonating with the fact that depression can be quite hidden,” Rottenberg said. “People can harbor it for a long time before they get help.”

High-functioning depression is not a clinical diagnosis

High-functioning depression is not a diagnosis or a recognized clinical disorder, and it doesn’t appear in the Diagnostic and Statistical Manual of Mental Disorders, the authoritative guide to mental health disorders.

Exactly where the term started isn’t clear, but “high-functioning depression” is a popular topic on TikTok and YouTube that attracts millions of viewers. It gained traction on social media in 2022 after Cheslie Kryst, a former Miss USA , died by suicide. In statements to the media, Kryst’s mother said her daughter was dealing with high-functioning depression, “which she hid from everyone.”

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Some health professionals say the term can be misleading and may stem from a lack of understanding about different mental health disorders. But other therapists and mental health experts say the term has helped people realize that depression isn’t always obvious.

It can help people think of depression in ways that “may be different” from the stereotypical symptoms people associate with the disorder, said Vaile Wright, a psychologist and senior director of health-care innovation for the American Psychological Association.

“There is no one-size-fits-all depression,” Wright said. “In children and adolescents, it looks much more like irritability. Same with men; it looks a lot more like anger and substance abuse.”

Signs of high-functioning depression

In the viral TikTok video, Meltzer offers seven signs that he said may signal high-functioning depression. Other mental health experts say Meltzer’s video does identify many of the feelings that could be symptoms for depression.

“The doctors that I work with and others, even myself sometimes, can feel those things,” said Srijan Sen , a professor and the executive director of the University of Michigan’s Eisenberg Family Depression Center. “Highlighting that and making people know they’re not alone in feeling that is valuable.”

The seven signs of high-functioning depression highlighted in Meltzer’s video include:

• Isolating from friends and family.
• No longer finding joy in the activities you loved.
• Persistently criticizing yourself.
• Frustration with small irritations or setbacks.
• Turning to mindless habits for hours on end.
• Always feeling low on energy.
• Managing day-to-day tasks but feeling empty inside.

Getting help from professionals

Depression is “a collection of symptoms” with some degree of sadness or melancholy, said the APA’s Wright. Sleeping too much or too little, an inability to concentrate, eating too much or too little, and “a sense of hopelessness” can all be signs of depression.

Pankhuri Aggarwal, the Madigan Family Clinical Research Fellow at the Family Institute at Northwestern University, said she doesn’t want people to self-diagnose based on a list of signs or symptoms they find online. “It’s really important for them to come and talk to a mental health professional,” she said.

She noted that there are two criteria that are “considered the crux of depression.” Either you’re feeling low — or “blue” — or you’re not finding joy from activities you once considered fun.

“If you used to enjoy swimming before, a whole lot, now you still go swimming, but you just don’t find the same level of pleasure that you used to once before,” Aggarwal said. “You keep doing the same activity. It just doesn’t bring you the same level of excitement, energy, that it used to.”

Aggarwal said the term high-functioning depression refers to people who feel depressed but who aren’t displaying signs to friends or family — they may be fighting to suppress their depression because “they don’t want to place this burden on other people.”

“Maybe it’s not safe for you to express depression in the setting, or the community or the group that you’re in,” she said. “You can’t necessarily go walk up to your boss and say you’re depressed.”

A term of ‘hope’ when talking about depression

Isabella, a 25-year-old graduate student who was diagnosed with depression a decade ago, said she first heard of high-functioning depression in high school while watching videos on YouTube. Now, she uses the term to explain her diagnosis to friends and therapists. She asked that her full name not be used to protect her medical privacy.

The term provides a sense of comfort “that this is something that I can get through,” Isabella said. “I can do this, and I can be successful.”

“The whole aspect of being high-functioning, it gave me a lot of hope,” she said. “I can be this normal person who goes through their life, and has their successes, and the depression is, kind of, the afterthought.”

Sen said he recommends people seek help from a clinician when stress, depression and anxiety start to affect daily life. Wright said, “for most people,” that’s going to start with their primary care physician.

Social media videos can be useful to help people recognize their symptoms and realize that depression “isn’t just one thing,” Rottenberg said. Self-diagnosis through watching videos on TikTok could be “an important first step” to seeking professional help, he said.

“Two different people can have depression, and they can look very different,” Rottenberg said. “From the person who’s flat on their back to the person who can report to work and put out a first-rate product, they’re both depressed. They’re both struggling.”

If you or someone you know needs help, visit 988lifeline.org or call or text the Suicide and Crisis Lifeline at 988.

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Role of Brain-Derived Neurotrophic Factor in Anxiety or Depression After Percutaneous Coronary Intervention

• Published: 10 November 2023

Cite this article

• Bo Ning 1 ,
• Teng Ge 1 ,
• Yongqing Wu 1 ,
• Yuting Wang 1 , 2 &
• Mingjun Zhao   ORCID: orcid.org/0009-0002-3601-7544 1 , 2 , 3  

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Anxiety or depression after percutaneous coronary intervention (PCI) is one of the key clinical problems in cardiology that need to be solved urgently. Brain-derived neurotrophic factor (BDNF) may be a potential biomarker for the pathogenesis and treatment of anxiety or depression after PCI. This article reviews the correlation between BDNF and cardiovascular system and nervous system from the aspects of synthesis, release and action site of BDNF, and focuses on the latest research progress of the mechanism of BDNF in anxiety or depression after PCI. It includes the specific mechanisms by which BDNF regulates the levels of inflammatory factors, reduces oxidative stress damage, and mediates multiple signaling pathways. In addition, this review summarizes the therapeutic potential of BDNF as a potential biomarker for anxiety or depression after PCI.

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The role of neurotrophins in psychopathology and cardiovascular diseases: psychosomatic connections

Andrea László, Lilla Lénárt, … János Nemcsik

Study of Anxiety/Depression in Patients with Coronary Heart Disease After Percutaneous Coronary Intervention

PeiYing Zhang

Additive clinical value of serum brain-derived neurotrophic factor for prediction of chronic heart failure outcome

Shinpei Kadowaki, Tetsuro Shishido, … Isao Kubota

Data Availability

Not applicable.

Abbreviations

Percutaneous coronary intervention

Coronary atherosclerotic heart disease

Acute myocardial infarction

Brain-derived neurotrophic factor

Precursor BDNF

Tyrosine kinase receptor B

p75 neurotrophin receptor

Mitogen-Activated Protein Kinase

Phosphatidylinositol 3-Kinase

Nuclear Factor- κ B

Protein kinase A

High-sensitivity C-reactive protein

Long pentraxin 3

Acute coronary syndrome

Tumor necrosis factor- α

Malondialdehyde

Glutathione

Superoxide dismutase 1

Cytoplasmic glutathione peroxidase

Nicotinamide Adenine Dinucleotide Phosphate Oxidase-2

Reactive oxygen species

cAMP-response element binding protein

chronic unpredictable mild stress

High-Frequency Repetitive Transcranial Magnetic Stimulation

Forkhead box transcription factor G1

Estrogen receptor α

Coronary artery disease

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This work was supported by the study of Key Scientific research Program of Education Department of Shaanxi Province (Shaanxi, China, Program No. 22JS005), Shaanxi Provincial Academician Workstation Construction Project (Shaanxi, China, Program No. 2019-49-03), and Construction project of famous Traditional Chinese Medicine Inheritance Studio in Shaanxi Province (Shaanxi, China, Program No. 2019007).

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Bo Ning and Teng Ge contributed equally to the research.

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First Clinical Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, China

Bo Ning, Teng Ge, Yongqing Wu, Yuting Wang & Mingjun Zhao

Affiliated Hospital, Shaanxi University of Chinese Medicine, Xianyang, 712046, China

Yuting Wang & Mingjun Zhao

Shaanxi Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Cardiovascular Diseases, Xianyang, 712046, China

Mingjun Zhao

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M.J. contributed to organizing this review and revising its content. B.N. and T.G. was responsible for writing the manuscript and figure design. Y.W. and Y.W. provided some valuable advice for this review. All authors have read and agreed to the published version of the manuscript.

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Ning, B., Ge, T., Wu, Y. et al. Role of Brain-Derived Neurotrophic Factor in Anxiety or Depression After Percutaneous Coronary Intervention. Mol Neurobiol (2023). https://doi.org/10.1007/s12035-023-03758-1

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    By the authority vested in me as President by the Constitution and the laws of the United States of America, it is hereby ordered as follows:

     Section 1.  Policy.  My Administration is committed to getting women the answers they need about their health.  For far too long, scientific and biomedical research excluded women and undervalued the study of women’s health.  The resulting research gaps mean that we know far too little about women’s health across women’s lifespans, and those gaps are even more prominent for women of color, older women, and women with disabilities.  

     The notion of including women in clinical trials used to be revolutionary — which means many diagnostics and treatments were developed without women in mind and thus failed to account for women’s health.  Over 30 years ago, the Congress passed the landmark National Institutes of Health Revitalization Act of 1993 (Public Law 103-43) to direct the National Institutes of Health (NIH), the largest public funder of biomedical research in the world, to include women and people of color in NIH-funded clinical research.  In 2016, the Congress built on these requirements in the 21st Century Cures Act (Public Law 114-255), which directed the NIH to further its pursuit of women’s health research, including by strengthening clinical trial inclusion and data analysis, developing research and data standards to advance the study of women’s health, and improving NIH-wide coordination on women’s health research.

     These policies led to significant increases in women’s participation in clinical trials, and ongoing investments in biomedical research have supported breakthroughs in women’s health.  Through the discovery of genetic factors that increase the risk of breast cancer and innovations in mammography, we have transformed our approach to prevention, early detection, and treatment, and have improved outcomes for women facing a breast cancer diagnosis.  We have improved access to life-saving treatments for women with severe heart failure by ensuring that the devices they need are the right size for a woman’s body.  We have also identified some of the most characteristic symptoms of heart attack in women, which are different from those in men — discoveries that have helped deliver faster treatment to women when every second counts.  This is what we can achieve when we invest in women’s health research.

     It is time, once again, to pioneer the next generation of discoveries in women’s health.  My Administration seeks to fundamentally change how we approach and fund women’s health research in the United States.  That is why I established the first-ever White House Initiative on Women’s Health Research (Initiative) — which is within the Office of the First Lady and includes a wide array of executive departments and agencies (agencies) and White House offices — to accelerate research that will provide the tools we need to prevent, diagnose, and treat conditions that affect women uniquely, disproportionately, or differently.

     Together with the First Lady’s tireless efforts, the Initiative is already galvanizing the Federal Government to advance women’s health, including through investments in innovation and improved coordination within and across agencies.  We are also mobilizing leaders across a wide range of sectors, including industry, philanthropy, and the medical and research communities, to improve women’s health.

     It is the policy of my Administration to advance women’s health research, close health disparities, and ensure that the gains we make in research laboratories are translated into real-world clinical benefits for women.  It is also the policy of my Administration to ensure that women have access to high-quality, evidence-based health care and to improve health outcomes for women across their lifespans and throughout the country.

     I will continue to call on the Congress to provide the transformative investments necessary to help our researchers and scientists answer today’s most pressing questions related to women’s health.  Investing in innovation in women’s health is an investment in the future of American families and the economy.  At the same time, agencies must use their existing authorities to advance and integrate women’s health across the Federal research portfolio, close research gaps, and make investments that maximize our ability to prevent, diagnose, and treat health conditions in women. 

     Sec. 2.  Definitions.  For purposes of this order:

     (a)  The term “women’s health research” means research aimed at expanding knowledge of women’s health across their lifespans, which includes the study and analysis of conditions specific to women, conditions that disproportionately impact women, and conditions that affect women differently.

     (b)  The term “White House Initiative on Women’s Health Research” means the interagency, advisory body established by the Presidential Memorandum of November 13, 2023 (White House Initiative on Women’s Health Research), to advance women’s health research.

     (c)  The term “agency Members of the Initiative” refers to the Secretary of Defense, the Secretary of Agriculture, the Secretary of Health and Human Services, the Secretary of Veterans Affairs, the Administrator of the Environmental Protection Agency, and the Director of the National Science Foundation.

     Sec. 3.  Further Integrating Women’s Health Research in Federal Research Programs.  (a)  Building on research and data standards issued by the NIH in 2016, agency Members of the Initiative shall consider actions to develop or strengthen research and data standards that enhance the study of women’s health across all relevant, federally funded research and other Federal funding opportunities.  Agency Members of the Initiative shall consider issuing new guidance, application materials, reporting requirements, and research dissemination strategies to advance the study of women’s health, including to:

(i)    require applicants for Federal research funding, as appropriate, to explain how their proposed study designs will consider and advance our knowledge of women’s health, including through the adoption of standard application language;

(ii)   consider women’s health, as appropriate, during the evaluation of research proposals that address medical conditions that may affect women differently or disproportionately;

(iii)  improve accountability for grant recipients, including, as appropriate, by requiring regular reporting on their implementation of, and compliance with, research and data standards related to women’s health, including compliance with recruitment milestones; and

(iv)   improve the recruitment, enrollment, and retention of women in clinical trials, including, as appropriate, by reducing barriers through technological and data sciences advances.

(b)  Within 30 days of the date of this order, the Chair of the Initiative and the Director of the NIH Office of Research on Women’s Health, in consultation with the Director of the Office of Management and Budget (OMB), shall establish and co-chair a subgroup of the Initiative to promote interagency alignment and consistency in the development of agency research and data standards to enhance the study of women’s health.

     (c)  Within 90 days of the date of this order, agency Members of the Initiative shall report to the Chair of the Initiative on actions taken to strengthen research and data standards to enhance the study and analysis of women’s health and related conditions.

(d)  Within 180 days of the date of this order and on an annual basis thereafter, agency Members of the Initiative shall report to the President on the status of implementation of research and data standards.

     Sec. 4.  Prioritizing Federal Investments in Women’s Health Research.  (a)  Agency Members of the Initiative shall identify and, as appropriate and consistent with applicable law, prioritize grantmaking and other awards to advance women’s health research, with an emphasis on:

(i)    promoting collaborative, interdisciplinary research across fields and areas of expertise;

(ii)   addressing health disparities and inequities affecting women, including those related to race, ethnicity, age, socioeconomic status, disability, and exposure to environmental factors and contaminants that can directly affect health; and

(iii)  supporting the translation of research advancements into improved health outcomes.

(b)  Agency Members of the Initiative shall take steps to promote the availability of federally funded research and other Federal funding opportunities to advance women’s health, including through the development and inclusion of standard language related to women’s health, as appropriate, in all relevant notices of funding opportunity and through better facilitating potential grant applicants’ access to information about funding opportunities related to women’s health research.

     (c)  To advance innovation, commercialization, and risk mitigation, agency Members of the Initiative shall:

(i)    identify and, as appropriate and consistent with applicable law, seek ways to use innovation funds, challenges, prizes, and other mechanisms to spur innovation in women’s health;

(ii)   invest in innovation to accelerate women’s health research, including through or in collaboration with the Advanced Research Projects Agency for Health and the Congressionally Directed Medical Research Programs;

(iii)  support the role of small businesses and entrepreneurs in advancing innovation in women’s health research, including through Small Business Innovation Research Programs and Small Business Technology Transfer Programs; and

(iv)   invest in translational science to convert research findings and discoveries into treatments and interventions that improve women’s health outcomes and reduce health disparities, including through the Department of Agriculture National Institute of Food and Agriculture research programs.

(d)  In implementing section 8(b) of Executive Order 14110 of October 30, 2023 (Safe, Secure, and Trustworthy Development and Use of Artificial Intelligence), the Secretary of Health and Human Services, in consultation with the Director of the National Science Foundation, shall consider the opportunities for and challenges that affect women’s health research in the responsible deployment and use of artificial intelligence (AI) and AI-enabled technologies in the health and human services sector.

     Sec. 5.  Galvanizing Research on Women’s Midlife Health.  (a)  Within 90 days of the date of this order, to address research gaps in understanding women’s health and diseases and conditions associated with women’s midlife and later years, the Secretary of Health and Human Services shall:

(i)    launch a comprehensive assessment of the current state of the science on menopause to develop an evidence-based research agenda that will guide Federal and private sector investments in menopause-related research;

(ii)   evaluate evidence-based interventions and strategies to improve women’s experiences in the menopausal and perimenopausal periods, including the delivery of treatments for women experiencing menopause in clinical care settings;

(iii)  consider developing new common data elements and survey tools to expand the ethical and equitable collection of data on issues related to women’s midlife health; and

(iv)   develop new comprehensive resources to help ensure that the public has evidence-based information about menopause, including menopause-related research initiatives, findings, and symptom-prevention and treatment options.

(b)  The Secretary of Defense and the Secretary of Veterans Affairs shall evaluate the needs of women service members and veterans related to midlife health and shall develop recommendations to support improved treatment and targeted research of midlife health issues, including menopausal symptoms.

     Sec. 6.  Assessing Unmet Needs to Support Women’s Health Research.  The Director of OMB and the Assistant to the President and Director of the Gender Policy Council (Directors) shall lead an effort, in collaboration with the Initiative, to identify current gaps in Federal funding for women’s health research and shall submit recommendations to the President describing the additional funding and programming necessary to catalyze research on women’s health, including in priority areas within women’s health as identified by the Initiative, as follows:

     (a)  Within 90 days of the date of this order, the Directors shall, in consultation with the Initiative, develop guidance for assessing additional funding that agencies need to close research gaps in women’s health.

     (b)  Within 180 days of the date of this order, Members of the Initiative shall consult the guidance described in subsection (a) of this section and shall each submit a report to the Directors that identifies the funding needed to catalyze research on women’s health.

     (c)  Based on the reports described in subsection (b) of this section, the Directors shall develop and submit recommendations to the President on steps the Federal Government should take to catalyze research on women’s health.  These recommendations shall identify any statutory, regulatory, budgetary, or other changes that may be necessary to ensure that Federal laws, policies, practices, and programs support women’s health research more effectively.

     (d)  Following the submission of the recommendations described in subsection (c) of this section, each Member of the Initiative shall report annually to the Directors on progress made in response to those recommendations and to improve the study of women’s health.  The Director of OMB shall provide a summary of Members’ progress and any new recommendations to the President on an annual basis, consult with each Member on their women’s health research funding needs during the annual budget process, and calculate Federal funding for women’s health research on an annual basis.

     Sec. 7.  General Provisions.  (a)  Nothing in this order shall be construed to impair or otherwise affect: (i)   the authority granted by law to an executive department or agency, or the head thereof; or

(ii)  the functions of the Director of the Office of Management and Budget relating to budgetary, administrative, or legislative proposals.

     (b)  This order shall be implemented consistent with applicable law and subject to the availability of appropriations.

     (c)  This order is not intended to, and does not, create any right or benefit, substantive or procedural, enforceable at law or in equity by any party against the United States, its departments, agencies, or entities, its officers, employees, or agents, or any other person.                                    JOSEPH R. BIDEN JR. THE WHITE HOUSE,     March 18, 2024.

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News Release

Tuesday, March 12, 2024

NIH opens long COVID trials to evaluate treatments for autonomic nervous system dysfunction

Part of NIH’s RECOVER Initiative, trials will test at least three treatments for symptoms such as fast heart rate, dizziness and fatigue.

Two phase 2 clinical trials to test the safety and effectiveness of three treatments for adults with autonomic nervous system dysfunction from long COVID have begun. The autonomic nervous system acts largely unconsciously and regulates bodily functions, such as heart rate, digestion and respiratory rate. Symptoms associated with autonomic nervous system dysfunction have been among those that patients with long COVID say are most burdensome. The trials are part of the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) Initiative, a nationwide research program to fully understand, diagnose and treat long COVID. Other RECOVER phase 2 clinical trials testing treatments to address viral persistence and neurological symptoms, including cognitive dysfunction (like brain fog), launched in July 2023.

“As a long COVID patient, I know firsthand how disruptive and frightening symptoms including rapid heart rate, dizziness and fatigue can be. Patient representatives across RECOVER have also shared that these symptoms are some of the most debilitating symptoms of long COVID,” said Heather Marti, co-chair of the RECOVER National Community Engagement Group. “These trials are giving me and others with long COVID hope that it will restore our health and get us back to the lives we so desire.”

The two trials, collectively known as RECOVER-AUTONOMIC, are testing three potential treatments in adults who, following COVID-19, now have postural orthostatic tachycardia syndrome (POTS). An autonomic nervous system disorder, POTS is characterized by unexpected fast heart rate, dizziness, fatigue or a combination of these symptoms when a person stands up from sitting or lying down. 

“The trials were developed with input from people living with long COVID, caregivers, community representatives, clinicians and scientists all with unique expertise in the field,” said Gary H. Gibbons, M.D., director of the National Heart, Lung, and Blood Institute at the NIH and co-chair of RECOVER. “We are grateful for their collective involvement which significantly shaped the trials and the choice of interventions.”

The trials will initially examine three potential treatments:

• Gamunex-C, a form of intravenous immunoglobulin (IVIG), contains antibodies to help the body protect itself against infection from various diseases and is given by intravenous infusion.
• Ivabradine, an oral medication that reduces heart rate.
• Coordinator-guided, non-drug care, which includes a series of activities managed through weekly phone calls with a care coordinator, such as wearing a compression belt and eating a high-salt diet, which are recommended for patients with POTS to counteract excessive loss of fluids.  

“Patients who develop POTS after having COVID-19 are often severely limited by their symptoms, and there are no proven effective treatments,” said Christopher Granger, M.D., Duke University Medical Center, who is co-leading RECOVER-AUTONOMIC. “These interventions were selected because they have shown potential benefit in treating symptoms for POTS. The theory we’re testing is that they might also help individuals with long COVID.”  

Participants will first be randomly assigned to receive either IVIG, ivabradine or a placebo. Participants will then be randomly assigned a second time to receive either coordinator-guided, non-drug care or what is considered the usual non-drug care for POTS following COVID-19, such as diet and lifestyle recommendations. RECOVER-AUTONOMIC is an adaptive clinical trial, meaning if additional potential interventions emerge, they can quickly be added and studied in the trial.

Researchers plan to enroll 380 total participants at 50 sites across the United States. Teams at the trial sites will recruit participants from their health systems and surrounding communities. The current list of sites for the trials can be found on ClinicalTrials.gov (search: NCT06305793, NCT06305806 and NCT06305780) and additional sites will be added to this list as they begin enrolling participants.

Diversity among the trial participants is a high priority for RECOVER. To support diverse and inclusive representation, study sites are chosen based on geographic location, their connections to communities, and their track records for enrolling diverse research participants.

With the launch of the RECOVER-AUTONOMIC trials, RECOVER is currently testing seven treatments across four clinical trials and continues to enroll participants. Those interested in learning more about RECOVER clinical trials should visit trials.recovercovid.org .

About RECOVER : The National Institutes of Health Researching COVID to Enhance Recovery (NIH RECOVER) Initiative brings together clinicians, scientists, caregivers, patients, and community members to understand, diagnose, and treat long COVID. RECOVER has created one of the largest and most diverse groups of long COVID study participants in the world. In addition, RECOVER clinical trials are testing potential interventions across five symptom focus areas. For more information, please visit recovercovid.org . 

HHS Long COVID Coordination: This work is a part of the National Research Action Plan , a broader government-wide effort in response to the Presidential Memorandum directing the Secretary for the Department of Health and Human Services to mount a full and effective response to long COVID. Led by Assistant Secretary for Health Admiral Rachel Levine, the Plan and its companion Services and Supports for Longer-term Impacts of COVID-19 report lay the groundwork to advance progress in the prevention, diagnosis, treatment, and provision of services for individuals experiencing long COVID.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov .

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February 2024 Clinical Trials

Clinical Trials Activity Update for February 2024

• Posted on 21 Mar 2024

Clinical trials are integral to providing optimal patient care, enhancing medical understanding, and developing new therapeutics as well as improving existing ones. From raising the standard of care for various diseases to laying the foundation of revolutionary medical devices, clinical trials significantly impact the healthcare landscape. As medical challenges turn more complex, clinical trials become increasingly important in addressing the unmet medical needs of a growing patient population, particularly those with chronic and new infectious diseases. 

Let’s explore some significant clinical trial activities of February 2024, poised to transform the healthcare landscape by treating unmet needs of patients.

Launch of PIVOT-006 Trial Offers New Hope for Non-Muscle-Invasive Bladder Cancer (NMIBC) Patients

In February 2024, CG Oncology Inc, a United States-based biotechnology company, announced the launch of the phase 3 PIVOT-006 trial (NCT06111235) to evaluate the efficacy of a novel therapy cretostimogene grenadenorepvec (CG0070) in the management of intermediate-risk non-muscle-invasive  bladder cancer  (NMIBC), following transurethral resection of the bladder tumor (TURBT). This innovative oncolytic immunotherapy might offer a promising treatment option for those with frequent disease recurrence and repetitive surgery. The trial plans to enrol 426 patients across the United States and Canada, with overall recurrence-free survival (RFS) as the primary endpoint. The secondary endpoints of the study are recurrence-free survival at 12 and 24 months, progression-free survival, and the incidence of adverse events. Besides the PIVOT-006 trial, which is expected to reach primary completion in 2028, cretostimogene is involved in other investigative studies focused on different NMIBC populations and combination studies.

According to the data published by the American Cancer Society, it is estimated that around 83,190 new cases of bladder cancer cases will emerge in 2024. Further, it is reported that bladder cancer will be the cause of 16,840 deaths. The rising global burden of this disease is expected to directly impact its treatment market. According to  EMR  calculations, the bladder cancer treatment market size is anticipated to grow at a CAGR of 9.31% during the forecast period of 2024-2032, likely to reach a market value of USD 8.98 billion by 2032.

Expansion of Greenwich LifeSciences’ Flamingo-01 Phase III Trial for Breast Cancer Treatment

On February 14, 2024, Greenwich Lifesciences, Inc., a clinical-stage biopharmaceutical company in the United States, announced the expansion of its Phase III clinical trial, Flamingo-01, which aims to evaluate the efficacy and safety profile of GLSI-100 in HER2/neu positive breast cancer patients. GLSI-100 is a cancer peptide vaccine with a combination of GP2 and GM-CSF, expected to carry therapeutic potential in preventing breast cancer recurrences. Led by Baylor College of Medicine (a medical school and research center in Houston, Texas), the randomized study has around 750 participants and is designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival.

The approval to expand Flamingo-01 in the five European countries including Spain, France, Germany, Italy, and Poland, it enables the activation of 105 sites post-completion of site contracts as well as site initiation visits scheduled as early as March 4, 2024. Moreover, this expansion will allow the trial to recruit up to 150 global sites to advance breast cancer treatment.

India Achieves Major Milestone with Human Clinical Trial of Gene Therapy for Haemophilia A

India made history in the field of medical science by conducting a pioneering human clinical trial of gene therapy for haemophilia A (deficiency in factor VIII or FVIII clotting activity). In this study, a lentiviral vector was utilized to express an FVIII transgene in the patient's haematopoietic stem cells. The trial was held at Christian Medical College (CMC) in Vellore in a collaborative initiative with the Department of Biotechnology, the Centre for Stem Cell Research (a unit of InStem Bengaluru), and Emory University in the United States along with the Christian Medical College.

Patients with haemophilia A are more susceptible to bleeding or experience prolonged bleeding after injury or surgery as they lack a protein required for blood to clot called FVIII. According to the EMR report, the haemophilia A market is likely to attain a value of USD 49.60 billion by 2032 and is anticipated to grow at a CAGR of 22.8% during the forecast period of 2024-2032. There is a growing demand for innovative therapeutic approaches such as gene therapies to treat this life-threatening condition, which is expected to augment gene therapy market growth in the coming years.

Biocomposites Launches Two New Phase II Clinical Trials of STIMULAN VG to Treat Diabetic Foot Osteomyelitis

Biocomposites Ltd, a medical device company headquartered in the United Kingdom, announced the launch of two-Phase II clinical trials of STIMULAN VG (STIMULAN mixed with vancomycin and gentamicin) in the United States. In the BLADE-VG2 trial, the safety and efficacy of STIMULAN VG will be tested to treat diabetic foot osteomyelitis whereas the BLADE-OPU2 trial will evaluate STIMULAN VG’s safety profile and effectiveness in the treatment of stage IV pressure ulcers.

The trials are part of an investigational new drug (IND) application and intend to show the STIMULAN VG’s potential to improve patient outcomes, reduce the incidence of recurrent infection, and minimize the use of antibiotics. The BLADE-VG2 trial has started to recruit patients and the BLADE-OPU2 trial is expected to start shortly. With the growing number of foot osteomyelitis and stage IV pressure ulcer patients, there is an urgent need to investigate the efficacy of such promising treatments that can help in infection management cases and reduce systemic antibiotic use.

Novel CAR T-Cell Therapy Shows Promise in Targeting Ovarian Tumors

In February 2024, Anixa Biosciences, Inc. announced that the first-in-human Phase I study to investigate the efficacy of a novel CAR T-cell therapy in ovarian cancer  patients has started with its second cohort of patients. Conducted through a research partnership with the H. Lee Moffitt Cancer Center and Research Institute, the trial is reported to have an estimated enrolment of 48 patients. The data in the first 3 patients receiving follicle-stimulating hormone receptor (FSHR T)-mediated T cell treatment exhibited positive results leading to the second cohort of patients where the therapy will be examined at triple the dose given in cohort 1.

In this trial, the researchers are directly administering the engineered T cells into the peritoneum, a site for most ovarian tumor lesions to prevent any adverse events. The FSHR-mediated CAR T technology or chimeric endocrine receptor T-cell (CER-T) therapy offers an innovative approach to treat ovarian cancer and other FSHR-expressing tumours by targeting hormone receptors. Although the study is in its initial phase, this CAR T-cell therapy is expected to offer a novel treatment option for patients with ovarian cancer.

Clinical trials act as a robust research tool to advance medical knowledge and improve patient outcomes. Not only do they measure the efficacy of new therapeutics, but they also help healthcare providers weigh the side effects of a treatment against its potential benefits, thereby assisting them in making the best possible treatment plan for the patient. Moreover, with the rise in technological advancements and research endeavours aimed at developing highly efficient therapeutics, the demand and diversity of clinical trials are likely to grow in the near future.

*At Expert Market Research, we strive to always give you current and accurate information. The numbers depicted in the description are indicative and may differ from the actual numbers in the final EMR report.

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