latest research on major depression

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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

Huntingtin CAG repeat size variations below the Huntington’s disease threshold: associations with depression, anxiety and basal ganglia structure

Magdalena Vater
Nicolas Rost
Elisabeth B. Binder

A retrospective two-center cohort study of the bidirectional relationship between depression and tinnitus-related distress

Lukas et al. investigate the co-development of tinnitus-related distress and depressiveness throughout treatment. The strong bidirectional relationship indicates a combined treatment of tinnitus and depression, suggesting enhanced treatment success in tinnitus-related distress when depression is addressed and vice versa.

Cosima F. Lukas
Birgit Mazurek
Christian Dobel

Sertraline modulates hippocampal plasticity via sigma 1 receptors, cellular stress and neurosteroids

Yukitoshi Izumi
Angela M. Reiersen
Charles F. Zorumski

Association of depression with severe non-alcoholic fatty liver disease: evidence from the UK Biobank study and Mendelian randomization analysis

Xiaorui Zhou

Structural neural plasticity evoked by rapid-acting antidepressant interventions

Rapid-acting antidepressant interventions, such as ketamine and psilocybin, are thought to enhance neural plasticity. This Review outlines evidence of synaptic deficits in individuals with major depressive disorder before discussing in vivo longitudinal studies of antidepressant-evoked structural plasticity in rodents. Translational opportunities, research gaps and challenges are also considered.

Alisha N. Dua
Alex C. Kwan

Accurately predicting mood episodes in mood disorder patients using wearable sleep and circadian rhythm features

Jaegwon Jeong
Jae Kyoung Kim

News and Comment

Comment on “perception of social inclusion/exclusion and response inhibition in adolescents with past suicide attempt: a multidomain task-based fmri study.” by gifuni et al..

Emilie Olié
Philippe Courtet

Brain stimulation at home helps to treat depression

A device that delivers a small electrical current to the brain has beneficial effects in cases of depression that doesn't respond to drugs or therapy.

Miryam Naddaf

How to (not) decide about the motor vs psychomotor origin of psychomotor disturbances in depression

Dusan Hirjak
Stefan Fritze
Georg Northoff

Total physical activity matters for brain health

Many people struggle to be physically active during the week. Research now shows that accumulating the recommended amount of physical activity within a shorter time period, such as the weekend, has benefits for brain health equal to those of a regular physical activity pattern, and that this reduces risk of brain disorders, depression and anxiety.

Kaarin J. Anstey

Determining pathways that link brain, body, lifestyle and mental health

Using multimodal brain imaging and organ-specific physiological markers from more than 18,000 adult participants of the UK Biobank database, this study reveals integrated pathways that explain the interplay between brain, body, environment and lifestyle, and their collective influence on mental health outcomes.

Mapping connectivity and network alterations in youth depression by functional brain imaging

Analyses of functional MRI brain images of young people with depression revealed that altered brain connectivity associated with this disorder is circumscribed to specific networks and hub regions, including the default mode and attentional networks. The magnitude of these connectivity changes is a reliable predictor of depression symptom severity.

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Experimental depression treatment is nearly 80% effective in controlled study

In a double-blind controlled study, high doses of magnetic brain stimulation, given on an accelerated timeline and individually targeted, caused remission in 79% of trial participants with severe depression.

October 28, 2021 - By Mandy Erickson

Since receiving an experimental depression treatment at Stanford, Tommy Van Brocklin has been walking Scout for "the sheer joy of it." Nellie Van Brocklin

A new type of magnetic brain stimulation brought rapid remission to almost 80% of participants with severe depression in a study conducted at the Stanford University School of Medicine .

The treatment, known as Stanford accelerated intelligent neuromodulation therapy (SAINT) or simply Stanford neuromodulation therapy, is an intensive, individualized form of transcranial magnetic stimulation. In the study, remission typically occurred within days and lasted months. The only side effects were temporary fatigue and headaches.

“It works well, it works quickly and it’s noninvasive,” said Nolan Williams , MD, an assistant professor of psychiatry and behavioral sciences. “It could be a game changer.” Williams is the senior author of the study, which was published Oct. 29 in the American Journal of Psychiatry .

Twenty-nine people with treatment-resistant depression participated in the study: About half received SAINT, and the rest underwent a placebo procedure that mimicked the real treatment. After five days of treatment, 78.6% of the participants in the treatment group were no longer depressed, according to several standard methods of evaluation. “It’s quite a dramatic effect, and it’s quite sustained,” said Alan Schatzberg , MD, the Kenneth T. Norris, Jr. Professor in Psychiatry and Behavioral Sciences, who was a co-author of the study.

A lifetime of depression

Tommy Van Brocklin, 60, has suffered from depression since he was 15. “In 1975, they didn’t have the medication and understanding they do now,” he said. “I was told I wasn’t trying hard enough.”

“I’ve functioned all these years, but it’s been very difficult at times,” the civil engineer added. Talk therapy helped “for about half a day after an appointment.” When selective serotonin reuptake inhibitors became available in the 1990s, he started on paroxetine, commonly sold under the brand name Paxil.

“It worked like a miracle drug,” he said, but after 10 or 15 years it started to lose its effect. After 25 years, it stopped working entirely. He tried other medications, but none helped; one even made him suicidal.

His sister, who lives near Stanford, connected him with the researchers studying SAINT. He flew from his home in Memphis, Tennessee, and underwent the treatment in September. He felt nothing the first day; on day two, he began feeling emotional — “I felt the struggle of what I’d been through all these years.”

“The next day, all of a sudden, it broke through,” he said. “I felt so much better, and it’s stuck with me.”

Specialized magnetic stimulation

The transcranial magnetic stimulation treatment currently approved by the Food and Drug Administration requires six weeks of once-daily sessions. Only about half of patients who undergo the treatment improve, and only about a third experience remission from depression.

SAINT advances that treatment by targeting the magnetic pulses according to each patient’s neurocircuitry and providing a greater number of pulses at a faster pace.

In the study, the researchers first used MRI to locate the best location to target within each participant’s dorsolateral prefrontal cortex, which regulates executive functions, such as problem solving and inhibiting unwanted responses. They applied the stimulation in a subregion that has the strongest relationship with the subgenual cingulate, a part of the brain that is overactive in people experiencing depression. The transcranial magnetic stimulation strengthens the connection between the two regions, facilitating dorsolateral prefrontal cortex control of the activity in the subgenual cingulate.

The researchers also used 1,800 pulses per session instead of 600. (The larger amount has been used safely in other forms of brain stimulation for neurological disorders such as Parkinson’s disease.) And instead of providing one treatment a day, they gave participants 10 10-minute treatments, with 50-minute breaks in between.

For the control group, the researchers disguised the treatment with a magnetic coil that mimicked the experience of the magnetic pulse; both the control and active treatment groups wore noise-canceling earphones and received a topical ointment to dull sensation. Neither the researcher administering the procedure nor the participant knew whether the participant was receiving real treatment.

A hard-to-treat group

The trial participants ranged in age from 22 to 80; on average, they had suffered depression for nine years. They had tried medications, but either they had had no effect or they had stopped working. During the trial, participants who were on medication maintained their regular dosage; participants who weren’t taking medications did not start any.

Nolan Williams demonstrates SAINT, the magnetic brain stimulation therapy he and his colleagues developed, on Deirdre Lehman, a participant in a previous study of the treatment. Steve Fisch

Within four weeks after treatment, 12 of the 14 participants who had received the treatment improved, and 11 of them met FDA criteria for remission. In contrast, only two of the 15 participants who had received the placebo met the criteria for remission.

Because the study participants typically felt better within days of starting SAINT, the researchers are hoping it can be used to quickly treat patients who are at a crisis point. Patients who start taking medication for depression typically don’t experience any reduction of symptoms for a month.

“We want to get this into emergency departments and psychiatric wards where we can treat people who are in a psychiatric emergency,” Williams said. “The period right after hospitalization is when there’s the highest risk of suicide.”

Van Brocklin said that since he returned home following treatment, he’s made some radical changes. “I have a really strong desire to get my life together,” he said.

“I don’t procrastinate anymore,” he added. “I’m sleeping better. I completely quit alcohol. I’m walking my dog and playing the guitar again, for nothing more than the sheer joy of it.”

Most importantly, he said, “I’m remaining positive and being respectful of others. These are big changes in my life.”

Other Stanford scientists who contributed to the study are former postdoctoral scholars Eleanor Cole, PhD, and Angela Phillips, PhD; Brandon Bentzley, MD, PhD, David Carreon, MD, Jennifer Keller, PhD, Kristin Raj, MD, and Flint Espil, PhD, all clinical assistant professors of psychiatry and behavioral sciences; clinical research coordinators Katy Stimpson, Romina Nejad, Clive Veerapal, Nicole Odenwald and Maureen Chang; former clinical research coordinators Fahim Barmak, MD, Naushaba Khan and Rachel Rapier; postdoctoral scholars Kirsten Cherian, PhD, James Bishop, PhD, Azeezat Azeez, PhD, and John Coetzee, PhD; life science research professional Heather Pankow; clinical research manager Jessica Hawkins; Charles DeBattista, MD, professor of psychiatry and behavioral sciences; and Booil Jo, PhD, associate professor of psychiatry and behavioral sciences.

Scientists from the U.S. Department of Veterans Affairs; Palo Alto University; the Centre for Neuroimaging and Cognitive Genomics at the National University of Ireland; and the School of Medicine at Southern Illinois University, Carbondale, contributed to the research.

The research was funded by a Brain and Behavior Research Foundation Young Investigator Award, 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, and the Gordie Brookstone Fund.

Stanford’s Department of Psychiatry and Behavioral Sciences also contributed to the work.

If you're interested in participating in a study, please email [email protected] .

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 .