JJ Schildkraut theorized depression is linked to brain chemical imbalances—in 1965

See how antidepressants—used by roughly 1 in 10 Americans—were discovered.

How depression affects the brain

Treatment for depression has historically hinged on the theory that the condition was caused by underactive or abnormal neurotransmitters, specifically serotonin and norepinephrine. This four-minute video by Yale Medicine details how these neurotransmitters didn't explain the symptoms of depression but, two other neurotransmitters involved in regulating mood and emotion did. GABA and glutamate, some of the brain's most plentiful neurotransmitters, may possibly be the source of depressive symptoms.

LSD-like drugs may inspire new antidepressants

LSD and psilocybin have shown promise as antidepressants. Using a virtual library of similar chemical compounds, researchers determined via animal studies that two molecules inspired by LSD have antidepressant effects without any associated hallucinogenic experience. These molecules were found to be 40 times more potent than the common antidepressant fluoxetine, also known as Prozac, with antidepressant effects lasting up to 21 days.

Gut microbiome experiments involving transfers of gut microbes from depressed people to rodents indicate that the rodents may then display depression-like symptoms.

Read Norman Rosenthal’s original 1984 paper describing SAD

The study helped formalize research and diagnosis of seasonal affective disorder, catalyzing the development of therapies (like bright light) and leading to broader adoption of effective treatments. It also helped connect the influence of light and seasons on biological mechanisms in the human body, spurring exploration of circadian rhythms.

How psilocybin could transform mental health treatment

How magical are magic mushrooms, at least where depression is concerned? Some 24 volunteers participated in a study to evaluate the efficacy of using psilocybin in combination with psychotherapy to treat individuals suffering from depression. While some controversies remain about its use—psilocybin is known to cause psychosis sometimes—some scientists think the benefits outweigh the risks.

Psychedelics interact with neurotransmitter systems to alter one's perception

LSD, psilocybin, and MDMA can suppress the brain's default mode network and enhance connectivity. Research shows that, when paired with therapy, psychedelics may help treat mental health conditions, including depression, addiction, and PTSD.

Depression changes the brain, causing distinct structural alterations visible on brain scans, but effective treatment can eventually make a depressed brain resemble a healthy one.

Mental health applications of psychedelics

Scientists are investigating psilocybin, ketamine, LSD, and MDMA (also known as ecstasy) as potential treatments for mental health issues. These drugs enable an altered state of consciousness, which can have beneficial or harmful impacts depending on the nature of the experience. Research suggests these drugs can be effective in treating substance use disorders, mental health conditions, including depression and anxiety, and psychiatric disorders, including schizophrenia.

Inflammation appears to cause specific symptoms of depression

A large analysis of existing studies published in 2021 found that systemic inflammation is associated with fatigue, appetite changes, and sleep disruption, rather than some of depression's broader symptoms including hopelessness about the future, or feeling fearful. This may suggest that inflammation influences specific symptoms of the condition, rather than the disease as a whole.

Explore this deep dive into how SSRIs work

This 101-style explainer on selective serotonin reuptake inhibitors explains how they work in the brain—complete with classroom-style whiteboard drawings. It covers common SSRIs, why someone might try this medication, and a deeper discussion about potential side effects.

Can microdosing improve mental health?

Animal studies involving microdoses of psilocybin, the psychoactive component in magic mushrooms and ketamine, found it helped to alleviate anxiety and inflammation, an immune response that can cause damage when chronically active. Human studies are ongoing. In at least one double-blind study, where researchers and patients don't know who got a placebo versus the real thing, about half of the participants incorrectly guessed they had been given placebos.

These areas of the brain are hard-hit in depression—but the changes are reversible

Depressed brains can have certain characteristic changes, including an overactive amygdala, reduced hippocampus size, and changes to the thalamus and neuromodulating chemicals in the brain.

Psychedelics are being fast-tracked for research after a 2026 executive order

Many such compounds (including LSD, psilocybin, and more) are classified as Schedule I drugs—illegal to possess and federally regarded as having no medical use. Researchers say such restrictions have created significant hurdles for formal clinical trials. With this executive order, the FDA will enable work particularly focused on depression, PTSD, and alcohol use disorder.

Roughly 10% of the world has SSAD—SAD’s milder, nonclinical cousin

Subsyndromal affective disorder is diagnosed when someone exhibits two of the nine major criteria for depression (but not more than five) as a result of seasonal changes. While it is milder than primary SAD, SSAD is still significant and impacts millions.

Australian psychiatrists already prescribe psilocybin and MDMA for depression and PTSD

The country green lighted the treatments for July 1, 2023, onward, with MDMA—ectasy—as a post-traumatic stress disorder treatment, and psilocybin—magic mushrooms—as an option for people with treatment-resistant depression.

Psychedelic side effects, including worsening mental health for some patients, give pause

This article explores whether the therapeutic potential of psychedelic drug use is really as good as current research suggests. Scientists are exploring its applications for conditions ranging from the existential crisis that can accompany terminal diagnoses to chronic mental health conditions, including anxiety and PTSD.

An engineer tracked his moods for decades and helped researchers identify SAD

Civil engineer Herb Kern had bipolar and would record his moods dating back to 1967. He noticed the seasons were a major factor in the increase and severity of his episodes. By reaching out to researchers at the National Institute of Mental Health, Kern became the first human to confirm increased melatonin levels during winter and to receive bright light therapy.

Bupropion is the only antidepressant approved for the preventive treatment of SAD

Clinical trials showed a 44% reduction in risk for recurrence of SAD for those who took the drug compared to a placebo group. Bupropion is a norepinephrine–dopamine reuptake inhibitor, which increases dopamine (other common antidepressants, known as selective serotonin reuptake inhibitors, sometimes can suppress dopamine, but not always).

A mescaline-induced hallucination stayed with Jean-Paul Sartre throughout his life

In 1935, Sartre was injected with mescaline, a psychedelic drug that was then used to treat alcoholism and depression, by his friend at the Hôpital Sainte-Anne in Paris. It was not a good trip: Sartre saw nightmarish crabs for days and suffered a mental breakdown. For the rest of his life, crustaceans like the ones he saw during the hallucination appeared in his works.

The term schizophrenia was coined by Swiss psychiatrist Eugen Bleuler in 1908

He launched the word during a lecture at the German Psychiatric Association in Berlin. In his talk he focused on the splitting of psychic functioning as a defining feature of the disease and noted it wasn't associated with dementia or factors like early puberty onset.

1 in 10 US adults are taking medication for depression

A US government report indicates that about 10% of US adults took prescription medication for this disorder in 2023. Women, at 15.3%, were more than twice as likely to take one of these medications than the 7.4% of men.

Could this pseudo-psychedelic VR experience decrease symptoms of depression?

Researchers report that virtual reality and psychedelics may be leave users with similar insights and therapeutic benefits. Try out this free psychedelic virtual reality experience to see if this holds true for you. According to the program’s creators, a study into the efficacy of this 45-minute experience indicates it may help alleviate symptoms of mild to moderate depression.

SAD 101 from the folks at NIMH—where the condition was first identified

Norman Rosenthal led the team at the National Institute of Mental Health that first identified and described seasonal affective disorder in 1984. This 101 from NIMH explores the basics of the condition, from who develops it to how it is treated.

Psychedelics set off a flurry of brain activity that may permanently alter it

The brain seems to experience a sharp increase in communication between areas that generally don't interact. New research suggests a thin, sheet-like gray matter structure tucked deep within the brain, between the insular cortex and striatum, may be the key to this change. The area is centrally located and home to many of the receptors that psychedelics target, potentially rewiring the brain and rewriting thought patterns.

People with schizophrenia are excluded from psychedelic research

Individuals with this mental health condition are routinely eliminated from any psychedelic research due to concerns about triggering or worsening psychosis. Yet there is little high-quality research in this area, raising questions about if further research into this question is warranted as interest grows in using psychedelics for therapeutic purposes.

Psychedelic drugs are having a scientific renaissance

After decades of repression, psychedelic research is making a resurgence. Hear from a host of experts in this 20-minute video on what that could mean for the future of mental health. The current science on psychedelics believes LSD can cause a particular brain network to quiet or deactivate.

US FDA recently approved the first new schizophrenia drug in decades

Though other antipsychotics block dopamine receptors, a new drug, Cobenfy, influences dopamine levels via a different pathway—it stimulates a pair of specialized receptors in the brain that control the release of a substance called acetylcholine. This alternative approach may help patients avoid serious side effects like weight gain. (Some users may experience a paywall.)

Depression is much more than sadness—and isn't fleeting

The American Psychiatric Association's DSM-5—used for defining diagnoses—says a person must be experiencing five or more symptoms of depression most of the day over at least two weeks. Research indicates older people are less likely than younger people to meet that depression benchmark, though this article says they still often have at least several of the depression symptoms.

Some data shows cold showers can help with depression

An icy water exposure can lead to the release of norepinephrine, cortisol, dopamine, and other stress hormones that are beneficial, among other potential effects. Some data shows that this type of exposure can help combat depression symptoms among some patients, but more research is still needed. (Some users may encounter a paywall.)

An overview of modern clinical research on LSD

Researchers have determined that LSD, taken in a medical setting, decreases anxiety related to "life-threatening disease," reduces brain reactivity to fearful faces, increases the meaning and emotional response derived from music, and more. No complications of LSD administration have been observed in medical settings, though acute adverse effects, including exhaustion, nausea, and difficulty concentrating.

Gene expression patterns are similar between ASD, schizophrenia, and bipolar disorder

Postmortem brain tissue analysis suggests there are genetic and epigenetic similarities between individuals with autism, schizophrenia and bipolar disorder. All three conditions appeared to have activation of genes in astrocytes and suppression of specific genes that function at the junction between neurons, called synapses. (Some users may encounter a paywall.)

Existentialism has been used as a therapeutic tool, with 2 Swiss psychiatrists pioneering the philosophy's concepts to help patients navigate their issues.

Studies of psychedelic use may help shed light on the nature of consciousness

The nature of consciousness—what it is, where it comes from, and how it manifests as moment-to-moment experience—remains under debate by scientists. Recent studies show psychedelics were found to boost low-frequency brain signals known as delta waves, a behavior also seen during dream states.

The science of spring fever

Researchers have confirmed what people have sensed for ages: Our emotions during the springtime can go a little wild. This piece breaks down the impact of the seasonal transition on our bodies and prescribes a few ways to mitigate the effects.

Could all mental health disorders have a unifying 'p-factor'?

Some researchers have argued in the past couple decades that all mental health disorders may have a unifying dimension—a theoretical "p-factor" that is common across mental illness, but life experiences and behaviors influence if and how illness manifests. Proponents point to similarities across different disorders, while detractors argue that such connections are largely exaggerated.

Stress and the brain

While an acute stress response is a normal bodily function, the effects of chronic stress can be extremely damaging to the human body. This is particularly true with regard to the brain. This article explores the effects of stress on the human brain, including how chronic stress may lead to psychological conditions such as depression and memory loss.

Women are four times as likely to be diagnosed with seasonal depression

This prevalence trend mirrors the broader incidence of depression among women and is well-documented. Researchers suggest the disparity stems from differences in hormones, social role expectations, coping mechanisms, and more. Men may also present with depression differently, and seek help less.

Using psychedelics to manage a cancer diagnosis

Dr. Roland Griffiths helped lead the revival of psychedelic research, often prescribing the use of psilocybin to address severe depression or anxiety in patients. This podcast explores how Griffiths leaned on his own career after being diagnosed with cancer and facing the prospect of death.

Antidepressants alone may fail to help an estimated one-third to one-half of depressed patients.

Some dementia cases may be linked to treatable microorganism infections in the brain.

How four types of psychedelics affect the brain

Brain imaging shows that ayahuasca, MDMA, DMT, and psilocybin profoundly affect neural activity, giving rise to higher states of introspection and consciousness. This article details exactly how each of these drugs physically affects the brain and what that means for mental health treatment. Some of these drugs quiet the brain or trigger the release of neurochemicals associated with mood regulation and learning.

Schizophrenia symptoms, like psychosis, often first emerge among young adults

A combination of genetics, significant brain changes to the frontal cortex, and hormonal changes during young adulthood—late teens to early 30s—result in schizophrenic symptoms often showing up during this period. The stress of life changes at that age may also be a contributing factor.

Having five of nine key symptoms constitutes a major depression

Before professional standards were adopted, practitioners used varying criteria to diagnose mental health disorders. By the 1970s, more objective lists were organized, culminating in this list of polythetic criteria—a list of symptoms where no single criterion is required, but a minimum number must be present.

How can octopuses and MDMA help scientists understand the human brain?

Research shows that psychedelics may induce something called "critical periods" in the adult brain, which can make our brains more open to learning and changing, like they once were back in early childhood. Psychedelics similarly change how social creatures like octopuses behave, which demonstrates that these animals could help us better understand our own neurobiology.

Schizophrenia is being studied with pea-sized 'mini-brains'

Brain organoid research is enabling researchers to study distinct electrical firing patterns associated with schizophrenia. These "mini-brains" that are constructed in the lab from patients' cells could lead to better diagnosis approaches and drug development.

The commercial and therapeutic potential of psychedelics

A 2006 study into the potential therapeutic benefits of psychedelics sparked a renewed interest in the field of psychedelic research, a development that has cascaded into commercialized ventures and experiences. This article details how growing research into the psychological benefits of psychedelics is matched by the rise of anecdotal reports, book deals, businesses, and corporate claims seeking to capitalize on psychedelic potential.

Norman Rosenthal’s struggle with SAD inspired him to understand it

The South African doctor migrated to New York City in the 1970s. During his first winter there, he noticed the shorter days had a significant impact on his mood compared to those in his hometown of Johannesburg, South Africa, which is much closer to the equator. After three years of this seasonal mood shift, he decided to focus his studies. Hear him speak in this quick narration.

Oregon voters in 2020 greenlit adult use of psilocybin—the active ingredient in magic mushrooms—in state-licensed centers, and a 2026 analysis indicates the program has good safety and satisfaction data.

Circadian rhythm disruption can influence various mental health disorders

This 2020 research overview surveys the relationship between disrupted circadian clocks and disorders including schizophrenia, anxiety, and bipolar disorder. It incorporates findings and therapeutic approaches drawing from human night shift studies and jet lag studies alongside animal research.