Brain Hacking:

The New Science of Curing Mental Illness

By Amy Ellis Nutt

Copyright © 2016 by The Washington Post

Introduction

In her writing for The Washington Post, Pulitzer Prize winning reporter Amy Ellis Nutt reveals the newest findings and the latest tools as scientists try to unravel the mysteries of what’s been called the most complex object in the universe: the human brain.

Her "Brain Hacking" project, which we present here, looks at a few of the most innovative approaches researchers are taking to combat the worldwide scourge of mental illness. From transcranial magnetic stimulation and near-infrared light therapy for depression, to the use of a common antibiotic for the obsessive compulsive disorder, these stories explore the scientists — and the patients — who are pushing beyond the boundaries of psychiatry and neuroscience to find new ways to help our mental health.

The Failure of Traditional Drugs

More than 61 million people have been diagnosed with a mental disorder in this country – one in four Americans, according to the National Institute of Mental Health – accounting for an astronomical $317 billion annually in lost wages, health care and disability.

Depression, by far, affects the widest range of people, and yet two out of three patients do no fully recover on current antidepressant medications. The complexity of treating mental illness has seen the number of new drugs reaching market plummet, and the few that do take to get there than medications in nearly every other branch of medicine.

The most recent statistics show that AIDS drugs go through nearly six years of clinical trials before being approved by the Food and Drug Administration; cancer drugs take 7.5 years; and respiratory drugs 8.3 years. Psychiatric drugs, on the other hand, average nine years once clinical trials have begun.

In the past five years, just 11 medications have received FDA approval for the treatment of a mental disorder, according to the clinical trials database, CenterWatch. Over that same period, 72 therapies were approved for the treatment of cancer.

No wonder so many major pharmaceutical companies are abandoning psychiatric research.

The lack of effective drugs is belied by the fact that so many people taking them believe the medications will help them. That state of affairs is likely attributable, at least in part, to the paeans that accompanied Prozac’s introduction back in 1987. The selective serotonin reuptake inhibitors, or SSRIs, of which Prozac is the market leader, arrived nearly 30 years after imipramine, the first tricyclic antidepressant to hit the market.

“I think there was a lot of suggestion that we had conquered depression when Zoloft and Prozac came around,” said Kenneth Kaitin, director of the Tufts Center for the Study of Drug Development.

But then came the studies indicating an increased risk of suicide in young people on SSRIs. Following fast on the heels of those findings was the controversy over whether certain SSRIs should carry warnings on their labels, which they now do.

Slowly, it become clear to an ever growing number of people both inside and outside the pharmaceutical industry that the SSRIs, and by extension all psychiatric medications, were failing to be the lifesavers so many had envisioned.

What has always been true is that treating the brain is much harder than, say, the heart, because the brain is the most complex organ in the human body. Scientists admit that despite the vast progress in neuroscience in recent years, they are still far away from even having a working model of how the brain functions.

“In the psychiatric area, there’s a whole host of problems,” Kaitin said, “and not just the technical risk. There are multiple [causes] and a variety of factors that are hard to localize. The drugs have to be given over a long period of time so safety has to be demonstrated, and the end points are difficult to measure so the trials must be very large. Some depressed people cycle in and out, so you don’t know if it’s the drug effect or not. The positive part is there is a concerted effort to validate and find biomarkers that will enable companies to have a better edge in developing these drugs.”

If there has been a breakthrough in drug treatment, it’s in figuring out which drugs work best for which patient. For the first time, advances in genetic testing have opened the door to personalized medicine in mental health, at least when it comes to treating illnesses with current medications.

Several companies, in fact, now offer blood and saliva tests that help psychiatrists match the medication to the patient.

Genomind, in King of Prussia, Pennsylvania, was one of the first. Four years ago, and just one year after being founded, the company began to sell a saliva-based genetic test for patients with various mental disorders from obsessive compulsive disorder to schizophrenia. Called the Genecept Assay, it measures variances in 10 specific genes that play a role in determining how slowly or quickly the body metabolizes a drug and also the drug’s effects on the body. The test can be performed in a doctor’s office and the results processed in three to five business days.

Currently, prescription drug treatment for psychiatric conditions is more art than science. Some have likened picking a drug for a patient to flipping a coin. Often the results are only discernible after weeks on the medication, and if it doesn’t work, it’s on to the next one in a pattern mental health professionals call the “diagnostic odyssey.”

Jay Lombard, a co-founder of Genomind, was chief of neurology at Bronx Lebanon Hospital in New York City when he met future-co-founder Ronald Dozoretz, a psychiatrist. The two men talked about their frustrations and hatched the idea of a company that treated psychiatric conditions like biological illnesses.

“If you have a chest pain, you take an EKG,” said Lombard, who is also Genomind’s chief scientific officer and medical director. “But what do you do if your kid starts to hallucinate?”

Lombard and Dozoretz, Genomind’s chairman, began by studying the problem, performing retrospective studies and meta-analyses until they realized what their first step should be: developing an inexpensive clinical tool to help doctors match patients with the right treatment.

Enter the Genecept Assay.

“It’s not a difficult test to take,” Nancy Grden said. “It’s simple to use. A saliva test. Cheek swab. Non-invasive. We collect saliva and send it to the lab. The report provides not just genetic information, but … information for clinicians to decide the kind of drug to use and the dosing.”

To date, however, there have been no large-scale prospective studies to look into the effectiveness of these tests, so not all researchers and clinicians are on board yet. Yet Grden, the company’s former general manager, thinks that’s just a matter of time. (s

“Right now, there are so many instances of untreated and unresolved mental health issues,” she said. “A lot of the emphasis on improving mental health is about more clinicians and better access. But what is striking is how something as simple as this test could make a difference. What it would do to mental health delivery – the ability to show a patient a report, a biological report – is extremely important.”

Taking a Holistic Approach to Finding New Treatments for Mental Illness

It was an experiment born of the strangest inspiration: Buddhist nuns, high in the remotest reaches of the Himalayas, practicing a form of meditation known as “tummo,” or “inner fire.” In sub-zero weather, these nuns perform an ancient ritual of wrapping themselves in wet sheets then meditating outside. Through special breathing techniques as well as visualizing a flames along their spines, the nuns raise their body temperatures to mildly feverish, rapidly drying the wet sheets.

When scientists finally began to study the nuns in 2013, they were able to show for the first time that a person’s core body temperature could be controlled by the brain.

Why were the scientists so intrigued? Higher core body temperatures are associated with increased energy, better focus and improved resistance to infection.

Charles Raison, a psychiatric researcher now at the University of Wisconsin, had another interest. As one of the many creative scientists now looking for new ways to treat mental illness without medication, he thought differently about mental disorders than most traditional psychiatric researchers. Mental illness isn’t just about the brain, he realized; it’s about the whole body.

Temperature and the sensory pathways that control body temperature have a high association with depression, he knew. Depressed patients, in fact, have higher core temperatures and also sweat less than non-depressed people.

Throughout history, saunas and the sweat lodges of Native Americans and other indigenous cultures around the world have been associated with spiritual and physical well-being.

Although depressed people may have higher body temperatures, their inability to sweat was another tip to Raison. “Why were these people hot? We think it’s because the [sensory] pathway wasn’t working correctly, so they couldn’t lose heat, which elevated their body temperature,” he told the U.S. Psychiatric and Mental Health Congress in 2015.

By getting these patients’ cooling systems working again, Raison reasoned he could reduce their depression as well. He was right.

Depressed subjects were randomized into two groups, one group received a placebo of “sham” treatment. The other subjects received the real thing: Reclined on a gurney, they were placed in a kind of tent that covered all but their heads. Their skin was then heated for a single 2 and ½ hour session. Those subjects who underwent the real treatment experienced a significant reduction of depression compared to the control group. And the hotter the subject’s body temperature before treatment, the greater the reduction of depression. The overall response of those undergoing the actual hyperthermia was an astounding 2-and-a-half times greater than the placebo group, far outstripping the differences normally seen in clinical trials of new antidepressant medications.

Another unexpected result: Although Raison predicted the benefit of the hyperthermia therapy would wear off by six weeks post-treatment, he was pleasantly surprised that many in the study who received the actual treatment reported still feeling “significantly improved” at six weeks.

“It doesn’t take a week or two to work,” Raison told the U.S. Psychiatric Congress. “People feel better very, very quickly, and the effects appear to persist for an extended period of time.”

Part 1

The Mind’s Biology

Doctors are reaching past the symptoms of mental illness to fix the circuits that breed them

She relaxed in the recliner, her eyes closed, her hands resting lightly in her lap. The psychiatrist’s assistant made small talk while pushing the woman’s hair this way and that, dabbing her head with spots of paste before attaching the 19 electrodes to her scalp.

As the test started, her anxiety ticked up. And that’s when it began: the sensation of being locked in a vise. First, she couldn’t move. Then she was shrinking, collapsing in on herself like some human black hole.

It was a classic panic attack — captured in vivid color on the computer screen that psychiatrist Hasan Asif was watching.

“It’s going to be okay,” he said, his voice quiet and soothing. “Just stay with it.”

The images playing out in front of him were entirely unexpected; this clearly wasn’t a resting state for his patient. With each surge of anxiety, a splotch of red bloomed on the computer screen. Excessive activity of high-energy brain waves near the top of her head indicated hyper-arousal and stress. Decreased activity in the front of her brain, where emotions are managed, showed she couldn’t summon the resources to keep calm.

“This was your brain as you were sitting there trying to relax,” Asif explained afterward, rerunning the sequence for the woman, who for many of her 37 years had struggled against crushing waves of dread. “Look at what just happened. This was the area of your brain that started firing. . . . It’s right there on the screen.”

For the 51-year-old psychiatrist, the episode last year in his Bronxville, N.Y., practice was yet another piece of evidence that he was on the right track, burrowing past his patient’s symptoms to probe the structures in her brain that produced them. Individually, all the tools he employs have been used before, but rarely, if ever, together. It’s an approach that parallels some of the most cutting-edge research in the field.

Scientists have long known that the most forward part of the brain is the seat of higher cognition. But only in recent years have they been able to link certain mental disorders with specific brain circuits, the connections between neurons that are responsible for every one of our thoughts, emotions and actions. Asif’s tools enable him to more precisely diagnose his patients’ problems and, ultimately, to treat them.

Neuroscience’s inroads have emboldened a small but growing number of clinicians and researchers to reject diagnostic protocols on which mental health practitioners have relied for years — the cataloguing of symptoms such as sadness, fatigue, loss of appetite — and instead focus on finding biological clues associated with these symptoms in a blood test, a brain image or a saliva sample.

These are the biomarkers, the concrete measurements of mental illness, that many think will move the mental health profession into the 21st century. For Asif, some of the tools being used in the search are already yielding practical results, such as sending a patient’s cheek swab for DNA analysis to help determine which psychotropic medication will be most effective and best tolerated.

Psychiatrist Hasan Asif and visiting neuroscientist Aza Mantashashvili analyze brain-wave activity of Marris Szeliga as she undergoes an EEG. (Yana Paskova for The Washington Post)

This new, if controversial, approach to mental illness got a boost in 2013 when the director of the National Institute of Mental Health announced that the government, the largest funder of mental health research in the world, would drastically shift its priorities. Research based solely on the Diagnostic and Statistical Manual of Mental Disorders, the chief tool of mental health professionals, would no longer be funded. The reason, Thomas Insel said, was “its lack of validity.”

First published in 1952, the manual has changed over the years. Yet its categorization of mental illnesses is based nearly entirely on symptoms either reported by the patient or observed by the clinician. New funding, Insel said, would be based on the premise that “mental disorders are biological disorders involving brain circuits.” Research into diagnosis and treatments such as talk therapy would be relegated to the bottom rung of the research ladder.

Insel later softened his criticism of the DSM. But the battle had been joined, and with millions of lives and billions of dollars at stake, the fight over the future of psychiatry was on.

“There are two camps: the very biologically oriented and the patient-oriented,” said Moira Rynn, director of child and adolescent psychiatry at the New York State Psychiatric Institute. Rynn, who is both a clinician and a researcher, describes herself as “in the middle” of this tug-of-war. She’s worried, she says, that “we’re going to lose a generation of researchers” who think that identifying the influences of a patient’s environment, relationships and access to care is just as important as finding the biological markers of their illness.

Other skeptics of Insel’s approach say it is impossible to understand mental illness solely by trying to understand the brain.

“The main thing is looking at what people say about their lives,” said Richard Shulman, a Hartford, Conn., clinical psychologist and one of the founders of Volunteers in Psychotherapy, a nonprofit that provides affordable psychotherapy to the community in exchange for volunteer work that clients perform for charities. “What has led to a real confusion or distress in their lives, and how these things come up, that’s when you get a real idea of how and why something upset them. . . . You look at things through their eyes and say, yes, this person has gone through the wringer.”

From the time of the ancient Greeks, medical practitioners have searched for biomarkers for physical illnesses. Hippocrates tasted patients’ urine for sweetness (he is thought to have been the first to diagnose diabetes mellitus), smelled their breath for signs of kidney and liver disease, and assessed the stickiness of their sweat. More recently, doctors relied on patients’ complaints about the severity of their chest pains in order to diagnose a heart attack. Today, they measure cardiac enzymes in the bloodstream.

“Cancer treatment doesn’t treat the symptoms of cancer. You don’t want the swelling to go down or the pain to disappear; you want to get rid of the cancer,” said Kenneth Kaitin, director of the Tufts University Center for the Study of Drug Development. “But that’s what we’re doing in psychiatry,” treating the symptoms of mental disorders — the sadness or the restlessness or the hallucinations — not the causes.

What is known is that the brain looks different in those who struggle with mental illness. This does not necessarily mean all mental disorders originate in the brain. Post-traumatic stress disorder, for instance, occurs because of emotionally scarring experiences, but those experiences change the brain and the brain’s responses to the environment.

Marris Szeliga, a patient and employee of psychiatrist Hasan Asif, is fitted with an EEG cap that will allow him to analyze her brain-wave activity. (Yana Paskova For The Washington Post)

Nearly every day, researchers report findings about genetic or cellular associations with mental illness. But despite years of searching, no one has identified a single biological cause for any mental illness, proved that a chemical imbalance in the brain is at the root of any mental disorder, or positively shown that any medication corrects such a chemical imbalance.

“There’s been an intense search for biomarkers for the last 40 years, and so far we’ve come up empty,” said psychiatrist Allen Frances, a professor emeritus at the Duke University School of Medicine. “It’s been oversold. The decade of the brain came up empty. It should teach us to be humbler.”

The leading drugs for depression — the selective serotonin reuptake inhibitors, or SSRIs — are designed to ease symptoms by boosting serotonin, one of the brain’s pleasure chemicals. But it’s not known whether that corrects an imbalance, because there’s no way to directly measure a person’s neurochemical levels. Experts also can’t explain why antidepressants work only 40 percent of the time or why, when they do, it takes weeks for most patients to feel the effects since the levels are boosted almost immediately.

The chief complaint about today’s psychiatric medications is the same one cited by those frustrated by the lack of progress on Alzheimer’s: They don’t treat the disease, just the symptoms, and they don’t even do that very well.

Rather than targeting brain chemistry to reduce symptoms, people such as Insel want to focus on brain circuitry. Their efforts have been bolstered by advances in technology and imaging that now allow scientists not only to see deeper into the brain, but also to study single brain cells to determine which circuits and neurons underlie specific mental and emotional states. Many of these advances come from fields as disparate as physics and electrical engineering — as well as the new field of optogenetics, which uses light to manipulate neurons.

In the past, brain imaging allowed scientists to identify which groups of neurons were active when, say, a lab mouse was aggressive, but not whether the neurons were causing the aggressive behavior. Then a few years ago, researchers at the California Institute of Technology injected into the hypothalamus of a mouse a modified gene that made certain cells sensitive to light.

They then inserted a hair-thin fiber-optic thread into the mouse’s skull and delivered bursts of light into those cells to activate them. The mouse became aggressive. When the researchers turned the light off, the activity in those specific hypothalamic cells ceased, and the mouse returned to a calm, normal state.

Because the technique is too invasive for people, researchers are now looking at nanotechnology and even magnets as a way to switch cells on and off in humans. Connecting specific symptoms with specific groups of neurons, and then manipulating those cells, would represent a watershed moment.

In a treatment room in his Bronxville, N.Y., office, psychiatrist Hasan Asif uses transcranial magnetic stimulation to adjust the firing of brain circuits in patients suffering from depression, anxiety and other mental disorders. (Yana Paskova for The Washington Post)

Hasan Asif, who was born and raised in Pakistan, is a board-certified psychiatrist who first trained as a psychoanalyst. When he came to the United States in 1990 for post-graduate training at New York Medical College in Valhalla, he was swept up in the biological psychiatry movement. He opened a private practice in New York and eventually spent tens of thousands of dollars outfitting his office with new neurological tools. On his walls are colorful microscopic close-ups of neurons, and on his bookcase and tables are replicas of Greek and Egyptian antiquities once collected by Freud.

Asif evolved into a “neurotherapist,” someone who first tries to understand a patient’s brain circuitry, then combines that with both psychological and physiological information to create a treatment plan. While a traditional psychotherapist might begin sessions by asking patients about their thoughts, feelings and problems, Asif has them fill out a color-coded form that matches statements about their thoughts and feelings with the parts of the brain most likely involved. Then his patients undergo a quantitative electroencephalograph, or qEEG.

The EEG, which has been around for more than 90 years, is a map of the brain’s electrical activity and reflects a patient’s emotional and cognitive states. The qEEG compares that information, in real time, to a digital database of hundreds of EEGs of healthy subjects. A patient’s brain map will pulse with red or blue if it is either overactive or underactive, compared with the norm.

“The brain is almost screaming out loud: ‘Read me! I’m showing you everything!’” Asif said.

Patient treatment plans might include psychotherapy and medication as well as neurofeedback, a technique in which patients are trained to increase or decrease brain-wave activity in the parts of the brain related to their complaints. Another tool is transcranial magnetic stimulation, a noninvasive method of delivering pulses of energy to the head, which has been approved by the Food and Drug Administration for the treatment of depression. But almost always, Asif begins with a qEEG. It acts as a kind of map, helping him to identify a patient’s troublesome brain circuits, which he then targets with his various therapeutic techniques.

Tina Raymond, 61, says her treatment produced almost immediate results. In 2006, Raymond was robbed and beaten inside her storefront office in Mount Vernon, N.Y., where she designed seasonal displays for department stores. She saw several doctors, including Asif, for memory loss and PTSD from the attack, and she eventually recovered. Then, in May 2014, just as Asif was ramping up his neurotherapy practice, Raymond returned, complaining of feelings of worthlessness.

“I was hitting a lull, an emotional lull,” she said. “I was depressed. Getting out of bed was harder than usual. I’m a pretty upbeat person in general, so for depression to hit me . . . was distressing.”

Raymond filled out the color-coded form and scored the statements on a scale of 0 to 10, with 10 being the highest.

“I feel unfocused, tired, and bored”: 7.

“I have difficulty planning and organizing”: 9.

“I worry a lot, and have difficulty stopping repetitive negative thoughts and actions”: 6.

Asif next wired Raymond for a qEEG. The most striking image was a red blotch on the right side of her brain map, indicating too much slow-wave delta activity in the temple area. It’s a part of the brain that plays a role in mood regulation and motivation, and it wasn’t firing properly or communicating well with the left side of her brain. Asif now had his target areas. He would use neurofeedback, employing a video-aided reward system, to retrain Raymond’s brain.

Neurofeedback is a descendant of biofeedback, which uses medical instruments, such as a blood pressure cuff, to monitor body functions and relay the information to patients who then try to alter their physical responses. Neurofeedback has had a popular, if controversial, commercial application as a kind of relaxation therapy, but recently psychiatry has studied it in combination with real-time brain imaging. In 2013, for example, a team at Yale University found that neurofeedback used with functional MRI, another brain imaging technology, substantially reduced depression and anxiety in patients.

For some neurofeedback sessions, Asif plays a pleasant nature movie during which the patient’s brain-wave activity is automatically compared every half-second to the goal. If the two are in sync, the patient’s brain is “rewarded” by the movie’s continuation. If they are not, the movie stops. Which means that in one 50-minute session, Raymond’s brain experienced 6,000 chances to be “rewarded” for learning how to reduce the delta-wave activity in the right hemisphere and re-establish its normal firing pattern. Her concentration kept the video — she substituted a 1992 comedy by Italian director Lina Wertmüller for the nature film — playing without interruption.

If all this seems mysterious, scientists say it is no more inexplicable than children learning on their own how to play a video game or ride a bicycle. Our brains simply figure things out because that’s what they were built to do. For patients, the sense of control over their own treatment, of helping to heal themselves, is often exhilarating.

After those five sessions, Raymond felt her depression lift. Those overactive delta waves nearly disappeared, and her improving mood matched her brain map, evident by the diagnostic form she filled in before each session. Soon the 9’s and 7’s she had recorded before her first session were manageable 2’s and 3’s. She felt better in the same amount of time it takes for most psychiatric medications to begin working, and she experienced no side effects, except for the goop in her hair after each session.

Asif, she said, “put my pieces back together.”

Marris Szeliga, a patient and employee of psychiatrist Hasan Asif, holds a stone in her hand for relaxation as Asif analyzes her brain-wave activity. (Yana Paskova for The Washington Post)

Internist Alexis Gopal often referred patients to Asif.

“I’ve sent him adolescents who have gone to successive psychiatrists and medication after medication, and he can turn them around in two or three treatments,” said Gopal, who lives in Danbury, Conn., and now runs her own medical communications business.

For several years the doctor had dealt with her own, occasionally paralyzing anxiety, for which she took medication. When the problems worsened in 2014, she turned to Asif.

Gopal was skeptical about neurofeedback, having undergone biofeedback sessions for migraines with another doctor; they hadn’t helped. Then Gopal went through Asif’’s movie-watching exercise. She also listened to a series of pleasant tones that degenerated into noise if she didn’t focus on modulating her brain-wave activity.

“You have to relax. And he tells you to focus on something,” she said. “I remember specifically one session feeling like I was going to crawl out of my skin. And I remember at the end of one session I felt so relaxed and so calm, I thought, ‘Wow, this really works.’”

Asif charges between $275 and $350 per session after an initial interview and evaluation, which includes a qEEG and costs about $550. Sessions are billed as either psychotherapy or medication management for insurance purposes.

Gopal said that she felt better with each visit, and there was a side benefit: Her migraines ended.

Another of Asif’s patients, who asked that she not be identified, said she began treatment for major depression in January 2014 when she lost weight, became paranoid about eating and isolated herself.

“He looked at me, and I’ll never forget it, he said, ‘Just give me nine days, and I’ll pull you out of this.’ From that moment, I thought, thank God, someone’s going to help me.”

Five times a week, she underwent transcranial magnetic stimulation, which delivers bursts of energy designed to stimulate the underactive area of the brain thought to be involved in depression. The progress was virtually immediate.

“As the treatments went on, I’d put a ring on or makeup. Then I noticed I started to cook. I hadn’t done my laundry in months and did it,” she said, and after two weeks she was significantly better.

“It was like being reborn,” she said.

Asif says that a person’s mental makeup is a kind of hierarchy, with personality on top, which is created by brain states that arise from circuits firing in a certain pattern below. With psychotherapy, you tweak the brain from the top down, dealing first with a patient’s personality and temperament. But with neurofeedback, combined with qEEG, he said, he tweaks his patients from the bottom up, identifying the brain areas involved and then retraining those circuits to fire differently, resulting in changed moods or mental outlooks.

“When they are shown the cause of their suffering in their brain circuits and body function,” Asif said, “it gives them immense power in having control over things.”

Because he is a full-time clinician, Asif has done little formal research, although he has been published in Neuroconnections, the journal of the International Society for Neurofeedback & Research. He also gives frequent talks to medical professionals, including the Society for the Advancement of Brain Analysis, the annual conference of the International Neuropsychoanalysis Society and the Biofeedback Federation of Europe.

Insel, who stepped down from NIMH last year, supports the direction clinicians such as Asif are taking. But he cautions that this is still “the beginning of a long road” and that “rigorous studies are required to establish evidence” for biological tests of mental illness.

“The field needs biomarkers and cognitive tools to define more specific diagnostic groups and to predict an individual's response to treatment,” Insel said. “We call that precision medicine. It sure beats trial and error."

In his Bronxville, N.Y., office, psychiatrist Hasan Asif studies and listens to a patient's brain wave activity. (Yana Paskova for The Washington Post)

Part 2

Hot-wired for happiness?

With fiber optics and an infrared ‘jolt,’ scientists test new ways to curb depression

CAMBRIDGE, MASS. — Inside a fifth-floor lab at the Massachusetts Institute of Technology, a 76-year-old neuroscientist is helping to reinvent psychiatry by hot-wiring the brains of mice.

Susumu Tonegawa has figured out how to reverse symptoms of depression in moody male rodents by reactivating the happy memories they created days earlier during a bit of sexual frolicking with female mice.

He injects a modified, light-sensitive gene into those happy-memory cells, then uses fiber optics to switch on the memories with a stream of blue light. The depressed mice perk up in seconds. When he turns the light off, their lethargy rapidly returns. Another flip of the switch, and they’re active again.

“We cured their depression,” he says.

Tonegawa’s approach in creating and manipulating memory cells has drawn praise from a normally staid academic community. Beyond those institutional confines, the potential of a radical new tool to treat one of the most complex mental illnesses could be a game-changer in psychiatry.

This is where Thomas Insel, the former director of the National Institute of Mental Health, hoped to push scientists when he announced in 2013 that the agency was refocusing its research to intensify the hunt for the physiological signs of mental diseases and disorders: the biomarkers, or concrete measurements of mental illness that many expect will move the field into the 21st century. After four decades of virtually no major advances in the treatment of mental illness, a profound shift was imperative, Insel thought.

Neuroscientist Susumu Tonegawa of the Massachusetts Institute of Technology is studying how to artificially reactivate happy-memory cells to treat depression. The Nobel Prize-winning scientist spends part of the year conducting research in Wako-shi, Japan. (Photo by Kosuke Okahara for The Washington Post)

There have already been small but significant successes in identifying depression biomarkers. Scientists at Duke University found that the stress response of the amygdala, an almond-shaped structure in the brain that is linked to fear and pleasure, can predict a person’s vulnerability to developing depression as much as four years into the future.

And Northwestern University researchers were able to pinpoint 11 genetic blood markers that distinguished teenagers who were depressed from those who weren’t.

Then in 2014, neurobiologist Eva Redei used molecular markers in RNA — the messengers that carry out the DNA’s instructions — to develop a blood test for depression in adults that would confirm a physiological basis for patients’ symptoms.

“The thinking is changing as the technology changes. . . . This test brings mental health diagnosis into the 21st century and offers the first personalized medicine approach to people suffering from depression,” said Redei, a professor of psychiatry and behavioral sciences at Northwestern’s Feinberg School of Medicine.

The need has never been more acute. Depression is already the leading cause of disability on the planet, affecting 350 million people of all ages, according to the World Health Organization. Despite its prevalence, the disorder is extremely difficult to study because it is so variable — which is why genetic research has so often failed. One psychiatrist likens it to looking for the genetic risk factors for fever.

Medication and psychotherapy remain the first-line treatments for major depression, though they help less than 40 percent of patients achieve remission of their symptoms. The state of the art in psychopharmacology remains the selective serotonin reuptake inhibitors, drugs such as Paxil, Prozac and Zoloft, which were first patented nearly 50 years ago. These SSRIs target the neurochemicals that carry information between neurons in the brain, but no one knows exactly how or why they work, and because the medications can’t lock in on specific neurons or regions of gray matter, they are more blunt instrument than precision tool.

That shortcoming is one major reason why scientists have shifted from neurochemicals to neurocircuits — the networks of cells that are activated every time we think, feel or move — to unravel the mysteries of depression.

MIT neuroscientist Susumu Tonegawa holds a picture of his younger son with the teen's music teachers. The son committed suicide several years ago -- a loss that motivates Tonegawa as he researches new treatments for depression. (Photo by Kosuke Okahara for The Washington Post)

At MIT, where he directs the Center for Neural Circuit Genetics, Tonegawa was ready.

Because he had trained as a molecular biologist, he already had a leg up on traditional neuroscientists. Because he was used to crossing disciplines — in 1987 he won the Nobel Prize in Physiology or Medicine for lifting the veil on antibody diversity — he already had the creativity necessary for discoveries. And because he continues to battle his own depression since the suicide of his teenage son more than four years ago, he understands better than most the importance of his potential breakthrough.

“My interests are very narrow now,” he admits. “I can’t enjoy many things.”

It was perhaps inevitable that Tonegawa’s research in memory would lead him to this current work. Over the past four years, he and his lab have shown that the physical traces of memories are not stored in the synapses, or connections, between cells, as previously thought, but in discrete circuits of cells, called memory engrams. Tonegawa then upended the common belief that the loss of long-term memory, which can result from a brain injury or disease such as Alzheimer’s, is not necessarily the result of damaged memory cells but of a damaged memory-retrieval system.

The first step was to identify and label happy-memory cells with the light-sensitive gene, then to stress those male mice with close confinement until they exhibited symptoms of depression — which meant, for instance, a lack of interest in sugar water. When reactivation of the positive memory neurons lessened the depression, Tonegawa wondered whether simply re-exposing those males to females to create new happy experiences would lift their depression. It did not, which didn’t surprise him at all.

“Depressed patients, they don’t seek pleasure. That’s a hallmark of depression. Enjoyable experiences don’t register anymore,” he said.

Tonegawa even found the curative sweet spot with his depressed mice: two light treatments a day on five consecutive days. While the same procedure cannot be performed on humans because of the invasiveness of fiber optics, Tonegawa says it is merely an “engineering problem.” In the not-too-distant future, he foresees a fast-acting treatment, with fewer of the side effects of current medications.

“People are working on this,” he said. “Others are using nanotechnology to try and activate the cells from outside the brain. It’s difficult, but I think this will be overcome.”

On the other side of the Charles River from Tonegawa, a 44-year-old physician-scientist named Paolo Cassano is also working on depression on the cellular level. His work, the first clinical trial of its kind, could similarly revolutionize patient treatment — not in a few years, but right now.

Paolo Cassano, a psychiatrist at Massachusetts General Hospital in Boston, is studying the use of near-infrared light to treat depression. (Michele McDonald for The Washington Post)

Like Tonegawa, Cassano came to psychiatric research in a roundabout fashion, through an infectious disease fellowship early in the AIDS epidemic. He became especially interested in patients’ emotional suffering, a major reason why he turned to neuropsychopharmacology, ultimately focusing on treatment-resistant depression.

One theory of depression is that it is a metabolic disorder, an underfunctioning of the cellular process by which complex molecules are broken down to produce the energy needed to maintain life. Some research has found that a depressed brain’s metabolism appears to be out of whack, storing energy instead of using it. How to unlock that became Cassano’s mission. He knew that near-infrared light — closest on the spectrum to visible light — had been successfully tested on the brains of stroke patients and had helped to restore function. At low levels, working in a similar way, it had been approved by the Food and Drug Administration for certain kinds of pain relief.

From his lab at the Massachusetts General Hospital, Cassano wondered: Could an infrared “jolt” also restore normal function within the brain of someone suffering from depression?

His underlying hypothesis was that in depression, “deeper areas are overly firing,” especially the emotion-driving amygdala, which overwhelm more superficial areas in the front of the brain that normally help control or inhibit that excessive activity.

Cassano’s idea was to target those sluggish neurons close to the surface where mitochondria, the power sources of cells, could convert the near-infrared light into chemical energy. More chemical energy would mean more neuronal growth and repair, and more and better-functioning neurons in the prefrontal cortex would mean better control over the hyperactive amygdala.

If the hypothesis is correct, then Jerrie Spencer’s prefrontal cortex has spent much of the past 52 years struggling to handle her amygdala’s negativity.

Single and self-employed, Spencer has long suffered through bouts of crying, social isolation and an inability to be fully engaged in her work as a real estate agent. She has tried psychotherapy and group therapy, self-help books and long baths, fish oil and exercise. She took an antidepressant for a month but couldn’t tolerate the side effects of fatigue and mental fuzziness. Depression wasn’t just something psychological. It was physical.

“In my body, in my gut — like a heavy weight in my stomach, all the time,” she said. “The feeling would come over me, and I felt helpless. It took away my life. . . . It brought me to my knees.”

She also admits she felt ashamed because the depression was something she couldn’t control. There were times when she might feel better for a few weeks or months, but they never lasted. Finally, in late spring, she sat down in front of her computer, went to Craigslist, and typed the word “depression” into the search engine for the Boston area where she lives. Up popped pictures of Depression-era glass and furniture for sale. But nestled between two of them was this simple question: “Are you feeling down, blue, in the dumps?”

It linked to information about Cassano’s clinical trial at Massachusetts General, posted by one of his research assistants, who creatively also used the Boston transit system, Facebook and Twitter to try to spread the word.

From the people who responded, 22 were chosen, including Spencer. All were between the ages of 18 and 65 and had been diagnosed with major depression. A third were women.

Over a period of about 18 months, ending last August, they all took part in research structured so that half were randomly assigned by a computer to the light treatment and half to a placebo treatment. Neither they nor Cassano would know who was in which group — all critical elements of a gold-standard clinical trial. All but four participants finished the study, receiving twice-weekly treatments for eight weeks.

Spencer’s sessions took place in a sparsely furnished room a few doors down from Cassano’s office. She had done her own research online and discovered that near-infrared light therapy has been used both medically and cosmetically for various ailments and conditions, including mouth ulcers in cancer patients and age-related wrinkles. Its use on the brain is still relatively new, however. Animal studies and human trials for stroke, Parkinson’s and traumatic brain injury have proved the procedure to be safe but of limited efficacy.

Psychiatrist Paolo Cassano takes measurements of Jerrie Spencer's head to identify the brain regions to be targeted with light therapy as part of his depression study at Massachusetts General Hospital. (Michele McDonald for The Washington Post)

Before beginning, Spencer had questions: What could she expect? Would it hurt? She would experience no pain, Cassano replied, just a sensation of heat on her head. She might have a slight headache afterward, but even that was unlikely.

Each visit was much the same. As Spencer lay on her back on an examination table, Cassano used a tape measure to locate an area either on the front left or right side of her head where the near-infrared light device, about the size and shape of a TV remote, would be placed. He then marked the spot, using pewter-colored eyeliner, where he wanted to concentrate the light beams. They would penetrate her scalp, skull and about a half-inch of brain tissue.

Spencer donned what looked like swim goggles to protect her eyes. Cassano plugged in the device, set an egg timer for 20 minutes and left the room. The timer went with him. There would be no talking during the session, no music, just Spencer lying still.

After just the first 20-minute session in June, she was convinced she was getting the real thing.

“Afterward, everything was really vivid visually,” she recounted recently. “I wasn’t sure if I was imagining it. Then I went outside, and everything was bright and crisp. I stood there looking around, and I thought, this is great.”

The biggest difference, though, was that heavy weight in her stomach. It was gone.

“I kept waiting for it that evening and the next day,” Spencer said. “I was really surprised.”

Of course, she still had no idea whether she was getting the real or the placebo treatment. “I said to Doctor Cassano, ‘If I’m not being treated, someone should follow me around with a clipboard.’”

Cassano tracked the data throughout the trial. Three of the 21 subjects were excluded from his final analysis because they hadn’t undergone the full series of treatments. Of the remaining 18, nine received the real therapy, nine the placebo.

Though near-infrared light for major depression had been tested only in a much smaller single-treatment trial, animal studies have shown it to have several beneficial biological effects. It increases connections in between neurons as well as stimulates the formation of new ones. It also decreases inflammation in the brain, which lessens cell damage.

Jerrie Spencer, a participant in a study run by psychiatrist Paolo Cassano at Massachusetts General Hospital, demonstrates a session in which near-infrared light is used to treat mood disorders. (Michele McDonald for The Washington Post)

Michael Hamblin, a principal investigator at Massachusetts General’s Wellman Center for Photomedicine, says he is “totally convinced” by Cassano’s approach. “Anything that is worn out, gotten old, you can stimulate tissue repair, improve function with light. The brain seems to respond well to near-infrared light. . . . It’s like shining a flashlight on someone, so why not treat patients?”

Indeed, Cassano thinks light therapy could provide a groundbreaking new tool for depression treatment — one that is affordable, without side effects and more immediate than medication. He jokingly refers to it as a “tanning bed for the brain.”

When the identities of the treatment groups were finally revealed at the conclusion of the trial in August, Cassano found his preliminary analysis had held up. Sadness, anxiety, lethargy, agitation — the results showed that all were dramatically reduced in the treatment group.

That group included Jerrie Spencer. And several months later, the weight in her stomach still hasn't returned.

Part 3

Beyond the catchphrase

The pain and intransigence of obsessive-compulsive disorder motivates researchers plumbing its depths.

The computer screen and joystick are similar to those used with many virtual-reality games. It’s just that at the New York State Psychiatric Institute, the players compete while lying inside a highly sensitive MRI scanner.

In one challenge, the youths maneuver through a maze of corridors, searching for bright green dollar signs. Another tests their ability to recognize an error on the screen. All the while, the scanner is photographing “slices” of their brains. The ultimate reward is far more than a game: In the first clinical trial of its kind, those multi-band images are mapping the unknown territory of obsessive-compulsive disorder.

The goal of psychologist Rachel Marsh is to uncover what goes wrong in the brain circuits of people with OCD, among the most intransigent of mental conditions. But the institute, part of Columbia University Medical Center, is probing on multiple fronts. Several investigators are tracking an intriguing but often overlooked neurochemical in patients. And still others are studying an antibiotic commonly used to treat acne, which they hope could be one of the missing pieces of the agonizing OCD puzzle.

With recent technological advances, Marsh and her colleagues are doing what their counterparts in other branches of medicine have been doing for more than a century: putting OCD under the microscope in the search for its biomarkers, the concrete signs of mental disorders that could revolutionize how they get diagnosed, treated and perhaps even prevented.

Psychologist Rachel Marsh studies obsessive-compulsive disorder. Her latest research, conducted at the New York State Psychiatric Institute at Columbia University Medical Center, is generating thousands of images of brain circuitry in children to young adults with OCD. (Photo by Ryan C. Jones/For The Washington Post)

“This is an illness that really gets people off track in their lives,” said Helen Blair Simpson, director of the Center for Obsessive-Compulsive and Related Disorders at Columbia. “And it tortures them.”

Approximately one in 40 American adults will be affected by obsessive-compulsive disorder at some point in their life, twice the rate of schizophrenia, according to the National Institute of Mental Health. The average age of onset for OCD is 19, earlier than most other mental illnesses. And more than 5o percent of people with an OCD diagnosis have severe symptoms.

All of these individuals battle persistent, intrusive thoughts, such as a fear of germs or a need for symmetry in their environment. They respond to these obsessive thoughts with ritualistic, repetitive behaviors: compulsions, such as counting their footsteps, excessively bathing or endlessly checking that a door is locked.

Just as a car depends on a well-oiled transmission, the brain relies on smooth-running neural circuits. Experts think that in OCD, misfiring occurs across those circuits, especially in the frontal and mid-brain regions. Core neural functions are then disrupted, including goal-directed vs. habit-driven behavior, fear control, error detection and reward processing.

This breakdown triggers the symptoms of OCD, as well as a kind of feedback loop from which patients are unable to escape.

Marsh’s previous imaging research indicated that when OCD patients played a virtual reality game, their brains’ reward circuits weren’t activated the way they were in control subjects. Her hypothesis for the current work is that she will see the same pattern but that it will return to normal after treatment.

The current, multiyear study, which aims to enroll as many as 80 children and teenagers, is generating thousands of images — so many, in fact, that Marsh is having a super-computer built to catalog and analyze the massive amount of data.

Other institute scientists are studying these brain circuits in mice, all with a singular goal.

“The holy grail,” Marsh said, “is we see the same patterns of brain activation.”

Moira Rynn, director of child and adolescent psychiatry at Columbia University, is testing whether an antibiotic typically used for acne will help individuals struggling with obsessive-compulsive disorder. She and colleagues are looking for changes in the brain scans of those patients with OCD. (Photo by Ryan C. Jones/For The Washington Post)

Obsessive-compulsive disorder is a type of anxiety disorder. And anxiety, which is something virtually every human being has experienced, has an evolutionary purpose.

“The difference between anxiety and other disorders, like schizophrenia, is there’s nothing normal about hearing voices. But anxiety is a safe emotion to have. It keeps you out of trouble,” said Moira Rynn, director of child and adolescent psychiatry at Columbia University.

Until, of course, it goes awry.

For people with OCD, it’s a case of form following dysfunction. One main theory is that when the balance of activity is disturbed within the frontal lobe and mid-brain, cognitive and motor functions are affected. The result: repetitive behaviors, or compulsions.

“A compulsion is like an itch,” said Jordan, a New Jersey high school student who asked to be identified only by his first name. “It gets worse and worse if you don’t itch it. It drives you crazy.”

Jordan’s “brand” of OCD falls into the “just right” category. “I need to have everything feel just right,” he said. “When it’s not, it’s the most excruciating thing imaginable. It’s a feeling that just takes over you. You can never be happy again. You can’t go on. Everything is on the line.”

Every day, every hour, every minute. “Every move has to be meticulous.”

Jordan has felt this way, he says, “as long as I can remember.” The worries can come when he least expects them, and the rituals change all the time. Last year the 17-year-old took part in a clinical trial at the New York State Psychiatric Institute, which is on Manhattan’s Upper West Side, but he found only partial relief. Hoping to get better control of his symptoms, he traveled to Wisconsin in January for a weeks-long inpatient program.

“People use OCD as a catchphrase: ‘That’s so OCD,’” said Jordan’s mother, Meg. “But it’s very different from that. I know how much my son suffers.”

No one is sure why the disorder develops, although there are clearly genetic components with some people. Studies suggest that early-onset OCD is the most hereditable. Often it begins with what may seem like childhood tics. When Jordan was 4, he would have a meltdown if his sleeves didn’t reach all the way to his wrist. When he was 7, he had to constantly rearrange the items on his desk at school. At 12, he found it impossible to stop asking his teachers if he was doing the right thing.

Helen Blair Simpson, director of the Center for Obsessive-Compulsive and Related Disorders at Columbia University Medical Center, is involved in myriad projects aimed at unraveling the mysteries of those conditions. OCD is an illness "that really gets people off track in their lives," Simpson says. (Photo by Ryan C. Jones/For The Washington Post)

“The brain, as it is developing, has little hiccups,” Rynn explained. “Everybody has their own trajectory. Most kids, the hiccups smooth out and pass, but for a small, significant subset of others, they do not.”

There are two traditional treatments for OCD, often given together: cognitive behavioral therapy and medication, with drugs chiefly targeting the neurotransmitter serotonin. In combination, these treatments alleviate all but minimal symptoms in up to 40 percent of adults. To have all symptoms disappear is rare.

Serotonin has long been the diva of human brain chemicals and, along with dopamine, has hogged the spotlight as researchers looked for new psychiatric treatments. But recently, scientists turned their attention to the amino acid glutamate. Some think this other neurotransmitter could be one of the chief culprits in OCD.

An accidental discovery in 2007 proved to be the breakthrough. Researchers at Duke University Medical Center had been examining how certain proteins provide a kind of infrastructure for the brain’s neurons. When they genetically eliminated the Sapap3 protein from the OCD loop, the mice being studied turned anxious and exhibited obsessive-compulsive grooming behavior.

Sapap3 assists in glutamate’s modulation after it carries a signal between neurons. Without the protein, the nervous rodents’ cleaned themselves so often and so vigorously they developed bloody facial sores.

“People talk about serotonin this and serotonin that,” psychiatrist Suck Won Kim, an OCD expert at the University of Minnesota Medical Center, wrote when the Duke study was released. “But the brain is a circuit and it’s a serious mistake to think that one neurotransmitter works alone. . . . This new finding will change the story of OCD.”

It did. Others began to look for glutamate-modulating medications already approved by the Food and Drug Administration. Clinical trials tested two drugs thought to prevent excessive glutamate from overstimulating neurons; one normally is prescribed for amyotrophic lateral sclerosis and the other for Alzheimer’s disease.

At the New York State Psychiatric Institute, the researchers decided to consider a different medication. They turned to a broad-spectrum antibiotic called minocycline, which is used mainly for acne and infections as disparate as cholera and gonorrhea.

Animal investigations and other brain studies suggested minocycline might work for OCD by rebalancing glutamate levels critical to the obsession-compulsion pattern. Another significant factor: The drug was approved for use in children and adolescents with acne, meaning it had already cleared a huge safety hurdle.

Maybe mincoycline could prove pivotal, Rynn and Simpson thought.

The main problem was they needed funding, and there wasn’t necessarily money available from the National Institute of Mental Health. Not only does NIMH allocate a relatively paltry $30 million a year to OCD — compared with $200 million for schizophrenia — but it also had recently reorganized research priorities toward disease mechanisms and biomarkers of mental illness, rather than clinical trials and treatments. No problem. Rynn and Simpson wanted to investigate not only the clinical effects of minocycline treatment but also its possible mechanism of action, which was directly in line with NIMH’s new goals.

The NIMH bought the idea, providing nearly half a million dollars over three years. Starting in 2012, children, adolescents and young adults, ages 8 to 20, were recruited and randomly assigned either minocycline or a placebo to test whether the antibiotic changed glutamate levels in the mid-brain region. Afterward, each of the 50 participants was told what he or she had received and, if it was the minocycline, was given the opportunity of continuing on the medication. Because the results are still being evaluated, the researchers don’t yet know exactly how many did.

At his family's home on Long Island, Cory Muraglio is several years past the worst of his obsessive-compulsive disorder. He is now studying for a degree in experimental psychology. (Photo by Ryan C. Jones/For The Washington Post)

Even when Marsh, Rynn and Simpson are not collaborating on specific projects, their work often overlaps. Marsh relies on data from Simpson’s trials for some of her research and turns to clinicians such as Rynn for access to patients already in treatment.

The suffering inherent with OCD was what initially piqued Simpson’s interest years ago. Only later did she realize how much anxiety issues had affected people with whom she was close. Simpson knows the mysteries of the disorder remain daunting; solving them has become her own mission. In the meantime, she and her colleagues are buoyed by victories like Cory Muraglio.

The 22-year-old college student, who lives on Long Island, took part in a minocycline pilot trial. Before that, he was barely able to attend high school, scared of being contaminated by germs or poisoned by drinking water, and fearful that something dire would happen to his family. His obsessions gave rise to ritualized compulsions.

Sometimes it was repeating a series of words at certain parts of the day, or washing his hands a specific number of times. But always the behavior arose out of an overwhelming sense of dread.

“When the rituals would start, I would try to resist,” he recounted recently. “But it's like drowning. It was mental, physical, completely overwhelming, and if I was at school I couldn’t pay attention because of the thoughts that were in my head and the amount of energy and time they took up.”

Eventually, school was too much. “He wasn’t bathing; he couldn’t change his clothes. It was horrible,” said his father, Steve.

Once a week for three months, Steve drove Cory to the New York Psychiatric Institute’s OCD clinic in Manhattan, where his son received regular doses of minocycline. Slowly, almost imperceptibly, the anxiety slipped away. What happened next occurred just as gradually, but by the end of the 12-week study, Cory’s life was dramatically different.

“I can’t remember the moment I realized it,” he said. “I was pretty much symptom-less.”

Cory Muraglio has moved ahead with college after a pilot study at the New York State Psychiatric Institute brought relief from his severe obsessive-compulsive symptoms, which included an overwhelming sense of dread. It felt like "drowning," he said. (Photo by Ryan C. Jones/For The Washington Post)

A Brief History of Mental Illness and Mental Health in the United States

1773: The Public Hospital for Persons of Insane and Disordered Minds, the first mental institution in America, opens in Williamsburg, Va.

1841: Boston schoolteacher Dorothea Dix visits a jail in east Cambridge, Mass., sees the horrible conditions under which the mentally ill are kept and begins a lifetime of activism on their behalf.

1880: Because of Dix’s efforts, 119 psychiatric hospitals have been established in the United States.

1908: Clifford Beers publishes A Mind That Found Itself, a memoir about his dehumanizing treatment in a Connecticut mental institution. By the following year, he establishes an advocacy group that will eventually become the National Mental Health Association.

1909: Sigmund Freud visits the United States, gives public lectures and causes a huge increase in the number of professionals giving psychotherapy (especially Freudian analysis) and patients undergoing it.

1938: Electroshock therapy comes into use.

1945: Connecticut becomes the first state in the United States to regulate the practice of clinical psychology.

1946: Because of the rising rates of alcoholism in World War II veterans and juvenile delinquency, Harry Truman signs the National Mental Health Act, which leads to the founding of the National Institute of Mental health on April 15, 1949.

1949: At a conference in Boulder, Colo., clinical psychologists establish the Boulder Model of training, which aims to produce psychologists who are both scientists and practitioners. This marks the establishment of the medical model of mental illness in psychology and the requirement that future clinicians who call themselves psychologists earn a Ph.D

1952: Thorazine is developed for the control of psychosis.

1955: Public mental health facilities hold a record 558,922 patients, or about 3.4 per 1,000 Americans.

1958: Psychologist Dr. Joyce Brothers becomes a household name when she hosts the first TV show dedicated to helping people with their emotional problems. The popularity of both psychotherapy and psychoanalysis rises rapidly.

1962: Kurt Vonnegut’s semi-autobiographical novel, “One Flew Over the Cuckoo’s Nest,” is published.

1963: The deinstitutionalization of mentally ill patients begins when President John F. Kennedy signs the Community Mental Health Act into law.

1970: Lithium becomes the first major psychiatric drug marketed for the treatment of bipolar disorder.

1972: The idea takes hold that depression is the result of a chemical imbalance in the brain, which drugs can fix.

1979: Psychology Today magazine proclaims this is the “Age of Depression” in the United States.

1980: The Diagnostic and Statistical Manual of Mental Disorders describes criteria of major mental illnesses for the first time.

1987: Prozac hits the market.

1999: A U.S. Surgeon General’s report says more than half of all Americans struggle with some form of mental illness.

2000: Total enrollment in mental health managed care programs (169 million) exceeds the number of people enrolled in non-mental health managed care programs.

2003: The number of people disabled by mental illness (and receiving Social Security disability), hits 5.7 million – a rate of 19.7 per 1,000 Americans, six times higher than in 1955.

2004: Sales of antidepressants and antipsychotics reach $40 billion.

2006: Fewer than 40,000 Americans are inpatients in mental institutions, a decline of more than 92 percent from the 1950s.

Sources: U.S. Department of Health and Human Services; Substance Abuse and Mental Health Services Administration; Ronald W. Dworkin, "Psychotherapy and the Pursuit of Happiness," The New Atlantis, Spring 2012; Colleen L. Barry, “Design of Mental Health Benefits,” Health Affairs, September 2003, “Imminent Danger: Mental Health in America,” Milwaukee Journal Sentinel, December 2011; “Timeline: Deinstitutionalization and its Consequences,” Mother Jones, April 2013.

THE END

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