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][THE O PT I MAL BRAIN DIET The field of nutritional psychiatry is taking

off as scientists home in on the ingredients

for good mental health and cognitive

staying power

BY BRET STETKA

IN SEARCH

OF

© 2016 Scientific American © 2016 Scientific American

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C arolyn feels great these days. She exercises. She’s socially active. She spends as much time with her four grandchildren as possi- ble. But it wasn’t always that way. A retired radiology film librarian from Pittsburgh, she began feeling apathetic and iso- lated seven years ago. “I’d just

lost my mother, and my two sons had moved away,” recalls Carolyn, now 75. She also strug- gled with excess weight, diabetes and chronic lung disease. She was grieving, eating a worri- some amount of junk food and slipping into what looked a lot like depression.

A few years later a friend told Carolyn about a depression-prevention study at the University of Pittsburgh. She signed up imme- diately. All 247 participants were, like her, old- er adults with mild depressive symptoms— people who without treatment face a 20 to 25 percent chance of succumbing to major depres- sion. Half received about five hours of problem- solving therapy, a cognitive-behavioral ap- proach designed to help patients cope with stressful life experiences. The rest, including Carolyn, received dietary counseling. Guided by a social worker, she discovered that she liked salmon, tuna and a number of other “brain- healthy” foods—which quickly replaced all the chips, cake and candy she was eating.

When the trial concluded in 2014, the re- sults came as a surprise—to the researchers at least. The dietary counseling was not meant to have any substantial effect; Carolyn’s group was the experiment’s control. And yet psychiatrist Charles Reynolds and his colleagues discovered that both interventions had significantly reduced the risk of depression—by approximately the same amount. When they reviewed the data, all the patients scored on average 40 to 50 percent lower on the Beck Depression Inventory test, a com- mon measure of depressive symptoms, 15 months after their ses-

sions ended. What is more, only about 8 percent, regardless of the therapy they received, had fallen into major depression.

It cannot be ruled out that a placebo effect contributed to the improvements seen in both groups. Meeting with a health care professional and being proactive about getting better in and of itself may have helped participants feel more upbeat. In Carolyn’s view, however, she had reversed her downward spi- ral largely by changing how she ate.

She is not alone in making that connection. Among scien- tists and clinicians there is a growing appreciation of the criti- cal interplay between diet and brain health. The evidence is preliminary, and it is hard to tease out cause and effect. Per- haps people who eat well are also apt to have other healthy brain habits, such as regular exercise and good sleep routines. Or maybe depressed people tend to self-medicate with Oreos. But the data continue to accumulate. Every year the list of cor- relations between certain foods and mental well-being grows: fish and other sources of omega-3 fatty acids might help fend off psychosis and depression; fermented foods such as yogurt, pickles and sauerkraut seem to ease anxiety; green tea and an-

© 2016 Scientific American

FAST FACTS PRESCRIPTION HAPPY MEALS

nn Research indicates that traditional diets from the Mediterranean, Scandinavia and Japan help to preserve our psychological and cognitive well-being.

no These diets all feature fish, one of the best sources of omega-3 fatty acids—nutrients that play a vital role in promoting neuronal health and that may have helped drive the evolution of the human brain.

np Studies indicate that diet changes may alleviate a range of psy- chiatric symptoms, and mental health practitioners may start to complement therapy and pharmaceutical treatments with recommended eating plans in the near future.

Evidence links stereotypical Western diets, which are heavy in processed and fatty foods, to higher rates of depression and anxiety. Unhealthy diets most likely contribute to a range of neuropsychiatric disorders by increasing inflammation.

M I N D . S C I E N T I F I C A M E R I C A N . C O M S C I E N T I F I C A M E R I C A N M I N D 2 9

tioxidant-rich fruits may help keep dementia at bay. And so on. There is probably no single ingredient, no happy seed from

the jungles of beyond, that is sure to secure a better mood or mental acuity into old age. But there do appear to be specific di- etary patterns—calibrated by millions of years of human evolu- tion—that boost our cognitive and psychological fitness. With- in the nascent field of nutritional psychiatry, consensus is build- ing about just what types of diets are best. And perhaps most exciting is the prospect that dietary intervention could serve as a valuable adjunct to medication and other therapies for mental disorders—just as it does in so many other areas of medicine.

Good Diet, Bad Diet When it comes to promoting brain health, the diet support-

ed by the strongest data draws on traditional eating patterns from Italy, Greece and Spain. The so-called Mediterranean diet con- sists primarily of fruits, vegetables, nuts, whole grains, fish, lean meats in moderation, olive oil and maybe a little red wine. In 2011 public health expert Almudena Sánchez-Villegas of the Uni- versity of Las Palmas de Gran Canaria and her colleagues as- sessed the relation between this diet and depression in more than 12,000 healthy Spaniards over the course of a median of six years each. They found that compared with people who did not eat a Mediterranean diet, those who did were significantly less likely

to succumb to depression. For the subjects who followed the diet most closely, the risk dropped by a substantial 30 percent.

Sánchez-Villegas later confirmed the association in another large trial. The PREDIMED (Prevention with Mediterranean Diet) study—a multicenter research project evaluating nearly 7,500 men and women across Spain—initially looked at wheth- er a Mediterranean diet, supplemented with extra nuts, protects against cardiovascular disease. It does. But in 2013 Sánchez- Villegas and other investigators also analyzed depression data among PREDIMED’s participants. Again, compared with sub- jects who ate a generic low-fat diet, those who adhered to the nut-enriched Mediterranean diet had a lower risk for depression. This was especially true among people with diabetes, who saw a 40 percent drop in risk. Perhaps these patients, who cannot ad- equately process glucose, benefited the most because the Medi- terranean diet minimized their sugar intake.

Indeed, a central feature of the diet is that it is low in sugar, as well as processed foods and fatty meats, which are common- place on most Western menus. Leading nutritional psychiatry researcher Felice N. Jacka of Deakin University and the Univer- sity of Melbourne in Australia was one of the first to demon- strate an association between stereotypical Western diets and depression and anxiety. Most recently, she has drawn another link between poor diet and, quite literally, a shrinking brain. In

Traditional Diets for Healthy Brains

M E D I T E R R A N E A N

Research consistently finds the dietary patterns of cultures hugging the Medi- terranean Sea to be among the healthi- est in the world. Ingredients common to Greek, Italian, Spanish and Middle East- ern cuisine (below) are linked with im- proved cardiovascular, mental and neu- rological function.

Olive oil > Omega-3-rich fish (sardines,

tuna, salmon) Antioxidant-rich fruits and vegetables (tomatoes, peppers, eggplant) Whole grains Legumes Moderate amounts of lean meat and red wine Limited sugar and processed food

O K I N AWA N

According to the World Health Organiza- tion, the Japanese have the highest life ex- pectancy in the world— in part thanks to the population of Okinawa. Staples of the island group’s traditional diet (below) in- clude the nutrient-rich purple sweet potato, often eaten in place of rice. Indeed, Oki- nawans tend to eat less fish, meat, rice and sugar—and fewer calories overall—than do those in other parts of the country.

> Antioxidant-rich vegetables (Okinawan purple sweet potatoes)

Seaweed Some fish Some meat Limited sugar and white rice intake

S C A N D I N AV I A N

Swedish meatballs aside, Scandinavians cook, collect and cultivate a host of foods that together constitute the new Nordic diet, one of the world’s healthiest. It is associated with re- duced inflammation and decreased risk for cardiovascular disease and diabetes, both of which can influence brain health. Of particular note, Scandinavians tend to cook with canola oil, also called rapeseed oil, which contains far more omega-3 fatty acids than olive oil.

Fruits (lingonberries) Vegetables (potatoes) Nuts/whole grains (rye breads very common) Seafood Moderate amounts of meat and dairy > Canola (rapeseed) oil

© 2016 Scientific American

A STUDY OF MORE THAN 12,000 HEALTHY SPANIARDS FOUND THAT THOSE WHO CLOSELY FOLLOWED A MEDITERRANEAN DIET HAD A 30 PERCENT REDUCED RISK OF DEPRESSION. ][

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September 2015 she and her colleagues discovered that older adults who consumed a Western diet for four years not only suf- fered higher rates of mood disorders but also had a significant- ly smaller left hippocampus on MRI scans. The hippocampus, composed of two seahorse-shaped arcs of brain tissue deep un- derneath our temples, is critical to memory formation. Jacka focused on the hippocampus because animal studies have also noted diet-related changes there.

Scientists have proposed a number of possible mechanisms to explain this damage. Jacka’s findings parallel other research revealing that high-sugar diets can prompt runaway inflam- mation and trigger a cascade of other metabolic changes that ultimately impair brain function. Ordinarily inflammation is part of our immune system’s arsenal to fight infection and en- courage healing, but when it is misdirected or overly aggres- sive, it can destroy healthy tissues as well. According to numer- ous studies, inflammation plays a role in a range of brain dis- orders—from depression and bipolar disorder to possibly autism, schizophrenia and Alzheimer’s disease.

Two meta-analyses from 2010 and 2012 collectively re- viewed data from 53 studies and reported significantly elevat- ed levels of several blood markers of inflammation in depressed patients. And numerous studies have reported increased or al- tered activity of immune cells called microglia—which play a key role in the brain’s inflammatory response—in patients with psychiatric disorders, including depression and schizophrenia. It is not clear whether inflammation causes mental illness in some cases, or vice versa. But the evidence suggests that many if not most known risk factors for psychiatric disorders, espe- cially depression, promote inflammation; these include abuse, stress, grief and certain genetic predilections.

Jacka’s work repeatedly points to traditional diets such as Mediterranean, Japanese and Scandinavian ones— all of which tend to be noninflammatory—as being best for our neu- rological and mental health. “There is no doubt that stress and uncomfortable emotions can cause us to reach for the biscuit tin—they don’t call them comfort foods for nothing!” she ad- mits. “But consistently the data show that the main constitu- ents of a healthy brain diet include fruits, vegetables, legumes, nuts, fish, lean meats and healthy fats such as olive oil.”

Brain-Building Fatty Acids Increasingly, researchers are finding that the power of these

more traditional diets extends beyond just supplanting bad food with good. Last summer neuroscientists Amandine Pelletier, Christine Barul, Catherine Féart and their colleagues at the Uni-

versity of Bordeaux in France discovered that a Mediterranean diet may actually help physically preserve neuronal connections in the brain. They used a highly sensitive neuroimaging analy- sis technique called voxel-based morphometry to identify subtle changes in brain anatomy over time. And last September nutri- tional epidemiologist Martha C. Morris of Rush University and her co-workers reported that the MIND diet—a hybrid of the Mediterranean and the high-nutrient, low-salt DASH diet—may help slow cognitive decline and possibly even help prevent Alz-

heimer’s. When they tested cognitive ability in 960 older adults, those who had followed the MIND diet for roughly five years achieved scores matching those of people 7.5 years younger.

Our evolutionary backstory could explain these neuro- protective effects. Sometime between 195,000 and 125,000 years ago, humans may have nearly gone extinct. A glacial period had set in that probably left much of the earth icy and barren for 70,000 years. The population of our hominin an- cestors plummeted to possibly only a few hundred in number, and most experts agree that everyone alive today is descend- ed from this group. Exactly how they—or early modern hu- mans, for that matter—managed to stay alive during recur- ring glacial periods is less clear. But as terrestrial resources dried up, foraging for marine life in reliable shellfish beds sur- rounding Africa most likely became essential for survival. Graduate student Jan De Vynck of Nelson Mandela Metro- politan University in South Africa has shown that one person working those shellfish beds can harvest a staggering 4,500 calories an hour.

In both animal and human studies, typical unhealthy Western diets appear to cause damage to the hippocampus (yellow on MRI scan above), a brain structure that plays an essential role in learning and memory. In one recent study, older adults who had consumed poor- quality diets over the course of four years had a smaller left hippo- campus compared with peers who ate more healthfully.

© 2016 Scientific American

THE AUTHOR

BRET STETKA is an editorial director at Medscape (a subsid- iary of WebMD) and a frequent contributor to Scientific Ameri- can Mind. His writing has appeared in Wired and online for the Atlantic and NPR.

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The archaeological record corroborates the idea and indi- cates that our ancestors depended on a diet heavy in shellfish and cold-water fish—both rich sources of omega-3 fatty acids. These fats may have driven the evolution of our uniquely com- plex brains, which are 60 percent fat in composition. One ome- ga-3 in particular, docosahexaenoic acid, or DHA, is arguably the single nutrient most strongly associated with brain health.

In 1972 psychiatrist Michael A. Crawford, now at Imperial College London, co-published a paper concluding that the brain

is dependent on DHA and that DHA sourced from the sea was critical to mammalian brain evolution, especially human brain evolution. For more than 40 years he has argued that the rising rates of brain disorders are a result of post–World War II dietary changes—especially a move toward land-sourced food and, sub- sequently, the embrace of low-fat diets. He feels that omega-3s from seafood were critical to the human species’ rapid neural march toward higher cognition [ see box above].

Many studies have confirmed DHA’s importance to the de-

By Land or by Sea? Experts debate how human ancestors found enough fatty acids to build better brains

Omega fatty acids, including docosahexaenoic acid, or DHA, are

key to brain health and most likely helped to drive the evolution

of the modern human brain. But how did early humans access

these vital nutrients? The answer is a matter of some debate.

For nearly two decades archaeologist Curtis W. Marean,

associate director of Arizona State University’s Institute of

Human Origins, has overseen excavations at a site called Pin-

nacle Point on South Africa’s southern coast, near where a

newly discovered early human species, Homo naledi, was

recently unearthed. His work there suggests that sometime

around 160,000 years ago, during a glacial period known as

Marine Isotope Stage 6 (MIS6), humans made a significant

shift in their eating habits, moving from foraging for terrestrial

plants, animals and the occasional inland fish to relying on the

rich, predictable shellfish beds in the area.

Marean believes this change occurred when early humans

learned to exploit the bimonthly spring tides. And to do so, he

says, our brains were already fairly well evolved. “Accessing

the marine food chain could have had huge impacts on fertili-

ty, survival and overall health, including brain health,” Marean

explains, in part because of the high return on omega-3 fatty

acids. But before MIS6, he speculates, hominins would have

had access to plenty of brain-healthy terrestrial nutrition,

including by feeding on animals that consumed omega-3- rich

plants and grains.

Others disagree, at least in part. “I’m afraid the idea that

ample DHA was available from the fats of animals on the savan-

na is just not true,” says psychiatrist Michael A. Crawford of

Imperial College London. “The animal brain evolved 600 million

years ago in the ocean and was dependent on DHA and com-

pounds essential to the brain such as iodine, which is also in

short supply on land. To build a brain, you would need building

blocks that were rich at sea and on rocky shores.”

His early biochemical work focused on showing that DHA is

not readily accessible from the muscle tissue of land animals.

Using DHA tagged with a radioactive isotope, Crawford and his

colleagues also demonstrated that “ready-made” DHA—such

as that found in shellfish—is incorporated into the developing

rat brain with 10-fold greater efficiency than plant-sourced DHA.

Crawford’s colleague and collaborator, physiologist Stephen

Cunnane of the University of Sherbrooke in Quebec, also feels

that aquatically sourced food was crucial to human evolution.

But he believes that before MIS6, inland hominins had already

incorporated fish from lakes and rivers into their diet for mil-

lions of years.

He suggests that it was not just omega-3s but a cluster of

nutrients found in fish (including iodine, iron, zinc, copper and

selenium) that contributed to our big brain. “I think DHA was

hugely important to our evolution and brain health, but I don’t

think it was a magic bullet all by itself,” Crawford says.

All three researchers are confident that higher intelligence

evolved gradually over millions of years as mutations inched the

cognitive needle forward, conferring survival and reproductive

advantages. But advantages such as, say, figuring out how to

shuck oysters—as well as track the spring tides—threw open

the Darwinian floodgates. Cunnane comments: “Once we were

able to access the coastal food chain in Africa—far more rich

and reliable than inland sources of fish—brain and cultural evo-

lution exploded.” — B.S.

Even before early humans began foraging for seafood, they may have incorporated nutrient-rich fish from lakes and rivers into their diets, helping them to build healthy brains.

© 2016 Scientific American

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velopment, structure and function of the human brain: it is a component of neuronal cell membranes, facilitates neuron-to- neuron communication, and is also thought to boost levels of brain-derived neurotrophic factor, a protein that supports the growth and survival of brain cells. Given the starring role this and other omega-3 fatty acids play in shaping and maintain- ing our most complex organ, it makes intuitive sense that in- corporating more of them into our diet—by emphasizing sea- food—might, as the nutritional data suggest, protect the brain from going haywire. Also of note, DHA appears to decrease chronic brain-harming inflammation.

Fatty acids aside, there is another important link between our ancestors’ diets, inflammation and mental health. As we evolved, the 100 trillion bacteria, fungi and other microorgan-

isms that colonize our bodies and constitute 90 percent of our cells came along for the ride. This so-called microbiota—and its collective genes, the microbiome—makes a critical contribution to the formation and function of our digestion and immune sys- tem. A growing number of findings now suggest that disrupting it through poor eating habits comes at a cost to the brain.

A Blow to the Gut In one striking (if slightly nauseating) experiment in 2014,

then 23-year-old student Tom Spector wiped out about a third of the bacterial species in his gut by limiting his diet to McDonald’s fast food. It took only 10 days. Spector played the guinea pig for two reasons: as a project to complete his genet- ics degree and to provide data for his father, Tim, a genetic epidemi ology professor at King’s College London, who stud- ies how processed diets affect gastrointestinal bacteria. The Spector family’s research did not assess specific health conse- quences—they were measuring only the drop in floral diversi- ty in Tom’s gut—but Tom did report feeling lethargic and down after days of burgers, fries and sugary soda. The decline in species was so drastic that Tim sent the results to three lab- oratories for confirmation.

Diet-induced shifts in the microbiota of the kind Spector brought on himself can rapidly ratchet up inflammation in the gut. On top of the ill effects just described, gastrointestinal in- flammation can deplete our supply of serotonin, a neurotrans- mitter long tied to depression and other psychiatric disorders. About 90 percent of our serotonin is produced in the gut when certain microbes interact with cells lining the gastrointestinal tract (some microbes even produce a portion of our serotonin themselves). But by-products of inflammation convert sero- tonin’s metabolic precursor, tryptophan, to a compound that generates neurotoxic metabolites linked with depression, schizophrenia and Alzheimer’s.

The good news is that dietary changes can not only wreck our microbial diversity, they can boost it, reducing gastrointes- tinal inflammation in the process. In 2015 a group at the Uni- versity of Pittsburgh conducted a study in which 20 African- Americans from Pennsylvania swapped diets with 20 rural black South Africans. In place of their usual low-animal-fat, high-fi- ber diet, the Africans consumed burgers, fries, hash browns, and the like. The Americans eschewed their normal fatty foods and refined carbohydrates for beans, vegetables and fish. After just two weeks the Americans’ colons were less inflamed, and fecal samples showed a 250 percent spike in butyrate-producing bac- terial species. Butyrate is thought to reduce the risk of cancer. The South Africans, on the other hand, underwent microbial changes associated with increased cancer risk.

“Dietary changes are the easiest way to alter your microbi- ome and help to control inflammation,” says psychiatrist Emi- ly Deans of Harvard Medical School. She believes diet is every bit as important as pills and psychotherapy in managing men- tal illness—a view informed by her own clinical practice. “I dis- cuss nutrition with just about all of my patients,” she adds, “and

Cold-water fish, such as salmon, tuna and sardines (above), are rich sources of DHA, a fatty acid that contributes to the growth, structure and function of nerve cells.

© 2016 Scientific American © 2016 Scientific American

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I think it can really help in managing conditions like depres- sion, at least in some people.” Deans also feels that timing of meals can influence mood, and research suggests that eating on a regular schedule can improve mental health.

Deans acknowledges that science has a long way to go before we fully understand the brain-diet relation. She is also wary of the massive probiotic industry that has, like the supplement in- dustry in general, barreled ahead of the minimal but growing sci- entific evidence suggesting that probiotics might be effective in preventing or treating mental illness. “You can do studies with, for example, certain vitamins, and some might turn out positive and others negative,” she explains. “But the truth is vitamins ex- ist in all sorts of different chemical states in food and in just one state in supplements.” This difference in form between nutrients in food versus pills explains why the data tend to favor nutrition through diet rather than supplementation. “I think we can safe- ly say that certain dietary patterns seem to promote a healthy mi- crobiome,” Deans speculates, “like the Mediterranean diet and diets that include lots of fiber, fermented foods and fish.” And a healthy microbiome may be essential for a healthy brain.

Food for Thought For seven years now Carolyn has been eating better—fo-

cusing on seafood and cutting back on sugar. She has lost weight, and her diabetes is under control. “It’s part of a whole new way of life,” she glows, “knowing that what I eat can af- fect how I feel.” That awareness is building momentum among patients and practitioners alike. In March 2015 a large team of clinicians and researchers published a report in the Lancet Psy- chiatry on behalf of the International Society for Nutritional Psychiatry Research— an organization Jacka co-founded in 2013. Citing modest therapeutic gains yielded by many psychi- atric drugs, the authors called for the integration of nutrition- based approaches into mental health care. “The emerging and compelling evidence for nutrition as a crucial factor in the high prevalence and incidence of mental disorders,” they wrote, “suggests that diet is as important to psychiatry as it is to car- diology, endocrinology, and gastroenterology.”

Thanks to our evolutionary lineage (and plenty of fish), at- tention to our diets may prove critical to reversing the rising rates of mental illness around the world; lowering the proportion of people struggling with various forms of dementia; and staving off milder psychiatric symptoms and disorders. There is little doubt that eating right can help shuttle us through tough times— just as it may have done 160,000 years ago for a small group of humans huddled in coastal African caves.

One of the leading proponents of leveraging diet to better brain health, Jacka is encouraged that interventional studies— in which patients are actually “prescribed” a particular diet and tracked over time—are finally getting under way. Such research will be able to offer more definitive proof of the connection be- tween diet and mental and cognitive well-being. Jacka’s own group is now conducting a randomized controlled investigation to assess the effectiveness of dietary changes in adults with ma- jor depression. “Our current trial is the first to attempt to direct- ly address the question: ‘If I improve my diet, will my depression improve?’” she says, adding, “The preliminary results look very exciting.” Her team hopes to have answers later this year.

In the meantime, many doctors and patients are begin- ning to see dietary interventions as a beacon of hope after sev- eral decades of disappointing psychiatric drug development. Too many patients suffering from mental illness or dementia do not respond adequately to existing medications, if at all. For example, selective serotonin reuptake inhibitors such as Prozac—one of the most commonly prescribed drug classes for treating depression—appear effective only in severe cas- es; they are often no better than placebo for mild to moder- ate disease. As scientists learn more about the pathologies be- hind mental and cognitive disorders, new and promising ther- apeutic targets will surely emerge. But it is clear that nutrition-based treatment plans—free from side effects and low in cost—will also figure prominently in the future of de- mentia and psychiatric care. M

MORE TO EXPLORE

■ Mediterranean Dietary Pattern and Depression: The PREDIMED Randomized Trial. Almudena Sánchez-Villegas et al. in BMC Medicine, Vol. 11, Article No. 208; September 20, 2013.

■ Early Intervention to Preempt Major Depression among Older Black and White Adults. Charles F. Reynolds et al. in Psychiatric Services, Vol. 65, No. 6, pages 765–773; June 2014.

■ The Origins and Significance of Coastal Resource Use in Africa and Western Eurasia. Curtis W. Marean in Journal of Human Evolution, Vol. 77, pages 17–40; December 2014.

■ Nutritional Medicine as Mainstream in Psychiatry. Jerome Sarris et al. in Lancet Psychiatry, Vol. 2, No. 3, pages 271–274; March 2015.

■ Western Diet Is Associated with a Smaller Hippocampus: A Longitudinal Investigation. Felice N. Jacka et al. in BMC Medicine, Vol. 13, Article No. 215; September 8, 2015.

From Our Archives ■ The Most Invasive Species of All. Curtis W. Marean; August 2015. ■ Brain Food. Dina Fine Maron; The Science of Health, September 2015.

© 2016 Scientific American

DIET MAY BE “AS IMPORTANT TO PSYCHIATRY AS IT IS TO CARDIOLOGY, ENDOCRINOLOGY, AND GASTROENTEROLOGY,”

SAYS A 2015 REPORT IN THE LANCET PSYCHIATRY. ][

© 2016 Scientific American