Images of psychiatry and psychiatrists

11 01 2015

By: Stuart H, Sartorius N, Liinamaa T, the Images Study Group. Acta Psychiatr Scand 2015: 131: 21–28

 

Objective: This study surveyed medical teaching faculty to determine
their attitudes toward psychiatry and psychiatrists.
 
Method: We conducted a multisite survey of a probability sample of
1057 teaching medical faculty members from 15 academic teaching
centers in the United Kingdom, Europe, and Asia stratified by early,
middle, and late career stage. The average response rate across
countries was 65%.
 
Results: The outstanding findings were that 90% of respondents
considered that psychiatrists were not good role models for medical
students, 84% thought psychiatric patients were unsuitable to be
treated outside of specialized facilities, and 73% thought psychiatric
patients were emotionally draining. We noted statistically significant
differences by country, gender, career stage, and specialty.
 
Conclusion: These results highlight why recruitment into psychiatry is
problematic in many countries and suggest that greater attention should
be given to improving the perception of psychiatrists as good role
models and the efficacy of psychiatric treatments
The full text of this interesting paper is available Here 




A Conceptual Framework for Understanding and Treating Trauma and PTSD in Persons with Serious Mental Illness

7 07 2014

Today I want to share two lectures by Prof. Kim T. Mueser, head of the Center for Psychiatric Rehabilitation at Boston University. In the first speak Prof. Mueser discusses a conceptual framework for understanding trauma and PTSD among persons with serious mental illness. At the second lecture, Prof. Mueser reviews treatment of PTSD among persons with serious mental illness. I find this topic and these talks very interesting and I hope that you will find it relevant and helpful.





THE UNCONSCIOUS: A bridge between psychoanalysis and cognitive science – Researchers and clinicians in dialogue

23 03 2014

This year the Joseph Sandler Research Conference was devoted to a central topic of the interdisciplinary dialogue between contemporary psychoanalysis and other scientific disciplines: the unconscious. In order to see the lectures of the leading researchers and practitioners that participated in this interesting conference click HERE.

I would like to thanks Ms. Irith Raveh, Founder and Chairperson at Israel Forum of Neuropsychoanalysis, that sent me the links to these great lectures.





Brain Awareness Month – What do we know and don’t know about the brain

12 03 2014

Brain Awareness

By Thomas Insel

This is the time of March Madness, Daylight Savings Time, and what Emily Dickinson famously called the “month of expectation.” March is also Brain Awareness Month, an annual celebration with school visits, community lectures, and lab tours to introduce the public to the mind-blowing world of neuroscience. A list of Brain Awareness events can be found at http://www.dana.org/brainweek/ , where you will also find that March 10 -16 is the peak for related public events around the world.

Since NIMH began focusing on mental disorders as brain disorders nearly two decades ago, educating people about the brain has been a priority for us. We often say that with the powerful tools of neuroscience, we can now use the brain to understand the mind, fulfilling the original vision that Freud had for a scientific psychology. But we have to remain humble about our understanding of the brain, because even our most powerful tools remain pretty blunt instruments for decoding the brain. In fact, we still do not know how to decipher the basic language of how the brain works.

A few numbers can help to define the challenge. The human brain is thought to have close to 86 billion neurons, each making on average about 10,000 connections. In contrast to most animals, our brains are largely made up of a heavily folded cortex, accounting for 80 percent of brain mass and about 100,000 miles of axons that provide the highways between neurons.1

How many different kinds of neurons are there in the brain? We really don’t know.  Unlike the heart or kidney, which have a small, defined set of cell types, we still do not have a taxonomy of neurons, and neuroscientists still argue whether specific types of neurons are unique to humans. But there is no disputing that neurons are only about 10 percent of the cells in the human brain. Most of our brain cells are glial cells, once thought to be mere support cells, but now understood as having a critical role in brain function. Glial cells in the human brain are markedly different from glial cells in other brains, suggesting that they may be important in the evolution of brain function. As one hint to their function, astrocytes, which are one form of glial cell, have been reported recently to “eat” synapses in the brain, providing a critical new mechanism for brain plasticity.2

How does the brain work? Again, we really don’t know. We have a very detailed understanding of how the heart pumps and the kidney filters, but how the brain encodes, stores, and retrieves information is still largely a mystery. We have known for over a century that most of the cortex is organized horizontally into six precise layers, and much of the cortex has vertical mini-columns, but how this matrix of horizontal and vertical structures computes information is not really clear.

Neuroscientists talk a lot about brain circuits. In fact, the word “circuit” is probably misleading. We do not know where most circuits begin and end. And unlike an electrical circuit, brain connections are heavily reciprocal and recursive, so that a direction of information flow can be inferred but sometimes not proven. We believe there are “emergent properties” of the brain that convert electrical signals into memories or dreams, but how this happens is still a mystery. Recent studies have shown that diffuse waves of synchronization across the brain may be critical for attention or learning, but we are just learning about these slow waves of activity, and whether they occur at the “speed of thought” is still debated.3

Of course, the spectacular images from MRI and PET scans have already given us maps for perception and fear and language and many other functions. As scanners have improved their resolution from 1.5T (tesla) to 3T to recent 7T magnets, and the protocols and analytic approaches have evolved, we now can map the cortical real estate associated with complex tasks like decision-making and face recognition. But these approaches, even with the best current technology, are still a 30,000-foot view of the action. Jay Giedd here at NIMH estimates that each gray matter voxel—the individual 3D pixels of 1 cubic mm that make up the scan—contains about 90,000 neurons, 400 meters of dendrites, and 4.5 million synapses. Each scan has over 650,000 voxels. And the actual measure is not neural activity per se but local blood flow, which changes slowly relative to the speed of thought.

In a sense, functional MRI (fMRI) is providing an image of something like the power grid of a city. fMRI slowly maps where and when different parts of the brain wake up, based on blood oxygen metabolism. By contrast, the street map of the brain is being mapped by the Human Connectome Project. Supported by the NIH Blueprint for Neuroscience Research , over 100 neuroscientists at ten sites in the United States and Europe are building something like a Google map for the human brain.  Scientists at Massachusetts General Hospital have created new MRI scanners with greatly enhanced resolution for looking at the geometric structure of the human brain.4 One remarkable claim from that work (still controversial) is that the fiber connections which heretofore looked like a bowl of spaghetti might actually have a relatively simple grid structure, allowing comparisons of connectomes between people. This kind of comparison is already underway at Washington University and the University of Minnesota where the Human Connectome Project  is obtaining the wiring diagrams of 1200 healthy adults, including 300 twin pairs. Thus far, data from the first 226 volunteers have been released on the Connectome website, with 10 gigabytes of data available for each subject. That’s right, this project is releasing the data as it becomes available to scientists everywhere—over 700 users are already mining the Connectome data to see how a Google map of the human brain might answer their questions.

Whether March for you means basketball, changing clocks, or expectations, I hope you will check out some of the Brain Awareness events. Brain science has become one of the most exciting frontiers of science. When I was a kid, the scientific frontier was “outer space.” Today it seems to be “inner space” that fascinates the boldest and brightest young minds (or should we say young brains). We are still at the beginning of what could be an era of brain exploration, with great promise for understanding more about how each of us thinks and dreams and loves, but perhaps even greater promise for helping people with mental disorders.

References

1 Lent R, Azevedo FA, Andrade-Moraes CH, Pinto AV. How many neurons do you have? Some dogmas of quantitative neuroscience under revision.  Eur J Neurosci. 2012 Jan;35(1):1-9. doi: 10.1111/j.1460-9568.2011.07923.x.

2 Chung WS et al. Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways . Nature. 2013 Dec 19;504(7480):394-400. doi: 10.1038/nature12776. Epub 2013 Nov 24.

3 Salazar RF, Dotson NM, Bressler SL, Gray CM. Content-specific fronto-parietal synchronization during visual working memory Science 2012 Nov 23;338(6110):109-100. doi: 10.1126/science.1224000.

4 Wedeen VJ et al. The geometric structure of the brain fiber pathways .Science. 2012 Mar 30;335(6076):1628-34. doi: 10.1126/science. 1215280.





Why did mental health got attention at the World Economic Forum in Davos

29 01 2014

You can find three main answers for the question above at the latest post of NIMH director, Dr. Thomas Insel:

Mental Health in Davos

By Thomas Insel

Just returning from the World Economic Forum (WEF) in Davos, Switzerland. While media reports covered speeches from some of the 40 heads of state attending or skewered the over-the-top parties of the rich and famous associated with this annual meeting, they missed a remarkable story: this was the year that mental health became a hot topic at the WEF. There were over 20 sessions on health, many of them focused on mental illness, dementia, or mindfulness. Philip Campbell, editor-in-chief of Nature, moderated a session on the “Mental Health Imperative.” An unprecedented health summit began with the Prime Minister of Norway declaring that mental health was her leading health care priority. And celebrities from Goldie Hawn to Arianna Huffington argued for the need to focus on mental health. One Davos regular compared mental health in 2014 to AIDS in 1994, when the WEF declared the need for a global focus on an emerging, heavily stigmatized, frequently misunderstood disorder.

Why did mental health get so much attention at a global economic meeting, dedicated to “improving the state of the world”? I heard three answers to this question. First, the WEF focuses on the developing world, or in WEF-speak “emerging markets” as well as the developed world. Health problems have become a major speed bump to development, with chronic, non-communicable diseases (diabetes, heart disease, cancer, pulmonary diseases, mental disorders) the major economic and public health threat. In a study  commissioned by the WEF, mental disorders emerged as the single largest health cost with global projections increasing to $6 trillion annually by 2030, more than diabetes, cancer, and pulmonary diseases combined. Perhaps that should not be surprising since mental disorders, which usually start before adulthood, greatly increase the risk for other chronic, non-communicable diseases throughout the lifespan. Hence, the expression “no health without mental health.”

Second, for employers, mental illnesses, especially anxiety and mood disorders, are a threat to productivity. Research has shown that the high rates of absenteeism and presenteeism (at work despite illness) associated with depression cost, on average, $250,000 for every 1000 workers each year.1 An NIMH-funded study showed that even a low-intensity intervention, cognitive behavior therapy delivered by telephone, could offset these costs.2 While Davos extols compassionate leaders dedicated to the well-being of their employees, for many CEOs the business case for detecting and treating depression was also compelling.

Third, the Davos meeting is a place for identifying macroeconomic and social trends. This year we heard about big data, the “internet of things” (sensors for mobile devices and wearable computers), and robotics. But an even bigger trend was the recognition that the 21st century will belong to brain-based economies. This explains, in part, the brain initiatives that have been launched in the European Union and the United States (both featured at this meeting) and it explains the concern with policies for brain health, from promoting resources for child development to preventing dementia. In the same way that infectious diseases were understood and curtailed in the 20th century, WEF speakers stressed that research and better care must reduce the public health challenge of brain disorders in the 21st century for nations to succeed. Importantly, one of the recurrent comments in sessions at Davos was the importance of including social factors in both research and treatments for brain disorders. In addition to “no health without mental health,” we can add from Davos “no wealth without mental health.”

Like the rarefied atmosphere in Thomas Mann’s The Magic Mountain(thought to be set in Davos), the WEF is famous for big ideas that might not survive at sea level. But the emergence of mental health as a hot topic at this year’s meeting is just one example of the increasing recognition that the time has come to focus on this profound public health problem that has received too little attention. Recent articles in the New York Times (see for example “For the Mentally Ill, It’s Worse ,” by op-ed columnist Joe Nocera, January 24, 2014), new legislation  in Congress, and the White House meeting  last year all point to a trend: the time is now. It will be important to use this moment to focus on science as well as services, to aspire for outcomes measured by well-being and not just symptom reduction, and to put people with mental disorders at the center of our efforts.

References

1 Kessler RC, Merikangas DR, Wang PS. The prevalence and correlates of workplace depression in the national comorbidity survey replication. J Occup Environ Med. 2008 Apr;50(4):381-90. doi: 10.1097/JOM.0b013e31816ba9b8.

2 Wang PS et al. Telephone screening, outreach, and care management for depressed workers and impact on clinical and work productivity outcomes: a randomized controlled trial.  JAMA. 2007 Sep 26;298(12):1401-11.





Depression, the secret we share

21 12 2013

A must see Ted Lecture by Andrew Solomon about depression: www.mat.co.il/euJ

 

Andrew Solomon





Top 10 selections for 2013 by NIMH director

15 12 2013

By Thomas Insel on December 13, 2013

It’s time again for the year’s ten best from NIMH. A year that included a 16-day government shutdown and a 5.2 percent sequester also saw some outstanding scientific breakthroughs and historic changes in policy. Befitting the complexity of the problems, many of the breakthroughs were not individually reported findings but the cumulative results of several groups contributing different pieces of the puzzle. And some of the most historic policy changes are just launching so their impact is unclear. Paring a lengthy list down to “ten best” is both difficult and unsatisfying, but here goes.

Illustration of neurotransmitters10. Nobel Prize—This year’s Nobel Prize in Physiology or Medicine (and Lasker Award) recognized NIMH grantee Thomas Südhof for his discoveries of how neurotransmitters are released from the pre-synaptic terminal. Südhof and his colleagues described the molecular machines that allow vesicles to empty their contents into the synapse and then re-form to collect more neurotransmitters. This process is critical for neurons to communicate efficiently. Recently, Südhof’s work on the post-synaptic compartment has revealed a new world of molecules important for translating these biochemical messages. The genes for many of these protein families (i.e., shanks, neuroligins, neurexins, etc.) are emerging as leading risk candidates for autism and schizophrenia, giving us a new vocabulary for the molecular basis of mental disorders.1

brain three-quarters view9. Beyond Magic Bullets—Several important new trends emerged this year in non-pharmacological treatments, sometimes from pharmaceutical companies. In April, a Nature commentary that included authors from the pharmaceutical giant GSK described “electroceuticals,” heralding a new era in treatment development focusing on devices to deliver electric signals rather than drugs to alter the activity of neurotransmitters in the brain. Neuromodulation, arguably a better term than electroceuticals, had already been gaining traction with treatment of depression using deep brain stimulation and direct current stimulation. This year neuromodulation was introduced for anorexia nervosa. But neuromodulation was also extended to include approaches beyond electrical stimulation. In September, the cover headline of Nature—“Game Changer”—referred to a study by Adam Gazzaley and colleagues on the impact of cognitive training with NeuroRacer, a video game for enhancement of cognitive control. Not only did older adults (60 – 85 years old) trained on this game surpass performance of untrained 20-year-olds, cognitive enhancement generalized to working memory and other forms of cognitive control, with improvements persisting 6 months later. Cognitive training changed local brain activity as well. The key concept: if mental disorders are brain circuit disorders, then successful treatments need to tune circuits with precision. Chemicals may be less precise than electrical or cognitive interventions that target specific circuits.2,3,4

8. Organoids—It’s been 6 years since the first report of induced pluripotent stem cells (iPSCs). These are cells derived from mature skin cells, induced to become undifferentiated stem cells in a dish, and then differentiated to form mature cells like neurons or heart muscle cells. It’s been a year since this work was awarded the 2012 Nobel Prize in Physiology or Medicine. The excitement of this new technique was the potential to take cells from an individual with a disorder and either regenerate new cells in vitro (imagine new dopamine cells for someone with Parkinson’s disease) or recapitulate the disorder in vitro to define its development and screen for new treatments. This year there were some remarkable reports of using iPSCs to explore the altered development of neurons in children with rare forms of autism. But if autism and mental illnesses are circuit disorders or “connectopathies,” how can individual cells teach us about the altered connections? Amazingly, according to a team from the Austrian Academy of Sciences in Vienna, when neurons are grown in a dish, they self-assemble into circuits that resemble the normal cortex. These “organoids” are not “mini-brains” capable of consciousness but they are functional enough to permit the study of connections. It now appears that iPSCs could be a powerful tool to study circuit disorders.5,6,7

7. DSM-5 and RDoC—For NIMH, probably the year’s most oft-quoted statement was my April blog post about transforming diagnosis. Referring to the pending release of the DSM-5, I said, “Patients with mental disorders deserve better.” To many, this was interpreted as a critique of mainstream psychiatry. In truth, I was complaining that we in the research community have failed to provide the objective measures for diagnosis present in every other area of medicine. The Research Domain Criteria (RDoC) project aims to do just that, by using biological, cognitive, and social information to build more precise classifiers for each patient. RDoC is not a diagnostic system. At this point it is simply a framework for organizing the data. But it is a promise from the NIMH to get beyond diagnostic categories based only on symptoms. Why is this important? For brain disorders, symptoms are generally a late manifestation of a years-long brain process. In medicine, early detection and early intervention have often been the best ways to improve outcomes. RDoC is a first step towards achieving these goals with mental disorders.8,9

6. EP3—A year that began with concerns about school shootings and mental illness saw more mass shootings, many of them connected to serious mental illness (SMI). For this unfortunate reason, there was more media attention on mental illness this year than any time in recent memory. The number of articles about “mental illness” in theNew York Times in 2013 were more than double the average of the previous five years. Among the many recurring themes—access to weapons, access to treatment, incarceration—one prominent one was the need for earlier detection and treatment for SMI. The Early Prediction and Prevention of Psychosis (EP3) program, launched this year at NIMH, is an example of efforts to answer that need. Building on the success of the Recovery After Initial Schizophrenia Episode (RAISE) project, which was implemented this year in New York and Maryland, EP3 will focus on tools for the prodrome, that period prior to psychosis when symptoms are just beginning to emerge and may be most treatable. New studies will build on results from the North American Prodrome Longitudinal Study (NAPLS), just completing 10 years of critical research to develop ways to identify individuals who are at risk for an initial psychotic episode. With a series of new funding announcements and with the success of RAISE and NAPLS, NIMH made EP3 its signature program this year.10,11

chromosones and double helix5. Psychiatric Genetics—In 2003,Science magazine named the identification of genes for mental illness as its #2 breakthrough of the year (just behind confirmation of the existence of dark energy in the cosmos). It has taken another decade to deliver results that are statistically significant and clearly reproducible. For schizophrenia there are now 128 genetic associations, all common variants found across the genome. None of these alone accounts for much of the risk, but groups of these “hits” point to specific biological pathways. For autism, there are many rare variants emerging, many of these “de novo” or spontaneous mutations not found in other family members. These mutations seem to be most common in children with both autism and intellectual disability. Studies that have looked across disorders find some common genomic associations, with some findings across childhood disorders and others across adult disorders, irrespective of diagnosis. Before concluding anything about the significance of these cross-disorder findings, it will be important to understand the actual variation (which gene is involved) and the functional role, if any, of the variant.12,13

4. Brain Exceptionalism—For me, 2013 will be the year when we began to realize how much the brain differs from other organs. We already knew that cells in the brain express (translate into protein) more of the genome and use more energy than any other organ. But two discoveries this year really made the case for the human brain as not only the most mysterious but the most exceptional of organs. Leveraging new tools for single cell biology, scientists working with Rusty Gage at the Salk Institute and Ira Hall at the University of Virginia reported that the brain has its own genome, with abundant and sometimes profound variation not found in other tissues. In human frontal cortex, they report as many as 41 percent of cells having at least one large mutation, with a million DNA bases either duplicated or deleted. These are mutations not seen in blood cells (which have been the basis for all psychiatric genetic studies) or in neurons elsewhere in the brain. Equally surprising, the brain epigenome also appears unique. The epigenome is a complex of molecules that coat the DNA helix, “silencing” parts of the genome to ensure that certain genes are not translated. The entire DNA strand consists of only four bases: cytosine, guanine, adenine, and thymine. Whereas in most cells in the body silencing occurs where cytosine and guanine are adjacent, brain cells follow a different set of rules with all the base pairs involved. This means that the mechanisms by which experience influence biology are completely different in brain cells compared to blood cells or liver cells. The lesson is that we cannot use peripheral cells to know what is happening in the brain.14,15

CLARITY 3D brain image3. CLARITY—It may be an inelegant acronym but the results are utterly beautiful. CLARITY = Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel. By replacing the brain’s fat with a clear gel, CLARITY turns the opaque and impermeable brain into a transparent and porous structure. Most important, the hydrogel holds the brain’s anatomy intact. And because the hydrogel is permeable, the brain can be stained to localize proteins, neurotransmitters, and genes at a high resolution. Unlike other recent breakthroughs in neuroanatomy, this one can be used in human brains. And unlike virtually all neuroanatomy of the past century, CLARITY is 3-dimensional. Flying through the tissue in 3-D allows the first comprehensive view of how cells and processes are arrayed across the entire brain. Karl Deisseroth earlier developed optogenetics as a revolutionary tool for studying brain circuits in behaving animals. This time his lab has revolutionized how we will look at the brain post-mortem.16

full color brain scan2. BRAIN—On April 2nd, President Obama in the East Room announced the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative. The speech should be read by everyone with a stake in brain research or brain disorders. Calling BRAIN the “next great American project,” he challenged a broad scientific community to explore the brain as we had once explored space. BRAIN will involve several government research agencies as well as several private sector partners. And it complements a large brain project underway in the European Union and projects being developed in Israel, Japan, China, and elsewhere. This global interest in neuroscience reflects both the growing awareness of the cost of brain disorders and the growing recognition that success in the 21st century will depend on a “brain economy” rather than a “brawn economy.” The U.S. BRAIN initiative will launch in 2014 with $110M, of which $40M will be from NIH. Funding announcements for the first wave of NIH projects will be released this month.17

Woman at NIMH Clinic1. Parity—My guess is that in terms of mental health issues, history will remember 2013 not for a scientific finding but for a long overdue policy change: mental health parity. While the Mental Health Parity and Addiction Equity Act was signed into law in October 2008, the final rule providing the guidance to implement this law was only released in November 2013. Most important, the Affordable Care Act, signed into law in 2010, affirmed mental health care as an “essential benefit.” As a result, mental health care must be provided in all health care plans and the provision of care for mental disorders must be on a par with other medical disorders (i.e., same co-pays, deductibles, certification requirements). When you add to these changes the removal of exclusions for pre-existing conditions, the extension of coverage to offspring until age 26, and in some states the expansion of Medicaid, you can see that this is really the most far-reaching change in mental health care since the Community Mental Health Act 50 years ago. And this is coming at an important time. Over the summer, the Global Burden of Disease project reported out on 291 medical disorders, updating its 1990 report with 2010 data. The new report finds mental illness and substance abuse disorders to be the leading source of years lost to disability, with the burden of illness from this group of disorders increasing 37 percent since 1990. Depression and anxiety were the largest contributors among the 20 mental and substance abuse disorders, accounting for 55 percent of the DALYs (disability adjusted life years—a composite measure of disability and premature mortality).

There are many questions about how parity will reduce DALYs: Who will provide the care? What will it cost? Where will mental health care be delivered? What is the dose and duration of psychosocial treatments that will be covered? None of these questions will be answered in 2013, but going forward NIMH can ensure that the best science informs this historic change.18,19

References

1 Südhof TC. A molecular machine for neurotransmitter release: synaptotagmin and beyond. Nat Med. 2013 Oct; 19(10):1227-31. doi: 10.1038nm.3338.

2 Anguera JA et al. Video game training enhances cognitive control in older adults. Nature. 2013 Sep 5;501(7465):97-101. doi: 10.1038/nature12486.

3 Lipsman N et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013 Apr 20;381(9875):1361-70. doi: 10.1016/S0140-6736(12)62188-6. Epub 2013 Mar 7.

4 Famm K et al. Drug discovery: a jump-start for electroceuticals. Nature. 2013 Apr 11;496(7444):159-61. doi: 10.1038/496159a.

5 Shcheglovitov A et al. SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients.Nature. 2013 Nov 14;503(7475):267-71. doi: 10.1038/nature12618. Epub 2013 Oct 16.

6 Krev JF et al. Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons.Nat Neurosci. 2013 Feb;16(2):201-9. doi: 10.1038/nn.3307. Epub 2013 Jan 13.

7 Lancaster et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013 Sep 19;501(7467):373-9. doi: 10.1038/nature12517. Epub 2013 Aug 28.

8 Cuthbert BN, Insel TR. Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med. 2013 May 14;11:126. doi: 10.1186/1741-7015-11-126.

9 Casey BJ et al. DSM-5 and RDoC: progress in psychiatry research?;
Nat Rev Neurosci. 2013 Oct 18;14(11):810-4. doi: 10.1038/nrn3621.

10 Fusar-Poli P et al. The psychosis high-risk state: a comprehensive state-of-the-art review. JAMA Psychiatry. 2013 Jan;70(1):107-20. doi: 10.1001/jamapsychiatry.2013.269.

11 Carrion RE et al. Prediction of functional outcome in individuals at clinical high risk for psychosis. JAMA Psychiatry. 2013 Nov 1;70(11):1133-42. doi: 10.1001/jamapsychiatry.2013.1909.

12 Cross-Disorder Group of the Psychiatric Genomics Consortium: Genetic Risk Outcome of Psychosis (GROUP) Consortium.Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013 Apr 20;381(9875):1371-9. doi: 10.1016/S0140-6736(12)62129-1. Epub 2013 Feb 28.

13 Ripke S et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia.Nat Genet. 2013 Oct;45(10):1150-9. doi: 10.1038/ng.2742. Epub 2013 Aug 25.

14 McConnell MJ et al. Mosaic copy number variation in human neurons. Science. 2013 Nov 1;342(6158):632-7. doi: 10.1126/science.1243472.

15 Lister R et al. Global epigenomic reconfiguration during mammalian brain development. Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.

16 Chung K et al. Structural and molecular interrogation of intact biological systems. Nature. 2013 May 16;497(7449):332-7. doi: 10.1038/nature12107. Epub 2013 Apr 10.

17 Insel TR et al. Research priorities. The NIH BRAIN Initiative.Science. 2013 May 10;340(6133):687-8. doi: 10.1126/science.1239276.

18 US Burden of Disease Collaborators. The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.JAMA. 2013 Aug 14;310(6):591-608. doi: 10.1001/jama.2013.13805.

19 Whiteford HA et al. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013 Nov 9;382(9904):1575-86. doi: 10.1016/S0140-6736(13)61611-6. Epub 2013 Aug 29.