Special |

Mental health

Worldwide, mental-health problems — such as depression, anxiety and substance-use disorders — are responsible for more years lost to disability than any other health condition is. The toll is exacted not just on the health and well-being of patients, but also on their families and on society around them. This collection brings together different facets of mental-health coverage, from original research to reviews of the latest science to in-depth journalism on public-health issues and first-hand accounts of the experience of mental illness.

News & Comment

Research suggests that mental illnesses lie along a spectrum — but the field's latest diagnostic manual still splits them apart.

News Feature | | Nature

Most people bounce back from trauma — but some never recover. Scientists are trying to work out what underlies the difference.

News Feature | | Nature

A consortium of researchers, advocates and clinicians announces here research priorities for improving the lives of people with mental illness around the world, and calls for urgent action and investment.

Comment | | Nature

Chris Gunter examines a comprehensive history of the science and culture surrounding autism studies.

Books & Arts | | Nature

Research & Reviews

This genomic analysis of more than 5,000 Chinese women with recurrent major depressive disorder (MDD) has identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10. One is near the sirtuin1 (SIRT1) gene, and the other is in an intron of the phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene. The authors suggest that the association close to SIRT1 may implicate abnormalities in mitochondria as risk factors for the disease.

News & Views | | Nature

By 2050, two-thirds of the world's population will be living in cities. Although city living has many advantages, rapidly increasing urbanization has major health implications — schizophrenia is more common in people born in cities than in those from less heavily populated districts, and living in cities increases the rates of depression and anxiety disorders. It has been suggested that social stress plays a part in these effects, but the mechanisms involved are unknown. Now, in a study of healthy German volunteers using functional magnetic resonance imaging, a key brain structure for negative emotion (the amygdala) was found to be more active during stress in city dwellers, and a regulatory brain area (the cingulate cortex) more active in people born in cities. These results identify potential mechanisms linking social environment and mental illness, and might contribute to planning healthier urban surroundings.

News & Views | | Nature

Although schizophrenia is a highly heritable disorder, its complex polygenic nature has impeded attempts to establish its genetic basis. This paper reports a genome-wide association study of more than 36,000 schizophrenia patients and 100,000 controls. The study identifies 128 independent associations in 108 loci, 83 of them new. Among them are many genes involved in glutamatergic neurotransmission, highlighting a potential therapeutic avenue. In addition, the results provide support for the hypothesized link between the immune system and schizophrenia.

News & Views | | Nature

This genomic analysis of more than 5,000 Chinese women with recurrent major depressive disorder (MDD) has identified and replicated two genome-wide significant loci contributing to risk of MDD on chromosome 10. One is near the sirtuin1 (SIRT1) gene, and the other is in an intron of the phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) gene. The authors suggest that the association close to SIRT1 may implicate abnormalities in mitochondria as risk factors for the disease.

Letter | | Nature

Although schizophrenia is a highly heritable disorder, its complex polygenic nature has impeded attempts to establish its genetic basis. This paper reports a genome-wide association study of more than 36,000 schizophrenia patients and 100,000 controls. The study identifies 128 independent associations in 108 loci, 83 of them new. Among them are many genes involved in glutamatergic neurotransmission, highlighting a potential therapeutic avenue. In addition, the results provide support for the hypothesized link between the immune system and schizophrenia.

Article | | Nature

A reduced tendency to make eye contact is a feature of autistic spectrum disorders (ASDs). It is used as a diagnostic marker, but it is not known when this behaviour arises. In a long-term study of 59 infants at high risk for ASD, and 51 at low risk, Warren Jones and Ami Klin tracked the development of eye movement in children through their first 3 years of life. Early levels of eye contact were normal in children eventually diagnosed with autism, but from soon after 2 months of age, eye contact behaviour declines. These findings may represent some of the earliest manifestations of autistic symptoms, but need to be replicated in an independent sample before being considered a potential diagnostic marker.

Letter | | Nature

By 2050, two-thirds of the world's population will be living in cities. Although city living has many advantages, rapidly increasing urbanization has major health implications — schizophrenia is more common in people born in cities than in those from less heavily populated districts, and living in cities increases the rates of depression and anxiety disorders. It has been suggested that social stress plays a part in these effects, but the mechanisms involved are unknown. Now, in a study of healthy German volunteers using functional magnetic resonance imaging, a key brain structure for negative emotion (the amygdala) was found to be more active during stress in city dwellers, and a regulatory brain area (the cingulate cortex) more active in people born in cities. These results identify potential mechanisms linking social environment and mental illness, and might contribute to planning healthier urban surroundings.

Letter | | Nature

The authors use computational modeling of participants' performance on an aversive learning task to examine how decision-making is altered in anxiety. Results indicate that anxious individuals struggle to use information regarding the stability of action-outcome relationships to guide their choices. Pupillometry data link this deficit to altered norepinephrinergic function.

Article | | Nature Neuroscience

Autism spectrum disorders (ASDs) are characterized by both phenotypic and genetic heterogeneity. Here the authors find that ASD functional genetic networks are enriched for genes expressed in deep layer cortical neurons, that mutations in females impact more highly expressed genes as compared to males and that intellectual scores reflect the severity of mutations.

Article | | Nature Neuroscience

Mutations in Mendelian disease genes often lead to distinct clinical presentations, and the same non-specific risk is now apparent for many neuropsychiatric disorders. In this Review, the authors analyze pathogenic mechanisms for known Mendelian disease and discuss what it means for understanding the causes of non-specific genetic risk in more complex brain diseases.

Review Article | | Nature Neuroscience

It is now possible to systematically identify, on a genome-wide scale, genetic variants for disease, how often they occur in the population and how large their impact is on risk. In this Review, the authors discuss recent findings regarding the genetic architecture of psychiatric disorders and the contribution of common but weak and rare but strong variants to disease risk.

Review Article | | Nature Neuroscience

Gustavo Turecki and colleagues report that miR-1202, a miRNA specific to primates, is decreased in individuals with depression and seems to be differentially regulated in individuals who will end up showing beneficial responses to antidepressant treatment compared to those who will not respond.

Letter | | Nature Medicine

Ronald Duman and colleagues report that synapse number is reduced in subjects with major depressive disorder. This is associated with decreased expression of synapse-related genes and increased expression of the transcriptional repressor, GATA1. Expression of GATA1 in prefrontal cortex neurons decreases the expression of synapse-related genes, reduces dendrite branching and produces depressive behavior in a rat model of depression.

Letter | | Nature Medicine

Effective treatment for schizophrenia is still an unmet clinical need. Alleviating problems associated with cognitive impairment and finding the root of the disease remain priorities for clinicians and scientists. The incomplete understanding of the basis of this pathology has urged for research that will unravel the genetic origin of schizophrenia. But studies involving environmental exposure and social impact have also hinted at extrinsic factors as players in the pathogenesis of schizophrenia, which may be exploited to prevent the development of the disease. In 'Bench to Bedside', Patrick Sullivan proposes a model putting forward how genetic variants may confer risk by functioning together within the same pathway. This disease pathway hypothesis would imply a polygenetic variation affecting the same pathway and the alteration of a transcriptional network as a root for increasing schizophrenia risk. In 'Bedside to Bench', Andreas Meyer-Linderberg and Heike Tost discuss human-based population studies that suggest that environmental factors linked to development of schizophrenia can affect brain regions involved in the human social-emotional processing network. Genetic risk variants for schizophrenia can also influence similar regions in the brain, suggesting that environmental and intrinsic factors may converge in the same neural circuit.

Between Bedside and Bench | | Nature Medicine

The classification of psychiatric disorders in the DSM has been influential in neuroscience research but has also been subject to criticism. In this Viewpoint, six leaders in the field discuss whether the latest version, DSM-5, as well as the dimensional approach provided by the RDoC, will move psychiatry research forward.

Viewpoint | | Nature Reviews Neuroscience

Recent evidence suggests that mood disorders are associated with altered reward function. Russo and Nestler review studies that have shown alterations in the brain reward circuitry in patients with, and animal models of, depression, and discuss the cellular and molecular underpinnings of these alterations.

Review Article | | Nature Reviews Neuroscience

Biomarkers for autism may reveal causes of the condition and could be used to improve diagnosis and enable earlier detection of autism spectrum disorders. Walsh and colleagues discuss the major scientific challenges in the search for autism biomarkers and consider a number of important social and ethical concerns arising from biomarker development and application.

Science and Society | | Nature Reviews Neuroscience

Innovative partnerships among researchers, patients, regulators, payors and industry are needed to reinvigorate drug discovery for central nervous system disorders. Here, representatives of the 2013 Collegium Internationale Neuro-Psychopharmacologicum (CINP) Summit group summarize plans to achieve this goal.

Comment | | Nature Reviews Drug Discovery

Vast efforts have been made to develop novel anxiolytic drugs that improve on those that target the GABA (γ-aminobutyric acid)–benzodiazepine system, but promising results in rodents have rarely translated into effectiveness in humans. Griebel and Holmes analyse the major trends from a database of published preclinical studies on novel anxiolytic agents in the past 50 years, highlight issues that may have hampered progress and offer recommendations to improve anxiolytic drug discovery.

Review Article | | Nature Reviews Drug Discovery

Studies of psychiatric disorders have traditionally focused on emotional symptoms, such as depression, anxiety and hallucinations, but poorly controlled cognitive deficits are also prominent and severely compromise quality of life. This article critically discusses our understanding of the nature and causes of cognitive impairment in psychiatric disorders, and reviews the opportunities and challenges in improving cognition in patients, including the development of more effective translational research approaches.

Review Article | | Nature Reviews Drug Discovery