Mental health

Smartphone apps claim to help conditions from addiction to schizophrenia, but few have been thoroughly tested.

Evidence is mounting that medication for ADHD doesn't make a lasting difference to schoolwork or achievement.

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

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

As threats to populations transcend national boundaries, it is crucial that responses to mental-health problems do too, say Pamela Y. Collins and Shekhar Saxena.

Clinicians and neuroscientists must work together to understand and improve psychological treatments, urge Emily A. Holmes, Michelle G. Craske and Ann M. Graybiel.

It is time for policy-makers, funders, researchers and clinicians to tackle high suicide rates, say André Aleman and Damiaan Denys.

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.

Welcome steps have been made in uncovering a biological basis for schizophrenia, but for many, the question of ‘why’ is unimportant, says David Adam.

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

Andrea Tone admires the history of a radical shift in the treatment of mental illness.

Susanne Ahmari applauds neuroscientist Joseph LeDoux's redefinition of anxiety.

Emily A. Holmes commends a theatrical meditation on obsessive–compulsive disorder.

Andrea Tone assesses a history of the mass release of US psychiatric patients into an uncertain future.

David Dobbs enjoys a brilliant look at the making of DSM-5, the new 'psychiatrists' Bible'.

Dominic ffytche contemplates Oliver Sacks' journey through the past and future science of hallucinations.

Two genetic regions associated with major depressive disorder have been revealed for the first time, through whole-genome sequencing of a population of Han Chinese women. See Letter p.588

Many of us were raised or currently live in an urban environment. A neuroimaging study now reveals how this affects brain function when an individual is faced with a stressful situation. See Letter p.498

The largest genome-wide analysis of schizophrenia performed so far has identified more than 100 genetic regions that contribute to disease risk, establishing new leads for understanding this form of mental illness. See Article p.421

Genomic analysis of 5,303 Chinese women with recurrent major depressive disorder (MDD) enables the identification and replication of two genome-wide significant loci contributing to risk of MDD on chromosome 10: one near the SIRT1 gene; the other in an intron of the LHPP gene.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

A prospective longitudinal study identifies the earliest known indicator of social disability in human infancy: decline in attention to others’ eyes in infants who are later diagnosed with autism; the decline is evident already within the first 2 to 6 months of life, which reveals the early unfolding of the disorder but also offers a promising opportunity for the future of early intervention.

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.

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.

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.

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.

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.

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.

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.

Obsessive–compulsive disorder has been scrutinized in many genetic, neuropsychological and neuroimaging studies. Pauls and colleagues provide an overview of our current understanding of the vulnerability factors, triggers and mechanisms underlying this devastating condition.

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.

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.

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.

Several changes to scientific culture and policy are needed to aid the identification of new drug targets and therapies for central nervous system disorders from the rapidly growing volume of 'big' data in 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.

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.

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.