Introduction: The global disease burden of major depressive disorder urgently requires prevention in high-risk individuals, such as recently discovered insomnia subtypes. Previous studies targeting insomnia with fully automated eHealth interventions to prevent depression are inconclusive: dropout was high and likely biased, and depressive symptoms in untreated participants on average improved rather

For many decades, psychiatric treatment has been primarily guided by two major paradigms of psychopathology: a neurochemical paradigm leading to the development of medications and a psychological paradigm resulting in the development of psychotherapies. A third paradigm positing that psychiatric dysfunction results from abnormal communication within a network of brain regions that regulate mood, thought

Background Negative symptoms of schizophrenia are associated with adverse clinical outcomes, but there are few effective treatments. We aimed to assess the effects of pimavanserin, a selective 5-HT2A inverse agonist and antagonist, on negative symptoms of schizophrenia. Methods The ADVANCE study was a phase 2, 26-week, randomised, double-blind, placebo-controlled study of pimavanserin in stable outpatients

Importance Recent accounts suggest that delusions and hallucinations may result from alterations in how prior knowledge is integrated with new information, but experimental evidence supporting this idea has been complex and inconsistent. Evidence from a simpler perceptual task would make clear whether psychotic symptoms are associated with overreliance on prior information and impaired updating. Objective

Brief psychotic episodes represent an intriguing paradox in clinical psychiatry because they elude the standard knowledge that applies to the persisting psychotic disorders such as schizophrenia. This Review describes key diagnostic considerations such as conceptual foundations, current psychiatric classification versus research-based operationalisations, epidemiology, and sociocultural variations;

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Background Poor attendance at school, whether due to absenteeism or exclusion, leads to multiple social, educational, and lifelong socioeconomic disadvantages. We aimed to measure the association between a broad range of diagnosed neurodevelopmental and mental disorders and recorded self-harm by the age of 24 years and school attendance and exclusion. Methods In this nationwide, retrospective, electronic

Background A childhood cancer diagnosis and treatment-induced somatic late effects can affect the long-term mental health of survivors. We aimed to explore whether childhood cancer survivors are at higher risk of psychiatric disorders later in life than their siblings and the general population. Methods In this register-based cohort study (part of the Socioeconomic Consequences in Adult Life after

Importance Older adults with insomnia have a high risk of incident and recurrent depression. Depression prevention is urgently needed, and such efforts have been neglected for older adults. Objective To examine whether treatment of insomnia disorder with cognitive behavioral therapy for insomnia (CBT-I) compared with an active comparator condition, sleep education therapy (SET), prevents major depressive

Importance Although the association between several recurrent genomic copy number variants (CNVs) and mental disorders has been studied for more than a decade, unbiased, population-based estimates of the prevalence, disease risks and trajectories, fertility, and mortality to contrast chromosomal abnormalities and advance precision health care are lacking. Objective To generate unbiased, population-based

Background For more than 150 years, controversy over the status of post-partum psychosis has hindered research and caused considerable confusion for clinicians and women, with potentially negative consequences. We aimed to explore the hypothesis that genetic vulnerability differs between women with first-onset post-partum psychosis and those with bipolar disorder more generally. Methods In this case-control

Background Depression often first emerges in adolescence and, for many, is a lifelong disorder. The long-term clinical course of depression is highly variable. We aimed to examine the adult outcomes of adolescent-onset trajectories of clinically significant depressive symptoms and to identify factors differentiating trajectories that persist and desist in adulthood. Methods We included participants

Background Although studies suggest that concentrations of omega-3 and omega-6 fatty acids are lower in individuals with schizophrenia, evidence for beneficial effects of fatty acid supplementation is scarce. Therefore, in this study, we aimed to determine whether omega-3 and omega-6 fatty acid concentrations are causally related to schizophrenia. Methods We did a two-sample Mendelian randomisation

Background The WHO Comprehensive Mental Health Action Plan 2013–2030 encourages routine collection and reporting of a set of essential mental health indicators, including the availability of psychotropic medicines. The global monitoring of country-level psychotropic medicine consumption trends can provide information on the extent of the availability of psychotropic medicines. The primary objective

Background Recent evidence on suicide rates among psychiatric patients from minority ethnic backgrounds is scarce. We aimed to examine suicide rates among minority ethnic psychiatric patients and describe their social and clinical characteristics. Methods We did a retrospective observational cohort study on a national case-series of patients in England and Wales who died by suicide within 12 months

Mental health research grapples with research waste and stunted field progression caused by inconsistent outcome measurement across studies and clinical settings, which means there is no common language for considering findings. Although recognising that no gold standard measures exist and that all existing measures are flawed in one way or another, anxiety and depression research is spearheading a

Objective: Obsessive-compulsive disorder (OCD) is known to be substantially heritable; however, the contribution of genetic variation across the allele frequency spectrum to this heritability remains uncertain. The authors used two new homogeneous cohorts to estimate the heritability of OCD from inherited genetic variation and contrasted the results with those of previous studies. Methods: The sample

Importance Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression. Objective To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide

Understanding the interface between opioid use disorder (OUD) and post-traumatic stress disorder (PTSD) is challenging. By use of a dimensional framework, such as research domain criteria, convergent and targetable neurobiological processes in OUD–PTSD comorbidity can be identified. We hypothesise that, in OUD–PTSD, circuitry that is implicated in two research domain criteria systems (ie, negative

Importance Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators. Objective To examine the association of the use of PRI periods

Objective: Structural neuroimaging findings in younger and older adults with major depressive disorder (MDD) are highly heterogeneous, possibly as a result of methodological limitations, lack of distinction between MDD and late-life depression (LLD), or clinical moderators. Using a novel meta-analytic network mapping approach, the authors sought to identify the circuits affected in different clinical

Objective: The authors sought to determine the association of cannabis indicators with self-reported psychotic disorders in the U.S. general population. Methods: Participants were from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; 2001–2002; N=43,093) and NESARC-III (2012–2013; N=36,309). Logistic regression was used to estimate standardized prevalences of past-year self-reported

Objective: Evidence from anti-inflammatory drug trials for the treatment of depression has been inconsistent. This may be ascribed to the differing symptom-specific effects of inflammation. Accordingly, the authors explored the associations between systemic inflammation and an array of individual symptoms of depression across multiple studies. Methods: This random-effects pooled analysis included 15

Objective: Research is lacking on the contribution of different types of substance use disorders (SUDs) to excess mortality across the full spectrum of eating disorders. The authors assessed the association of alcohol use disorders and other SUDs with mortality in anorexia nervosa, bulimia nervosa, and unspecified eating disorder compared with matched control subjects. Methods: A retrospective cohort

Objective: A fine-tuned balance of glucocorticoid receptor (GR) activation is essential for organ formation, with disturbances influencing many health outcomes. In utero, glucocorticoids have been linked to brain-related negative outcomes, with unclear underlying mechanisms, especially regarding cell-type-specific effects. An in vitro model of fetal human brain development, induced human pluripotent

Objective: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing

Objective: Major negative life events, such as trauma exposure, can play a key role in igniting or exacerbating psychopathology. However, few disorders are diagnosed with respect to precipitating events, and the role of these events in the unfolding of new psychopathology is not well understood. The authors conducted a multisite transdiagnostic longitudinal study of trauma exposure and related mental

Alzheimer’s disease is a neuropsychiatric disorder with devastating clinical and socioeconomic consequences. Since the original description of the neuropathological correlates of the disorder, neuritic plaques and neurofibrillary tangles have been presumed to be critical to the underlying pathophysiology of the illness. The authors review the clinical and neuropathological origins of Alzheimer’s disease