Importance Past studies have identified associations between brain macrostructure and alcohol use behaviors. However, identifying directional associations between these phenotypes is difficult due to the limitations of observational studies. Objective To use mendelian randomization (MR) to identify directional associations between brain structure and alcohol use and elucidate the transcriptomic and

Importance The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. Objective To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal

Importance Transcranial direct current stimulation (tDCS) may improve symptoms of inattention in adults with attention-deficit/hyperactivity disorder (ADHD). However, previous trials are characterized by small sample sizes, heterogeneous methodologies, and short treatment periods using clinic-based tDCS. Objective To determine the efficacy and safety of home-based tDCS in treating inattention symptoms

Importance Genetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences. Objective To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design. Design,

Importance Nucleic acid damage from oxidative stress (NA-OXS) may be a molecular mechanism driving the severely increased morbidity and mortality from somatic causes in adults with psychiatric disorders. Objective To systematically retrieve and analyze data on NA-OXS across the psychiatric disorder diagnostic spectrum. Data Sources The PubMed, Embase, and PsycINFO databases were searched from inception

Importance Identifying neurobiological differences between patients with major depressive disorder (MDD) and healthy individuals has been a mainstay of clinical neuroscience for decades. However, recent meta-analyses have raised concerns regarding the replicability and clinical relevance of brain alterations in depression. Objective To quantify the upper bounds of univariate effect sizes, estimated

Importance The COVID-19 pandemic has coincided with an increase in depressive symptoms as well as a growing awareness of health inequities and structural racism in the United States. Objective To examine the association of mental health with everyday discrimination during the pandemic in a large and diverse cohort of the All of Us Research Program. Design, Setting, and Participants Using repeated assessments

Importance Although hypothesis-driven research has identified several factors associated with psychosis, this one-exposure-to-one-outcome approach fails to embrace the multiplicity of exposures. Systematic approaches, similar to agnostic genome-wide analyses, are needed to identify genuine signals. Objective To systematically investigate nongenetic correlates of psychotic experiences through data-driven

Importance There are no approved medications for the core symptoms of autism spectrum disorder (ASD), socialization and communication difficulties. Objective To evaluate the efficacy and safety of balovaptan, an oral selective vasopressin 1a receptor antagonist, compared with placebo in children and adolescents with ASD. Design, Setting, and Participants The aV1ation study was a randomized, double-blind

Importance Several maternal exposures during pregnancy are considered predisposing factors for offspring neurodevelopmental conditions. However, many of these exposures may be noncausal and biased by maternal genetic liability. Objective To assess whether pregnancy-related predisposing factors for offspring neurodevelopmental conditions are associated with maternal genetic liability for attention-

Importance Intersecting factors of social position including ethnoracial background may provide meaningful ways to understand disparities in pathways to care for people with a first episode of psychosis. Objective To examine differences in pathways to care by ethnoracial groups and by empirically derived clusters combining multiple factors of social and clinical context in an ethnoracially diverse

Importance Rare genetic disorders modulating gene expression-as exemplified by gene dosage disorders (GDDs)-represent a collectively common set of high-risk factors for neuropsychiatric illness. Research on GDDs is rapidly expanding because these variants have high effect sizes and a known genetic basis. Moreover, the prevalence of recurrent GDDs (encompassing aneuploidies and certain copy number variations)

Importance Neuropsychiatric symptoms have been reported as a prominent feature of postacute sequelae of COVID-19 (PASC), with common symptoms that include cognitive impairment, sleep difficulties, depression, posttraumatic stress, and substance use disorders. A primary challenge of parsing PASC epidemiology and pathophysiology is the lack of a standard definition of the syndrome, and little is known

Importance Negative symptoms have a detrimental impact on functional outcomes and quality of life in people with schizophrenia, and few therapeutic options are considered effective for this symptomatic dimension. Studies have suggested that noninvasive brain stimulation (NIBS) interventions may be effective in treating negative symptoms. However, the comparative efficacy of different NIBS protocols

Importance Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P). Objective To examine whether mismatch negativity (MMN) event-related potential

Importance Reducing the use of coercion in mental health care is crucial from a human rights and public health perspective. Psychiatric advance directives (PADs) are promising tools that may reduce compulsory admissions. Assessments of PADs have included facilitation by health care agents but not facilitation by peer workers. Objective To determine the efficacy of PADs facilitated by peer workers (PW-PAD)

Importance Craving, which is a strong desire for drugs, is a new DSM-5 diagnostic criterion for substance use disorders (SUDs), which are the most prevalent, costly, and deadly forms of psychopathology. Despite decades of research, the roles of drug cues and craving in drug use and relapse remain controversial. Objective To assess whether 4 types of drug cue and craving indicators, including cue exposure

Importance Cannabis use disorder (CUD) is increasing in the US. Clarification of the potential mechanisms underlying the comorbidity between mood disorders and CUD may help prevent CUD. Objective To examine co-occurrence and familial aggregation of CUD and mood disorder subtypes. Design, Setting, and Participants In this cross-sectional, community-based study in the Washington, DC, metropolitan area

Importance Considerably less is known about self-injurious thoughts and behaviors (SITBs) in preadolescence than older age groups, owing partly to the common view that young children are incapable of suicidal thoughts. Yet, preadolescent suicide has increased in recent years and is now the fifth leading cause of death in this age group, leading the National Institute of Mental Health to identify it

Importance Approaches are needed to stratify individuals in early psychosis stages beyond positive symptom severity to investigate specificity related to affective and normative variation and to validate solutions with premorbid, longitudinal, and genetic risk measures. Objective To use machine learning techniques to cluster, compare, and combine subgroup solutions using clinical and brain structural

Importance Psychiatric care following somatic treatment for deliberate self-harm (DSH) is pivotal in patients' lives both in the short and long term, but evidence to guide such care is limited. Objective To examine follow-up psychiatric care for patients treated for DSH (ie, intentional self-injury or self-poisoning, irrespective of motivation) at hospital emergency departments and to assess the association

Importance Schizophrenia is associated with major cognitive deficits and has been conceptualized as both a neurodevelopmental and a neurodegenerative disorder. However, when deficits develop and how they change over the course of illness is uncertain. Objective To trace cognition from elementary school to old age to test neurodevelopmental and neurodegenerative theories of psychotic disorders. Design

Importance Individuals surviving severe COVID-19 may be at increased risk of neuropsychiatric sequelae. Robust assessment of these risks may help improve clinical understanding of the post-COVID syndrome, aid clinical care during the ongoing pandemic, and inform postpandemic planning. Objective To quantify the risks of new-onset neuropsychiatric conditions and new neuropsychiatric medication prescriptions

Importance Suicide attempts are prevalent among female youths, yet little is known about the subsequent development of substance use disorders. Objective To assess the association between suicide attempts among females before 20 years of age and future risk of substance use disorders. Design, Setting, and Participants In this longitudinal cohort study, females aged 8 to 19 years (hereafter referred

Importance Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined. Objective To determine how CNV risk scores, common genetic variation

Importance Certain psychiatric and immune-related disorders are reciprocal risk factors. However, the nature of these associations is unclear. Objective To characterize the pleiotropy between psychiatric and immune-related traits, as well as risk factors of hypothesized relevance. Design, Setting, and Participants This genetic association study was conducted from July 10, 2020, to January 15, 2022

Importance Questions of whether and how cortical thickness (CTh) alterations differ over the course of schizophrenia (SCZ) have yet to be resolved. Objective To characterize CTh alterations across illness stages in SCZ. Data Sources PubMed, Embase, Web of Science, and Science Direct were screened for CTh studies published before June 15, 2021. Study Selection Original studies comparing whole-brain

Importance Little is known about the extent to which secondhand exposure to household firearms is associated with risk of suicide in adults who do not own guns, most of whom are women. Objective To evaluate changes in risk of suicide among women living in gun-free households after one of their cohabitants became a handgun owner. Design, Setting, and Participants This cohort study observed participants

Importance The COVID-19 pandemic disproportionately affected mental health in socioeconomically disadvantaged children in the US. However, little is known about the relationship of preexisting and time-varying social determinants of health (SDoH) at individual and structural levels, vaccination eligibility/rates, and the racial and ethnic differences to trajectories of child mental health during the

Importance Black women are at risk for insomnia disorder. Despite interest in addressing sleep health disparities, there is limited research investigating the efficacy of criterion-standard treatment (cognitive behavioral therapy for insomnia [CBT-I]) among this racial minority population. Objective To compare the efficacy of a standard version of an internet-delivered CBT-I program, a culturally tailored

Importance Major depressive disorder (MDD) affects approximately 10% of the population globally. Approximately 20% to 30% of patients with MDD do not sufficiently respond to standard treatment. Therefore, there is a need to develop more effective treatment strategies. Objective To investigate whether the efficacy of cognitive behavioral therapy (CBT) for the treatment of MDD can be enhanced by concurrent

Importance Depression has been associated with alterations in neurotransmitters, hormones, and inflammatory and neurodegenerative biomarkers, and biomarkers quantified in the cerebrospinal fluid (CSF) are more likely to reflect ongoing biochemical changes within the brain. However, a comprehensive overview of CSF biomarkers is lacking and could contribute to the pathophysiological understanding of