OBJECTIVE Three leading neurobiological hypotheses about autism spectrum disorder (ASD) propose underconnectivity between brain regions, atypical function of the amygdala, and generally higher variability between individuals with ASD than between neurotypical individuals. Past work has often failed to generalize, because of small sample sizes, unquantified data quality, and analytic flexibility. This

OBJECTIVE There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder. METHOD Cox models were used with data from a population-based Swedish cohort (N=655,327). Outcomes were drug use

OBJECTIVE Although repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depression, little is known about the comparative effectiveness of rTMS and other treatment options, such as antidepressants. In this multicenter randomized controlled trial, rTMS was compared with the next pharmacological treatment step in patients with treatment-resistant depression. METHODS Patients

OBJECTIVE Sexual minority disparities in behavioral health (e.g., mental health and substance use) are well-established. However, sexual identity is dynamic, and changes are common across the life course (e.g., identifying with a monosexual [lesbian or gay] label and later with a plurisexual [queer, pansexual, etc.] label). This study assessed whether behavioral health risks coincide with sexual identity

The recent worldwide surge of warfare and hostilities exposes increasingly large numbers of individuals to traumatic events, placing them at risk of developing posttraumatic stress disorder (PTSD) and challenging both clinicians and service delivery systems. This overview summarizes and updates the core knowledge of the genetic, molecular, and neural circuit features of the neurobiology of PTSD and

OBJECTIVE Associations were examined between six psychiatric diagnoses in parents and a broad range of psychiatric and nonpsychiatric outcomes in their offspring. METHODS All individuals born in Sweden between 1970 and 2000 were linked to their biological parents (N=3,286,293) through Swedish national registers. A matched cohort design, with stratified Cox regression and conditional logistic regression

OBJECTIVE The authors compared the associated risk of incident depression between first-time users of low-, medium-, and high-dose levonorgestrel-releasing intrauterine systems (LNG-IUSs). METHODS This national cohort study was based on Danish register data on first-time users of LNG-IUSs, 15-44 years of age, between 2000 and 2022. Cox regression and a G-formula estimator were used to report 1-year

OBJECTIVE The authors sought to assess the prosocial, entactogen effects of ketamine. METHODS Pleasure from social situations was assessed in a sample of participants with treatment-resistant depression from randomized, double-blind, placebo-controlled studies, using four items of the Snaith-Hamilton Pleasure Scale (SHAPS) at five time points over 1 week following treatment with ketamine (0.5 mg/kg

Objective: Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression

Objective: Specific phobia is a common anxiety disorder, but the literature on associated brain structure alterations exhibits substantial gaps. The ENIGMA Anxiety Working Group examined brain structure differences between individuals with specific phobias and healthy control subjects as well as between the animal and blood-injection-injury (BII) subtypes of specific phobia. Additionally, the authors

Objective: Many but not all persons with bipolar disorder require hospital care because of severe mood episodes. Likewise, some but not all patients experience long-term occupational dysfunction that extends beyond acute mood episodes. It is not known whether these dissimilar outcomes of bipolar disorder are driven by different polygenic profiles. Here, polygenic scores (PGSs) for major psychiatric

Objective: Twin studies have demonstrated that posttraumatic stress disorder (PTSD) is moderately heritable, and the pattern of findings across studies suggests higher heritability in females compared with males. Formal testing of sex differences has yet to be done in twin studies of PTSD. The authors sought to estimate the genetic and environmental contributions to PTSD, and to formally test for sex

Objective: This study estimated national annual trends and characteristics of emergency department visits for suicide attempts and intentional self-harm in the United States from 2011 to 2020. Methods: Data were from the National Hospital Ambulatory Medical Care Survey, an annual cross-sectional national sample survey of emergency departments. Visits for suicide attempts and intentional self-harm were

Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem

Objective: Understanding prognosis is critical to anticipating public health needs and providing care to individuals with psychotic disorders. However, the long-term course of remission and recovery remains unclear. In this study, the most common trajectories of illness course are described for a cohort of individuals followed for 25 years since first admission for psychosis. Methods: Participants

Objective: Treatment-resistant depression (TRD) occurs in roughly one-third of all individuals with major depressive disorder (MDD). Although research has suggested a significant common variant genetic component of liability to TRD, with heritability estimated at 8% when compared with non-treatment-resistant MDD, no replicated genetic loci have been identified, and the genetic architecture of TRD remains

Objective: The co-occurrence of unhealthy alcohol use and opioid misuse is high and associated with increased rates of overdose, emergency health care utilization, and death. The current study examined whether receipt of an alcohol-related brief intervention is associated with reduced risk of negative downstream opioid-related outcomes. Methods: This retrospective cohort study included all VISN-6 Veterans

Objective: Substance use initiation during early adolescence is associated with later development of substance use and mental health disorders. This study used various domains to predict substance use initiation, defined as trying any nonprescribed substance (e.g., alcohol, tobacco, cannabis), by age 12, using a large longitudinal data set. Methods: Substance-naive youths from the Adolescent Brain

Objective: Stress and alcohol cue reactivity are associated with poor treatment outcomes in alcohol use disorder (AUD), but sex-specific neural correlates of stress and alcohol cue–induced craving compared with neutral cue–induced craving and of heavy drinking outcomes in AUD have not been examined. Thus, this study prospectively examined these associations and assessed sex differences. Methods: Treatment-seeking

Objective: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms—rs2832407 (in GRIK1) and rs1799971 (in OPRM1)—on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness

Alcohol use disorder (AUD) and chronic pain disorders are pervasive, multifaceted medical conditions that often co-occur. However, their comorbidity is often overlooked, despite its prevalence and clinical relevance. Individuals with AUD are more likely to experience chronic pain than the general population. Conversely, individuals with chronic pain commonly alleviate their pain with alcohol, which

The fourth wave of the United States overdose crisis—driven by the polysubstance use of fentanyl with stimulants and other synthetic substances—has driven sharply escalating racial/ethnic inequalities in drug overdose death rates. Here the authors present a detailed portrait of the latest overdose trends and synthesize the literature to describe where, how, and why these inequalities are worsening

Opioid overdose deaths and opioid-related harms have reached unprecedented levels, particularly as compounds such as xylazine and fentanyl have infiltrated the drug supply. Harm reduction strategies are especially relevant in this climate, as they aim to reduce drug-related harms independently of whether an individual chooses to enter treatment or abstain from opioid use. Assessment of harm reduction

Substance use disorders (SUD) present a worldwide challenge with few effective therapies except for the relative efficacy of opioid pharmacotherapies, despite limited treatment access. However, the proliferation of illicit fentanyl use initiated a dramatic and cascading epidemic of lethal overdoses. This rise in fentanyl overdoses regenerated an interest in vaccine immunotherapy, which, despite an

Objective: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. Methods: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection

Objective: Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive

Objective: To investigate shared and specific neural correlates of cognitive functions in attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), the authors performed a comprehensive meta-analysis and considered a balanced set of neuropsychological tasks across the two disorders. Methods: A broad set of electronic databases was searched up to December 4, 2022, for task-based