OBJECTIVE Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels in the CNS of individuals with schizophrenia. However, the factors that cause elevated KYNA

OBJECTIVE Estimating the current association between childhood adversity and the risk of psychosis is crucial for prevention and intervention. We provided an updated synthesis of evidence from the past four decades, expanded the available data by investigating a broad array of adversity subtypes, and explored sex differences and the age of psychosis onset as relevant factors. METHODS We searched PubMed

The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings

Twenty years ago Shitij Kapur's "Psychosis as a state of aberrant salience" captured the attention of clinicians and cognitive and behavioral neuroscientists. It has become the de facto way of talking about delusion formation in labs and clinics. Here, evidence for this theory is critically evaluated in consideration of evolving data since its publication. A particular focus is placed on its specific

OBJECTIVE The authors provide recommendations on incorporating recent advances in psychiatric genetics into clinical practice for mental health clinicians. METHOD The International Society for Psychiatric Genetics Education Committee met monthly to come to a consensus on priority topics in psychiatric genetics. Topics were then assigned to small teams of subspecialty experts to summarize the current

OBJECTIVE Amid continuously rising concentrations of delta-9-tetrahydrocannabinol (THC) in cannabis (i.e., potency), high-potency cannabis is a major topic in contemporary cannabis policy discussions, yet its impact on health is not well understood. The authors conducted a systematic review of observational and experimental studies examining the relationship between high-potency cannabis use and a

OBJECTIVE Posttraumatic stress disorder (PTSD) and alcohol use disorder (AUD) frequently co-occur. Prolonged exposure (PE) is an effective treatment for PTSD but shows smaller effects in patients with co-occurring AUD. Topiramate may help reduce alcohol use and PTSD symptoms. This double-blind, placebo-controlled outpatient clinical trial compared 12 sessions of PE plus either topiramate or placebo

OBJECTIVE Limited data are available to inform clinicians on how to manage concurrent substance use in the context of repetitive transcranial magnetic stimulation (rTMS) for the treatment of depressive, obsessive-compulsive, psychotic, or trauma-related disorders. The authors convened an international panel of 24 rTMS experts, representative of different geographic regions and subspecialities, and

OBJECTIVE The authors synthesized evidence from studies quantifying the relationship between anticholinergic medication and cognitive function in psychosis, and additionally explored studies that investigated whether reducing anticholinergic medications affects cognitive function in individuals with psychosis. METHODS A database search was conducted in MEDLINE, Embase, and PsycINFO, from database inception

OBJECTIVE It is not known what proportion of patients experience relapse in first-episode schizophrenia despite continuous dopamine D2 receptor blockade and whether breakthrough psychosis is attributable to long-term use of D2-blocking antipsychotics. Using data from a Finnish nationwide cohort, the authors sought to test the hypothesis that the incidence of breakthrough psychosis is accelerated among

OBJECTIVE The authors examined prospective associations between tobacco product use and mental health and substance use problems among U.S. adolescents and adults. METHODS Covariate-adjusted models using discrete-time survival analysis of five annual waves (2013-2014 to 2018-2019) were used to examine the links between specific tobacco product use and mental health and substance use problems among

OBJECTIVE The allostasis theory states that, as addiction develops, alcohol is consumed to relieve negative affect rather than to produce positive effects. This study aimed to investigate the real-time subjective effects of alcohol in individuals with alcohol use disorder (AUD) and those prone to negative affect by virtue of having comorbid depressive disorder (DEP). METHODS Participants (N=221) completed

OBJECTIVE Intranasal esketamine has been approved as an adjunctive therapy for treatment-resistant major depressive disorder with acute suicidal ideation and behavior. The authors conducted a systematic review and meta-analysis of the available data on its efficacy against depression and suicidality as well as its side effects. METHODS MEDLINE was searched with the keyword "esketamine" on March 24

OBJECTIVE This study investigated spaced transcranial direct current stimulation for major depressive disorder, focusing on feasibility. METHODS In a prospective open-label study, 30 participants with major depressive disorder were enrolled to receive a 50-session transcranial direct current stimulation (tDCS) treatment over 2 weeks. The feasibility, safety, tolerability, and preliminary therapeutic

OBJECTIVE Sensory phenomena (SP) are aversive sensations driving repetitive behaviors in obsessive-compulsive disorder (OCD) and Tourette's disorder that are not well addressed by standard treatments. SP are related to the functioning of an interoceptive-sensorimotor circuit that may be modulated by the 5-HT3 receptor antagonist ondansetron. The present study employed an experimental medicine approach

OBJECTIVE The behavioral and diagnostic heterogeneity within the opioid use disorder (OUD) diagnosis is not readily captured in current animal models, limiting the translational relevance of the mechanistic research that is conducted in experimental animals. The authors hypothesized that a nonlinear clustering of OUD-like behavioral traits would capture population heterogeneity and yield subpopulations

Ketamine is a racemic compound and medication comprised of (S)-ketamine and (R)-ketamine enantiomers and its metabolites. It has been used for decades as a dissociative anesthetic, analgesic, and recreational drug. More recently, ketamine, its enantiomers, and its metabolites have been used or are being investigated for the treatment of refractory depression, as well as for comorbid disorders such

OBJECTIVE Rates of substance use disorders (SUDs) remain significantly above national targets for health promotion and disease prevention in Canada and the United States. This study investigated the 5-year SUD outcomes following a selective drug and alcohol prevention program targeting personality risk factors for adolescent substance misuse. METHODS The Co-Venture trial is a cluster randomized trial

OBJECTIVE Evidence suggests that psilocybin-assisted therapy (PAT) leads to durable shifts in personality structure. However, such changes have yet to be characterized in disorders of addiction. In this secondary analysis from a randomized controlled trial, the authors examined the effect of PAT on personality dimensions in patients with alcohol use disorder (AUD), hypothesizing that PAT would attenuate

The last few years have seen exponential growth in interest, investment, advocacy, and research into psychedelics as therapeutics. This reflects an optimism about the potential promise of psychedelics as therapeutics. As with all therapeutic interventions, research is needed not only into their benefits but also potential risks. Indeed, when substances with therapeutic potential are scrutinized over

During the past decade, there has been extraordinary public, media, and medical research interest in psychedelics as promising therapeutics for difficult-to-treat psychiatric disorders. Short-term controlled trial data suggest that certain psychedelics are effective and safe in the treatment of major depressive disorder, treatment-resistant depression, and posttraumatic stress disorder. Preliminary

OBJECTIVE Depression varies along a difficulty-to-treat spectrum. Patients whose illness fails to respond to at least five treatments may be considered to have severely treatment-resistant depression (TRD). The objective of this study was to document the safety and efficacy of psilocybin in patients with severe TRD. METHODS This was a 12-week, open-label trial conducted at Sheppard Pratt Hospital.

Unlike classical antidepressants, psychedelics such as psilocybin have been shown to induce a rapid antidepressant response. In the wake of this development, interest has emerged in ultra-fast, short-acting psychedelics such as 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and N,N-dimethyltryptamine (DMT) with the expectation that these can produce rapid antidepressant effects following an intense but

The psychedelic experience can be challenging. There is a need for a structured framework for providing psychological support to individuals with mental health conditions receiving investigational psilocybin treatment. The primary benefit of such a framework is to support a safe and meaningful psilocybin experience. It also enables future research on the facets of psychological support and/or psychotherapy

OBJECTIVE The authors critically examine the evidence base for psilocybin administered with psychological support/therapy (PST) in the treatment of psychiatric disorders and offer practical recommendations to guide future research endeavors. METHODS PubMed was searched for English-language articles from January 1998 to November 2023, using the search term "psilocybin." A total of 1,449 articles were

OBJECTIVE Binge-eating disorder (BED) is a prevalent, costly public health problem associated with serious functional impairments and heightened rates of psychiatric and medical comorbidities. Few evidence-based treatments are currently available for BED. We tested the effectiveness of cognitive-behavioral therapy (CBT), lisdexamfetamine (LDX), and combined CBT+LDX, for BED comorbid with obesity. METHODS

OBJECTIVE The aim of this study was to compare the safety and efficacy of the leading smoking cessation medications among individuals with current versus past major depressive disorder (MDD). METHODS This was a secondary analysis of a randomized, double-blind trial over 12 weeks with varenicline or bupropion, followed by a 12-week assessment, in participants ages 18-75 with past (N=2,174) or current

Gambling disorder is the only behavioral addiction recognized as a clinical disorder in DSM-5, and Internet gaming disorder is included as a condition requiring further research. ICD-11 categorizes gambling and gaming disorders as disorders due to addictive behaviors. Additional behavioral addictions may include compulsive sexual behavior disorder, compulsive buying-shopping disorder, and problematic

OBJECTIVE Xanomeline and trospium chloride (formerly known as KarXT), a novel M1/M4 muscarinic receptor agonist, demonstrated efficacy across phase 2 and 3 trials as monotherapy for the treatment of inpatients with acute schizophrenia on the Positive and Negative Syndrome Scale total score primary endpoint. In the phase 2 trial, xanomeline/trospium improved performance on a cognitive outcome measure