Importance Psychiatric diagnoses are not defined by neurobiological measures hindering the development of therapies targeting mechanisms underlying mental illness. Research confined to diagnostic boundaries yields heterogeneous biological results, whereas transdiagnostic studies often investigate individual symptoms in isolation. Objective To develop a framework that groups clinical symptoms compatible

ImportanceIntake of sweetened beverages, including sugar-sweetened beverages (SSB) and artificially sweetened beverages (ASB), has been linked to multiple health outcomes, but their associations with dementia risk among older adults are unclear.ObjectiveTo assess whether the consumption of SSB and ASB is associated with the risk of all-cause dementia in older adults.Design, Setting, and ParticipantsThis

ImportanceIn 2023, the US Department of Health and Human Services (HHS) issued a letter to the administrator of the Drug Enforcement Administration (DEA) recommending rescheduling of cannabis (marijuana) from Schedule I to Schedule III under the Controlled Substances Act (CSA). This recommendation marked a significant departure from previous, consistent, and long-standing federal decisions on cannabis

ImportanceCannabis use is common in people with severe mental illness and its adverse effects on outcomes are well established. However, adverse outcomes may also result from cannabis withdrawal syndrome (CWS). CWS includes symptoms such as agitation, irritability, and aggression, and typically peaks after 3 to 5 days of abstinence.ObjectiveTo assess whether cannabis use prior to admission is associated

ImportanceMechanistic biomarkers for guiding treatment selection require selective sensitivity to specific pharmacological interventions. Reinforcement learning processes show potential, but there have been conflicting and sometimes inconsistent reports on how dopamine and serotonin—2 key targets in treating common mental illnesses—affect reinforcement learning in humans.ObjectiveTo perform a meta-analysis

ImportanceMajor depressive disorder (MDD) and obesity are common noncommunicable disorders associated with substantial disease burden, which frequently occur comorbidly. Intriguingly, converging lines of evidence from animal models and genetic and observational studies have suggested a biological link between obesity, metabolic syndrome, and depression. Several small randomized clinical trials (RCTs)

This Viewpoint provides suggestions to address challenges after elimination of the Clozapine Risk Evaluation and Mitigation Strategies (REMS) system by the US Food and Drug Administration (FDA).

ImportanceTranscranial magnetic stimulation (TMS), a form of noninvasive brain stimulation used to treat major depressive disorder, obsessive-compulsive disorder (OCD), and nicotine dependence, has well-established state-dependent effects on brain circuitry. However, a major question for TMS remains: does brain state affect clinical response?ObjectiveTo quantify the association between symptom provocation

ImportanceAnorexia nervosa is a prevalent psychiatric illness associated with exceptionally poor outcomes, including high rates of morbidity and premature mortality. Current evidence-based treatments for anorexia nervosa were developed several decades ago and have limited efficacy. The anorexia nervosa field—and the eating disorders field more broadly—has yet to make significant scientific breakthroughs

ImportanceAlthough early maternal warmth strongly predicts adolescent health, questions remain about the biopsychosocial mechanisms underlying this association.ObjectiveTo understand how maternal warmth at 3 years of age shapes adolescent social safety schemas at 14 years of age and physical and mental health at 17 years of age.Design, Setting, and ParticipantsThe Millennium Cohort Study tracks approximately

ImportancePrivate equity (PE) ownership in health care has increased, but evidence for its association with health care quality is mixed. Moreover, there is no evidence regarding inpatient psychiatric hospitals, despite considerable patient vulnerabilities.ObjectiveTo describe trends in PE ownership of psychiatric hospitals from 2013 through 2021 and the cross-sectional association between PE ownership

ImportanceIn recent decades, evidence-based psychotherapies to treat posttraumatic stress disorder (PTSD) have been developed with robust evidence bases. However, efficacy observed in clinical trials is not always directly applicable to clinical practice.ObjectiveTo estimate the percentage of patients in both military and veteran (hereafter milvet) and nonmilvet populations that lose their PTSD diagnosis

This Viewpoint examines the use of local anesthetics to adulterate synthetic opioids, particularly illicitly manufactured fentanyl, and the dangers associated with exposure to these drugs.

This Viewpoint discusses a proposal to identify candidates for drug repurposing and allocate US Food and Drug Administration funds to cover the cost of evaluating and approving such drugs for their novel indications.

ImportanceAmong hospitalized older adults, prolonged use of antipsychotic medications (APMs) following hospital discharge may increase the risk of APM-associated adverse events. There are limited data on whether early discontinuation of APMs is associated with reduced adverse clinical outcomes compared with APM continuation after discharge.ObjectiveTo compare clinical outcomes between discontinuation

ImportancePeople with obesity and diabetes have poorer psychiatric and cognitive outcomes and lower quality of life (QOL) compared with those without. Glucagon-like peptide 1 receptor agonists (GLP1-RAs) are treatments for diabetes and obesity that may also influence psychiatric outcomes.ObjectiveTo conduct a meta-analysis of randomized placebo-controlled trials to evaluate psychiatric, cognitive,

ImportanceThe rates of suicide and suicide attempts are rising precipitously among early adolescents aged 10 to 14 years in the US. While suicide attempts in this age group are more common and associated with lower lethality than in older age groups, very little is known about these individuals’ long-term social and psychiatric outcomes.ObjectivesTo examine the adult outcomes of individuals making

Importance Childhood maltreatment (CM) is associated with psychiatric disorders. The underlying mechanisms are complex and involve genetics. Objective To investigate the polygenic architecture of CM-exposed individuals across psychiatric conditions and if genetics modulates absolute CM risk in the presence of high-impact risk factors such as parental psychiatric diagnoses. Design, Setting, and Participants

ImportanceRepresentation of race and ethnicity in randomized clinical trials (RCTs) is critical for understanding treatment efficacy across populations with different racial and ethnic backgrounds.ObjectiveTo examine race and ethnicity representation and reporting across RCTs of pharmacotherapies for mental disorders.Data SourcesPubMed (Medline), Embase (Ovid), APA PsycInfo, and Web of Science were

ImportanceEmotional well-being (EWB) is an emerging therapeutic target for managing and preventing symptoms associated with Alzheimer disease and related dementias (ADRD). However, more research is needed to establish causal inferences between brain changes, EWB, and behavioral changes observed in typical aging and ADRD.ObservationsThis article presents a framework for using a cross-species behavioral

ImportanceIt has been hypothesized that the association between acute-phase treatment with antipsychotic (vs placebo) and outcomes might be larger in individuals who were not recently treated compared to recently treated individuals. However, evidence is still lacking.ObjectiveTo compare the association between antipsychotic (vs placebo) acute-phase treatment and outcomes in individuals who were not

ImportanceIt remains unknown whether difficulties in positive emotion regulation (ER) drive opioid use disorder (OUD) and whether these difficulties may be remediated.ObjectiveTo test whether OUD is associated with attenuated positive ER and whether such positive emotion dysregulation may be treated by mindfulness-based intervention.Design, Setting, and ParticipantsIn this mechanistic substudy of a

ImportanceSleep disorders have different etiologies yet share some nocturnal and daytime symptoms, suggesting common neurobiological substrates; healthy individuals undergoing experimental sleep deprivation also report analogous daytime symptoms. However, brain similarities and differences between long-term sleep disorders and short-term sleep deprivation are unclear.ObjectiveTo investigate the shared

ImportanceCognitive behavior therapy (CBT) is a first-line treatment for most mental disorders. However, no meta-analytic study has yet integrated the results of randomized clinical trials on CBT across different disorders, using uniform methodologies and providing a complete overview of the field.ObjectiveTo examine the effect sizes of CBT for 4 anxiety disorders, 2 eating disorders, major depression

This Viewpoint explores potential justifications underlying the US Food and Drug Administration (FDA)’s rejection of methylenedioxymethamphetamine (MDMA) as a treatment for posttraumatic stress disorder, including lack of blinding and issues around the integrity of relevant clinical trials.

ImportanceAnalyzing effects within placebo groups allows for transdiagnostic comparisons, as placebo is the only substance systematically studied across all major psychiatric diagnoses. Recently, the study team meta-analytically showed that improvement under placebo varies across major psychiatric diagnoses. However, comprehensive transdiagnostic comparisons of negative effects under placebo (nocebo

ImportanceIndividuals whose chronic pain is managed with opioids are at high risk of developing an opioid use disorder. Electronic health records (EHR) allow large-scale studies to identify a continuum of problematic opioid use, including opioid use disorder. Traditionally, this is done through diagnostic codes, which are often unreliable and underused.ObjectiveTo determine whether regular expressions

ImportanceDespite evidence that individuals with a cannabis use disorder (CUD) are at elevated risk of psychosis and that the neurotransmitter dopamine has a role in psychosis, the mechanism linking cannabis use and psychosis remains unclear.ObjectiveTo use neuromelanin-sensitive magnetic resonance imaging (MRI), referred to as the neuromelanin-MRI signal, a practical, proxy measure of dopamine function

ImportanceClinical practice guidelines recommend suicide risk screening and assessment across behavioral health settings. The predictive accuracy of real-world clinician assessments for stratifying patients by risk of future suicidal behavior, however, remains understudied.ObjectiveTo evaluate routine clinical suicide risk assessment for prospectively predicting suicide attempt.Design, Setting, and

ImportanceMajor depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern–based biomarker for MDD that is linked to the underlying pathophysiology.ObjectiveTo

ImportanceTreatment-resistant depression (TRD) remains a critical challenge in psychiatry, with limited effective options. Esketamine, a rapid-acting antidepressant, is usually combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), but comparative evidence of these combinations’ effectiveness in real-world settings is sparse.ObjectiveTo

This Viewpoint discusses the opportunity to include inflammatory biomarkers as specifiers for major depression in the upcoming Sixth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-6).

ImportanceTraumatic brain injury is common and occurs across all ages. Observational studies have shown that traumatic brain injury is associated with a wide range of mental disorders and suicide. Whether these associations represent a causal effect is, however, difficult to establish, and confounding by genetic liability for mental disorder may play a substantial role.ObjectiveTo investigate whether

This Viewpoint discusses assessing decision-making capacity in patients with severe anorexia nervosa and why a multidisciplinary approach is preferred.

This Viewpoint discusses developing better evidence about appropriate use of stimulants, understanding and reducing nonmedical use of these medications, and responding to shortages.

Importance Collaborative care is a multicomponent intervention for patients with chronic disease in primary care. Previous meta-analyses have proven the effectiveness of collaborative care for depression; however, individual participant data (IPD) are needed to identify which components of the intervention are the principal drivers of this effect. Objective To assess which components of collaborative

ImportanceBariatric surgery, once the criterion standard in obesity treatment, has a small but concerning association with increased suicidality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), originally developed to treat diabetes, now provide substantial efficacy in the treatment of obesity. However, concerns of risk of suicidality with these medicines have been raised.ObjectiveTo evaluate

ImportanceStimulants are increasingly prescribed for US adults. Whether such prescribing is associated with misuse and prescription stimulant use disorder (PSUD) is less understood.ObjectivesTo examine (1) sex- and age-specific trends in the number of persons dispensed stimulants and trends in dispensed prescription stimulants by prescriber specialty in 2019 through 2022; (2) prevalence of misuse and

ImportanceMicrodosing psychedelics, including lysergic acid diethylamide (LSD), has gained attention for its potential benefits in several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, LSD’s efficacy in reducing ADHD symptoms remains unknown.ObjectiveTo determine the safety and efficacy of repeated low doses of LSD in reducing ADHD symptoms compared with

IMPORTANCEMaternal inflammation during pregnancy has been associated with an increased risk of neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD) and autism, and cognitive deficits in early childhood. However, little is known about the contributions of a wider range of inflammatory proteins to this risk.OBJECTIVETo determine whether maternal inflammatory proteins

ImportancePeripheral (blood-based) biomarkers for psychiatric illness could benefit diagnosis and treatment, but research to date has typically been low throughput, and traditional case-control studies are subject to potential confounds of treatment and other exposures. Large-scale 2-sample mendelian randomization (MR) can examine the potentially causal impact of circulating proteins on neuropsychiatric

ImportanceExpectancy effects are significant confounding factors in psychiatric randomized clinical trials (RCTs), potentially affecting the interpretation of study results. This narrative review is the first, to our knowledge, to explore the relationship between expectancy effects, compromised blinding integrity, and the effects of active treatment/placebo in psychiatric RCTs. Additionally, we present

ImportanceThis study aims to provide robust evidence to support or challenge the immune hypothesis of schizophrenia.ObjectiveTo conduct a meta-analysis of reports on blood leukocyte subpopulations in schizophrenia vs healthy controls, examining disease- and treatment-related differences as well as potential confounders.Data SourcesSystematic database search for English and non-English peer-reviewed

ImportanceSports gambling has become one of the most accessible forms of gambling in the United States, and recent research suggests that sports gambling coupled with frequent alcohol use may have deleterious health consequences.ObjectiveTo examine the trajectories of sports gambling frequency and alcohol-related problems over time and the associations between these trajectories.Design, Setting, and

This Viewpoint explores the shift from the process-oriented concept of evidence-based practicing toward the development and distribution of evidence-based practices within the sphere of mental health care.

ImportanceIntermittent theta-burst stimulation (iTBS) is an established treatment for treatment-resistant depression (TRD). Sessions conducted more than once daily (ie, accelerated TBS [aTBS]) may enhance antidepressant effects. However, evidence is limited to small trials, and protocols are time-consuming and can require neuroimaging-based targeting.ObjectiveTo evaluate the efficacy and safety of

ImportanceAccessing mental health care is challenging for youths, especially those facing intersectional disadvantages, but whether enhancing youth services increases reach and timeliness has rarely been investigated. ACCESS Open Minds (ACCESS-OM) transformed services at urban, rural, and Indigenous sites in Canada using 5 principles (early identification, rapid access, appropriate care, no age-based

ImportanceTreatment-resistant depression (TRD) is a major challenge in mental health, affecting a significant number of patients and leading to considerable burdens. The etiological factors contributing to TRD are complex and not fully understood.ObjectiveTo investigate the genetic factors associated with TRD using polygenic scores (PGS) across various traits and explore their potential role in the