Neuropsychopharmacology

Despite decades of clinical implementation of medications for opioid use disorder (OUD), overdose mortality rates remain high, underscoring a critical gap in treatments that target brain mechanisms driving addiction. Mindfulness-Oriented Recovery Enhancement (MORE) has demonstrated efficacy in reducing opioid use and craving, hypothetically by restructuring the salience of drug and natural rewards. Yet, to date, MOREs neurobiological mechanisms remain unclear. In this first functional magnetic r...

BackgroundTheta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD)...

Alcohol use disorder (AUD) remains a major public health problem, with few effective medications and suboptimal adherence. L-type calcium channel blockers (LTCCBs) have genetic and preclinical support as potential treatments for AUD. We evaluated whether brain penetrant (BP)-LTCCBs are associated with reduced alcohol consumption by conducting two preregistered (https://osf.io/huawv) observational cohort studies using electronic health records (EHRs) from the US Department of Veterans Affairs (VA...

Tobacco use disorder (TUD) remains a leading cause of preventable mortality, and existing pharmacotherapies yield 12-month abstinence rates below 30%. As cannabis legalization expands, approximately 18-22% of people who use tobacco report concurrent cannabis use, yet the impact of co-use on cessation outcomes and the therapeutic potential of endocannabinoid system (ECS) modulation remain unclear. We conducted a translational systematic review and meta-analysis following PRISMA 2020 guidelines, s...

Background and AimsAlcohol use disorder (AUD) remains a major public health concern, with persistent disparities in access to evidence-based treatment. This study aimed to examine associations between perceived discrimination in healthcare settings (PDHS), patient-clinician communication (PCC), and receipt of treatment for AUD, and compared these with sociodemographic and insurance-related factors. DesignCross-sectional analysis using structural equation modeling (SEM), logistic and multinomial...

BackgroundSubstance use disorders (SUD) are associated with a high global burden of disease, with 5.4% of all disability-adjusted life years lost due to alcohol and illicit drugs. Highly prevalent multimorbidity includes polysubstance use, mental health conditions, and other non-communicable and infectious diseases. Where traditional treatments are insufficient alone, music therapy (MT) is highly engaging and improves motivation and reduces craving; however, its long-term effects are unknown. Th...

In 2024, approximately 30% of U.S. adolescents reported having consumed alcohol at least once in their lifetime, with about 25% of these individuals engaging in binge drinking. Adolescent alcohol use is associated with neurodevelopmental impairments, elevated risk of later alcohol use, and mental health disorders. These findings underscore the importance of identifying the variables driving adolescent alcohol use and leveraging them for early identification and targeted intervention. Previous st...

BackgroundThe prevalences of suicidal ideation (SI) and suicide attempt (SA) are influenced by genetic, behavioral, and environmental factors. Alcohol use disorder (AUD) and adverse childhood experiences (ACEs) may mediate or moderate genetic liability for suicidality. MethodsUsing data from 10,275 participants (43.8% female; 47.2% African-like genetic ancestry [AFR], 52.8% European-like genetic ancestry [EUR]), we tested whether polygenic scores (PGS) for SI and SA predicted lifetime SI or SA....

BackgroundLipidomic alterations have been reported across schizophrenia (SCZ) and bipolar disorder (BD), but findings are heterogeneous and often overlap across diagnoses, limiting diagnostic specificity. Associations between lipid profiles and illness severity have also been inconsistent when assessed using single symptom scales, raising the possibility that unidimensional measures fail to capture biologically relevant variation. Whether plasma lipidomic alterations relate to multidimensional p...

IntroductionMaternal mental health conditions, comprising maternal suicide and drug overdose, are currently the leading cause of maternal mortality in the United States. However, the relationship between suicidality and drug use behavior in the perinatal period is not well understood. We examined the association between suicidality and drug use behavior among perinatal individuals. Given the racial disparities in both drug use and suicide rates in the U.S., we also examined any differences in su...

Background and HypothesisAbnormal default mode network (DMN) connectivity was observed in both tobacco use and psychotic spectrum disorders, but it remains unknown how psychosis impacts the relationship between connectivity and tobacco use. Interventions targeting the left lateral parietal DMN node (LLPDMN) have modulated DMN connectivity and nicotine craving in psychosis. We aimed to investigate relationships between DMN connectivity, psychotic illness, and tobacco use. Study Design336 partici...

BackgroundPsychotherapy is proven efficacious for the treatment of alcohol use disorder (AUD). However, the patient-perceived importance of its effect is not fully appreciated in the evidence base. The smallest worthwhile difference (SWD) represents the smallest beneficial effect of an intervention that patients deem worthwhile in exchange for the harms, expenses, and inconveniences associated with the intervention, and facilitates the interpretation of patient perceived worthiness of an interve...

Psychotic disorders are increasingly recognized as the extreme end of a progressive psychopathology continuum, with less advanced stages including the asymptomatic familial high-risk state (FHR), the help-seeking clinical high-risk state (CHR), and first episode psychosis (FEP). However, we lack a comprehensive study of clinical, cognitive, functional, and neuroanatomical markers across all three early stages of psychosis, limiting our understanding of how the multimodal phenotypes which define ...

Understanding factors that predict the course of schizophrenia remains essential for improving long-term clinical management. Rate and severity of symptom exacerbations vary widely across individuals, and although prior studies have examined potential predictors, findings have been inconsistent and often limited by small samples, infrequent assessments, and non-standardized measures. Using data from phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE), which include...

BackgroundTo clarify the working mechanisms of psychotherapy for obsessive-compulsive disorder (OCD), we studied the neural effects of two psychotherapies: cognitive behavioral therapy with exposure and response prevention (CBT-ERP) and inference-based cognitive behavioral therapy (I-CBT). MethodsFifty-five individuals with OCD completed an emotional processing task during fMRI before and after 20 weekly psychotherapy sessions, using general fear and OCD-related visual stimuli. Forty-two health...

ObjectiveCognitive deficits are a leading cause of disability in schizophrenia and are linked to poor functional outcomes. There are no first line treatments for these deficits, and their neural basis is poorly understood. While schizophrenia is associated with widespread cognitive deficits, information processing speed is most profoundly impaired. Processing speed deficits have been associated with hyperconnectivity in the Default Mode Network (DMN). We therefore tested if modulating DMN connec...

ObjectiveWe examined the clinical utility of resting state electroencephalography (rsEEG) by evaluating its temporal stability, discriminant validity for B-SNIP psychosis Biotypes, and suitability as a treatment target for brain stimulation. MethodsWe collected 5 minutes of eyes-open rsEEG from 1401 participants with psychosis and 750 healthy persons. A subset of participants was re-tested after 6 months and 12 months (N=109). In a pilot target engagement study (n=5) we collected rsEEG before a...

BackgroundMajor depressive disorder (MDD) involves immune-metabolic dysregulation, psychosocial adversity, and multidomain cognitive disturbances, yet single cognitive indices often show small and inconsistent effects. We derived a multivariate Cambridge Neuropsychological Test Automated Battery (CANTAB)-based cognitive phenotype ("cognitype") and tested whether it adds explanatory value beyond adverse childhood experiences (ACEs) and an acute-phase protein (APP) index in acute-phase MDD. Metho...

Opioid use disorder (OUD) is characterized by compulsive drug seeking and impaired executive control arising from maladaptive plasticity within cortico-striatal circuits. While transcriptomic studies have identified coding gene alterations in the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC), the contribution of the noncoding genome remains poorly defined. Here, we performed integrative transcriptomic analysis of postmortem human NAc and DLPFC to systematically identify and ...

Background and HypothesisClozapine is the only antipsychotic with protective effects against suicide in schizophrenia (SCZ). Newer third-generation antipsychotics (TGA) have better tolerability and modulate serotonin, dopamine, and N-methyl-d-aspartate neurotransmission pathways implicated in suicide. We aimed to investigate the effects of TGAs on suicide in SCZ. MethodsWe searched seven databases up to December 2023 for SCZ studies that reported suicide data. The primary outcome was suicide de...