Recent ucsdpsych items

What Dose of Methamphetamine Do Regular Consumers Use Daily? Estimating Oral Amphetamine Milligram Equivalents

Fri, 11 Sep 2026 00:00:00 +0000

OBJECTIVES: The purity, accessibility, and affordability of illicit methamphetamine have increased in recent decades, which has been linked to rising rates of methamphetamine-involved overdoses, psychosis, cardiovascular events, and other health consequences. Nevertheless, information about the quantity of methamphetamine used by regular consumers has been limited, despite the potential clinical utility of exposure quantification. METHODS: From August 2024 to April 2026, self-reported daily methamphetamine consumption was assessed among n = 94 individuals in Los Angeles County. Methamphetamine samples (n = 256) were analyzed for purity using liquid chromatography-mass spectrometry. Bioavailability by route of administration and stimulant equivalency were obtained from the literature. A simulation model leveraging bootstrapping with 1,000,000 draws was used to estimate oral amphetamine milligram equivalents (AME). RESULTS: The average reported methamphetamine consumption was 1.09...

Genome-wide association studies of lifetime and frequency of cannabis use in 131,895 individuals

Fri, 28 Aug 2026 00:00:00 +0000

Cannabis is one of the most widely used drugs globally. We performed genome-wide association studies (GWASs) of lifetime (N = 131,895) and frequency (N = 73,374) of cannabis use. For lifetime cannabis use, we identified two loci, one near CADM2 (rs35827242, p = 4.63E-12) and another near GRM3 (rs12673181, p = 6.90E-09). For frequency of cannabis use, we identified one locus near CADM2 (rs4856591, p = 8.10E-09; r2 = 0.76 with rs35827242). Lifetime and frequency of cannabis use were heritable (12.88 vs. 6.63%) and genetically correlated with previous GWASs of lifetime use and cannabis use disorder (CUD), as well as other substance use and cognitive traits. Polygenic scores (PGSs) for lifetime and frequency of cannabis use predicted cannabis use phenotypes in All of Us participants. A phenome-wide association study using a PGS for lifetime cannabis use to interrogate a hospital cohort replicated prior associations with substance use and mood disorders, and uncovered novel associations...

Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits

Fri, 21 Aug 2026 00:00:00 +0000

BACKGROUND: Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement. METHODS: We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes. RESULTS: We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E-11 in EUR; lead SNP = rs2036527, p = 6.49e-13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational...

A single-nucleus transcriptomic atlas of medium spiny neurons in the rat nucleus accumbens

Fri, 21 Aug 2026 00:00:00 +0000

Neural processing of rewarding stimuli involves several distinct regions, including the nucleus accumbens (NAc). The majority of NAc neurons are GABAergic projection neurons known as medium spiny neurons (MSNs). MSNs are broadly defined by dopamine receptor expression, but evidence suggests that a wider array of subtypes exist. To study MSN heterogeneity, we analyzed single-nucleus RNA sequencing data from the largest available rat NAc dataset. Analysis of 48,040 NAc MSN nuclei identified major populations belonging to the striosome and matrix compartments. Integration with mouse and human data indicated consistency across species and disease-relevance scoring using genome-wide association study results revealed potentially differential roles for MSN populations in substance use disorders. Additional high-resolution clustering identified 34 transcriptomically distinct subtypes of MSNs definable by a limited number of marker genes. Together, these data demonstrate the diversity...

Executive Function and Impulsivity Predict Distinct Genetic Variance in Internalizing Problems, Externalizing Problems, Thought Disorders, and Compulsive Disorders: A Genomic Structural Equation Modeling Study

Fri, 21 Aug 2026 00:00:00 +0000

Individual differences in self-control predict many health and life outcomes. Building on twin literature, we used genomic structural equation modeling to test the hypothesis that genetic influences on executive function and impulsivity predict independent variance in mental health and other outcomes. The impulsivity factor (comprising urgency, lack of premeditation, and other facets) was only modestly genetically correlated with low executive function (r_g =.13). Controlling for impulsivity, low executive function was genetically associated with increased internalizing (β_g =.15), externalizing (β_g =.13), thought disorders (β_g =.38), compulsive disorders (β_g =.22), and chronotype (β_g =.11). Controlling for executive function, impulsivity was positively genetically associated with internalizing (β_g =.36), externalizing (β_g =.55), body mass...

Psychiatric genetics in the diverse landscape of Latin American populations

Fri, 21 Aug 2026 00:00:00 +0000

Psychiatric disorders are highly heritable and polygenic, influenced by environmental factors and often comorbid. Large-scale genome-wide association studies (GWASs) through consortium efforts have identified genetic risk loci and revealed the underlying biology of psychiatric disorders and traits. However, over 85% of psychiatric GWAS participants are of European ancestry, limiting the applicability of these findings to non-European populations. Latin America and the Caribbean, regions marked by diverse genetic admixture, distinct environments and healthcare disparities, remain critically understudied in psychiatric genomics. This threatens access to precision psychiatry, where diversity is crucial for innovation and equity. This Review evaluates the current state and advancements in psychiatric genomics within Latin America and the Caribbean, discusses the prevalence and burden of psychiatric disorders, explores contributions to psychiatric GWASs from these regions and highlights...

Impulsivity facets and substance use involvement: insights from genomic structural equation modeling

Fri, 21 Aug 2026 00:00:00 +0000

BACKGROUND: Impulsivity is a multidimensional trait associated with substance use disorders (SUDs), but the relationship between distinct impulsivity facets and stages of substance use involvement remains unclear. METHODS: We used genomic structural equation modeling and genome-wide association studies (N = 79,729-903,147) to examine the latent genetic architecture of nine impulsivity traits and seven substance use (SU) and SUD traits. RESULTS: We found that the SU and SUD factors were strongly genetically inter-correlated (r_G=0.77) but their associations with impulsivity facets differed. Lack of premeditation, negative and positive urgency were equally positively genetically correlated with both the SU (r_G=.0.30-0.50) and SUD (r_G=0.38-0.46) factors; sensation seeking was more strongly genetically correlated with the SU factor (r_G=0.27 versus r_G=0.10); delay discounting was...

Do Polygenic Indices Capture “Direct” Effects on Child Externalizing Behavior Problems? Within-Family Analyses in Two Longitudinal Birth Cohorts

Fri, 21 Aug 2026 00:00:00 +0000

Failures of self-control can manifest as externalizing behaviors (e.g., aggression, rule-breaking) that have far-reaching negative consequences. Researchers have long been interested in measuring children's genetic risk for externalizing behaviors to inform efforts at early identification and intervention. Drawing on data from the Environmental Risk Longitudinal Twin Study (N = 862 twins) and the Millennium Cohort Study (N = 2,824 parent-child trios), two longitudinal cohorts from the UK, we leveraged molecular genetic data and within-family designs to test for genetic associations with externalizing behavior that are not affected by common sources of environmental influence. We found that a polygenic index (PGI) calculated from genetic variants discovered in previous studies of self-controlled behavior in adults captures direct genetic effects on externalizing problems in children and adolescents when evaluated with rigorous within-family designs (β's = 0.13-0.19...

Automating the Addiction Behaviors Checklist for Problematic Opioid Use Identification

Fri, 21 Aug 2026 00:00:00 +0000

Importance: Individuals 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. Objective: To determine whether regular expressions, an interpretable natural language processing technique, could automate a validated clinical tool (Addiction Behaviors Checklist) to identify problematic opioid use. Design, Setting, and Participants: This cross-sectional study reports on a retrospective cohort with data analyzed from 2021 through 2023. The approach was evaluated against a blinded, manually reviewed holdout test set and validated against an independent test set at a separate institution. The study used data from Vanderbilt University Medical Center's Synthetic Derivative, a deidentified version of the EHR for...

Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking

Fri, 21 Aug 2026 00:00:00 +0000

Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use, and substance use disorders. There is interest in understanding the extent to which these relationships are causal, and to what extent shared genetic factors play a role. We explored the relationships between schizophrenia (Scz; European ancestry N = 161,405; African ancestry N = 15,846), cannabis use disorder (CanUD; European ancestry N = 886,025; African ancestry N = 120,208), and ever-regular tobacco smoking (Smk; European ancestry N = 805,431; African ancestry N = 24,278) using the largest available genome-wide studies of these phenotypes in individuals of African and European ancestries. All three phenotypes were positively genetically correlated (rgs = 0.17–0.62). Genetic instrumental variable analyses suggested the presence of shared heritable factors, but evidence for bidirectional causal relationships was also found between all three phenotypes...

Multivariate genetic analyses of 2.2 million individuals reveal broad and substance-specific pathways of addiction risk

Fri, 21 Aug 2026 00:00:00 +0000

Ongoing efforts to identify genes involved in substance use disorders (SUDs) often focus on individual disorders despite high rates of co-occurrence with each other and other externalizing traits. Here we investigate whether incorporating data on other externalizing traits can boost power to detect without sacrificing specificity of SUD genetic signal. We used multivariate genomic analyses and downstream biological annotation and genetic association analyses to explore this question. We found that joint analysis of SUDs and other externalizing traits resulted in increased insights into the neurobiology of broad and substance-specific SUD risk. We found no evidence of loss of specificity for SUD genetic signal but note improvements in our ability to characterize the neurobiology of broad and substance-specific SUD genetic effects. Our findings suggest that genetic risk for SUDs operates largely via pathways shared with other behaviors characterized by behavioral disinhibition,...

Transdiagnostic and Disorder-Level Genome-Wide Association Studies Enhance Precision of Substance Use and Psychiatric Genetic Risk Profiles in African and European Ancestries

Fri, 21 Aug 2026 00:00:00 +0000

BACKGROUND: Substance use disorders (SUDs) and psychiatric disorders frequently co-occur, and their etiology likely reflects both transdiagnostic (i.e., common/shared) and disorder-level (i.e., independent/nonshared) genetic influences. Understanding the genetic influences that are shared and those that operate independently of the shared risk could enhance precision in diagnosis, prevention, and treatment, but this remains underexplored, particularly in non-European ancestry groups. METHODS: We applied genomic structural equation modeling to examine the common and independent genetic architecture among SUDs and psychotic, mood, and anxiety disorders using summary statistics from genome-wide association studies (GWASs) conducted in European ancestry (EUR) and African ancestry (AFR) individuals. To characterize the biological and phenotypic associations, we used FUMA, conducted genetic correlations, and performed phenome-wide association studies (PheWASs). RESULTS: In EUR individuals,...

Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort

Fri, 14 Aug 2026 00:00:00 +0000

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). Design, Setting, and Participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed....

Genome-wide association study of delay discounting identifies 11 loci and reveals transdiagnostic associations across mental and physical health

Fri, 14 Aug 2026 00:00:00 +0000

Delay discounting (DD), a person’s preference for smaller immediate rewards over larger delayed rewards, is a heritable trait that is associated with psychiatric and physical outcomes, yet the biological mechanisms underlying these links are not known. We performed a GWAS of DD using 134,935 23andMe research participants and identified 11 genome-wide significant loci. We did not replicate our previously reported association with rs6528024 (chrXq13.3, GPM6B; P = 5.30 × 10−02). The SNP-heritability of DD was 9.85 ± 0.57%. We observed genetic correlations between DD and 73 behavioral, physical, and neuroimaging traits, many of which persisted even after accounting for educational attainment, intelligence, and executive function. Network analysis revealed that the associations between DD and certain traits were explained by both overlapping and trait-specific biological processes. In a hospital-based cohort (N = 66,917), DD polygenic scores were associated with 212 medical conditions....

Substance Use Patterns from Late Childhood to Mid-Adolescence: Updates on the Adolescent Brain Cognitive Development Study

Thu, 30 Jul 2026 00:00:00 +0000

Background Adolescent substance use is a continued public health concern. The objective of this manuscript is to detail the prevalence of substance use, polysubstance use, and investigate sex differences in the Adolescent Brain Cognitive Development (ABCD) Study from ages 9-17. Methods 11,880 youth across the U.S., recruited at ages 9-10, completed annual study visits from September 2016 to January 2024. The ABCD 6.0 data release comprises baseline to year-6 data. Lifetime and annual substance use prevalence rates, sex differences, and polysubstance use are described and analyzed. Results Past-year substance use prevalence increased with age; 38% report lifetime use by age 16. Alcohol, cannabis, and nicotine were the most reported substances. There were non-significant differences observed between unweighted trends and census-weighted trends. More boys reported substance use prior to age 12, then from age 13 onward, more girls reported use. Polysubstance use analyses detail the...

Psychological Risk Stratification before Spine Surgery Using PCS, PHQ-9, and ODI

Thu, 16 Jul 2026 00:00:00 +0000

Outcomes following spine surgery vary widely, and a substantial proportion of patients continue to experience persistent postoperative pain, functional limitations, and reduced quality of life following surgical intervention. Psychological factors—including depression, pain catastrophizing, and baseline disability—are among the most consistent predictors of poorer postoperative outcomes and persistent spinal pain syndrome following surgery. Despite growing evidence supporting psychosocial risk assessment, systematic psychological screening remains inconsistently implemented across many spine programs. This article presents a practical psychological risk stratification framework integrating three brief and widely validated instruments: the Pain Catastrophizing Scale (PCS), the Patient Health Questionnaire-9 (PHQ-9), and the Oswestry Disability Index (ODI). Together, these measures assess cognitive, emotional, and functional domains associated with surgical outcomes. The article...

Brain morphology in Anorexia Nervosa and its subtypes: A multi-cohort study of individual participant data.