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ContextBiospecimen analysis may enhance confidence in the accuracy of self-reported substance use among adolescents and transitional age youth (TAY). Associations between biospecimen types and self-reported use, however, are poorly characterized in the existing literature. Objective: We performed a systematic review of associations between biospecimen-confirmed and self-reported substance use. Data sources: PubMed, Embase, and Web of Science. Study selection: We included studies documenting associations between self-reported and biospecimen-confirmed substance use among adolescents (12-18 years) and TAY (19-26 years) published 1990-2020. Data extraction: Three authors extracted relevant data using a template and assessed bias risk using a modified JBI Critical Appraisal Tool. Results: We screened 1523 titles and abstracts, evaluated 73 full texts for eligibility, and included 28 studies. Most studies examined urine (71.4%) and hair (32.1%) samples. Self-report retrospective recall period varied from past 24 h to lifetime use. Agreement between self-report and biospecimen results were low to moderate and were higher with rapidly metabolized substances (e.g., amphetamines) and when shorter retrospective recall periods were applied. Frequently encountered sources of potential bias included use of non-validated self-report measures and failure to account for confounding factors in the association between self-reported and biospecimen-confirmed use. Limitations: Study heterogeneity prevented a quantitative meta-analysis. Studies varied in retrospective recall periods, biospecimen processing, and use of validated self-report measures. Conclusions: Associations between self-reported and biospecimen-confirmed substance use are low to moderate and are higher for shorter recall periods and for substances with rapid metabolism. Future studies should employ validated self-report measures and include demographically diverse samples.

We examined the effects of family functioning and beliefs regarding peers' cannabis use among minority (n = 112) and non-minority (n = 275) sexual orientation and gender identity (SOGI), first-time court-involved adolescents. We examined longitudinally the effects of baseline general family functioning and peer cannabis use beliefs on self-reported cannabis use and cannabis-related consequences after 12 months. At baseline, 39.2 percent of adolescents reported using cannabis. Minority SOGI adolescents reported worse family functioning (p = .017) and higher peer cannabis use beliefs (p = .047). Higher peer cannabis use beliefs at baseline predicted recent cannabis use at the 12-month assessment for both minority and non-minority SOGI adolescents. Better family functioning predicted a lower likelihood of recent cannabis use at 12 months for non-minority SOGI adolescents, but not for minority SOGI adolescents. Baseline peer cannabis use beliefs and family functioning predicted cannabis-related consequences for both cohorts at 12 months when accounting for intermediate (i.e., four-month and eight-month) data. Among all first-time court-involved adolescents, those who believed greater cannabis use among their peers reported more subsequent cannabis use themselves. Conversely, higher general family functioning may be less of a protective factor for minority SOGI adolescents. These results suggest the utility of feedback interventions to modify peer norm beliefs among first-time court-involved adolescents.

Amidst a rapidly changing legal landscape, cannabis use in the United States has become increasingly common in the past several years. There is strong evidence to suggest that chronic and early cannabis use increases the risk of developing a psychotic disorder, and there is at least moderate evidence that suggests ongoing cannabis use among individuals with a psychotic disorder worsens clinical outcomes (eg, decreased psychiatric medication adherence, more frequent psychiatric hospitalizations). In this Review Article, we provide a focused, clinically oriented overview of the epidemiology and characteristics of cannabis use among individuals with first-episode psychosis; evaluation of cannabis use; and treatment modalities, focusing on behavioral interventions suitable for outpatient primary care settings. We discuss the limited data supporting pharmacologic interventions for cannabis use disorder, specifically among individuals with first-episode psychosis, and the unique potential of cannabidiol to serve as a harm-reduction strategy for individuals who are not able or willing to achieve abstinence for cannabis.

BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.

Purpose of ReviewThis review discusses recent advances in research on the intersection of HIV prevention and substance use among youth involved with the justice system. We discuss current themes of recent findings and provide guidance for researchers, policymakers, and clinicians on the next steps in advancing work in this nascent area.Recent FindingsOf the 46 studies that measured HIV risk and substance use among justice-involved youth, 56% were cross-sectional designs, 22% were intervention trials, and 22% were longitudinal designs. Cross-sectional studies suggested that substance use is highly associated with HIV risk behaviors. Longitudinal analyses underscored the importance of understanding contextual risk factors, such as trauma and violence. Intervention trials demonstrated improved scientific rigor of behavioral approaches. Summary Despite recent advances, research in this field remains limited. Future directions include longer follow-up periods, consideration of biomedical HIV -prevention interventions, and a focus on dissemination and implementation science of efficacious interventions.

ObjectivesConcomitant excessive alcohol consumption and benzodiazepine use is associated with adverse health outcomes. We examined associations of unhealthy alcohol use and other patient characteristics with benzodiazepine use.Study designA cross-sectional analysis of 2,089,525 Kaiser Permanente of Northern California outpatients screened for unhealthy alcohol use in primary care between November 1, 2014, and December 31, 2016.MethodsWe fit multivariable generalized linear models to estimate the associations between unhealthy alcohol use and benzodiazepine dispensation and, among patients who were dispensed a benzodiazepine, mean doses (in mean lorazepam-equivalent daily doses [LEDDs]) and prescription durations. We controlled for patient sex, age, race/ethnicity, estimated household income, Charlson Comorbidity Index (CCI) score, anxiety disorder, alcohol use disorder, insomnia, musculoskeletal pain, and epilepsy.ResultsIn the 12 months centered around (6 months before and 6 months after) the first alcohol-screening visit, 7.5% of patients used benzodiazepines. The following characteristics were independently associated with higher rates of benzodiazepine use, higher LEDD, and longer prescription duration: older age, white race/ethnicity, lower estimated household income, higher CCI score, and the presence of an anxiety disorder, insomnia, musculoskeletal pain, or epilepsy. Women and patients with an alcohol use disorder or unhealthy alcohol use, compared with men and patients with low-risk drinking or abstinence, were more likely to use a benzodiazepine; however, their LEDDs were lower and their prescription durations were shorter.ConclusionsBenzodiazepine use in primary care was associated with older age, female sex, white race/ethnicity, lower socioeconomic status, and unhealthy alcohol use. These findings may be applied to develop policies and interventions to promote judicious benzodiazepine use.

PurposeWe sought to compare the demographic characteristics, drug and alcohol use, sexual behaviors, delinquency, and mental health indicators of sexual minority and nonsexual minority first-time offending, court-involved, nonincarcerated adolescents.MethodsUsing adolescent- and caregiver-reported baseline data from the Epidemiologic Study Involving Children in the Court, a prospective cohort study of 423 adolescent-caregiver dyads recruited from a Northeastern family court system, we compared demographic and behavioral health characteristics of sexual minority and nonsexual minority first-time offending, court-involved, nonincarcerated adolescents.ResultsNearly one-third of the adolescents (31.4%, n = 133) were classified as a sexual minority; 19.6% (n = 81) self-identified with a nonheterosexual sexual orientation. Sexual minority adolescents were more likely than their nonsexual minority peers to identify as female, to have used psychiatric services or psychotropic medications, to have used an illicit drug or alcohol or to know peers who use these substances, to report alcohol/drug use during sex, to endorse more severe mental health problems, to have more recent post-traumatic symptoms, and to have engaged in self-harm behaviors. However, sexual minority adolescents did not differ from nonsexual minority adolescents in other demographic characteristics (including school performance) or delinquent behavior.ConclusionsOne-third of court-involved, nonincarcerated adolescents may be sexual minorities. Specificscreening methods are necessary to identify these adolescents and to address their unique risk characteristics, which include more severe mental health difficulties and higher rates of high-risk sexual behavior and drug/alcohol use compared with their nonsexual minority peers.

BackgroundHazardous alcohol use with depression may exacerbate health conditions and complicate medical care. We examined the rate of depression screening by alcohol use severity among primary care patients screened for hazardous alcohol use and, among those screened, examined patterns of significant depressive symptoms.MethodsUsing cross-sectional data from primary care patients (n = 2,894,906), we examined past-90-day alcohol use (number of typical drinking days/week and typical number of drinks consumed daily); depression screening rates (using the Patient Health Questionnaire 9 [PHQ-9]); and symptom severity, demographics, and prevalence of selected psychiatric diagnoses.ResultsWithin 30 days of routine, in-clinic alcohol use screening by medical assistants, 2.4% (n = 68,686) of patients also completed a PHQ-9; these patients were more likely to be female, younger, white, Medicaid insured, and to have a nondepressive psychiatric diagnosis and a lower Charlson comorbidity score. Abstainers and moderate drinkers (1 to 7 drinks/week or 1 to 4 drinks/week for women and individuals >65 years or for men ≤65 years, respectively) were less likely than hazardous drinkers (exceeding weekly limits) to complete the PHQ-9 or to have significant depressive symptoms (PHQ-9 score ≥10). Nonwhite patients with higher Charlson comorbidity scores were more likely to endorse significant depressive symptoms.ConclusionsOnly a small fraction of patients in this cohort were screened for depression. Nonwhite patients and those with higher comorbidity burden were more likely to report depression but less likely to be screened. These discrepancies between depression-screening rates and significant depressive symptoms suggest that screening for depression should be enhanced in these at-risk groups.

Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.

The combined use of opioid and benzodiazepine medications increases the risk of hazardous effects, such as respiratory depression. Although recent increases in outpatient use of opioid prescriptions have been documented, there are limited data regarding rates and correlates of combined opioid and benzodiazepines among adults in outpatient settings. Our objective was to examine annual trends in outpatient visits including opioids, benzodiazepines, and their combination among adults as well as clinical and demographic correlates. We used data from the 1993-2014 National Ambulatory Medical Care Survey (NAMCS) among non-elderly (i.e., ages 18-64 years) adults to examine the probability of a visit including an opioid, benzodiazepine, or their combination, in addition to clinical and demographic correlates. From 1993 to 2014, benzodiazepines-with-opioids visits increased from 9.8 to 62.5 (OR = 9.23, 95% CI = 5.45-15.65) per 10,000 visits. Highest-represented groups among benzodiazepines-with-opioids visits were older (50-64 years) (49.1%), white (88.8%), commercially insured (58.0%) patients during their first visit (87.6%) to a primary-care physician (41.9%). We identified a significant increase in the outpatient co-prescription of opioids and benzodiazepines, notably among adults aged 50-64 years during primary-care visits. Educational and policy changes to provide alternatives to benzodiazepine-with-opioid co-prescription and limiting opioid prescription to pain specialists may reduce rates of this potentially hazardous combination.

ObjectiveTourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD).MethodParticipants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms.ResultsSRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone.ConclusionHigher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae.

ObjectivePhenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.MethodAssessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.ResultsThe authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.ConclusionsThe analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.

ObjectiveTo identify heritable symptom-based subtypes of Tourette syndrome (TS).MethodsForty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.ResultsA 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)).ConclusionsExpanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.

ImportanceTourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (

BackgroundElectronic health record (EHR)–based disease registries have aided health care professionals and researchers in increasing their understanding of chronic illnesses, including identifying patients with (or at risk of developing) conditions and tracking treatment progress and recovery. Despite excessive alcohol use being a major contributor to the global burden of disease and disability, no registries of alcohol problems exist. EHR-based data in Kaiser Permanente Northern California (KPNC), an integrated health system that conducts systematic alcohol screening, which provides specialty addiction medicine treatment internally and has a membership of over 4 million members that are highly representative of the US population with access to care, provide a unique opportunity to develop such a registry. ObjectiveOur objectives were to describe the development and implementation of a protocol for assembling the KPNC Adult Alcohol Registry, which may be useful to other researchers and health systems, and to characterize the registry cohort descriptively, including underlying health conditions. MethodsInclusion criteria were adult members with unhealthy alcohol use (using National Institute on Alcohol Abuse and Alcoholism guidelines), an alcohol use disorder (AUD) diagnosis, or an alcohol-related health problem between June 1, 2013, and May 31, 2019. We extracted patients’ longitudinal, multidimensional EHR data from 1 year before their date of eligibility through May 31, 2019, and conducted descriptive analyses. ResultsWe identified 723,604 adult patients who met the registry inclusion criteria at any time during the study period: 631,780 with unhealthy alcohol use, 143,690 with an AUD diagnosis, and 18,985 with an alcohol-related health problem. We identified 65,064 patients who met two or more criteria. Of the 4,973,195 adult patients with at least one encounter with the health system during the study period, the prevalence of unhealthy alcohol use was 13% (631,780/4,973,195), the prevalence of AUD diagnoses was 3% (143,690/4,973,195), and the prevalence of alcohol-related health problems was 0.4% (18,985/4,973,195). The registry cohort was 60% male (n=432,847) and 41% non-White (n=295,998) and had a median age of 41 years (IQR=27). About 48% (n=346,408) had a chronic medical condition, 18% (n=130,031) had a mental health condition, and 4% (n=30,429) had a drug use disorder diagnosis. ConclusionsWe demonstrated that EHR-based data collected during clinical care within an integrated health system could be leveraged to develop a registry of patients with alcohol problems that is flexible and can be easily updated. The registry’s comprehensive patient-level data over multiyear periods provides a strong foundation for robust research addressing critical public health questions related to the full course and spectrum of alcohol problems, including recovery, which would complement other methods used in alcohol research (eg, population-based surveys, clinical trials).