Emergence of Sex Differences in U.S. Adolescent Substance Use.

Background: Adolescence is a common time for experimentation with substance use and the emergence of sex differences in substance use patterns. Although similar in early adolescence, male and female substance use patterns historically diverge by young adulthood, with males using more substances than females. We aim to add to current literature by utilizing a nationally representative sample, assessing a broad range of substances used, and focusing on a sentinel period during which sex differences emerge. We hypothesized that certain sex-specific substance use patterns emerge in adolescence. Methods: Data are from the 2019 Youth Risk Behavior Survey (n = 13,677), a nationally representative sample of high school students. Weighted logistic analyses of covariance adjusting for race/ethnicity evaluated males' and females' substance use (14 outcomes) by age category. Results: Among all adolescents, more males reported illicit substance use and cigarette smoking than females, whereas more females reported prescription opioid misuse, synthetic cannabis use, recent alcohol use, and binge drinking. Divergence between male and female use usually occurred at 18+ years. Odds of using most illicit substances were significantly greater among males than females at age 18+ years (aORs 1.7-4.47). Among 18+ year-olds, males and females did not differ in electronic vapor product use, alcohol use, binge drinking, cannabis use, synthetic cannabis use, cigarette smoking, or prescription opioid misuse. Conclusions: Sex differences in adolescent use of most but not all substances emerge by age 18+ years. Sex-specific patterns of adolescent substance use may inform specific prevention efforts and identify peak ages for intervention.

Adolescents in Treatment for Substance Use Disorders: Callous-Unemotional Traits Moderate Associations Between Transdiagnostic Symptoms and Adolescent Suicidality.

Suicide, a common cause of death in adolescents, is linked to internalizing and externalizing symptoms. These associations are pronounced amongst adolescents who use substances. But these relationships are complex. For example, sex differences are present in association with internalizing/externalizing symptoms as well as differences in suicidality. A rarely explored factor that may account for this complexity as a moderator is callous-unemotional traits. The present study examines associations of internalizing and externalizing in relation to suicidality in the context of callous-unemotional traits amongst adolescents in substance use treatment. Additionally, sex differences were explored. A sample of 317 adolescents (13-18; 16.05 ± 1.22) in treatment for substance use completed measures for internalizing, externalizing, and suicidal symptoms. The main result suggested the presence of callous-unemotional (CU) traits attenuated the positive association between internalizing and a latent suicidality factor. This novel result contextualizes the association between transdiagnostic symptoms and suicidality. Assessing CU traits in the presence of internalizing symptoms may be an important component of understanding suicide risk amongst adolescents in treatment for substance use.

Discriminative validity and clinical utility of an abuse-neglect interview for adolescents with conduct and substance use problems.

OBJECTIVE: Many youths with conduct and substance use problems experience abuse and neglect. A valid measure of the severity of abuse-neglect events could facilitate research and clinical care. The authors' goal was to examine the discriminative validity, clinical utility, and severity correlations of the Colorado Adolescent Rearing Inventory, a structured, 20-45-minute abuse-neglect interview in the assessment of adolescents with conduct and substance use problems. METHOD: Ninety-eight adolescent patients with conduct and substance use problems and 102 comparison subjects (about 40% of the subjects in each group were female) completed the Colorado Adolescent Rearing Inventory, the Diagnostic Interview Schedule for Children, and the Composite International Diagnostic Interview-Substance Abuse Module. RESULTS: Although the subjects were advised that reports of abuse-neglect would be communicated to child welfare agencies, nearly two-thirds of the patients with conduct and substance use problems endorsed items indicating probable abuse-neglect, compared with about a third of the comparison subjects, a highly significant difference. Clinicians judged that 68%-80% of the cases of the patients and comparison subjects who endorsed such items warranted reporting to child welfare agencies. Scores on the Colorado Adolescent Rearing Inventory correlated significantly with severity of substance involvement, conduct disorder, and major depression. Compared to males, significantly more females (including 15% of comparison females) reported sexual abuse. Patients were significantly more likely than comparison subjects to attribute adverse life effects to their reported abuse-neglect experiences. CONCLUSIONS: Colorado Adolescent Rearing Inventory scores revealed many cases of serious abuse-neglect, generated many reports to child welfare agencies, demonstrated discriminative validity, correlated with clinical measures, and reflected important gender differences. The Colorado Adolescent Rearing Inventory can contribute to clinical evaluation and research involving youths with conduct and substance use problems.

A genome-wide search for quantitative trait loci influencing substance dependence vulnerability in adolescence.

This study describes results from a genome-wide search for quantitative trait loci (QTL) influencing substance dependence vulnerability in adolescence. We utilized regression-based multipoint (and single-point) QTL mapping procedures designed for selected sibpair samples. Selected sibling pairs included 250 proband-sibling pairs from 192 families. Clinical probands (13-19 years of age) were drawn from consecutive admissions to substance abuse treatment facilities in the Denver metropolitan area; siblings of probands ranged in age from 12 to 25 years. In addition to the selected sample, a community-based sample of 3676 adolescents and young adults were utilized to define a clinically-significant, heritable, age- and sex-normed index of substance dependence vulnerability-a priori and independent of our linkage results. Siblings and their parents were genotyped for 374 STR micro-satellite markers distributed across the 22 autosomes (average inter-marker distance=9.2 cM). Non-parametric single-point linkage results indicated 17 markers on 11 chromosomes with nominally significant tests of linkage; six markers with LOD scores greater than 1.0 and one marker (D3S1614) with a LOD score of 2.2. Multipoint mapping corroborated two locations and provided preliminary evidence for linkage to regions on chromosome 3q24-25 (near markers D3S1279 and D3S1614) and chromosome 9q34 (near markers D9S1826 and D9S1838).

Improving entry to methadone maintenance among out-of-treatment injection drug users.

This study of 577 out-of-treatment drug injectors was designed to assess predictors of methadone maintenance treatment entry, including offering free treatment coupons. Using targeted sampling methods, participants were recruited through street outreach; randomly, they were either assigned a coupon for 90 days of free treatment or required to pay for their treatment. Regardless of assignment, all subjects who desired treatment were provided transportation, rapid intake, and a waiver of the treatment entry fee. Overall, 33% entered treatment, including 66% of those who received a free coupon. Other factors associated with treatment entry included desire for treatment, heroin use, prior treatment experience, associating with fewer drug-using friends, and injecting with a previously used unsterile needle/syringe. Injecting cocaine and smoking crack reduced the probability of treatment entry. Findings lend support to street outreach efforts designed to increase rates of treatment entry among chronic out-of-treatment drug injectors. Additional treatment options are required for those abusing cocaine.

Comparing linear and nonlinear mixed model approaches to cosinor analysis.

The cosinor model, used for variables governed by circadian and other biological rhythms, is a nonlinear model in the amplitude and acrophase parameters that has a linear representation upon transformation. With linear cosinor analysis, amplitude and acrophase for each harmonic can be computed as nonlinear functions of the estimated linear regression coefficients. Here a flexible mixed model approach to cosinor analysis is considered, where the fixed effect parameters may enter nonlinearly as acrophase and amplitude for each harmonic or linearly after transformation to regression coefficients. In addition, the random effects may enter nonlinearly as subject-specific deviations from the acrophases and amplitudes or linearly as subject-specific deviations from the regression coefficients. It is also possible for the fixed effects to enter nonlinearly while the random effects enter linearly. Additionally, we evaluate whether including higher order linear harmonic terms as random effects, that is, Rao-Khatri 'covariance adjustment', improves precision. Applying the delta method to nonlinear functions of the parameters from linear mixed cosinor models to obtain approximate variances produces results that are often identical to results from nonlinear mixed models. Consequently, traditional linear cosinor analysis can often be used to estimate and compare the nonlinear parameters of interest, that is, amplitudes and acrophases, via the delta method. This is advantageous since the nonlinear mixed model may have convergence difficulties for more complex models. However, for some multiple-group analyses, the linear cosinor transformation should not be used and we clarify when the two methods are equivalent and when they differ.

Admixture analysis of smooth pursuit eye movements in probands with schizophrenia and their relatives suggests gain and leading saccades are potential endophenotypes.

Abnormalities during a smooth pursuit eye movement task (SPEM) are common in schizophrenic patients and their relatives. This study assessed various components of SPEM performance in first-degree unaffected relatives of schizophrenic patients. One hundred individuals with schizophrenia, 137 unaffected first-degree relatives, and 69 normal controls completed a 16.7 degrees/s SPEM task. Smooth pursuit gain, catch-up saccades (CUS), large anticipatory saccades, and leading saccades (LS) were identified. Groups were compared with parametric and admixture analyses. Schizophrenic patients performed more poorly than unaffected relatives and normals on gain, CUS, and LS. Unaffected relatives were more frequently impaired than normals only on gain and LS. Relatives of childhood-onset and adult-onset probands had similar impairments. Gain and frequency of leading saccades may be genetic endophenotypes in childhood-onset and adult-onset schizophrenia.