Cumulative Effects of Resting-State Connectivity Across All Brain Networks Significantly Correlate with Attention-Deficit Hyperactivity Disorder Symptoms.

Identification of replicable neuroimaging correlates of attention-deficit hyperactivity disorder (ADHD) has been hindered by small sample sizes, small effects, and heterogeneity of methods. Given evidence that ADHD is associated with alterations in widely distributed brain networks and the small effects of individual brain features, a whole-brain perspective focusing on cumulative effects is warranted. The use of large, multisite samples is crucial for improving reproducibility and clinical utility of brain-wide MRI association studies. To address this, a polyneuro risk score (PNRS) representing cumulative, brain-wide, ADHD-associated resting-state functional connectivity was constructed and validated using data from the Adolescent Brain Cognitive Development (ABCD, N = 5,543, 51.5% female) study, and was further tested in the independent Oregon-ADHD-1000 case-control cohort (N = 553, 37.4% female). The ADHD PNRS was significantly associated with ADHD symptoms in both cohorts after accounting for relevant covariates (p < 0.001). The most predictive PNRS involved all brain networks, though the strongest effects were concentrated among the default mode and cingulo-opercular networks. In the longitudinal Oregon-ADHD-1000, non-ADHD youth had significantly lower PNRS (Cohen's d = -0.318, robust p = 5.5 × 10-4) than those with persistent ADHD (age 7-19). The PNRS, however, did not mediate polygenic risk for ADHD. Brain-wide connectivity was robustly associated with ADHD symptoms in two independent cohorts, providing further evidence of widespread dysconnectivity in ADHD. Evaluation in enriched samples demonstrates the promise of the PNRS approach for improving reproducibility in neuroimaging studies and unraveling the complex relationships between brain connectivity and behavioral disorders.

Optimizing Individual HIV Testing and Counseling for Emerging Adult Sexual Minority Men (Aged 18 to 24) in Relationships: A Pilot Randomized Controlled Trial of Adjunct Communication Components.

The majority of new HIV infections in the US occur among sexual minority men (SMM) with older adolescent and emerging adult SMM at the highest risk. Those in relationships face unique HIV prevention challenges. Existing sexual HIV transmission risk interventions for male couples often encounter implementation challenges and engaging younger SMM early in relationships may be particularly difficult. This pilot randomized controlled trial evaluated the acceptibility and feasibility of We Test HIV testing - a behavioral health intervention tailored for younger SMM in realtionships - and generated preliminary estimates of effect size. The intervention comprises two adjunct moduls - video-based communication skills training as well as communication goal setting and planning - delivered in conjunction with routine HIV testing and counseling in individual or dyadic formats. A sample of 69 SMM aged 17 to 24 were recruited online. Following baseline assessment, youth were randomized to receive either the experimental, We Test, intervention or routine HIV testing (the control condition). Follow-up assessments were completed 3 and 6 months post-baseline. Results suggested the study was feasible and the individually delivered format was acceptible. We Test HIV testing was associated with significant improvements in communication skills. In addition, youth who remained in a relationship experienced an increase in communal coping to reduce HIV infection risk and relationship power. While groups did not differ with respect to condomless anal sex with casual partners, these psycho-social constructs (communication, communal coping with HIV prevention, and relationship power) may serve as mediators of intervention effects on sexual risk reduction in a larger study.

Gene-by-Environment Interaction Effects of Social Adversity on Externalizing Behavior in ABCD Youth.

This study tested whether multiple domains of social adversity, including neighborhood opportunity/deprivation and life stress, moderate genetic (A), common environmental (C), and unique environmental (E) influences on externalizing behaviors in 760 same-sex twin pairs (332 monozygotic; 428 dizygotic) ages 10-11 from the ABCD Study. Proportion of C influences on externalizing behavior increased at higher neighborhood adversity (lower overall opportunity). A decreased and C and E increased at lower levels of educational opportunity. A increased at lower health-environment and social-economic opportunity levels. For life stress, A decreased and E increased with number of experienced events. Results for educational opportunity and stressful life experiences suggest a bioecological gene-environment interaction pattern such that environmental influences predominate at higher levels of adversity, whereas limited access to healthcare, housing, and employment stability may potentiate genetic liability for externalizing behavior via a diathesis-stress mechanism. More detailed operationalization of social adversity in gene-environment interaction studies is needed.

Prevention of hazardous use of alcohol among high school students: a study protocol for the randomized controlled trial 'Our choice'.

BACKGROUND: Adolescent hazardous alcohol use is prevalent and has serious short- and long-term consequences. The trial 'Our Choice' examines efficacy, feasibility and acceptability of prevention interventions targeting school, parent, and student levels at Danish high schools. We hypothesize that students in a structural intervention (school and parent levels) reduce hazardous alcohol use and related health behaviors compared to students in an assessment only control group 12 months post baseline; and that adding group-based Motivational Interviewing (group MI) yields further improvements. The study examines the efficacy of interventions targeting multiple levels with the aim of providing novel insights into prevention of adolescent hazardous alcohol use and related health outcomes. METHOD: The study employs a parallel group cluster randomized controlled trial design with three conditions: (1) structural condition targeting school and parent levels, (2) structural condition combined with group MI which also targets the student level, and (3) assessment-only control condition. A participatory approach is used to adapt and develop interventions. Sixteen high schools in Denmark and about N = 3100 first-year students (15-18 years) enrolled in high school in August 2023 will be recruited. Data will be collected via online questionnaires pre-interventions (baseline), 2, 6, 9 and 12 month post baseline and analyzed with generalized linear mixed models. The primary outcome is past month high intensity drinking; secondary outcomes are alcohol use, alcohol-related consequences, well-being, tobacco, and illegal substance use. Feasibility and acceptability will be assessed via surveys (students) and interviews (high school staff) to inform future implementation. DISCUSSION: 'Our Choice' is the first trial to compare the efficacy of a structural intervention targeting school- and parent levels to an intervention targeting these levels and the student level via group MI - on hazardous drinking and related health outcomes among students. Preventing and reducing hazardous alcohol use during adolescence is crucial due to the short- and long-term negative consequences. The tested interventions can be implemented at low cost. The study has significant implications for adolescent health and well-being and has potential to inform evidence-based decisions on alcohol prevention policy, education, and health professions. TRIAL REGISTRATION NUMBER: The trial was retrospectively registered at ClinicalTrials.gov on August 24th, 2023. TRIAL REGISTRATION NUMBER: ID NCT06018389.

Long-Term RCT outcomes for adolescent alcohol and cannabis use within a predominantly Hispanic sample.

Because adolescents are unlikely to seek, receive, or complete treatment for alcohol and/or cannabis misuse, it is important to enhance the lasting impact of clinical contacts when they do occur. Adolescents (N = 506; 72.5% Hispanic) were randomized to motivational interviewing (MI) versus alcohol and cannabis education (ACE). Latent growth models estimated change over time. Significant reductions in alcohol use were observed, with slightly greater reductions by 12-month follow-up for MI. Both interventions significantly reduced cannabis use, with no treatment group differences. When outcomes were examined comparing Hispanic to non-Hispanic participants, there were no significant differences in intervention efficacy by group. MI's inherently client-centered and culturally adaptive approach may contribute to its equitable degree of behavior change for youth across race/ethnic backgrounds.

Correlates of HIV Testing across the lifespan - adolescence through later adulthood - among sexual minority men in the US who are not on PrEP.

Regular HIV testing is an essential component of the HIV prevention and care cascade. Sexual minority males (SMM) account for most new HIV infections in the US and testing rates among SMM vary substantially across the lifespan. Research has largely overlooked the developmental context of HIV testing. The current study compared correlates of HIV testing among adolescents (aged 13-17; n = 1,641), emerging adults (aged 18-29; n = 50,483), early adults (aged 30-39; n = 25,830), middle adults (aged 40-64; n = 25,326), and late adults (65 and older; n = 1,452) who were recruited online. Overall, HIV testing rates were lowest among adolescent SMM. Having condomless anal sex in the past 3-months was a consistentpredictor of HIV testing across all age cohorts.The association between relationship status and frequency of HIV testing varied across ages. Being in a non-monogamous relationship (versus single) was associated with more frequent HIV testing among adolescent and emerging adult SMM , while being in a monogamous relationship (versus single) was associated with lower odds of HIV testing among early, middle, and late adults.

Trajectories and biopsychosocial predictors of daily acute pain in adolescents receiving treatment for pain: a daily diary study.

Research regarding daily acute pain and its correlates has primarily been conducted with adolescents who have had major surgery or musculoskeletal pain, restraining efforts towards adapting interventions for adolescents with other sources of acute pain. We explored the trajectories and correlates of pain intensity. Adolescents with an opioid prescription to treat acute pain (N = 157) completed demographic questions, and the PROMIS pediatric depression and anxiety subscales. A 10-day daily diary assessed pain intensity, pain interference, sleep quality, and opioid use. Three trajectories of pain intensity emerged: (1) slow decreases in pain, (2) rapid decreases in pain, and (3) stable or slight increases in pain. Teens with stable pain demonstrated the greatest anxiety levels. Higher sleep quality predicted lower next day pain intensity and pain interference, when controlling for opioid use. Future research should employ intensive longitudinal methodology to further guide intervention development and prevent the transition to chronic pain.

Early adolescent gender diversity and mental health in the Adolescent Brain Cognitive Development study.

BACKGROUND: There are known associations between mental health symptoms and transgender identity among adults. Whether this relationship extends to early adolescents and to gender domains other than identity is unclear. This study measured dimensions of gender in a large, diverse, sample of youth, and examined associations between diverse gender experiences and mental health. METHODS: The ABCD study is an ongoing, longitudinal, US cohort study. Baseline data (release 2.0) include 11,873 youth age 9/10 (48% female); and the 4,951 1-year follow-up visits (age 10/11; 48% female) completed prior to data release. A novel gender survey at the 1-year visit assessed felt-gender, gender noncontentedness, and gender nonconformity using a 5-point scale. Mental health measures included youth- and parent-reports. RESULTS: Roughly half a percent of 9/10-year-olds (n = 58) responded 'yes' or 'maybe' when asked, 'Are you transgender' at baseline. Recurrent thoughts of death were more prevalent among these youth compared to the rest of the cohort (19.6% vs. 6.4%, χ2  = 16.0, p < .001). At the 1-year visit, when asked about the three dimensions of gender on a 5-point scale, 33.2% (n = 1,605) provided responses that were not exclusively and totally aligned with one gender. Significant relationships were observed between mental health symptoms and gender diversity for all dimensions assessed. CONCLUSIONS: Similar to adult studies, early adolescents identifying as transgender reported increased mental health symptoms. Results also point to considerable diversity in other dimensions of gender (felt-gender, gender noncontentedness, gender nonconformity) among 10/11-year-olds, and find this diversity to be related to critical mental health symptoms. These findings add to our limited understanding of the relationship between dimensions of gender and wellness for youth.

Developmental Barriers to Couples' HIV Testing and Counseling Among Adolescent Sexual Minority Males: A Dyadic Socio-ecological Perspective.

Couples HIV Testing and Counseling (CHTC) is now a standard of care for partnered sexual minority men. While adolescent sexual minority men (ASMM; ages 15-19) face disproportionate HIV risk, the emergent nature of relationships and communication skills may present challenges to accessing and engaging in CHTC. This study utilized qualitative data from 28 ASMM recruited in 4 urban centers in the USA during the formative stage of Adolescent Trials Network study ATN-156. Participants were cis-male, HIV-negative, and in a relationship with a similarly-aged cis-male partner. Thematic analysis indicated low and high levels of commitment were barriers to CHTC. Concerns about caregiver attitudes towards HIV testing were salient. Adolescents' perception of structural barriers highlighted reliance on caregiver resources, which limited access to sexual health services. Prevention programming must address structural barriers to access encountered by adolescents. ASMM in relationships may benefit from programming that includes options for individual and dyadic participation.

Randomized Controlled Trial of an Alcohol-related Sexual Risk Reduction Intervention with Adolescents: The Role of Neurocognitive Activation During Risky Decision-Making.

Justice-involved youth are at a higher risk of negative outcomes from sexual activity and alcohol use relative to their non-justice involved peers. In the current study, we tested the extent to which variability in neurocognitive response (i.e., activation in the right superior parietal lobule; rSPL) during a risky decision-making task moderated the success of a sexual risk reduction intervention. In a cluster randomized trial blocked by gender, justice-involved adolescents (N = 269) first completed a risky decision-making task during a magnetic resonance imaging (MRI) session, then were assigned to an information-only control (GINFO) or sexual risk reduction intervention incorporating alcohol risk reduction content (GPI + GMET) and then re-contacted every three months for one year. Youth in the GPI + GMET intervention reported less sexual risk behavior 12 months after intervention than those in the control. Although neurocognitive activation was associated with sexual risk behavior, it did not moderate intervention outcomes. This risk-reduction intervention appears to work equally well across a range of neurocognitive responses.

The future of translational research on alcohol use disorder.

In March 2019, a scientific meeting was held at the University of California, Los Angeles (UCLA) Luskin Center to discuss approaches to expedite the translation of neurobiological insights to advances in the treatment of alcohol use disorder (AUD). A guiding theme that emerged was that while translational research in AUD is clearly a challenge, it is also a field ripe with opportunities. Herein, we seek to summarize and disseminate the recommendations for the future of translational AUD research using four sections. First, we briefly review the current landscape of AUD treatment including the available evidence-based treatments and their uptake in clinical settings. Second, we discuss AUD treatment development efforts from a translational science viewpoint. We review current hurdles to treatment development as well as opportunities for mechanism-informed treatment. Third, we consider models of translational science and public health impact. Together, these critical insights serve as the bases for a series of recommendations and future directions. Towards the goal of improving clinical care and population health for AUD, scientists are tasked with bolstering the clinical applicability of their research findings so as to expedite the translation of knowledge into patient care.

Application of the common base method to regression and analysis of covariance (ANCOVA) in qPCR experiments and subsequent relative expression calculation.

BACKGROUND: Quantitative polymerase chain reaction (qPCR) is the technique of choice for quantifying gene expression. While the technique itself is well established, approaches for the analysis of qPCR data continue to improve. RESULTS: Here we expand on the common base method to develop procedures for testing linear relationships between gene expression and either a measured dependent variable, independent variable, or expression of another gene. We further develop functions relating variables to a relative expression value and develop calculations for determination of associated confidence intervals. CONCLUSIONS: Traditional qPCR analysis methods typically rely on paired designs. The common base method does not require such pairing of samples. It is therefore applicable to other designs within the general linear model such as linear regression and analysis of covariance. The methodology presented here is also simple enough to be performed using basic spreadsheet software.

Correction of respiratory artifacts in MRI head motion estimates.

Head motion represents one of the greatest technical obstacles in magnetic resonance imaging (MRI) of the human brain. Accurate detection of artifacts induced by head motion requires precise estimation of movement. However, head motion estimates may be corrupted by artifacts due to magnetic main field fluctuations generated by body motion. In the current report, we examine head motion estimation in multiband resting state functional connectivity MRI (rs-fcMRI) data from the Adolescent Brain and Cognitive Development (ABCD) Study and comparison 'single-shot' datasets. We show that respirations contaminate movement estimates in functional MRI and that respiration generates apparent head motion not associated with functional MRI quality reductions. We have developed a novel approach using a band-stop filter that accurately removes these respiratory effects from motion estimates. Subsequently, we demonstrate that utilizing a band-stop filter improves post-processing fMRI data quality. Lastly, we demonstrate the real-time implementation of motion estimate filtering in our FIRMM (Framewise Integrated Real-Time MRI Monitoring) software package.

Exploring Cannabis and Alcohol Co-Use in Adolescents: A Narrative Review of the Evidence.

Objective: Amidst the evolving policy surrounding cannabis legalization in the United States, cannabis use is becoming increasingly prevalent as perceptions of harm decrease, particularly among adolescents. Cannabis and alcohol are commonly used by adolescents and are often used together. However, developmental research has historically taken a "single substance" approach to examine the association of substance use and adolescent brain and behavior rather than examining co-(or poly-substance) use of multiple substances, such as cannabis and alcohol. Thus, the acute effects of cannabis and alcohol, and the impact of co-use of cannabis and alcohol on the adolescent brain, cognitive function and subsequent psychosocial outcomes remains understudied. This narrative review aims to examine the effects of cannabis and alcohol on adolescents across a number of behavioral and neurobiological outcomes. Methods: The PubMed and Google Scholar databases were searched for the last 10 years to identify articles reporting on acute effects of cannabis and alcohol administration, and the effects of cannabis and alcohol on neuropsychological, neurodevelopmental, neural (e.g., structural and functional neuroimaging), and psychosocial outcomes in adolescents. When adolescent data were not available, adult studies were included as support for potential areas of future direction in adolescent work. Results: Current studies of the impact of cannabis and alcohol on adolescent brain and behavior have yielded a complicated pattern. Some suggest that the use of cannabis in addition to alcohol during adolescence may have a "protective" effect, yielding neuropsychological and structural brain outcomes that are better than those for adolescents who use only alcohol. However, other adolescent studies suggest that cannabis and alcohol co-use is associated with negative health and social outcomes such as poorer academic performance and impaired driving. Conclusion: Variation in study methodologies, policy-level limitations and our limited understanding of the developmental neurobiological effects of cannabis preclude the straightforward interpretation of the existing data on adolescent cannabis and alcohol use. Further research on this topic is requisite to inform the development of effective intervention and prevention programs for adolescent substance users, which hinge on a more comprehensive understanding of how cannabis-and its intersection with alcohol-impacts the developing brain and behavior.

Hunting for What Works: Adolescents in Addiction Treatment.

Although adolescents are developmentally distinct from adults, they often receive addiction treatment based on adult models. This is problematic because adolescents face significantly different conditions in addiction treatment, including distinct basic biological and neurodevelopmental stages, unique sociodevelopmental concerns, distinctive addiction trajectories, and, in turn, disparate treatment goals and outcomes. In sum, it can be difficult for even savvy clinicians to know how to approach addiction treatment with this important age group. In an effort to help clinicians and researchers consider substance use via a neurodevelopmental lens, we approached this review with 4 goals: (i) characterize the prevalence, and related health and safety implications of substance use within this age group; (ii) identify the nature of the adolescent brain, including characteristic features of this phase of neurodevelopment relevant to adolescent substance use treatment; (iii) provide an overview of current adolescent addiction interventions and avenues to improve clinical treatment and clinical research efforts for adolescents; and (iv) examine the intersection between the nature of the developing brain and adolescent substance use, and utilize that information to inform alternative routes and directions for substance use treatment in this critical age group. This review concludes by offering a novel neurodevelopmental model and framework to examine substance use interventions, along with a series of recommendations to optimize adolescent substance use treatment and clinical research.

Perspectives on facilitating whole exome sequencing for international patients at Mayo Clinic.

Whole exome sequencing (WES) has become a fundamental component of genetic evaluation and diagnosing rare genetic diseases. This test is now offered to patients from a wide variety of cultural backgrounds and in various clinical and research settings. This commentary is a reflection of one group of clinical genetic counselors' experiences in facilitating WES for patients who come from outside the United States for genetic evaluation and pursue WES. This patient population in our clinic primarily consists of individuals from the Middle East and presents recurrent logistical and counseling challenges. We aim to describe our international patient population, illuminate the challenges we have faced and illustrate how we have addressed these challenges.

The Somatic Marker Hypothesis and Sexual Decision Making: Understanding the Role of Iowa Gambling Task Performance and Daily Sexual Arousal on the Sexual Behavior of Gay and Bisexual Men.

Background: The sexual decision-making literature suggests that sexual arousal and behavior are associated. The somatic marker hypothesis suggests that individual neuropsychological differences in decision making, as measured by the Iowa Gambling Task (IGT), may moderate these associations; however, this hypothesis has yet to be tested with event-level sexual behavior data. Purpose: We hypothesized that (a) daily sexual arousal would be positively associated with likelihood of engaging in sex and condomless anal sex (CAS) and (b) IGT scores would moderate these associations such that the associations would be stronger among those with higher IGT scores. Methods: We used daily diary data from 334 highly sexually active gay and bisexual men to examine the main and interaction effects of sexual arousal and IGT scores on sexual engagement and CAS. Results: As hypothesized, daily sexual arousal was positively associated with greater odds of both sexual engagement and CAS with casual male partners. Individual-level IGT performance significantly moderated the day-level association between arousal and sexual engagement, which was stronger for men with higher IGT scores. There was no main effect of IGT scores on either sexual behavior outcome, nor did it moderate the association between arousal and CAS. Conclusions: These findings highlight the influence of sexual arousal on sexual engagement, which differed by IGT scores; the effect of arousal on CAS was much less variable and may not be moderated by neurocognitive factors. This study supports the importance of exploring integrated behavioral/biomedical interventions to improve individual decision making to prevent HIV infection.

Sexual risk-taking and subcortical brain volume in adolescence.

Background: The developmental period of adolescence marks the initiation of new socioemotional and physical behaviors, including sexual intercourse. However, little is known about neurodevelopmental influences on adolescent sexual decision-making. Purpose: We sought to determine how subcortical brain volume correlated with condom use, and whether those associations differed by gender and pubertal development. Methods: We used FreeSurfer to extract subcortical volume among N = 169 sexually experienced youth (mean age 16.07 years; 31.95% female). We conducted multiple linear regressions to examine the relationship between frequency of condom use and subcortical volume, and whether these associations would be moderated by gender and pubertal development. Results: We found that the relationship between brain volume and condom use was better accounted for by pubertal development than by gender, and moderated the association between limbic brain volume and condom use. No significant relationships were observed in reward areas (e.g., nucleus accumbens) or prefrontal cortical control areas. Conclusions: These data highlight the potential relevance of subcortical socioemotional processing structures in adolescents' sexual decision-making.

Risky Sex in High-Risk Adolescents: Associations with Alcohol Use, Marijuana Use, and Co-Occurring Use.

Risky sexual behavior and substance use appear to be interconnected behaviors among adolescents, but data are scarce regarding the extent to which sexual risk behavior is associated with high levels of marijuana and alcohol use, both separately and in combination. 301 adolescents were recruited from a short-term detention facility, and substance use and risky sexual behavior were assessed. We found that adolescents who frequently used marijuana, but not alcohol, reported significantly less risky sex as well as greater intentions to use condoms than either adolescents who frequently used alcohol, but not marijuana, or adolescents who frequently used both substances. Substance use status as a predictor of future risky sexual behavior followed a similar pattern. When designing interventions to reduce substance use in the context of risky sex, it might be especially effective to target efforts toward reducing harm associated with alcohol use, either alone or in combination with marijuana use.

Featured Article: Adolescent Condom Use and Connectivity in the Social-Planful Brain.

Objective: To reduce rates of sexually transmitted infections (STIs) and unwanted pregnancy among adolescents, it is critical to investigate brain connectivity that may underlie adolescents' sexual health decision-making in the context of intercourse. This study explored relationships between adolescent condom use frequency and the brain's resting-state functional connectivity, to identify differential patterns of social-affective processing among sexually active youth. Methods: In this study, N = 143 sexually active adolescents (68.5% male, Mage = 16.2 years, SD = 1.06) completed magnetic resonance imaging and reported past 3-month frequency of condom use. Resting-state connectivity, seeded on a social region of the brain, the temporoparietal junction (TPJ), was assessed to determine its correspondence with protected sex (condom use). Results: Condom use was associated with positive connectivity between the left TPJ and bilateral inferior frontal gyrus (IFG). This relationship was observed in adolescent males only; no connectivity differences were observed with adolescent females. Conclusions: This study reflects functional synchrony between nodes of the "social brain," including the TPJ, and a region of planfulness and control, the IFG. The relationship between these regions suggests that adolescents who have more coordinated systems of communication between these critical components of the brain are more likely to be successful in planning and engaging in safer sexual decision-making; for young males, this differentiated more frequent from less frequent condom use. In turn, interventions designed to reduce STIs/human immunodeficiency virus may benefit from targeting social-planfulness dimensions to help youth implement safer sex behaviors.