Faculty Bibliography

[This corrects the article on p. 409 in vol. 20, PMID: 30881565.].

OBJECTIVE:Disturbances in self-regulatory control are involved in the initiation and maintenance of addiction, including cannabis use disorder (CUD). In adults, chronic cannabis use is associated with disturbances in fronto-striatal circuits during tasks that require the engagement of self-regulatory control, including the resolution of cognitive conflict. Understudied are the behavioral and neural correlates of these processes earlier in the course of cannabis use, disentangled from effects of long-term use. The present study investigates the functioning of fronto-striatal circuits during the resolution of cognitive conflict in cannabis-using youth. METHOD/METHODS:Functional magnetic resonance imaging data was acquired from 28 cannabis-using (CU) youth and 32 age-matched healthy participants (HC) during the performance of a Simon task. General linear modeling was used to compare patterns of brain activation during correct responses to conflict stimuli across groups. Psychophysiological interaction analyses were used to examine conflict-related fronto-striatal connectivity across groups. Associations of fronto-striatal activation and connectivity with cannabis use measures were explored. RESULTS:Reduced conflict-related activity was detected in CU relative to HC youth in fronto-striatal regions, including ventromedial prefrontal cortex (vmPFC), striatum, pallidum and thalamus. Fronto-striatal connectivity did not differ across groups, but negative connectivity between vmPFC and striatum was detected in both groups. CONCLUSION/CONCLUSIONS:These findings are consistent with previous reports of cannabis-associated disturbances in fronto-striatal circuits in adults and point to the specific influence of cannabis on neurodevelopmental changes in youth. Future studies should examine whether fronto-striatal functioning is a reliable marker of CUD severity and potential target for circuit-based interventions.

BACKGROUND:The retention of youth living with HIV (YLHIV) in adult care after transfer from pediatric care in the United States is a challenge. A targeted comprehensive retention strategy (CRS) may improve retention among YLHIV. METHODS:A retrospective cohort study of YLHIV after transfer from pediatric to adult care for patients with at least 1 adult visit at 2 urban HIV care programs in the United States employing CRSs with internal medicine/pediatrics-trained providers, peer navigators, social workers and mental health resources. Primary outcomes were successful retention in care after transfer (≥2 provider visits in the adult clinic ≥90 days apart within 1 year of transfer) and successful transition (successful retention plus a stable HIV viral load (VL) defined as VL 1 year after transfer that was less than or equal to the VL obtained at or immediately before transfer). Logistic regression assessed factors associated with successful transition. A subgroup analysis was performed to examine rates of successful transfer and linkage from pediatric to adult clinics (attending at least 1 adult visit after transition). RESULTS:Of the 89 patients included in the study, 79 (89%) patients had successful retention and 53 (60%) had successful transition to the adult program. Factors associated with successful transition included non-African American race [adjusted odds ratio (aOR) = 11.26, 95% confidence interval (CI): 1.32-95.51], perinatal HIV (aOR = 8.00, 95% CI: 1.39-46.02) and CD4 count > 500 cells/mm (aOR = 5.22, 95% CI: 1.54-17.70). Of those who were retained, 53/79 (67%) had stable or improved virologic control at 1 year after transition. In a subgroup analysis, 54/56 (96%) patients who were targeted to transition successfully linked to adult care. CONCLUSIONS:Overall, YLHIV in the United States engaged in a CRS program appear to have high retention rates but suboptimal virologic control after transfer from pediatric HIV care.

Recent surveys demonstrate skyrocketing rates of adolescent vaping,¹ while the opioid epidemic, rightfully, is daily front page news. At the same time, the public perceives cannabis as a harmless source of recreation or even as cure-all therapy. Now more than ever, child and adolescent psychiatrists, politicians, policy leaders, and parents need empirical support to bolster the position that drugs of abuse should be avoided by young people. We have a robust literature connecting cannabis use to earlier and worse psychotic disorders,² as well as strong longitudinal data implicating cannabis in various neuropsychological deficits.³ What our field lacks, however, are brain imaging studies that definitively document the negative neurobiological impact of substance use on the developing human brain. The key to appreciating why this research literature is so limited has to do with one of the core tenets of substance use disorder (SUD) etiology: SUDs do not emerge de novo in adulthood or late adolescence when people typically present with impairing symptoms. Decades of research now suggests that certain latent childhood traits predispose some youth to initiate and then escalate drug and alcohol use more often than is typical.⁴ Children born into families with SUDs are more likely to express these highly heritable traits and are additionally subject to environmental risk factors and adversity. Therefore, children born into families with SUDs are disproportionately laden with genetic and environmental factors that shape brain structure and function. In other words, before exposure to drugs of abuse (which themselves may influence the brain), some children's brains already differ from those of typically developing youth. This observation limits the usefulness of cross-sectional neuroimaging studies that compare youth who have used drugs to those who have not, because of the nonrandom interaction of latent traits, environmental factors, and pre-existing brain differences. This interaction likely accelerates these adolescents' propensity to initiate and continue to use drugs of abuse.

Characterization of patterns of alcohol consumption during pregnancy encompasses multiple factors such as magnitude, frequency, and timing of exposure throughout gestation. Traditional statistical models are limited in dealing with multivariate and diverse patterns of exposure as in the context of this analysis. We propose a finite mixture model-based approach to derive clusters of alcohol exposure of participants in the Safe Passage Study (PASS). Daily alcohol consumption data for 11,083 pregnant women have been clustered in 10 different exposed groups. The resulting cluster analysis was able to characterize alcohol consumption in a comprehensive framework capable of taking into account both quantity and timing of exposure as well as the occurrence of binge drinking.

Adolescents are an important population to represent in biobanks. Inclusion of biospecimens from adolescents advances our understanding of the long-term consequences of pediatric disease and allows the discovery of methods to prevent adult diseases during childhood. Consent for biobanking is complex, especially when considering adolescent participation, as it brings up issues that are not present with general clinical research. The development and successful implementation of an adolescent capacity assessment tool applied specifically to biobanking can potentially provide researchers and clinicians with contextualized information on participants' understanding, appreciation, reasoning, and voluntary choice for biobanks. This tool would enhance current studies looking at the role of shared decision-making in biobanking, as well as provide a formal measurement when considering decisions around pediatric and adolescent biobanking participation. This study adapted the MacCAT-CR for use with a hypothetical adolescent biobank study and examines predictors of MacCAT-CR scores on healthy and chronically ill adolescents.

Children's perceptions are important to understanding family environment in the bipolar disorder (BD) high-risk context. Our objectives were to empirically derive patterns of offspring-perceived family environment, and to test the association of family environment with maternal or paternal BD accounting for offspring BD and demographic characteristics. Participants aged 12-21 years (266 offspring of a parent with BD, 175 offspring of a parent with no psychiatric history) were recruited in the US and Australia. We modeled family environment using latent profile analysis based on offspring reports on the Conflict Behavior Questionnaire, Family Adaptability and Cohesion Evaluation Scales, and Home Environment Interview for Children. Parent diagnoses were based on the Diagnostic Interview for Genetic Studies and offspring diagnoses were based on the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Latent class regression was used to test associations of diagnosis and family environment. Two-thirds of all offspring perceived well-functioning family environment, characterized by nurturance, flexibility, and low conflict. Two 'conflict classes' perceived family environments low in flexibility and cohesion, with substantial separation based on high conflict with the father (High Paternal Conflict), or very high conflict and rigidity and low warmth with the mother (High Maternal Conflict). Maternal BD was associated with offspring perceiving High Maternal Conflict (OR 2.8, p = 0.025). Clinical care and psychosocial supports for mothers with BD should address family functioning, with attention to offspring perceptions of their wellbeing. More research is needed on the effect of paternal BD on offspring and family dynamics.

Office-Based Vergence/Accommodative Therapy (OBVAT) is an effective treatment for convergence insufficiency (CI) and remediates symptoms in about 75% of patients. Hence, the study of CI patients can serve as a systems-level model to understand the neural mechanisms evoked from rehabilitation. Symptomatic young adult CI patients (N=25) participated in 12 hours of OBVAT and were compared to 25 binocularly normal controls (BNC) using unpaired t-tests. CI patients have significantly lower near point of convergence and positive fusional vergence and were more symptomatic compared to BNC (p<; 0.0001). Using paired t-tests, significant differences (p<; 0.0001) were observed between CI patients' baseline and post-OBVAT measurements where the near point of convergence decreased, positive fusional vergence increased, and the results from the Convergence Insufficiency Symptom Survey (CISS) decreased. Using paired t-tests, the mean beta weights of the functional activity significantly increased for the frontal eye fields (p<; 0.01) and the oculomotor vermis (p<; 0.05) for CI patients post-OBVAT compared to baseline measurements. These data demonstrate that OBVAT increases functional activity within the brain and improves clinical function and visual symptoms in CI patients.

There is a paucity of information concerning adaptive parenting strategies utilised by mothers with physical disabilities, particularly during early motherhood. The purpose of this study is to describe the adaptive strategies used by mothers with physical disabilities during early motherhood. This qualitative study included semi-structured telephone interviews between January and March 2014 with US mothers with a range of physical disabilities who had a baby within the past 10 years (N = 25). Interviews were audio-recorded, professionally transcribed, and coded using content analysis. Analysis revealed five broad themes indicating important adaptive parenting strategies for mothers with physical disabilities caring for infants and toddlers: They are as follows: (a) acquiring or modifying baby-care equipment, (b) adapting the home environment, (c) accessing information and supports, (d) developing communication strategies to facilitate safety, and (e) receiving assistance from others. This study indicates that mothers with physical disabilities employ a variety of adaptive strategies during early motherhood. The findings from the study suggest the need for more availability of supports and equipment for mothers with physical disabilities as well as information for prospective mothers with disabilities. In addition, healthcare and social work professionals must receive training about adaptive parenting strategies.

OBJECTIVE:Sleep problems are common in adults with attention-deficit/hyperactivity disorder (ADHD). The presence of sleep problems at the time of presentation for ADHD treatment could impact the level of improvement in ADHD symptoms or executive function occurring with ADHD pharmacotherapy. Therefore, we examined the influence of baseline sleep quality on the effects of SHP465 mixed amphetamine salts (MAS) extended-release. METHODS:Adults (18-55 years) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥ 24 were randomized to once-daily SHP465 MAS (12.5-75 mg) or placebo in a 7-week, double-blind, dose-optimization study. Post-hoc analyses evaluated SHP465 MAS treatment effects on ADHD symptoms, using the ADHD-RS-IV, and executive function, using the Brown Attention-Deficit Disorder Scale (BADDS), based on baseline sleep quality as defined by Pittsburgh Sleep Quality Index (PSQI) scores [sleep quality impaired (PSQI total score > 5; PSQI component scores 2 or 3) versus not impaired (PSQI total score ≤ 5; PSQI component scores 0 or 1)]. Analyses were conducted in the intent-to-treat population. RESULTS:Of 280 enrolled participants, 272 were randomized (placebo, n = 135; SHP465 MAS, n = 137). The intent-to-treat population consisted of 268 participants (placebo, n = 132; SHP465 MAS, n = 136), and 170 participants (placebo, n = 76; SHP465 MAS, n = 94) completed the study. Treatment differences nominally favored SHP465 MAS over placebo in both sleep impairment groups regarding ADHD-RS-IV total score changes (all nominal p < 0.05), except for those with impairment defined by sleep efficiency (p = 0.2696), and regarding BADDS total score changes (all nominal p < 0.05), except for those with impairment defined by sleep duration (p = 0.1332) and sleep efficiency (p = 0.8226). There were no statistically significant differences in SHP465 MAS treatment effects between sleep impairment groups. CONCLUSIONS:Improvements in ADHD symptoms and executive function occurred with dose-optimized SHP465 MAS, regardless of baseline impairment in some aspects of sleep in adults with ADHD, with no significant differences observed as a function of sleep impairment. CLINICAL TRIALS REGISTRATION/BACKGROUND:ClinicalTrials.gov identifier-NCT00150579.