Distinct and shared white matter abnormalities when ADHD is comorbid with ASD: A preliminary diffusion tensor imaging study.

Attention deficit/hyperactivity disorder (ADHD), a common neurodevelopmental disorder, is the most frequent comorbid condition seen in children with autism spectrum disorder (ASD). This high comorbidity between ADHD and ASD worsens symptom manifestations and complicates disease treatment and prognosis. It remains unclear whether individuals suffering with both ADHD and ASD, compared to individuals with ADHD only, share overlapping neural correlates associated with ADHD neuropathology, or exhibit a distinct neuropathological profile. Answering this question is critical to the understanding of treatment outcomes for the challenging comorbid ADHD symptoms. To identify the shared and the differentiated neural correlates of the comorbidity mechanisms of ADHD with ASD, we use diffusion tensor imaging (DTI) to characterize white-matter microstructure integrity in youth diagnosed with ADHD+ASD and youth with ADHD-only (excluding both the diagnosis and symptoms of ASD) compared with a healthy control group. Results show that the ADHD-only cohort exhibits impaired microstructural integrity (lower fractional anisotropy, FA) in the callosal-cingulum (CC-CG) tracts compared to the control cohort. The ADHD+ASD comorbid cohort shows impaired FA in an overlapping region within the CC-CG tracts and, additionally, shows impaired FA in the frontolimbic tracts including the uncinate fasciculus and anterior thalamic radiation. Across all participants, FA in the CC-CG showed a significantly negative relationship with the degree of ADHD symptom severity. Findings of this study suggest a specific role of CC-CG underlying ADHD neuropathology and symptom manifestations, and when comorbid with ASD a shared ADHD profile with a shift toward an anterior-brain, frontal impact. Results of this study may facilitate future targeted therapeutics and assist in diagnostic precision for individuals suffering with differing levels of comorbid ADHD with ASD, and ultimately contribute to improve prognostication and outcomes for these two highly prevalent and comorbid neurodevelopmental disorders.

Decreased risk for substance use disorders in individuals with high-functioning autism spectrum disorder.

The objective of this study was to evaluate the risk for developing a substance use disorder (SUD, alcohol or drug abuse or dependence) in individuals with high-functioning autism spectrum disorder (ASD). Subjects with high-functioning ASD were derived from consecutive referrals to a specialized ambulatory program for ASD at a major academic center from 2007 to 2016. Age-matched controls and attention-deficit hyperactivity disorder (ADHD) comparison subjects were derived from three independent studies of children and adults with and without ADHD using identical assessment methodology. Cox proportional hazard models were used to analyze the prevalence of SUD (alcohol or drug use disorder). Age of onset of SUD was analyzed with linear regression models. Our sample included 230 controls, 219 subjects with ADHD, and 230 subjects with ASD. The mean age for the ASD subjects was 20.0 ± 10.3 years. Among ASD subjects, 69% had a lifetime prevalence of ADHD, and the ASD subjects had significantly higher rates of other psychiatric psychopathology compared to ADHD and control subjects (p < 0.001) ASD subjects were at significantly decreased risk for developing a SUD compared to ADHD (hazard ratio (HR) = 0.22, p < 0.001) and control subjects (HR = 0.62, p = 0.04). The age of onset of a SUD was significantly older in ASD subjects, mean age 21.7 years, when compared to ADHD and control subjects (both p < 0.005). Individuals with ASD are at decreased risk to develop a SUD, and when they do, the onset is significantly later than ADHD and controls.

Transcranial Photobiomodulation in Adults with High-Functioning Autism Spectrum Disorder: Positive Findings from a Proof-of-Concept Study.

Objective: To assess the efficacy and safety of transcranial photobiomodulation (tPBM) in adults with autism spectrum disorder (ASD). Methods: Adults with high-functioning-ASD, between 18 and 59 years of age, were enrolled to receive twice a week tPBM for 8 weeks in an open-label single group design. ASD symptom severity was assessed at baseline, midpoint, and end-point, by clinician-, self-, and informant-rated measures. Treatment response was defined as a ≥30% reduction in Social Responsiveness Scale-2nd Edition (SRS-2) total score and ASD Clinical Global Impression-Improvement score ≤2. Any possible adverse events were recorded at each visit. Paired-samples t-test analyses were performed. Results: Eleven participants were enrolled, and 10 participants (9 males; 30.0 ± 11.9 years) completed the study. One participant withdrew consent before baseline. All 10 completers were included in efficacy and safety analyses. Five participants (50%) met responder criteria at end-point. Overall, 8-week tPBM was associated with significant reduction in SRS-2 total scores at end-point (SRS-2: -30.6 ± 23, p < 0.001) particularly in Social Awareness (-3.0 ± 1.9, p < 0.001), Social Communication (-10.3 ± 6, p < 0.001), Social Motivation (-5.0 ± 2.4, p < 0.001), and Restricted/Repetitive Behaviors (-7.4 ± 4.1, p < 0.001). There were statistically significant improvements at end-point in Global Assessment of Functioning scores (+12.8 ± 4.2, p < 0.001) and Quality of Life Enjoyment and Satisfaction Questionnaire scores (+6.0 ± 7.9, p = 0.02). Three participants experienced transient, mild side effects (insomnia, headache, and warmth at treatment application site). No adverse events required changes in tPBM protocol. Adherence rate was 98%. Conclusions: tPBM is a safe and feasible treatment approach that has the potential to treat core features of ASD. Further research is necessary and warranted. ClinicalTrials.gov Identifier: NCT03724552.

Predictive utility of autistic traits in youth with ADHD: a controlled 10-year longitudinal follow-up study.

The objective of this study was to investigate the stability and predictive utility of autistic traits (ATs) in youth with attention-deficit/hyperactivity disorder (ADHD). Participants were referred youth with and without ADHD, without a diagnosis of autism spectrum disorder, and their siblings, derived from identically designed longitudinal case-control family studies of boys and girls with ADHD. Subjects were assessed with structured diagnostic interviews and measures of social, cognitive, and educational functioning. The presence of ATs at baseline was operationalized using a unique profile of the Child Behavior Checklist (CBCL) consisting of an aggregate T score of ≥ 195 on the Withdrawn, Social, and Thought Problems subscales (CBCL-AT profile). At the follow-up, 83% of the ADHD youth with a positive AT profile at baseline continued to have a positive CBCL-AT profile. The presence of a positive CBCL-AT profile at baseline in youth with ADHD heralded a more compromised course characterized by a greater burden of psychopathology that emerged at an earlier age, along with poorer interpersonal, educational, and neurocognitive outcomes. Findings indicate a high level of persisting ATs in ADHD youth over time, as indexed through the CBCL-AT profile, and the presence of this profile prognosticates a compromised course in adult life in multiple domains of functioning.

Which girls, which boys? The intersectional risk for depression by race and ethnicity, and gender in the U.S.

We sought to conduct the first systematic review of studies applying an intersectional lens to assessing risk and protective factors for depression in minority adolescents in the United States. Twenty-five studies were identified which investigated the role of racial and ethnic identity and gender for minority groups and how marginalization may be associated with differential outcomes in depression symptomology. The results showed substantial variability in whether studies intentionally operationalized intersectionality through theoretical frameworks, study design, sampling, and analyses. Studies were rated on a scale of 1 through 5; those with scores of 3 or higher were included in the review. A rating of 5 indicated studies had explicitly used an intersectional theoretical framework, integrating the process of racial/ethnic identity development and gender socialization during adolescence. Three studies met the criteria for 5, one study was rated 4, and 21 studies were rated 3. Attention to experiences with discrimination was common throughout. Overall, the collective findings point to the importance of using an intersectional lens for understanding differential mechanisms for how and why specific adolescent minority youth are at greater risk for reporting depression symptoms, identifying cultural and developmental protective factors, and informing how interventions can effectively target specific mechanisms for prevention and treatment.