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.

Pharmacotherapy of attention deficit/hyperactivity disorder in individuals with autism spectrum disorder: A systematic review of the literature.

AIM: To assess the empirical evidence for the treatment of attention deficit/hyperactivity disorder (ADHD) in populations with autism spectrum disorder (ASD). METHODS: A systemic PubMed, PsychINFO, Embase, and Medline database search of peer-reviewed literature was conducted. Included in the review were controlled trials published in English with sample sizes ⩾10 participants examining the safety and efficacy of anti-ADHD medication in ASD populations. Data was extracted on relevant variables of study design, demographics, associated psychopathology, medication dose, efficacy, and tolerability. RESULTS: Nine controlled trials met the inclusion and exclusion criteria: five with methylphenidate, three with atomoxetine, and one with guanfacine. Sample sizes ranged from 10 to 128 with 430 children participating across all the trials. In all the trials, treatment response was significantly superior to placebo. However, almost all trials assessed only hyperactivity, and most included only participants with intellectual disability with high levels of irritability. None of the trials distinguished agitation from hyperactivity. The response on hyperactivity for methylphenidate and atomoxetine was less than that observed in the neurotypical population; however, the response for guanfacine surpassed results observed in neurotypical populations. Treatment-emergent mood lability (i.e. mood dysregulation and mood-related adverse events) was frequently associated with methylphenidate and guanfacine treatments. Worse treatment outcomes were associated with individuals with lower intellectual capability compared with those with higher IQs. CONCLUSIONS: here is a scarcity of controlled trials examining ADHD treatments in ASD populations, particularly in intellectually capable individuals with ASD and in adults. Response to ADHD medications in ASD were adversely moderated by the presence of intellectual disability and mood lability.

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.

A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder.

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD).Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures.Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), -22.8 ± 8.8, P < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, -8.2 ± 15.3, P < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)).Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

A Retrospective Chart Review of Buspirone for the Treatment of Anxiety in Psychiatrically Referred Youth with High-Functioning Autism Spectrum Disorder.

OBJECTIVES: Anxiety disorders (ADs) are commonly associated with high-functioning Autism Spectrum Disorder (HF-ASD) and often worsen with age. Buspirone is a commonly prescribed anxiolytic drug with a favorable tolerability profile that may offer potential benefits in anxiety management for patients with HF-ASD. This study examines inadequately explored tolerability and effectiveness of buspirone in treating ADs comorbid with high-functioning ASD. METHODS: A retrospective chart review of a 1-year period was conducted in psychiatrically referred population of HF-ASD youth with AD (age 8-17 years) who were treated with buspirone (N = 31). Information on the demographics and treatment history was recorded. Effectiveness was assessed through the Clinical Global Impressions Scale (CGI) severity (CGI-S) and improvement (CGI-I) scores noted by the treating clinician. RESULTS: A total of 31 patients were prescribed buspirone during the determined period, at a mean dose of 41.61 ± 24.10 mg for an average duration of 272 ± 125 days. Change in the CGI-S mean scores with treatment suggests an overall improvement in the severity of anxiety symptoms (MT1 = 4.9 ± 0.7; MT2 = 2.8 ± 0.87; p < 0.001). Significant improvement in anxiety symptoms (CGI-I ≤ 2) was observed in 58% and mild improvement (CGI-I = 3) in 29% of the HF-ASD patients who received buspirone treatment. Buspirone was well tolerated with no adverse events reported by the majority of participants, with the exception of two subjects who developed treatment emergent adverse events (activation and mood lability). CONCLUSIONS: Findings from this retrospective chart review suggest a promising role of buspirone in managing anxiety among youth with HF-ASD. Further research with prospective and randomized-controlled trials is necessary.

New applications of pHluorin--measuring intracellular pH of prototrophic yeasts and determining changes in the buffering capacity of strains with affected potassium homeostasis.

pHluorin is a pH-sensitive variant of green fluorescent protein for measuring intracellular pH (pH(in)) in living cells. We constructed a new pHluorin plasmid with the dominant selection marker KanMX. This plasmid allows pH measurements in cells without auxotrophic mutations and/or grown in chemically indefinite media. We observed differing values of pH(in) for three prototrophic wild-types. The new construct was also used to determine the pH(in) in strains differing in the activity of the plasma membrane Pma1 H(+)-ATPase and the influence of glucose on pH(in). We describe in detail pHluorin measurements performed in a microplate reader, which require much less hands-on time and much lower cell culture volumes compared to standard cuvettes measurements. We also utilized pHluorin in a new method of measuring the buffering capacity of yeast cell cytosol in vivo, shown to be ca. 52 mM/pH for wild-type yeast and moderately decreased in mutants with affected potassium transport.

Solvatochromic effect in the optical spectra of calcofluor and its relation to fluorescent staining of yeast cell walls.

Fluorescence spectral properties of calcofluor (a popular stain used to visualize cell walls of bacteria, yeast and fungi) has been studied. The analysis of calcofluor fluorescence emission spectra measured in a wide range of solvents (including media containing chitin), and in yeast cell suspensions has revealed that the solvatochromic properties of calcofluor ensue essentially from the by solvent-solute hydrogen bonding, or from the hydrogen bonding to cell wall polysaccharides with an eventual contribution of calcofluor aggregation at the cell surface. Preliminary data suggest that calcofluor emission spectra can be employed as a practical marker of variations in the quality of yeast cell wall.