Propranolol, a nonselective beta-adrenergic antagonist, has shown potential for improving anxiety in autistic individuals. Heart rate variability (HRV), a noninvasive cardiac marker of autonomic nervous system functioning, may help identify individuals most likely to benefit from propranolol. Objectives: Determine if baseline resting HRV and other cardiac measures predict the response to propranolol for anxiety and core autism symptomology in autistic children and young adults. Methods: Sixty-two autistic individuals (ages 7–24) participated in a two-phase (i.e., a 12-week randomized controlled trial and a 12-week open-label extension) trial of propranolol. Baseline (i.e., resting state, prior to treatment) HRV and other cardiac measures were obtained from an electrocardiogram. Clinical global impression for anxiety symptoms and overall behavioral treatment impact were assessed after the 12-week trial period. Group-level (i.e., all participants) and responder groups (i.e., strong, minimal, and non-responders to propranolol) were analyzed for treatment effects. Results: HRV variables predicted group-level anxiety response to propranolol, particularly for strong responders. Also, lower baseline values of parasympathetic HRV indices were significantly correlated with greater behavioral improvement after treatment with propranolol. Last, several baseline cardiac variables were associated with improvement in multiple behavioral domains after treatment with propranolol. Conclusions: HRV may be a potential biomarker for predicting reduced anxiety and behavioral symptoms in response to propranolol in autistic children and young adults. Identifying autonomic profiles associated with positive treatment outcomes could guide future personalized interventions in autism. The results presented herein should be regarded as preliminary until the findings are replicated in future clinical trials.

Background: The neurobiology underlying ASD is largely unknown but altered neural excitability/inhibitory ratios have been reported. Memantine is an N-methyl-D-aspartate (NMDA) glutamatergic antagonist studied for the treatment of core ASD symptoms, with mixed results. We examined whether glutamatergic levels were associated with and predicted response to memantine in an exploratory pilot study.Methods: Ten adult participants with ASD underwent proton magnetic resonance spectroscopy (¹H-MRS) imaging at baseline and behavioral assessments before and after 12-weeks of open-label memantine. Post-treatment scores on Clinical Global Impressions–Improvement (CGI-I) for social interaction were the primary outcome measure, and scores on the Social Responsiveness Scale (SRS) were included as a secondary outcome. LCModel was used to quantify the concentrations of Point RESolved Spectroscopy-detected glutamate+glutamine (Glx) (and other neurometabolites, i.e., N-acetylaspartate, NAA; creatine+phosphocreatine, Cr+PCr, and myo-inositol, Ins), within the left dorsolateral prefrontal cortex (LDLPFC) and right (R) posterolateral cerebellum. SPM was used to perform brain tissue segmentation within the spectroscopic voxels. CGI-I scores post-treatment were used to classify the participants into two groups, responders (scores 1–3; n = 5) and non-responders (scores 4–7, or withdrew due to increase behaviors; n = 5). Independent samples t-tests, partial correlations and linear hierarchical regression models (SPSS) were used to determine between-group differences in neurometabolite concentrations and associations between neurometabolites and behavioral scores.Results: Responders and non-responders did not significantly differ in Glx levels in any region of interest, but differed in NAA levels in LDLPFC (higher in responders vs. non-responders). Although changes in CGI-I social scores were not correlated with Glx in any region of interest, the linear hierarchical regression did reveal that Glx and Ins levels in LDLPFC were predictors of post-treatment CGI-I social scores. Changes in SRS scores were correlated with baseline Cr+PCr levels in the LDLPFC.Discussion: Our pilot data suggest that baseline Glx, a marker of glutamatergic neurotransmission, did not directly predict response to memantine for social outcomes in adults with ASD. However, interactions between Glx and the neurometabolite associated with glial integrity (Ins) may help predict treatment response. Further, those with highest baseline NAA, a putative neuronal marker, and Cr+pCr, a brain energy metabolism marker, were the best responders. These preliminary results may explain some of the mixed results reported in previous memantine trials in ASD. Future studies will need to examine these results in a larger sample.

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition etiologically related to suboptimal levels of dopamine (DA) and norepinephrine (NE) that is typically treated with psychostimulant medication. In individuals with ADHD, divergent thinking abilities have been shown to improve with the use of psychostimulants. Furthermore, psychostimulants affect autonomic nervous system (ANS) functioning, which can impact creative cognition. However, it is not known how DA and NE affect creative cognition in this setting and how this effect is related to autonomic activity in ADHD. Therefore, our objective was to elucidate ANS function and its relationship with divergent creativity gains related to psychostimulant treatment in ADHD. Method: Seventeen individuals diagnosed with ADHD (age 27.9 ± 6.7 sd) participated in two counterbalanced sessions—one while on their prescribed stimulant medication and another after abstaining for at least 24 h. During each session, participants completed convergent (anagrams) and divergent (Torrance Test of Creative Thinking) thinking tasks. An 8 min electrocardiogram prior to cognitive testing was taken to measure heart rate variability (HRV), which is an index of ANS functioning. Results: The hypothesized baseline pNN50 HRV measure was not predictive of enhanced creativity gains on convergent anagrams or divergent creativity on the Torrance when taking stimulants. Conclusions: In this pilot study, the relationship between baseline HRV and the impact of stimulants on anagram performance suggests the noradrenergic system may not play a role in the effect of stimulants on convergent or divergent creativity. The lack of a relationship between baseline HRV and stimulant-related changes in TTCT and anagram scores lends some support to the hypothesis that dopaminergic effects may be the predominant factor in the effect of stimulants on creativity in ADHD. Future research should further investigate the interaction between hypoactive neurotransmitter systems, particularly dopamine in divergent and norepinephrine in convergent creativity, using neuroimaging techniques to assess neurotransmitter dynamics during creativity-based tasks.