Psychotropic Medication Use in Autism Spectrum Disorders May Affect Functional Brain Connectivity

Abstract

Background Prescription of psychotropic medications is common in autism spectrum disorders (ASDs), either off-label or to treat comorbid conditions such as ADHD or depression. Psychotropic medications are intended to alter brain function. Yet, studies investigating the functional brain organization in ASDs rarely take medication usage into account. This could explain some of the inconsistent findings of atypical brain network connectivity reported in the autism literature. Methods The current study tested whether functional connectivity patterns, as assessed with functional magnetic resonance imaging (fMRI), differed in a cohort of 49 children and adolescents with ASDs based on psychotropic medication status, and in comparison with 50 matched typically developing (TD) participants. Twenty-five participants in the ASD group (51%) reported current psychotropic medication usage, including stimulants, antidepressants, antipsychotics, and anxiolytics. Age, IQ, head motion, and ASD symptom severity did not differ between groups. Whole-brain functional connectivity between 132 regions of interest was assessed. Results Different functional connectivity patterns were identified in the ASD group taking psychotropic medications (ASD-on), as compared to the TD group and the ASD subgroup not using psychotropic medications (ASD-none). The ASD-on group showed distinct underconnectivity between the cerebellum and basal ganglia but cortico-cortical overconnectivity compared to the TD group. Cortical underconnectivity relative to the TD pattern, on the other hand, was pronounced in the ASD-none group. Conclusions These results suggest that psychotropic medications may affect functional connectivity, and that medication status should be taken into consideration when studying brain function in autism.

Reproducible functional connectivity alterations are associated with autism spectrum disorder

“…Overall, further research is needed to understand the specific reasons for these discrepant findings. Potential confounding effects of medication on functional connectivity have been raised for previous ASD studies (22). Here, we did not find consistent effects of psychotropic medication on the functional connectivity measures with the only significant effect pointing to reduced functional connectivity alterations with psychotropic medication use.…”

“…While some reports points to an under-connectivity phenotype (15)(16)(17), others reported the opposite (11,18), and some observed a mix of both phenomena (9,19). Besides inherent disease heterogeneity, this discordance has been proposed to arise from age or methodological differences between studies (17,20,21), or failures to account for medication effects in the analyses (22). Yet other work highlights the importance of spatial variability in connectivity as a key source of heterogeneity in ASD (19,23).…”

Transient states of network connectivity are atypical in autism: A dynamic functional connectivity study

“…Unfortunately, most fcMRI studies of ASDs do not report these important sample characteristics. Future studies with larger samples should consider focusing specifically on the effects of medication and comorbid diagnosis on dFC metrics (Linke, Olson, Gao, Fishman, & Müller, ).…”

Hyper-connectivity of the striatum related to restricted and repetitive behaviors’ severity in children with ASD

“…Correlation analyses were applied to examine whether iFC within clusters was associated IQ, subscores of RBS-R, medication status (44) , comorbidities and other clinical (ADOS-2 and ADI-R) indices, when data was available data. Finally, we divided the ASD group into low and high RBS-R total scores using the mean of the sample (n = 21) as the threshold.…”