Autism, obsessive-compulsive disorder, and attention-deficit hyperactivity disorder : are they connected?

Abstract

Background and Objectives: There are considerable amount of overlaps in symptomatology in Autism Spectrum Disorder (ASD), Obsessive-Compulsive disorder (OCD), and Attention-deficit hyperactivity disorder (ADHD). For example, repetitive behaviors are core symptom domains in ASD and OCD, including excessive hand washing, stacking objects by size or colors, unreasonable flapping hands and repetitive counting, and roughly 30-80 percent of children with ASD have symptoms which are compatible with an ADHD diagnosis. I attempt to explore whether there are similarities and differences in ASD, ADHD, and OCD using neuroimaging methods.

Methods: To summarize all the data into a more meaningful biological representation, Anatomical Likelihood Estimation (ALE), a cutting edge meta-analytic approach was applied. The rationale behind ALE is that it identifies brain differences most consistently reported across studies, while filtering away differences that are least documented. In this thesis, a novel application of ALE known as “dual disorder ALE” is introduced, which serves to estimate the extent of brain regional differences implicated in either disorder – in other words, a method to quantify which areas of the brain are more likely to be affected by ASD, OCD, and ADHD. The relationship of ASD, OCD, and ADHD was further investigated using a local datasets of ASD children with ADHD and OCD traits. This was achieved by making use of resting-states functional MRI (rsfMRI), a brain imaging methods in which subjects were asked not to perform any explicit task while being scanned. Resting-states fMRI is especially useful in exploring brain neuropathology and determine if it is disturbed in psychiatric disorders.

Findings: The analysis is separated into two parts. First, dual disorder ALE technique was applied to investigate the relationship between ASD & OCD, and ASD & ADHD. In ASD & OCD analysis, there are a total of 538 ASD subjects (mean age 18.66) matched with 500 typical controls (mean age 18.57), and 635 OCD subjects (mean age 26.21) matched with 634 controls (mean age 25.66). . In ASD & ADHD analysis, there are a total of 449 ASD subjects (mean age 19.59) matched with 435 typical controls (mean age 19.2). and 318 ADHD subjects (mean age 18.23) and 316 controls (mean age 18.11). Overall, there were similar brain differences near the "cortico-striato-thalamo-cortical" (CSTC) pathway, and distinctive brain differences including amygdala, caudate, frontal medial gyrus. In the second part of the study, I made use of resting-states fMRI on a group of ASD children with OCD traits and ADHD traits and controls. ASD individuals with OCD traits exhibited greater ALFF in the left cerebellum, bilateral orbitofrontal cortex, occipital gyrus, caudate, and other temporal regions, associating with some of the core regions of the CSTC pathway. ASD individuals with ADHD exhibited greater amplitude of low frequency fluctuations (ALFF), a value which reflect abnormal intrinsic neuronal activities, in anterior cingulate cortex, dorsolateral prefrontal cortex, caudate, and other temporal regions. Lower ALFF was found in right cerebellum. These regions are related to the CSTC pathway and also the DMN.

Conclusions: Both parts of the analysis suggest that there are similar aetiological pressures affecting neurodevelopmental disorders including ASD, ADHD, and OCD.