White Matter Integrity Associated with Symptoms of Co-Occurring Mood and Anxiety Disorder in Autism Spectrum Disorder: A Tract-Based Spatial Statistics and Tractography Analysis

Background:  Adults with autism spectrum disorder (ASD) have a very high risk of experiencing mood and anxiety disorders. These symptoms can cause significant impairment to quality of life and place a high burden on family and carers. To inform better preventative and treatment strategies, it is important to examine the neurobiological basis of mood and anxiety disorders within people with ASD.

Objectives: To examine brain white matter (WM) tract integrity associated with symptoms of mood and anxiety disorder in adults with ASD. 

Methods:  We examined WM tract integrity using diffusion tensor imaging (DTI). We recruited 50 adults with ASD and 59 healthy controls who were assessed by gold standard self-report screening tools for symptoms of mood and anxiety disorders. The analysis consisted of whole-brain tract-based spatial statistics (TBSS) and atlas based tractography of the extended limbic pathways (uncinate fasciculus, cingulum, fornix, inferior longitudinal fasciculus (ILF) and inferior fronto-occipital fasciculus (IFOF)) and subregions of the corpus callosum (CC). We compared DTI measures (number of streamlines, fractional anisotropy, mean diffusivity and perpendicular diffusivity) between the ASD cases and the controls and correlated them with clinical symptom severity.

Results:  Our TBSS results demonstrated that ASD cases had significantly lower fractional anisotropy in a number of regions including; the CC, the uncinate fasciculus, cingulum and IFOF. We also observed higher mean diffusivity in the genu of the CC, IFOF and superior longitudinal fasciculus. Although there were no significant correlations with mood and anxiety symptoms in the TBSS analysis, the tractography analysis revealed significant correlations with these symptoms, particularly in the anterior regions of the CC, the left cingulum, uncinate fasciculus and ILF and the right IFOF.

Conclusions:  To our knowledge, this is the first DTI study correlating co-occurring symptoms in adults with ASD. We demonstrate that many of the same WM regions that differ between ASD and controls are also associated with mood and anxiety symptoms within people with an ASD. This suggests a limbic system-related common aetiological pathway for mood/anxiety disorders and ASD. We also found preliminary evidence that the WM underlying symptoms of co-occurring conditions may be different in ASD. Further investigation is needed to relate these differences to differences in treatment response.