Functional connectivity within an anxiety network and associations with anxiety symptom severity in middle‐aged adults with and without autism

Abstract

Anxiety is highly prevalent in autism spectrum disorders (ASDs). However, few functional magnetic resonance imaging (fMRI) studies of ASDs have focused on anxiety (and fewer still on anxiety in middle-aged adults). Thus, relationships between atypical connectivity and anxiety in this population are poorly understood. The current study contrasted functional connectivity within anxiety network regions across adults (40-64 years) with and without autism, and tested for group by functional connectivity interactions on anxiety. Twenty-two adults with ASDs (16 males) and 26 typical control (TC) adults (22 males) completed the Beck Anxiety Inventory and a resting-state fMRI scan. An anxiety network consisting of 12 regions of interest was defined, based on a meta-analysis in TC individuals and two studies on anxiety in ASDs. We tested for main effects of group and group by anxiety interactions on connectivity within this anxiety network, controlling for head motion using ANCOVA. Results are reported at an FDR adjusted threshold of q < 0.1 (corrected) and p < 0.05 (uncorrected). Adults with ASDs showed higher anxiety and underconnectivity within the anxiety network, mostly involving bilateral insula. Connectivity within the anxiety network in the ASD group showed distinct relationships with anxiety symptoms that did not relate to ASD symptom severity. Functional connectivity involving the bilateral posterior insula was positively correlated with anxiety in the ASD (but not the TC) group. Increased anxiety in middle-aged adults with ASD is associated with atypical functional connectivity, predominantly involving bilateral insula. Results were not related to ASD symptom severity suggesting independence of anxietyrelated effects. Lay SummaryAnxiety is very common in adults with autism but the brain basis of this difference is not well understood. We compared functional connectivity between anxietyrelated brain regions in middle-aged adults with and without autism. Adults with autism were more anxious and showed weaker functional connections between these regions. Some relationships between functional connectivity and higher anxiety were specific to the autism group. Results suggest that anxiety functions differently in autism.

Paternal Prenatal and Lactation Exposure to a High-Calorie Diet Shapes Transgenerational Brain Macro- and Microstructure Defects, Impacting Anxiety-Like Behavior in Male Offspring Rats

“…Offspring's vulnerability to anxiety and depression-like behavior may be attributed to changes in the structure of the brain. Both preclinical and clinical investigations support the notion that abnormal structure and function in several brain regions, including the amygdala, periaqueductal gray, dorsomedial prefrontal cortex, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, and the locus ceruleus, potentially play a role in the development of anxiety and depressive disorders ( Cross et al, 2016 ; Garcia, 2017 ; Donnici et al, 2021 ; Tung et al, 2021 ); however, the cause of such brain volume alterations in subjects diagnosed with anxiety and depression-like behavior has not been completely identified. A recent study found that fetal programming through exposure to a high-energy diet (HED) led to reduced volume in the nucleus accumbens, hippocampus, and prefrontal cortex of rats displaying depression-like behavior ( Trujillo-Villarreal et al, 2021 ).…”

“…Leslie, Donnici et al, 2021;Garcia, 2017;Tung et al, 2021), however, the cause of such brain volume alterations in subjects diagnosed with anxiety and depression-like behavior has not been completely identified. A recent study found that fetal programming through exposure to a high-energy diet (HED) led to reduced volume in the nucleus accumbens, hippocampus, and prefrontal cortex of rats displaying depression-like behavior (Trujillo-Villarreal et al, 2021).…”