Generalized and social anxiety disorder interactomes show distinctive overlaps with striosome and matrix interactomes

Abstract

Mechanisms underlying anxiety disorders remain elusive despite the discovery of several associated genes. We constructed the protein–protein interaction networks (interactomes) of six anxiety disorders and noted enrichment for striatal expression among common genes in the interactomes. Five of these interactomes shared distinctive overlaps with the interactomes of genes that were differentially expressed in two striatal compartments (striosomes and matrix). Generalized anxiety disorder and social anxiety disorder interactomes showed exclusive and statistically significant overlaps with the striosome and matrix interactomes, respectively. Systematic gene expression analysis with the anxiety disorder interactomes constrained to contain only those genes that were shared with striatal compartment interactomes revealed a bifurcation among the disorders, which was influenced by the anterior cingulate cortex, nucleus accumbens, amygdala and hippocampus, and the dopaminergic signaling pathway. Our results indicate that the functionally distinct striatal pathways constituted by the striosome and the matrix may influence the etiological differentiation of various anxiety disorders.

Excessive self-grooming, gene dysregulation and imbalance between the striosome and matrix compartments in the striatum ofShank3mutant mice

“…Links between Gad2 and Shank3 were previously reported with an increase of GAD65 immunoreactivity in the Shank3 ß -/- mice 40 and a decrease of Gad2 transcript in the striatum of a Shank3 -overexpressing model 45 . GAD65 is associated with different disorders related to anxiety, such as obsessive-compulsive disorder (OCD), panic disorder or generalized anxiety disorder 46 . To our knowledge, there is no direct evidence in the literature for an association between Drd4 expression and grooming behaviour.…”

“…The two compartments, initially distinguished by differential expression of numerous molecular markers [for a review see 49 ], also differ in their input and output connectivity and electrophysiological characteristics 50 , such as D1-MSN excitability 51 , rates of dopamine release 52 , and response to chronic stress 53 . Imbalances in striosome to matrix activity have been suggested in several movement disorders [Huntington’s disease, Parkinson’s disease, dyskinesia, dystonia, for a review see 49 ], psychostimulant-induced motor stereotypies 54 , and more recently in anxiety disorder 46 . Corticostriatal path targeting striosomes also control decision-making under cost-benefit conflict 55,56 and habit formation 57 .…”

“…Studies by Kuo and Liu 58,59 have recently suggested that aberrant striatal compartmentation may be involved in autism. Furthermore, through the investigation of protein-protein interactions, a role for the striosomes in anxiety disorder such as social anxiety has been recently proposed 46 .…”

Transcriptome characteristics during cell wall formation of endosperm cellularization and embryo differentiation in Arabidopsis

“…The hierarchical clustering of heatmap analyses was generated using the online tool ( ) ( Babicki et al., 2016 ). Pairwise distances were measured using Pearson correlation, and average linkage was set as the clustering method in heatmap analyses ( Karunakaran et al., 2021 ; Lemke et al., 2021 ).…”

Agomelatine for the treatment of generalized anxiety disorder: focus on its distinctive mechanism of action

“… 40 Another example is provided by active Social Interaction with an unknown conspecific: 26 , 41 this is of note because there is increasing interest in overlapping features and cellular substrates of GAD and social anxiety. 42 , 43 In these and certain other procedures of potential anxiolytic properties, agomelatine displayed robust efficacy, though it has not invariably proven active in elevated plus maze and conditioned ultrasonic vocalization (USV) procedures 23 , 24 , 26 , 41 , 44 , 45 ( Table 1 ). Where active, the anxiolytic actions of agomelatine are expressed both acutely and upon sustained (several weeks) administration.…”