Striosome‐Like Structural Connectivity Is Reduced in the Rostral Putamen in Anxiety Disorder

Anxiety disorders affect roughly a third of adults, and treatment of anxiety-related symptoms costs more than any other mental health condition. Symptoms often begin in adolescence and are usually lifelong. Identifying shared neuroanatomical features of anxiety is essential for understanding its causes and improving treatments. Developmental abnormalities in the striatum, an obligate node in cortico-striato-thalamo-cortical networks, could predispose to the diverse symptoms of anxiety. The striatum is comprised of two interdigitated tissue compartments, striosome and matrix, that have different embryologic origins, divergent afferent/efferent connectivity, opposing responses to dopamine, and are embedded in distinct structural and functional networks. We used quantitative diffusion tractography to perform connectivity-based parcellation, identifying striosome-like and matrix-like striatal voxels in a 295-subject cohort (youth-onset anxiety vs. matched controls). In anxiety, striosome-like connectivity was depleted and dispersed, especially in a bilateral zone in the rostral putamen. Striosome-like connectivity was inversely correlated with standardized assessments of anxiety. Matrix-favoring connectivity was increased in a broad swath of cortico-striate projections. Increases in the striatal matrix:striosome ratio may predispose individuals to anxiety.