Association of Striatal Connectivity Gradients to Functional Domains Across Psychiatric Disorders

Abstract

ObjectiveTo uncover transdiagnostic domains of functioning across stress- and neurodevelopmental disorders, and to map these on to the topographic functional organization of cortico-striatal circuitry. MethodsIn a clinical sample (n=186) of subjects with high rates of comorbidity of major depressive disorder, anxiety disorder, attention-deficit/hyperactivity disorder and/or autism spectrum disorder, we use exploratory factor analysis on a wide range of clinical questionnaires to identify consistent functional domains of symptomatology across disorders, then replicate these functional domains in an independent dataset (n=188). Then, we use canonical correlation analysis link these functional domains to the topographic organization of the striatum as represented by connectopic maps. ResultsWe reveal four functional domains that transcend current diagnostic categories relating to negative valence, cognition, social functioning and inhibition/arousal. These functional domains are replicated in an independent sample and are associated with the fine-grained topographical organization of functional connectivity in the striatum (out of sample r=0.20, p=0.026), a central hub in motor, cognitive, affective and reward-related brain circuits. Conclusions and relevanceFunctional domains across stress- and neurodevelopmental disorders are associated with the functional organization of the striatum. We propose that investigating psychiatric symptoms across disorders is a promising path to linking them to underlying biology, and can help bridge the gap between neuroscience and clinical psychiatry.