Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses

Abstract

The high comorbidity among neuropsychiatric disorders suggests a possible common neurobiological phenotype. Resting-state regional cerebral blood flow (CBF) can be measured noninvasively with magnetic resonance imaging (MRI) and abnormalities in regional CBF are present in many neuropsychiatric disorders. Regional CBF may also provide a useful biological marker across different types of psychopathology. To investigate CBF changes common across psychiatric disorders, we capitalized upon a sample of 1042 youths (ages 11-23 years) who completed cross-sectional imaging as part of the Philadelphia Neurodevelopmental Cohort. CBF at rest was quantified on a voxelwise basis using arterial spin labeled perfusion MRI at 3T. A dimensional measure of psychopathology was constructed using a bifactor model of item-level data from a psychiatric screening interview, which delineated four factors (fear, anxious-misery, psychosis and behavioral symptoms) plus a general factor: overall psychopathology. Overall psychopathology was associated with elevated perfusion in several regions including the right dorsal anterior cingulate cortex (ACC) and left rostral ACC. Furthermore, several clusters were associated with specific dimensions of psychopathology. Psychosis symptoms were related to reduced perfusion in the left frontal operculum and insula, whereas fear symptoms were associated with less perfusion in the right occipital/fusiform gyrus and left subgenual ACC. Follow-up functional connectivity analyses using resting-state functional MRI collected in the same participants revealed that overall psychopathology was associated with decreased connectivity between the dorsal ACC and bilateral caudate. Together, the results of this study demonstrate common and dissociable CBF abnormalities across neuropsychiatric disorders in youth.

Figure 1. Bifactor model of psychopathology reveals common and divergent dimensions of psychopathology across categorical screening diagnoses

A) Confirmatory bifactor analysis of 112 items from the GOASSESS screening interview revealed four orthogonal dimensions of psychopathology (anxious-misery, psychosis, behavioral, and fear), plus a general factor shared across disorders (overall psychopathology). B) Mean factor scores for each orthogonal dimension of psychopathology are presented by screening categories with at least 20 subjects. Overall psychopathology was common across diagnostic screening categories. ADHD = attention deficit hyperactivity disorder; GAD = generalized anxiety disorder; MDD = major depressive disorder; OCD = obsessive-compulsive disorder; ODD = oppositional defiant disorder; PTSD = posttraumatic stress disorder; TD = typically developing.

Figure 2. Overall psychopathology is linked to elevated perfusion in the anterior cingulate circuit

Greater overall psychopathology across categorical clinical diagnoses was associated with elevated perfusion in A) right dorsal anterior cingulate cortex (ACC) and B) left rostral ACC. Images thresholded at z > 3.09, cluster corrected p < 0.01.

Figure 3. Dissociable dimensions of psychopathology are associated with cerebral perfusion

Greater psychosis-spectrum symptoms were related to reduced perfusion in A) left frontal operculum/left insula, whereas fear symptoms were associated with less perfusion in B) left subgenual ACC and C) right occipital/fusiform gyrus. Images thresholded at z > 3.09, cluster corrected p < 0.01.

Figure 4. Overall psychopathology is associated with diminished functional connectivity between the dorsal ACC and bilateral caudate

Resting-state functional connectivity data was collected in the same subjects (n=833), and a seed analysis from the dorsal ACC (see Figure 2A) was conducted. This data revealed diminished functional connectivity between the dorsal ACC and the head of the both A) the right caudate and B) the left caudate. Images thresholded at z > 3.09, cluster corrected p < 0.01.