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.
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Thanks to the acquisition and recruitment team: Karthik Prabhakaran, Jeff Valdez, Raphael Gerraty, Marisa Riley, Jack Keefe, Elliott Yodh and Rosetta Chiavacci. Thanks to Chad Jackson and Larry Macy for data management and systems support. Thanks to Kathleen Merikangas and Marcy Burstein at the NIMH. This work was supported by RC2 grants from the National Institute of Mental Health MH089983 and MH089924 and P50MH096891. Additional support was provided by R01MH107703 to TDS, R01MH101111 to DHW, K01MH102609 to DRR, K08MH079364 to MEC, R01NS085211 to RTS, and the Dowshen Program for Neuroscience. Support for developing statistical analyses (to RTS and TDS) was provided by a seed grant by the Center for Biomedical Computing and Image Analysis (CBICA) at Penn. Support was also provided by a Building Interdisciplinary Research Careers in Women’s Health (BIRCWH) grant (K12 HD085848) and Penn PROMOTES Research on Sex and Gender in Health at the University of Pennsylvania.
The data reported in this paper have been deposited in database of Genotypes and Phenotypes (dbGaP), www.ncbi.nlm.nih.gov/gap (accession no. phs000607.v1.p1).
Conflict of Interest
EBF receives royalties from the sale of the books, ‘Prolonged Exposure Therapy for PTSD: Emotional Processing of Traumatic Experiences Therapist Guide,’ and ‘Reclaiming your Life from a Traumatic Experience Workbook’ by Oxford University Press. EBF also receives payment for training workshops she conducts on prolonged exposure therapy. RTS has received legal consulting and advisory board income from Genentech/Roche. The remaining authors declare no conflict of interest.
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Kaczkurkin, A.N., Moore, T.M., Calkins, M.E. et al. Common and dissociable regional cerebral blood flow differences associate with dimensions of psychopathology across categorical diagnoses. Mol Psychiatry 23, 1981–1989 (2018). https://doi.org/10.1038/mp.2017.174
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