Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth

• Published in: The American journal of psychiatry 2016-05, Vol.173 (5), p.517-526
• Main Authors: Shanmugan, Sheila, Wolf, Daniel H., Calkins, Monica E., Moore, Tyler M., Ruparel, Kosha, Hopson, Ryan D., Vandekar, Simon N., Roalf, David R., Elliott, Mark A., Jackson, Chad, Gennatas, Efstathios D., Leibenluft, Ellen, Pine, Daniel S., Shinohara, Russell T., Hakonarson, Hakon, Gur, Ruben C., Gur, Raquel E., Satterthwaite, Theodore D.
• Format: Article
• Language: English
• Subjects: Adolescent; Cerebellum - physiopathology; Cerebral Cortex - physiopathology; Executive Function - physiology; Female; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Male; Memory, Short-Term - physiology; Mental disorders; Mental Disorders - physiopathology; Neuropsychological Tests; Psychiatry; Psychopathology; Psychosis
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2015.15060725

Objective:Disruption of executive function is present in many neuropsychiatric disorders. However, determining the specificity of executive dysfunction across these disorders is challenging given high comorbidity of conditions. Here the authors investigate executive system deficits in association with dimensions of psychiatric symptoms in youth using a working memory paradigm. The authors hypothesize that common and dissociable patterns of dysfunction would be present.Method:The authors studied 1,129 youths who completed a fractal n-back task during functional magnetic resonance imaging at 3-T as part of the Philadelphia Neurodevelopmental Cohort. Factor scores of clinical psychopathology were calculated using an item-wise confirmatory bifactor model, describing overall psychopathology as well as four orthogonal dimensions of symptoms: anxious-misery (mood and anxiety), behavioral disturbance (attention deficit hyperactivity disorder and conduct disorder), psychosis-spectrum symptoms, and fear (phobias). The effect of psychopathology dimensions on behavioral performance and executive system recruitment (2-back > 0-back) was examined using both multivariate (matrix regression) and mass-univariate (linear regression) analyses.Results:Overall psychopathology was associated with both abnormal multivariate patterns of activation and a failure to activate executive regions within the cingulo-opercular control network, including the frontal pole, cingulate cortex, and anterior insula. In addition, psychosis-spectrum symptoms were associated with hypoactivation of the left dorsolateral prefrontal cortex, whereas behavioral symptoms were associated with hypoactivation of the frontoparietal cortex and cerebellum. In contrast, anxious-misery symptoms were associated with widespread hyperactivation of the executive network.Conclusions:These findings provide novel evidence that common and dissociable deficits within the brain’s executive system are present in association with dimensions of psychopathology in youth.