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

Autor:	Shanmugan S; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Wolf DH; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Calkins ME; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Moore TM; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Ruparel K; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Hopson RD; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Vandekar SN; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Roalf DR; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Elliott MA; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Jackson C; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Gennatas ED; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Leibenluft E; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Pine DS; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Shinohara RT; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Hakonarson H; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Gur RC; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Gur RE; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia., Satterthwaite TD; From the Departments of Psychiatry, of Biostatistics and Epidemiology, of Radiology, and of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia; the NIMH Mood and Anxiety Disorders Program, Bethesda, Md.; the Center for Applied Genomics, Children's Hospital of Philadelphia; and the Philadelphia Veterans Administration Medical Center, Philadelphia.
Jazyk:	angličtina
Zdroj:	The American journal of psychiatry [Am J Psychiatry] 2016 May 01; Vol. 173 (5), pp. 517-26. Date of Electronic Publication: 2016 Jan 22.
DOI:	10.1176/appi.ajp.2015.15060725
Abstrakt:	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.
Databáze:	MEDLINE
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