title: Common and Dissociable Mechanisms of Executive System Dysfunction Across Psychiatric Disorders in Youth.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: Sheila
authors.initials: S
authors.lastname: Shanmugan
authors.affiliation: 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.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Wolf
authors.affiliation: 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.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: 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.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Moore
authors.affiliation: 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.
authors.forename: Kosha
authors.initials: K
authors.lastname: Ruparel
authors.affiliation: 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.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Hopson
authors.affiliation: 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.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Vandekar
authors.affiliation: 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.
authors.forename: David R
authors.initials: DR
authors.lastname: Roalf
authors.affiliation: 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.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Elliott
authors.affiliation: 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.
authors.forename: Chad
authors.initials: C
authors.lastname: Jackson
authors.affiliation: 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.
authors.forename: Efstathios D
authors.initials: ED
authors.lastname: Gennatas
authors.affiliation: 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.
authors.forename: Ellen
authors.initials: E
authors.lastname: Leibenluft
authors.affiliation: 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.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Pine
authors.affiliation: 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.
authors.forename: Russell T
authors.initials: RT
authors.lastname: Shinohara
authors.affiliation: 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.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: 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.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: 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.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: 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.
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Satterthwaite
mesh_terms: D000293:Adolescent; D002531:Cerebellum / Q000503:physiopathology; D002540:Cerebral Cortex / Q000503:physiopathology; D056344:Executive Function / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology; D001523:Mental Disorders / Q000503:physiopathology*; D009483:Neuropsychological Tests