title: White matter structure in youth with behavioral and emotional dysregulation disorders: a probabilistic tractographic study.
abstract: OBJECTIVE
  Psychiatric disorders in youth characterized by behavioral and emotional dysregulation are often comorbid and difficult to distinguish. An alternative approach to conceptualizing these disorders is to move toward a diagnostic system based on underlying pathophysiologic processes that may cut across conventionally defined diagnoses. Neuroimaging techniques have potentials for the identification of these processes.
  
  
  OBJECTIVE
  To determine whether diffusion imaging, a neuroimaging technique examining white matter (WM) structure, can identify neural correlates of emotional dysregulation in a sample of youth with different psychiatric disorders characterized by behavioral and emotional dysregulation.
  
  
  METHODS
  Using global probabilistic tractography, we examined relationships between WM structure in key tracts in emotional regulation circuitry (ie, cingulum, uncinate fasciculus, and forceps minor) and (1) broader diagnostic categories of behavioral and emotional dysregulation disorders (DDs) and (2) symptom dimensions cutting across conventional diagnoses in 120 youth with behavioral and/or emotional DDs, a referred sample of the Longitudinal Assessment of Manic Symptoms (LAM) study. Thirty age- and sex-matched typically developing youth (control participants) were included. Multivariate multiple regression models were used. The study was conducted from July 1, 2010, to February 28, 2014.
  
  
  METHODS
  Fractional anisotropy as well as axial and radial diffusivity were estimated and imported into a well-established statistical package. We hypothesized that (1) youth with emotional DDs and those with both behavioral and emotional DDs would show significantly lower fractional anisotropy compared with youth with behavioral DDs in these WM tracts and (2) that there would be significant inverse relationships between dimensional measures of affective symptom severity and fractional anisotropy in these tracts across all participants.
  
  
  RESULTS
  Multivariate multiple regression analyses revealed decreased fractional anisotropy and decreased axial diffusivity within the uncinate fasciculus in youth with emotional DDs vs those with behavioral DDs, those with both DDs, and the controls (F6,160 = 2.4; P = .032; all pairwise comparisons, P < .002). In the same model, greater severity of manic symptoms was positively associated with higher fractional anisotropy across all affected youth (F3,85 = 2.8; P = .044).
  
  
  CONCLUSIONS
  These findings suggest that abnormal uncinate fasciculus and cingulum WM structure may underlie emotional, but not behavioral, dysregulation in pediatric psychiatric disorders and that a different neural mechanism may exist for comorbid emotional and behavioral DDs.
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amelia
authors.initials: A
authors.lastname: Versace
authors.affiliation: Medical Science Training Program, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Heather
authors.initials: H
authors.lastname: Acuff
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Michele A
authors.initials: MA
authors.lastname: Bertocci
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Genna
authors.initials: G
authors.lastname: Bebko
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Jorge R C
authors.initials: JR
authors.lastname: Almeida
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Susan B
authors.initials: SB
authors.lastname: Perlman
authors.affiliation: Image Sciences Institute, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Leemans
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Claudiu
authors.initials: C
authors.lastname: Schirda
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Haris
authors.initials: H
authors.lastname: Aslam
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Amanda
authors.initials: A
authors.lastname: Dwojak
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Lisa
authors.initials: L
authors.lastname: Bonar
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Michael
authors.initials: M
authors.lastname: Travis
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mary Kay
authors.initials: MK
authors.lastname: Gill
authors.affiliation: Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Christine
authors.initials: C
authors.lastname: Demeter
authors.affiliation: Department of Psychiatry and Behavioral Neuroscience, Wayne State University, Detroit, Michigan.
authors.forename: Vaibhav A
authors.initials: VA
authors.lastname: Diwadkar
authors.affiliation: Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Sunshine
authors.affiliation: Department of Psychiatry, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio.
authors.forename: Scott K
authors.initials: SK
authors.lastname: Holland
authors.affiliation: Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kowatch
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Boris
authors.initials: B
authors.lastname: Birmaher
authors.affiliation: Department of Psychiatry, The Ohio State University, Columbus.
authors.forename: David
authors.initials: D
authors.lastname: Axelson
authors.affiliation: Department of Child and Adolescent Psychiatry, School of Medicine, New York University, New York.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Horwitz
authors.affiliation: Pediatric Institute, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Frazier
authors.affiliation: Department of Psychiatry, The Ohio State University, Columbus.
authors.forename: L Eugene
authors.initials: LE
authors.lastname: Arnold
authors.affiliation: Department of Psychiatry, The Ohio State University, Columbus.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Fristad
authors.affiliation: Department of Psychology, University of North Carolina at Chapel Hill.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Youngstrom
authors.affiliation: Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio12Department of Psychiatry, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Findling
authors.affiliation: Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Mary L
authors.initials: ML
authors.lastname: Phillips
mesh_terms: D000293:Adolescent; D000342:Affective Symptoms / Q000150:complications / Q000473:pathology*; D016880:Anisotropy; D001526:Behavioral Symptoms / Q000150:complications / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D008297:Male; D066127:White Matter / Q000473:pathology*