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White matter structure in youth with behavioral and emotional dysregulation disorders: A probabilistic tractographic study
Versace A, Acuff H, Bertocci MA, Bebko G, Almeida JRC, Perlman SB, Leemans A, Schirda C, Aslam H, Dwojak A, Bonar L, Travis M, Gill MK, Demeter C, Diwadkar VA, Sunshine JL, Holland SK, Kowatch RA, Birmaher B, Axelson D, Horwitz SM, Frazier TW, Arnold LE, Fristad MA, Youngstrom EA, Findling RL and Phillips ML
JAMA Psychiatry, Published Online

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 elucidated using techniques such as neuroimaging, and frameworks that may cut across conventionally-defined diagnoses.  

Dr. Amelia Versace and researchers in the Clinical and Translational Affective Neuroscience Program investigated whether diffusion imaging can identify neural correlates of emotional dysregulation.  Study participants were 120 youth with psychiatric disorders characterized by behavioral and emotional dysregulation.  The investigators examined relationships between white matter structure in key tracts in emotional regulation circuitry and: 1) broader-diagnostic categories of behavioral and emotional dysregulation disorders; and 2) symptom dimensions cutting across conventional diagnoses. Thirty typically developing youth were also included in the study.

Dr. Versace and her team used global probabilistic tractography to reconstruct the cingulum, uncinate fasciculus and forceps minor, key white matter tracts in emotional regulation circuitry.  A multivariate multiple regression analyses revealed statistically significantly decreased fractional anisotropy in the uncinate fasciculus of youth with emotional dysregulation disorders vs. those with behavioral dysregulation disorders and those with both, emotional and behavioral, disorders. In the same model, greater severity of manic symptoms was positively associated with higher fractional anisotropy across all affected youth. 

The findings from this study suggest that abnormal uncinate fasciculus and cingulum white matter structure may underlie emotional, but not behavioral, dysregulation in pediatric psychiatric disorders, while a different neural mechanism may exist for comorbid (emotional and behavioral dysregulation) disorders.


Contributors:
Amelia Versace, MD, Michele A. Bertocci, PhD1, Genna Bebko, PhD, Jorge R. C. Almeida, MD, PhD, Susan B. Perlman, PhD, Claudiu Schirda, PhD, Haris Aslam, BA, Amanda Dwojak, BA, Lisa Bonar, BS, Michael Travis, MD, Mary Kay Gill, RN, MSN, Boris Birmaher, MD and Mary L. Phillips, MD, MD(Cantab) (Department of Psychiatry, University of Pittsburgh)

Heather Acuff, BS (Medical Science Training Program, University of Pittsburgh School of Medicine) 

Alexander Leemans, PhD (Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands) 

Christine Demeter, MA and Jeffrey L. Sunshine, MD, PhD (University Hospitals Case Medical Center/Case Western Reserve University) 

Vaibhav A. Diwadkar, PhD (Department of Psychiatry and Behavioral Neuroscience, Wayne State University) 

Scott K Holland, PhD (Cincinnati Children’s Hospital Medical Center, University of Cincinnati) 

Robert. A. Kowatch, MD, PhD (The Research Institute at Nationwide Children’s Hospital) 

Sarah M. Horwitz, PhD (Department of Child and Adolescent Psychiatry, New York University School of Medicine) 

Thomas W. Frazier, PhD, (Pediatric Institute, Cleveland Clinic) 

David Axelson, MD, L. Eugene Arnold, MD, MEd, Mary. A Fristad, PhD, ABPP, (Department of Psychiatry, Ohio State University) 

Eric A. Youngstrom, PhD (Department of Psychology, University of North Carolina at Chapel Hill) 

Robert L. Findling, MD, MBA (Department of Psychiatry, Johns Hopkins University)

This article appeared online in JAMA Psychiatry.  To view the abstract, click here.