White matter structure in youth with behavioral and emotional dysregulation disorders: a probabilistic tractographic study

Abstract

Importance: 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.

Design, setting, and participants: 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.

Main outcomes and measures: 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 and relevance: 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.

Figure-1

Panel A. Pie graph represents proportions and corresponding percentages of youth with-BehavioralDD(in blue), youth with-EmotionalDD(in red) and youth with-Both(in purple) in the LAMS neuroimaging sample. Panel B. Pie graph represents proportions and corresponding percentages of different diagnoses in LAMS youth. Single diagnoses(blue tones): ADHD(11%), BPSD(6%), DBD(2%), DD(2%), and AXD(1%). Lifetime comorbidities(grey tones): DD+DBD+ADHD(18%), DBD+ADHD(13%), BD+DBD+ADHD+AXD(11%), BD+DBD+ADHD(8%), DD+DBD+ADHD+AXD(8%), BD+AXD(5%), BD+ADHD(3%), BD+ADHD+AXD(3%), BD+DBD+AXD(3%), DD+ADHD+AXD(2%), ADHD+AXD(1%), DBD+ADHD+AXD(1%), DD+ADHD(1%), DD+AXD(1%), DD+DBD(1%), DD+DBD+AXD(1%).

Figure-2

Panel A. Reconstruction of forceps minor(red), uncinate fasciculus(blue) and cingulum(green) in one of our participants, using the global probabilistic algorithm proposed in TRACULA. The cortico-spinal tract(purple) served as ‘control region’. On the left side, three boxes show the same tracts reconstructed in the same participant using the deterministic algorithm proposed in ExploreDTI, for graphical comparison. Here, different colors within tracts represent the orientation of the fiber segments(red: segments with a left to right orientation of the fibers; green: segments with an anterior to posterior orientation of the fibers; blue: segments with an inferior to superior orientation of the fibers), based on the color coding convention used in DI. Panel B. Estimated Marginal Means and Standard Error of FA in forceps minor(left) and uncinate fasciculus(right) in youth with-BehavioralDD(in blue), youth with-EmotionalDD(in red), youth with-Both(in purple) and CONT(in green), after controlling for site and IQ. Panel C. Estimated Marginal Means and Standard Error of L1 in forceps minor(left) and uncinate fasciculus(right) in youth with-BehavioralDD(in blue), youth with-EmotionalDD(in red), youth with-Both(in purple) and CONT(in green), after controlling for site and IQ. FA: fractional anisotropy; IQ: intelligence quotient; Youth with-Behav.DD: youth with behavioral dysregulation disorders; Youth with-Emot.DD: youth with emotional dysregulation disorders; Youth with-Both: youth with both behavioral and emotional dysregulation disorders, CONT: typically developing youth.