Abstract
To characterize the structural and functional neurobiology of a large group of adolescents exhibiting a behaviorally and emotionally dysregulated phenotype. Adolescents aged 14 years from the IMAGEN study were investigated. Latent class analysis (LCA) on the Strengths and Difficulties Questionnaire (SDQ) was used to identify a class of individuals with elevated behavioral and emotional difficulties ("dysregulated"; n= 233) who were compared to a matched sample from a low symptom class (controls, n= 233). Whole-brain gray matter volume (GMV) images were compared using a general linear model with 10,000 random label permutations. Regional GMV findings were then probed for functional differences from three functional magnetic resonance imaging (fMRI) tasks. Significant brain features then informed mediation path models linking the likelihood of psychiatric disorders (DSM-IV) with dysregulation. Whole-brain differences were found in the right orbitofrontal cortex (R.OFC; p< .05; k= 48), with dysregulated individuals exhibiting lower GMV. The dysregulated group also exhibited higher activity in this region during successful inhibitory control (F1,429= 7.53, p< .05). Path analyses indicated significant direct effects between the likelihood of psychopathologies and dysregulation. Modeling the R.OFC as a mediator returned modest partial effects, suggesting that the path linking the likelihood of an anxiety or conduct disorder diagnoses to dysregulation is partially explained by this anatomical feature. A large sample of dysregulated adolescents exhibited lower GMV in the R.OFC relative to controls. Dysregulated individuals also exhibited higher regional activations when exercising inhibitory control at performance levels comparable to those of controls. These findings suggest a neurobiological marker of dysregulation and highlight the role of the R.OFC in impaired emotional and behavioral control.
Highlights
Adolescents exhibiting severe difficulties regulating behavior and emotion are commonly referred for psychiatric evaluation but are difficult to classify into discrete diagnostic categories, with “comorbidity” being the rule rather than the exception in child psychiatry
These findings are consistent with studies reporting high prevalence rates of any level of psychiatric symptomatology in adolescence 33
61, p
Summary
Adolescents exhibiting severe difficulties regulating behavior and emotion are commonly referred for psychiatric evaluation but are difficult to classify into discrete diagnostic categories, with “comorbidity” being the rule rather than the exception in child psychiatry. Previous labels for these dysregulated children included severe mood dysregulation (SMD) or irritability[1] with the acknowledgement that these individuals will likely meet diagnostic criteria for other disorders. Considering the addition of this disorder into the DSM, and research showing the functional outcomes of dysregulated youths are strikingly poor[5], it is imperative to identify the neurobiological correlates of dysregulation. Characterizing the pathophysiological substrates will help inform dysregulation nosology, provide diagnostic biomarkers, and help inform targeted treatment methods
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