White Matter Abnormality Underlies Emotional Dysregulation in Children

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Emotional dysregulation (ED) in childhood is now known to represent a prodrome to various adult psychopathologies, notably mood disorders and suicidality. Symptoms of ED—quickness to anger, inability to refocus attention from strong emotions and low tolerance of frustration—are thought to reflect a difficulty in cortical regulation of emotions.

Now, researchers have determined that abnormal connectional microstructure between the frontal cortical and subcortical (limbic) systems, which is detectable on MRI, predicts ED symptom severity in children. It may therefore be possible to use brain imaging as an early biomarker of pediatric mood disorders. Joseph Biederman, MD, chief of the Pediatric Psychopharmacology & Adult ADHD Program at Massachusetts General Hospital, John D. E. Gabrieli, PhD, director of the Martinos Imaging Center, part of the McGovern Institute at Massachusetts Institute of Technology, and colleagues present their findings in NeuroImage: Clinical.

Study Details

The Child Behavior Checklist (CBCL) is made up of eight subscales. The researchers asked parents of 32 children (16 boys, 16 girls, average age 9.5 years) to complete three of those subscales: attention, aggression and anxiety/depression (A–A–A).

In previous research, an abnormal CBCL-ED profile (combined A–A–A score >180) identified children at higher risk of developing mood disorders. A severe ED profile (score >210) was particularly sensitive for pediatric bipolar disorder. Children with a score ≤150 are considered free of ED. In this study the participants' scores ranged from 151 to 265.

The Kiddie Schedule for Affective Disorder and Schizophrenia–Epidemiological version modules on mood disorders were used to define the presence or absence of major depressive disorder or bipolar disorder. The participants underwent MRI scanning, including T1-weighted whole-head anatomical and diffusion-weighted imaging scans.

Results

Higher CBCL-ED scores were linked with weakened microstructural integrity of cingulum–callosal neurocircuitry. Specifically, children with greater ED severity showed increased radial diffusivity and decreased fractional anisotropy in these regions, which suggest problems with axonal myelination.

The cingulum and callosal bundles are the largest white matter tracts in the brain. They connect dorsal cortical brain areas (including the frontal, visuoparietal and sensorimotor cortex) with ventral brain areas in the medial temporal lobe, including the limbic system. These neural pathways are implicated in emotional attribution, attentional allocation and executive control, which are key to emotion regulation.

Clinical Relevance

Altered cingulum and callosal microstructure might prove to be useful as a biomarker to guide physicians' treatment choices. Incipient mood disorders can follow a unipolar or bipolar course, and the treatment approaches differ, so it would be helpful to know as soon as possible which is indicated.

The findings might also help scientists discover targets for drugs that would reduce the severity of mood disorders—or even prevent them.

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