New research
Comparing Brain Morphometry Across Multiple Childhood Psychiatric Disorders

This study was presented as an abstract at the annual meeting of the American College of Neuropsychopharmacology, Phoenix, Arizona, December 7–11, 2014.
https://doi.org/10.1016/j.jaac.2016.08.008Get rights and content

Objective

In both children and adults, psychiatric illness is associated with structural brain alterations, particularly in the prefrontal cortex (PFC). However, most studies compare gray matter volume (GMV) in healthy volunteers (HVs) to one psychiatric group. We compared GMV among youth with anxiety disorders, bipolar disorder (BD), disruptive mood dysregulation disorder (DMDD), attention-deficit/hyperactivity disorder (ADHD), and HVs.

Method

3-Tesla T1-weighted magnetic resonance imaging scans were acquired in 184 youths (39 anxious, 20 BD, 52 DMDD, 20 ADHD, and 53 HV). Voxel-based morphometry analyses were conducted. One-way analysis of variance tested GMV differences with whole-brain familywise error (p < .05) correction; secondary, exploratory whole-brain analyses used a threshold of p < .001, ≥200 voxels. Given recent frameworks advocating dimensional approaches in psychopathology research, we also tested GMV associations with continuous anxiety, irritability, and inattention symptoms.

Results

Specificity emerged in the left dorsolateral PFC (dlPFC), which differed among youth with BD, anxiety, and HVs; GMV was increased in youth with anxiety, but decreased in BD, relative to HVs. Secondary analyses revealed BD-specific GMV decreases in the right lateral PFC, right dlPFC, and dorsomedial PFC, and also anxiety-specific GMV increases in the left dlPFC, right ventrolateral PFC, frontal pole, and right parahippocampal gyrus/lingual gyrus. Both BD and DMDD showed decreased GMV relative to HVs in the right dlPFC/superior frontal gyrus. GMV was not associated with dimensional measures of anxiety, irritability, or ADHD symptoms.

Conclusion

Both disorder-specific and shared GMV differences manifest in pediatric psychopathology. Some differences were specific to anxiety disorders, others specific to BD, and others shared between BD and DMDD. Further developmental research might map commonalities and differences of structure and function in diverse pediatric psychopathologies.

Section snippets

Participants

Participants included 184 children and adolescents 8 to 19 years of age who were recruited from the community and participating in research studies at NIMH. As approved by the NIMH Institutional Review Board, after receiving a complete description of the study, parents and 18- to 19-year-old youth provided written informed consent, and youth provided written assent.

Participant characteristics are summarized in Table 1. Inclusion criteria for all groups included no siblings enrolled in the

Primary Voxelwise Analysis

One region in the left dlPFC survived peak-level whole-brain FWE correction (FWE-corrected p = .017) (Table 2, Figure 1). Post hoc pairwise comparisons showed that GMV in the left dlPFC differed in HVs both from patients with BD and from those with anxiety, but with opposite patterns: compared to HVs, GMV was increased in the anxious group, but decreased in the BD group. In addition, patients with anxiety showed increased GMV relative to each of the other four groups.

Secondary, Exploratory Voxelwise Analysis

Using the whole-brain

Discussion

The current study provides unique evidence of both disorder-specific and shared GMV differences across four pediatric mental disorders. Two key findings emerged. First, primary analyses revealed diagnostic specificity in the left dlPFC; relative to HVs, there was increased GMV in patients with anxiety, but decreased GMV in patients with BD. In secondary exploratory analyses, there was further evidence of BD-specific decreases and anxiety-specific increases in GMV relative to HVs in other PFC

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      Jirsaraie et al. (2019) found irritability was associated with reduced cortical thickness in orbitofrontal, medial temporal, and lateral temporal regions. Compared to healthy youth, children with severe irritability have smaller gray matter volume (GMV) in the pre-supplementary motor area (Adleman et al., 2012), dorsolateral prefrontal cortex (Adleman et al., 2012; Gold et al., 2016), superior frontal gyrus (Gold et al., 2016), and larger insula volume (Adleman et al., 2012). These studies all compared GMV between diagnostic groups.

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    This article was reviewed under and accepted by ad hoc editor Guido K.W. Frank, MD.

    This research was supported by the Intramural Research Program of the National Institute of Mental Health/National Institutes of Health (NIMH/NIH), ZIAMH002781 (Pine), ZIAMH002778-15 (Leibenluft), ZIAMH002786-13 (Leibenluft), and based on Clinical Study Protocols 01-M-0192, 00-M-0198, and 02-M-0021.

    Dr. Fromm served as the statistical expert for this research.

    The authors acknowledge the work of the staff of the Section on Bipolar Spectrum Disorders, the Section on Development and Affective Neuroscience, and the NIH Functional Magnetic Resonance Imaging Core Facility. Most importantly, they thank the children and families who participated in this research.

    Disclosure: Drs. Gold, Brotman, Adleman, Fromm, Mueller, Pine, Leibenluft, and Mss. Lever and Steuber report no biomedical financial interests or potential conflicts of interest.

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