Cross-sectional and longitudinal abnormalities in brain structure in children with severe mood dysregulation or bipolar disorder.
BACKGROUND
There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time. Furthermore, the developmental trajectories of structural abnormalities in BD or SMD are unknown. This study provides such data in BD, SMD, and HV.


METHODS
An optimized, modulated voxel-based morphometry (VBM) analysis was conducted on structural MRI scans from 201 children (78 SMD, 55 BD, and 68 HV). In addition, 92 children (31 SMD, 34 BD, and 27 HV) were rescanned after 2 years (mean interval 1.99 ± 0.94 years), to compare time-related changes among the three groups.


RESULTS
Cross-sectionally, the groups differed in gray matter (GM) volume in presupplementary motor area (pre-SMA), dorsolateral prefrontal cortex (DLPFC), insula, and globus pallidus. The cortical differences were driven mainly by increased GM volume in HV compared with BD and SMD. In globus pallidus, there was increased GM in BD compared with HV and SMD. Longitudinally, group-by-time interactions were evident in two clusters in the superior/inferior parietal lobule (R SPL/IPL) and in the precuneus. In both clusters, the interactions were driven by an abnormal increase in volume in BD.


CONCLUSIONS
Cross-sectionally, both BD and SMD are associated with structural abnormalities in frontal cortex, insula, and basal ganglia. Although some of these deficits overlap (insula and DLPFC), others differentiate SMD and BD (pre-SMA and globus pallidus). Abnormal developmental trajectories in lateral parietal cortex and precuneus are present in, and unique to, BD. Because of the high proportion of co-occurring ADHD in the SMD subjects, we could not separate effects of ADHD from those of SMD, and future research including a nonirritable ADHD group must address this issue.
National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. adlemann@mail.nih.gov
Nancy E
NE
Adleman
Stephen J
SJ
Fromm
Varun
V
Razdan
Reilly
R
Kayser
Daniel P
DP
Dickstein
Melissa A
MA
Brotman
Daniel S
DS
Pine
Ellen
E
Leibenluft
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000503:physiopathology; D001714:Bipolar Disorder / Q000503:physiopathology*; D001921:Brain / Q000473:pathology*; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D007508:Irritable Mood / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D014888:Wechsler Scales