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.

[1]  E. Leibenluft,et al.  Neural recruitment during failed motor inhibition differentiates youths with bipolar disorder and severe mood dysregulation , 2012, Biological Psychology.

[2]  Ellen Leibenluft,et al.  Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder. , 2011, Journal of the American Academy of Child and Adolescent Psychiatry.

[3]  Katya Rubia,et al.  Gray matter volume abnormalities in ADHD: voxel-based meta-analysis exploring the effects of age and stimulant medication. , 2011, The American journal of psychiatry.

[4]  Allan Reiss,et al.  Striatal volumes in pediatric bipolar patients with and without comorbid ADHD , 2011, Psychiatry Research: Neuroimaging.

[5]  S. Mostofsky,et al.  Comprehensive Examination of Frontal Regions in Boys and Girls with Attention-Deficit/Hyperactivity Disorder , 2011, Journal of the International Neuropsychological Society.

[6]  S. Strakowski,et al.  Progressive neurostructural changes in adolescent and adult patients with bipolar disorder , 2011, Bipolar disorders.

[7]  Ellen Leibenluft,et al.  Severe mood dysregulation, irritability, and the diagnostic boundaries of bipolar disorder in youths. , 2011, The American journal of psychiatry.

[8]  P. Matthews,et al.  Structural brain and neuropsychometric changes associated with pediatric bipolar disorder with psychosis. , 2011, Bipolar disorders.

[9]  R. Murray,et al.  Pattern of neural responses to verbal fluency shows diagnostic specificity for schizophrenia and bipolar disorder , 2011, BMC psychiatry.

[10]  Dorret I Boomsma,et al.  Genetic and environmental influences on focal brain density in bipolar disorder. , 2010, Brain : a journal of neurology.

[11]  E. Leibenluft,et al.  Pediatric bipolar disorder versus severe mood dysregulation: risk for manic episodes on follow-up. , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[12]  E. Bullmore,et al.  Anatomy of bipolar disorder and schizophrenia: A meta-analysis , 2010, Schizophrenia Research.

[13]  T. Paus,et al.  Cortical Gray Matter in Attention-Deficit/Hyperactivity Disorder: A Structural Magnetic Resonance Imaging Study , 2010, Journal of the American Academy of Child and Adolescent Psychiatry.

[14]  A. Reiss,et al.  Neural correlates of response inhibition in pediatric bipolar disorder. , 2010, Journal of child and adolescent psychopharmacology.

[15]  Daniel S Pine,et al.  Amygdala activation during emotion processing of neutral faces in children with severe mood dysregulation versus ADHD or bipolar disorder. , 2010, The American journal of psychiatry.

[16]  Klaus P. Ebmeier,et al.  Magnetic resonance imaging studies in bipolar disorder and schizophrenia: meta-analysis. , 2009, The British journal of psychiatry : the journal of mental science.

[17]  Céline R. Gillebert,et al.  Parcellation of parietal cortex: Convergence between lesion-symptom mapping and mapping of the intact functioning brain , 2009, Behavioural Brain Research.

[18]  J. Duncan,et al.  Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder , 2009, Journal of the International Neuropsychological Society.

[19]  E. Bora,et al.  Cognitive endophenotypes of bipolar disorder: a meta-analysis of neuropsychological deficits in euthymic patients and their first-degree relatives. , 2009, Journal of affective disorders.

[20]  J. Sweeney,et al.  Theory of mind and social inference in children and adolescents with bipolar disorder , 2008, Psychological Medicine.

[21]  Karl J. Friston,et al.  Voxel-Based Morphometry , 2015 .

[22]  Derek G. V. Mitchell,et al.  Common regions of dorsal anterior cingulate and prefrontal–parietal cortices provide attentional control of distracters varying in emotionality and visibility , 2007, NeuroImage.

[23]  G. Logan,et al.  Converging Evidence for a Fronto-Basal-Ganglia Network for Inhibitory Control of Action and Cognition , 2007, The Journal of Neuroscience.

[24]  Kiralee M. Hayashi,et al.  Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. , 2007, Journal of child psychology and psychiatry, and allied disciplines.

[25]  L. Kassem,et al.  Parental diagnoses in youth with narrow phenotype bipolar disorder or severe mood dysregulation. , 2007, The American journal of psychiatry.

[26]  Caleb M. Adler,et al.  Voxel-Based Study of Structural Changes in First-Episode Patients with Bipolar Disorder , 2007, Biological Psychiatry.

[27]  A. Saykin,et al.  Functional magnetic resonance imaging of executive control in bipolar disorder , 2006, Neuroreport.

[28]  M. J. Meloy,et al.  Striatopallidal regulation of affect in bipolar disorder. , 2006, Journal of affective disorders.

[29]  A. Cavanna,et al.  The precuneus: a review of its functional anatomy and behavioural correlates. , 2006, Brain : a journal of neurology.

[30]  J. Soliva,et al.  Global and regional gray matter reductions in ADHD: A voxel-based morphometric study , 2005, Neuroscience Letters.

[31]  Nikos Makris,et al.  Cortical gray matter differences identified by structural magnetic resonance imaging in pediatric bipolar disorder. , 2005, Bipolar disorders.

[32]  B. Peterson,et al.  Preliminary evidence for persistent abnormalities in amygdala volumes in adolescents and young adults with bipolar disorder. , 2005, Bipolar disorders.

[33]  S. Strakowski,et al.  Changes in Gray Matter Volume in Patients with Bipolar Disorder , 2005, Biological Psychiatry.

[34]  E. Leibenluft,et al.  Frontotemporal alterations in pediatric bipolar disorder: results of a voxel-based morphometry study. , 2005, Archives of general psychiatry.

[35]  Marko Wilke,et al.  Voxel-based morphometry in adolescents with bipolar disorder: first results , 2004, Psychiatry Research: Neuroimaging.

[36]  S. Strakowski,et al.  Magnetic resonance imaging analysis of amygdala and other subcortical brain regions in adolescents with bipolar disorder. , 2004, Bipolar disorders.

[37]  Eduard Vieta,et al.  Cognitive function across manic or hypomanic, depressed, and euthymic states in bipolar disorder. , 2004, The American journal of psychiatry.

[38]  Corianne Rogalsky,et al.  Increased activation in the right insula during risk-taking decision making is related to harm avoidance and neuroticism , 2003, NeuroImage.

[39]  Gregory G Brown,et al.  An fMRI study of affective state and medication on cortical and subcortical brain regions during motor performance in bipolar disorder , 2003, Psychiatry Research: Neuroimaging.

[40]  E. Leibenluft,et al.  Defining clinical phenotypes of juvenile mania. , 2003, The American journal of psychiatry.

[41]  Karl J. Friston,et al.  A Voxel-Based Morphometric Study of Ageing in 465 Normal Adult Human Brains , 2001, NeuroImage.

[42]  A. Bechara,et al.  Neurobiology of decision-making: risk and reward. , 2001, Seminars in clinical neuropsychiatry.

[43]  G. Moore,et al.  Clinical and preclinical evidence for the neurotrophic effects of mood stabilizers: implications for the pathophysiology and treatment of manic–depressive illness , 2000, Biological Psychiatry.

[44]  Karl J. Friston,et al.  Voxel-Based Morphometry—The Methods , 2000, NeuroImage.

[45]  Joel S. Perlmutter,et al.  The Behavioral Complications of Pallidal Stimulation: A Case Report , 2000, Brain and Cognition.

[46]  G. Mangun,et al.  The neural mechanisms of top-down attentional control , 2000, Nature Neuroscience.

[47]  S. Kiebel,et al.  Detecting Structural Changes in Whole Brain Based on Nonlinear Deformations—Application to Schizophrenia Research , 1999, NeuroImage.