Preliminary evidence for progressive prefrontal abnormalities in adolescents and young adults with bipolar disorder

Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut 06511, USA.
Journal of the International Neuropsychological Society (Impact Factor: 2.96). 05/2009; 15(3):476-81. DOI: 10.1017/S1355617709090584
Source: PubMed


Previous cross-sectional study of ventral prefrontal cortex (VPFC) implicated progressive volume abnormalities during adolescence in bipolar disorder (BD). In the present study, a within-subject, longitudinal design was implemented to examine brain volume changes during adolescence/young adulthood. We hypothesized that VPFC volume decreases over time would be greater in adolescents/young adults with BD than in healthy comparison adolescents/young adults. Eighteen adolescents/young adults (10 with BD I and 8 healthy comparison participants) underwent two high-resolution magnetic resonance imaging scans over approximately 2 years. Regional volume changes over time were measured. Adolescents/young adults with BD displayed significantly greater volume loss over time, compared to healthy comparison participants, in a region encompassing VPFC and rostral PFC and extending to rostral anterior cingulate cortex (p < .05). Additional areas where volume change differed between groups were observed. While data should be interpreted cautiously due to modest sample size, this study provides preliminary evidence to support the presence of accelerated loss in VPFC and rostral PFC volume in adolescents/young adults with BD.

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Available from: E. Kale Edmiston, Oct 09, 2015
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    • "Based on previous studies (Altshuler et al., 2005; Ochsner and Gross, 2005; Gogtay et al., 2007; Foland et al., 2008; Pavuluri et al., 2008; Kalmar et al., 2009; Passarotti et al., 2010; Ladouceur et al., 2011; Deveney et al., 2013; Wu et al., 2013), we used the WFU PickAtlas (Maldjian et al., 2003) to create a single ROI mask including the striatum (caudate head and body, putamen, and ventral striatum [bilateral spheres centered on MNI coordinates À 9, 9, À 8 and 9, 9, À 8; radius¼ 8 mm (Postuma and Dagher, 2006; Di Martino et al., 2008)]), prefrontal cortical regions: medial prefrontal cortex (mPFC; BA10), orbitofrontal cortex (OFC; BA11), ventrolateral prefrontal cortex (VLPFC; BA47), dorsal anterior cingulate cortex (dACC; BA24/32), and insula. Using one large ROI mask avoided problems associated with conducting multiple statistical tests over the entire brain. "
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    ABSTRACT: The Research Domain Criteria (RDoC) adopts a dimensional approach for examining pathophysiological processes underlying categorically defined psychiatric diagnoses. We used this framework to examine relationships among symptom dimensions, diagnostic categories, and resting state connectivity in behaviorally and emotionally dysregulated youth selected from the Longitudinal Assessment of Manic Symptoms study (n=42) and healthy control youth (n=18). Region of interest analyses examined relationships among resting state connectivity, symptom dimensions (behavioral and emotional dysregulation measured with the Parent General Behavior Inventory-10 Item Mania Scale [PGBI-10M]; dimensional severity measures of mania, depression, anxiety), and diagnostic categories (Bipolar Spectrum Disorders, Attention Deficit Hyperactivity Disorder, Anxiety Disorders, and Disruptive Behavior Disorders). After adjusting for demographic variables, two dimensional measures showed significant inverse relationships with resting state connectivity, regardless of diagnosis: 1) PGBI-10M with amygdala-left posterior insula/bilateral putamen; and 2) depressive symptoms with amygdala-right posterior insula connectivity. Diagnostic categories showed no significant relationships with resting state connectivity. Resting state connectivity between amygdala and posterior insula decreased with increasing severity of behavioral and emotional dysregulation and depression; this suggests an intrinsic functional uncoupling of key neural regions supporting emotion processing and regulation. These findings support the RDoC dimensional approach for characterizing pathophysiologic processes that cut across different psychiatric disorders. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 11/2014; 231(1). DOI:10.1016/j.pscychresns.2014.10.015 · 2.42 Impact Factor
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    • "In the anterior cingulate (ACC), increases in cytosolic choline and reduced glutamate concentrations have been noted in youth with MDD (MacMaster and Kusumakar 2006; Rosenberg et al. 2005). A greater decrease in ACC volume over a 2-years period was found in adolescents with BD as compared to healthy controls (Kalmar et al. 2009). Smaller left ACC volume was also noted in BD versus control subjects (Chiu et al. 2008). "
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    ABSTRACT: Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.
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    • "Moreover, reductions in amygdala volume have consistently been observed in pediatric and adolescent, but not adult, bipolar patients [139], and chronic lithium exposure is associated with increased hippocampal and amygdala volumes compared with unmedicated patients and healthy controls [134]. A longitudinal structural MRI study further suggests that bipolar disorder is associated with accelerated loss in gray matter volume in subregions of the prefrontal cortex during adolescence compared with typically developing controls [140]. Longitudinal structural MRI studies have also found that schizophrenic patients exhibit greater decreases over time in whole brain volume, whole brain gray matter, frontal gray and white matter, parietal white matter, and temporal white matter volume, as well as greater increases in lateral ventricular volume, compared with healthy controls [141]. "
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