Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Journal of the American Academy of Child and Adolescent Psychiatry (Impact Factor: 7.26). 05/2008; 47(5):532-9. DOI: 10.1097/CHI.0b013e318167656e
Source: PubMed


A growing number of structural neuroimaging studies have shown that bipolar disorder (BD) is associated with gray matter (GM) volume abnormalities in brain regions known to support affect regulation. The goal of this study was to examine whole-brain regional GM volume in healthy bipolar offspring (HBO) relative to age-matched controls to identify possible structural abnormalities that may be associated with risk for BD.
Participants were 20 youths (8-17 years old) with at least one parent diagnosed with BD, and 22 age-matched healthy individuals. All of them were free of Axis I diagnoses. High-resolution magnetic resonance imaging structural images were acquired using a 3-T Siemens scanner. Voxel-based morphometric analyses were conducted using SPM5.
Relative to controls, HBO had significantly increased GM volume in left parahippocampal/hippocampal gyrus (p <.05 corrected), following whole-brain analyses. This increase was correlated with puberty but not age in HBO. Region-of-interest analyses on the amygdala and orbitomedial prefrontal cortex did not yield any significant group differences after conducting small volume correction.
The pattern of increased GM volume in parahippocampal/hippocampal gyrus in HBO suggests a potential marker for risk for BD. It can also be considered as a potential neuroprotective marker for the disorder because HBO were free of current psychopathology. Prospective studies examining the relationship between changes in GM volume in these regions and subsequent development of BD in HBO will allow us to elucidate further the role of this region in either conferring risk for or protecting against the development of BD.

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Available from: Kelly Monk, Oct 29, 2014
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    • "Methodological differences between those studies and ours may explain, at least in part, the differences in results. For instance, some of the earlier VBM studies have used previous versions of the SPM software (McIntosh et al., 2004; Ladouceur et al., 2008; Kempton et al., 2009) as opposed to our use of SPM8 with DARTEL Toolbox. Some authors have demonstrated that the use of the DARTEL Toolbox provides superior results when compared to previous versions of the program (Klein et al., 2009; Tahmasebi et al., 2009; Ashburner, 2009). "
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    ABSTRACT: Bipolar disorder (BD) is highly heritable. First-degree relatives of BD patient have an increased risk to develop the disease. We investigated abnormalities in gray matter (GM) volumes in healthy first-degree relatives of BD patients to identify possible brain structural endophenotypes for the disorder. 3D T1-weighted magnetic resonance images were obtained from 25 DSM-IV BD type I patients, 23 unaffected relatives, and 27 healthy controls (HC). A voxel-based morphometry protocol was used to compare differences in GM volumes between groups. BD patients presented reduced GM volumes bilaterally in the thalamus compared with HC. Relatives presented no global or regional GM differences compared with HC. Our negative results do not support the role of GM volume abnormalities as endophenotypes for BD. Thalamic volume abnormalities may be associated the pathophysiology of the disease.
    Full-text · Article · Sep 2015 · Psychiatry Research: Neuroimaging
    • "In a recent study investigating the relationship between genes and anatomy in BD, metaanalysis of 18 VBM studies yielded larger left parahippocampal gyrus in BD patients in comparison to controls and parahippocampal gyrus showed enriched expression of 18 BD-associated genes among 22 genes identified in this study (McCarthy et al., 2014). Consistent with our findings, one VBM study by Ladouceur et al. (2008) found larger left parahippocampal gyrus volume in the healthy offsprings (8–17 years old) of BD I or II patients in comparison to age-matched healthy controls. Moreover, a recent fMRI study in youth with bipolar disorder and unaffected youth at risk reported abnormal parahippocampal gyrus activation during emotional face encoding ; bipolar youth (N ¼27) showed decreased whereas youth at risk (N ¼ 13) showed increased right parahippocampal gyrus activation (Tseng et al., 2015). "
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    ABSTRACT: Bipolar disorder (BD) is a highly heritable mental illness which is associated with neuroanatomical abnormalities. Investigating healthy individuals at high genetic risk for bipolar disorder may help to identify neuroanatomical markers of risk and resilience without the confounding effects of burden of illness or medication. Structural magnetic resonance imaging scans were acquired from 30 euthymic patients with BD-I (BP), 28 healthy first degree relatives of BD-I patients (HR), and 30 healthy controls (HC). Data was analyzed using DARTEL for voxel based morphometry in SPM8. Whole-brain analysis revealed a significant main effect of group in the gray matter volume in bilateral inferior frontal gyrus, left parahippocampal gyrus, left lingual gyrus and cerebellum, posterior cingulate gyrus, and supramarginal gyrus (alphasim corrected (≤0.05 FWE)). Post-hoc t-tests showed that inferior frontal gyrus volumes were bilaterally larger both in BP and HR than in HC. BP and HR also had smaller cerebellar volume compared with HC. In addition, BP had smaller left lingual gyrus volume, whereas HR had larger left parahippocampal and supramarginal gyrus volume compared with HC. This study was cross-sectional and the sample size was not large. All bipolar patients were on medication, therefore we were not able to exclude medication effects in bipolar group in this study. Our findings suggest that increased inferior frontal gyrus and decreased cerebellar volumes might be associated with genetic predisposition for bipolar disorder. Longitudinal studies are needed to better understand the predictive and prognostic value of structural changes in these regions. Copyright © 2015 Elsevier B.V. All rights reserved.
    No preview · Article · Jul 2015 · Journal of Affective Disorders
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    • "Twin studies have suggested that neuroanatomical abnormalities of the hippocampal and parahippocampal cortex (Noga et al., 2001) are implicated in the pathology of bipolar disorder. Other studies in offspring of patients with bipolar disorder suggested that the dynamic relationship between the amygdala and the parahippocampal gyrus may be crucially involved in disturbed emotional regulation (Ladouceur et al., 2008). Nevertheless, the findings of studies in subjects at genetic risk for bipolar disorder have not been consistent. "

    Full-text · Article · Jun 2012 · Psychiatry Research
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