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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    • "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.
    Journal of Affective Disorders 07/2015; 186:110-118. DOI:10.1016/j.jad.2015.06.055 · 3.38 Impact Factor
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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. "
    Psychiatry Research 06/2012; 202(3):273-4. DOI:10.1016/j.pscychresns.2011.12.005 · 2.47 Impact Factor
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    • "These researchers also used voxel-based morphometry and did not perform manual tracings on regions including the amygdala. Thus, this sample, being fairly old and free of psychopathology , might be considered a particularly low-risk " at-risk " group and may even be displaying neurobiological markers of resilience, such as the reported finding of increased volume of the left hippocampal gyrus (Ladouceur et al., 2008). The study by Hajek et al. (2009a) included a wider age range of at-risk subjects, from ages 15 to 30, included offspring of parents with MDD (but with a second-degree relative with BD), and their affected high-risk group included subjects with MDD as well as subjects with bipolar I or II disorder. "
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    ABSTRACT: Children of parents with bipolar disorder (BD), especially those with attention deficit hyperactivity disorder (ADHD) and symptoms of depression or mania, are at significantly high risk for developing BD. As we have previously shown amygdalar reductions in pediatric BD, the current study examined amygdalar volumes in offspring of parents (BD offspring) who have not yet developed a full manic episode. Youth participating in the study included 22 BD offspring and 22 healthy controls of comparable age, gender, handedness, and IQ. Subjects had no history of a manic episode, but met criteria for ADHD and moderate mood symptoms. MRI was performed on a 3T GE scanner, using a 3D volumetric spoiled gradient echo series. Amygdalae were manually traced using BrainImage Java software on positionally normalized brain stacks. Bipolar offspring had similar amygdalar volumes compared to the control group. Exploratory analyses yielded no differences in hippocampal or thalamic volumes. Bipolar offspring do not show decreased amygdalar volume, possibly because these abnormalities occur after more prolonged illness rather than as a preexisting risk factor. Longitudinal studies are needed to determine whether amygdalar volumes change during and after the development of BD.
    Psychiatry Research 12/2011; 194(3):319-25. DOI:10.1016/j.pscychresns.2011.03.006 · 2.47 Impact Factor
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