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: 6.35). 05/2008; 47(5):532-9. DOI: 10.1097/CHI.0b013e318167656e
Source: PubMed

ABSTRACT 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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    • "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 · 2.68 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.
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    • "Nevertheless, the volumetric MRI data are inconsistent. While some studies return negative results in adults (Lyoo et al., 2004; Swayze et al., 1992), children (Frazier et al., 2005), and high-risk offspring (Ladouceur et al., 2008; Singh et al., 2008), others report enlargement of the amygdala in adult samples with BD relative to healthy control samples (Altshuler et al., 1998, 2000; Brambilla et al., 2003; Strakowski et al., 1999b; Velakoulis et al., 2006). "
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    ABSTRACT: MRI-based reports of both abnormally increased and decreased amygdala volume in bipolar disorder (BD) have surfaced in the literature. Two major methodological weaknesses characterizing extant studies are treatment with medication and inaccurate segmentation of the amygdala due to limitations in spatial and tissue contrast resolution. Here, we acquired high-resolution images (voxel size=0.55 x 0.55 x 0.60 mm) using a GE 3T MRI scanner, and a pulse sequence optimized for tissue contrast resolution. The amygdala was manually segmented by one rater blind to diagnosis, using coronal images. Eighteen unmedicated (mean medication-free period 11+/-10 months) BD subjects were age and gender matched with 18 healthy controls, and 17 medicated (lithium or divalproex) subjects were matched to 17 different controls. The unmedicated BD patients displayed smaller left and right amygdala volumes than their matched control group (p<0.01). Conversely, the BD subjects undergoing medication treatment showed a trend towards greater amygdala volumes than their matched HC sample (p=0.051). Right and left amygdala volumes were larger (p<0.05) or trended larger, respectively, in the medicated BD sample compared with the unmedicated BD sample. The two control groups did not differ from each other in either left or right amygdala volume. BD patients treated with lithium have displayed increased gray matter volume of the cortex and hippocampus relative to untreated BD subjects in previous studies. Here we extend these results to the amygdala. We raise the possibility that neuroplastic changes in the amygdala associated with BD are moderated by some mood stabilizing medications.
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