Corticolimbic metabolic dysregulation in euthymic older adults with bipolar disorder

UCLA Semel Institute, Los Angeles, CA 90025, USA.
Journal of Psychiatric Research (Impact Factor: 3.96). 11/2008; 43(5):497-502. DOI: 10.1016/j.jpsychires.2008.08.001
Source: PubMed


The corticolimbic dysregulation hypothesis of bipolar disorder suggests that depressive symptoms are related to dysregulation of components of an anterior paralimbic network (anterior cingulate, anterior temporal cortex, dorsolateral prefrontal cortex, parahippocampal gyrus, and amygdala) with excessive anterior limbic activity accompanied by diminished prefrontal activity. In younger patients, such abnormalities tend to resolve with remission of depression, but it remains to be established whether the same is true for older patients. This was a cross-sectional, between-subjects design conducted with 16 euthymic, medicated patients with bipolar disorder (10 type I, six type II) and 11 age-matched healthy controls. All participants were over age 50. Our main outcome measures were relative rates of cerebral metabolism derived from a resting (18)flourodeoxyglucose positron emission tomography scan in specified regions of interest in the corticolimbic network. Resting metabolic rates in bipolar patients were significantly greater than in controls in bilateral amygdalae, bilateral parahippocampal gyri, and right anterior temporal cortex (BA 20, 38); they were significantly lower in bipolar patients than in controls in the bilateral dorsolateral prefrontal cortices (BA 9, 10, 46). The evidence of corticolimbic dysregulation observed is consistent with the hypothesis that bipolar disorder entails progressive, pernicious neurobiological disruptions that may eventually persist during euthymia. Persistent corticolimbic dysregulation may be related to residual affective, behavioral, and cognitive symptoms in older patients with bipolar disorder, even when not experiencing syndromal mood disturbance.

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Available from: Allyson Rosen, Oct 09, 2015
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    • "Functional deficits during euthymia are related to neural changes and resting state functional neuroimaging studies (performed when subjects are not engaged in a particular task) have revealed baseline alterations in cerebral function. For example, in a group of recovered older patients with bipolar disorder, Brooks et al. (Brooks et al., 2009a) measured resting glucose metabolism with 18 FDG-PET and found that patients with bipolar disorder, compared to healthy controls, exhibited decreased bilateral dorsolateral prefrontal metabolism in conjunction with increased bilateral metabolism in the amygdala and parahippocampal gyrus. The degrees of prefrontal hypometabolism and parahippocampal hypermetabolism were correlated with poorer memory performance (Brooks et al., 2009b). "
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    ABSTRACT: Advances in functional neuroimaging have ushered in studies that have enhanced our understanding of the neuropathophysiology of bipolar disorder, but do not yet have clinical applications. We describe the major circuits (ventrolateral, dorsolateral, ventromedial, and anterior cingulate) thought to be involved in the corticolimbic dysregulation that may underlie mood states in patients with bipolar disorder. The potential clinical application of functional neuroimaging in bipolar disorder is considered in terms of prognostic, predictive, and treatment biomarkers. To date, most research has focused on prognostic biomarkers to differentiate patients with bipolar disorder from those with other affective or psychotic diagnoses, or healthy subjects. The search for treatment biomarkers, which suggest mechanisms of pharmacodynamic or treatment response, and predictive biomarkers has thus far involved only pediatric patients diagnosed with bipolar disorder. The results to date are encouraging and suggest that functional neuroimaging may be of eventual benefit in determining biomarkers of treatment response. Further refinement of biomarker identification, and perhaps even illness characterization are needed to find prognostic and predictive biomarkers of bipolar disorder.
    Journal of Psychiatric Research 10/2014; DOI:10.1016/j.jpsychires.2014.05.018 · 3.96 Impact Factor
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    • "function within which has long been posited to underlie mood disorders ( Price and Drevets , 2010 , 2012 ) . Among de - pressed samples , reductions in gray - matter volume ( Arnone et al . , 2012 ; Baumann and Bogerts , 1999 ; Ongür et al . , 1998 ) coupled with glucose metabolic perturbations ( Baxter Jr . et al . , 1989 ; Biver et al . , 1994 ; Brooks III et al . , 2009 ; Drevets et al . , 2002 ) have been observed in prefrontal cortex and striatum . Furthermore , similar to the current study , atten - uated hemodynamic responses to appetitive cues in these regions have characterized depressed participants across a range of elicitation procedures . Foremost in vSTR , although also in prefrontal cortex "
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    ABSTRACT: A cortico-limbic network consisting of the amygdala, medial prefrontal cortex (mPFC), and ventral striatum (vSTR) has been associated with altered function in emotional disorders. Here we used rapidly-sampled fMRI and Granger causality analyses to assess the directional connectivity between these brain structures in a sample of healthy and age-matched participants endorsing moderate to severe depressive symptomatology as they viewed a series of natural scene stimuli varying systematically in pleasantness and arousal. Specifically during pleasant scene perception, dysphoric participants showed reduced activity in mPFC and vSTR, relative to healthy participants. In contrast, amygdala activity was enhanced to pleasant as well as unpleasant arousing scenes in both participant groups. Granger causality estimates of influence between mPFC and vSTR were significantly reduced in dysphoric relative to control participants during all picture contents. These findings provide direct evidence that during visual perception of evocative emotional stimuli, reduced reward-related activity in dysphoria is associated with dysfunctional causal connectivity between mPFC, amygdala and ventral striatum.
    Brain Connectivity 02/2014; 5(1). DOI:10.1089/brain.2013.0186
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    • "Positron emission tomography studies using fluorodeoxyglucose- F18 (FDG-PET) have pointed out in bipolar disorder the potential presence of a corticolimbic metabolic dysregulation at rest, involving excessive anterior limbic metabolic rates (anterior temporal cortex, parahippocampal gyrus, and amygdala) accompanied by diminished prefrontal activity (i.e., dorsolateral prefrontal cortex, DLPFC, and anterior cingulate) (Brooks III et al., 2009a), which also correlated to cognitive deficits, such as impaired sustained attention and verbal memory, even during euthymia (Brooks III et al., 2009b, 2010). This anterior paralimbic dysregulation has recently been confirmed by a meta-analysis conducted on functional neuroimaging studies including 774 adult patients with bipolar disorder and 810 healthy adult controls (Kupferschmidt and Zakzanis, 2011). "
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    ABSTRACT: (18)Flourodeoxyglucose positron emission tomography studies (FDG-PET) have shown similar corticolimbic metabolic dysregulation in bipolar disorder and schizophrenia, with hypoactive prefrontal cortex coupled with hyperactive anterior limbic areas. However, it is not clear whether white matter metabolism connecting these regions is differently affected in the two disorders. Twenty-six patients with schizophrenia (mean age±S.D.=30.23±9.7 year-old; 19 males; mean weight±S.D.=71±3kg) and 26 patients with bipolar disorder (mean age±S.D.=48.73±13 year-old; 18 males; mean weight±S.D.=75±15kg) underwent an FDG-PET scan. Normalized datasets the two groups of patients were compared on a voxel-by-voxel basis using a two-sample t statistic test as implemented in SPM8, and adding age as covariate. Group differences were assessed applying a threshold of p<0.0005. White matter metabolic rates significantly differed between schizophrenia and bipolar disorder, whereas no differences were shown for cortical activity. This is the first FDG-PET, to our best knowledge, directly comparing subjects with schizophrenia to those with bipolar disorder. It reports decreased activity in the center of large fronto-temporal and cerebellar white matter tracts in patients with schizophrenia in respect to those with bipolar disorder. This feature may characterize and differentiate the regional brain metabolism of the two illnesses.
    10/2013; 214(3). DOI:10.1016/j.pscychresns.2013.08.011
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