Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Birner, A.
Associations of Brain Structural Characteristics with Clinical Parameters in Bipolar Disorder with Special Emphasis on Sex and Obesity
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Graz Medical University; 2018. pp.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Enzinger Christian
- Kapfhammer Hans-Peter
- Reininghaus Eva
- Altmetrics:
- Abstract:
- Background/Aims The majority of neuroimaging studies in bipolar affective disorder (BD) to date largely ignore the influence of sex and health issues, such as obesity, on the brain morphology of affected individuals. Hence, the current thesis tests the following hypotheses in 124 adults with BD and 86 healthy controls (HC): (I) BD individuals exhibit an increased load of white matter hyperintensities (WMH) (Ia) as well as gray matter volume reduction in brain areas affected in BD (Ib), such as the anterior limbic striatal networks (ALSN), when compared to HC and between sexes; (II), these morphological changes of white matter (IIa) and gray matter (IIb) will be related to life style related factors such as body weight (i.e. being overweight or obese); (III) WMH-load (IIIa) and gray matter volume of the ALSN (IIIb) will correlate with clinical parameters (i.e. the number of disease episodes) and type of medication. Methods By applying a cross-sectional study design, 124 adult BD and 86 adult HC underwent 3T-MRI scans of the brain and clinical assessment. WMH were delineated using in-house developed software. Anatomical segmentation was performed by combined region growing and local thresholding following manual selection by a single instructed rater. Gray matter volume of the ALSN was calculated following cortical reconstruction and volumetric segmentation performed in Freesurfer version 5.3. All brain volumes were normalized to the individual total intracranial volume. ANCOVAs or correlation analyses were performed for hypothesis testing controlling for confounding factors like age. Results (Ia): Individuals with BD had a significantly higher value (F=3.968, p<0.05) of WMH (Mdn=3710mm3; IQR=2961mm3) than HC (Mdn=2185mm3; IQR=1665mm3); BD men (Mdn=4095mm3; IQR=3295mm3) and BD women (Mdn=3032mm3; IQR=2816mm3) did not significantly differ in their WMH-load; (IIa) There was no association of WMH with lifestyle related factors was found; (IIIa) In men only, the number of manic or hypomanic episodes (r=0.75; p<0.001) as well as depressive episodes (r=0.51; p<0.001) correlated positively with WMH-load; (Ib) BD individuals had significantly reduced normalized gray volume of the ALSN compared to HC (F=5.935, p=.016, Eta=.028); men also had reduced normalized gray volume of the ALSN compared to women (F=4.594, p=.033, Eta=.022); (IIb) After including Body Mass Index (BMI) and smoking into the same ANCOVA, the significant group differences disappeared, while BMI was found to be a significant confounding factor (F=5.666, p=.018, Eta=.010). (IIIa) BD individuals taking atypical antipsychotics had significantly reduced normalized gray volume of the ALSN compared to BD not taking atypical antipsychotics (F=12.034, p=.001, Eta=.105). Conclusions: WMH-load was significantly associated with the number of manic episodes in male BD patients, suggesting that men are more vulnerable to develop manic symptoms in the presence of cerebral white matter changes. The finding of reduced ALSN volumes indicates the importance of including proxies of obesity and/or the metabolic syndrome (e.g. BMI, body fat content, or waist circumference) as well sex as moderating variables when analyzing morphological brain imaging data in BD. Moreover, BD individuals treated with atypical antipsychotic medication showed significantly reduced ALSN volumes compared to individuals with BD not being treated with atypical antipsychotics at the time of the study.