Dataset Information

Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder.

ABSTRACT: OBJECTIVES:Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cognitive aging. DESIGN:Cross-sectional study. SETTING:University of California San Diego and the Veterans Administration San Diego Healthcare System. PARTICIPANTS:33 euthymic BD and 38 HC participants. MEASUREMENTS:Diffusion tensor imaging was acquired as a measure of WM integrity, and tract-specific fractional anisotropy (FA) was extracted utilizing the Johns Hopkins University probability atlas. PS was assessed with the Number and Letter Sequencing conditions of the Delis-Kaplan Executive Function System Trail Making Test. RESULTS:BD participants demonstrated slower PS compared with the HC group, but no group differences were found in FA across tracts. Multiple linear regressions revealed a significant group-by-age interaction for the right uncinate fasciculus, the left hippocampal portion of the cingulum, and for PS, such that older age was associated with lower FA values and slower PS in the BD group only. The relationship between age and PS did not significantly change after accounting for uncinate FA, suggesting that the observed age associations occur independently. CONCLUSIONS:Results provide support for future study of the accelerated aging hypothesis by identifying markers of brain health that demonstrate a differential age association in BD.

SUBMITTER: Dev SI

PROVIDER: S-EPMC5479871 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder.

Dev Sheena I SI Nguyen Tanya T TT McKenna Benjamin S BS Sutherland Ashley N AN Bartsch Hauke H Theilmann Rebecca J RJ Eyler Lisa T LT

The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry 20170216 7

<h4>Objectives</h4>Bipolar disorder (BD) is associated with compromised white matter (WM) integrity and deficits in processing speed (PS). Few studies, however, have investigated age relationships with WM structure and cognition to understand possible changes in brain health over the lifespan. This investigation explored whether BD and healthy counterpart (HC) participants exhibited differential age-related associations with WM and cognition, which may be suggestive of accelerated brain and cogn ...[more]

PMID: 28342644

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Project description:Background. Schizophrenia (SZ) and bipolar disorder (BD) have both been associated with reduced microstructural white matter integrity using, as a proxy, fractional anisotropy (FA) detected using diffusion tensor imaging (DTI). Genetic susceptibility for both illnesses has also been positively correlated in recent genome-wide association studies with allele A (adenine) of single nucleotide polymorphism (SNP) rs1344706 of the ZNF804A gene. However, little is known about how the genomic linkage disequilibrium region tagged by this SNP impacts on the brain to increase risk for psychosis. This study aimed to assess the impact of this risk variant on FA in patients with SZ, in those with BD and in healthy controls. Methods. 230 individuals were genotyped for the rs1344706 SNP and underwent DTI. We used tract-based spatial statistics (TBSS) followed by an analysis of variance, with threshold-free cluster enhancement (TFCE), to assess underlying effects of genotype, diagnosis and their interaction, on FA. Results. As predicted, statistically significant reductions in FA across a widely distributed brain network (p < 0.05, TFCE-corrected) were positively associated both with a diagnosis of SZ or BD and with the double (homozygous) presence of the ZNF804A rs1344706 risk variant (A). The main effect of genotype was medium (d = 0.48 in a 44,054-voxel cluster) and the effect in the SZ group alone was large (d = 1.01 in a 51,260-voxel cluster), with no significant effects in BD or controls, in isolation. No areas under a significant diagnosis by genotype interaction were found. Discussion. We provide the first evidence in a predominantly Caucasian clinical sample, of an association between ZNF804A rs1344706 A-homozygosity and reduced FA, both irrespective of diagnosis and particularly in SZ (in overlapping brain areas). This suggests that the previously observed involvement of this genomic region in psychosis susceptibility, and in impaired functional connectivity, may be conferred through it inducing abnormalities in white matter microstructure.

Dataset Information

Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder.

Publications

Steeper Slope of Age-Related Changes in White Matter Microstructure and Processing Speed in Bipolar Disorder.

Similar Datasets

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