Dataset Information

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

ABSTRACT: Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified clusters.Cluster analysis was used to identify cognitive clusters in BD (N = 60). UAS (N = 49) were classified into groups according to their proband sibling's cluster assignment; comparisons were made across all clusters and healthy controls (HCs; N = 71).Three cognitive clusters in BD emerged: a globally impaired (36.7%), a selectively impaired (30%), and a cognitively intact cluster (33.3%). UAS showed a qualitatively similar pattern to their BD siblings; UAS of the globally impaired BD cluster showed verbal memory and general cognitive impairments relative to HCs. In contrast, UAS of the other two clusters did not differ from HCs.This study corroborates findings from prior work regarding the presence of cognitive heterogeneity in BD. UAS of subjects in the globally impaired BD cluster presented with a qualitatively similar cognitive profile to their siblings and performed worse than all other BD clusters and UAS groups. This suggests that inherited risk factors may be contributing to cognitive deficits more notably in one subgroup of patients with BD, pointing toward differential causes of cognitive deficits in discrete subgroups of patients with the disorder.

SUBMITTER: Russo M

PROVIDER: S-EPMC5856455 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

Russo M M Van Rheenen T E TE Shanahan M M Mahon K K Perez-Rodriguez M M MM Cuesta-Diaz A A Larsen E E Malhotra A K AK Burdick K E KE

Psychological medicine 20170607 16

<h4>Background</h4>Our previous work revealed substantial heterogeneity in the cognitive profile of bipolar disorder (BD) due to the presence of three underlying cognitive subgroups characterized as: globally impaired, selectively impaired, or cognitively intact. In an effort to determine whether these subgroups are differentially related to genetic risk for the illness, we investigated whether cognitive deficits were more pronounced in unaffected siblings (UAS) of BD probands within identified ...[more]

PMID: 28587689

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Project description:BackgroundLittle is known about the pathogenesis of Bipolar Disorder, and even less is known about the genetic differences between its subtypes. Bipolar Disorder is classified into different subtypes, which present different symptoms and lifetime courses. While genetic studies have been conducted in Bipolar Disorder, most examined the gene expression of only Bipolar Disorder Type 1. Studies that include Bipolar Disorder Type 1 and Bipolar Disorder Type 2 often fail to differentiate them into separate conditions. Few large transcriptomic meta-analyses in Bipolar Disorder have been conducted to identify genetic pathways. Thus, using publicly available data sets we aim here to uncover significant differential gene expression that allows distinguishing Type 1 and Type 2 Bipolar Disorders, as well as find patterns in Bipolar Disorder as a whole.MethodsWe analyze 17 different gene expression data sets from different tissue in Bipolar Disorder using GEO2R and manual analysis, of which 15 contained significant differential gene expression results. We use STRING and Cytoscape to examine Gene Ontology to find significantly affected genetic pathways. We identify hub genes using cytoHubba, a plugin in Cytoscape. We find genes common to data sets of the same material or subtype.Results12 out of 15 data sets are enriched for immune system and RNA related pathways. 9 out of 15 data sets are enriched for neurocognitive and metal ion related GO terms. Analysis of Bipolar Disorder Type 1 vs Bipolar Disorder Type 2 revealed most differentially expressed genes were related to immune function, especially cytokines. Terms related to synaptic signaling and neurotransmitter secretion were found in down-regulated GO terms while terms related to neuron apoptosis and death were up-regulated. We identify the gene SNCA as a potential biomarker for overall Bipolar Disorder diagnosis due to its prevalence in our data sets.ConclusionsThe immune system and RNA related pathways are significantly enriched across the Bipolar Disorder data sets. The role of these pathways is likely more critically important to the function of Bipolar Disorder than currently understood. Further studies should clearly label the subtype of Bipolar Disorder used in their research and more effort needs to be undertaken to collect samples from Cyclothymic Disorder and Bipolar Disorder Type 2.

Dataset Information

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

Publications

Neurocognitive subtypes in patients with bipolar disorder and their unaffected siblings.

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