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Modeling association between times to recurrence of the different polarities in bipolar disorder among service seekers in urban Nigeria: a survival analysis approach.

ABSTRACT: Bipolar disorder (BD) remains both a clinical and public health challenge worldwide, especially in developing countries such as Nigeria. Many studies have focused on prevalence and recurrences among BD service seekers but little has been documented on the nature, strength, direction, existence, and estimation of association between times to recurrence of the two possible polarities or mood episodes in BD. In this study, we explored the association between durations before recurrence of depression and manic episodes among people seeking treatment for BD.This analytical study used retrospective data of 467 persons who sought treatment for BD at the psychiatric clinic of University College Hospital, Ibadan, Nigeria between 2005 and 2014. Descriptive statistics were used to explore the data. We right-censored the data and obtained Kaplan-Meier estimates of the time to recurrence of the outcomes and transformed the estimates to standardized binormal data using quantile-quantile transformation. The likelihood was maximized to obtain the maximum likelihood estimate of the association parameter at 5% significance level.The mean (± standard deviation) age of the respondents was 32.9±12.9 years, this was lower among service seekers who were initially diagnosed with mania than among those initially diagnosed with depression (31.3±11.6, 33.2±11.9, respectively). The median survival time to recurrence of mania and depression among the patients was 1,120 and 745 days, respectively, whereas association between times to recurrence of mania and depression was maximized at 0.67 (95% confidence interval: 0.62-0.71).There exists a strong and positive association between times to recurrence of depression and mania in BD. The longer the time to recurrence of mania, the longer the time to recurrence of depression and vice versa.

SUBMITTER: Fagbamigbe AF

PROVIDER: S-EPMC5533472 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:Comorbidity of psychiatric and substance use disorders represents a significant complication in the clinical course of both disorders. Bipolar Disorder (BD) is a psychiatric disorder characterized by severe mood swings, ranging from mania to depression, and up to a 70% rate of comorbid Tobacco Use Disorder (TUD). We found epidemiological evidence consistent with a common underlying etiology for BD and TUD, as well as evidence of both genetic and environmental influences on BD and TUD. Therefore, we hypothesized a common underlying genetic etiology, interacting with nicotine exposure, influencing susceptibility to both BD and TUD.Using meta-analysis, we compared TUD rates for BD patients and the general population. We identified candidate genes showing statistically significant, replicated, evidence of association with both BD and TUD. We assessed commonality among these candidate genes and hypothesized broader, multi-gene network influences on the comorbidity. Using Fisher Exact tests we tested our hypothesized genetic networks for association with the comorbidity, then compared the inferences drawn with those derived from the commonality assessment. Finally, we prioritized candidate SNPs for validation.We estimate risk for TUD among BD patients at 2.4 times that of the general population. We found three candidate genes associated with both BD and TUD (COMT, SLC6A3, and SLC6A4) and commonality analysis suggests that these genes interact in predisposing psychiatric and substance use disorders. We identified a 69 gene network that influences neurotransmitter signaling and shows significant over-representation of genes associated with BD and TUD, as well as genes differentially expressed with exposure to tobacco smoke. Twenty four of these genes are known drug targets.This work highlights novel bioinformatics resources and demonstrates the effectiveness of using an integrated bioinformatics approach to improve our understanding of complex disease etiology. We illustrate the development and testing of hypotheses for a comorbidity predisposed by both genetic and environmental influences. Consistent with our hypothesis, the selected network models multiple interacting genetic influences on comorbid BD with TUD, as well as the environmental influence of nicotine. This network nominates candidate genes for validation and drug testing, and we offer a panel of SNPs prioritized for follow-up.

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Modeling association between times to recurrence of the different polarities in bipolar disorder among service seekers in urban Nigeria: a survival analysis approach.

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