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Genes Encoding GABA-? and HT1D Receptors in Bipolar I (Manic Phase) Patients.

ABSTRACT: Introduction:According to the cumulative evidence, genes encoding GABA receptors inhibit neurotransmitters in CNS and are intricately involved in the pathogenesis of mood disorders. Based on this hypothesis, these genes may be expressed in bipolar patients. As a result, we evaluated the gene expressions of GABA-?3 and HT1D receptors to assess their associations with bipolar mood disorder. Methods:In this study, 22 patients with bipolar I disorder (single manic episode) and 22 healthy individuals were enrolled. All participants were older than 15 years and had referred to Farshchian Hospital, Hamadan, Iran. They were diagnosed based on DSM IV-TR criteria and young mania rating scale in order to determine the severity of mania by a psychiatrist as bipolar Type 1 disorder in manic episode. We evaluated the expression of GABA-?3 and HT1D receptor genes in peripheral blood mononuclear cells, using real-time RT-PCR analysis. Results:In our study, a reduction in the gene expression of GABA-?3 and HT1D receptors was observed in peripheral blood mononuclear cells of the patients with bipolar disorders compared to the healthy controls. Conclusion:The results of this study supports the hypothesis that the gene expression for serotonin and GABA receptors can be employed in elucidating the pathogenesis of bipolar disorders.

SUBMITTER: Moradi M

PROVIDER: S-EPMC6026092 | biostudies-literature | 2018 Mar-Apr

REPOSITORIES: biostudies-literature

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Genes Encoding GABA-β and HT1D Receptors in Bipolar I (Manic Phase) Patients.

Moradi Mohammadreza M Saidijam Massoud M Yadegarazari Reza R Jahangard Leila L Seifi Maryam M Matinnia Nasrin N Ghaleiha Ali A

Basic and clinical neuroscience 20180301 2

<h4>Introduction</h4>According to the cumulative evidence, genes encoding GABA receptors inhibit neurotransmitters in CNS and are intricately involved in the pathogenesis of mood disorders. Based on this hypothesis, these genes may be expressed in bipolar patients. As a result, we evaluated the gene expressions of GABA-β3 and HT1D receptors to assess their associations with bipolar mood disorder.<h4>Methods</h4>In this study, 22 patients with bipolar I disorder (single manic episode) and 22 heal ...[more]

PMID: 29967672

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Project description:IntroductionBipolar disorder is characterized by severe mood symptoms including major depressive and manic episodes. During manic episodes, many patients show cognitive dysfunction. Dopamine and glutamate are important for cognitive processing, thus the COMT and DAOA genes that modulate the expression of these neurotransmitters are of interest for studies of cognitive function.MethodologyFocusing on the most severe episode of mania, a factor was found with the combined symptoms of talkativeness, distractibility, and thought disorder, considered a cognitive manic symptoms (CMS) factor. 488 patients were genotyped, out of which 373 (76%) had talkativeness, 269 (55%) distractibility, and 372 (76%) thought disorder. 215 (44%) patients were positive for all three symptoms, thus showing CMS (Table 1). As population controls, 1,044 anonymous blood donors (ABD) were used. Case-case and case-control design models were used to investigate genetic associations between cognitive manic symptoms in bipolar 1 disorder and SNPs in the COMT and DAOA genes. [Table: see text].ResultsThe finding of this study was that cognitive manic symptoms in patients with bipolar 1 disorder was associated with genetic variants in the DAOA and COMT genes. Nominal association for DAOA SNPs and COMT SNPs to cognitive symptoms factor in bipolar 1 disorder was found in both allelic (Table 2) and haplotypic (Table 3) analyses. Genotypic association analyses also supported our findings. However, only one association, when CMS patients were compared to ABD controls, survived correction for multiple testing by max (T) permutation. Data also suggested interaction between SNPs rs2391191 in DAOA and rs5993883 in COMT in the case-control model. [Table: see text] [Table: see text].ConclusionIdentifying genes associated with cognitive functioning has clinical implications for assessment of prognosis and progression. Our finding are consistent with other studies showing genetic associations between the COMT and DAOA genes and impaired cognition both in psychiatric disorders and in the general population.

Project description:BackgroundBipolar disorder is a mental illness in which manic and depressive states are repeated, causing psychosocial dysfunction. Manic/hypomanic episodes cause problems with interpersonal, social and financial activities, but there is limited evidence regarding the predictors of manic/hypomanic episodes in real-world clinical practice.MethodsThe multicenter treatment survey on bipolar disorder (MUSUBI) in Japanese psychiatric clinics was administered in an observational study that was conducted to accumulate evidence regarding bipolar disorder in real-world clinical practice. Psychiatrists were asked to complete a questionnaire about patients with bipolar disorder who visited 176 member clinics of the Japanese Association of Neuro-Psychiatric Clinics by conducting a retrospective medical record survey. Our study extracted baseline patient characteristics from September to October 2016, including comorbidities, mental status, duration of treatment, Global Assessment of Functioning (GAF) score, and pharmacological treatment details. We investigated the presence or absence of manic/hypomanic episodes over the course of one year from baseline to September-October 2017.ResultsIn total, 2231 participants were included in our study, 29.1% of whom had manic/hypomanic episodes over the course of one year from baseline. Binomial logistic regression analysis revealed that the presence of manic/hypomanic episodes was correlated with lower baseline GAF scores, rapid cycling, personality disorder, bipolar I disorder, and a mood state with manic or mixed features. Substance abuse was also a risk factor for manic episodes. There was no significant association between a baseline antidepressant prescription and manic/hypomanic episodes.ConclusionsIn Japan, 29.1% of outpatients with bipolar disorder had manic/hypomanic episodes over the course of one year. Our study suggested that a low GAF score, rapid cycling, personality disorder, bipolar I disorder, substance abuse, and baseline mood state could be predictors of manic/hypomanic episodes. Based on our findings, an antidepressant prescription is not a predictor of manic/hypomanic episodes.

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Genes Encoding GABA-? and HT1D Receptors in Bipolar I (Manic Phase) Patients.

Publications

Genes Encoding GABA-β and HT1D Receptors in Bipolar I (Manic Phase) Patients.

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