Dataset Information

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

ABSTRACT: Background:A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide. Methods:We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (N = 219). We analyzed these variants for a possible association with the suicide severity score (ranging from suicidal ideation/plan to serious suicide attempt) from the Schedule for Clinical Assessment in Neuropsychiatry. We conducted tests of individual variants and gene-based tests. Results:We found a number of DNA variants in the transforming growth factor beta receptor 1 gene (TGFBR1) to be suggestively associated with suicide severity scores (p < 0.005). The gene-based tests also pointed to TGFBR1 to be associated with suicide severity (p = 0.0001). However, these findings were not replicated in an independent bipolar disorder sample. Conclusions:We report no significant association between DNA sequences of drug target genes and suicidal behavior. Additional larger sequencing studies could further interrogate associations between variants in drug target genes and suicidal behavior.

SUBMITTER: Zai CC

PROVIDER: S-EPMC6032032 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

Zai Clement C CC Tiwari Arun K AK Zai Gwyneth C GC de Luca Vincenzo V Shaikh Sajid A SA King Nicole N Strauss John J Kennedy James L JL Vincent John B JB

Molecular neuropsychiatry 20180503 1

<h4>Background</h4>A number of genes have been implicated in recent genome-wide association studies of suicide attempt in bipolar disorder. More focused investigation of genes coding for protein targets of existing drugs may lead to drug repurposing for the treatment and/or prevention of suicide.<h4>Methods</h4>We analyzed 2,457 DNA variants across 197 genes of interest to GlaxoSmithKline across the pipeline in our sample of European patients suffering from bipolar disorder (<i>N</i> = 219). We ...[more]

PMID: 29998113

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Project description:ImportanceMajor depressive disorder (MDD) is an important risk factor of suicidal behavior, but the added burden of suicidal behavior and MDD on the patient and societal level, including all-cause mortality, is not well studied. Also, the contribution of various prognostic factors for suicidal behavior has not been quantified in larger samples.ObjectiveTo describe the clinical and societal outcomes, including all-cause mortality, of suicidal behavior in patients with MDD and to explore associated risk factors and clinical management to inform future research and guidelines.Design, setting, and participantsThis population-based cohort study used health care data from the Stockholm MDD Cohort. Patients aged 18 years or older with episodes of MDD diagnosed between January 1, 2012, and December 31, 2017, in any health care setting were included. The dates of the data analysis were February 1 to November 1, 2022.ExposuresPatients with MDD with and without records of suicidal behavior.Main outcomes and measuresThe main outcome was all-cause mortality. Secondary outcomes were comorbid conditions, medications, health care resource utilization (HCRU), and work loss. Using Region Stockholm registry variables, a risk score for factors associated with suicidal behavior within 1 year after the start of an MDD episode was calculated.ResultsA total of 158 169 unipolar MDD episodes were identified in 145 577 patients; 2240 (1.4%) of these episodes, in 2219 patients, included records of suicidal behavior (mean [SD] patient age, 40.9 [18.6] years; 1415 episodes [63.2%] in women and 825 [36.8%] in men). A total of 11 109 MDD episodes in 9574 matched patients with MDD without records of suicidal behavior were included as controls (mean [SD] patient age, 40.8 [18.5] years; 7046 episodes [63.4%] in women and 4063 [36.6%] in men). The all-cause mortality rate was 2.5 per 100 person-years at risk for the MDD-SB group and 1.0 per 100 person-years at risk for the MDD-non-SB group, based on 466 deaths. Suicidal behavior was associated with higher all-cause mortality (hazard ratio, 2.62 [95% CI, 2.15-3.20]), as well as with HCRU and work loss, compared with the matched controls. Patients with MDD and suicidal behavior were younger and more prone to have psychiatric comorbid conditions, such as personality disorders, substance use, and anxiety, at the start of their episode. The most important factors associated with suicidal behavior within 1 year after the start of an MDD episode were history of suicidal behavior and age, history of substance use and sleep disorders, and care setting in which MDD was diagnosed.Conclusions and relevanceThis cohort study's findings suggest that high mortality, morbidity, HCRU, and work loss associated with MDD may be substantially accentuated in patients with MDD and suicidal behavior. Use of medication aimed at decreasing the risk of all-cause mortality during MDD episodes should be systematically evaluated to improve long-term outcomes.

Project description:ObjectiveStudies on alterations in the regional neural activity in the brain of patients with bipolar disorder (BD) have provided conflicting results because of different medications used and study designs. A low bone mineral density (BMD) is also observed in patients with BD. This study aimed to further explore regional neural activities in unmedicated patients with BD and their association with BMD.MethodsIn this study, 40 patients with BD and 42 healthy controls were scanned through resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with regional homogeneity (ReHo) and pattern classification. Pearson's correlation analyses were performed to explore the correlations between abnormal ReHo and BMD.ResultsA significant increase in ReHo values in the left inferior frontal gyrus (IFG)/temporal pole, left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem, and right superior temporal gyrus (STG) and a decrease in ReHo in the occipital gyrus (OG; left middle OG/superior OG/bilateral cuneus) were found in the patients with BD (p < 0.05) compared with those in the healthy controls. No significant correlation was observed between the abnormal ReHo values in any of the brain regions of the patients with BMD.Support vector machine (SVM) analyses revealed that the ReHo values in the right STG for distinguishing patients from healthy controls showed an accuracy of 91.89%, a sensitivity of 75.68%, and a specificity of 83.78%. The ReHo values in the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem indicated an accuracy of 78.38%, a sensitivity of 75.68%, and a specificity of 81.08%.ConclusionThis study further confirms the abnormal brain activities in extensive regions, and these brain regions are primarily located in the fronto-temporal-occipital circuit and the cerebellum vermis of patients with BD. The regional neural activity in the right STG and the left cerebellum vermis I/vermis II/parahippocampal gyrus/brainstem may serve as potential imaging markers to distinguish patients with BD from healthy controls.

Dataset Information

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

Publications

Sequence Analysis of Drug Target Genes with Suicidal Behavior in Bipolar Disorder Patients.

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