As lithium has been shown to have a protective effect against suicidal behavior, genes on which mood stabilizers act may be involved in biological susceptibility to suicide. A recent study showed that endoplasmic reticulum (ER) stress response was impaired in the bipolar disorders and the impairment was ameliorated by a mood stabilizer, valproate. We hypothesized that an alteration of ER stress response is involved in the biological susceptibility to suicide through genetic polymorphisms, and examined the association of polymorphisms of X-box binding protein 1 (XBP1) and heat shock 70-kDa protein 5 (HSPA5) genes with suicide. We found no significant difference in the distribution of these polymorphisms between the suicide victims and the controls. These results suggest that the polymorphisms examined in this study are not involved in the susceptibility to suicide of the Japanese. Language: en
Altered endoplasmic reticulum stress (ER) response signaling is suggested in bipolar disorder. Previously, we preliminarily reported the genetic association of HSPA5 (GRP78/BiP) with bipolar disorder. Here, we extended our analysis by increasing the number of Japanese case-control samples and NIMH Genetics Initiative bipolar trio samples (NIMH trios), and also analyzed schizophrenia samples. In Japanese, nominally significant association of one haplotype was observed in extended samples of bipol...
We analyzed nine multigenerational families with ascertained affective spectrum disorders in northern Sweden's geographically isolated population of Vasterbotten. This northern Swedish population, which originated from a limited number of early settlers ∼8,000 years ago, is genetically more homogeneous than outbred populations. In a genomewide linkage analysis, we identified three chromosomal loci with multipoint LOD scores (MPLOD) ⩾2 at 9q31.1-q34.1 (MPLOD 3.24), 6q22.2-q24.2 (MPLOD 2.48), and ...
Abstract Schizophrenia and bipolar disorder share some clinical features and linkage studies have shown that several loci are common. Recently, the authors found that the −116CG substitution in the promotor region of XBP1, a pivotal gene in endoplasmic reticulum (ER) stress response, causes the impairment of ER stress response, and that the −116C/C genotype is a protective factor; in other words the presence of the G allele increases the risk for bipolar disorder. The gene is located on 22q12.1,...
#1Wuyan Chen(CAS: Chinese Academy of Sciences)H-Index: 12
#2Shiwei Duan(CAS: Chinese Academy of Sciences)H-Index: 38
Last. Lin He(CAS: Chinese Academy of Sciences)H-Index: 50
view all 8 authors...
Abstract Schizophrenia and bipolar disorder are two major psychiatric illnesses that may share specific genetic risk factors to a certain extent. Increasing evidence suggests that the two disorders might be more closely related than previously considered. In order to test this hypothesis, we investigated a functional polymorphism −197C/G in XBP1 , which was reported to increase the risk of bipolar disorder, in a case–control study (374 cases vs. 371 controls) to evaluate its genetic role in the ...
Genes encoding proteins involved in serotonergic metabolism are major candidates in association studies of suicidal behavior. The tryptophan hydroxylase (TPH) gene, which codes for the rate-limiting enzyme of serotonin biosynthesis, is a major candidate gene and has been extensively studied in association studies of suicidal behavior, providing conflicting results. It is difficult to interpret these conflicting results due to lack of power, ethnic heterogeneity, and variations in the sampling st...
The pathophysiology of bipolar disorder is still unclear, although family, twin and linkage studies implicate genetic factors 1 . Here we identified XBP1, a pivotal gene in the endoplasmic reticulum (ER) stress response, as contributing to the genetic risk factor for bipolar disorder. Using DNA microarray analysis of lymphoblastoid cells derived from two pairs of twins discordant with respect to the illness, we found downregulated expression of genes related to ER stress response in both affecte...
BACKGROUND: Evidence that therapeutic benefits of psychiatric treatments include reduction of suicide risk is remarkably limited and poorly studied. An exception is growing evidence for such suicidal risk reduction with long-term lithium maintenance. This report updates and extends analyses of lithium treatment and suicides and attempts. METHOD: We pooled data from studies providing data on suicidal acts, patients at risk, and average exposure times with or without lithium maintenance therapy, a...
Abstract ATF6 is an endoplasmic reticulum (ER) stress-regulated transmembrane transcription factor that activates the transcription of ER molecular chaperones. Upon ER stress, ATF6 translocates from the ER to the Golgi where it is processed to its active form. We have found that the ER chaperone BiP/GRP78 binds ATF6 and dissociates in response to ER stress. Loss of BiP binding correlates with the translocation of ATF6 to the Golgi, which was slowed in cells overexpressing BiP. Two Golgi localiza...
Abstract Disruption of oxidant/anti-oxidant ratio as well as endoplasmic reticulum (ER) stress are thought to be involved in the pathophysiology of schizophrenia. These stresses can lead to impairments in brain functions progressively leading to neuronal inflammation followed by neuronal cell death. Moreover, the cellular stresses are interlinked leading us to the conclusion that protein misfolding, oxidative stress and apoptosis are intricately intertwined events requiring further research into...
Social interaction and communication are complex behavioral paradigms involving many components. Many different neurotransmitters, hormones, sensory inputs, and brain regions are involved in the act of social engagement and verbal or nonverbal communication. Autism spectrum disorder (ASD) and schizophrenia are two neurodevelopmental disorders that have social and language deficits as hallmark symptoms but show very different etiologies. The output of social dysfunction is common to both ASD and ...
The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, sepa...
