Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gene expression analyses of postmortem cerebral cortex suggest that transcription of the regulator of G-protein signaling 4 (RGS4) is decreased in a diagnosis-specific manner in subjects with schizophrenia. To evaluate the possible role of RGS4 in the pathogenesis of schizophrenia, we conducted genetic association and linkage studies using samples ascertained independently in Pittsburgh and New Delhi and by the NIMH Collaborative Genetics Initiative. Using the transmission disequilibrium test, significant transmission distortion was observed in the Pittsburgh and NIMH samples. Among single-nucleotide polymorphisms (SNPs) spanning approximately 300 kb, significant associations involved four SNPs localized to a 10 kb region at RGS4, but the associated haplotypes differed. A trend for transmission distortion was also present in the Indian sample for haplotypes incorporating the same SNPs. Consistent with the linkage/association observed from the family-based tests, samples with affected siblings (NIMH, India) showed higher levels of allele sharing, identical by descent, at RGS4. When the US patients were contrasted to two population-based control samples, however, no significant differences were observed. To check the specificity of the transmission bias, we therefore examined US families with bipolar I disorder (BD1) probands. This sample also showed a trend for transmission distortion, and differed significantly from the population-based controls for the four-SNP haplotypes tested in the other samples. The transmission distortion is unlikely to be due to chance, but its mechanism and specificity require further study. Our results illustrate the potential power of combining gene expression profiling and genomic analyses to identify susceptibility genes for genetically complex disorders.
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PMID:Association and linkage analyses of RGS4 polymorphisms in schizophrenia. 1202 79

Linkage and association studies in five independently ascertained samples have suggested that polymorphisms of the regulator of G-protein signaling 4 (RGS4) may confer risk for schizophrenia (SCZ). Suggestive evidence for association with bipolar disorder (BD) has also been presented. However, the associated alleles and haplotypes have differed among the samples. Data from other independent samples may clarify the putative associations. Hence, we investigated an independent, ethnically diverse Brazilian population comprising patients with SCZ (n=271) or BD1 (n=306), who were contrasted with 576 community-based controls. Parents of 49 SCZ cases and 44 BD cases were available for transmission disequilibrium tests (TDTs). Four RGS4 single-nucleotide polymorphisms (SNPs) 1, 4, 7 and 18 putatively associated with SCZ were investigated. In the SCZ samples, significant case-control differences were not observed for individual SNPs or haplotypes, though the TDT suggested transmission distortion similar to that observed in the initial report. For the BD sample, case-control comparisons revealed no significant differences for individual SNPs, but an omnibus test suggested differences in the overall distribution of haplotypes bearing all four SNPs (SNP-EM Omnibus likelihood ratio test; P=0.003). The TDT revealed over-transmission of allele A at SNP7 (P=0.016), as well as haplotypes incorporating this allele. However, global tests incorporating all haplotypes yielded only suggestive trends for association (P=0.19). In conclusion, association with SCZ was not detected in the present analyses. The failure to detect an association may be related to inadequate power or to confounds related to ethnic admixture. Suggestive associations with BD detected here require further investigation in a larger sample.
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PMID:Association and linkage analysis of RGS4 polymorphisms with schizophrenia and bipolar disorder in Brazil. 1566 Jun 67

Abnormalities in circadian rhythms are prominent features of bipolar I disorder (BD1). To investigate circadian variation in BD1, we evaluated morningness-eveningness (M/E), a stable trait reflecting circadian phase, using the composite scale (CS) among BD1 patients (DSM IV criteria; n = 75), unscreened controls (n = 349), and patients with schizophrenia (SZ) or schizoaffective disorder (SZA) (n = 81). Our analyses showed that CS scores correlated significantly with age but did not differ by gender among the controls. BD1 patients differed significantly from controls and from SZ/SZA patients when age was considered. CS scores were distributed bi-modally among BD1 cases. There are several possible reasons for the observed heterogeneity. Younger BD1 patients, and those with rapid mood swings, were significantly more likely to have lower CS scores (i.e., to score in the 'evening' range and to have later circadian phase). CS scores were also positively correlated with the age at onset and the duration of the most severe depressive episodes. These relationships were not observed among the SZ/SZA groups. Thus, distinct patterns of M/E were noted among BD1 patients and among BD1 subgroups. The impact of medication, mood state, and chronicity on CS scores needs to be considered.
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PMID:Circadian phase variation in bipolar I disorder. 1607 55

We hypothesize that circadian dysfunction could underlie, at least partially, the liability for bipolar 1 disorder (BD1). Our hypothesis motivated tests for the association between the polymorphisms of genes that mediate circadian function and liability for BD1. The US Caucasian patients with BD1 (DSM-IV criteria) and available parents were recruited from Pittsburgh and surrounding areas (n = 138 cases, 196 parents) and also selected from the NIMH Genetics Collaborative Initiative (n = 96 cases, 192 parents). We assayed 44 informative single-nucleotide polymorphisms (SNPs) from eight circadian genes in the BD1 samples. A population-based sample, specifically cord blood samples from local live births, served as community-based controls (n = 180). It was used as a contrast for genotype and haplotype distributions with those of patients. US patients with schizophrenia/schizoaffective disorder (SZ/SZA, n = 331) and available parents from Pittsburgh (n = 344) were assayed for a smaller set of SNPs based on the results from the BD1 samples. Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples. The associations were detected using family-based and case-control analyses, albeit with different SNPs. Associations with TIMELESS and PERIOD3 were also detected in the Pittsburgh SZ/SZA group. Thus far, evidence for association between specific SNPs at the circadian gene loci and BD1 is tentative. Additional studies using larger samples are required to evaluate the associations reported here.
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PMID:Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. 1650 6

Lifetime prevalence of child and adolescent bipolar 1 disorder (BD1) is nearly 0.1 %. Even though it is not a frequent disorder in young people, there is an increased interest for this disorder at this age, because of the poor outcome, the severe functional impairments and the major risk of suicide. Diagnosis is complex in view of the more frequent comorbidities, the variability with an age-dependant clinical presentation, and the overlap in symptom presentation with other psychiatric disorders (e.g. disruptive disorders in prepubertal the child and schizophrenia in the adolescent). The presentation in adolescents is very similar to that in adults and in prepubertal children chronic persistent irritability and rapid mood oscillation are often at the foreground. For a while, such presentations were considered as BD-not otherwise specified (BD-NOS), which can explain the outburst of the prevalence of bipolar disorder in children in the US. Longitudinal studies that look for the outcome of such emotional dysregulations have not revealed an affiliation with bipolar disorder spectrum, but with depressive disorders in adulthood. The diagnosis of Disruptive Mood Dysregulation Disorder was proposed in the DSM-5 to identify these children and to prevent confusion with bipolar disorder. The goals of the pharmacological and psychosocial treatments are to control or ameliorate the symptoms, to avoid new episodes or recurrences, to improve psychosocial functioning and well-being, and to prevent suicide. In the US, lithium and four atypical antipsychotics have been approved by the FDA for 10 to 13-year-olds (risperidone, olanzapine, aripiprazole and quetiapine). In France, only lithium salts (after the age of 16) and aripiprazole (after the age of 13) are recommended. Psychosocial treatments, such as a familial or individual approach are developing.
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PMID:[Management of bipolar 1 disorder in children and adolescents]. 2465 84

There is ample evidence that the acute stress response is altered in schizophrenia and bipolar disorder. However, it is not clear whether such changes are related to the illness, a genetic vulnerability, or is the result of medication that is used in the majority of these patients. Therefore, we investigated determinants of the acute endocrine and autonomic stress response in healthy controls (n=48), euthymic BD1 patients (n=49) and unaffected siblings of BD1 patients (n=27). All participants completed a validated psychosocial stress task, the Trier Social Stress Test for Groups (TSST-G). Saliva levels of alpha-amylase and cortisol were measured before, during, and after exposure to stress. Compared to controls, we found a significantly blunted cortisol stress response in BD1 patients. Conversely, BD1 patients displayed exaggerated alpha-amylase levels in response to stress. Antipsychotic use was a significant contributing factor to the blunted cortisol stress response in BD1 patients. Unaffected BD1 siblings displayed similar stress-induced cortisol and alpha-amylase levels as controls, suggesting that familial risk for BD1 did not have a large effect on the functionality of the stress system. In conclusion, this study shows that euthymic BD1 patients have a substantially blunted endocrine stress response but an exaggerated autonomic stress response and that the endocrine stress response differences can be largely contributed to antipsychotic use rather than constitute a specific BD1 phenotype or vulnerability.
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PMID:Antipsychotic use is associated with a blunted cortisol stress response: a study in euthymic bipolar disorder patients and their unaffected siblings. 2545 85

Prodromal symptoms of bipolar disorder (BD) and early onset schizophrenia spectrum disorder (EOSSD) overlap. To date, there has been no study directly comparing the prodromal stage of both disorders. Thus, the current study is aimed at determining which prodromal symptom clusters differentiate BD and EOSSD. One hundred twenty one adolescents (33 BD-1, 30 EOSSD, 58 healthy controls) were evaluated for the presence of 79 prodromal symptoms, divided into 7 prodromal symptom clusters. Great than 2 subsyndromal manic symptoms and ADHD comorbidity were significantly more specific for BD than schizophrenia; brief limited intermittent psychotic symptoms (BLIPS) were more likely to be part of EOSSD. In contrast, attenuated psychotic symptoms, and negative symptoms were not specifically related to the diagnosis of EOSSD. In conclusion, subsyndromal manic symptoms, BLIPS, and ADHD might be useful for predicting the trajectory of an emerging affective disorder versus schizophrenia and thus valuable for early detection, and intervention strategies.
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PMID:Distinguishing prodromal stage of bipolar disorder and early onset schizophrenia spectrum disorders during adolescence. 3095 77