| 1 | J. Psychopharmacol. (Oxford) 2010 May 24: 677-82 |
|---|---|
| PMID | 18838498 |
| Title | Association of HPA axis genes with suicidal behaviour in schizophrenia. |
| Abstract | Family, adoption and twin studies show that genetics influences suicidal behaviour, but do not indicate specific susceptibility variants. Stress response is thought to be mediated by the corticotrophin-releasing hormone (CRH), which is known to be a regulator of the hypothalamic-pituitary-adrenal pathway (HPA). Alterations in HPA system have been related to impulsivity, aggression and suicidal behaviour, common feature in schizophrenia. CRH is the hypothalamic factor that stimulates the pituitary gland. To search for markers conferring genetic susceptibility to suicide, we typed six HPA axis genes (CRH, CRHR1, CRHR2, CRHBP, MC2R, NC3R1) in a cohort of 231 subjects with schizophrenia in which 81 attempted suicide. The genotype analyses yielded significant association between CRH binding protein (CRHBP) and suicide attempt (P = 0.035). The genotype analysis for quantitative measures of suicidal behaviour showed no association. The interaction analysis showed a significant interaction between CRH receptor type 1 (CRHR1) and CRH binding protein (CRHBP) in influencing suicide attempt and the severity of suicidal behaviour. Current results show that genetic variation in HPA axis genes could be associated with suicidal behaviour in schizophrenia. This is to our knowledge the first study on suicidal behaviour investigating the interaction among the HPA axis genes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Arch. Gen. Psychiatry 2011 Dec 68: 1247-56 |
| PMID | 21810631 |
| Title | Prediction of the risk of comorbid alcoholism in schizophrenia by interaction of common genetic variants in the corticotropin-releasing factor system. |
| Abstract | Stress plays a major role in the development of comorbid alcohol use disorder (AUD). In turn, AUD worsens the outcome of psychiatric patients with respect to global disease severity, social situation, and socioeconomic burden. Prediction of persons at risk for AUD is crucial for future preventive and therapeutic strategies. To investigate whether genetic variants of the corticotropin-releasing factor system or their interaction influence the risk of developing AUD in chronic disease populations. Genotype analysis comprising selected single-nucleotide polymorphisms within the CRHR1 and CRHBP genes in patients with schizophrenia and in a nonschizophrenic psychiatric disease control sample should allow the extraction of predictors of comorbid AUD. Gene expression (messenger RNA) analysis in peripheral blood mononuclear cells was performed to gain the first mechanistic insight. An ideal setup for this study was the Göttingen Research Association for schizophrenia Data Collection of schizophrenic patients, specifically intended to enable association of genetic information with quantifiable phenotypes in a phenotype-based genetic association study. Patients A total of 1037 schizophrenic patients (Göttingen Research Association for schizophrenia sample), 80 nonschizophrenic psychiatric disease controls as a small replicate sample, and a case-control study including 1141 healthy subjects. Association of CRHR1 and CRHBP genotypes with the following: (1) AUD; (2) a newly developed alcoholism severity score comprising 5 AUD-relevant variables; and (3) quantitative CRHR1 and CRHBP messenger RNA expression. An interaction of CRHR1 rs110402 and CRHBP rs3811939 predicts high risk of comorbid AUD in schizophrenic patients (odds ratio = 2.27; 95% confidence interval, 1.56-3.30; P < .001) as well as psychiatric disease controls (odds ratio = 4.02; 95% confidence interval, 0.95-17.05; P = .06) and leads to the highest CRHR1/CRHBP messenger RNA ratio (P = .02; dysbalanced stress axis). The high predictive value of a genetic interaction within the stress axis for the risk of comorbid AUD may be used for novel preventive and individualized therapeutic approaches. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Arch. Gen. Psychiatry 2011 Dec 68: 1247-56 |
| PMID | 21810631 |
| Title | Prediction of the risk of comorbid alcoholism in schizophrenia by interaction of common genetic variants in the corticotropin-releasing factor system. |
| Abstract | Stress plays a major role in the development of comorbid alcohol use disorder (AUD). In turn, AUD worsens the outcome of psychiatric patients with respect to global disease severity, social situation, and socioeconomic burden. Prediction of persons at risk for AUD is crucial for future preventive and therapeutic strategies. To investigate whether genetic variants of the corticotropin-releasing factor system or their interaction influence the risk of developing AUD in chronic disease populations. Genotype analysis comprising selected single-nucleotide polymorphisms within the CRHR1 and CRHBP genes in patients with schizophrenia and in a nonschizophrenic psychiatric disease control sample should allow the extraction of predictors of comorbid AUD. Gene expression (messenger RNA) analysis in peripheral blood mononuclear cells was performed to gain the first mechanistic insight. An ideal setup for this study was the Göttingen Research Association for schizophrenia Data Collection of schizophrenic patients, specifically intended to enable association of genetic information with quantifiable phenotypes in a phenotype-based genetic association study. Patients A total of 1037 schizophrenic patients (Göttingen Research Association for schizophrenia sample), 80 nonschizophrenic psychiatric disease controls as a small replicate sample, and a case-control study including 1141 healthy subjects. Association of CRHR1 and CRHBP genotypes with the following: (1) AUD; (2) a newly developed alcoholism severity score comprising 5 AUD-relevant variables; and (3) quantitative CRHR1 and CRHBP messenger RNA expression. An interaction of CRHR1 rs110402 and CRHBP rs3811939 predicts high risk of comorbid AUD in schizophrenic patients (odds ratio = 2.27; 95% confidence interval, 1.56-3.30; P < .001) as well as psychiatric disease controls (odds ratio = 4.02; 95% confidence interval, 0.95-17.05; P = .06) and leads to the highest CRHR1/CRHBP messenger RNA ratio (P = .02; dysbalanced stress axis). The high predictive value of a genetic interaction within the stress axis for the risk of comorbid AUD may be used for novel preventive and individualized therapeutic approaches. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | J. Alzheimers Dis. 2016 Feb 51: 417-25 |
| PMID | 26890750 |
| Title | Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory. |
| Abstract | Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases. |
| SCZ Keywords | schizophrenia, schizophrenic |