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Schizophrenia Bulletin 05/2013; · 8.80 Impact Factor
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American Journal of Respiratory and Critical Care Medicine 12/2012; 186(12):1307. · 11.08 Impact Factor
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ABSTRACT: Early growth response genes (EGR1, 2, 3, and 4) encode a family of nuclear proteins that function as transcriptional regulators. They are involved in the regulation of synaptic plasticity, learning, and memory, and are implicated in the pathogenesis of schizophrenia.
We conducted a genetic association analysis of 14 SNPs selected from the EGR1, 2, 3, and 4 genes of 564 patients with schizophrenia and 564 control subjects. We also conducted Western blot analysis and promoter activity assay to characterize the EGR genes associated with schizophrenia
We did not detect a true genetic association of these 14 SNPs with schizophrenia in this sample. However, we observed a nominal over-representation of C/C genotype of rs9990 of EGR2 in female schizophrenia as compared to female control subjects (p=0.012, uncorrected for multiple testing). Further study showed that the average mRNA level of the EGR2 gene in the lymphoblastoid cell lines of female schizophrenia patients was significantly higher than that in female control subjects (p=0.002). We also detected a nominal association of 4 SNPs (rs6747506, rs6718289, rs2229294, and rs3813226) of the EGR4 gene that form strong linkage disequilibrium with schizophrenia in males. Reporter gene assay showed that the haplotype T-A derived from rs6747506 and rs6718289 at the promoter region had significantly reduced promoter activity compared with the haplotype A-G.
Our data suggest a tendency of gender-specific association of EGR2 and EGR4 in schizophrenia, with an elevated expression of EGR2 in lympoblastoid cell lines of female schizophrenia patients and a reduced EGR4 gene expression in male schizophrenia patients.
Progress in Neuro-Psychopharmacology and Biological Psychiatry 06/2012; 39(1):149-55. · 3.25 Impact Factor
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ABSTRACT: Background: Both genetic and environmental factors have been reasoned for cancer development in schizophrenia patients. However, the influence of age of onset and duration of schizophrenia on cancer incidence has rarely been emphasized. Besides, bipolar disorder tends to resemble schizophrenia from the perspective of multiple rare mutations. Comparing pattern and risk of cancers between schizophrenia and bipolar patients is illuminating. Methods: This study used the Taiwan National Health Insurance Database. A total of 71 317 schizophrenia and 20 567 bipolar disorder patients from 1997 to 2009 were enrolled. Both cohorts were followed up for cancer during the same period by record linkage with the cancer certification in Taiwan. Age and gender standardized incidence ratios (SIRs) of overall and site-specific cancers were calculated. Results: The SIR for all cancers was 1.17 for the schizophrenia cohort. Increased cancer risk (SIR: 1.31, 95% CI: 1.17-1.48) was observed in females but not males. For the bipolar disorder cohort, the SIR for all cancers was 1.29, but the excess risk was found in males (SIR: 1.42, 95% CI: 1.14-1.77) and not females. Cancer risk decreases as the duration and age of onset of schizophrenia increases. If schizophrenia is diagnosed before 50, the SIRs for colorectal, breast, cervical, and uterine cancers increase but if diagnosed after 50, the SIRs for all cancers decrease except for breast cancer. In bipolar disorder, the SIRs for all site-specific cancers were insignificant. Conclusions: Among schizophrenia patients, overall cancer risk varies inversely with age at diagnosis and disease duration. Besides, gender-specific cancer risks differ between schizophrenia and bipolar disorder.
Schizophrenia Bulletin 11/2011; · 8.80 Impact Factor
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ABSTRACT: Aripiprazole, a novel antipsychotic agent, acts as a partial agonist at dopamine D2 receptors (DRD2). We investigate whether its efficacy is predictable by DRD2/ANKK1 gene polymorphisms and clinical factors in Han Chinese hospitalized patients with acutely exacerbated schizophrenia.
After hospitalization, the patients (n=128) were given aripiprazole for up to 4 weeks. They were genotyped for four functional DRD2/ANKK1 polymorphisms: -141 Ins/Del, Ser311Cys, C957T, and TaqIA. Clinical factors such as gender, age, illness duration, education level, diagnostic subtype, and medication dosage were also recorded. Psychopathology was measured biweekly with the positive and negative syndrome scale (PANSS). The effects of genetic and clinical factors on PANSS performance upon aripiprazole treatment were analyzed by a mixed modeling approach (SAS Proc MIXED).
Compared to the patients with TaqI A2/A2 genotype, A1 carriers are associated with superior therapeutic response on positive symptoms after 4-week aripiprazole treatment. Regarding the C957T polymorphism, patients with C/C genotype were associated with poor aripiprazole response for excitement symptoms when compared with T/T patients. The other two polymorphisms, -141 Ins/Del, and Ser311Cys, have no significant effects on PANSS performance. The clinical factors including medication dosage, illness duration, and diagnostic subtype could influence PANSS performance upon aripiprazole treatment.
This study suggests that DRD2/ANKK1 gene variations and some clinical factors may predict individual response to aripiprazole.
Journal of Psychiatric Research 11/2008; 43(6):600-6. · 4.66 Impact Factor
