Relationship of hypothalamus-pituitary-adrenal (HPA) axis function and suicidal behavior in patients with depression.

BACKGROUND: There have been few neuroendocrinology studies of suicidal behaviors among patients with depression and the results of these studies have been inconsistent. AIM: To explore the association between the function of the hypothalamus-pituitary-adrenal (HPA) axis and suicidal behaviors in Chinese patients with depression. METHODS: Several measures of HPA functioning in 14 depressed patients who had had suicidal behaviors in the two prior months ('depressed cases') were compared to those of 15 depressed inpatients who did not have prior suicidal behaviors ('depressed controls'): a dexamethasone suppression test (DST), the diurnal changes in serum cortisol levels during a single day before and after 6 weeks of treatment with paroxetine; and 24 h urinary 17-OH cortisol and free corticosterone before and after treatment. The Hamilton Depression Scale (HAMD) was used to measure the severity of depression. Daytime cortisol levels were also assessed in 15 non-depressed controls selected from individuals who had a routine health exam. RESULTS: There were no statistically significant differences in the 24 h urinary measures of cortisol and corticosterone between depressed cases and depressed controls. In both groups the normal midnight drop in serum cortisol was nonsignificant prior to treatment but after treatment it became more pronounced. The DST was positive in more of the depressed cases than depressed controls (57% v. 20%, χ(2)=4.24, p=0.039). The correlation of cortisol serum levels with the HAMD total score and the item scores for hopelessness and suicidal ideation were statistically significant in the depressed case group both before and after treatment, but in the depressed control group these correlation coefficients did not reach statistical significance. The 08.00 h serum cortisol level in depressed cases was significantly greater than the level in non-depressed controls both before and after treatment, but the level in depressed controls was not significantly greater than that in non-depressed controls. CONCLUSION: These findings are broadly consistent with those of prior studies about the relationship of depression and the functioning of the HPA axis. There were, however, some differences between depressed patients that did and did not report prior suicidal behavior which may indicate suicide-specific characteristics of HPA axis dysfunction. These differences merit further assessment in larger studies that distinguish patients who have made suicide attempts from those who only report prior suicidal ideation.

Case-control association study of Disrupted-in-Schizophrenia-1 (DISC1) gene and schizophrenia in the Chinese population.

Disrupted-in-Schizophrenia-1 (DISC1) has first been identified as a candidate gene for schizophrenia through study of a Scottish family with a balanced (1; 11) (q42.1; q14.3) translocation. Lots of linkage and association studies supported DISC1 as a risk factor for schizophrenia. In this study, we genotyped three SNPs in DISC1 using a set of Han Chinese samples of 560 schizophrenics and 576 controls. No positive association was detected in the whole samples but analysis of allele frequencies in female samples showed weak association between SNP rs2295959 and the disease (chi(2)=6.188, P=0.0135, OR=0.728, 95% CI=0.567-0.935). Our results provide further evidence for sex difference for the effect of the gene on the aetiology of schizophrenia. Our findings also would encourage further studies, particularly family-based association studies with larger samples, to analyze the association between DISC1 and schizophrenia.

Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population.

Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin which plays important roles in the development of the brain. BDNF has been suggested as a factor that increases the risk of schizophrenia. In this study, we genotyped three single nucleotide polymorphisms (SNPs) in the BDNF gene using a set sample of Han Chinese subjects consisting of 560 schizophrenes and 576 controls. No significant differences were found for either the genotype or allele distribution of analyzed polymorphisms, nor was any gender-specific association found. Thus, our data suggest that the BDNF gene may not be an important factor in susceptibility to schizophrenia.

Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population.

The close homolog of L1 (CHL1), located on human chromosome 3p26.1, is a newly identified member of the L1 family of cell adhesion molecules which play important roles in cell migration, axonal growth, and synaptic remodeling. A positive association has been reported between a missense polymorphism in CHL1 gene and schizophrenia in the Japanese population [Sakurai, K., Migita, O., Toru, M., Arinami, T., 2002. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412-415]. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. In order to test this finding, we genotyped four SNPs in the gene in the Han Chinese population using a sample of 560 cases and 576 controls. Analysis of allele frequencies in both samples also showed strong association between SNP rs2272522 (the same marker studied by K. Sakurai) and the disease (X2=31.591, P<0.000001, OR=1.745, 95% CI=1.435-2.121). Our results confirm the positive association between CHL1 gene and schizophrenia and indicate that CHL1 may be involved in the etiology of schizophrenia.