Age of Onset in Schizophrenia Spectrum Disorders: Complex Interactions between Genetic and Environmental Factors

In this study we evaluated the role of a candidate gene for major psychosis, Sialyltransferase (ST8SIA2), in the risk to develop a schizophrenia spectrum disorders, taking into account exposure to stressful life events (SLEs). Eight polymorphisms (SNPs) were tested in 94 Schizophreniainpatients and 176 healthy controls. Schizophrenia patients were also evaluated for SLEs in different life periods. None of the SNPs showed association with schizophrenia. Nevertheless, when crossing genetic variants with childhood SLEs, we could observe trends of interaction with age of onset. Though several limitations, our results support a protective role of ST8SIA2 in individuals exposed to moderate childhood stress.

Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

OBJECTIVE: The present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders. METHODS: One hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the chi2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy. RESULTS: The rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects. CONCLUSION: Our findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations.

No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.