Epidemiological support for genetic variability at hypothalamic–pituitary–adrenal axis and serotonergic system as risk factors for major depression

Background: Major depressive disorder (MDD) is a serious, and common psychiatric disorder worldwide. By the year 2020, MDD will be the second cause of disability in the world. The Granad∑p study is the first, to the best of our knowledge, epidemiological study of mental disorders carried out in Andalusia (South Spain), being one of its main objectives to identify genetic and environmental risk factors for MDD and other major psychiatric disorders. In this study, we focused on the possible association of 91 candidate single nucleotide polymorphisms (SNPs) with MDD.Methods: A total of 711 community-based individuals participated in the Granad∑p study. All individuals were extensively assessed for clinical, psychological, sociodemographic, life style, and other environmental variables. A biological sample was also collected for subsequent genetic analyses in 91 candidate SNPs for MDD. DSM-IV diagnosis of MDD was used as the outcome variable. Logistic regression analysis assuming an additive genetic model was performed to test the association between MDD and the genetic data. The experiment-wide significance threshold adjusted with the SNP spectral decomposition method provided a maximum P-value (8×10-3) required to identify an association. Haplotype analyses were also performed.Results: One SNP (rs623580) located in the tryptophan hydroxylase 1 gene (TPH1; chromosome 11), one intergenic variant (rs9526236) upstream of the 5-hydroxytryptamine receptor 2A gene (HTR2A; chromosome 13), and five polymorphisms (rs17689966, rs173365, rs7209436, rs110402, and rs242924) located in the corticotropin-releasing hormone receptor 1 gene (CRHR1; chromosome 17), all showed suggestive trends for association with MDD (P<0.05). Within CRHR1 gene, the TATGA haplotype combination was found to increase significantly the risk for MDD with an odds ratio =1.68 (95% CI: 1.16–2.42, P=0.006).Conclusion: Although limited, perhaps due to insufficient sample size power, our results seem to support the notion that the hypothalamic–pituitary–adrenal and serotonergic systems are likely to be involved in the genetic susceptibility for MDD. Future studies, including larger samples, should be addressed for further validation and replication of the present findings.This work was mostly funded by an Andalusian Health System Health Council grant (PI0322/2009) and partially by Astra-Zeneca in agreement with CIBERSAM. It was also supported by a PhD grant from the Spanish Ministry of Education (AP2010-3563), and by the Andalusian Council of Innovation (CTS-6682)

Estudios sobre personalidad en los trastornos depresivos

Tesis Univ. Granada. Departamento de Medicina Legal, Toxicología y Psiquiatría. Leída el 21 de junio de 201

Deficits in Executive and Memory Processes in Delusional Disorder: A Case-Control Study

[Objective] Delusional disorder has been traditionally considered a psychotic syndrome that does not evolve to cognitive deterioration. However, to date, very little empirical research has been done to explore cognitive executive components and memory processes in Delusional Disorder patients. This study will investigate whether patients with delusional disorder are intact in both executive function components (such as flexibility, impulsivity and updating components) and memory processes (such as immediate, short term and long term recall, learning and recognition). [Methods] A large sample of patients with delusional disorder (n = 86) and a group of healthy controls (n = 343) were compared with regard to their performance in a broad battery of neuropsychological tests including Trail Making Test, Wisconsin Card Sorting Test, Colour-Word Stroop Test, and Complutense Verbal Learning Test (TAVEC). [Results] When compared to controls, cases of delusional disorder showed a significantly poorer performance in most cognitive tests. Thus, we demonstrate deficits in flexibility, impulsivity and updating components of executive functions as well as in memory processes. These findings held significant after taking into account sex, age, educational level and premorbid IQ. [Conclusions] Our results do not support the traditional notion of patients with delusional disorder being cognitively intact.This study was partially funded by grants from the Fondo de Investigaciones Sanitarias Instituto de Salud Carlos III, Ministry of economy and competitivity (Project No. FIS PI021813 and FIS PF09/01671), and by Proyecto de Excelencia, Consejeria de Innovacion, Junta de Andalucia (Project No. CTS 1686)