AIMS: To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. METHODS: The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. RESULTS: A functional polymorphism at 3'UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. CONCLUSIONS: Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.
RCT Entities:
AIMS: To investigate the role of genetic polymorphisms in candidate genes associated with the HPA axis and their interactions with environmental stressors in antidepressant response. METHODS: The remission of depressive symptoms after 8 weeks of antidepressant treatment was tested against 21 single nucleotide polymorphisms (SNPs) in five candidate genes associated with the HPA axis in a Chinese Han sample suffering from unipolar depression (n = 273). Any history of childhood trauma and recent negative life events were measured using the Childhood Trauma Questionnaire-Short Form (CTQ-SF) (n = 206) and the Life Event Scale (48 item, LES) (n = 207), respectively. Reporter gene assays were used to evaluate the possible effects of the most significant SNP on gene expression. RESULTS: A functional polymorphism at 3'UTR of the corticotropin-releasing hormone receptor 1 (CRHR1) gene (rs28364032) and three haplotypes containing it showed significant relationships with antidepressant remission. Further laboratory-based genomic studies showed that the G-to-A change of rs28364032 resulted in a 10-12% decrease in the intensity of luciferase activity. However, we failed to find association of environments and their interaction with HPA system-related genes with antidepressant remission. CONCLUSIONS: Our results support a definite role for CRHR1 in the pharmacogenetics of antidepressant drugs. This may contribute to interpatient differences in their responses to antidepressant drugs.
Authors: David P Bernstein; Judith A Stein; Michael D Newcomb; Edward Walker; David Pogge; Taruna Ahluvalia; John Stokes; Leonard Handelsman; Martha Medrano; David Desmond; William Zule Journal: Child Abuse Negl Date: 2003-02
Authors: Thomas Nickel; Annette Sonntag; Julia Schill; Astrid W Zobel; Nibal Ackl; Alexander Brunnauer; Harald Murck; Marcus Ising; Alexander Yassouridis; Axel Steiger; Josef Zihl; Florian Holsboer Journal: J Clin Psychopharmacol Date: 2003-04 Impact factor: 3.153
Authors: J Licinio; F O'Kirwan; K Irizarry; B Merriman; S Thakur; R Jepson; S Lake; K G Tantisira; S T Weiss; M-L Wong Journal: Mol Psychiatry Date: 2004-12 Impact factor: 15.992