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Polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis and antidepressant response - Systematic
Susanne Fischer1, Elena S Gardini2, Florence Haas3
1King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, Centre for Affective Disorders, London, United Kingdom; University of Zurich, Institute of Psychology, Clinical Psychology and Psychotherapy, Zurich, Switzerland.
Objective:
Around 50% of depressed patients do not respond to antidepressants. Evidence from familial studies suggests a genetic component to this. This study investigated whether patients with polymorphisms in genes related to the hypothalamic-pituitary-adrenal (HPA) axis were less likely to respond to antidepressants.
Method:
EMBASE, MEDLINE, PsycINFO, and the Cochrane Library were searched. Inclusionary criteria were: 1) patients with depression, 2) study of HPA axis-related candidate genes, 3) at least four weeks of antidepressants, and 4) assessment of depressive symptoms dividing patients into non-responders and responders.
Results:
Nineteen studies were identified. Non-responders and responders did not differ in single nucleotide polymorphisms (SNPs) in genes encoding arginine vasopressin. Findings were equivocal regarding genes encoding the FK506 binding protein 5 and glucocorticoid and mineralocorticoid receptors. Specific SNPs and haplotypes within genes related to corticotropin-releasing hormone (CRHBP, CRHR1) and melanocortins (POMC) predicted non-responder status.
Conclusions:
Replication studies and additional investigations exploring gene x environment and drug x environment interactions are necessary before pharmacological treatments may be adjusted based on a patient's genetic profile.
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