Polymorphisms in genes related to the hypothalamic-pituitary-adrenal axis and antidepressant response – systematic review

Susanne Fischer, Elena S. Gardini, Florence Haas, Anthony J. Cleare

Research output: Contribution to journalReview articlepeer-review

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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.


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.

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.


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.
Original languageEnglish
Article numberNBR 3269
Pages (from-to)182-196
Number of pages15
JournalNeuroscience and biobehavioral reviews
Early online date19 Nov 2018
Publication statusPublished - Jan 2019


  • Antidepressant
  • Depression
  • Hypothalamic-pituitary-adrenal axis
  • Polymorphism
  • Treatment response


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