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

doi:10.1016/j.neubiorev.2018.11.009

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

Neurosci Biobehav Rev. 2019 Jan:96:182-196. doi: 10.1016/j.neubiorev.2018.11.009. Epub 2018 Nov 19.

Authors

Susanne Fischer¹, Elena S Gardini², Florence Haas³, Anthony J Cleare⁴

Affiliations

¹ King'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. Electronic address: s.fischer@psychologie.uzh.ch.
² University of Zurich, Institute of Psychology, Clinical Psychology and Psychotherapy, Zurich, Switzerland; University of Zurich, University Research Priority Program (URPP) Dynamics of Healthy Aging, Zurich, Switzerland.
³ University of Zurich, Institute of Psychology, Clinical Psychology and Psychotherapy, Zurich, Switzerland.
⁴ King's College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, Centre for Affective Disorders, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Denmark Hill, Camberwell, London, SE5 8AZ, United Kingdom.

PMID: 30465786
DOI: 10.1016/j.neubiorev.2018.11.009

Abstract

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.

Keywords: Antidepressant; Depression; Hypothalamic-pituitary-adrenal axis; Polymorphism; Treatment response.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Antidepressive Agents / therapeutic use*
Depression / drug therapy
Depression / genetics
Depression / physiopathology
Depressive Disorder / genetics*
Depressive Disorder / physiopathology
Depressive Disorder / therapy*
Humans
Hypothalamo-Hypophyseal System* / physiopathology
Pituitary-Adrenal System* / physiopathology
Polymorphism, Genetic*

Substances

Antidepressive Agents