A splice site polymorphism in the G-protein beta subunit influences antidepressant efficacy in depression.
OBJECTIVE
Recent evidence suggests that signalling cascades located downstream of monoamine receptors are altered following antidepressant treatment. Our objective was to investigate whether genetic polymorphisms in genes involved in these signalling cascades influenced antidepressant efficacy.


METHODS
Polymorphisms in the G-protein beta subunit GNB3, the cAMP response element binding protein 1 gene (CREB1), the brain derived neurotrophic factor (BDNF) and CREB binding protein (CREBBP) were studied in well characterised unipolar (n=166) and early onset (n=102) depressive populations and correlated with treatment response.


RESULTS
The GNB3 C825T polymorphism, which results in a 41 amino acid deletion, was significantly associated with lack of remission (OR=0.18, P=0.02) and lack of response (OR=0.26, P=0.03) following 2nd switch treatment. A cytosine deletion 16 base pairs from the start of exon 8 in CREB1 was found more frequently in remitters and responders to 2nd switch antidepressant drug therapy, although these differences failed to reach significance. Polymorphisms detected BDNF (G196A) and CREBBP (T651 C) did not appear to influence antidepressant response.


CONCLUSIONS
These results suggest that inheritance of the GNB3C825T allele may significantly influence antidepressant response and emphasises the potential importance of polymorphisms in genes in signalling cascades activated by commonly prescribed antidepressants.
Wilkie
Murray J V
MJ
Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK.
Smith
Daniel
D
Reid
Ian C
IC
Day
Richard K
RK
Matthews
Keith
K
Wolf
Charles Roland
CR
Blackwood
Douglas
D
Smith
Gillian
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics; D050882:CREB-Binding Protein / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D003863:Depression / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D044387:GTP-Binding Protein beta Subunits / Q000235:genetics*; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics*; D016896:Treatment Outcome
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; C454420:G-protein beta3 subunit; D044387:GTP-Binding Protein beta Subunits; D022821:RNA Splice Sites; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D020962:Heterotrimeric GTP-Binding Proteins