Pharmacogenetics of selective serotonin reuptake inhibitor response: a 6-month follow-up.
BACKGROUND
We previously reported the association between some genetic factors and short-term antidepressant outcome. In the present paper we investigated the same gene variants in a prospective 6-months naturalistic follow-up.


METHODS
The sample included 185 inpatients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospectively followed for 6 months after their recovery. All the patients were undertaking continuation therapy. The functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR), the tryptophan hydroxylase A218C substitution, a VNTR polymorphism located 1.2 kb upstream of the monoamine oxidase-A coding sequences, the CLOCK gene T3111C and the PER3exon15 gene T1940G substitutions were analysed, using PCR-based techniques.


RESULTS
No association was found between clinical variables and relapses; subjects showing TT genotype at CLOCK gene tended to relapse within 6 months after recovery more than TC and CC subjects taken together. A non-significant tendency of SERTPR*s/s subjects to a minor frequency of relapse was also observed.


CONCLUSIONS
Some subjects showing remission after acute treatment relapsed within 6 months, despite undertaking a maintenance treatment; the causes could be heterogeneous, but CLOCK gene variants may influence the outcome.
Department of Psychiatry, Vita-Salute University, San Raffaele Hospital, Milan, Italy. serretti.alessandro@hsr.it
Alessandro
A
Serretti
Raffaella
R
Zanardi
Linda
L
Franchini
Paola
P
Artioli
Danilo
D
Dotoli
Adele
A
Pirovano
Enrico
E
Smeraldi
D000328:Adult; D000483:Alleles; D000928:Antidepressive Agents / Q000494:pharmacology*; D056926:CLOCK Proteins; D004247:DNA / Q000378:metabolism; D003865:Major Depressive Disorder / Q000235:genetics*; D005091:Exons; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007093:Imidazoles; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D008995:Monoamine Oxidase / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D015534:Trans-Activators / Q000235:genetics; D016896:Treatment Outcome
D000928:Antidepressive Agents; D056926:CLOCK Proteins; D004247:DNA; D007093:Imidazoles; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008995:Monoamine Oxidase; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D015534:Trans-Activators; C493230:SLC6A4 protein, human; C020999:clodanolene; C538943:CLOCK protein, human