Genetic features of antidepressant induced mania and hypo-mania in bipolar disorder.
OBJECTIVE
The present study investigated possible genetic association between some polymorphisms possibly involved in antidepressant response and the occurrence of manic or hypo-manic switches during antidepressant treatment.


METHODS
We retrospectively examined 169 individuals with a diagnosis of bipolar disorder (BP) type I ( n=103) and II ( n=66), who presented at least one sudden manic or hypo-manic episode (according to DSM IV criteria) during antidepressant therapy, that occurred within a period of 3 weeks from the beginning of the treatment and without any interposed period of well being ("manic switch"). They were compared with a sex, age, and ethnicity-matched group of 247 subjects, randomly selected from our pool of bipolar subjects, who never showed switches. We then randomly selected from the whole sample ("switched" and "not switched") a sub-sample of patients not under mood stabiliser treatment at the time of the index episode (65 "switched" and 117 "not switched") and compared them with a sex, age and ethnicity matched group of 133 subjects, randomly selected from our pool of major depressed patients, who did not present manic switches. The functional polymorphism in the upstream regulatory region of the serotonin transporter (SERTPR), tryptophan hydroxylase (TPH), G-protein beta 3 subunit (Gbeta3), monoamine oxidase A (MAO-A), catechol- O-methyltransferase (COMT), serotonin receptor 2A (5-HT2A), dopamine receptor D2 (DRD2) and dopamine receptor D4 (DRD4) gene variants were analysed using PCR-based techniques.


CONCLUSIONS
The distribution of the genetic polymorphisms was not significantly different between switched and not-switched patients ( P>0.006-Bonferroni corrected). Moreover, no significant difference was found between switched and not switched sub-samples and the sample of major depressed subjects. Further studies are required to investigate other possible related genetic variants influencing the timing of manic-depressive cycle.
Serretti
Alessandro
A
Department of Psychiatry, School of Medicine, Vita-Salute University San Raffaele, Via Stamira D'Ancona 20, 20127 Milan, Italy. serretti.alessandro@hsr.it
Artioli
Paola
P
Zanardi
Raffaella
R
Lorenzi
Cristina
C
Rossini
David
D
Cusin
Cristina
C
Arnoldi
Alessia
A
Catalano
Marco
M
D000328:Adult; D000928:Antidepressive Agents / Q000009:adverse effects*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics*; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D016009:Chi-Square Distribution; D005260:Female; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D012045:Regulatory Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase / Q000235:genetics
D000928:Antidepressive Agents; C493599:DRD4 protein, human; C454420:G-protein beta3 subunit; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D017448:Receptors, Dopamine D2; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D050638:Receptors, Dopamine D4; D014365:Tryptophan Hydroxylase; D002394:Catechol O-Methyltransferase; D020962:Heterotrimeric GTP-Binding Proteins