Acute antipyschotic efficacy and side effects in schizophrenia: association with serotonin transporter promoter genotypes.
BACKGROUND
The serotonin transporter (5-HTT) plays an important role in serotonergic neurotransmission. In the present study, we investigated the effects of the 44 bp insertion/deletion polymorphism in the promoter region of 5-HTT gene (5-HTTLPR) on symptomatology of psychosis and clinical response to antipsychotic drugs.


METHODS
In total 56 patients acutely treated with haloperidol or risperidone either for the first episode of schizophrenia, schizophreniform or schizoaffective disorders, or for the relapse of these psychotic disorders after tapering their maintenance treatment, were genotyped for the 5-HTTLPR L and S alleles and for the new A/G functional variant within the L alelle (La/g). Psychopathological symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS) and with Clinical Global Impression (CGI) twice: at 8-12 days after the first dose of antipsychotic and after 4 weeks. Extrapyramidal side effects were assessed with the Simpson-Angus Extrapyramidal Side Effects Scale (EPS), the Barnes Akathisia Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS).


RESULTS
Age, body mass index (BMI), illness duration, drug type and dosage were considered as covariates when analysing association with genetic variants as they were associated with baseline or final BPRS and CGI scores and/or extrapyramidal side effects. 5-HTTLPR was not associated with baseline and final BPRS and CGI scores or with the CGI% reduction. However, the 5-HTTLPR S allele was associated with a lower improvement in BPRS scores (P=0.022) and this effect was even stronger after pooling subjects with S or Lg containing alleles (P=0.006). We did not observe any effect of 5-HTTLPR on acute antipsychotics side effects.


CONCLUSIONS
Present result supports a contribution of serotonin system to neuroleptics efficacy for the treatment of schizophrenia. The analysis of the La/g functional variant may significantly improve the predictive power of 5-HTTLPR genotyping and represent a step further towards the development of the personalized antipsychotic treatment.
Dolzan
Vita
V
University of Ljubljana, Faculty of Medicine, Institute of Biochemistry, Vrazov trg 2, SI-1000 Ljubljana, Slovenia. vita.dolzan@mf.uni-lj.si
Serretti
Alessandro
A
Mandelli
Laura
L
Koprivsek
Jure
J
Kastelic
Matej
M
Plesnicar
Blanka Kores
BK
D000328:Adult; D000483:Alleles; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
D014150:Antipsychotic Agents; D005819:Genetic Markers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D006220:Haloperidol; D018967:Risperidone