II-81Posters
DRD1 AND DRD2 POLYMORPHISMS AND LONG TERM
ANTIPSYCHOTIC TREATMENT
Jure Koprivšek1,Vita Dolžan2, Alessandro Serretti3, Laura Mandelli3, Katja Breskvar 2,
Blanka Kores-Plesničar1
1 Department of Psychiatry, Teaching Hospital Maribor, Maribor, Slovenia
2 Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
3 Institute of Psychiatry, University of Bologna, Bologna, Italy; jure.koprivsek@guest.arnes.si
Introduction Disturbances of dopamine mediated transmission are involved in the pathogenesis of schizo-
phrenia and dopamine receptors are important targets of the antipsychotic treatment. As
the density of the D2 receptor is influenced by the genetic polymorphism of the dopamine
D2-receptor gene (DRD2) the effects of the antipsychotic drugs that are antagonists of this
receptor may be modulated by its polymorphisms (1). DRD2 311 Ser/Cys variant was asso-
ciated both with the clinical symptoms of schizophrenia, in particular with delusions and
symptoms of disorganization (2) and with the efficacy of the antipsychotic treatments, but
not with the extrapyramidal side effects (3). Studies with other polymorphisms were not so
conclusive.
To assess the complex interaction between genetic and clinical factors, we studied the possi-
ble cross-interactions between DRD1 and DRD2 dopamine receptor gene polymorphisms,
symptomatology of schizophrenia and schizoaffective disorders and the occurrence of treat-
ment induced side effects taking into consideration possible clinical confounding variables.
Methods One hundred and thirty one outpatients in stable remission meeting the DSMIV criteria for
schizophrenia spectrum disorders and receiving long-term maintenance therapy with ha-
loperidol, fluphenazine, zuclopethixole or risperidone (4) were genotyped for DRD1 A-
48G, DRD2 Ins-141CDel and DRD2 Ser311Cys polymorphisms. Psychopathological symp-
toms were assessed with the Positive and Negative Syndrome Scale for Schizophrenia
(PANSS). Regarding extrapyramidal side effects, tardive dyskinesia was assessed with the
Abnormal Involuntary Movement Scale (AIMS), akathisia with the Barnes Akathisia Scale
(BARS) and parkinsonism with the Simpson-Angus Extrapyramidal Side Effects (SAS). For
the statistical analysis χ2 test, t-test, one-way analysis of variance (ANOVA), analysis of
covariants (ANCOVA) and Spearman R test were used.
Results Drug dosage was included as covariant for the genetic analyses because a cross correla-
tion was observed between drug dose, symptomatology and extrapyramidal side effects (p
< 0.001). In our sample, all genotypes were in Hardy-Weinberg equilibrium. Genetic vari-
ants did not differentiate patients regarding symptomatology, except DRD1 -48GG geno-
type, which showed a trend towards a positive effect on delusions (p = 0.043) and DRD2 –
141C Del allele, which showed an effect on the negative symptom of stereotypy (p = 0.0011).
The DRD2 311 Ser/Cys genotype showed a non significant association with tardive dyski-
nesia (p = 0.05). All three 311 Ser/Cys subjects showed an overall higher rate of side effects,
independent from the drug used (typical versus atypical). The DRD1 showed a marginal
effect on abnormal involuntary movement of the trunk (p = 0.028).
Conclusions Only some marginal associations were observed between DRD1 and DRD2 polymorphisms
and symptomatology. A non signifficant association was observed between DRD2 311
Ser/Cys genotype and tardive dyskinesia, but this finding was due to only 3 subjects. Our
study evidenced that DRD1 and DRD2 variants are not influencing liability to tardive
dyskinesia independently from the other clinical variables we included in the model.
References
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