Letter to the Editor
A DRD2 polymorphism predicts PANSS score variability in
schizophrenia patients treated with antipsychotics
Keywords:
Dopamine
Genotype
Psychological disorder
Medication
Genetics
Antipsychotic medications act as either antagonists or partial
agonists of the dopamine D2 receptor (DRD2) and antipsychotic drugs
vary widely in their binding affinity for the D2 receptor (Kapur and
Seeman, 2000). The DRD2 957C NT (rs6277) polymorphism has
previously been associated with schizophrenia (Lawford et al.,
2005) and the T-allele of the 957C N T polymorphism is associated
with reduced mRNA stability and synthesis of the dopamine D2
receptor (Duan et al., 2003). The aim of the study was to determine if
the rs6277 polymorphism predicts some of the variability of positive
and negative symptoms observed in schizophrenia patients being
treated with antipsychotic medication.
Positive and negative symptom scale (PANSS) ratings and DRD2
957CNT genotypes were determined in 142 schizophrenia patients who
were treated with antipsychotic drugs (clozapine, olanzapine, typicals
and risperidone). DSM (Diagnostic and Statistical Manual of Mental
Disorders) IV diagnosis of schizophrenia was confirmed by at least two
independent psychiatrists. Patients had never been diagnosed with
other psychiatric disorders, including schizoaffective disorder, major
depressive episode with psychotic features, or bipolar disorder. No
patients were treated with antidepressants, anxiolytic agents, or mood-
stabilizing psychotropic medications and all were maintained on a
constant dose of antipsychotic medication for a minimum of 3 weeks.
The mean age of patients was 36.2 years (S.D.± 12.1 years) and the
mean age of patients first diagnosed with schizophrenia was 23.4 years
(S.D.±7.47 years). Patients had been diagnosed with schizophrenia for
an average of 13 years and despite treatment with antipsychotic
medication they continued to experience positive and negative
symptoms. PANSS scales analysed included PANSS rating scale-positive
scale-Likert scoring system, PANSS rating scale-negative scale-Likert
scoring system, PANSS rating scale-general scale G14: poor impulse
control, PANSS rating scale-positive scale-total score/49, PANSS rating
scale-negative scale-total score/49, and PANSS rating scale-general scale
G11: poor attention, PANSS rating scale-general scale G12: lack of
judgement and insight and PANSS rating scale (modified version)-total
score/119. All statistical tests including analysis of variance (ANOVA),
post-hoc pair-wise comparisons and t-tests were performed by SPSS
version 16.
Firstly, PANSS rating scores were correlated with antipsychotic
drug treatment. Analysis of variance revealed significant differences
in PANSS G12 general score (lack of judgement and insight) among
the four medication groups (P = 0.018, F = 3.484). PANSS G12 scores
the impaired awareness or understanding of one's own psychiatric
condition and life situation as well as measuring compliance of
treatment. This is an important measure as a large percentage of
schizophrenia patients are noncompliant in treatment and between
50% and 80% of patients with schizophrenia do not believe they have a
mental disorder (Amador and Gorman, 1998). Response to treatment
and side effects may affect compliance in patients with schizophrenia
(Hofer et al., 2002). Patients treated with typicals had poorer G12
scores compared to patients treated with clozapine (Tukey P = 0.016,
Bonferroni P=0.018) or olanzapine (Tukey P=0.048, Bonferroni
P=0.060). Analysis of variance revealed no significant differences in
other PANSS rating measurements between drug groups. No signif-
icant differences between drug groups were observed for gender, age,
BMI, onset age, family history, number of admissions and drug use.
In the second part of the study PANSS ratings were correlated with
genotype in patients receiving one of four types of antipsychotic
medications. Signi
ficant associations were found between alleles and
PANSS poor attention ratings (P=0.019, T= −2.441) and PANSS
negative ratings (P=0.031, T= −2.203) (Table 1). No significant
associations were found between alleles and PANSS Positive, PANSS
poor impulse control, PANSS positive total, PANSS negative total and
PANSS total rating scores. Association with PANSS poor attention was also
significantatthegenotypelevel(P=0.042). Post-hoc pair-wise compar-
isons including Tukey and Bonferroni were undertaken to test differences
between groups revealing significant PANSS (poor attention) mean score
differences between individuals with the CC and TT genotypes (Tukey
P= 0.038, Bonferroni P= 0.045) but not between CC vs. CT and CT vs. TT
groups. The association seen between PANSS negative rating and alleles
did not hold up at the genotype level (P=0.156) and was not significant
after Tukey and Bonferroni multiple comparisons.
Psychiatry Research 177 (2010) 367–368
Table 1
PANSS G11 poor attention and PANSS negative symptom scores in patients with the C or T DRD2 allele receiving antipsychotic medication for schizophrenia.
Drug group Mean PANSS G11 (S.D.) Mean Negative symptoms (S.D.)
C-allele T-allele P C-allele T-allele P
All groups n= 142 2.16 (0.95) n= 160 2.32 (1.28) n= 124 0.245 2.99 (1.06) n = 160 3.15 (1.23) n = 124 0.250
Clozapine n= 31 2.25 (0.91) n= 36 3.04 (1.46) n= 26 0.019 2.94 (1.19) n = 36 3.62 (1.17) n = 26 0.031
Olanzapine n= 37 2.05 (1.01) n= 40 2.35 (1.50) n= 34 0.320 2.85 (1.27) n = 40 3.35 (1.54) n = 34 0.128
Typicals n= 28 2.21 (0.99) n= 28 2.00 (0.94) n= 28 0.420 3.32 (0.67) n = 28 3.12 (0.91) n = 26 0.345
Risperidone n= 46 2.09 (0.87) n = 54 2.03 (0.94) n = 38 0.730 2.93 (0.93) n= 54 2.68 (1.02) n= 38 0.240
0165-1781/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.psychres.2010.02.015
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