Influence of the catechol-O-methyltransferase Val108/158Met polymorphism on the plasma concentration of catecholamine metabolites and on clinical features in type I bipolar disorder--a preliminary report.
BACKGROUND
The activity of catechol-O-methyltransferase (COMT) may be related to psychosis susceptibility. The Val108/158Met polymorphism of the COMT gene influences its enzymatic activity and may result in altered concentrations of monoamine metabolites and different clinical responses of patients to pharmacological treatments.


METHODS
We examined in a sample of 42 bipolar patients if the Val108/158Met polymorphism influences: (a) the presence of psychosis in type I bipolar patients; (b) the blood plasma concentration of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), which are metabolites of dopamine and noradrenaline respectively and (c) the severity of the clinical characteristics of these patients and their response to pharmacological treatment.


RESULTS
No significant associations were found between the studied COMT genotypes and the studied parameters. However, a non-significant aggregation of bipolar patients presenting with psychosis was found in the homozygous Val-Val group. Clinical improvement was found to significantly correlate with the levels of plasma MHPG prior to treatment. Moreover, a significant difference was found between the standard deviations of the concentrations of HVA in the three genotypes, but not in their mean values. Significant associations were not detected between COMT polymorphisms and the initial severity of the disorder, or the clinical response to pharmacological treatment.


CONCLUSIONS
The size of the studied sample is somewhat small and comparisons have been made with a previously studied control group.


CONCLUSIONS
The Val108/158Met polymorphism does not appear to be a crucial determinant in type I bipolar disorder.
Departamento de Investigación Neuroquímica, Hospital Psiquiátrico de Zamudio, Servicio Vasco de Salud (Osakidetza), Vizcaya, Spain. rdavila@hzam.osakidetza.net
Ricardo
R
Dávila
Mercedes
M
Zumárraga
Nieves
N
Basterreche
Aurora
A
Arrúe
M Isabel
MI
Zamalloa
Juan B
JB
Anguiano
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000097:blood* / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015870:Gene Expression / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006719:Homovanillic Acid / Q000097:blood*; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood*; D008875:Middle Aged; D000077152:Olanzapine; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D012720:Severity of Illness Index; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D015306:Biogenic Monoamines; D001569:Benzodiazepines; D016651:Lithium Carbonate; D008734:Methoxyhydroxyphenylglycol; D002394:Catechol O-Methyltransferase; D000077152:Olanzapine; D006719:Homovanillic Acid