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The catecholamine hypothesis of affective disorders suggests that depression is associated with a functional decrease of catecholamines. There is consistent evidence that COMT gene would be a candidate gene for studies of bipolar disorder.
The study was performed on patients with bipolar disorder n=298 (male n=126, female n=172). Control subjects were blood donors n=336 (male n=130, female n=206), who were not psychiatrically assessed. The subgroup of patients with psychotic features not congruent with mood contained n=88 patients, males n=41, females n=47. The subgroup of patients with psychotic features congruent with mood contained n=89 patients, males n=47, females n=42. The subgroup of patients with melancholic depression contained n=197 patients, males n=76, females n= 121. A polymorphism was analysed by PCR-RFLP method.
There were no differences in the frequency of genotypes, alleles between patients and controls in the whole group (p=0,286 for genotypes, p= 0,652 for alleles). Dividing the patients according to the gender, no differences in the frequency of either genotypes or alleles were found (p=0,298 for genotype males, p=0,456 for genotypes females). We did not find the association in the subgroup of patients with psychotic features congruent (p=0,828 for genotypes, p= 0,866 for alleles), or not congruent with mood (p=0,116 for genotypes, p= 0,673 for alleles) and with the subgroup of patients with depression with melancholic features (p= 0,758 for genotypes, p= 0,849 for alleles).
Results of our study suggest that the polymorphism of COMT gene is not associated with the susceptibility to bipolar disorder.
Working memory and executive functions, connected with the activity of prefrontal cortex play an important role in complex mental processes. Wisconsin Card Sorting Test (WCST) is a main tool used for neuropsychological assessment of prefrontal cortex activity. Molecular genetics studies show the association between the performance on WCST and polymorphism of dopaminergic system genes in schizophrenia and healthy subjects, also with polymorphism of BDNF gene in bipolar disorders.
In this study an association between performance on WCST and polymorphisms of selected candidate genes was assessed.
The study included 200 healthy volunteers aged 18-60 years. Neuropsychological assessment was performed using WCST and following domains were evaluated: perseverative errors (inability to change the reaction), nonperseverative errors (attentional inability to avoid distraction), number of completed categories (ability to utilize new information), percent of conceptual responses (ability of conceptual thinking) and set to complete 1st category (ability to formulate a logical conception). Genotyping were done for polymorphism of dopaminergic: D1receptor (-48A/G) and catechol-O-methyltransferase (COMT108/158Val/Met), serotoninergic (5-HTTLPR), glutamatergic: FYNkinase (93A/G, IVS10+37T/C, Ex12+894T/G) and neurotrophic: brain-derived neurotrophic factor (BDNF:C-270T,Val66Met) genes.
A/G polymorphism of DRD1 gene was connected with better results on trials to complete 1st category. Better performance on nonperseverative errors was observed in females with Val/Val genotype of COMT. The C/T genotype of C-270T BDNF polymorphism was associated with higher percentage of conceptual responses.
The results obtained suggest a contribution of studied candidate genes to working memory and executive functions efficiency, connected with prefrontal cortex activity, in healthy subjects.
A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales.
The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery–Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores.
The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely ‘observed mood and anxiety’, ‘cognitive’ and ‘neurovegetative’, provided a more detailed description of depression severity.
The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.
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