Pathological obesity may be related with impairment of impulse control and cognitive disturbances. In this study the cognitive frontal functions in relation to the polymorphism of candidate genes in patients with pathological obesity were assessed. The prefrontal functions were evaluatedmusing Wisconsin Card Sorting Test. The polymorphisms of genes connected with serotoninergic and dopaminergic system : 5HT2A, 5HT2C, 5HTT, DAT1, and COMT, and also the polymorphism of BDNF - involved with modulation of nervous system development and neuroplasticity were assessed. Polymorphisms of the genes were detected by RFLP and VNTR PCR methods.

The 100 subjects with pathological obesity, BMI>40 operated with Mason method were enrolled. The results of WCST were compared with the results of healthy sex, age and education matched controls.

Subjects with pathological obesity show significant worse results on all domains of WCST, compared to controls. The frequencies of the polymorphisms in the obese group were: 5HT2A -1438A->G - A/A - 11%, A/G - 50%, G/G - 39%; DAT1 VNTR in 15th exon - short/short - 13%, short/long - 34%, long/long - 53%; BDNF Val66Met (G->A) - A/A - 3%, A/G - 24%, G/G - 73%. Interesting results were obtained in the case of 5HT2C: a known polymorphism (-759C->T) could not explain the banding pattern observed. It is possible that we have found a novel polymorphism that strongly correlates with obesity. The results obtained show significant prefrontal dysfunctions in patients with pathological obesity which may be related to the polymorphisms of serotonin and dopaminergic system genes and possible association of the obesity with the new polymorphism of 5HT2C gene.