Depression is one of the most common psychiatric disorders nowadays characterized by reduced mood, loss of interest and satisfaction, guilt and low self-value, appetite and sleep disorders, reduced concentration, lack of life energy and increased suicid risk. The occurence of this serious disease is very complex and it involves many risk genes and environmental factors so various theories try to explain its origin. According to the monoamine hypothesis, on which current pharmacological therapy is based, depression is characterized by the disruption of monoamine (serotonin, dopamine, noradrenaline) neurotransmitter systems of the brain. Catechol-O-methyltransferase (COMT) is an enzyme that degrades catecholamines, including neurotransmitter dopamine and noradrenaline, which play an important role in the occurrence of depression symptoms. The enzyme is encoded by the gene COMT, which is located on the 22nd chromosome in humans and it contains a large number of polymorphisms that may have an effect on neurotransmission and thus contribute to the development of depression. Although various studies have investigated COMT gene variants associated with neurophysiological, behavioral and clinical phenotypes of depression, as well as responding to antidepressant therapy, the literature results are often contradictory. As the role of the COMT gene in the development of depression is not clear, the aim of the study was to determine whether there is any association between the rs4680 and rs4818 COMT genetic polymorphisms with the severity of depression symptoms in depressed patients. The results of this study showed that there was no statistically significant association of the two COMT gene variants with severity of depression symptoms, except rs4680 with hypochondriacal symptoms of HAMD scale.