engleski

Serotonin receptor gene polymorphisms and the side effects of antipsychotic drugs

Schizophrenia is a chronic psychotic illness that impairs mental and social functioning and affects approximately 1% of the world population. It is characterized by positive and negative symptoms, disorganization in speech and behavior, as well as by cognitive deficits. However, this complex disorder is diverse in its clinical presentation, course of the disease and response to therapy. Although various studies suggest strong genetic component, its etiology is still unclear. The antipsychotic drugs used for schizophrenia treatment are usually divided into first- generation (FGA) and second-generation antipsychotics (SGA), which differ in their pharmacological profile. Namely, FGA which are especially effective in the treatment of positive symptoms, primarily act via antagonism of dopamine D2 receptors, while SGA which can reduce both the positive and negative symptoms of schizophrenia, are also serotonin 5-HT2A receptor antagonists. However, despite many available antipsychotic drugs, some patients do not respond satisfactorily to therapy, while others develop side-effects that substantially compromise the treatment, leading to discontinuation of therapy and frequent relapse of the disease. The main side-effects of FGA treatment are acute or chronic extrapyramidal symptoms (EPS), developed as a result of reduced dopaminergic neurotransmission in the nigrostriatal dopamine pathway. In contrast to the tight blockade of D2 receptors by FGA, the binding of SGA to D2 receptors does not last long enough to induce EPS. On the other hand, SGA treatment is often associated with metabolic side effects including metabolic syndrome, probably due to their greater affinity to serotonin receptors. In order to improve schizophrenia therapy, recent studies are focusing on the genetic background of individual differences in the response to antipsychotic treatment, as well as in the development of different side-effects. As the role of serotonin receptor genes in the development of antipsychotics side-effects is not clear, the aim of our study was to examine the association of various serotonin receptor gene polymorphisms with the development of extrapyramidal and metabolic side-effects in schizophrenic patients following haloperidol and olanzapine therapy, respectively.

Schizophrenia; antipsychotic; side-effect; metabolic syndrome; extrapyramidal symptom; serotonin receptor gene; polymorphism; haloperidol; olanzapine

nije evidentirano