Body Weight and Plasma Levels of Ghrelin and Leptin during Treatment with Olanzapine

Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanisms underlying these side effects are poorly understood. Leptin and ghrelin were recently identified as hormones that play crucial roles in the regulation of energy balance and glucose metabolism. To elucidate relationships between weight change and plasma levels of ghrelin and leptin, we investigated the circulating ghrelin and leptin levels and body weight during olanzapine treatment. Twenty-four patients with schizophrenia were examined during 6-month administration of olanzapine. Ghrelin, leptin, weight and body mass index (BMI) were measured before and after 2, 4, 8, 12, 16, and 24 weeks of olanzapine treatment. The concentration of glucose and various lipid metabolic parameters were measured at baseline and at 24 weeks. Significant increases in weight, BMI and leptin were observed at week 24. On the other hand, the serum levels of ghrelin decreased significantly after olanzapine treatment. In addition, the level of ghrelin was negatively correlated with the leptin level, BMI and weight. The leptin level was positively correlated with both BMI and weight. Ghrelin is associated with metabolic changes, in combination with leptin, during olanzapine treatment. However, further large-scale and longitudinal studies are warranted to elucidate the metabolic changes involving ghrelin, leptin and insulin during treatment with antipsychotics.

Association between Alcoholism and the Genetic Polymorphisms of the GABA(A) Receptor Genes on Chromosome 5q33-34 in Korean Population

Family, twin, and adoption studies have demonstrated that genes play an important role in the development of alcoholism. We investigated the association between alcoholism and the genetic polymorphisms of the GABA(A) receptor genes on chromosome 5q33-34 in Korean population. The genotype of the GABA(A) receptor gene polymorphisms were determined by performing polymerase chain reaction genotyping for 172 normal controls and 162 male alcoholics who are hospitalized in alcoholism treatment institute. We found a significant association between the genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene and alcoholism. The GG genotype of the GABA(A) alpha1 receptor gene was associated with the onset age of alcoholism and alcohol withdrawal symptoms, and a high score on the Korean version of the ADS. However, there was no association between the genetic polymorphisms of the GABA(A) beta2 and gamma2 receptor gene and alcoholisms. Our finding suggest that genetic polymorphisms of the GABA(A) alpha1 and GABA(A) alpha6 receptor gene may be associated with the development of alcoholism and that the GG genotype of the GABA(A) alpha1 receptor gene play an important role in the development of the early onset and the severe type of alcoholism.