Increased levels of lipid and protein oxidation in rat prefrontal cortex after treatment by lithium, valproic acid, and olanzapine.

Oxidative stress is widely accepted to contribute to the pathogenesis of several psychiatric diseases. Many antipsychotic drugs and mood stabilizers act through restoration of the dysregulated oxidative homeostasis in the brain. However, the long-term effect of these drugs per se in terms of their potential to interfere with the oxidative status in the brain remains largely controversial. The present study aimed to investigate the sole effect of three commonly used psychoactive drugs, lithium, valproic acid, and olanzapine, on lipid and protein oxidation status in the prefrontal cortex of healthy rats. A total of 80 adult male albino Wistar rats were used, and groups were treated with saline (control), lithium, valproic acid, or olanzapine daily for 30 days. Following sacrification, right prefrontal cortexes were dissected and homogenized. Lipid peroxidation (LPO) and protein oxidation (AOPP) assays were performed by ELISA. LPO levels were significantly higher in lithium and valproic acid-treated rats by 45% and 40%, respectively. Olanzapine treatment caused a mild 26% increase in LPO levels, but the effect was non-significant. Lithium, valproic acid, and olanzapine treatments significantly increased AOPP levels by 58%, 54%, and 36.5%, respectively. There was a strong positive correlation between the lipid peroxidation and protein oxidation levels. Our results call attention to the need to consider the pro-oxidative capacity of antipsychotic drugs per se and their potential to disturb the oxidative homeostasis in the brain during long-term medication for psychiatric diseases.

Increased growth hormone secretagogue receptor-1a (GHSR-1a) in hypothalamus during olanzapine treatment in rats.

Weight gain is the one of the most important factors which increases global burden of psychiatric disorder. Second-generation antipsychotics, olanzapine (Olz) and valproic acid (Vpa) in particular, are held responsible for weight gain. However, it is still uncertain how these drugs cause this. Thus, the rats selected for the experiment were randomly divided into 3 groups. The 1st group received only 0.5 ml saline solution intraperitoneally (n = 20, control group); the second group was given 200 mg / kg Vpa intraperitoneally (n = 20, Vpa group) and 2 mg / kg Olz was given intraperitoneally to the 3rd group (n = 20, Olz group) between 8 and 10 am for 30 days. We examined serum leptin, adiponectin, resistin, TNF-α, IL-6, ghrelin level and, the amount of ghrelin secreting cells in the stomach and growth hormone secretagogue receptor-1a (GHSR-1a, ghrelin receptor) expression in the hypothalamus. The hypothalamic GHS-1a receptor index was significantly higher in the Olz group compared with the control group and Vpa group (p = 0.036 and p = 0.016 respectively). Ghrelin immune positive cell index in stomach was statistically significantly lower in the Vpa group compared with the control and Olz groups (p = 0.028 and p = 0.013 respectively) There was no difference between the groups in terms of serum leptin, resistin, IL-6 and ghrelin levels. In the Vpa group, a statistically significant increase was found in serum adiponectin level compared with both the control group and the Olz group (p = 0009 and p = 0024 respectively) and, significant decrease was found in serum TNF-α level compared to Olz group (p = 0007). In conclusion, we found that the main cause of weight gain in Olz use was the increase in the number of hypothalamic ghrelin receptors. Investigating the mechanism by which Olz increases the number of ghrelin receptors may help to develop effective treatment strategies in preventing obesity in psychiatric patients.

Neurotrophic factors in bipolar disorders patients with manic episode

Background/aim: Neurotrophins are one of the most important molecule groups affecting cerebral neuroplasticity. The amount of evidence about the role of changes in neuroplasticity in the pathophysiology of bipolar disease is growing. Materials and methods: We measured serum levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), glial cell-line derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor (FGF)-2, neuritin 1 (Nrn 1) in bipolar 1 manic episode patients (n = 45) and healthy control group. Results: When controlled for age, BMI and cortisol, it was found that the serum levels of BDNF, NGF, NT-3, VEGF and FGF-2 of bipolar manic episode patients were not statistically different compared to those of the control group. GDNF level and Nrn 1 levels were significantly lower (P = 0.003 and P = 0.025 respectively) while IGF-1 levels were significantly higher than the control group (P = 0.0001). ROC analysis was performed and the area under the the curve was calculated as 0.737, 0.766 for GDNF, IGF-1 respectively. Conclusion: The changes in the levels of GDNF, IGF-1 and Nrn 1 might be involved in pathopysiology of bipolar disorder, and GDNF, IGF-1 may be considered as state markers in bipolar manic episode.