Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients

Wed, 12 Feb 2020 00:00:00 GMT

Название: Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients Авторы: Losenkov, Innokentiy S.; Mulder, Nathaniël J. V.; Levchuk, Lyudmila A.; Vyalova, Natalya M.; Loonen, Anton J. M.; Bosker, Fokko J.; Simutkin, German G.; Boiko, Anastasiia S.; Bokhan, Nikolay A.; Wilffert, Bob; Hak, Eelko; Schmidt, Amand F.; Ivanova, Svetlana A. Краткий осмотр (реферат): Background: Brain-derived neurotrophic factor (BDNF) plays an important role in neuronal plasticity, and its dysregulation has been associated with the pathogenesis of mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone which is also produced as a cytokine by immune cells and could be a neurotrophic factor regulating the functional activity of stress-related mechanisms. Aim: To investigate the possible relationship between depressive state and BDNF and PRL genotypes or levels with special reference to severity of depression. Methods: Participants of 18–70 years with a clinical diagnosis of depressive disorder of at least moderate severity were included. These patients had not been treated with antidepressant drugs before admission to hospital during the preceding period of the last 6 months, and 54.5% had never been treated with antidepressant drugs during their entire life. The DNA was genotyped for rs1341239 within the prolactin and for rs6265, rs7124442, and rs11030104 within the BDNF gene. Rs11030104 violated the Hardy-Weinberg equilibrium distribution and was excluded from further analyses. BDNF and prolactin concentration was measured in serum by MAGPIX multiplex analyzer (Luminex, USA) using MILLIPLEX® MAP kit (Merck, Germany). Genetic associations were determined by sequentially regressing prolactin, BDNF, 17-items Hamilton's Depression (HAMD-17) and Clinical Global Impression scale, Severity (CGI-S) ratings, and depression (absent/present) on the available SNPs. Genetic associations were evaluated assuming an additive model. Results: A total of 186 depressed patients (of which 169 were women) and 94 healthy controls (67 women) were genotyped. After excluding subjects without genetic information on all three study SNPs, 217 remained of whom 138 suffered from depression. Within depressed patients we observed an association of rs6265 with HAMD-17: mean difference (MD) 2.33 (95%CI 0.49; 4.16; p = 0.014) and CGI-S: MD 0.38 (95%CI 0.09; 0.66; p = 0.011). No significant association was observed between the prolactin SNP rs1341239 and prolactin levels. Similarly the mean differences of BDNF SNPs did not show an association with BDNF: rs6265 −0.042 ln(pg/ml) (95%CI −0.198; 0.113), and rs7124442 0.006 ln(pg/ml) (95%CI −0.117; 0.130). No other association reached statistical significance. Conclusion: We observed a significant association between BDNF gene variant rs6265 and the severity of depression in newly admitted, antidepressant treatment-free, depressed patients. Actual PRL and BDNF levels were not elevated sufficiently in depressed patients to reach statistical significance and were not associated with the studied genotypes.

Changes in Body Fat and Related Biochemical Parameters Associated With Atypical Antipsychotic Drug Treatment in Schizophrenia Patients With or Without Metabolic Syndrome

Fri, 01 Nov 2019 00:00:00 GMT

Название: Changes in Body Fat and Related Biochemical Parameters Associated With Atypical Antipsychotic Drug Treatment in Schizophrenia Patients With or Without Metabolic Syndrome Авторы: Kornetova, Elena G.; Kornetov, Alexander N.; Mednova, Irina A.; Dubrovskaya, Viktoria V.; Boiko, Anastasia S.; Bokhan, Nikolay A.; Loonen, Anton J. M.; Ivanova, Svetlana A. Краткий осмотр (реферат): Background: Metabolic syndrome (MetS) is a common problem in schizophrenia patients and associated with increased mortality due to cardiovascular disease. Second-generation antipsychotics (SGAs) play an important role in facilitating MetS. Objective: The study aimed to assess weight changes and alterations of indicators of body fat composition and lipid-glucose metabolism induced by reinitiating atypical antipsychotics in patients with schizophrenia when with or without MetS. Methods: After giving informed consent, newly admitted patients with a clinical diagnosis of schizophrenia (ICD-10: F20) and an age between 18 and 55 years were included. MetS was diagnosed according to International Diabetes Federation (IDF) criteria. At entry and after 6 weeks of treatment, anthropometry and biochemical analysis were carried out. Total and visceral fats were measured with the use of non-invasive bioimpedance analysis and subcutaneous fat with calculation of total adipose tissue with the use of caliperometry. Based on biochemical assessments low density (LDL) and very low-density lipoproteins (VLDL), atherogenic index and Homeostatic Model Assessment of Insulin Resistance (IR-HOMA) were calculated. Statistical analysis was conducted using Wilcoxon signed-rank test, Mann-Whitney U-test, and chi-squared test. Differences were considered statistically significant at p < 0.05. Results: A total of 114 patients (59M/55F) with schizophrenia were examined; they were divided into two groups with (n = 43; 37.7%) and without (n = 71; 62.3%) MetS. After a 6-week SGA treatment, only the total fat fold, waist circumference, triglyceride level, and atherogenic index underwent statistically significant changes in patients with MetS. In those without MetS, statistically significant changes across all fat indicators were noted. Also, a significant increase in blood glucose and HOMA-IR parameters, triglyceride, and VLDL levels and atherogenic index was observed in this group. Discussion: The study illustrates the benefits of estimating both anthropometric and biochemical parameters shortly after (re)installing treatment of schizophrenia in order to minimize the risk of MetS development.

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Association Between BDNF Gene Variant Rs6265 and the Severity of Depression in Antidepressant Treatment-Free Depressed Patients

Changes in Body Fat and Related Biochemical Parameters Associated With Atypical Antipsychotic Drug Treatment in Schizophrenia Patients With or Without Metabolic Syndrome