| [Objective] To investigate the relationship between serum concentration of the brain-derived neurotrophic factor (BDNF) , single nucleotide polymorphisms (SNP) and bipolar disorder. To study the relationship between serum concentration of BDNF, SNP and the effect of acute mania with drug treatment.[Methods] 1. Patients meet the diagnostic criteria of bipolar disorder in Diagnostic and Statistical Manual for mental disorder-IV in Shanghai Mental Health Center and other mental health center from July to December in 2008 were included with informed consent. Blood sample were got to test the serum concentration of BDNF and the genotype of rs6265 and rs11030101 and the assessment of Young Mania Rating Scale, Hamilton Depression Rating Scale and Clinical Global Impression were collected at the same time. The BDNF concentration and the genotype of rs6265 and rs11030101 were compared to the clinical characters of bipolar disorder.2. Those meet the criteria of acute mania were treated for 4 weeks with drugs which were not strictly defined but titrated to full treatment dosage in a week. YMRS, CGI and Treatment Emergent Symptoms Scale (Tess) were assessed in the base line, the first, second, third and forth week in the treatment. The BDNF concentration and genotype of rs6265 and rs11030101 were compared to the clinical characters of bipolar disorder.3. All the studies of the relationship between BDNF polymorphisms and bipolar disorder with Chinese samples were included and analysized with mate-analysis.[Results]Part I: Two hundred and twenty eight bipolar disorder patients were included with 107 males, 60 with family history and 200 divided into type I. The average age was 38.28±14.03 years old and the average course were 138.15±134.9 months. The median onset age was 23.62 years old. 86.84% patients used two or more drugs in the latest 12 months. At the baseline, 87.72% patients used two or more drugs and the most used drug were antipsychotic drugs(62.28%) and valproate(53.95%). All among the patients, 85 were in acute mania and 14 were in depression with the other 129 were in euthymic phase.The average concentration of BDNF were 18.75±8.98 ng/ml and were significantly lower than the normal control ( 23.72±5.60 ng/ml), p<0.001. The average BDNF concentration of mania group, depression group and euthymic group were respectively 20.64±8.49 ng/ml, 17.55±8.45 ng/ml and 17.66±9.20 ng/ml, with statistically lower than the normal control.The average BDNF concentration has no relationship with gender, age, type, family history, onset age, severity and the tolerance of drug treatment. However, in the all patients group and euthymic group, the average BDNF concentration of deterioration group in the global improvement was the highest while that of obviously group was the lowest. The difference has statistical meaning, P=0.003 and P=0.015. The average BDNF concentration between rs6265 G/G and A/A genotype were significantly different, P=0.036.The genotype and allele of rs6265 and rs11030101 has no relationship with age, gender, type, family history, treatment effect and tolerance in bipolar disorder.Part 2: Fifty-eight patients were included in this study and 43 finished it. 26 patients were male. The average age was 38.43±14.65 years old and the average course was 138.28±116.23 months. The YMRS scores were lower step by step at the base line, 1, 2, 3, 4 weeks after treatment. The difference has statistical meaning, P<0.001. The distribution of severity and change degree of CGI were significantly changed at the base line, 1, 2, 3 , 4 weeks after treatment, P<0.001. The BDNF concentration were significantly increased after 4-week-treatment(19.74±7.94ng/ml and 24.68±10.78 ng/ml), P=0.001. The change of BDNF concentration has no relationship with the change of symptoms. Compared to the normal control, the G allele of rs6265 were significantly higher than other allele in the response group. The adverse events were rare and need not any treatment. The most common adverse event was 8.62%.Part 3: Three articles were found and it was 4 studies with our investigate included. There were 627 bipolar patients and 920 normal controls. There was no significant difference between two groups in the genotype of rs6265. And there was no significant difference between early onset bipolar disorder and normal controls.[Conclusions]1. The BDNF concentration was significantly lower than normal controls, whether it was in mania, depression or euthymic phase.2. There was no relationship between the change of BDNF concentration and the change of symptoms. 3. The genotype of rs6265 maybe related to the BDNF concentration.4. The BDNF concentration increased significantly after 4 weeks drugs treatment. The BDNF concentration maybe is a marker of mania symptoms. |
