| Background:Bipolar disorder (BD), a serious mood disorders characterized by recurrent clinical episodes of mania/hypomania and depression (depression could be absent in BDI) usually lead to disability. Compare with BDI, BDII is less understood. Recently, many studies focus on the comparison of clinical features between these two bipolar subtypes. One of the controversy is whether BDII is a less severe variant of BDI or a independent diagnostic categories, the aim of these studies is to better understand these two common bipolar subtypes.Recent researches on the pathogenesis of BD are more concerned about the changes of post-receptor (such as intracellular signal transduction system, gene transcription, gene regulation, neuron apoptosis and regeneration).Among them, the role of brain derived neurotropin factor (BDNF) is given serious attention. BDNF participate in many sections of post-receptor regulation and probably play a critical role in the pathophysiology of BD, which indicates BDNF might be a biomarker of BD. Furthermore, animal studies have showed that BDNF is related to the glycometabolism, which may partially explain the higher prevalence of diabetes mellitus in BD.Currently, though there are many external reaserches focus on the clinical characteristics of BDI and BDII, however the results are not consistent with each other and there is little reaserch focus on the Chinese population. The study of BDNF on BD mostly focus on the argument of state or trait issue, however, among those studies little recuit BDII patients. The studies focus on the BDNF level and glycometabolism indicators on BD isn't found so far. For these reason, we Interview with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P) to those patients who originally dignosised as affective disorders. To the patients who fulfill the criteria of BDI or BDII, questionnaire and scales will be evaluated subsequently. Specimens of blood will be taken from the BDI and BDII patients and the normal controls. All of the samples will be tested to evaluated the levels of BDNF, fasting blood glucose, fasting insulin and glycosylated hemoglobin.Objective:1. To compare the clinical features between bipolar disorder I and II, provide evidences to answer whether BDII is a less severe type of BDI or a valid diagnostic categories.2. To explore the possibility of BDNF as a biomarker (trait or state) of BD, and probe into the role of BDNF in the pathophysiology of BD.3. To test whether BD patients appear higher levels in some of the glycometabolism indicators.4. To examine the role of BDNF in the phenomenon of the high prevalence with diabetes mellitus in BD.Methods:1. Interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P) to those patients who were originally dignosised as affective disorders. To the patients who fulfill the criteria of BDI or BDII, questionnaire and scales (self-made demographic and clinical feature questionnaire, GAF, YMRS, MADRS) were evaluated subsequently.2. Recruited the nomal controls, eliminated those who fulfilled the criteria of axis I disorder. Specimens of blood were taken from the BDI and BDII patients and the normal controls. All of the samples were tested to evaluate the levels of BDNF, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and glycosylated hemoglobin (HbA1c).3. The levels of serum BDNF were tested by enzyme-linked immunosorbent assay (ELISA); 1) Compared the serum BDNF levels between BD patients and normal control. 2) Compared the serum BDNF levels between differert subgroups of BD (drugfree vs medicated, comorbid vs sigle diagnosis, BDI vs BDII).3) Compared the serum BDNF levels between different state of BD patients and nomal controls.4) Analyzed the correlation between the serum BDNF levels and the score of YMRS and MADRS.4. Tested the fasting blood glucose by glucose-oxidase method; tested the level of insulin by radioimmunoassay; Tested the HbA1c by high performance liquid chromatography. Calculated the insulin resistance index by the level of blood insulin and glucose with software of HOMA2-IR.5. Software SPSS 13.0 was used to analyze the results of our study. P<0.05 was decided for having statistical significance.Results:1. Among 156 patients, 151 of them completed the evaluation of SCID-I/P. 41 nomal controls were recruited to the study. 72 BDI and 39 BDII patients were found. Among the patients whose original diagnosis was depression, 35.5% of them were BDI and 4.8% were BDII. BDI showed more (hypo)mania episodes(3vs1, Z=-5.475, P<0.001) and greater incidence of psychotic symptoms (62.5%vs25.6%,χ~2=13.75, P<0.001), use of mood stabilizers (95.8%vs64.1%,χ~2=19.64, P<0.001) and higher rate of overweight/obesity (38.4%vs17.9%,χ~2=5.14, P=0.023) and score of YMRS (15vs2, Z=-5.68, P<0.001). Bipolar II patients had significant more previous episodes of both hypomania (1vs1, Z=-2.85, P=0.004) and depression (3vs1, Z=-4.42, P<0.001). Depressive episode as the first onset was much common in Bipolar II patients (76.9%vs55.6%,χ~2=4.96, P=0.026). Atypical features (23.1%vs5.6%,χ~2=5.91, P=0.015), suicide attempts rate (41.0%vs13.9%,χ~2=10.39, P=0.001) and MADRS score (13vs5, Z=-3.64, P<0.001) were also higher in bipolar II disorder. There were no significant differences in sexual, age, educational time, marriage, career of the two subtypes.2. The serum level of BDNF in BD was significantly lower than the normal controls (17.60±11.24 vs 26.04±12.85, t=-3,953, P<0.001), and the serum BDNF levels were still decreased of different periods of BD. There were no significant differences between various subgroups (paitents with or without medicated, with or without axis I comorbidity and between BDI and BDII.) of BD. The correlations between serum BDNF levels with YMRS, MADRS, BMI and WHR were negative.3. The FPI (6.5vs4.3, Z=-3.689, P<0.001) and HOMA2-IR (0.90vs0.70, Z=-3.121, P=0.002) in BD patients were significantly lower than the controls; The incidence rate of IR was higher in patients (44.1%vs24.4%,χ~2 =4.920, P=0.027), However, this differences disappeared after contolled for obesisty.4. Positve correlations were found between serum BDNF level and FPI(r=0.351, P<0.001) or HOMA2-IR(r=0.346,P<0.001), such correlations exist after control for WHR and BMI. We also found that this correlation only exist in the patients who has IR(r=0.361, P<0.001).Conclusions:1. BDII is not a less sever type of BDI, the result of the study indicates that it is better to classify them as vary disorder.2. The serum BDNF level are significantly lower in BD patients, this phenomenon seems not be affected by medicine, commobidity and subtype of BD, indicates that BDNF play a role in the pathophysiology of BD; The result shows that BDNF might be the biomarker even the trait marker of BD.3. The FPI and HOMA2-IR are higher in the BD patients group. The incidence rate of IR is much higher in BD patients, which could partly explain the reason why diabetes mellitus is highly prevalent in BD. The IR in BD patients is associated with obesity, much attentions should be paid to the obesity issue in BD patients.4. The serum BDNF levels are lower in BD, which could lead to the decrease of insulin sensitivity, BDNF may play a role in the the high prevalence rate of diabetes mellitus in BD is higher than general population. |
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