Munkholm Klaus, Pedersen Bente Klarlund, Kessing Lars Vedel, Vinberg Maj
Psychiatric Center Copenhagen, Rigshospitalet, University of Copenhagen, Denmark.
The Centre of Inflammation and Metabolism and The Centre for Physical Activity Research, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
Psychoneuroendocrinology. 2014 Sep;47:199-211. doi: 10.1016/j.psyneuen.2014.05.011. Epub 2014 May 27.
Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3 were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder patients during a 6-12 months period and compared with repeated measurements in healthy control subjects. Careful attention was given to standardization of all procedures and adjustment for potential confounders of BDNF and NT-3. In linear mixed models, adjusting for demographical and lifestyle factors, levels of BDNF were significantly elevated in bipolar disorder patients in euthymic- (p<0.05), depressed- (p<0.005) and manic/hypomanic (p<0.005) states compared with healthy control subjects. Within bipolar disorder patients, adjusting for medication, there was no significant difference in BDNF levels between affective states, with equally elevated levels present in euthymic-, depressive- and manic/hypomanic patients. Levels of BDNF were higher in patients with longer duration of illness compared with patients with shorter duration of illness. We found no difference in NT-3 levels between bipolar disorder patients in any affective state compared with healthy control subjects and no difference in NT-3 levels between affective states in bipolar disorder patients. The results suggest that BDNF may be a marker related to illness stage in bipolar disorder, not varying with affective states in rapid cycling bipolar disorder patients. Due to the nature of comparison, it cannot be excluded that the finding of elevated BDNF levels in bipolar disorder patients compared with healthy controls could be influenced by medication.
神经可塑性受损可能与双相情感障碍的病理生理学有关，涉及神经营养因子脑源性神经营养因子（BDNF）和神经营养因子3（NT-3）的外周改变。证据受到方法学问题的限制，且主要基于病例对照设计。本研究的目的是调查快速循环型双相情感障碍患者与健康对照者之间BDNF和NT-3水平是否存在差异，以及快速循环型双相情感障碍患者的BDNF和NT-3水平是否随情感状态而改变。使用酶联免疫吸附测定（ELISA）法测量了37例快速循环型双相情感障碍患者和40例年龄及性别匹配的健康对照者的血浆BDNF和NT-3水平。在纵向设计中，对双相情感障碍患者在6至12个月期间的各种情感状态下的BDNF和NT-3进行重复测量，并与健康对照者的重复测量结果进行比较。对所有程序的标准化以及BDNF和NT-3潜在混杂因素的调整给予了仔细关注。在线性混合模型中，在调整人口统计学和生活方式因素后，与健康对照者相比，双相情感障碍患者在心境正常（p<0.05）、抑郁（p<0.005）和躁狂/轻躁狂（p<0.005）状态下的BDNF水平显著升高。在双相情感障碍患者中，在调整药物治疗后，情感状态之间的BDNF水平无显著差异，心境正常、抑郁和躁狂/轻躁狂患者的BDNF水平均同样升高。病程较长的患者的BDNF水平高于病程较短的患者。我们发现，与健康对照者相比，双相情感障碍患者在任何情感状态下的NT-3水平均无差异，且双相情感障碍患者情感状态之间的NT-3水平也无差异。结果表明，BDNF可能是双相情感障碍中与疾病阶段相关的标志物，在快速循环型双相情感障碍患者中不随情感状态而变化。由于比较的性质，不能排除双相情感障碍患者与健康对照者相比BDNF水平升高的发现可能受药物影响。
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