Ray M T, Shannon Weickert C, Webster M J
1] Stanley Medical Research Institute, Laboratory of Brain Research, Rockville, MD, USA [2] Trinity Washington University, NE Washington, DC, USA.
1] Schizophrenia Research Institute, Sydney, NSW, Australia [2] Neuroscience Research Australia, Randwick, NSW, Australia [3] School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Transl Psychiatry. 2014 May 6;4(5):e389. doi: 10.1038/tp.2014.26.
Abnormalities in brain-derived neurotrophic factor (BDNF)/trkB signaling have been implicated in the etiology of schizophrenia and mood disorders. Patients with schizophrenia, bipolar disorder (BPD) and major depression (MDD) have reduced levels of neurotrophins in their brains when compared with normal unaffected individuals; however, only a few brain areas have been examined to date. Owing to the broad range of symptoms manifested in these disorders, we hypothesized that multiple associative areas of the neocortex may be implicated and that the degree of change in BDNF and trkB-TK+ mRNA expression and the cortical region or layers involved may vary according to Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnosis. We compared BDNF and trkB-TK+ mRNA levels across all layers of the prefrontal cortex (dorsolateral prefrontal cortex, DLPFC), orbital frontal cortex (OFC), anterior cingulate cortex (ACC), inferior temporal gyrus (ITG) and superior temporal gyrus (STG) in four groups: schizophrenia, BPD, MDD and unaffected controls (n=60). BDNF mRNA levels were significantly decreased in layers IV and V of DLPFC in schizophrenia patients, in layer VI of ACC in schizophrenia and MDD and in layer VI of ITG in schizophrenia, BPD and MDD. BDNF mRNA levels were also significantly decreased in layer V and/or VI of STG in schizophrenia, BPD and MDD. TrkB-TK+ mRNA levels were only significantly decreased in the cortical layer VI of OFC in BPD. The shared and distinct patterns of neurotrophin transcript reductions, with some specific to each group, may compromise the function and plasticity of distinct cortical areas to various degrees in the different groups and contribute to the range and overlap of symptoms manifested across the diagnoses.
脑源性神经营养因子（BDNF）/酪氨酸激酶受体B（trkB）信号通路异常与精神分裂症和心境障碍的病因有关。与未受影响的正常个体相比，精神分裂症、双相情感障碍（BPD）和重度抑郁症（MDD）患者大脑中的神经营养因子水平降低；然而，迄今为止仅对少数脑区进行了检查。由于这些疾病表现出广泛的症状，我们推测新皮层的多个联合区域可能受累，并且BDNF和trkB-TK+ mRNA表达的变化程度以及所涉及的皮质区域或层可能因《精神疾病诊断与统计手册》（DSM）诊断而异。我们比较了四组患者（精神分裂症、BPD、MDD和未受影响的对照组，n = 60）前额叶皮质（背外侧前额叶皮质，DLPFC）、眶额皮质（OFC）、前扣带回皮质（ACC）、颞下回（ITG）和颞上回（STG）各层的BDNF和trkB-TK+ mRNA水平。精神分裂症患者DLPFC的IV层和V层、精神分裂症和MDD患者ACC的VI层以及精神分裂症、BPD和MDD患者ITG的VI层中BDNF mRNA水平显著降低。精神分裂症、BPD和MDD患者STG 的V层和/或VI层中BDNF mRNA水平也显著降低。仅BPD患者OFC皮质VI层的TrkB-TK+ mRNA水平显著降低。神经营养因子转录本减少的共同和独特模式，其中一些模式特定于每组，可能在不同程度上损害不同组中不同皮质区域的功能和可塑性，并导致各诊断中表现出的症状范围和重叠。
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