High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides
High throughput lipidomic profiling of schizophrenia and bipolar disorder brain tissue reveals alterations of free fatty acids, phosphatidylcholines, and ceramides
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DOI：
10.1021/pr800188y
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发表时间：
2008-10-01
影响因子：
4.4
通讯作者：
Bahn, Sabine
中科院分区：
文献类型：
--
作者：
Schwarz, Emanuel;Prabakaran, Sudhakaran;Bahn, Sabine
采用基于质谱的高通量方法来分析 45 名受试者（包括 15 名精神分裂症患者和 15 名双相情感障碍患者）以及 15 名对照样本的前额皮质（布罗德曼 9 区）白质和灰质脂质水平。我们发现，与对照组相比，精神分裂症和躁郁症样本的灰质和白质中的游离脂肪酸和磷脂酰胆碱水平发生了统计学上的显着变化。此外，与对照水平相比，两种神经精神疾病的白质中的神经酰胺显着增加。本研究调查的患者队列包括许多未曾接受药物治疗和未经治疗的患者，可以评估药物对血脂水平的影响。我们的研究结果表明，虽然灰质磷脂酰胆碱水平受到抗精神病药物的影响，但白质中的磷脂酰胆碱水平却并非如此。白质或灰质中游离脂肪酸或神经酰胺的变化似乎也不受抗精神病药物治疗的影响。为了评估活体患者的血脂谱，我们还对 40 个红细胞样本的血脂进行了分析，其中 7 个样本来自未接受过药物治疗的首次发病患者。我们发现游离脂肪酸和神经酰胺的浓度发生了显着变化。总体而言，我们的研究结果表明，脂质异常可能是精神分裂症和双相情感障碍的疾病固有特征，反映在中枢神经系统和周围组织的显着变化。
A mass spectrometry based high throughput approach was employed to profile white and gray matter lipid levels in the prefrontal cortex (Brodmann area 9) of 45 subjects including 15 schizophrenia and 15 bipolar disorder patients as well as 15 controls samples. We found statistically significant alterations in levels of free fatty acids and phosphatidylcholine in gray and white matter of both schizophrenia and bipolar disorder samples compared to controls. Also, ceramides were identified to be significantly increased in white matter of both neuropsychiatric disorders as compared to control levels. The patient cohort investigated in this study includes a number of drug naive as well as untreated patients, allowing the assessment of drug effects on lipid levels. Our findings indicate that while gray matter phosphatidylcholine levels were influenced by antipsychotic medication, this was not the case for phosphatidylcholine levels in white matter. Changes in free fatty acids or ceramides in either white or gray matter also did not appear to be influenced by antipsychotic treatment. To assess lipid profiles in the living patient, we also profiled lipids of 40 red blood cell samples, including 7 samples from drug naive first onset patients. We found significant alterations in the concentrations of free fatty acids as well as ceramide. Overall, our findings suggest that lipid abnormalities may be a disease intrinsic feature of both schizophrenia and bipolar disorder reflected by significant changes in the central nervous system as well as peripheral tissues.