Mann J John, Oquendo Maria A, Watson Kalycia Trishana, Boldrini Maura, Malone Kevin M, Ellis Steven P, Sullivan Gregory, Cooper Thomas B, Xie Shan, Currier Dianne
Department of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University, 1051 Riverside Drive, New York, New York; Department of Psychiatry, Columbia University, 1051 Riverside Drive, New York, New York; Department of Radiology, Columbia University, 1051 Riverside Drive, New York, New York.
Depress Anxiety. 2014 Oct;31(10):814-21. doi: 10.1002/da.22278. Epub 2014 May 27.
Low gamma-aminobutyric acid (GABA) is implicated in both anxiety and depression pathophysiology. They are often comorbid, but most clinical studies have not examined these relationships separately. We investigated the relationship of cerebrospinal fluid (CSF) free GABA to the anxiety and depression components of a major depressive episode (MDE) and to monoamine systems.
Patients with a DSM-IV major depressive episode (N = 167: 130 major depressive disorder; 37 bipolar disorder) and healthy volunteers (N = 38) had CSF free GABA measured by gas chromatography mass spectroscopy. Monoamine metabolites were assayed by high performance liquid chromatography. Symptomatology was assessed by Hamilton depression rating scale.
Psychic anxiety severity increased with age and correlated with lower CSF free GABA, controlling for age. CSF free GABA declined with age but was not related to depression severity. Other monoamine metabolites correlated positively with CSF GABA but not with psychic anxiety or depression severity. CSF free GABA was lower in MDD compared with bipolar disorder and healthy volunteers. GABA levels did not differ based on a suicide attempt history in mood disorders. Recent exposure to benzodiazepines, but not alcohol or past alcoholism, was associated with a statistical trend for more severe anxiety and lower CSF GABA.
Lower CSF GABA may explain increasing severity of psychic anxiety in major depression with increasing age. This relationship is not seen with monoamine metabolites, suggesting treatments targeting the GABAergic system should be evaluated in treatment-resistant anxious major depression and in older patients.
低γ-氨基丁酸（GABA）与焦虑症和抑郁症的病理生理学均有关联。焦虑症和抑郁症常合并存在，但大多数临床研究并未分别考察这些关系。我们研究了脑脊液（CSF）中游离GABA与重度抑郁发作（MDE）的焦虑和抑郁成分以及单胺系统之间的关系。
采用气相色谱质谱法测量了167例符合《精神疾病诊断与统计手册》第四版（DSM-IV）重度抑郁发作的患者（130例重度抑郁症；37例双相情感障碍）及38名健康志愿者脑脊液中的游离GABA。采用高效液相色谱法测定单胺代谢产物。通过汉密尔顿抑郁量表评估症状学。
在控制年龄因素后，精神性焦虑严重程度随年龄增长而增加，且与脑脊液中较低的游离GABA相关。脑脊液游离GABA随年龄下降，但与抑郁严重程度无关。其他单胺代谢产物与脑脊液GABA呈正相关，但与精神性焦虑或抑郁严重程度无关。与双相情感障碍患者及健康志愿者相比，重度抑郁症患者脑脊液中的游离GABA较低。基于情绪障碍患者的自杀未遂史，GABA水平并无差异。近期使用苯二氮䓬类药物（而非酒精或既往酒精成瘾）与更严重的焦虑及更低的脑脊液GABA存在统计学趋势相关。
脑脊液中较低的GABA可能解释了重度抑郁症中随着年龄增长精神性焦虑严重程度增加的现象。单胺代谢产物未见这种关系，这表明针对GABA能系统的治疗应在难治性焦虑性重度抑郁症及老年患者中进行评估。
