Cheetham S C, Crompton M R, Katona C L, Parker S J, Horton R W
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, U.K.
Brain Res. 1988 Sep 13;460(1):114-23. doi: 10.1016/0006-8993(88)91211-5.
We have investigated the involvement of gamma-aminobutyric acid (GABA) in depression by quantitating benzodiazepine (BZ) binding sites, the ability of GABA to stimulate BZ binding and glutamic acid decarboxylase activity in frontal and temporal cortex obtained at postmortem examination from 21 suicide victims and 21 age- and sex-matched controls. We limited our study to suicide victims with clear evidence of depression, in the absence of symptoms of other psychiatric disorders. Thirteen of the depressed suicide victims had not been prescribed psychoactive drugs recently and none were found in their blood at postmortem; of the remaining 8 suicides, 6 were receiving antidepressant drugs, alone or in combination with other drugs. The number of BZ binding sites was significantly greater (by 18%) in the frontal cortex of the total group of depressed suicides compared to controls, but did not differ in the temporal cortex. The increase in the number of BZ binding sites in the frontal cortex was of similar magnitude when drug-free (16%), drug-treated (21%) and antidepressant-treated suicides (16%) were compared to matched controls, although the increase was only statistically significant for the drug-treated suicides. The Kd of BZ binding and the ability of GABA to stimulate BZ binding did not differ significantly between controls and the total, drug-free, drug-treated or antidepressant-treated suicides in either cortical area. Glutamic acid decarboxylase activity did not differ significantly between control and suicide groups, but was markedly reduced in subjects dying by carbon monoxide poisoning. The present study provides evidence for a greater number of BZ binding sites in the frontal cortex of depressed suicide victims, which could not clearly be attributed to drug treatment.
我们通过对21名自杀受害者和21名年龄及性别匹配的对照者死后尸检获得的额叶和颞叶皮质中苯二氮䓬（BZ）结合位点进行定量、γ-氨基丁酸（GABA）刺激BZ结合的能力以及谷氨酸脱羧酶活性进行研究，探讨了GABA与抑郁症的关系。我们将研究局限于有明确抑郁症证据且无其他精神疾病症状的自杀受害者。13名抑郁自杀受害者近期未服用精神活性药物，死后血液中也未检测到；其余8名自杀者中，6名正在接受抗抑郁药物治疗，单独或与其他药物联合使用。与对照组相比，抑郁自杀者总群体额叶皮质中的BZ结合位点数量显著增加（增加了18%），但颞叶皮质中无差异。将未用药（16%）、用药治疗（21%）和接受抗抑郁治疗的自杀者（16%）与匹配对照组相比，额叶皮质中BZ结合位点数量的增加幅度相似，尽管仅用药治疗的自杀者增加具有统计学意义。在两个皮质区域中，对照组与自杀者总群体、未用药、用药治疗或接受抗抑郁治疗的自杀者之间，BZ结合的解离常数（Kd）以及GABA刺激BZ结合的能力均无显著差异。对照组和自杀组之间谷氨酸脱羧酶活性无显著差异，但死于一氧化碳中毒的受试者中该活性明显降低。本研究为抑郁自杀受害者额叶皮质中存在更多BZ结合位点提供了证据，且这一现象不能明确归因于药物治疗。
