Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims.
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.
Cheetham
S C
SC
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, U.K.
Crompton
M R
MR
Katona
C L
CL
Parker
S J
SJ
Horton
R W
RW
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003863:Depression / Q000378:metabolism*; D003866:Depressive Disorder / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009928:Organ Specificity; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013405:Suicide; D013702:Temporal Lobe / Q000378:metabolism
D000928:Antidepressive Agents; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D005968:Glutamate Decarboxylase