Altered concentrations of dopamine transporter and D2/D3 receptors have been observed in the amygdaloid complex of subjects with major depression. These findings are suggestive of neurochemical abnormalities in the limbic dopamine system in depression. Monoamine oxidase-B (MAO-B) is a key enzyme in the catabolism of biogenic amines, including dopamine, and alterations in this enzyme may underlie dopaminergic abnormalities associated with depression. The specific binding of [ 3 H]lazabemide to MAO-B was measured in the right amygdaloid complex of 15 major depressive subjects and 16 psychiatrically normal controls. Subjects of the two study groups were matched as close as possible for age, sex, and postmortem interval. Examination of the regional distribution of MAO-B revealed lower [ 3 H]lazabemide binding to MAO-B in the lateral and basal nuclei of the amygdala and higher binding in the medial nucleus. A modest elevation in binding to MAO-B observed in all amygdaloid nuclei in major depressive subjects as compared to control subjects failed to reach statistical significance. A significant decrease in binding to MAO-B was observed when cigarette smokers were compared to nonsmoking subjects. The amount of MAO-B binding positively correlated with the age of subjects in all nuclei investigated. A decreased amount of MAO-B in smokers further validates the pharmacological effect of tobacco smoke on this enzyme.

Major depression and suicide are associated with altered concentrations of specific noradrenergic proteins in the human locus coeruleus (LC). Based on experimental studies that can reproduce these LC abnormalities in laboratory animals, we hypothesized that noradrenergic pathobiology in depression is a result of over-activity of the LC. LC activity is under the control of both excitatory and inhibitory inputs. A major inhibitory input to the LC is GABAergic, arising from the nucleus prepositus hypoglossi. Numerous studies demonstrating low levels of GABA in the CSF and plasma of subjects with major depressive disorder (MDD) raise the possibility that LC over-activity in depression may be secondary to reduced GABAergic input to the LC. Here, GABAergic input to the LC in depression was evaluated by studying the binding of [ 3 H]flunitrazepam to GABA A receptors at three anatomically-defined levels of the human postmortem LC. LC tissues were collected from subjects with MDD, subjects with depressive disorders including MDD that died as a result of suicide, and psychiatrically normal control subjects. A modest rostral-caudal gradient of GABA A receptor binding density was observed amongst all subjects. No significant differences in the amount of binding to GABA A receptors were observed between control subjects (n=21) and MDD subjects (n=9) or depressed suicide victims (n=17). These results demonstrate that GABA A receptor binding in the LC measured with [ 3 H]flunitrazepam is not altered in subjects with depressive illnesses.

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