Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression

An abnormal expression of noradrenergic proteins (e.g., tyrosine hydroxylas e, norepinephrine transporters) in the locus coeruleus has recently been de monstrated in subjects with major depression and/or victims of suicide. Mon oamine oxidase A (MAO-A) is a key enzyme in the catabolism of biogenic amin es and is expressed in brain noradrenergic neurons. In this study, the bind ing of [H-3]Ro41-1049 to MAO-A was measured by quantitative autoradiography at multiple levels along the rostral-caudal axis of the noradrenergic locu s coeruleus from subjects with major depression and age- and postmortem int erval-matched control subjects who were psychiatrically normal. [H-3]Ro41-1 049 binding to MAO-A was unevenly distributed along the axis of the locus c oeruleus, paralleling an uneven number of neuromelanin-containing (noradren ergic) neurons throughout the nucleus. Accordingly, there was a significant correlation between the number of neuromelanin-containing neurons per sect ion and the specific binding of [H-3]Ro41-1049 at any particular level of t he locus coeruleus in control subjects (r(2) = 0.25; p < 0.001) and in subj ects with major depression (r(2) = 0.14; p < 0.001). Moderate levels of [H- 3]Ro41-1049 binding were observed in regions surrounding the locus coeruleu s, including the central gray and the dorsal and median raphe nuclei. No si gnificant differences in [H-3]Ro41-1049 binding to MAO-A were observed at a ny level of the locus coeruIeus, or raphe nuclei, comparing subjects with m ajor depression to psychiatrically normal control subjects. These findings demonstrate that the pathophysiology of major depression is not likely to i nvolve abnormalities in MAO-A. (C) 1999 Elsevier Science B.V. All rights re served.