There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.
Abstract
Neurophysiological studies of major depression performed using PET imaging have shown
abnormalities of regional cerebral blood flow (CBF) and glucose metabolism in multiple
prefrontal cortical and limbic structures that have been more generally implicated
in emotional processing. The current study investigated the effects of antidepressant
drug treatment in these regions using PET measures of glucose metabolism. Subjects
with primary MDD (n=27) were imaged while unmedicated and depressed, and, of these,
20 were rescanned following chronic antidepressant drug treatment. Regional metabolism
was compared between unmedicated depressives and controls and between the pre- and
post-treatment conditions in regions-of-interest (ROI) where metabolism or flow had
previously been shown to be abnormal in unmedicated depressives. At baseline, the
mean metabolism was increased in the left and right lateral orbital cortex/ventrolateral
prefrontal cortex (PFC), left amygdala, and posterior cingulate cortex, and decreased
in the subgenual ACC and dorsal medial/dorsal anterolateral PFC in the unmedicated
depressives relative to controls, consistent with the results of previous studies.
Following treatment, metabolism significantly decreased in the left amygdala and left
subgenual ACC, and corresponding changes in the orbital and posterior cingulate cortices
approached significance. The metabolic reduction in the amygdala and right subgenual
ACC appeared largely limited to those subjects who both responded to treatment and
remained well at 6 months follow-up, in whom the reduction in amygdala metabolism
tightly correlated with the reduction in HDRS scores. The magnitude of the treatment-associated,
metabolic change in the amygdala also correlated positively with the change in the
stressed plasma cortisol levels measured during scanning. These data converge with
those from other PET studies to indicate that primary MDD is associated with abnormal
metabolism in limbic and paralimbic structures of the mesiotemporal and prefrontal
cortices. Chronic antidepressant drug treatment reduces metabolism in the amygdala
and ventral ACC in subjects showing a persistent, positive treatment response. In
contrast, the persistence of the abnormal metabolic deficits in the dorsomedial/dorsal
anterolateral PFC in MDD during treatment may conceivably relate to the histopathological
changes reported in these regions in post mortem studies of MDD.