J Neuropsychiatry Clin Neurosci 1997; 9:471-481
Copyright © 1997 by American Neuropsychiatric Association
HS Mayberg
Department of Medicine (Neurology), University of Texas Health Science Center at San Antonio 78284-6240, USA. mayberg@uthscsa.edu
A working model of depression implicating failure of the coordinated
interactions of a distributed network of limbic-cortical pathways is
proposed. Resting state patterns of regional glucose metabolism in
idiopathic depressed patients, changes in metabolism with antidepressant
treatment, and blood flow changes with induced sadness in healthy subjects
were used to test and refine this hypothesis. Dorsal neocortical decreases
and ventral paralimbic increases characterize both healthy sadness and
depressive illness; concurrent inhibition of overactive paralimbic regions
and normalization of hypofunctioning dorsal cortical sites characterize
disease remission. Normal functioning of the rostral anterior cingulate,
with its direct connections to these dorsal and ventral areas, is
postulated to be additionally required for the observed reciprocal
compensatory changes, since pretreatment metabolism in this region uniquely
predicts antidepressant treatment response. This model is offered as an
adaptable framework to facilitate continued integration of clinical imaging
findings with complementary neuroanatomical, neurochemical, and
electrophysiological studies in the investigation of the pathogenesis of
affective disorders.
