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Goldapple K, Segal Z, Garson C, et al. Modulation of Cortical-Limbic Pathways in Major Depression: Treatment-Specific Effects of Cognitive Behavior Therapy. Arch Gen Psychiatry. 2004;61(1):34–41. doi:https://doi.org/10.1001/archpsyc.61.1.34
Functional imaging studies of major depressive disorder demonstrate
response-specific regional changes following various modes of antidepressant
To examine changes associated with cognitive behavior therapy (CBT).
Brain changes underlying response to CBT were examined using resting-state
fluorine-18–labeled deoxyglucose positron emission tomography. Seventeen
unmedicated, unipolar depressed outpatients (mean ± SD age, 41 ±
9 years; mean ± SD initial 17-item Hamilton Depression Rating Scale
score, 20 ± 3) were scanned before and after a 15- to 20-session course
of outpatient CBT. Whole-brain, voxel-based methods were used to assess response-specific
CBT effects. A post hoc comparison to an independent group of 13 paroxetine-treated
responders was also performed to interpret the specificity of identified CBT
A full course of CBT resulted in significant clinical improvement in
the 14 study completers (mean ± SD posttreatment Hamilton Depression
Rating Scale score of 6.7 ± 4). Treatment response was associated with
significant metabolic changes: increases in hippocampus and dorsal cingulate
(Brodmann area [BA] 24) and decreases in dorsal (BA 9/46), ventral (BA 47/11),
and medial (BA 9/10/11) frontal cortex. This pattern is distinct from that
seen with paroxetine-facilitated clinical recovery where prefrontal increases
and hippocampal and subgenual cingulate decreases were seen.
Like other antidepressant treatments, CBT seems to affect clinical recovery
by modulating the functioning of specific sites in limbic and cortical regions.
Unique directional changes in frontal cortex, cingulate, and hippocampus with
CBT relative to paroxetine may reflect modality-specific effects with implications
for understanding mechanisms underlying different treatment strategies.
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