Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy

Arch Gen Psychiatry. 2004 Jan;61(1):34-41. doi: 10.1001/archpsyc.61.1.34.


Background: Functional imaging studies of major depressive disorder demonstrate response-specific regional changes following various modes of antidepressant treatment.

Objective: To examine changes associated with cognitive behavior therapy (CBT).

Methods: 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 effects.

Results: 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.

Conclusions: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ambulatory Care
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Blood Glucose / metabolism*
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / physiopathology
  • Cognitive Behavioral Therapy*
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / physiopathology
  • Depressive Disorder, Major / therapy*
  • Energy Metabolism / physiology
  • Female
  • Fluorodeoxyglucose F18
  • Follow-Up Studies
  • Frontal Lobe / diagnostic imaging
  • Frontal Lobe / physiopathology
  • Humans
  • Limbic System / diagnostic imaging*
  • Limbic System / physiopathology
  • Male
  • Middle Aged
  • Nerve Net / diagnostic imaging
  • Nerve Net / physiopathology
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Outcome and Process Assessment, Health Care
  • Paroxetine / therapeutic use
  • Personality Inventory
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / physiopathology
  • Sensitivity and Specificity
  • Tomography, Emission-Computed*


  • Antidepressive Agents, Second-Generation
  • Blood Glucose
  • Fluorodeoxyglucose F18
  • Paroxetine