Reduced right ventrolateral prefrontal cortex activity while inhibiting positive affect is associated with improvement in hedonic capacity after 8 weeks of antidepressant treatment in major depressive disorder

Biol Psychiatry. 2011 Nov 15;70(10):962-8. doi: 10.1016/j.biopsych.2011.06.031. Epub 2011 Aug 25.

Abstract

Background: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.

Methods: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software.

Results: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3.

Conclusions: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.

Trial registration: ClinicalTrials.gov NCT00909155.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anhedonia / drug effects*
  • Anhedonia / physiology
  • Antidepressive Agents
  • Cyclohexanols / therapeutic use
  • Depressive Disorder, Major* / drug therapy
  • Depressive Disorder, Major* / pathology
  • Depressive Disorder, Major* / physiopathology
  • Double-Blind Method
  • Emotions / drug effects
  • Female
  • Fluoxetine / therapeutic use
  • Follow-Up Studies
  • Functional Laterality / drug effects
  • Functional Laterality / physiology*
  • Humans
  • Image Processing, Computer-Assisted
  • Linear Models
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiopathology*
  • Psychiatric Status Rating Scales
  • Pupil / drug effects
  • Surveys and Questionnaires
  • Venlafaxine Hydrochloride
  • Young Adult

Substances

  • Antidepressive Agents
  • Cyclohexanols
  • Fluoxetine
  • Venlafaxine Hydrochloride

Associated data

  • ClinicalTrials.gov/NCT00909155