Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression

Am J Psychiatry. 2003 Mar;160(3):522-32. doi: 10.1176/appi.ajp.160.3.522.

Abstract

Objective: Serotonin reuptake inhibitor (SRI) medications are effective in the treatment of both major depressive disorder and obsessive-compulsive disorder (OCD), but it is unknown whether the neural substrates of treatment response for the two disorders are the same or different. The authors sought to identify pretreatment cerebral glucose metabolic markers of responsiveness to SRI treatment in patients with OCD versus major depressive disorder and to determine whether the pretreatment patterns associated with improvement of OCD symptoms were the same as or different from those associated with improvement of major depressive disorder symptoms.

Method: [(18)F]Fluorodeoxyglucose positron emission tomography was used to measure cerebral glucose metabolism in 27 patients with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent OCD and major depressive disorder, who were all then treated with 30-60 mg/day of paroxetine for 8-12 weeks. Correlations were calculated between pretreatment regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms, depressive symptoms, and overall functioning.

Results: While improvement of OCD symptoms was significantly correlated with higher pretreatment glucose metabolism in the right caudate nucleus (partial r=-0.53), improvement of major depressive disorder symptoms was significantly correlated with lower pretreatment metabolism in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91).

Conclusions: These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment.

Publication types

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

MeSH terms

  • Adult
  • Brain / drug effects
  • Brain / metabolism*
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Functional Laterality
  • Glucose / metabolism*
  • Gyrus Cinguli / drug effects
  • Gyrus Cinguli / metabolism
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / drug therapy*
  • Obsessive-Compulsive Disorder / metabolism
  • Paroxetine / pharmacology
  • Paroxetine / therapeutic use*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Probability
  • Prognosis
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Tomography, Emission-Computed / statistics & numerical data
  • Treatment Outcome

Substances

  • Serotonin Uptake Inhibitors
  • Fluorodeoxyglucose F18
  • Paroxetine
  • Glucose