Switching schizophrenia patients from typical neuroleptics to aripiprazole: effects on working memory dependent functional activation

Schizophr Res. 2010 May;118(1-3):189-200. doi: 10.1016/j.schres.2010.01.022. Epub 2010 Feb 26.

Abstract

Background: Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance.

Methods: We measured BOLD-response during a WM task in a longitudinal fMRI-study in eleven schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to aripiprazole (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. Data was analyzed with SPM5 in a 2 x 2 x 2 design (groupxsessionxtask).

Results: Schizophrenia patients showed fewer correct responses compared to healthy controls at T1 and a trend-wise normalization at T2. The task activated the fronto-parietal network during the contrast 2-back>0-back in all participants. At T1 patients revealed a hypoactivation in the dorsal anterior cingulate cortex (ACC), which normalized after switch to aripiprazole and correlated with improved task performance. This was due to a significant increase in the patients group while the control group did not change, as corroborated by a significant groupxtime interaction in this region.

Conclusions: This study showed for the first time that the partial dopamine antagonist aripiprazole increases BOLD-signal during a WM task in the cognitive part of the ACC in schizophrenia patients, which may reflect its beneficial effect on cognitive deficits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / pharmacology*
  • Antipsychotic Agents / therapeutic use*
  • Aripiprazole
  • Brain Mapping
  • Chlorpromazine / therapeutic use
  • Female
  • Gyrus Cinguli / blood supply
  • Gyrus Cinguli / drug effects
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging / methods
  • Male
  • Memory Disorders / drug therapy*
  • Memory Disorders / etiology
  • Memory, Short-Term / drug effects*
  • Middle Aged
  • Neuropsychological Tests
  • Oxygen / blood
  • Photic Stimulation / methods
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use*
  • Quinolones / pharmacology*
  • Quinolones / therapeutic use*
  • Reaction Time / drug effects
  • Schizophrenia / complications
  • Schizophrenia / drug therapy*
  • Schizophrenia / pathology
  • Schizophrenic Psychology
  • Time Factors
  • Visual Cortex / blood supply
  • Visual Cortex / drug effects
  • Young Adult

Substances

  • Antipsychotic Agents
  • Piperazines
  • Quinolones
  • Aripiprazole
  • Oxygen
  • Chlorpromazine