Switching schizophrenia patients from typical neuroleptics to aripiprazole: effects on working memory dependent functional activation.
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.
Schlagenhauf
Florian
F
Department of Psychiatry, Charité-Universitaetsmedizin Berlin, Campus Mitte, Germany. florian.schlagenhauf@charite.de
Dinges
Martin
M
Beck
Anne
A
Wüstenberg
Torsten
T
Friedel
Eva
E
Dembler
Theresa
T
Sarkar
Rahul
R
Wrase
Jana
J
Gallinat
Jürgen
J
Juckel
Georg
G
Heinz
Andreas
A
D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000068180:Aripiprazole; D001931:Brain Mapping; D002746:Chlorpromazine / Q000627:therapeutic use; D005260:Female; D006179:Gyrus Cinguli / Q000098:blood supply / Q000187:drug effects; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D008570:Memory, Short-Term / Q000187:drug effects*; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D010775:Photic Stimulation / Q000379:methods; D010879:Piperazines / Q000494:pharmacology* / Q000627:therapeutic use*; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use*; D011930:Reaction Time / Q000187:drug effects; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D012565:Schizophrenic Psychology; D013997:Time Factors; D014793:Visual Cortex / Q000098:blood supply / Q000187:drug effects; D055815:Young Adult
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D010100:Oxygen; D002746:Chlorpromazine