Increased prefrontal cerebral blood flow in first-episode schizophrenia following treatment: longitudinal positron emission tomography study.
OBJECTIVE
Cognitive deficits, particularly those related to executive function and behavioural control, are a core feature of patients with schizophrenia and implicate disturbances of the prefrontal cortex (PFC). Consistent with this, functional imaging studies have identified abnormalities of PFC activity in chronically affected patients. The objective of the current study was to investigate executive-control related neural activity from first onset of the illness through to symptom stabilization.


METHODS
The authors examined eight neuroleptic-naïve first-episode psychosis (FEP) patients within 3 days of first presentation and eight healthy age- premorbid-IQ, and gender-matched controls (CTL). All FEP patients were later confirmed with a diagnosis of schizophrenia. Subjects underwent H2-15O positron emission tomography (PET) while performing the Stroop interference task that has previously been shown to engage the PFC in healthy samples. In a double-blind paradigm, FEP patients were randomly treated with either haloperidol or risperidone for 8 weeks, after which CTLs and all but one of the FEP patients were re-scanned.


RESULTS
Behaviorally, there was no change in task performance from baseline to follow up for either the FEPs or CTLs. However, there were significant changes in functional activation in both groups across the same period. For CTLs, task-performance was associated with greater recruitment of posterior brain regions at follow up compared to baseline, while for FEP this involved greater recruitment frontal regions. Concurrently, FEP also showed significant improvement in positive symptomatology.


CONCLUSIONS
These findings suggest that disturbances of the PFC often seen in FEP may be, at least partially, associated with acute symptom expression. However, it is still unclear whether this increase in frontal activity is due to symptom stabilization per se, the effects of medication, a lack of neurophysiological 'learning' with experience/practice, or a combination of these factors. In the context of the CTLs performance, we interpret the patient findings as reflective of greater neurophysiological effort required for task accomplishment relative to the learned, more automated, processing apparent in the CTLs.
Brewer
Warrick J
WJ
ORYGEN Research Centre, Locked Bag 10, Parkville, Vic. 3052, Australia and Early Psychosis Prevention and Intervention Centre, Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia. w.brewer@unimelb.edu.au
Yücel
Murat
M
Harrison
Ben J
BJ
McGorry
Patrick D
PD
Olver
James
J
Egan
Gary F
GF
Velakoulis
Dennis
D
Pantelis
Christos
C
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003072:Cognition Disorders / Q000175:diagnosis; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000098:blood supply* / Q000000981:diagnostic imaging*; D011930:Reaction Time / Q000502:physiology; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D012720:Severity of Illness Index
D014150:Antipsychotic Agents