Short-term effects of antipsychotic treatment on cerebral function in drug-naive first-episode schizophrenia revealed by "resting state" functional magnetic resonance imaging.
BACKGROUND
Most of what we know about antipsychotic drug effects is at the receptor level, distal from the neural system effects that mediate their clinical efficacy. Studying cerebral function in antipsychotic-naive patients with schizophrenia before and after pharmacotherapy can enhance understanding of the therapeutic mechanisms of these clinically effective treatments.


OBJECTIVE
To examine alterations of regional and neural network function in antipsychotic-naive patients with first-episode schizophrenia before and after treatment with second-generation antipsychotic medication.


METHODS
Case-control study.


METHODS
Huaxi MR Research Center and Mental Health Centre of the West China Hospital.


METHODS
Thirty-four antipsychotic-naive patients with first-episode schizophrenia were scanned using gradient-echo echo-planar imaging while in a resting state. After 6 weeks of antipsychotic treatment, patients were rescanned. Thirty-four matched healthy control subjects were studied at baseline for comparison purposes.


METHODS
The amplitude of low-frequency fluctuations (ALFF) of blood oxygen level-dependent signals, believed to reflect spontaneous neural activity, was used to characterize regional cerebral function. Functional connectivity across brain regions was evaluated using a seed voxel correlation approach and an independent component analysis. Changes in these measures after treatment were examined to characterize effects of antipsychotic drugs on regional function and functional integration.


RESULTS
After short-term treatment with second-generation antipsychotic medications, patients showed increased ALFF, particularly in the bilateral prefrontal and parietal cortex, left superior temporal cortex, and right caudate nucleus. Increased regional ALFF was associated with a reduction of clinical symptoms, and a widespread attenuation in functional connectivity was observed that was correlated with increased regional ALFF.


CONCLUSIONS
We demonstrate for the first time, to our knowledge, that widespread increased regional synchronous neural activity occurs after antipsychotic therapy, accompanied by decreased integration of function across widely distributed neural networks. These findings contribute to the understanding of the complex systems-level effects of antipsychotic drugs.
Lui
Su
S
Huaxi MR Research Center, Department of Radiology, State Key Lab of Biotherapy,West China Hospital of Sichuan University, Chengdu, China.
Li
Tao
T
Deng
Wei
W
Jiang
Lijun
L
Wu
Qizhu
Q
Tang
Hehan
H
Yue
Qiang
Q
Huang
Xiaoqi
X
Chan
Raymond C
RC
Collier
David A
DA
Meda
Shashwath A
SA
Pearlson
Godfrey
G
Mechelli
Andrea
A
Sweeney
John A
JA
Gong
Qiyong
Q
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping / Q000706:statistics & numerical data; D016022:Case-Control Studies; D017352:Echo-Planar Imaging / Q000706:statistics & numerical data*; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009434:Neural Pathways / Q000503:physiopathology; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000187:drug effects / Q000503:physiopathology; D012146:Rest / Q000502:physiology*; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology
D014150:Antipsychotic Agents; D018967:Risperidone; D010100:Oxygen