Abstract
It is unclear whether abnormal spontaneous neural activation patterns found in chronic schizophrenia patients (CSP) are part of the pathogenesis of disease, consequences of chronic illness, or effects of antipsychotic treatment. We performed a longitudinal resting-state functional magnetic resonance imaging (fMRI) study in 42 treatment-naïve first-episode schizophrenia patients (FESP) at baseline and then after 8-weeks of risperidone monotherapy, and compared the findings to 38 healthy volunteers. Spontaneous brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) and compared between patients and controls. Pretreatment, patients exhibited higher fALFF in left caudate compared with controls. After treatment, patients had elevated fALFF in bilateral putamen and right caudate, and increased ReHo in right caudate and left putamen. Greater increase of fALFF in the left putamen correlated with less improvement in positive symptoms. Thus, abnormalities of spontaneous neural activity in chronic schizophrenia is at least partly due to a medication effect. The observed post-treatment increase in striatal intrinsic activity may reflect counter-therapeutic functional adaptation to dopamine D2 receptor occupancy required for medication effects on psychosis.
Highlights
IntroductionOne longitudinal study[19] has examined the effect of 6-weeks of antipsychotic treatment on resting-state ALFF measures in 34 drug-naïve first-episode schizophrenia patients (FESP)
We hypothesized that risperidone monotherapy would modulate regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF) in regions with dopaminergic input, and that change would be related to clinical improvement
There were no significant correlations between the longitudinal alterations of fALFF/ ReHo and the changes in Positive and Negative Syndrome Scale (PANSS)-T or PANSS-G symptom scores after treatment (Ps > 0.05). This is the first longitudinal study examining the effect of risperidone monotherapy on fALFF and ReHo in treatment-naïve first-episode schizophrenia patients (FESP)
Summary
One longitudinal study[19] has examined the effect of 6-weeks of antipsychotic treatment on resting-state ALFF measures in 34 drug-naïve first-episode schizophrenia patients (FESP). To distinguish effects of medication from early disease effect requires a longitudinal study of drug-naïve FESP treated with standardized protocol-driven, antipsychotic monotherapy to separately determine disease effects and pharmacological effects on spontaneous brain activities. In 34 drug-naïve FESP treated with different antipsychotics, such as olanzapine, sulpiride, risperidone and clozapine, Lui et al.[19] found that longitudinal increases of ALFF in frontal gyrus, parietal lobule, temporal gyrus and right caudate were negatively correlated with improvement of positive symptoms. Medication-naïve FESP treated with risperidone, olanzapine or quetiapine[23] showed no correlation between improvement of symptoms and alteration of cortex activation examined by fMRI. We hypothesized that risperidone monotherapy would modulate ReHo and fALFF in regions with dopaminergic input, and that change would be related to clinical improvement
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