Short-term Effects of Risperidone Monotherapy on Spontaneous Brain Activity in First-episode Treatment-naïve Schizophrenia Patients: A Longitudinal fMRI Study

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.

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18F]fallypride PET and functional MRI study

“…Low frequency fluctuations comprising the ALFF signals are a fundamental aspect of the resting brain. Present exploratory findings of increased ALFF values in striatal and several extrastriatal regions in patients compared to controls concur with earlier findings in patients receiving antipsychotic medication (Hu et al, ; Li et al, ; Lui et al, ). Acute and chronic effects of antipsychotics on regional ALFF values in healthy subjects are largely unknown, although region‐specific alterations of ALFF values were reported in patients with schizophrenia on stable antipsychotic treatment (Lui et al, ).…”

Glutamatergic Deficits in Schizophrenia – Biomarkers and Pharmacological Interventions within the Ketamine Model

“…Pretreatment with risperidone tended to attenuate ketamine-induced alterations in the respective studies. In fMRI studies with schizophrenia patients, short-term treatment with risperidone led to inconsistent results [ 107 , 108 ]. Lamotrigine likewise reduced bold-changes in the ketamine model, whereas functional connectivity was not affected.…”

Longitudinal studies of functional magnetic resonance imaging in first-episode psychosis: A systematic review

“…1. A total of 13 clinical studies were included [23][24][25][26][27][28][29][30][31][32][33][34][35]. By aggregating the included samples, a total of 290 FEP patients and 401 healthy volunteers were assessed.…”