Antipsychotic dose and diminished neural modulation: A multi-site fMRI study

Abstract

Background-The effect of antipsychotics on the blood oxygen level dependent signal in schizophrenia is poorly understood. The purpose of the present investigation is to examine the effect of type (typical or atypical) and dose of antipsychotic medication on independent neural networks during a motor task in a large, multi-site functional magnetic resonance imaging investigation.Methods-Seventy-nine medicated patients with schizophrenia and 114 comparison subjects from the Mind Clinical Imaging Consortium database completed a paced, auditory motor task during functional magnetic resonance imaging (fMRI). Independent component analysis identified temporally cohesive but spatially distributed neural networks. The independent component analysis time course was regressed with a model time course of the experimental design. The resulting beta weights were evaluated for group comparisons and correlations with chlorpromazine equivalents.Results-Group differences between patients and comparison subjects were evident in the cortical and subcortical motor networks, default mode networks, and attentional networks. The chlorpromazine equivalents correlated with the unimotor/bitemporal (rho = −0.32, P = 0.0039), motor/caudate (rho = − 0.22, P = 0.046), posterior default mode (rho = 0.26, P = 0.020), and anterior default mode networks (rho = 0.24, P = 0.03). Patients on typical antipsychotics also had NIH Public Access Conclusion-The results indicate that antipsychotic dose diminishes neural activation in motor (cortical and subcortical) and default mode networks in patients with schizophrenia. The higher potency, typical antipsychotics also diminish positive modulation in subcortical motor networks. Antipsychotics may be a potential confound limiting interpretation of fMRI studies on the disease process in medicated patients with schizophrenia.

Effect of rTMS on brain activation in schizophrenia with negative symptoms: A proof-of-principle study

“…The studies on rTMS treatment for negative symptoms of schizophrenia are conducted among medicated patients. Antipsychotics cause dopamine antagonism at the D2 receptor, and there is evidence that antipsychotics diminish neural activation in motor and default mode network in patients with schizophrenia (Abbott et al, 2011). In addition, there is evidence for reduced inhibition, impaired connectivity and reduced plasticity in both medicated and unmedicated patients with schizophrenia in all stages of the illness.…”

Association of GRM3 polymorphism with white matter integrity in schizophrenia

“…Dose year of antipsychotics were calculated using the formula described by Abbott et al, 2011: $$\text{Dose}\text{year}=false[false(\text{dose}false(\text{mg}false)\ast 100\text{CPZ}false)/\text{drugequivalent}false]\ast false[\text{daysondose}/365.25false]\ast false[1\text{year}/false(100\text{CPZ}\ast 1\text{year}false)false]$$…”

Neuroimaging Biomarkers for Early Drug Development in Schizophrenia

“…Using PET, Tomasi et al (91) reported a negative correlation between dopamine transporter availability and DMN deactivation during an attention task, suggesting that dopamine release may reduce DMN activity. The most direct link between DMN function and dopaminergic function comes from the observation that conventional antipsychotic medications, which act via dopaminergic antagonism, show a dose-dependent correlation with DMN activity in schizophrenia patients (92). …”