DOI: 10.1097/01.yic.0000405885.40580.08
,
Issn Print: 0268-1315
Publication Date: 2011/09/01
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Excerpt
Methods: Thirteen schizophrenic patients (assessed using DSM-IV criteria) were clinically evaluated (using Positive and Negative Syndrome Scale–PANSS, Calgary Depression Scale - CDS) and were scanned using functional magnetic resonance imaging (fMRI), before starting and at the end of 16 weeks of ziprasidone treatment (118 mg/day on average). Their results were compared with those of 15 healthy subjects. In each neuroimaging session, participants watched 14 blocks of emotionally laden images taken from the standardized sets developed by International Affective Picture System [NIMH Center for Emotion and Attention (CSEA) at the University of Florida]. In each block, one type of image (e.g. positive, negative) predominated and subjects were instructed to select all images of a given type, which could be either concordant (e.g. select all positive images in a block with a majority of positive images) or non-concordant (e.g. select all positive images in a block with a majority of negative images). The blood oxygenation level dependent (BOLD) signal in response to emotional stimuli was used as dependent measure for the brain activity.
Results: Despite observing no significant changes on clinical measures (PANSS and CDS) before and after 16 weeks of ziprasidone treatment, several prefrontal regions (i.e. anterior cingulate - ACC, orbitofrontal–OFC, and dorsolateral prefrontal–DLPFC cortices) increased significantly their response to positive than to negative stimuli. Moreover, in the regions typically involved in cognitive control (ACC and DLPFC), this pattern was accentuated whenever patients were instructed to select only the negative stimuli. Among the healthy controls, we found that prefrontal activity was more sensitive to the type of instruction, than to the type of image in a block; specifically, the prefrontal areas had a higher BOLD signal whenever subjects had to select the negative, than the positive images.
We also found more similarities in prefrontal functioning (both in the volume and the strength of activation) between patients and controls after the treatment, when taking into account the instruction type (select negative vs. positive stimuli), than when comparing the emotional valence of images.
Conclusion: The results of the present study suggest that antipsychotic treatment with ziprasidone restores the cognitive functioning related to the processing of emotional information in prefrontal cortex in patients with schizophrenia. Given the neuro-pharmacological action mechanism of ziprasidone (more affinity for serotonin than dopamine receptors in prefrontal cortex), we believe that our findings demonstrate that cognitive control and regulation of reactions when facing emotionally laden stimuli in schizophrenia benefit from a higher concentration of dopamine in mesocortical pathways.
