Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment

E Stip, O V Lungu, K Anselmo, G Letourneau, A Mendrek, B Stip, O Lipp, P Lalonde, L A Bentaleb, E Stip, O V Lungu, K Anselmo, G Letourneau, A Mendrek, B Stip, O Lipp, P Lalonde, L A Bentaleb

Abstract

There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation.

Trial registration: ClinicalTrials.gov NCT00290121.

Figures

Figure 1
Figure 1
Patients were scanned before and after 16 weeks of olanzapine treatment. In each functional magnetic resonance imaging (fMRI) session, given that appetite is a state that may last for some time after food stimuli are presented, the blocks of appetitive stimuli were always presented last to prevent the appetite to develop during the presentation of the neutral stimuli. In each block, there were 11 neutral or appetite-related pictures (depending on the block type) presented.
Figure 2
Figure 2
Brain regions in which the difference in blood oxygenation level dependent (BOLD) signal between appetitive and neutral condition increased significantly among patients as a result of olanzapine treatment.
Figure 3
Figure 3
Changes in blood oxygenation level dependent (BOLD) signal for appetitive and neutral condition in each group (patients pre-treatment, patients post-treatment, healthy controls) in each region of interest (ROI). (a) Regions in which the BOLD signal for appetitive stimuli was similar in magnitude among patients post-treatment with that corresponding for healthy controls. (b) Regions in which the BOLD signal for appetitive stimuli was significantly higher in patients after treatment than that among healthy controls. *P<0.05.

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