Could Reward-Disturbances Caused by Antipsychotic Medication Lead to Weight Gain?

BACKGROUND
Disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia, and antipsychotic medication partly acts by modulating the reward system. Further, the reward system is known to be central to the regulation of appetite, and most antipsychotics cause some degree of weight gain. Recently, a relation between weight gain caused by one week of olanzapine treatment and change in reward signalling was found in healthy volunteers. To our knowledge there are no previous studies examining how the effect of antipsychotic treatment on the reward system relate to weight gain in patients.

METHODS
50 antipsychotic-naïve first-episode patients with schizophrenia and 40 healthy controls were included in the study at baseline. 38 patients and 31 healthy controls were re-examined after six weeks where patients were treated with individual doses of Amisulpride. Weight gain was monitored during the period. At both baseline and follow-up the participants went through a functional Magnetic Resonance Imaging (fMRI) while playing a monetary reward task. Relation between weight gain and the salience related activity in three parts of striatum was analyzed.

RESULTS
During the treatment period the patients received on average 248 mg of Amisulpride and improved significantly in PANSS total, positive and general score (all p<0.001). Further they had an average weight gain of 2.2 kilograms in the treatment period.
Regarding fMRI a decreased activation in ventral striatum in the salience contrast was found in the patients at baseline. Further, patients with the most blunted fMRI response at baseline were the patients with the highest degree of weight gain during the next 6 weeks (r=0.412, p=0.017) .
At follow up there was a slightly but non significant normalization of the salience related fMRI response in patients. We found a correlation between weight change and the improvement of contrast signal in right putamen: the patients with the highest weight gain were the ones showing the most normalized BOLD response in right putamen (r=0.541, p=0.001). There was no relation between weight gain and treatment response or medication dose.

DISCUSSION
As expected, antipsychotic treatment on average caused a moderate weight gain in the patients. The highest weight gain was found in the patients with the most aberrant fMRI anticipation signal at baseline, and the patients with the highest weight gain were also showing the highest increase in salience contrast signal over time. We do not know what this change in BOLD response in striatum correspond to at the cellular level. However based on previous work, it seems reasonable to assume that it is related to changes in dopamine transmission. Thus our results suggest that by altering the dopaminergic transmission in putamen, antipsychotic medication might through the influence on reward system affect appetite regulation and thereby, together with other mechanisms, lead to weight gain.