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Brain activity during reward processing may be associated with antipsychotic-related weight gain

Recent findings suggest that activity in striatal regions of the reward system is associated with individual variability in the predisposition for weight gain related to antipsychotics.

“Histamine H₁ receptor blockade may explain in part the pronounced weight gain often associated with clozapine and olanzapine treatment, whereas serotonin_2A receptor blockade may be of importance in quetiapine fumarate–associated weight gain. However, antipsychotics with lower histaminergic or serotonergic affinity, such as chlorpromazine hydrochloride and the relatively selective dopamine D₂ receptor antagonist amisulpride, are associated with weight gain,” Mette Ø. Nielsen, PhD, of University of Copenhagen, Denmark, and colleagues wrote. “This association suggests that dopamine D₂ receptor antagonism may play a critical role in antipsychotic-associated weight gain.”

To determine if attenuated striatal activity during reward anticipation is associated with amisulpride-induced weight change in individuals with schizophrenia who begin antipsychotic therapy, researchers evaluated 69 antipsychotic-naïve individuals with schizophrenia. Functional MRI was conducted while 58 participants performed a monetary reward task. After 6 weeks of treatment with amisulpride, 39 participants underwent a second functional MRI and measurement of body weight change. The mean daily dose of amisulpride was 272 mg, ranging from 50 mg to 800 mg.

Study participants gained a mean of 2.3 kg in body weight.

Mean positive, general and total scores on the Positive and Negative Syndrome Scale improved from baseline to follow-up (P < .001 for all).

Low mean baseline reward-related activity in the right-sided putamen predicted weight gain (P = .003).

After 6 weeks of treatment, weight gain was associated with an increase in mean reward activity in the same region during treatment (P = .04).

“In summary, this interesting new study reports an index of striatal function that correlates with weight gain after the use of a relatively selective dopamine blocker. The study is to be commended for its ability to find antipsychotic-naïve participants, provide longitudinal follow-up and use a selective antipsychotic. Although the effect size is too small for the findings to be used for individual prediction in the clinic, the link to the reward-deficiency hypothesis of obesity provides a central piece of what is likely a rather complex puzzle,” Shitij Kapur, MD, PhD, of King’s College London, and Tiago Reis Marques, MD, PhD, of Imperial College London, wrote in an accompanying editorial.  – by Amanda Oldt

Disclosure: Nielsen reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.