Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment

Abstract

IMPORTANCE Weight gain is a common and serious adverse effect of antipsychotic treatment. A variable individual predisposition to development of metabolic disturbances calls for predictive biological markers. OBJECTIVES To investigate whether attenuated striatal activity during reward anticipation is associated with amisulpride-induced weight change in antipsychotic-naive patients with schizophrenia undergoing initial treatment and to examine the association between weight change and changes in reward anticipation activity after treatment. DESIGN, SETTING, AND PARTICIPANTS Sixty-nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment with amisulpride, a relatively selective dopamine D 2 antagonist, 39 patients underwent a second fMRI scan and measurement of change in body weight. Final follow-up

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

“…The only longitudinal study in this area used a MID paradigm to study weight change in patients treated with the highly selective D2-and D3-receptor antagonist amisulpride (Nielsen et al, 2016). Confirming our proposal, a decrease in reward anticipation over the course of 6 weeks predicted greater weight gain.…”

“…Only one recent longitudinal study looked at the relation between weight gain, striatal activity and antipsychotic treatment in schizophrenia. At follow-up, six weeks after baseline measurement with amisulpride, Nielsen and colleagues (Nielsen et al, 2016) found in N = 39 patients treated with amisulpride that reward anticipatory responses in the MID task were associated with weight gain. Patients with lower baseline reward anticipation in the right putamen showed stronger weight gain.…”

“…Numbers with black background point to the reference proving the specific point: 1) genetic basis of low reward anticipation (Grimm et al, 2014) 2) acute psychosis comes with a dysregulated dopaminergic regulation converging to illicit salience attribution of stimuli Howes and Kapur, 2009) 3.) antidopaminergic medication suppresses reward anticipation and initiates weight gain (Juckel et al, 2006a;Nielsen et al, 2016) 4.) antipsychotic therapy can induce normalization of reward signaling while weight plateaus (Nielsen et al, 2012).…”

“…These studies should enable direct comparisons of patients with schizophrenia and weight-matched obese controls. For example, following Nielsen and colleagues (Nielsen et al, 2016), we should try to study the predictive ability of striatal reward anticipation in patients with respect to weight gain, psychopathology and comorbid disorders over longer terms (6-18 months). Shorter-term studies would result in less variance and weight gain would plateau after about 12 months (Perez-Iglesias et al, 2008).…”

Converging effects of diverse treatment modalities on frontal cortex in schizophrenia: A review of longitudinal functional magnetic resonance imaging studies

“…As a noninvasive and relatively safe tool for investigating in vivo brain function with high spatial resolution, fMRI can be used to measure the biological effects of candidate treatment strategies, and may provide a useful biomarker in clinical trials (29, 32). The promise of these approaches have been demonstrated in recent work indicating that functional connectivity of the striatum can predict response to APMs in first episode psychosis (33) and that striatal activity during reward anticipation predicts weight gain in response to subsequent APM therapy (34). …”