Salience Abnormalities May Play a Role in the Reward System in Schizophrenia

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A study found a link between D2 receptor blockade, BOLD signal normalization, and treatment response in patients with schizophrenia.

Alterations of the reward system contribute to psychotic symptoms in patients with schizophrenia and may respond to blockade of dopamine D2 receptors, according to the results of a study published in Psychological Medicine.

In antipsychotic-naive and unmedicated patients with schizophrenia, an attenuated blood oxygen level-dependent (BOLD) response in the ventral striatum occurs during reward anticipation. Other evidence indicates that dopamine plays a role in this reward-related BOLD response.

Sanne Wulff, PhD, from the Center for Neuropsychiatric Schizophrenia Research and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Mental Health Centre, Glostrup, Copenhagen, Denmark, and colleagues combined functional magnetic resonance imaging (fMRI) and single-photon emission computed tomography (SPECT) data to determine how D2 receptor blockade in the caudate nucleus affects salience abnormalities and improves positive schizophrenia symptoms.

The authors recruited 22 antipsychotic-naive patients with a first episode of schizophrenia from both inpatient and outpatient mental health facilities in Denmark and 23 healthy controls. They used a modified version of the monetary incentive delay task and assessed subjects before and after 6 weeks of amisulpride therapy. Amisulpride was selected because of its selective, high affinity binding to D2 and D3 receptors.

At baseline, but not at follow-up, fMRI responses were lower, and a change in the fMRI signal weakly correlated with improvements in positive symptoms, as measured by the Positive and Negative Syndrome Scale (P =.049). Furthermore, among patients who responded to amisulpride therapy, improvements in the fMRI signal correlated with receptor occupancy (P =.035).

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“Taken together, our present and previous data….support abnormalities in salience processing throughout striatum and a relationship between symptom improvement and normalization of the BOLD response in the caudate nucleus, as well as in the [ventral striatum] following treatment with a dopamine D2 blocker,” the authors noted.

They concluded that psychotic symptoms may be improved by normalizing abnormalities in the salience reward system.

The power of the study was limited by the small sample size and post hoc results require replication.


Wulff S, Nielsen MO, Rostrup E, et al. The relationship between dopamine D2 receptor blockade and the brain reward system: a longitudinal study of first-episode schizophrenia patients. Psychol Med. 2020;50(2):220-228.