Striatal dopamine synthesis capacity and its association with negative symptoms upon resolution of positive symptoms in first-episode schizophrenia and delusional disorder

Rationale: How striatal dopamine synthesis capacity (DSC) contributes to the pathogenesis of negative symptoms in first-episode schizophrenia (SZ) and delusional disorder (DD) has seldom been explored. As negative symptoms during active psychotic episodes can be complicated by secondary influences, such as positive symptoms, longitudinal investigations may help to clarify the relationship between striatal DSC and negative symptoms and differentiate between primary and secondary negative symptoms.

Objective: A longitudinal study was conducted to examine whether baseline striatal DSC would be related to negative symptoms at 3 months in first-episode SZ and DD patients.

Methods: Twenty-three first-episode age- and gender-matched patients (11 DD and 12 SZ) were consecutively recruited through an early intervention service for psychosis in Hong Kong. Among them, 19 (82.6%) patients (9 DD and 10 SZ) were followed up at 3 months. All patients received an ¹⁸F-DOPA PET/MR scan at baseline.

Results: Baseline striatal DSC (K^occ;30-60) was inversely associated with negative symptoms at 3 months in first-episode SZ patients (r_s = - 0.80, p = 0.010). This association remained in SZ patients even when controlling for baseline negative, positive, and depressive symptoms, as well as cumulative antipsychotic dosage (β = - 0.69, p = 0.012). Such associations were not observed in first-episode DD patients. Meanwhile, the severity of negative symptoms at 3 months was associated with more positive symptoms in DD patients (r_s = 0.74, p = 0.010) and not in SZ patients.

Conclusions: These findings highlight the role of striatal DSC in negative symptoms upon resolution of active psychotic episodes among first-episode SZ patients. Baseline striatal dopamine activity may inform future symptom expression with important treatment implications.