Heterogeneity of Striatal Dopamine Function in Schizophrenia:Meta-analysis of Variance

Background: It has been hypothesized that dopamine function in schizophrenia exhibits heterogeneity in excess of that seen in the general population. However, no previous study has systematically tested this hypothesis. Methods: We employed meta-analysis of variance to investigate interindividual variability of striatal dopaminergic function in patients with schizophrenia and in healthy control subjects. We included 65 studies that reported molecular imaging measures of dopamine synthesis or release capacities, dopamine D2/3 receptor (D2/3R) or dopamine transporter (DAT) availabilities, or synaptic dopamine levels in 983 patients and 968 control subjects. Variability differences were quantified using variability ratio (VR) and coefficient of variation ratio. Results: Interindividual variability of striatal D2/3R (VR = 1.26, p <.0001) and DAT (VR = 1.31, p =.01) availabilities and synaptic dopamine levels (VR = 1.38, p =.045) but not dopamine synthesis (VR = 1.12, p =.13) or release (VR = 1.08, p =.70) capacities were significantly greater in patients than in control subjects. Findings were robust to variability measure. Mean dopamine synthesis (g = 0.65, p =.004) and release (g = 0.66, p =.03) capacities, as well as synaptic levels (g = 0.78, p =.0006), were greater in patients overall, but mean synthesis capacity did not differ from that of control subjects in treatment-resistant patients (p >.3). Mean D2/3R (g = 0.17, p =.14) and DAT (g = -0.20, p =.28) availabilities did not differ between groups. Conclusions: Our findings demonstrate significant heterogeneity of striatal dopamine function in schizophrenia. They suggest that while elevated dopamine synthesis and release capacities may be core features of the disorder, altered D2/3R and DAT availabilities and synaptic dopamine levels may occur only in a subgroup of patients. This heterogeneity may contribute to variation in treatment response and side effects.