Neuromelanin accumulation in patients with schizophrenia: A systematic review and meta-analysis

Abstract

Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.

Keywords: Dopamine; NM-MRI; Neuromelanin; Review; Schizophrenia; Substantia nigra.

Fig. 1.

Preferred reporting items for systematic reviews and meta-analyses (PRISMA) diagram for study search. The figure was generated with the R package “PRISMA2020” version 0.0.1 (Haddaway and McGuinness, 2020).

Fig. 2.

Study effect sizes of differences in neuromelanin levels between schizophrenia and healthy controls in the substantia nigra.The size of the marker is proportional to the total number of individuals in each study. The summarized effect size is denoted by a diamond. Abbreviations. CI, confidence interval; MRI, magnetic resonance imaging; PI, prediction interval; SMD, standardized mean difference.

Fig. 3.

Study effect sizes of differences in neuromelanin levels between schizophrenia and healthy controls in the locus coeruleus. The size of the marker is proportional to the total number of individuals in each study. The summarized effect size is denoted by a diamond. Abbreviations. CI, confidence interval; MRI, magnetic resonance imaging; PI, prediction interval; SMD, standardized mean difference.