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

Fumihiko Ueno, Yusuke Iwata, Shinichiro Nakajima, Fernando Caravaggio, Jose M. Rubio, Guillermo Horga, Clifford M. Cassidy, Edgardo Torres-Carmona, Vincenzo de Luca, Sakiko Tsugawa, Shiori Honda, Sho Moriguchi, Yoshihiro Noda, Philip Gerretsen, Ariel Graff-Guerrero

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1205-1213
Number of pages9
JournalNeuroscience and Biobehavioral Reviews
Publication statusPublished - 2022 Jan


  • Dopamine
  • NM-MRI
  • Neuromelanin
  • Review
  • Schizophrenia
  • Substantia nigra

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience


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