Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Associations of neuromelanin in the substantia nigra with antipsychotic response in schizophrenia

Neuropsychopharmacology volume 51, pages 682–690 (2026)Cite this article

Subjects

Abstract

Approximately 30% of patients with schizophrenia do not respond to antipsychotics. While schizophrenia has been primarily explained by the dopamine dysfunction hypothesis, treatment-resistant schizophrenia (TRS) may involve a different pathophysiology. Neuromelanin (NM), a product of dopamine metabolism in the substantia nigra (SN), indirectly measures long-term dopamine synthesis capacity. Few studies have examined SN NM levels in TRS. Therefore, we investigated the relationship between SN NM levels and treatment responsiveness in schizophrenia. We included age- and sex-matched TRS, patients with schizophrenia in remission of positive symptoms (SZ-R), and healthy controls (HCs). Neuromelanin-sensitive magnetic resonance imaging was used to measure SN NM signals. We also evaluated clinical symptoms and cognitive impairment. We conducted voxel-wise analyses of NM contrast-to-noise ratio (CNR) to compare groups pairwise. Correlation analyses examined relationships between NM signals and symptom severity. Seventy-two participants (n = 24 per group) completed the study. The TRS group had higher dorsal SN CNR than the HC group (510 out of 1948 voxels at p < 0.05, corrected p = 0.005, permutation test). In contrast, no significant differences were observed in the other comparisons. No significant correlations were found between NM CNR and clinical severity. Our findings contrast with previous positron emission tomography studies on dorsal striatal dopamine function. Since the dorsal SN contributes to both the mesolimbic and nigrostriatal pathways, with a relatively greater role in the former, dopamine functions in these pathways may play different roles for treatment responsiveness. Further research with multimodal imaging is needed to examine dopamine function and antipsychotic treatment responsiveness in schizophrenia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The substantia nigra (SN) and reference region mask (crus cerebri) overlaid on the contrast-to-noise ratio (CNR) mean image for all participants.
Fig. 2: The signal from significant voxels where TRS showed higher values than HC was averaged and visualized across the three groups (while these voxels were statistically significant for TRS vs.
Fig. 3: A map of significant voxels where TRS exhibited a higher neuromelanin-MRI contrast-to-noise ratio (CNR) than HCs (thresholded at p < 0.05; permutation test p = 0.005).

Similar content being viewed by others

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

References

  1. Kennedy JL, Altar CA, Taylor DL, Degtiar I, Hornberger JC. The social and economic burden of treatment-resistant schizophrenia: a systematic literature review. Int Clin Psychopharmacol. 2014;29:63–76.

    Article  PubMed  Google Scholar 

  2. Wada M, Noda Y, Iwata Y, Tsugawa S, Yoshida K, Tani H, et al. Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment. Mol Psychiatry. 2022;27:2950–67.

    Article  PubMed  CAS  Google Scholar 

  3. Abi-Dargham A, Rodenhiser J, Printz D, Zea-Ponce Y, Gil R, Kegeles LS, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA. 2000;97:8104–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Caravaggio F, Borlido C, Wilson A, Graff-Guerrero A. Examining endogenous dopamine in treated schizophrenia using [11C]-(+)-PHNO positron emission tomography: A pilot study. Clin Chim Acta. 2015;449:60–2.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Howes OD, Montgomery AJ, Asselin M-C, Murray RM, Grasby PM, McGuire PK. Molecular imaging studies of the striatal dopaminergic system in psychosis and predictions for the prodromal phase of psychosis. Br J Psychiatry. 2007;51:s13–8.

    Article  Google Scholar 

  6. McCutcheon R, Beck K, Jauhar S, Howes OD. Defining the locus of dopaminergic dysfunction in schizophrenia: A meta-analysis and test of the mesolimbic hypothesis. Schizophr Bull. 2018;44:1301–11.

    Article  PubMed  Google Scholar 

  7. Jauhar S, Veronese M, Nour MM, Rogdaki M, Hathway P, Turkheimer FE, et al. Determinants of treatment response in first-episode psychosis: an 18F-DOPA PET study. Mol Psychiatry. 2019;24:1502–12.

    Article  PubMed  Google Scholar 

  8. Kim E, Howes OD, Veronese M, Beck K, Seo S, Park JW, et al. Presynaptic dopamine capacity in patients with treatment-resistant schizophrenia taking clozapine: An [18F]DOPA PET study. Neuropsychopharmacology. 2017;42:941–50.

    Article  PubMed  CAS  Google Scholar 

  9. Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD. Dopamine synthesis capacity in patients with treatment-resistant schizophrenia. Am J Psychiatry. 2012;169:1203–10.

    Article  PubMed  Google Scholar 

  10. Egerton A, Murphy A, Donocik J, Anton A, Barker GJ, Collier T, et al. Dopamine and Glutamate in Antipsychotic-Responsive Compared With Antipsychotic-Nonresponsive Psychosis: A Multicenter Positron Emission Tomography and Magnetic Resonance Spectroscopy Study (STRATA). Schizophr Bull. 2020;47:505–16.

    Article  PubMed Central  Google Scholar 

  11. Avram M, Brandl F, Cabello J, Leucht C, Scherr M, Mustafa M, et al. Reduced striatal dopamine synthesis capacity in patients with schizophrenia during remission of positive symptoms. Brain. 2019;142:1813–26.

    Article  PubMed  Google Scholar 

  12. Demjaha A, Egerton A, Murray RM, Kapur S, Howes OD, Stone JM, et al. Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function. Biol Psychiatry. 2014;75:e11–3.

    Article  PubMed  CAS  Google Scholar 

  13. Cassidy CM, Zucca FA, Girgis RR, Baker SC, Weinstein JJ, Sharp ME, et al. Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain. Proc Natl Acad Sci. 2019;116:5108–17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Ueno F, Iwata Y, Nakajima S, Caravaggio F, Rubio JM, Horga G, et al. Neuromelanin accumulation in patients with schizophrenia: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022;132:1205–13.

    Article  PubMed  CAS  Google Scholar 

  15. van der Pluijm M, Wengler K, Reijers PN, Cassidy CM, Tjong Tjin Joe K, de Peuter OR, et al. Neuromelanin-Sensitive MRI as Candidate Marker for Treatment Resistance in First-Episode Schizophrenia. Am J Psychiatry. 2024;181:512–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Wengler K, Baker SC, Velikovskaya A, Fogelson A, Girgis RR, Reyes-Madrigal F, et al. Generalizability and out-of-sample predictive ability of associations between neuromelanin-sensitive magnetic resonance imaging and psychosis in antipsychotic-free individuals. JAMA Psychiatry. 2024;81:198–208.

    Article  PubMed  Google Scholar 

  17. Conn K-A, Burne THJ, Kesby JP. Subcortical dopamine and cognition in schizophrenia: Looking beyond psychosis in preclinical models. Front Neurosci. 2020;14:542.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Slifstein M, van de Giessen E, Van Snellenberg J, Thompson JL, Narendran R, Gil R, et al. Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study. JAMA Psychiatry. 2015;72:316–24.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Arbanas G. Diagnostic and statistical manual of mental disorders (DSM-5). Alcoholism Psychiatry Res. 2015;51:61–4.

    Google Scholar 

  20. Howes OD, McCutcheon R, Agid O, de Bartolomeis A, van Beveren NJM, Birnbaum ML, et al. Treatment-Resistant Schizophrenia: Treatment Response and Resistance in Psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology. Am J Psychiatry. 2017;174:216–29.

    Article  PubMed  Google Scholar 

  21. Iwata Y, Nakajima S, Plitman E, Caravaggio F, Kim J, Shah P, et al. Glutamatergic Neurometabolite Levels in Patients With Ultra-Treatment-Resistant Schizophrenia: A Cross-Sectional 3T Proton Magnetic Resonance Spectroscopy Study. Biol Psychiatry. 2019;85:596–605.

    Article  PubMed  CAS  Google Scholar 

  22. Andreasen NC, Carpenter WT Jr, Kane JM, Lasser RA, Marder SR, Weinberger DR. Remission in schizophrenia: proposed criteria and rationale for consensus. Am J Psychiatry. 2005;162:441–9.

    Article  PubMed  Google Scholar 

  23. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13:261–76.

    Article  PubMed  CAS  Google Scholar 

  24. Guy W ECDEU assessment manual for psychopharmacology. U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976.

  25. Jones SH, Thornicroft G, Coffey M, Dunn G. A brief mental health outcome scale-reliability and validity of the Global Assessment of Functioning (GAF). Br J Psychiatry. 1995;166:654–9.

    Article  PubMed  CAS  Google Scholar 

  26. Randolph C, Tierney MC, Mohr E, Chase TN. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): preliminary clinical validity. J Clin Exp Neuropsychol. 1998;20:310–9.

    Article  PubMed  CAS  Google Scholar 

  27. Matsui M, Kasai Y, Nagasaki M. Reliability and validity for the Japanese version of the repeatable battery for the assessment of neuropsychological status (RBANS). Toyama Med J. 2010;21:31–6.

    Google Scholar 

  28. Royall DR, Mahurin RK, Gray KF. Bedside assessment of executive cognitive impairment: the executive interview. J Am Geriatr Soc. 1992;40:1221–6.

    Article  PubMed  CAS  Google Scholar 

  29. Matsuoka T, Kato Y, Taniguchi S, Ogawa M, Fujimoto H, Okamura A, et al. Japanese versions of the executive interview (J-EXIT25) and the executive clock drawing task (J-CLOX) for older people. Int Psychogeriatr. 2014;26:1387–97.

    Article  PubMed  Google Scholar 

  30. Matsuoka K, Uno M, Kasai K, Koyama K, Kim Y. Estimation of premorbid IQ in individuals with Alzheimer’s disease using Japanese ideographic script (Kanji) compound words: Japanese version of National Adult Reading Test. Psychiatry Clin Neurosci. 2006;60:332–9.

    Article  PubMed  Google Scholar 

  31. Avants BB, Epstein CL, Grossman M, Gee JC. Symmetric diffeomorphic image registration with cross-correlation: evaluating automated labeling of elderly and neurodegenerative brain. Med Image Anal. 2008;12:26–41.

    Article  PubMed  CAS  Google Scholar 

  32. Wengler K, He X, Abi-Dargham A, Horga G. Reproducibility assessment of neuromelanin-sensitive magnetic resonance imaging protocols for region-of-interest and voxelwise analyses. Neuroimage. 2020;208:116457.

    Article  PubMed  CAS  Google Scholar 

  33. Zecca L, Fariello R, Riederer P, Sulzer D, Gatti A, Tampellini D. The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson’s disease. FEBS Lett. 2002;510:216–20.

    Article  PubMed  CAS  Google Scholar 

  34. Myran DT, Pugliese M, Harrison LD, Solmi M, Anderson KK, Fiedorowicz JG, et al. Changes in incident schizophrenia diagnoses associated with cannabis use disorder after cannabis legalization. JAMA Netw Open. 2025;8:e2457868.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bloomfield MAP, Ashok AH, Volkow ND, Howes OD. The effects of Δ9-tetrahydrocannabinol on the dopamine system. Nature. 2016;539:369–77.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Ahrens J, Ford SD, Schaefer B, Reese D, Khan AR, Tibbo P, et al. Convergence of cannabis and psychosis on the dopamine system. JAMA Psychiatry. 2025;82:609–17.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Perlman G, Wengler K, Moeller SJ, Kotov R, Klein DN, Weinstein JJ, et al. Association of neuromelanin-sensitive MRI signal with lifetime substance use in young women. Am J Psychiatry. 2024;181:997–1005.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Zucca FA, Vanna R, Cupaioli FA, Bellei C, De Palma A, Di Silvestre D, et al. Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease. NPJ Parkinsons Dis. 2018;4:17.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Graham DG. On the origin and significance of neuromelanin. Arch Pathol Lab Med. 1979;103:359–62.

    PubMed  CAS  Google Scholar 

  40. Kumakura Y, Cumming P. PET studies of cerebral levodopa metabolism: a review of clinical findings and modeling approaches. Neuroscientist. 2009;15:635–50.

    Article  PubMed  CAS  Google Scholar 

  41. Vano LJ, McCutcheon RA, Rutigliano G, Kaar SJ, Finelli V, Nordio G, et al. Mesostriatal Dopaminergic Circuit Dysfunction in Schizophrenia: A Multimodal Neuromelanin-sensitive MRI and [18F]-DOPA PET Study. Biol Psychiatry. 2024;96:674–683.

  42. van Hooijdonk CFM, van der Pluijm M, Smith C, Yaqub M, van Velden FHP, Horga G, et al. Striatal dopamine synthesis capacity and neuromelanin in the substantia nigra: A multimodal imaging study in schizophrenia and healthy controls. Neuroscience Appl. 2023;2:101134.

    Article  Google Scholar 

  43. Jeste DV, Maglione JE. Treating older adults with schizophrenia: challenges and opportunities. Schizophr Bull. 2013;39:966–8.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Jeste DV, Wolkowitz OM, Palmer BW. Divergent trajectories of physical, cognitive, and psychosocial aging in schizophrenia. Schizophr Bull. 2011;37:451–5.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Nakajima S, Uchida H, Bies RR, Caravaggio F, Suzuki T, Plitman E, et al. Dopamine D2/3 receptor occupancy following dose reduction is predictable with minimal plasma antipsychotic concentrations: An open-label clinical trial. Schizophr Bull. 2016;42:212–9.

    PubMed  Google Scholar 

  46. Nakajima S, Caravaggio F, Boileau I, Chung JK, Plitman E, Gerretsen P, et al. Lack of age-dependent decrease in dopamine D3 receptor availability: a [(11)C]-(+)-PHNO and [(11)C]-raclopride positron emission tomography study. J Cereb Blood Flow Metab. 2015;35:1812–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Graff-Guerrero A, Rajji TK, Mulsant BH, Nakajima S, Caravaggio F, Suzuki T, et al. Evaluation of antipsychotic dose reduction in late-life schizophrenia: A prospective dopamine D2/3 receptor occupancy study: A prospective dopamine D2/3Receptor occupancy study. JAMA Psychiatry. 2015;72:927–34.

    Article  PubMed  Google Scholar 

  48. Weidenauer A, Sauerzopf U, Bauer M, Bum C, Diendorfer C, Dajic I, et al. Amphetamine-induced dopamine release predicts 1-year outcome in first-episode psychosis: A naturalistic observation. Schizophr Bull. 2024;51:159–69.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Sigvard AK, Nielsen MØ, Gjedde A, Bojesen KB, Fuglø D, Tangmose K, et al. Dopaminergic activity in antipsychotic-naïve patients assessed with positron emission tomography before and after partial dopamine D2 receptor agonist treatment: Association with psychotic symptoms and treatment response. Biol Psychiatry. 2022;91:236–45.

    Article  PubMed  CAS  Google Scholar 

  50. Brugger SP, Angelescu I, Abi-Dargham A, Mizrahi R, Shahrezaei V, Howes OD. Heterogeneity of Striatal Dopamine Function in Schizophrenia: Meta-analysis of Variance. Biol Psychiatry. 2020;87:215–24.

    Article  PubMed  CAS  Google Scholar 

  51. Haber SN. The place of dopamine in the cortico-basal ganglia circuit. Neuroscience. 2014;282:248–57.

    Article  PubMed  CAS  Google Scholar 

  52. Matsuda W, Furuta T, Nakamura KC, Hioki H, Fujiyama F, Arai R, et al. Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J Neurosci. 2009;29:444–53.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Prensa L, Giménez-Amaya JM, Parent A, Bernácer J, Cebrián C The nigrostriatal pathway: axonal collateralization and compartmental specificity. J Neural Transm Suppl. 2009;73:49–58.

  54. Nakajima S, Gerretsen P, Takeuchi H, Caravaggio F, Chow T, Le Foll B, et al. The potential role of dopamine D₃ receptor neurotransmission in cognition. Eur Neuropsychopharmacol. 2013;23:799–813.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Lakhani DA, Zhou X, Tao S, Patel V, Wen S, Okromelidze L, et al. Diagnostic utility of 7T neuromelanin imaging of the substantia nigra in Parkinson’s disease. NPJ Parkinsons Dis. 2024;10:13.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. van Hooijdonk CFM, Drukker M, van de Giessen E, Booij J, Selten J-P, van Amelsvoort TAMJ. Dopaminergic alterations in populations at increased risk for psychosis: A systematic review of imaging findings. Prog Neurobiol. 2022;213:102265.

    Article  PubMed  Google Scholar 

  57. Huttunen J, Heinimaa M, Svirskis T, Nyman M, Kajander J, Forsback S, et al. Striatal dopamine synthesis in first-degree relatives of patients with schizophrenia. Biol Psychiatry. 2008;63:114–7.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the Japan Society for the Promotion of Science (18H02755, 22H03002), Japan Agency for Medical Research and Development (AMED: JP24wm0625302), Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Watanabe Foundation and Takeda Science Foundation. We thank Mr. Nishikata for his technical support. We thank the participants and their families for their cooperation in this research.

Funding

SH has received the JSPS Research Fellowship for Young Scientists (DC1), and The Keio University Doctorate Student Grant-in-Aid Program from Ushioda Memorial Fund. FU has received grants from Discovery Fund, Nakatani Foundation, Canadian Institutes of Health Research (CIHR), and Brain & Behavior Research Foundation (BBRF); manuscript fees from Dainippon Sumitomo Pharma; and consultant fees from VeraSci, and Uchiyama Underwriting within the past three years. SN has received grants from Japan Society for the Promotion of Science (18H02755, 22H03002), Japan Agency for Medical Research and development (AMED: JP24wm0625302, JP24wm0625307), Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, Watanabe Foundation, Osakeno-Kagaku Foundation, and Astellas Foundation within the past three years. SN has also received research support, manuscript fees or speaker’s honoraria from Asahi Quality & Innovations, Ltd., Teijin Pharma, Sumitomo Pharma, Meiji Seika Pharma, Otsuka, PDR pharma, and MSD within the past three years. YN has received Grants-in-Aid for Scientific Research (B) (18H02755; 20H04092; 21H02813) from the Japan Society for the Promotion of Science (JSPS), research grants (a) from Japan Agency for Medical Research and Development (AMED), investigator-initiated clinical study grants from TEIJIN PHARMA LIMITED (Tokyo, Japan) and Inter Reha Co., Ltd. (Tokyo, Japan). YN also receives research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Taiju Life Social Welfare Foundation, and Daiichi Sankyo Scholarship Donation Program. YN has received speaker’s honoraria from Dainippon Sumitomo Pharma, MOCHIDA PHARMACEUTICAL CO., LTD. (Tokyo, Japan), and Yoshito-miyakuhin Corporation within the past three years. AG-G received the grants from Canadian Institutes of Health Research (S). AG-G also receives research grants from Ministry of Economic Development and Innovation Ontario, Ontario Mental Health Foundation Type A grant, and NARSAD Independent Investigator (AG-G). Other authors do not have any conflict of interest to declare.

Author information

Author notes

  1. These authors contributed equally: Ryosuke Tarumi, Shiori Honda.

Authors and Affiliations

  1. Department of Neuropsychiatry, School of Medicine, Keio University, Shinjuku, Tokyo, 160-8582, Japan

    Ryosuke Tarumi, Shiori Honda, Shunya Sekihara, Sotaro Moriyama, Yui Tobari, Koki Takahashi, Fumihiko Ueno, Sakiko Tsugawa, Yoshihiro Noda, Hiroyuki Uchida & Shinichiro Nakajima

  2. Seikei-Kai Komagino Hospital, Hachioji, Tokyo, 193-8505, Japan

    Ryosuke Tarumi

  3. Department of Psychiatry and Behavioral Health, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY, 11794, USA

    Shiori Honda & Clifford Cassidy

  4. Graduate School of Media and Governance, Keio University, Fujisawa, Kanagawa, 252-0882, Japan

    Takahide Etani & Saki Homma

  5. Faculty of Policy Management, Keio University, Fujisawa, Kanagawa, 252-0882, Japan

    Yuka Kaneko

  6. Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada

    Fumihiko Ueno, Ariel Graff-Guerrero & Shinichiro Nakajima

  7. New York State Psychiatric Institute, New York, NY, 10032, USA

    Guillermo Horga

  8. Department of Psychiatry, Columbia University, New York, NY, 10032, USA

    Guillermo Horga

  9. Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, 11004, USA

    Jose M. Rubio

  10. Department of Clinical Cognitive Neuroscience, Institute of Liberal Arts and Science, Kanazawa University, Kanazawa, Ishikawa, 920-1164, Japan

    Mie Matsui

  11. Faculty of Environment and Information Studies, Keio University, Fujisawa, Kanagawa, 252-0882, Japan

    Shinya Fujii

Authors
  1. Ryosuke Tarumi
    View author publications

    Search author on:PubMed Google Scholar

  2. Shiori Honda
    View author publications

    Search author on:PubMed Google Scholar

  3. Clifford Cassidy
    View author publications

    Search author on:PubMed Google Scholar

  4. Takahide Etani
    View author publications

    Search author on:PubMed Google Scholar

  5. Saki Homma
    View author publications

    Search author on:PubMed Google Scholar

  6. Shunya Sekihara
    View author publications

    Search author on:PubMed Google Scholar

  7. Yuka Kaneko
    View author publications

    Search author on:PubMed Google Scholar

  8. Sotaro Moriyama
    View author publications

    Search author on:PubMed Google Scholar

  9. Yui Tobari
    View author publications

    Search author on:PubMed Google Scholar

  10. Koki Takahashi
    View author publications

    Search author on:PubMed Google Scholar

  11. Fumihiko Ueno
    View author publications

    Search author on:PubMed Google Scholar

  12. Guillermo Horga
    View author publications

    Search author on:PubMed Google Scholar

  13. Sakiko Tsugawa
    View author publications

    Search author on:PubMed Google Scholar

  14. Jose M. Rubio
    View author publications

    Search author on:PubMed Google Scholar

  15. Mie Matsui
    View author publications

    Search author on:PubMed Google Scholar

  16. Shinya Fujii
    View author publications

    Search author on:PubMed Google Scholar

  17. Ariel Graff-Guerrero
    View author publications

    Search author on:PubMed Google Scholar

  18. Yoshihiro Noda
    View author publications

    Search author on:PubMed Google Scholar

  19. Hiroyuki Uchida
    View author publications

    Search author on:PubMed Google Scholar

  20. Shinichiro Nakajima
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Ryosuke Tarumi: Conceptualization; Investigation; Resources; Data Curation; Writing – Original Draft; Supervision; Project Administration. Shiori Honda: Conceptualization; Methodology; Formal Analysis; Investigation; Data Curation; Writing – Original Draft; Visualization; Supervision. Clifford Cassidy: Methodology; Software; Validation; Writing – Review & Editing; Visualization. Takahide Etani: Validation; Formal Analysis; Data Curation; Writing – Original Draft; Visualization. Saki Homma: Validation; Formal Analysis; Investigation; Data Curation; Writing – Original Draft; Visualization. Shunya Sekihara: Formal Analysis; Data Curation; Writing – Original Draft; Visualization. Yuka Kaneko: Data Curation; Writing – Review & Editing. Sotaro Moriyama: Investigation; Data Curation; Writing – Review & Editing. Yui Tobari: Investigation; Data Curation; Writing – Review & Editing. Koki Takahashi: Validation; Data Curation; Writing – Review & Editing. Fumihiko Ueno: Writing – Review & Editing. Guillermo Horga: Writing – Review & Editing. Sakiko Tsugawa: Validation; Writing – Review & Editing. Jose M. Rubio: Writing – Review & Editing. Mie Matsui: Writing – Review & Editing. Shinya Fujii: Writing – Review & Editing. Ariel Graff-Guerrero: Writing – Review & Editing. Yoshihiro Noda: Conceptualization; Resources; Writing – Review & Editing. Hiroyuki Uchida: Conceptualization; Resources; Writing – Review & Editing; Supervision. Shinichiro Nakajima: Conceptualization; Resources; Writing – Original Draft; Supervision; Project Administration; Funding Acquisition.

Corresponding author

Correspondence to Shinichiro Nakajima.

Ethics declarations

Competing interests

The authors have nothing to disclose.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tarumi, R., Honda, S., Cassidy, C. et al. Associations of neuromelanin in the substantia nigra with antipsychotic response in schizophrenia. Neuropsychopharmacol. 51, 682–690 (2026). https://doi.org/10.1038/s41386-025-02275-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41386-025-02275-0

Search

Advanced search

Quick links