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Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients

Molecular Psychiatry volume 28, pages 2049–2057 (2023)Cite this article

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Abstract

Sleep and rest-activity-rhythm (RAR) abnormalities are commonly reported in schizophrenia spectrum disorder (SSD) patients. However, an in-depth characterization of sleep/RAR alterations in SSD, including patients in different treatment settings, and the relationship between these alterations and SSD clinical features (e.g., negative symptoms) is lacking. SSD (N = 137 altogether, N = 79 residential and N = 58 outpatients) and healthy control (HC) subjects (N = 113) were recruited for the DiAPAson project. Participants wore an ActiGraph for seven consecutive days to monitor habitual sleep-RAR patterns. Sleep/rest duration, activity (i.e., M10, calculated on the 10 most active hours), rhythm fragmentation within days (i.e., intra-daily variability, IV; beta, steepness of rest-active changes), and rhythm regularity across days (i.e., inter-daily stability, IS) were computed in each study participant. Negative symptoms were assessed in SSD patients with the Brief Negative Symptom Scale (BNSS). Both SSD groups showed lower M10 and longer sleep/rest duration vs. HC, while only residential patients had more fragmented and irregular rhythms than HC. Compared to outpatients, residential patients had lower M10 and higher beta, IV and IS. Furthermore, residential patients had worse BNSS scores relative to outpatients, and higher IS contributed to between-group differences in BNSS score severity. Altogether, residentials and outpatients SSD had both shared and unique abnormalities in Sleep/RAR measures vs. HC and relative to one another, which also contributed to the patients’ negative symptom severity. Future work will help establish whether improving some of these measures may ameliorate the quality of life and clinical symptoms of SSD patients.

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Fig. 1: Sleep and rest-activity rhythm (RAR) parameters that differed across control (green), schizophrenia spectrum disorder (SSD) outpatients (yellow), and SSD residential patients (red).
Fig. 2: Brief Negative Symptom Scale (BNSS) comparison between SSD groups and BNSS relationship with inter-daily stability (IS) across groups.

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Data availability

Dataset referring to this manuscript is published with restricted access on Zenodo platform and accessible at this link: https://doi.org/10.5281/zenodo.7738228. The data analysis scripts used in this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank the Italian Ministry of Health for the funding received for this research project. We thank all members of the DiAPAson Consortium who actively worked to make this project possible: DMH, ASL Ancona (P. D’Elia, S. Impicci, M. Mari, F.M. Quintieri); RF Passaggi Srl-Oricola, Aquila (A. Bellotta, F. Jacoponi, A. Maurizi, L. Tranquilli); DMH, ASL Bari (V. Latorre, G. Nappi, D. Semisa); DMH, ASST Bergamo Ovest (S. Fenaroli, E. Monzani); DMH, ASST Spedali Civili Brescia (S. Barlati, M. Facchi, N. Necchini, A. Vita); IRCCS Fatebenefratelli, Brescia (G. de Girolamo, A. Martinelli, G. Tura, M. Zamparini, C. Zarbo); Dept of Molecular and Translational Medicine, University of Brescia (S. Calza, M. Rota); RF Centro Ippocrate CRA Macchiareddu, Cagliari (C. Lanzi, P. Paribello, B. Piccicacchi, C. Schiavo); Fatebenefratelli Sant’Ambrogio e Sacro Cuore di Gesù, Cernusco sul Naviglio, Milano (R. Bussi, D. Di Cosimo, G.M. Giobbio, R. Placenti); DMH, ASST Cremona (G. Giordano, C. Greco, I. Rossoni, F. Spinogatti); DMH ASST Rhodense, Garbagnate (C. Rovera, M. Toscano); DMH, ASL 3 Genova (L. Ghio, L. Lattanzi, D. Malagamba, M. Tosato); RF CREST ‘La Perla’, Grumello del Monte, Bergamo (L. Rancati, S. Zizolfi); DMH, ASST Lodi (G. Cerveri, C. Cibra, V. Cuman, E. Pionetti); DMH, ASST Melegnano and Martesana, Melegnano (A. Di Gregorio, F. Durbano, L. Fussi, V. Masseroni); Fondazione Castellini ONLUS, Melegnano (A. Cicceri, A. de Giovanni); DMH, AUSL Modena (S. Agosta, A. de Novellis, F. Starace); DMH, ASST Monza (C. Calini, M. Clerici, R. Pessina); DMH, Napoli 2 Nord (A. Cucciniello, C. D’Anna, M.G. Foia, M.C. Miranda); DMH, ASST Pavia (L. Casiraghi, P. Politi, M. Rocchetti, A. Silva); RF Fondazione Giuseppe Costantino, Pavia (M. Marina, S. Panigada, S. Riavera); DMH, ASL Pescara (A. Cirincione, V. Di Michele, F. Paolone); DMH, AUSL Parma (E. Leuci, G. Paulillo, L. Pelizza); DMH USL Toscana Centro, Prato (A. Baroncelli, G. Cardamone, G. D’Anna, L. Tatini); DMH ASL Roma1 (G. Ducci, A. Maone, T.A. Poliseno, B. Rufelli); Fatebenefratelli Beata Vergine Consolata, San Maurizio Canavese (M.E. Boero, E. Castagno, F. De Dominicis); DMH, ASL Teramo (C. Della Croce, P. Giosuè); DMH, ASL Città di Torino (F. Facchini, G. Gallino); RF Progetto Du Parc, Torino (J. Orticola, N. Rossetto); DMH, APSS Trento (M. Goglio, F. Lucchi); DMH, ULSS 2 Marca Trevigiana, Treviso (A. Brega, R. De Marchi, P. Di Prisco); RF Le Vele ONLUS, Trezzo sull’Adda e Vaprio d’Adda (E. Bonetti, L. Colasuonno, A. Pozzi, M. Roncalli); DMH, ASUGI Trieste (R. Mezzina, A. Norbedo, A. Rippa); DMH, AOUI Verona (E. Canova, E. Dal Corso, C. D’Astore, M. Ruggeri); Dept of Neurosciences, University of Verona (D. Bertorelle, S. Pogliaghi); RF CTRP Associazione Don Giuseppe Girelli, Verona (G. Ferro, G. Gardelli, S. Pagani, A. Signoretti); DMH ULSS 8 Berica, Vicenza (I. Rodolfile, R. Tessari, S. Zanolini); RF CREST, Vinago (C.M. Dentali, M. Minotto).

Funding

The DiAPAson project was funded by the Italian Ministry of Health (Bando per la Ricerca Finalizzata 2018: RF-2018-12365514). The Ministry of Health has no role in analyzing and interpreting study findings. The corresponding author was supported by the National Institute of Mental Health (NIMH) grant, with the grant number R01 MH113827.

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Author notes

  1. These authors contributed equally: Ahmad Mayeli, Alice D. LaGoy.

Authors and Affiliations

  1. Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    Ahmad Mayeli, Alice D. LaGoy, Stephen F. Smagula, James D. Wilson & Fabio Ferrarelli

  2. Unit of Epidemiological Psychiatry and Evaluation, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Cristina Zarbo, Manuel Zamparini & Giovanni de Girolamo

  3. Department of Mental Health and Dependence, ASST of Pavia, Pavia, Italy

    Matteo Rocchetti, Letizia Casiraghi & Andrea Silva

  4. Department of Mental Health and Dependence, AUSL of Modena, Modena, Italy

    Fabrizio Starace

  5. Unit of Biostatistics and Bioinformatics, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    Stefano Calza & Matteo Rota

  6. Department of Health Sciences, University of Milan, Milan, Italy

    Armando D’Agostino

  7. IRCCS Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy

    Alessandra Martinelli

  8. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

    Gabriele Nibbio

  9. Department of Mental Health and Dependence, AUSL of Parma, Parma, Italy

    Lorenzo Pelizza

  10. Department of Mental Health and Dependence, ASST of Monza, Monza, Italy

    Rodolfo Pessina

  11. Centro Sacro Cuore di Gesù, San Colombano al Lambro, Lodi, Italy

    Roberto Placenti

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  1. Ahmad Mayeli
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  2. Alice D. LaGoy
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Consortia

DiAPAson Consortium

  • Alessandra Martinelli
  • , Gabriele Nibbio
  • , Lorenzo Pelizza
  • , Rodolfo Pessina
  • , Roberto Placenti
  • , Andrea Silva
  •  & Giovanni de Girolamo

Contributions

Conceptualized and designed the research: AM, ADL, SFS, GDG, and FF. Data and statistical analyses: AM, ADL, SFS, and JD. Writing the draft: AM, ADL, and FF. Critical revision of the manuscript: SFS, JDW, CZ, MR, FS, MZ, LC, SC, MR, AD, GDG, and FF. Funding resources: GDG and FF. All authors contributed to the interpretation of the results, and all authors read, edited, and approved the draft.

Corresponding author

Correspondence to Fabio Ferrarelli.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study has been approved by the ethical committees (Ecs) of the three main participating centers: EC of IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli (31/07/2019; no. 211/2019), EC of Area Vasta Emilia Nord (25/ 09/2019; no. 0025975/19), and EC of Pavia (02/09/2019, no. 20190075685) and by the Ecs of all participating sites.

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Mayeli, A., LaGoy, A.D., Smagula, S.F. et al. Shared and distinct abnormalities in sleep-wake patterns and their relationship with the negative symptoms of Schizophrenia Spectrum Disorder patients. Mol Psychiatry 28, 2049–2057 (2023). https://doi.org/10.1038/s41380-023-02050-x

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