Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications

Squassina, Alessio; Manchia, Mirko; Pisanu, Claudia; Ardau, Raffaella; Arzedi, Carlo; Bocchetta, Alberto; Caria, Paola; Cocco, Cristina; Congiu, Donatella; Cossu, Eleonora; Dettori, Tinuccia; Frau, Daniela Virginia; Garzilli, Mario; Manca, Elias; Meloni, Anna; Montis, Maria Antonietta; Mura, Andrea; Nieddu, Mariella; Noli, Barbara; Paribello, Pasquale; Pinna, Federica; Robledo, Renato; Severino, Giovanni; Sogos, Valeria; Del Zompo, Maria; Ferri, Gian Luca; Chillotti, Caterina; Vanni, Roberta; Carpiniello, Bernardo

doi:10.1038/s41386-020-00844-z

Article
Published: 12 September 2020

Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications

Alessio Squassina ORCID: orcid.org/0000-0001-7415-7607¹^na1,
Mirko Manchia ORCID: orcid.org/0000-0003-4175-6413^2,3,4^na1,
Claudia Pisanu ORCID: orcid.org/0000-0002-9151-4319¹^na1,
Raffaella Ardau⁵,
Carlo Arzedi^2,3,
Alberto Bocchetta^1,5,
Paola Caria⁶,
Cristina Cocco⁷,
Donatella Congiu¹,
Eleonora Cossu^2,3,
Tinuccia Dettori⁶,
Daniela Virginia Frau⁶,
Mario Garzilli^2,3,
Elias Manca⁷,
Anna Meloni¹,
Maria Antonietta Montis^2,3,
Andrea Mura^2,3,
Mariella Nieddu⁶,
Barbara Noli⁷,
Pasquale Paribello^2,3,
Federica Pinna^2,3,
Renato Robledo⁶,
Giovanni Severino ORCID: orcid.org/0000-0002-6354-2662¹,
Valeria Sogos⁸,
Maria Del Zompo^1,5,
Gian Luca Ferri⁷,
Caterina Chillotti⁵^na2,
Roberta Vanni⁶^na2 &
…
Bernardo Carpiniello^2,3^na2

Neuropsychopharmacology volume 45, pages 2229–2238 (2020)Cite this article

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Abstract

Individuals with severe psychiatric disorders have a reduced life expectancy compared to the general population. At the biological level, patients with these disorders present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). To date, the role of the interplay between inflammation and telomere dynamics in the pathophysiology of severe psychiatric disorders has been scarcely investigated. In this study we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort comprised of 40 patients with bipolar disorder (BD), 41 with schizophrenia (SZ), 37 with major depressive disorder (MDD), and 36 non-psychiatric controls (NPC). TL was shorter in SZ and in MDD compared to NPC, while it was longer in BD (model F_{6, 137} = 20.128, p = 8.73 × 10⁻¹⁷, effect of diagnosis, F₃ = 31.870; p = 1.08 × 10⁻¹⁵). There was no effect of the different classes of psychotropic medications, while duration of treatment with mood stabilizers was associated with longer TL (Partial correlation controlled for age and BMI: correlation coefficient = 0.451; p = 0.001). Levels of high-sensitivity C-Reactive Protein (hsCRP) were higher in SZ compared to NPC (adjusted p = 0.027), and inversely correlated with TL in the whole sample (r = −0.180; p = 0.042). Compared to NPC, patients with treatment resistant (TR) SZ had shorter TL (p = 0.001), while patients with TR MDD had higher levels of tumor necrosis factor-α (TNFα) compared to NPC (p = 0.028) and to non-TR (p = 0.039). Comorbidity with cardio-metabolic disorders did not influence the observed differences in TL, hsCRP, and TNFα among the diagnostic groups. Our study suggests that patients with severe psychiatric disorders present reduced TL and increased inflammation.

Shorter telomere length predicts poor antidepressant response and poorer cardiometabolic indices in major depression

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Systemic inflammation, oxidative damage and neurocognition predict telomere length in a transdiagnostic sample stratified by global DNA methylation levels

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A multi-omic dissection of molecular hallmarks of accelerated aging in schizophrenia

Article Open access 22 May 2025

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Author information

These authors contributed equally: Alessio Squassina, Mirko Manchia, Claudia Pisanu
These authors jointly supervised this work: Caterina Chillotti, Roberta Vanni, Bernardo Carpiniello

Authors and Affiliations

Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, 09042, Monserrato, Cagliari, Italy
Alessio Squassina, Claudia Pisanu, Alberto Bocchetta, Donatella Congiu, Anna Meloni, Giovanni Severino & Maria Del Zompo
Unit of Psychiatry, Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy
Mirko Manchia, Carlo Arzedi, Eleonora Cossu, Mario Garzilli, Maria Antonietta Montis, Andrea Mura, Pasquale Paribello, Federica Pinna & Bernardo Carpiniello
Unit of Clinical Psychiatry, University Hospital Agency of Cagliari, Cagliari, Italy
Mirko Manchia, Carlo Arzedi, Eleonora Cossu, Mario Garzilli, Maria Antonietta Montis, Andrea Mura, Pasquale Paribello, Federica Pinna & Bernardo Carpiniello
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
Mirko Manchia
Unit of Clinical Pharmacology, University Hospital Agency of Cagliari, Cagliari, Italy
Raffaella Ardau, Alberto Bocchetta, Maria Del Zompo & Caterina Chillotti
Department of Biomedical Sciences, Unit of Biology and Genetics, University of Cagliari, Monserrato, Cagliari, Italy
Paola Caria, Tinuccia Dettori, Daniela Virginia Frau, Mariella Nieddu, Renato Robledo & Roberta Vanni
Department of Biomedical Sciences, NEF Laboratory, University of Cagliari, Monserrato, Cagliari, Italy
Cristina Cocco, Elias Manca, Barbara Noli & Gian Luca Ferri
Department of Biomedical Sciences, Section of Cytomorphology, University of Cagliari, Monserrato, Cagliari, Italy
Valeria Sogos

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Alessio Squassina
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Contributions

AS conceived and designed the work, acquired the data, contributed interpreting the results, drafted and revised the manuscript, approved the final version; MM performed and coordinated the recruitment of patients, participated conceiving the study and drafting the manuscript; CP run part of the experiments, drafted the methods and result section, contributed analyzing and interpreting the findings; DC, performed part of the TL experiments and coordinated the activity of the laboratory of pharmacogenomics; AM, performed part of the experiments on telomeres; RA, CA, AB, EC, MG, MAM, AM, PP, FP, GS, contributed recruiting the patients and controls; PC, TD, DVF performed the Q-FISH experiments; MN, RR, VS contributed conceiving the study and interpreting the results; CC, EM, BN performed the ELISA experiments; GLF coordinated the ELISA experiments and contributed interpreting the findings; MDZ and CC coordinated the recruitment of patients and controls at the Unit of Clinical Pharmacology, and contributed designing the study; RV contributed conceiving the study, interpreting findings and finalizing the manuscript; BC coordinated the clinical activity of the Unit of Psychiatry and contributed interpreting the findings and finalizing the manuscript.

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Correspondence to Alessio Squassina.

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The authors declare no competing interests.

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Supplementary information

Table S1

Table S2

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Squassina, A., Manchia, M., Pisanu, C. et al. Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications. Neuropsychopharmacol. 45, 2229–2238 (2020). https://doi.org/10.1038/s41386-020-00844-z

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Received: 12 May 2020
Revised: 14 August 2020
Accepted: 26 August 2020
Published: 12 September 2020
Issue date: December 2020
DOI: https://doi.org/10.1038/s41386-020-00844-z

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