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Telomere attrition and inflammatory load in severe psychiatric disorders and in response to psychotropic medications
Authors:Alessio Squassina  Mirko Manchia  Claudia Pisanu  Raffaella Ardau  Carlo Arzedi  Alberto Bocchetta  Paola Caria  Cristina Cocco  Donatella Congiu  Eleonora Cossu  Tinuccia Dettori  Daniela Virginia Frau  Mario Garzilli  Elias Manca  Anna Meloni  Maria Antonietta Montis  Andrea Mura  Mariella Nieddu  Barbara Noli  Pasquale Paribello  Federica Pinna  Renato Robledo  Giovanni Severino  Valeria Sogos  Maria Del Zompo  Gian Luca Ferri  Caterina Chillotti  Roberta Vanni  Bernardo Carpiniello
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 F6, 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.Subject terms: Schizophrenia, Diagnostic markers, Bipolar disorder, Depression
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