Mitochondrial DNA copy number is significantly increased in bipolar disorder patients and is correlated with long-term lithium treatment

IF 6.1 2区医学 Q1 CLINICAL NEUROLOGY

European Neuropsychopharmacology Pub Date : 2024-11-28 DOI:10.1016/j.euroneuro.2024.10.012

Anna Meloni , Pasquale Paribello , Marco Pinna , Martina Contu , Raffaella Ardau , Caterina Chillotti , Donatella Congiu , Massimo Gennerelli , Alessandra Minelli , Lisa Buson , Giovanni Severino , Claudia Pisanu , Mirko Manchia , Alessio Squassina

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引用次数: 0

Abstract

Mitochondrial dysfunctions have been reported in bipolar disorder (BD), but their role in the etiopathogenesis of BD as well as their implications in modulating response to pharmacological treatments with psychotropic medications have been scarcely explored. Mitochondrial DNA copy number (mtDNA-cn) has been linked to mitochondria functioning, and, despite some degree of inconsistence, previous findings showed that BD patients present significant differences in mtDNA-cn compared to healthy controls. Here we measured mtDNA-cn in a sample of 89 patients with BD and 78 healthy controls (HC). Patients in the BD sample were treated either with lithium (n = 47) and characterized as responders (n = 22) or non-responders (n = 25), or with other mood stabilizers (n = 42). BD patients had larger mtDNA-cn compared to HC (adjusted model: F₂=9.832; p = 0.000095; contribution of diagnosis F₁= 10.798; p = 0.001). When the BD sample was stratified for treatment exposure, mtDNA-cn was lower in patients treated with lithium compared to those treated with other mood stabilizers (adjusted model: F₄=23.770, p = 7.0929E-13; contribution of treatment: F₁=54.300, p = 1.55E-10). Moreover mtDNA-cn was higher in patients treated with other mood stabilizers compared to controls and Li-treated BD patients (F₃=28.125, p = 1.36E-14; contribution of groups F₂=36.156, p = 1.25E-13). Finally, there was no difference in mtDNA-cn levels in lithium responders compared to non-responders and neither between the two diagnostic groups (BD type 1 and 2). Our findings suggest that BD may be associated with mitochondrial dysfunctions, and that exposure to lithium but not to other mood stabilizers may restore these abnormalities, though this does not appear correlated with the clinical efficacy of lithium.

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来源期刊

European Neuropsychopharmacology 医学-精神病学

CiteScore

10.30

自引率

5.40%

发文量

730

审稿时长

41 days

期刊介绍： European Neuropsychopharmacology is the official publication of the European College of Neuropsychopharmacology (ECNP). In accordance with the mission of the College, the journal focuses on clinical and basic science contributions that advance our understanding of brain function and human behaviour and enable translation into improved treatments and enhanced public health impact in psychiatry. Recent years have been characterized by exciting advances in basic knowledge and available experimental techniques in neuroscience and genomics. However, clinical translation of these findings has not been as rapid. The journal aims to narrow this gap by promoting findings that are expected to have a major impact on both our understanding of the biological bases of mental disorders and the development and improvement of treatments, ideally paving the way for prevention and recovery.