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Primary mitochondrial diseases (PMD) are heterogeneous disorders caused by mutations in nuclear DNA-encoded and mitochondrial DNA (mtDNA)-encoded genes. Neurological impairment is common and reflects the susceptibility of the central nervous system to alterations in mitochondrial oxidative metabolism. Case reports and small-scale cross-sectional studies in PMD have suggested a high comorbidity with neuropsychiatric syndromes, including mood disorders (online supplementary table 1).1 However, the prevalence of affective syndromes in a large cohort of patients with PMD has not been systematically evaluated. The putative link between mitochondria and mood psychopathology is further strengthened by converging evidence that implicates mitochondrial dysfunction in bipolar affective disorder (BPAD) syndromes.2 3 BPAD affects approximately 1% to 4% of the population worldwide;4 Type I is diagnosed on the basis of ≥1 lifetime occurrence of mania, while Type II is characterised by episodes of depression and hypomania.
We present a large-scale cross-sectional cohort study of the prevalence of BPAD and other affective syndromes, including major depressive episode (MDE) and generalised anxiety disorder (GAD), in adults with genetically confirmed PMD.
Patients and methods
Informed consent was obtained from all participants. Consecutive adults (aged ≥16 years) with genetically confirmed PMD attending our specialist mitochondrial disorders clinic between July 2017 and October 2018 were included. Clinical and molecular data were collected, including the Newcastle Mitochondrial Disease Scale for Adults (NMDAS) scores and mtDNA heteroplasmy levels, as part of routine assessment. Four validated, self-administered questionnaires were used to evaluate affect as follows: (1) Mood Disorder Questionnaire (MDQ), (2) Hypomania Symptom Checklist (HCL)-32, (3) Patient Health Questionnaire (PHQ)-9 and (4) Generalised Anxiety Disorder (GAD)-7, to assess symptoms of mania, hypomania, MDEs and GAD, respectively. Criteria for positiveness and use of normative data for comparisons of prevalence are explained in the online supplementary methods. Additional analysis was undertaken in a subgroup of …
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AC and EB contributed equally.
Contributors AC and EB are joint first authors. Study concept and design: AC, EB, SA, AHY, RQ, MGH, RDSP. Data acquisition and analysis: AC, EB, SA, OVP, IS, MS, LG, DK, SH, NJ, CW. Drafting the manuscript: AC, EB, RDSP.
Funding Part of this work was undertaken in the University College London Hospitals/University College London Queen Square Institute of Neurology sequencing facility, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. The clinical and diagnostic 'Rare Mitochondrial Disorders' Service in London is funded by the UK NHS Highly Specialised Commissioners. We gratefully acknowledge the generous support of a Clore Duffield Foundation grant. RDSP is supported by a Medical Research Council Clinician Scientist Fellowship (MR/S002065/1).
Competing interests None declared.
Patient consent for publication Not required.
Ethics approval The study was approved by the Queen Square Research Ethics Committee, London (09/H0716/76).
Provenance and peer review Not commissioned; externally peer reviewed.