Hypothalamus volumes in adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): impact of self-reported fatigue and illness duration

Brain Struct Funct. 2023 Sep;228(7):1741-1754. doi: 10.1007/s00429-023-02682-3. Epub 2023 Aug 3.

Abstract

Adolescent Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex illness of unknown aetiology. Emerging theories suggest ME/CFS may reflect a progressive, aberrant state of homeostasis caused by disturbances within the hypothalamus, yet few studies have investigated this using magnetic resonance imaging in adolescents with ME/CFS. We conducted a volumetric analysis to investigate whether whole and regional hypothalamus volumes in adolescents with ME/CFS differed compared to healthy controls, and whether these volumes were associated with fatigue severity and illness duration. 48 adolescents (25 ME/CFS, 23 controls) were recruited. Lateralised whole and regional hypothalamus volumes, including the anterior-superior, superior tubular, posterior, anterior-inferior and inferior tubular subregions, were calculated from T1-weighted images. When controlling for age, sex and intracranial volume, Bayesian linear regression models revealed no evidence for differences in hypothalamus volumes between groups. However, in the ME/CFS group, a weak linear relationship between increased right anterior-superior volumes and fatigue severity was identified, which was absent in controls. In addition, Bayesian quantile regression revealed a likely-positive association between illness duration and right superior tubular volumes in the ME/CFS group. While these findings suggest overall comparability in regional and whole hypothalamus volumes between adolescents with ME/CFS and controls, preliminary evidence was identified to suggest greater fatigue severity and longer illness duration were associated with greater right anterior-superior and superior-tubular volumes, respectively. These regions contain the anterior and superior divisions of the paraventricular nucleus, involved in the neuroendocrine response to stress, suggesting involvement in ME/CFS pathophysiology. However, replication in a larger, longitudinal cohort is required.

Keywords: Adolescence; Chronic Fatigue Syndrome; Hypothalamus; Myalgic Encephalomyelitis; Structural magnetic resonance imaging; Volumetric analysis.

MeSH terms

  • Adolescent
  • Bayes Theorem
  • Fatigue Syndrome, Chronic* / diagnostic imaging
  • Fatigue Syndrome, Chronic* / pathology
  • Humans
  • Hypothalamus / pathology
  • Magnetic Resonance Imaging
  • Self Report