Clinical Symptomatology, Cognition and Psychosocial Wellbeing in Adolescents With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Cross-Sectional Observational Study

Abstract:

Aim: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling illness that frequently begins in adolescence, yet adolescents with ME/CFS remain an under-researched population. We aimed to characterise the cognitive and psychosocial wellbeing of adolescents with ME/CFS relative to normative benchmarks and unaffected age-peers.

Methods: Adolescents with mild-to-moderate ME/CFS (n = 25) and healthy controls (n = 25) aged 10-19 years were recruited in Melbourne, Australia. Each completed a set of clinical questionnaires and cognitive assessments to assess ME/CFS symptomatology, school functioning, psychosocial wellbeing and cognition. Their caregivers also completed questionnaires regarding their psychosocial wellbeing and everyday executive functioning.

Results: Adolescents with ME/CFS showed significantly reduced information processing speed, though other measures of intellectual functioning did not differ consistently between groups. The ME/CFS group also reported significantly poorer sleep, quality of life and higher levels of anxiety and depression. Caregivers further identified significant attention and working memory concerns in the ME/CFS group, but reported no differences in internalising behaviours between groups.

Conclusion: Adolescents with ME/CFS experience substantial psychosocial and physical burden because of their illness. Cognitive difficulties in ME/CFS may reflect inefficiencies in information processing speed and fluctuating symptom burden. Discrepancies between adolescent self-report and caregiver ratings underscore the importance of inclusive perspectives in ME/CFS management. These findings support the need for flexible, paced educational and clinical accommodations and for further research into the dynamic cognitive profile of adolescents with ME/CFS across a more representative population.

Source: Chau T, Josev EK, Scheinberg A, Thomas N, McDonald F, Reveley C, Gooley PR, Armstrong C, Knight S. Clinical Symptomatology, Cognition and Psychosocial Wellbeing in Adolescents With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Cross-Sectional Observational Study. J Paediatr Child Health. 2026 Sep 20. doi: 10.1111/jpc.70587. Epub ahead of print. PMID: 42764669. https://onlinelibrary.wiley.com/doi/10.1111/jpc.70587 (Full text)

Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study

Abstract:

Background: In recent years, evidence has indicated a metabolic shift towards increased demand for lipids in various lymphoid cell populations from people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We previously screened the mitochondrial function and gene expression of B cell-derived lymphoblastoid cell lines (LCLs) generated from the blood of people with ME/CFS to characterise a model for hypothesis discovery and testing, observing elevated expression of gene products facilitating amino acid and fatty acid degradation for energy.

Method: In this follow-up study we have expanded this characterisation by profiling the polar metabolomes and non-polar lipidomes of an all-female cohort of 17 healthy control and 15 ME/CFS LCLs, and we integrated this new data with the previously generated proteomic and transcriptomic data.

Results: In the polar metabolome we detected no significantly altered individual features, while integrated multi-omic analysis by MetaboAnalyst indicated 15 dysregulated pathways. Next, in the non-polar lipidome, we identified that PC(O-38:4) had significantly reduced levels in ME/CFS LCLs and was almost entirely discriminative of ME/CFS status. Among all detected classes of lipids we found that triradylglycerolipids (“triglycerides”), diradylglycerolipids and fatty acids were the most significantly affected and were elevated, and that most lipids exhibited average levels higher than in healthy controls. BioPAN pathway analysis of the lipidomic data predicted a more-active gene product that we confirmed to be significantly elevated in both our proteomic and transcriptomic data, this being phosphatidylserine synthase 1 (PTDSS1), plus 7 other gene products that were concordantly altered in expression in the transcriptomic data. We also found that ME/CFS LCLs exhibited a significant tendency towards more saturated lipid content.

Conclusions: LCLs generated from circulating B cells from people with ME/CFS show accumulation of lipids, skewed lipid profiles and altered activity of related metabolic enzymes such as PTDSS1. These findings will inform future hypothesis-driven studies of primary lymphoid cell populations from people with ME/CFS to dissect specific immunometabolic mechanisms that may be involved in the syndrome, particularly relating to intersections between lipid abnormalities and potential effects on immune cell effector functions.

Source: Missailidis D, Armstrong CW, Anderson D, Allan CY, Sanislav O, Smith PK, Esmaili T, Creek DJ, Annesley SJ, Fisher PR. Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study. J Transl Med. 2026 Jan 8. doi: 10.1186/s12967-025-07620-x. Epub ahead of print. PMID: 41508032. https://link.springer.com/article/10.1186/s12967-025-07620-x (Full text available as PDF file)