Part 3: Autism and Health Issues Unpacked: Exploring the Intersection of Autism and Chronic Fatigue Syndrome

Written by Claire Eliza Sehinson, MS with Dr. Megan Anna Neff, PsyD. Originally posted on Neurodivergent Insights

This is a continuation from Part 2.

Autism and Chronic Fatigue Syndrome:

Overlapping Experiences

As highlighted by the Venn diagram, there are significant overlaps between autism and Chronic Fatigue Syndrome (CFS/ME), often leading to diagnostic overshadowing. Let's explore some of these shared experiences:

Brain Fog

Brain fog is a widely used term encompassing various symptoms of cognitive and executive dysfunction, commonly seen in ME/CFS and other chronic illnesses. Typically, it includes:

  • Confusion

  • Mental fatigue

  • Lack of clarity

  • Disorganization

  • Concentration difficulties

  • Slowed information processing

  • Newly apparent memory issues

In Autistic people, many symptoms associated with brain fog often surface during periods of sensory overload, stress, shutdowns, and meltdowns. Hormonal fluctuations, such as those occurring during cyclical changes or transitions like perimenopause/menopause, can also exacerbate these symptoms. Moreover, brain fog is a recognized feature of conditions like anxiety and depression, with potential links to infection and neuroinflammation.

Brain fog is not exclusive to autism or ME/CFS; it's also a common element in other health conditions, including long COVID. Importantly, brain fog should not be an experience people are expected to “just live with.” Appropriate accommodations and healthcare support, targeting the underlying causes, can significantly alleviate these symptoms.

Post-Viral/Long COVID and Its Connection to ME/CFS

The historical link between ME/CFS and infectious diseases has been well-documented. Notable examples include the "cluster outbreaks" of ME/CFS, such as the Royal Free Hospital Outbreak in London in 1955 and the Nevada (Incline Village) outbreak in 1985 (Acheson,1959). 

Research indicates that a variety of microbial infections can lead to a chronic fatigue symptom profile persisting long after the acute infection phase (Hickie et al., 2006). Interestingly, up to 12% of people may experience prolonged illness post-infection, a statistic mirrored in Long-COVID prevalence data from the UK, where approximately 1 in 10 COVID-19 cases result in persistent illness (Atchinson et al., 2023).

Long-COVID and post-viral ME/CFS share nearly identical clinical characteristics, with emerging research suggesting Long-COVID may be an immune subtype of ME/CFS. This is supported by overlapping pathological processes observed in both conditions.

Furthermore, individuals in the neurodivergent community, both diagnosed and undiagnosed, have been reported to face a higher risk of Long-COVID or COVID-related health complications (All Brain’s Belong). 

Immune Dysregulation & Autoimmunity in Autism and CFS/ME

A key factor in the post-viral fatigue and complications observed in both Autistic and CFS/ME patients is "immune dysregulation" and autoimmunity. Similar Immune Abnormalities in CFS/ME and Autism including: 

  • Insufficient Antiviral Defense: One notable similarity is the reduced number of Natural Killer (NK) Cells in both autistic and CFS/ME patients. NK cells, a type of T-lymphocyte, are crucial for eliminating viral infections and monitoring early cancer processes. Effective infection control is closely linked to the count and function of these cells  (Espinosa et al., 2019)(Sarasella et al., 2023)

  • Autoimmunity Trends: Another observation is the higher incidence of autoimmune conditions within families of both Autistic and CFS/ME individuals, hinting at a genetic predisposition (Sotzny, 2018). Autoimmunity is a complex disease process where the immune system, which typically balances defense and tolerance, becomes dysfunctional. This breakdown in immune communication leads to the mistaken attack and destruction of healthy tissues. Numerous lifestyle factors can influence the progression of autoimmune diseases – these include vitamin D levels, nutrition, sleep quality, and stress. We plan to explore these modifiable factors in future articles.

Chronic Infections and Their Impact on Autism and CFS/ME

The Role of Stealth Infections

Both Autistic and CFS/ME individuals commonly encounter chronic and persistent infections. Notably, the herpes virus family, including Epstein-Barr Virus (EBV), Cytomegalovirus, HHV-6, Herpes Simplex, along with hepatitis and enteroviruses, play a significant role in the ongoing disease process in ME/CFS. These viruses often target either neurons (“neurotropic”) or immune cells (“immunotropic”), leading to the neurological and immune-related symptoms frequently observed. Their ability to evade immune detection makes them particularly challenging to address (Rasa et al, 2018).

Chronic Infections in Autism Research

Research has shown a significant correlation between chronic infections and Autistic individuals. However, there is a notable challenge in this area of scientific study. Often, the narrative mistakenly frames autism as a disease. This perspective can divert attention away from a crucial understanding: chronic infections in Autistic people may often be a consequence of underlying immune dysfunction and decreased resistance, which are more common in this population. Importantly, this understanding steers us away from the misleading notion that chronic infections in childhood are a cause of autism. Recognizing and maintaining this distinction is vital for practicing medicine and health therapies within a neurodivergent-affirming paradigm.

Opportunistic Infections and EBV

While 95% of the general population may have been exposed to EBV, most are asymptomatic. However, individuals with chronic fatigue are more susceptible to illnesses from such opportunistic viruses due to underlying immune dysfunction and decreased resistance.

The Interplay of Stress and Viruses

Cortisol, the stress hormone, has been shown to reactivate EBV and other herpes viruses (Yang et al., 2010). Consequently, post-viral fatigue may follow periods of high stress, burnout, or constant sensory overload, which is particularly relevant for Autistic individuals facing daily sensory challenges.

Infections and Behavior

While PANS/PANDAS is a complex topic beyond the scope of this article, it's worth noting that this area is highly relevant to Autistic health, especially in children, and deserves attention in discussions about autism and health.

Understanding Sleep Issues in Autism and ME/CFS

Sleep difficulties and unrefreshing sleep are a near constant feature of autism and affect between 85-90% of people with ME/CFS where sleep issues can precede the onset of illness by years.(Gotts et al., 2013). This research outlines many types of sleep disorder patterns that can occur, including: 

Sleep Disorders in Autism and ME/CFS

  • Prevalence: Between 85-90% of people with ME/CFS face sleep difficulties. Similarly, 50-80% of Autistic children experience sleep disorders, significantly higher than the 9-50% in neurotypical children (Reynolds et al., 2019; Gotts et al., 2013).

  • Circadian Rhythm Disorders: Many Autistic individuals have mutations affecting their circadian rhythms, yet autism is often overlooked in CRSWD (Circadian Rhythm Sleep-Wake Disorders) diagnoses.

  • Melatonin Regulation in Autism: A common feature in autism is a mutation in melatonin-regulating genes, leading to altered sleep cues at night and increased sleepiness during other parts of the day (Furfaro, 2020).

  • Obstructive Sleep Apnea and Periodic Limb Movement: Around 30% of individuals with ME/CFS meet criteria for conditions like obstructive sleep apnea or periodic limb movement. These conditions are also more common among Autistic people. 

  • Insomnia or Hypersomnolence: Significant rates of insomnia or excessive sleepiness are reported in both ME/CFS (89.1%) and autism (Furfaro, 2020). 

Impact of Disrupted Sleep Stages:

Within these groups different stages of sleep i.e. REM sleep or stage 3 may be disrupted. For example, Autistic individuals on average spend about 15% of their sleep in the REM phase, compared to 25% in neurotypicals. REM sleep, crucial for learning and memory, is therefore often reduced in autism (Buckley et al., 2010; Neumeyer et al., 2019). In autism, poor sleep can intensify repetitive behaviors and hyperactivity, creating a cycle where these behaviors further disrupt sleep.

Each sleep phase serves critical health functions, and disruptions in these stages can impair different biological processes. The architecture of normal sleep is influenced by several factors, including daylight exposure, dietary habits, physical activity, insulin secretion, ambient temperature, and hormonal levels, particularly melatonin and cortisol.

The box below outlines physiological factors that can contribute to sleep disturbances and some common effects of sleep deprivation.

Mitochondrial Dysfunction

Mitochondria, often described as the cell's "batteries," are crucial for providing energy (ATP) to every cell in the body. Their dysfunction has been notably linked to chronic fatigue syndrome (CFS), particularly in differentiating “post-exertional malaise” seen in ME/CFS from general burnout or tiredness. In cases of ME/CFS, rest alone often doesn't restore energy (Booth et al., 2012). 

Recent advancements in mitochondrial science have expanded our understanding of their role. Beyond energy generation, mitochondria are integral to overall health, with functions including hormone and melatonin production, antioxidant synthesis, regulation of cell death and cancer processes, aging, and immune system/inflammation management.

Given this broad scope of influence, it's unsurprising that mitochondrial dysfunction is implicated in a wide array of chronic health conditions, including:

This dysfunction may explain why these conditions frequently cluster in family lineages, particularly along maternal lines, as mitochondria are inherited maternally. This inheritance pattern can lead to higher ratios of conditions like CFS, Fibromyalgia, and certain autoimmune diseases in females. In Functional Medicine, we delve into these associations and utilize therapeutic tools to address specific mitochondrial dysfunctions.

continued in part 4

References

Aaron RV, Fisher EA, de la Vega R, Lumley MA, Palermo TM. Alexithymia in individuals with chronic pain and its relation to pain intensity, physical interference, depression, and anxiety: a systematic review and meta-analysis. Pain. 2019 May;160(5):994-1006. doi: 10.1097/j.pain.0000000000001487. PMID: 31009416; PMCID: PMC6688175.

Afari, N., & Buchwald, D. (2003). Chronic fatigue syndrome: a review. American Journal of Psychiatry, 160(2), 221-236.

Aronica L, Ordovas JM, Volkov A, Lamb JJ, Stone PM, Minich D, Leary M, Class M, Metti D, Larson IA, Contractor N, Eck B, Bland JS. Genetic Biomarkers of Metabolic Detoxification for Personalized Lifestyle Medicine. Nutrients. 2022 Feb 11;14(4):768. doi: 10.3390/nu14040768. PMID: 35215417; PMCID: PMC8876337.

Acheson ED. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med. 1959 Apr;26(4):569-95. doi: 10.1016/0002-9343(59)90280-3. PMID: 13637100.

Atchison CJ, Davies B, Cooper E, Lound A, Whitaker M, Hampshire A, Azor A, Donnelly CA, Chadeau-Hyam M, Cooke GS, Ward H, Elliott P. Long-term health impacts of COVID-19 among 242,712 adults in England. Nat Commun. 2023 Oct 24;14(1):6588. doi: 10.1038/s41467-023-41879-2. PMID: 37875536; PMCID: PMC10598213.

Bennett JA, Germani T, Haqq AM, Zwaigenbaum L. Autism spectrum disorder in Prader-Willi syndrome: A systematic review. Am J Med Genet A. 2015 Dec;167A(12):2936-44. doi: 10.1002/ajmg.a.37286. Epub 2015 Aug 29. PMID: 26331980.

Bested AC, Marshall LM. Review of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: an evidence-based approach to diagnosis and management by clinicians. Rev Environ Health. 2015;30(4):223-49. doi: 10.1515/reveh-2015-0026. PMID: 26613325.

Booth NE, Myhill S, McLaren-Howard J. Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Int J Clin Exp Med. 2012;5(3):208-20. Epub 2012 Jun 15. PMID: 22837795; PMCID: PMC3403556.

Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol. 2016 Oct 15;594(20):5781-5790. doi: 10.1113/JP271539. Epub 2016 May 1. PMID: 27059884; PMCID: PMC5063949.

Bonaz B, Lane RD, Oshinsky ML, Kenny PJ, Sinha R, Mayer EA, Critchley HD. Diseases, Disorders, and Comorbidities of Interoception. Trends Neurosci. 2021 Jan;44(1):39-51. doi: 10.1016/j.tins.2020.09.009. PMID: 33378656.

Bonaz B, Sinniger V, Pellissier S. The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract. Front Immunol. 2017 Nov 2;8:1452. doi: 10.3389/fimmu.2017.01452. PMID: 29163522; PMCID: PMC5673632.

Brewer JH, Thrasher JD, Straus DC, Madison RA, Hooper D. Detection of mycotoxins in patients with chronic fatigue syndrome. Toxins (Basel). 2013 Apr 11;5(4):605-17. doi: 10.3390/toxins5040605. PMID: 23580077; PMCID: PMC3705282.

Buckley L, MacHale SM, Cavanagh JT, Sharpe M, Deary IJ, Lawrie SM. Personality dimensions in chronic fatigue syndrome and depression. J Psychosom Res. 1999 Apr;46(4):395-400. doi: 10.1016/s0022-3999(98)00120-2. PMID: 10340240.

Chao LL, Kriger S, Buckley S, Ng P, Mueller SG. Effects of low-level sarin and cyclosarin exposure on hippocampal subfields in Gulf War Veterans. Neurotoxicology. 2014 Sep;44:263-9. doi: 10.1016/j.neuro.2014.07.003. Epub 2014 Jul 21. PMID: 25058901; PMCID: PMC5464327.

Chu, L., Valencia, I. J., Garvert, D. W., & Montoya, J. G. (2019). Onset patterns and course of myalgic encephalomyelitis/chronic fatigue syndrome. Frontiers in pediatrics, 7, 12.

Crompton, C. J., Sharp, M., Axbey, H., Fletcher-Watson, S., Flynn, E. G., & Ropar, D. (2020). Neurotype-matching, but not being autistic, influences self and observer ratings of interpersonal rapport. Frontiers in Psychology, 11, 2961.

Csecs JLL, Iodice V, Rae CL, Brooke A, Simmons R, Quadt L, Savage GK, Dowell NG, Prowse F, Themelis K, Mathias CJ, Critchley HD, Eccles JA. Joint Hypermobility Links Neurodivergence to Dysautonomia and Pain. Front Psychiatry. 2022 Feb 2;12:786916. doi: 10.3389/fpsyt.2021.786916. PMID: 35185636; PMCID: PMC8847158.

Dancey CP, Friend J. Symptoms, impairment and illness intrusiveness--their relationship with depression in women with CFS/ME. Psychol Health. 2008;23(8):983-99. doi: 10.1080/08870440701619957. PMID: 25160923.

Daniels, J., Brigden, A., & Kacorova, A. (2017). Anxiety and depression in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): examining the incidence of health anxiety in CFS/ME. Psychology and Psychotherapy: Theory, Research and Practice, 90(3), 502-509.

Dargenio VN, Dargenio C, Castellaneta S, De Giacomo A, Laguardia M, Schettini F, Francavilla R, Cristofori F. Intestinal Barrier Dysfunction and Microbiota-Gut-Brain Axis: Possible Implications in the Pathogenesis and Treatment of Autism Spectrum Disorder. Nutrients. 2023 Mar 27;15(7):1620. doi: 10.3390/nu15071620. PMID: 37049461; PMCID: PMC10096948.

de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, Carteni M, De Rosa M, Francavilla R, Riegler G, Militerni R, Bravaccio C. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24. doi: 10.1097/MPG.0b013e3181dcc4a5. PMID: 20683204.

Dong H, Zhang X, Qian Y. Mast cells and neuroinflammation. Med Sci Monit Basic Res. 2014 Dec 21;20:200-6. doi: 10.12659/MSMBR.893093. PMID: 25529562; PMCID: PMC4282993.

Eisenlohr-Moul T, Divine M, Schmalenberger K, Murphy L, Buchert B, Wagner-Schuman M, Kania A, Raja S, Miller AB, Barone J, Ross J. Prevalence of lifetime self-injurious thoughts and behaviors in a global sample of 599 patients reporting prospectively confirmed diagnosis with premenstrual dysphoric disorder. BMC Psychiatry. 2022 Mar 19;22(1):199. doi: 10.1186/s12888-022-03851-0. PMID: 35303811; PMCID: PMC8933886.

Giloteaux, L., Goodrich, J.K., Walters, W.A. et al. Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. Microbiome 4, 30 (2016). 

Gotts ZM, Deary V, Newton J, Van der Dussen D, De Roy P, Ellis JG. Are there sleep-specific phenotypes in patients with chronic fatigue syndrome? A cross-sectional polysomnography analysis. BMJ Open. 2013 Jun 20;3(6):e002999. doi: 10.1136/bmjopen-2013-002999. PMID: 23794547; PMCID: PMC3669720.

Groenman AP, Torenvliet C, Radhoe TA, Agelink van Rentergem JA, Geurts HM. Menstruation and menopause in autistic adults: Periods of importance? Autism. 2022 Aug;26(6):1563-1572. doi: 10.1177/13623613211059721. Epub 2021 Nov 26. PMID: 34825585; PMCID: PMC9344571.

Engineer CT, Hays SA, Kilgard MP. Vagus nerve stimulation as a potential adjuvant to behavioral therapy for autism and other neurodevelopmental disorders. J Neurodev Disord. 2017 Jul 4;9:20. doi: 10.1186/s11689-017-9203-z. PMID: 28690686; PMCID: PMC5496407.

Espinosa P, Urra JM. Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome. Mol Neurobiol. 2019 Sep;56(9):6581-6585. doi: 10.1007/s12035-019-1549-7. Epub 2019 Mar 21. PMID: 30895436.

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. PMID: 21376230.

Heim C, Wagner D, Maloney E, Papanicolaou DA, Solomon L, Jones JF, Unger ER, Reeves WC. Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study. Arch Gen Psychiatry. 2006 Nov;63(11):1258-66. doi: 10.1001/archpsyc.63.11.1258. PMID: 17088506. 

Heim C, Nater UM, Maloney E, Boneva R, Jones JF, Reeves WC. Childhood trauma and risk for chronic fatigue syndrome: association with neuroendocrine dysfunction. Arch Gen Psychiatry. 2009 Jan;66(1):72-80. doi: 10.1001/archgenpsychiatry.2008.508. PMID: 19124690.

Kojima, M. Alexithymia as a prognostic risk factor for health problems: a brief review of epidemiological studies. BioPsychoSocial Med 6, 21 (2012). https://doi.org/10.1186/1751-0759-6-21

Kong, X., Zhu, J., Tian, R., Liu, S., Sherman, H. T., Zhang, X., ... & Wan, G. (2020). Early screening and risk factors of autism spectrum disorder in a large cohort of Chinese patients with Prader-Willi syndrome. Frontiers in psychiatry, 11, 594934.

Kossewska J, Bierlit K, Trajkovski V. Personality, Anxiety, and Stress in Patients with Small Intestine Bacterial Overgrowth Syndrome. The Polish Preliminary Study. Int J Environ Res Public Health. 2022 Dec 21;20(1):93. doi: 10.3390/ijerph20010093. PMID: 36612414; PMCID: PMC9819554.

Lee M, Krishnamurthy J, Susi A, Sullivan C, Gorman GH, Hisle-Gorman E, Erdie-Lalena CR, Nylund CM. Association of Autism Spectrum Disorders and Inflammatory Bowel Disease. J Autism Dev Disord. 2018 May;48(5):1523-1529. doi: 10.1007/s10803-017-3409-5. PMID: 29170940.

Li Y, Qiu S, Shi J, Guo Y, Li Z, Cheng Y, Liu Y. Association between MTHFR C677T/A1298C and susceptibility to autism spectrum disorders: a meta-analysis. BMC Pediatr. 2020 Sep 24;20(1):449. doi: 10.1186/s12887-020-02330-3. PMID: 32972375; PMCID: PMC7517654.

Liu CH, Yang MH, Zhang GZ, Wang XX, Li B, Li M, Woelfer M, Walter M, Wang L. Neural networks and the anti-inflammatory effect of transcutaneous auricular vagus nerve stimulation in depression. J Neuroinflammation. 2020 Feb 12;17(1):54. doi: 10.1186/s12974-020-01732-5. PMID: 32050990; PMCID: PMC7017619.

Lievesley K, Rimes KA, Chalder T. A review of the predisposing, precipitating and perpetuating factors in Chronic Fatigue Syndrome in children and adolescents. Clin Psychol Rev. 2014 Apr;34(3):233-48. doi: 10.1016/j.cpr.2014.02.002. Epub 2014 Mar 1. PMID: 24632047.

Maes M, Mihaylova I, De Ruyter M. Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS. J Affect Disord. 2006 Feb;90(2-3):141-7. doi: 10.1016/j.jad.2005.11.002. Epub 2005 Dec 9. PMID: 16338007.

Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40. doi: 10.1016/j.jad.2006.08.021. Epub 2006 Sep 27. PMID: 17007934.

Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10. PMID: 19112401.

Magnusson AE, Nias DK, White PD. Is perfectionism associated with fatigue? J Psychosom Res. 1996 Oct;41(4):377-83. doi: 10.1016/s0022-3999(96)00189-4. PMID: 8971668.

Maintz L, Novak N. Histamine and histamine intolerance. Am J Clin Nutr. 2007 May;85(5):1185-96. doi: 10.1093/ajcn/85.5.1185. PMID: 17490952.

Makris G, Agorastos A, Chrousos GP, Pervanidou P. Stress System Activation in Children and Adolescents With Autism Spectrum Disorder. Front Neurosci. 2022 Jan 13;15:756628. doi: 10.3389/fnins.2021.756628. PMID: 35095389; PMCID: PMC8793840.

Mallorquí-Bagué N, Garfinkel SN, Engels M, Eccles JA, Pailhez G, Bulbena A, Critchley HD. Neuroimaging and psychophysiological investigation of the link between anxiety, enhanced affective reactivity and interoception in people with joint hypermobility. Front Psychol. 2014 Oct 14;5:1162. doi: 10.3389/fpsyg.2014.01162. PMID: 25352818; PMCID: PMC4196473

McElhanon BO, McCracken C, Karpen S, Sharp WG. Gastrointestinal symptoms in autism spectrum disorder: a meta-analysis. Pediatrics. 2014 May;133(5):872-83. doi: 10.1542/peds.2013-3995. PMID: 24777214.

McGinnis WR, Audhya T, Walsh WJ, Jackson JA, McLaren-Howard J, Lewis A, Lauda PH, Bibus DM, Jurnak F, Lietha R, Hoffer A. Discerning the Mauve Factor, Part 1. Altern Ther Health Med. 2008 Mar-Apr;14(2):40-50. Erratum in: Altern Ther Health Med. 2008 May-Jun;14(3):15. PMID: 18383989.

McGinnis WR, Audhya T, Walsh WJ, Jackson JA, McLaren-Howard J, Lewis A, Lauda PH, Bibus DM, Jurnak F, Lietha R, Hoffer A. Discerning the Mauve factor, Part 2. Altern Ther Health Med. 2008 May-Jun;14(3):56-62. PMID: 18517107.

Monzio Compagnoni G, Di Fonzo A, Corti S, Comi GP, Bresolin N, Masliah E. The Role of Mitochondria in Neurodegenerative Diseases: the Lesson from Alzheimer's Disease and Parkinson's Disease. Mol Neurobiol. 2020 Jul;57(7):2959-2980. doi: 10.1007/s12035-020-01926-1. Epub 2020 May 22. PMID: 32445085; PMCID: PMC9047992.

Morris G, Berk M, Walder K, Maes M. The Putative Role of Viruses, Bacteria, and Chronic Fungal Biotoxin Exposure in the Genesis of Intractable Fatigue Accompanied by Cognitive and Physical Disability. Mol Neurobiol. 2016 May;53(4):2550-71. doi: 10.1007/s12035-015-9262-7. Epub 2015 Jun 17. PMID: 26081141.

Nakanishi G, Pita-Oliveira M, Bertagnolli LS, Torres-Loureiro S, Scudeler MM, Cirino HS, Chaves ML, Miwa B, Rodrigues-Soares F. Worldwide Systematic Review of GSTM1 and GSTT1 Null Genotypes by Continent, Ethnicity, and Therapeutic Area. OMICS. 2022 Oct;26(10):528-541. doi: 10.1089/omi.2022.0090. Epub 2022 Sep 16. PMID: 36112350.

Peters SL, Yao CK, Philpott H, Yelland GW, Muir JG, Gibson PR. Randomised clinical trial: the efficacy of gut-directed hypnotherapy is similar to that of the low FODMAP diet for the treatment of irritable bowel syndrome. Aliment Pharmacol Ther. 2016 Sep;44(5):447-59. doi: 10.1111/apt.13706. Epub 2016 Jul 11. PMID: 27397586.

Poznyak AV, Ivanova EA, Sobenin IA, Yet SF, Orekhov AN. The Role of Mitochondria in Cardiovascular Diseases. Biology (Basel). 2020 Jun 25;9(6):137. doi: 10.3390/biology9060137. PMID: 32630516; PMCID: PMC7344641.

Rasa S, Nora-Krukle Z, Henning N, Eliassen E, Shikova E, Harrer T, Scheibenbogen C, Murovska M, Prusty BK; European Network on ME/CFS (EUROMENE). Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med. 2018 Oct 1;16(1):268. doi: 10.1186/s12967-018-1644-y. PMID: 30285773; PMCID: PMC6167797.

Rauch SAM, King A, Kim HM, Powell C, Rajaram N, Venners M, Simon NM, Hamner M, Liberzon I. Cortisol awakening response in PTSD treatment: Predictor or mechanism of change. Psychoneuroendocrinology. 2020 Aug;118:104714. doi: 10.1016/j.psyneuen.2020.104714. Epub 2020 May 15. PMID: 32446108; PMCID: PMC7984524.

Reynolds, A. M., Soke, G. N., Sabourin, K. R., Hepburn, S., Katz, T., Wiggins, L. D., Schieve, L. A., & Levy, S. E. (2019). Sleep Problems in 2- to 5-Year-Olds With Autism Spectrum Disorder and Other Developmental Delays. Pediatrics, 143(3), e20180492. https://doi.org/10.1542/peds.2018-0492

Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A. The Heritability of Autism Spectrum Disorder. JAMA. 2017 Sep 26;318(12):1182-1184. doi: 10.1001/jama.2017.12141. PMID: 28973605; PMCID: PMC5818813.

Sharp HEC, Critchley HD, Eccles JA. Connecting brain and body: Transdiagnostic relevance of connective tissue variants to neuropsychiatric symptom expression. World J Psychiatry. 2021 Oct 19;11(10):805-820. doi: 10.5498/wjp.v11.i10.805. PMID: 34733643; PMCID: PMC8546774.

Schmidt R, Hiemisch A, Kiess W, von Klitzing K, Schlensog-Schuster F, Hilbert A. Macro- and Micronutrient Intake in Children with Avoidant/Restrictive Food Intake Disorder. Nutrients. 2021 Jan 27;13(2):400. doi: 10.3390/nu13020400. PMID: 33513954; PMCID: PMC7911718.

Shoemaker RC, House D, Ryan JC. Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®. Neurotoxicol Teratol. 2014 Sep-Oct;45:18-26. doi: 10.1016/j.ntt.2014.06.004. Epub 2014 Jun 17. PMID: 24946038.

Sotzny F, Blanco J, Capelli E, Castro-Marrero J, Steiner S, Murovska M, Scheibenbogen C; European Network on ME/CFS (EUROMENE). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome - Evidence for an autoimmune disease. Autoimmun Rev. 2018 Jun;17(6):601-609. doi: 10.1016/ j.autrev.2018.01.009. Epub 2018 Apr 7. PMID: 29635081. 

Springer A, Oleksa-Marewska K, Basińska-Zych A, Werner I, Białowąs S. Occupational burnout and chronic fatigue in the work of academic teachers-moderating role of selected health behaviours. PLoS One. 2023 Jan 26;18(1):e0280080. doi: 10.1371/journal.pone.0280080. PMID: 36701360; PMCID: PMC9879519. 

Szyf M. The epigenetics of early life adversity and trauma inheritance: an interview with Moshe Szyf. Epigenomics. 2022 Mar;14(6):309-314. doi: 10.2217/epi-2021-0483. Epub 2021 Dec 8. PMID: 34877868.

Theoharides TC, Kavalioti M, Tsilioni I. Mast Cells, Stress, Fear and Autism Spectrum Disorder. Int J Mol Sci. 2019 Jul 24;20(15):3611. doi: 10.3390/ijms20153611. PMID: 31344805; PMCID: PMC6696098.

Tomas C, Newton J, Watson S. A review of hypothalamic-pituitary-adrenal axis function in chronic fatigue syndrome. ISRN Neurosci. 2013 Sep 30;2013:784520. doi: 10.1155/2013/784520. PMID: 24959566; PMCID: PMC4045534.

Traianos E, Dibnah B, Lendrem D, et alAB0051 THE EFFECTS OF NON-INVASIVE VAGUS NERVE STIMULATION ON IMMUNOLOGICAL RESPONSES AND PATIENT REPORTED OUTCOME MEASURES OF FATIGUE IN PATIENTS WITH CHRONIC FATIGUE SYNDROME, FIBROMYALGIA, AND RHEUMATOID ARTHRITISAnnals of the Rheumatic Diseases 2021;80:1057-1058.

Tsai SY, Chen HJ, Lio CF, Kuo CF, Kao AC, Wang WS, Yao WC, Chen C, Yang TY. Increased risk of chronic fatigue syndrome in patients with inflammatory bowel disease: a population-based retrospective cohort study. J Transl Med. 2019 Feb 22;17(1):55. doi: 10.1186/s12967-019-1797-3. PMID: 30795765; PMCID: PMC6387539.

Tsilioni I, Patel AB, Pantazopoulos H, Berretta S, Conti P, Leeman SE, Theoharides TC. IL-37 is increased in brains of children with autism spectrum disorder and inhibits human microglia stimulated by neurotensin. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21659-21665. doi: 10.1073/pnas.1906817116. Epub 2019 Oct 7. PMID: 31591201; PMCID: PMC6815178.

van Rensburg R, Meyer HP, Hitchcock SA, Schuler CE. Screening for Adult ADHD in Patients with Fibromyalgia Syndrome. Pain Med. 2018 Sep 1;19(9):1825-1831. doi: 10.1093/pm/pnx275. PMID: 29099955.

Wang SX, Wu WC. Effects of psychological stress on small intestinal motility and bacteria and mucosa in mice. World J Gastroenterol. 2005 Apr 7;11(13):2016-21. doi: 10.3748/wjg.v11.i13.2016. PMID: 15800998; PMCID: PMC4305729.

Wang T, Yin J, Miller AH, Xiao C. A systematic review of the association between fatigue and genetic polymorphisms. Brain Behav Immun. 2017 May;62:230-244. doi: 10.1016/j.bbi.2017.01.007. Epub 2017 Jan 12. PMID: 28089639; PMCID: PMC5947855.

Weiss RB, Stange JP, Boland EM, Black SK, LaBelle DR, Abramson LY, Alloy LB. Kindling of life stress in bipolar disorder: comparison of sensitization and autonomy models. J Abnorm Psychol. 2015 Feb;124(1):4-16. doi: 10.1037/abn0000014. PMID: 25688428; PMCID: PMC4332547.

Wojcik DP, Godfrey ME, Christie D, Haley BE. Mercury toxicity presenting as chronic fatigue, memory impairment and depression: diagnosis, treatment, susceptibility, and outcomes in a New Zealand general practice setting (1994-2006). Neuro Endocrinol Lett. 2006 Aug;27(4):415-23. PMID: 16891999.

Yang EV, Webster Marketon JI, Chen M, Lo KW, Kim SJ, Glaser R. Glucocorticoids activate Epstein Barr virus lytic replication through the upregulation of immediate early BZLF1 gene expression. Brain Behav Immun. 2010 Oct;24(7):1089-96. doi: 10.1016/j.bbi.2010.04.013. Epub 2010 May 11. PMID: 20466055; PMCID: PMC2939213.

Yap CX, Henders AK, Alvares GA, Wood DLA, Krause L, Tyson GW, Restuadi R, Wallace L, McLaren T, Hansell NK, Cleary D, Grove R, Hafekost C, Harun A, Holdsworth H, Jellett R, Khan F, Lawson LP, Leslie J, Frenk ML, Masi A, Mathew NE, Muniandy M, Nothard M, Miller JL, Nunn L, Holtmann G, Strike LT, de Zubicaray GI, Thompson PM, McMahon KL, Wright MJ, Visscher PM, Dawson PA, Dissanayake C, Eapen V, Heussler HS, McRae AF, Whitehouse AJO, Wray NR, Gratten J. Autism-related dietary preferences mediate autism-gut microbiome associations. Cell. 2021 Nov 24;184(24):5916-5931.e17. doi: 10.1016/j.cell.2021.10.015. Epub 2021 Nov 11. PMID: 34767757.

Yuzefovych LV, Pastukh VM, Ruchko MV, Simmons JD, Richards WO, Rachek LI. Plasma mitochondrial DNA is elevated in obese type 2 diabetes mellitus patients and correlates positively with insulin resistance. PLoS One. 2019 Oct 10;14(10):e0222278. doi: 10.1371/journal.pone.0222278. PMID: 31600210; PMCID: PMC6786592.

Autism, Chronic healthKiley Hanish