Early markers of chronic disease in people with autism and their caregivers
Autism spectrum disorders (ASD) are an urgent global mental health problem with an estimated prevalence ~ 1%, concerning 52 million cases and 7.7 million disability adjusted life years1,2. Having an ASD, can give chronic distress during the life course, as shown in small scale studies3,4. People with ASD experience often additional physical complaints and disease5,6,7. Children with ASD displayed 40% more obesity than their peers without ASD, also 94% of the children with ASD had comorbidities, compared to 17% in their peers without ASD5. Comorbidity consisted for example of CNS anomalies, diabetes, epilepsy, bowel disease and schizophrenia5 being precursors of chronic disease in adulthood. However, as systematically reviewed in Muskens et al, the compared studies were of limited to quality due to their study design, and limited systematic diagnostic assessment6. Adults with ASD had more diagnoses of hyperlipidemia, constipation and epilepsy than controls but were less likely to have medication for these diseases than people without ASD in the control group5. Next to cohort studies in which adults with ASD report medical complaints, diverse approaches have been taken to taken to describe the relation between ASD and cancer risk8,9,10. Etiological studies into causes of ASD revealed overlapping genes with risk of cancer as for example the PI3K-Akt-mTOR pathway. Epidemiological studies displayed that people with ASD seem to have an increased risk for cancer8, specifically concerning ovarian and CNS cancers (neurofibromatosis).
Thus, ASD, and at least autistic disorder as specified in the follow-up of the Global Burden of Disease Study, coincides with excess mortality in especially people between 45 and 54 years of age11. Several studies suggest that not ASD itself but comorbid medical disorders and intellectual disability determine this increased mortality12. Comorbid medical conditions resulting in increased mortality comprised respiratory, cardiac and epileptic events12. In summary, medical comorbidity in children and adults with ASD is abundant. However, it is unknown whether there are early markers of these chronic diseases in adults with ASD.
Caregivers of children with ASD, defined as adults giving the primary parental care for the child, experience 4-7 times increased distress compared to caregivers of typically developing children resulting in physical and mental problems13–18. Parenting stress was especially associated with externalizing problem behavior in youth with ASD (reviewed in 19). Caregiver distress is a main theme in patient-care of children with ASD as their distress level affects the distress level in the child and vice versa20. In addition to the synergy between caregiver and child distress, caregiver distress may also lead to other health issues such as increased risk of chronic disease in the caregiver which may also result in adverse effects on the child. This bidirectional relation between family environment and child behavior has not only been established by psychological studies, but also by cortisol expression studies in caregivers21–26. Extremely elevated cortisol levels (e.g. in Cushing’s syndrome) are leading to abdominal obesity, diabetes, dyslipidemia, hypertension, cardiovascular disease and depression27–29. Maternal caregivers of children with ASD are known for lower hair cortisol levels, greater reward-related eating and worse metabolic function compared to mothers of typically developing children30. Mothers of children with ASD have a 50% higher risk of death, especially by cancer (HR 1.54) compared to non-ASD mothers31. Maternal mortality is hypothesized to be increased due to pre-existing mental and physical disease, and lower self-care due to the care for their child31. Surprisingly, although studies evaluating distress levels in caregivers of children with ASD are already present from at least the 1990s onwards32, explicit physical and mental care for caregivers is not for granted in everyday clinical practice. Besides the absence of regular physical care for caregivers, also early markers of chronic disease are unknown.