Associations between cytokines, endocrine stress response, and gastrointestinal symptoms in autism spectrum disorder

Abstract

Many children and adolescents with autism spectrum disorder (ASD) have significant gastrointestinal (GI) symptoms, but the etiology is currently unknown. Some individuals with ASD show altered reactivity to stress and altered immune markers relative to typically-developing individuals, particularly stress-responsive cytokines including tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Acute and chronic stress is associated with the onset and exacerbation of GI symptoms in those without ASD. The present study examined whether GI symptoms in ASD were associated with increases in cortisol, a stress-associated endocrine marker, and TNF-α and IL-6 in response to stress. As hypothesized, a greater amount of lower GI tract symptoms were significantly associated with post-stress cortisol concentration. The relationship between cortisol response to stress and GI functioning was greater for children who had a history of regressive autism. Exploratory analyses revealed significant correlations between cortisol response, intelligence, and inappropriate speech. In contrast, symptoms of the lower GI tract were not associated with levels of TNF-α or IL-6. Significant correlations were found, however, between TNF-α and IL-6 and irritability, socialization, and intelligence. These findings suggest that individuals with ASD and symptoms of the lower GI tract may have an increased response to stress, but this effect is not associated with concomitant changes in TNF-α and IL-6. The relationship between cortisol stress response and lower GI tract symptoms in children with regressive autism, as well as the relationships between cortisol, IL-6, and intelligence in ASD, warrant further investigation.

An approach to gut microbiota profile in children with autism spectrum disorder

“…Changes in redox signalling, epigenetic transcriptional factors, lipid and mitochondrial metabolism, ion channel/ gap junction/transporter regulation protein and posttranslational modification have also been reported (Frye et al, 2016;Rose et al, 2017). In addition, other biomarkers such as serotonin, p-cresol and cortisol have also been related to aetiology and behaviour in mental disorders such as Autism Spectrum Disorder (ASD) (Yang et al, 2015;Ferguson et al, 2016;Ooi et al, 2017;Kang et al, 2018).…”

“…Specifically, they have a greater sensitivity to certain foods or food allergies (Xu et al, 2018) and they have a significantly lower intake of calcium and protein (McElhanon et al, 2014). However, the aetiology of the nutritional and GI problems of ASD remains unknown (McElhanon et al, 2014;Ferguson et al, 2016;Martínez-González and Andreo-Martínez, 2019) and everything seems to indicate that it is a combination of associated factors (Buie, 2015). Other authors suggest that abnormal GM in ASD may be caused by the overuse of antibiotics (Sandler et al, 2000;Krajmalnik-Brown et al, 2015;Wimberley et al, 2018) or a pathophysiological cascade of interactions between environmental factors and key genes.…”

Comparing the effects of age, pubertal development, and symptom profile on cortisol rhythm in children and adolescents with autism spectrum disorder

“…Chronic HPA dysfunction in ASD likely has significant negative effects on physical and mental health. Chronic stress is related to cognitive deficits in ASD [Ogawa, Lee, Yamaguchi, Shibata, & Goto, ], and heightened stress reactivity is associated with increased prevalence of gastrointestinal symptoms [Ferguson et al, ]. Elevated basal cortisol levels are frequently reported in individuals with depression [e.g., Burke, Davis, Otte, & Mohr, ], and in neurotypical adolescents, elevated evening cortisol is associated with depressive symptoms [Van den Bergh & Van Calster, ; Dahl et al, ] and elevated trait anxiety [Van den Bergh, Van Calster, Pinna Puissant, & Van Huffel, ].…”

Background cortisol versus social anxiety as correlates of HPA‐axis recovery from stress in boys with Autism Spectrum Disorder

“…T 2014). There is some initial evidence that this dysregulation of the HPA axis may also be associated with gastrointestinal disorders in these children (Ferguson et al, 2016). In contrast, there are studies demonstrating no significant differences in the HPA axis diurnal variation and CAR across ASD and non-ASD samples (Corbett and Schupp, 2014;Gabriels et al, 2013;Marnovic-Curin et al, 2008;Tomarken et al, 2015).…”

“…One population that has been shown to have dysregulated HPA axis patterns compared to their peers is children with Autism Spectrum Disorder (ASD) (Brosnan et al, 2009; Kidd et al, 2012; Tordjman et al, 2014). There is some initial evidence that this dysregulation of the HPA axis may also be associated with gastrointestinal disorders in these children (Ferguson et al, 2016). In contrast, there are studies demonstrating no significant differences in the HPA axis diurnal variation and CAR across ASD and non‐ASD samples (Corbett and Schupp, 2014; Gabriels et al, 2013; Marnovic‐Curin et al, 2008; Tomarken et al, 2015).…”