Psychophysiological Associations with Gastrointestinal Symptomatology in Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is often accompanied by gastrointestinal disturbances, which also may impact behavior. Alterations in autonomic nervous system functioning are also frequently observed in ASD. The relationship between these findings in ASD is not known. We examined the relationship between gastrointestinal symptomatology, examining upper and lower gastrointestinal tract symptomatology separately, and autonomic nervous system functioning, as assessed by heart rate variability and skin conductance level, in a sample of 120 individuals with ASD. Relationships with co-occurring medical and psychiatric symptoms were also examined. While the number of participants with significant upper gastrointestinal tract problems was small in this sample, 42.5% of participants met criteria for functional constipation, a disorder of the lower gastrointestinal tract. Heart rate variability, a measure of parasympathetic modulation of cardiac activity, was found to be positively associated with lower gastrointestinal tract symptomatology at baseline. This relationship was particularly strong for participants with co-occurring diagnoses of anxiety disorder and for those with a history of regressive ASD or loss of previously acquired skills. These findings suggest that autonomic function and gastrointestinal problems are intertwined in children with ASD; although it is not possible to assess causality in this data set. Future work should examine the impact of treatment of gastrointestinal problems on autonomic function and anxiety, as well as the impact of anxiety treatment on gastrointestinal problems. Clinicians should be aware that gastrointestinal problems, anxiety, and autonomic dysfunction may cluster in children with ASD and should be addressed in a multidisciplinary treatment plan.

Association of Rigid-Compulsive Behavior with Functional Constipation in Autism Spectrum Disorder

“…While a connection with the serotonin system is possible (and is long implicated in ASD) (Muller et al, 2015), our assessment of whole blood serotonin levels in this same population did not identify a significant association with rigid-compulsive behavior (Marler et al, In Press). Similarly, associations between GI symptoms and measures of autonomic function were much more modest than the behavioral symptoms observed here (Ferguson et al, In Press). A larger, longitudinal follow-up study, including careful monitoring of any treatment, as well as a control group of participants without ASD, would be necessary to better understand the specificity and directionality of the relationship between GI and behavioral symptoms.…”

“…As previously described, 120 6- to 18-year-olds were recruited through the Autism Speaks Autism Treatment Network and affiliated clinics (Ferguson et al, In Press). Parents of potential participants were screened over the phone using the Questionnaire on Pediatric Gastrointestinal Symptoms-Rome III (QPGS-RIII) (Baber et al, 2008), in an attempt to recruit a similar number of participants with and without prominent GI symptoms.…”

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

“…The QPGS-RIII has been used to assess GI dysfunction in ASD with clinician-parent agreement at 92.1% for presence of any QPGS-RIII disorder, and fair agreement for functional constipation (Gorrindo et al, 2012). Consistent with previous work from our team, continuous variables were created for upper and lower GI tract symptoms (Ferguson et al, in press). Briefly, the multiple choice responses to the questions pertaining to the ten functional pediatric GI disorders assessed by the QPGS-RIII were assigned ratings, and a quantitative score was created by summing the ratings (scored on scales of 1–3, 0–4, 1–5, or 0–5, in accordance with the QPGS-RIII scoring criteria for each designated item; Yes/No responses were assigned 1 point each).…”

“…Electrocardiogram (ECG) and skin conductance level data were collected from participants throughout the duration of the study. For the ECG data, motion artifacts were excluded, and R-R intervals were determined as previously described (Ferguson et al, in press; Tarvainen et al, 2014). Heart-rate variability, a measure of the balance of sympathetic and parasympathetic influences on the heart, was represented by the percent of successive normal R-R intervals that varied by 50 ms or more, referred to as pNN50.…”

“…We hypothesized that GI symptoms would be positively correlated with change in cortisol concentrations after stress, and also with levels of IL-6 and TNF-α. We also examined the relationship between psychophysiological markers of autonomic nervous system functioning and GI symptomatology, which are known to be interrelated with lower GI symptomatology in ASD (Ferguson et al, in press). Furthermore, relationships between these measures and intelligence, ASD-associated behaviors, and adaptive functioning were explored, to determine how these findings relate to other co-occurring conditions associated with GI symptomatology.…”