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Digestion and Developmental Disorders

By Margaret Lahey and Shari Rosen
BAMFORD-LAHEY CHILDREN'S FOUNDATION

DIGESTION AND DEVELOPMENTAL DISORDERS

We will not go into detail about the digestive process in this paper. The topic is raised and briefly discussed because diet affects digestion and problems with digestion can influence neurotransmitters and thus potentially learning and behavior.

INTRODUCTION

Some digestive problems are caused, or exacerbated, by adverse reactions to foods. Such adverse reactions can cause alterations of gastric acid secretions, of the motility of the intestine, and of the mucosal barrier of the intestine. An extreme case of this connection can be seen in celiac disease, which is an allergic reaction to gluten, where the intestinal wall is smoothed thus interfering with nutrient absorption. When the barrier is disturbed permeability of the intestinal wall may be increased allowing foreign substances into the blood stream. Either of these conditions (i.e., problems with nutrient absorption or permeability) can potentially influence neurotransmitters. A number of neurotransmitters influence digestion (e.g., gastrin, secretin, acetylcholine, histamine, epinephrine) and in turn, a number of neurotransmitters are influenced by digestion (e.g., serotonin, dopamine, acetylcholine). The integration of digestive system with systems such as the nervous system and the endocrine system as well as the health of the intestines, particularly the small intestine, is important for normal absorption of nutrients. Evidence of the recognition of the brain-gut connection is a relatively new subspecialty of clinical gastroenterology and digestive science; it is called neuro-gastroenterology (Wood, Alpers & Andrews, 1999).

DEVELOPMENTAL DISORDERS

Problems with the digestion system are commonly reported in individuals with psychiatric problems, neurologic dysfunction, and developmental disorders (e.g., DiEufemia, Celli, Finocchiano, et al., 1996; Horvath, et al., 1999; Pfeiffer, 1996; Wakefield, Murch, Anthony, et al., 1998; Quigley & Hurley, 2000). In an examination of 36 children with autism, Horvath and colleague (1999) found that the most common symptoms were abdominal pain, chronic diarrhea, and gaseousness/bloating. According to parent report, over one-third of the subjects these researchers saw had a history of intolerance of milk and soy and/or allergies to certain foods.

Secretin is a 27-amino acid polypeptide secreted by the S-cells of the duodenum in response to acidification of the stomach. It stimulates the release of bicarbonate and peptidase enzymes from the pancreas and bile from the liver. Thus, it can potentially aid in digestion. Some suggest that its role in helping digestion may nourish the brain as well as prevent toxins from escaping through the intestinal wall and then reaching the brain. Secretin may possibly have a role in CNS function, but it is not clear what that specific role may be. Animal studies indicate secretin has physiological effects and that it facilitates GABA transmission suggesting it can modulate motor and other functions (e.g., Babu & Vijayan, 1983; Conter, Huges, & Kauffman, 1996; Ng, Yung & Chow, 2002).

With humans, the injection of porcine or synthetic secretin is primarily used for diagnostic tests related to pancreatic function and is not used for therapy. However, a group of investigators noticed that following the administration of secretin as part of an evaluation of gastrointestinal function, three autistic children had considerable improvement in gastrointestinal symptoms as well as a dramatic improvement in behavior including eye contact, alertness and expressive language (Horvath, Stefanatos, Sokolski, et al., 1998). These findings plus similar positive results in anecdotal reports and in some studies reported at conventions sparked interest in the association between gastrointestinal function and brain function and initiated a body of research investigating the effectiveness of using secretin as a therapy for children with autism (e.g., Blatt, Meguid, & Church, 2000; for review of some of these check the Autism Research Institute on their website, autism.com/ari). One non-blind study reported positive effects on gastrointestinal symptoms as well as language function and social skills in some children with autism after one dose of secretin (Chez, Buchanan, Bagan, et al., 2000). Seventeen of the most responsive children from this first study were then selected for a double-blind crossover study about six weeks following the first injection. Authors reported transient changes in speech and behavior in some children but few clinically significant changes when compared to the placebo condition (Chez et al., 2000). Other published studies have reported no effect. For example, Owley and colleagues found no improvement on the social-communication portion of the Autism Diagnostic Observation Schedule among 20 subjects who were given secretin treatments over a four-week period (Owley, Steele, Corsello, et al., 1999) and no effect on language and behavior of children with autism and gastrointestinal symptoms in a 5-week period of intravenous infusion of secretin (Lightdale, Hayer, Duer, et al., 2001). Similarly, no significant improvement was reported by other researchers using a variety of outcome measures with double-blind placebo-controlled crossover designs (e.g., Dunn-Geier, Ho, Auersperg, et al., 2000; Owley, McMahon, Cook, et al., 2001; Sandler, Sutton, DeWeese, et al., 1999). Even repeated doses of secretin did not yield positive results (Roberts, Weaver, Brian, et al., 2001). Some suggest anecdotal reports can be explained by a placebo effect and that further research must involve double-blind placebo-controlled designs (e.g., Unis, Munson, Rogers, et al., 2002). Thus, evidence to date does not support the use of secretin as a therapy although it does not negate the possible relation between gastrointestinal function and brain function (for a review of studies, see Patel, Yeh, Shepherd, & Crismon, 2002).

Much of the work on digestive problems and developmental disorders has focused on autism and, as noted in Hypothesis B, digestive disorders are common with this syndrome. However, the relation between digestive dysfunction and learning and behavior is less clear and attempts to improve learning and behavior by administration of secretin have not been successful in most studies. Further aspects of digestive problems involving particular foods are included in the sections below.

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