The Relationship between Repetitive Behaviors and Growth Hormone Response to Sumatriptan Challenge in Adult Autistic Disorder

Abstract

Autism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autismAutism is heterogeneous with respect to clinical symptoms and etiology. To sort out this heterogeneity in autism, one might determine whether specific neurobiological markers vary in parallel to key clinical symptoms. Autism is characterized by three unique behavioral dimensions: social impairment, communication difficulties and rigid, restricted interests, and repetitive behaviors. One recent study explored the relationship between repetitive behaviors in autism and D8/17, a B-lymphocyte antigen marker expressed at increased levels in patients with rheumatic fever, as well as in patients with neuropsychiatric disorders characterized by repetitive behaviors such as Sydenham's chorea, Tourette's syndrome and obsessivecompulsive disorder. Of interest, obsessive compulsive disorder (OCD) occurs with increased frequency in first degree relatives of autistic patients and is associated with the broader phenotype of autism (Bolton et al. 1998). D8/17 expression was found to be significantly positively correlated with the severity of repetitive behaviors as measured by the Yale-Brown Obsessive Compulsive Scale-compulsivity subscale in childhood and adolescent autism . We have hypothesized that repetitive behaviors in autism may also be related to serotonergic (5-HT) dysfunction (Hollander et al. 1998).Pharmacological treatment studies support a role of 5-HT in autistic disorders. (Mehlinger et al. 1990) and sertraline (Steingard et al. 1997) have documented efficacy in treating both global autistic symptoms as well as symptoms of repetitive behaviors and restricted interests in up to 60% of patients treated.Several biological studies have also suggested 5-HT dysregulation in autistic patients, however the findings have not been uniform, but rather replicated in subgroups of patients. For example, contradictory results in linkage disequilibrium analyses of two common alleles (long and short) of the 5HT transporter (5HTT) gene have been reported. While there was linkage between the short allele and a narrowly defined group of autistic probands (Cook et al. 1997), an association between the long allele and a more broadly defined group of autistic probands has also been reported (Klauck et al. 1997).Pharmacological challenge studies with 5-hydroxytryptophan and fenfluramine have demonstrated reduced prolactin response in some patients with autism (Hoshino et al. 1984;McBride et al. 1989), however age, gender, and racial/ethnic factors may account for some of the heterogeneity. Depletion of the 5-HT precursor, tryptophan, induced a worsening of autistic symptoms in some, but not all, patients (McDougle et al. 1996a). There is evidence for increased whole blood serotonin not only in patients with autism (Hoshino et al. 1984;Anderson et al. 1987), but also in their first degree relatives (Piven et al. 1991;Cook et al. 1994;Leboyer et al. 1999). Of interest, parents of autistic patients with increased whole blood ser...

Serotonergic Dissection of Obsessive Compulsive Symptoms: A Challenge Study with m-Chlorophenylpiperazine and Sumatriptan

“…This is in line with the relative affinities of the two drugs to the 5-HT 1D receptor. These results are in line with previous challenge studies with sumatriptan [15][16][17] but contradict others [16,18], possibly because there are two types of OCD patients -responders and non-responders to sumatriptan -depending on genetic factors such as polymorphisms at the 5-HT 1D receptor locus [19].…”

Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and Asperger's Disorders

“…Gene therapy strategies that may alter oxytocin receptor expression in specific brain regions may eventually hold promise (Young et al, 1997). Despite the limitations of this study, the findings are potentially clinically relevant in helping to evaluate the contribution of oxytocin to one specific behavioral domain (repetitive behaviors) in autism spectrum disorder patients, and complement prior studies that link this behavioral domain to specific alterations in 5HT (Hollander et al, 2000) and immune (Hollander et al, 1999) function.…”

“…We have previously reported on the repetitive behavior domain in autism, and linked the severity of these core symptoms to one aspect of serotonin function (5HT1d sensitivity) (Hollander et al, 2000) and one specific B cell immune marker (D8/17) (Hollander et al, 1999). In this study, it was hypothesized that infusion of synthetic oxytocin might modulate the severity of this repetitive behavior domain in patients with autism spectrum disorders.…”

Asperger Syndrome, Obsessive-Compulsive Disorder, and Major Depression in a Patient with 45,X/46,XY Mosaicism

“…Levels of monoclonal antibody D8/17, which identifies a B cell antigen that denotes susceptibility to rheumatic fever, were found to be increased among patients with either OCD [19] or PDD (autistic disorder) [20]. Hollander et al [21] have suggested that the 5-HT1D receptor, which was reported to be hypersensitive in OCD [22], may also be implicated in the pathophysiology of repeti-Fontenelle et al…”