Original article| Volume 28, ISSUE 2, P99-103, March 2006

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Administration of secretin for autism alters dopamine metabolism in the central nervous system


      We evaluated the clinical effects of intravenously administered secretin in 12 children with autism (age range: 4–6 years, median age: 9 years, boy:girl=8:4). In addition, we investigated the association between improvement in symptoms and changes in the cerebrospinal fluid (CSF) homovanillic acid (HVA),5-hydroxyindole-3-acetic acid (5-HIAA), and 6R-5,6,7,8-tetrahydro-L-biopterin (BH4) levels after administration. After administration of secretin, the Autism Diagnostic Interview-Revised (ADI-R) score improved in 7 of the 12 children. However, the score deteriorated in 2 of the 12 children (in the item of ‘restricted and repetitive, stereotyped interests and behaviors’). The HVA and BH4 levels in CSF were increased in all children with improvement in the ADI-R score. In contrast, no patient without the elevation of the BH4 level showed improvement in the score. These findings suggest that secretin activated metabolic turnover of dopamine in the central nervous system via BH4, improving symptoms.


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        • Segawa M.
        A neurological model of infantile autism (in Japanese).
        No No Kagaku (Tokyo). 1998; 20: 169-175
        • Mcdougle C.J.
        • Naylor S.T.
        • Cohen D.J.
        • Volkman F.R.
        • Heninger G.R.
        • Price L.H.
        A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder.
        Arch Gen Psychiatry. 1996; 53: 1001-1008
        • Horvath K.
        • Stefanatos G.
        • Sokolski K.N.
        • Wachtel R.
        • Nabros L.
        • Tildon J.T.
        Improved social and language skills after secretin administration in patients with autistic spectrum disorders.
        J Assoc Acad Minor Phys. 1998; 9: 9-15
        • Naruse H.
        • Hayashi T.
        • Takesada M.
        • Nakane A.
        • Yamazaki K.
        Metabolic changes in aromatic amino acids and monoamines in infantile autism and development of new treatment related to the finding (in Japanese).
        No To Hattatsu. 1989; 21: 181-189
        • Fernell E.
        • Watanabe Y.
        • Adolfsson I.
        • Tany Y.
        • Bergstrom M.
        • Hartvig P.
        • et al.
        Possible effects of tetrahydrobiopterin treatment in six children with autism—clinical and positron emission tomography data: a pilot study.
        Dev Med Child Neurol. 1997; 39: 313-318
        • Komori H.
        • Matsuishi T.
        • Yamada S.
        • Yamashita Y.
        • Ohtaki E.
        • Kato H.
        Cerebrospinal fluid biopterin and biogenic amine metabolites during oral R-THBP therapy for infantile autism.
        J Autism Dev Disord. 1995; 25: 183-193
        • Blau N.
        • Thoy B.
        • Cotton R.G.H.
        • et al.
        Disorder of tetrahydrobiopterin and related biogenic amines.
        in: Scriver C.R. Beaudet A.L. Sly W. Valle D. Childs B. Kinzler K.W. Vogelstein B. The metabolic and molecular bases of inherited disease. McGraw Hill, London2000: 1725-1776
        • Sandler A.D.
        • Sutton K.A.
        • DeWeese J.
        • Girardi M.A.
        • Sheppard V.
        • Bodfish J.W.
        Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder.
        N Engl J Med. 1999; 341: 1801-1806
        • Lightdale J.R.
        • Hayer C.
        • Duer A.
        • Lind-White C.
        • Jenkins S.
        • Siegel B.
        • et al.
        Effects of intravenous secretin on language and behavior of children with autism and gastrointestinal symptoms: a single-blinded, open-label pilot study.
        Pediatrics. 2001; 108: E90
        • Usdin T.B.
        • Bonner T.I.
        • Mezey E.
        Two receptors for vasoactive intestinal polypeptide with similar specificity and complementary distributions.
        Endocrinology. 1994; 135: 2662-2680
        • Schwarzschild M.A.
        • Zigmond R.E.
        Secretin and vasoactive intestinal peptide activate tyrosine hydroxylase in sympathetic nerve endings.
        J Neurosci. 1989; 9: 160-166