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The Role of Serotonin in Autism-Spectrum Disorders

Abstract
Abstract

While the etiologies of pervasive developmental disorders (PDDs) appear complicated, multifactorial, and relatively poorly understood research over the last 30 to 40 years has implicated certain neurochemicals in the pathophysiology of these diseases. From these studies, a great deal of evidence has emerged supporting a role for serotonergic dysfunction in individuals with autism and related disorders. Recent clinical trials of drugs influencing serotonergic systems have demonstrated promising effects in children, adolescents, and adults with PDDs.

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1.American Psychiatric Association Committee on Nomenclature and Statistics. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:65-78,417423.
2.Kaplan HI, Sadock BJ, Grebb JF. Kaplan and Sadock's Synopsis of Psychiatry. 7th ed. Philadelphia, Pa: William & Wilkins; 1994:10521062.
3.Rapin I. Introduction and overview. In: Bauman ML, Kemper TL, eds. The Neurobiology of Autism. Baltimore, Md: The Johns Hopkins University Press; 1994:117.
4.McDougle CJ, Kresch LE, Goodman WK, et al.A case-controlled study of repetitive thoughts and behavior in adults with autistic disorder and obsessive-compulsive disorder. Am J Psychiatry. 1995;152:772777.
5.Lotter V. Follow-up studies. In: Rutter M, Schopler E, eds. Autism: A Reappraisal of Concepts And Treatment. New York, NY: Plenum Press; 1978.
6.Gillberg C. Outcome in autism and autistic-like conditions. J Am Acad Child Adolesc Psychiatry. 1991;30:375382.
7.Gillberg C, Coleman M. The Biology of the Autistic Syndromes. 2nd ed. London: MacKeith Press; 1992.
8.Bauman ML, Kemper TL. The Neurobiology of Autism. Baltimore, Md: Johns Hopkins University Press; 1994.
9.McDougle CJ, Price LH, Volkmar FR. Recent advances in the pharmacotherapy of autism and related conditions. In: Volkmar FR, ed. Psychoses and Pervasive Developmental Disorders. Philadelphia, Pa: W.B. Saunders; 1994:7189.
10.Volkmar F, Klin A, Marans W, McDougle CJ. Autistic disorder. In: Volkmar F, ed. Psychoses and Pervasive Developmental Disorders in Childhood and Adolescence. Washington, DC: American Psychiatric Press; 1996:129190.
11.Rubenstein JLR, Lotspeich L, Ciaranello RD. The neurobiology of developmental disorders. In: Lahey BB, Kazdin AE, eds. Advances in Clinical Child Psychology. New York, NY: Plenum Publishing Corporation; 1990; 13:152.
12.Gillberg C, Svennerholm L, Hamilton-Hellberg C. Childhood psychosis and monoamine metabolites in spinal fluid. J Autism Dev Disord. 1983;13:383396.
13.Campbell M, Anderson LT, Meier M, et al.A comparison of haloperidol and behavior therapy and their interaction in autistic children. J Am Acad Child Adolesc Psychiatry. 1978:17:640655.
14.Cohen IL, Campbell M, Posner D, Small AM, Triebel D, Anderson LT. Behavioral effects of haloperidol in young autistic children. J Am Acad Child Adolesc Psychiatry. 1980;19:665677.
15.Anderson LT, Campbell M, Grega DM, Perry R, Small AM, Green WH. Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. Am J Psychiatry. 1984; 141:11951202.
16.Anderson L, Campbell M. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord. 1989:19:227239.
17.Naruse H, Nagahata M, Nakane Y, Shirahashi K, Takesada M, Yamazaki K. A multi-center double-blind trial of pimozide (Orap), haloperidol and placebo in children with behavior disorders, using cross-over design. Acta Paedopsychiatrica. 1982:48:173184.
18.Schain RJ, Freedman DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatr. 1961:58:315320.
19.Anderson GM. Monoamines in autism: an update of neurochemical research on a pervasive developmental disorder. Medical Biology. 1987:65:6774.
20.Narayan M, Srinath S, Anderson GM, Meundi DB. Cerebrospinal fluid levels of homovanillic acid and 5-hydroxyindoleacetic acid in autism. Biol Psychiatry. 1993:33:630635.
21.Kuperman S, Beeghly JH, Burns TL, Tsai LY. Serotonin relationships of autistic probands and their first-degree relatives. J Am Acad Child Adolesc Psychiatry. 1985:24:186190.
22.Abramson RK, Wright HH, Carpenter R, et al.Elevated blood serotonin in autistic probands and their first-degree relatives. J Autism Dev Disord. 1989:19:397407.
23. Cook E.H.Autism: review of neurochemical investigation. Synapse. 1990:6:292308.
24.Leventhal BL, Cook EH, Morford M, Ravitz A, Freedman DX. Relationships of whole blood serotonin and norepinephrine within families. J Autism Dev Disord. 1990:20:499511.
25.Piven J, Tsai GC, Nehme E, Coyle JT, Chase GA, Folstein SE. Platelet serotonin, a possible marker for familial autism. J Autism Dev Disord. 1991:21:5159.
26.Perry BD, Cook EH Jr, Leventhal BL, Wainwright MS, Freedman DX. Platelet 5-HT2 serotonin receptor binding sites in autistic children and their first-degree relatives. Biol Psychiatry. 1991:30:121130.
27.Hanley HG, Stahl SM, Freedman DX. Hyperserotonemia and amine metabolites in autistic and retarded children. Arch Gen Psychiatry. 1977:34:521531.
28.Kuperman S, Beeghly J, Burns T, Tsai L. Association of serotonin concentration to behavior and IQ in autistic children. J Autism Dev Disord. 1987:17:133140.
29.Todd RD, Ciaranello RD. Demonstration of inter- and intraspecies differences in serotonin binding sites by antibodies from an autistic child. Proc Natl Acad Sci U S A. 1985:82:612616.
30.Hoshino Y, Yamamoto T, Kaneko M, et al.Blood serotonin and free tryptophan concentration in autistic children. Neuropsychobiology. 1984; 11:2227.
31.McBride PA, Anderson GM, Hertzig ME, et al.Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study. Arch Gen Psychiatry. 1989;46:213221.
32.Rose WC, Haines WJ, Warner DT. The amino acid requirements of man. J Biol Chem. 1954:206:421430.
33.Gal EM, Dreses PA. Studies on the metabolism of 5-hydrox-ytryptamine (serotonin), II: effect of tryptophan deficiency in rats. Proc Soc Exp Biol Med. 1962:110:368371.
34.Fernstrom JD. Effects of the diet on brain neurotransmitters. Metabolism. 1977:26:207223.
35.Curzon G. Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity. In: Haber G, Gabay S, eds. Serotonin: Current Aspects of Neurochemistry and Function. New York, NY: Plenum Press; 1981:207219.
36.Young SN, Ervin FR, Phil RO, Finn P. Biochemical aspects of tryptophan depletion in primates. Psychopharmacology (Berl). 1989:95:508511.
37.Moja EA, Cipollo P, Castoldi D, Tofanetti O. Dose-response decrease in plasma tryptophan and in brain tryptophan and serotonin after tryptophan-free amino acid mixtures in rats. Life Sci. 1989:44:971976.
38.Moir ATB, Eccleston D. The effects of precursor loading in the cerebral metabolism of 5-hydroxyindoles. J Neurochem. 1968:15:10931108.
39.Fernstrom JD, Hirsch MJ. Rapid repletion of brain serotonin in malnourished corn-fed rats following L-tryptophan injection. Life Sci. 1975:17:455464.
40.Delgado PL, Charney DS, Price LH, Aghajanian GK, Landis H, Heninger GR. Serotonin function and the mechanism of antidepressant action: reversal of antidepressant induced remission by rapid depletion of plasma tryptophan. Arch Gen Psychiatry. 1990:47:411418.
41.Barr LC, Goodman WK, McDougle CJ, et al.Tryptophan depletion in patients with obsessive-compulsive disorder who respond to serotonin reuptake inhibitors. Arch Gen Psychiatry. 1994:51:309317.
42.Delgado PL, Price LH, Miller HL, et al.Serotonin and the neurobiology of depression: effects of tryptophan depletion in drug-free depressed patients. Arch Gen Psychiatry. 1994:51:865874.
43.Barr LC, Goodman WK, Delgado PL, McDougle CJ, Price LH. Effects of tryptophan depletion in drug-free obsessive compulsive disorder patients. Biol Psychiatry. In press.
44.Goddard AW, Sholomskas DE, Augeri FM, et al.Effects of tryptophan depletion in panic disorder. Biol Psychiatry. 1994:36:775777.
45.Young SN, Smith SE, Pihl RD, Ervin FR. Tryptophan depletion causes a rapid lowering of mood in normal males. Psychopharmacology (Berl). 1985:87:173177.
46.Smith SE, Pihl RO, Young SWErvin FR. A test of possible cognitive and environmental influences on the mood lowering effect of tryptophan depletion in normal males. Psychopharmacology. 1987:91:451457.
47.McDougle CJ, Naylor ST, Goodman WK, Volkmar FR, Cohen DJ, Price LH. Acute tryptophan depletion in autistic disorder: a controlled case study. Biol Psychiatry. 1993:33:547550.
48.McDougle CJ, Naylor ST, Cohen CJ, Aghajanian GK, Heninger GR, Price LH. Effects of tryptophan depletion in drug-free adults with autistic disorder. Arch Gen Psychiatry. 1996:53:9931000.
49.Schuster CR, Lewis M, Seiden LS. Fenfluramine: neurotoxicity. Psychopharmacol Bull. 1986:22:148151.
50.Geller E, Ritvo ER, Freeman BJ, Yuwiler A. Preliminary observations on the effect of fenfluramine on blood serotonin and symptoms in three autistic boys. N Engl J Med. 1982:307:165169.
51.Ritvo ER, Freeman BJ, Geller E, Yuwiler A. Effects of fenfluramine on 14 outpatients with the syndrome of autism. J Am Acad Child Adolesc Psychiatry. 1983:22:549558.
52.Ritvo ER, Freeman BJ, Yuwiler A, et al.Fenfluramine treatment of autism: UCLA collaborative study of 81 patients at nine medical centers. Psychopharmacol Bull. 1986:22:133140.
53.Stubbs EG, Budden SS, Jackson RH, Terdal LG, Ritvo ER. Effects of fenfluramine on eight outpatients with the syndrome of autism. Dev Med Child Neurol. 1986:28:229235.
54.Stern LM, Walker MK, Sawyer MG, Oades RD, Badcock NR, Spence JG. A controlled crossover trial of fenfluramine in autism. J Child Psychol Psychiatry. 1990:31:569585.
55.Campbell M, Perry R, Small AM, Green WH. Overview of drug treatment in autism. In: Schopler E, Mesibov GB, eds. Neurobiological Issues in Autism. New York, NY: Plenum Press; 1987.
56.Ekman G, Miranda-Linné F, Gillberg C, Garle M, Wetterberg L. Fenfluramine treatment of twenty children with autism. J Autism Dev Disord. 1989;19:511532.
57.Sherman J, Factor DC, Swinson R, Darjes RW. The effects of fenfluramine (hydrochloride) on the behaviors of fifteen autistic children. J Autism Dev Disord. 1989:19:533543.
58.Duker PC, Welles K, Seys D, Rensen H, Vis A. Brief report: effects of fenfluramine on communicative, stereotypic, and inappropriate behaviors of autistic-type mentally handicapped individuals. J Autism Dev Disord. 1991:21:355363.
59.Campbell M, Fish B, Shapiro T, Floyd AK Jr., Imipramine in preschool autistic and schizophrenic children. Journal of Autism and Childhood Schizophrenia. 1971; 1:267282.
60.Fish B, Campbell M, Shapiro T, Floyd A Jr., Schizophrenic children treated with methysergide (Sansert). Dis Nerv Syst. 1969; 30:534540.
61.Blier P, de Montigny C, Chaput Y. A role for the serotonin system in the mechanism of action of antidepressant treatments: preclinical evidence. J Clin Psychiatry. 1990:51 (suppl):1420.
62.Realmuto GM, August GJ, Garfinkel BD. Clinical effect of buspirone in autistic children. J Clin Psychopharmacol. 1989:9:122125.
63.Ratey JJ, Sovner R, Mikkelsen E, Chmielinski HE. Buspirone therapy for maladaptive behavior and anxiety in developmentally disabled persons. J Clin Psychiatry. 1989:50:382384.
64.Gedye A. Buspirone alone or with serotonergic diet reduced aggression in a developmentally disabled adult. Biol Psychiatry. 1991:30:8891.
65.Ricketts RW, Goza AB, Ellis CR, et al.Clinical effects of buspirone on intractable self-injury in adults with mental retardation. J Am Acad Child Adolesc Psychiatry. 1994:33:270276.
66.Gedye A. Serotonergic treatment for aggression in a Down's syndrome adult showing signs of Alzheimer's disease. Journal of Mental Deficiency Research. 1991:35:247258.
67.O'Neill M, Page N, Adkins W. Tryptophan-trazodone treatment of aggressive behavior. Lancet. 1986:2:859860.
68.McDougle CJ, Price LH, Volkmar FR, et al.Clomipramine in autism: preliminary evidence of efficacy. J Am Acad Child Adolesc Psychiatry. 1992:31:746750.
69.Garber HJ, McGonigle JJ, Slomka GT, Monteverde E. Clomipramine treatment of stereotypic behaviors and self-injury in patients with developmental disabilities. J Am Acad Child Adolesc Psychiatry. 1992:31:11571160.
70.Gordon CT, Rapoport JL, Hamburger SD, State RC, Mannheim GB. Differential response of seven subjects with autistic disorder to clomipramine and desipramine. Am J Psychiatry. 1992:149:363366.
71.Gordon CT, State RC, Nelson JE, Hamburger SD, Rapoport JL. A double-blind comparison of clomipramine, desipramine, and placebo in the treatment of autistic disorder. Arch Gen Psychiatry. 1993:50:441447.
72.Brodkin ES, McDougle CJ, Naylor ST, Cohen DJ, Price LH. Clomipramine in adults with pervasive developmental disorders: A prospective, open-label investigation. Journal of Child and Adolescent Psychopharmocology. In press.
73.Brasic JR, Barnett JY, Kaplan D, et al.Clomipramine ameliorates adventitious movements and compulsions in prepubertal boys with autistic disorder and severe mental retardation. Neurology. 1994:44:13091312.
74.Sanchez LE, Campbell M, Small AM, Cueva JE, Armenteros JL, Adams PB. A pilot study of clomipramine in young autistic children. J Am Acad Child Adolesc Psychiatry. 1996:35:537544.
75.Buck OD. Sertraline for reduction of violent behavior. Am J Psychiatry. 1995:152:953.
76.Hellings JA, Kelley LA, Gabrielli WF, Kilgore E, Shah P. Sertraline response in adults with mental retardation and autistic disorder. J Clin Psychiatry. 1996:53:333336.
77.Cook EH Jr, Rowlett R, Jaselskis C, Leventhal BL. Fluoxetine treatment of children and adults with autistic disorder and mental retardation. J Am Acad Child Adolesc Psychiatry. 1992:31:739745.
78.Mehlinger R, Scheftner WA, Poznanski E. Fluoxetine and autism. J Am Acad Child Adolesc Psychiatry. 1990:29:985. Letter.
79.Hamdan-Allen G. Brief report: trichotillomania in an autistic male. J Autism Dev Disord. 1991:21:7982.
80.Todd RD. Fluoxetine in autism. Am J Psychiatry. 1991:148:1089. Letter.
81.Ghaziuddin M, Tsai L, Ghaziuddin N. Fluoxetine in autism with depression. J Am Acad Child Adolesc Psychiatry. 1991:30:508509. Letter.
82.Ghaziuddin M, Tsai L. Depression in autistic disorder. Br J Psychiatry. 1991:159:721723.
83.Koshes RJ. Use of fluoxetine for obsessive-compulsive behavior in adults with autism. Am J Psychiatry. 1997:154:578.
84.Snead RW, Boon F, Presberg J. Paroxetine for self-injurious behavior. J Am Acad Child Adolesc Psychiatry. 1994:33:909910. Letter.
85.McDougle CJ, Price LH, Goodman WK. Fluvoxamine treatment of coincident autistic disorder and obsessive compulsive disorder: a case report. J Autism Dev Disord. 1990:20:537543.
86.McDougle CJ, Naylor ST, Cohen DJ, Volkmar FR, Heninger GR, Price LH. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry. 1996:53:10011008.
87.Goodman WK, Price LH, Rasmussen SA, et al.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS): part I. Development, use, and reliability. Arch Gen Psychiatry. 1989:46:10061011.
88.Goodman WK, Price LH, Rasmussen SA, et al.The Yale-Brown Obsessive Compulsive Scale (Y-BOCS): part II. Validity. Arch Gen Psychiatry. 1989:46:10121016.
89.Meltzer HY. Atypical antipsychotic drugs. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press; 1995:12771286.
90.Potenza MN, McDougle CJ. Potential of “atypical” antipsychotics in the treatment of non-psychotic disorders. CNS Drugs. In press.
91.Zuddas A, Ledda MG, Fratta A, Muglia P, Cianchetti C. Clinical effects of clozapine on autistic disorder. Am J Psychiatry. 1996:153:738. Letter.
92.Borison RL, Pathiraja AP, Diamond BL, Meibach RC. Risperidone clinical safety and efficacy in schizophrenia. Psychopharmacol Bull. 1992:28:213218.
93.Owens DGC. Extrapyramidal side effects and tolerability of risperidone: a review. J Clin Psychiatry. 1994:55:2935.
94.Purdon SE, Lit WLabelle A, Jones BD. Risperidone in the treatment of pervasive developmental disorder. Can J Psychiatry. 1994:39:400405.
95.McDougle CJ, Brodkin ES, Yeung PP, Naylor ST, Cohen DJ, Price LH. Risperidone in adults with autism or pervasive developmental disorder. Journal of Child and Adolescent Psychopharmacology. 1995:5:273282.
96.Simeon JG, Carrey NJ, Wiggins DM, Milin RP, Hosendocus SN. Risperidone effects in treatment-resistant adolescents: preliminary case reports. Journal of Child and Adolescent Psychopharmacology. 1995:5:6979.
97.Fisman S, Steele M, Short J, Byrne T, Lavallee C. Case study: anorexia nervosa and autistic disorder in an adolescent girl. J Am Acad Child Adolesc Psychiatry. 1996:35:937940.
98.Demb HB. Risperidone in young children with pervasive developmental disorders and other developmental disabilities. Journal of Child and Adolescent Psychopharmacology 1996:6:7980. Letter.
99.Fisman S, Steele M. Use of risperidone in pervasive developmental disorders: A case series. Journal of Child and Adolescent Psychopharmacology. 1996:6:177190.
100.Hardan A, Johnson K, Johnson C, Hrecznyj B. Case study: risperidone treatment of children and adolescents with developmental disorders. J Am Acad Child Adolesc Psychiatry. 1996:35:15511556.
101.Lott RS, Kerrick JM, Cohen SA. Clinical and economic aspects of risperidone treatment in adults with mental retardation and behavioral disturbance. Psychopharmacol Bull. 1994:32:721729.
102.McDougle CJ, Holmes JP, Bronson MR, et al.Risperidone treatment of children and adolescents with pervasive developmental disorders: a prospective open-label study. J Am Acad Child Adolesc Psychiatry. 1997(36):685693.
103.Bymaster FP, Calligaro DO, Falcone JF, et al.Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996; 14:8796.
104.Rubin MLUse of atypical antipsychotics in children with mental retardation, autism, and other developmental disabilities. Psychiatric Annals. 1997:27:219221.
105.Megens AAHP, Niemegeers CJE, Awouters FHL. Behavioral disinhibition and depression in amphetaminized rats: a comparison of risperidone, ocaperidone and haloperidol. J Pharmacol Exp Ther. 1992:260:160167.
106.Dixon AK, Huber C, Lowe DA. Clozapine promotes approach-oriented behavior in male mice. J Clin Psychiatry. 1994;55(suppl B):47.
107.Prinssen EPM, Ellenbroek BA, Cools AR. Combined antagonism of adrenoceptors and dopamine and 5-HT receptors underlies the atypical profile of clozapine. Eur J Pharmacol. 1994:262:167170.
108.Corbett R, Hartman H, Kerman LL, et al.Effects of atypical antipsychotic agents on social behavior in rodents. Pharmacol Biochem Behav. 1993:45:917.
109.van der Linden C, Bruggeman R, van Woerkom TCAM. Serotonin-dopamine antagonist and Gilles de la Tourette's syndrome: an open pilot dose-titration study with risperidone. Mov Disord. 1994:9:687688. Letter.
110.Swedo SE, Leonard HL. Trichotillomania: an obsessive compulsive spectrum disorder? Psychiatric Clin North Am. 1992:15:777790.
111.Swedo SE, Leonard HL, Rapoport JL, Lenane MC, Goldberger EL, Cheslow DL. A double-blind comparison of clomipramine and desipramine in the treatment of trichotillomania (hair pulling). N Engl J Med. 1989:321:497501.
112.Stein DJ, Hollander E, Cohen L, Simeon D, Aronowitz B. Serotonergic responsivity in trichotillomania: neuroendocrine effects of m-chlorophenylpiperazine. Biol Psychiatry. 1995:37:414416.
113.Ninan FT, Rothbaum BO, Stipetic M, Lewine RJ, Risch SC. CSF 5-HIAA as a predictor of treatment response in trichotillomania. Psychopharmacol Bull. 1992:28:451455.
114.Rapoport JL, Swedo SE, Leonard HL. Childhood obsessive-compulsive disorder. J Clin Psychiatry. 1992:53:1116.
115.Lindley P, Marks I, Philpott R, Snowden J. Treatment of obsessive-compulsive neurosis with history of childhood autism. Br J Psychiatry. 1977:130:592597.
116.McDougle CJ, Goodman WK, Price LH. The pharmacotherapy of obsessive compulsive disorder. Pharmacopsychiatry. 1993;26(suppl):2429.
117.Foa EB. Failures in treating obsessive-compulsives. Behav Res Ther. 1979:17:169176.
118.Insel TR, Mueller EA, Alterman A, Linnoila M, Murphy DL. Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry. 1985:20:11741188.
119.Kanner L. Autistic disturbances of affective contact. Journal of Nervous Child. 1943:2:217250.
120.McDougle CJ, Fleischmann RL, Epperson CN, Wasylink S, Leckman JF, Price LH. Risperidone addition in fluvoxamine-refractory obsessive compulsive disorder: three cases. J Clin Psychiatry. 1995:56:526528.
121.Saxena S, Wang D, Bystritsky A, Baxter LR Jr., Risperidone augmentation of SRI treatment for refractory obsessive-compulsive disorder. J Clin Psychiatry. 1996:57:303306.
122.Stein DJ, Bouwer MB, Hawkridge S, Emsley RA. Risperidone augmentation of serotonin reuptake inhibitors in obsessive-compulsive and related disorders. J Clin Psychiatry. 1997:58:119122.
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