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The Role of Serotonin in Autism-Spectrum Disorders

Published online by Cambridge University Press:  07 November 2014

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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Feature Article
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Copyright © Cambridge University Press 1997

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References

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.Google Scholar
2.Kaplan, HI, Sadock, BJ, Grebb, JF. Kaplan and Sadock's Synopsis of Psychiatry. 7th ed. Philadelphia, Pa: William & Wilkins; 1994:10521062.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
6.Gillberg, C. Outcome in autism and autistic-like conditions. J Am Acad Child Adolesc Psychiatry. 1991;30:375382.Google Scholar
7.Gillberg, C, Coleman, M. The Biology of the Autistic Syndromes. 2nd ed. London: MacKeith Press; 1992.Google Scholar
8.Bauman, ML, Kemper, TL. The Neurobiology of Autism. Baltimore, Md: Johns Hopkins University Press; 1994.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
12.Gillberg, C, Svennerholm, L, Hamilton-Hellberg, C. Childhood psychosis and monoamine metabolites in spinal fluid. J Autism Dev Disord. 1983;13:383396.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
18.Schain, RJ, Freedman, DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatr. 1961:58:315320.Google Scholar
19.Anderson, GM. Monoamines in autism: an update of neurochemical research on a pervasive developmental disorder. Medical Biology. 1987:65:6774.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
23. Cook, E.H.Autism: review of neurochemical investigation. Synapse. 1990:6:292308.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
27.Hanley, HG, Stahl, SM, Freedman, DX. Hyperserotonemia and amine metabolites in autistic and retarded children. Arch Gen Psychiatry. 1977:34:521531.Google Scholar
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.Google Scholar
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.Google Scholar
30.Hoshino, Y, Yamamoto, T, Kaneko, M, et al.Blood serotonin and free tryptophan concentration in autistic children. Neuropsychobiology. 1984; 11:2227.Google Scholar
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.Google Scholar
32.Rose, WC, Haines, WJ, Warner, DT. The amino acid requirements of man. J Biol Chem. 1954:206:421430.Google Scholar
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.Google Scholar
34.Fernstrom, JD. Effects of the diet on brain neurotransmitters. Metabolism. 1977:26:207223.Google Scholar
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.Google Scholar
36.Young, SN, Ervin, FR, Phil, RO, Finn, P. Biochemical aspects of tryptophan depletion in primates. Psychopharmacology (Berl). 1989:95:508511.Google Scholar
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.Google Scholar
38.Moir, ATB, Eccleston, D. The effects of precursor loading in the cerebral metabolism of 5-hydroxyindoles. J Neurochem. 1968:15:10931108.Google Scholar
39.Fernstrom, JD, Hirsch, MJ. Rapid repletion of brain serotonin in malnourished corn-fed rats following L-tryptophan injection. Life Sci. 1975:17:455464.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
44.Goddard, AW, Sholomskas, DE, Augeri, FM, et al.Effects of tryptophan depletion in panic disorder. Biol Psychiatry. 1994:36:775777.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
49.Schuster, CR, Lewis, M, Seiden, LS. Fenfluramine: neurotoxicity. Psychopharmacol Bull. 1986:22:148151.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
60.Fish, B, Campbell, M, Shapiro, T, Floyd, A Jr., Schizophrenic children treated with methysergide (Sansert). Dis Nerv Syst. 1969; 30:534540.Google Scholar
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.Google Scholar
62.Realmuto, GM, August, GJ, Garfinkel, BD. Clinical effect of buspirone in autistic children. J Clin Psychopharmacol. 1989:9:122125.Google Scholar
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.Google Scholar
64.Gedye, A. Buspirone alone or with serotonergic diet reduced aggression in a developmentally disabled adult. Biol Psychiatry. 1991:30:8891.Google Scholar
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.Google Scholar
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.Google Scholar
67.O'Neill, M, Page, N, Adkins, W. Tryptophan-trazodone treatment of aggressive behavior. Lancet. 1986:2:859860.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
75.Buck, OD. Sertraline for reduction of violent behavior. Am J Psychiatry. 1995:152:953.Google Scholar
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.Google Scholar
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.Google Scholar
78.Mehlinger, R, Scheftner, WA, Poznanski, E. Fluoxetine and autism. J Am Acad Child Adolesc Psychiatry. 1990:29:985. Letter.Google Scholar
79.Hamdan-Allen, G. Brief report: trichotillomania in an autistic male. J Autism Dev Disord. 1991:21:7982.Google Scholar
80.Todd, RD. Fluoxetine in autism. Am J Psychiatry. 1991:148:1089. Letter.Google Scholar
81.Ghaziuddin, M, Tsai, L, Ghaziuddin, N. Fluoxetine in autism with depression. J Am Acad Child Adolesc Psychiatry. 1991:30:508509. Letter.Google Scholar
82.Ghaziuddin, M, Tsai, L. Depression in autistic disorder. Br J Psychiatry. 1991:159:721723.Google Scholar
83.Koshes, RJ. Use of fluoxetine for obsessive-compulsive behavior in adults with autism. Am J Psychiatry. 1997:154:578.Google Scholar
84.Snead, RW, Boon, F, Presberg, J. Paroxetine for self-injurious behavior. J Am Acad Child Adolesc Psychiatry. 1994:33:909910. Letter.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
90.Potenza, MN, McDougle, CJ. Potential of “atypical” antipsychotics in the treatment of non-psychotic disorders. CNS Drugs. In press.Google Scholar
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.Google Scholar
92.Borison, RL, Pathiraja, AP, Diamond, BL, Meibach, RC. Risperidone clinical safety and efficacy in schizophrenia. Psychopharmacol Bull. 1992:28:213218.Google Scholar
93.Owens, DGC. Extrapyramidal side effects and tolerability of risperidone: a review. J Clin Psychiatry. 1994:55:2935.Google Scholar
94.Purdon, SE, Lit, WLabelle, A, Jones, BD. Risperidone in the treatment of pervasive developmental disorder. Can J Psychiatry. 1994:39:400405.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
99.Fisman, S, Steele, M. Use of risperidone in pervasive developmental disorders: A case series. Journal of Child and Adolescent Psychopharmacology. 1996:6:177190.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
103.Bymaster, FP, Calligaro, DO, Falcone, JF, et al.Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology. 1996; 14:8796.Google Scholar
104.Rubin, MLUse of atypical antipsychotics in children with mental retardation, autism, and other developmental disabilities. Psychiatric Annals. 1997:27:219221.Google Scholar
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.Google Scholar
106.Dixon, AK, Huber, C, Lowe, DA. Clozapine promotes approach-oriented behavior in male mice. J Clin Psychiatry. 1994;55(suppl B):47.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
110.Swedo, SE, Leonard, HL. Trichotillomania: an obsessive compulsive spectrum disorder? Psychiatric Clin North Am. 1992:15:777790.CrossRefGoogle ScholarPubMed
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.Google Scholar
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.Google Scholar
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.Google Scholar
114.Rapoport, JL, Swedo, SE, Leonard, HL. Childhood obsessive-compulsive disorder. J Clin Psychiatry. 1992:53:1116.Google Scholar
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.Google Scholar
116.McDougle, CJ, Goodman, WK, Price, LH. The pharmacotherapy of obsessive compulsive disorder. Pharmacopsychiatry. 1993;26(suppl):2429.Google Scholar
117.Foa, EB. Failures in treating obsessive-compulsives. Behav Res Ther. 1979:17:169176.Google Scholar
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.Google Scholar
119.Kanner, L. Autistic disturbances of affective contact. Journal of Nervous Child. 1943:2:217250.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar