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Fluoxetine and Impulsive Aggressive Behavior in Personality-Disordered Subjects

Fluoxetine and Impulsive Aggressive Behavior in Personality-Disordered Subjects Abstract Background: Evidence of an inverse relationship between central serotonergic (serotonin [5-hydroxytryptamine]) system function and impulsive aggressive behavior has been accumulating for more than 2 decades. If so, pharmacological enhancement of serotonin activity should be expected to reduce impulsive aggressive behavior in subjects in whom this behavior is prominent. Methods: A double-blind, placebo-controlled trial of the selective serotonin-uptake inhibitor fluoxetine hydrochloride was conducted in 40 nonmajor-depressed, nonbipolar or schizophrenic, DSM-III-R personality—disordered individuals with current histories of impulsive aggressive behavior and irritability. Measures included the Overt Aggression Scale—Modified for Outpatients, Clinical Global Impression Rating of Improvement, and several secondary measures of aggression, depression, and anxiety. Results: Fluoxetine, but not placebo, treatment resulted in a sustained reduction in scores on the lrritability and Aggression subscales of the Overt Aggression Scale—Modified for Outpatients that was first apparent during months 2 and 3 of treatment, respectively. Fluoxetine was superior to placebo in the proportion of "responders" on the Clinical Global Impression Rating of Improvement: first at the end of month 1, and then finally demonstrating a sustained drug-placebo difference from the end of month 2 through the end of month 3 of treatment. These results were not influenced by secondary measures of depression, anxiety, or alcohol use. Conclusion: Fluoxetine treatment has an antiaggressive effect on impulsive aggressive individuals with DSM-III-R personality disorder. References 1. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK. Low cerebrospinal fluid 5-hydroxyindolacetic acid concentration differentiates impulsive from nonimpulsive violent behavior . Life Sci . 1983;33:2609-2614.Crossref 2. Virkkunen M, Rawlins R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers . Arch Gen Psychiatry . 1994;51:20-27.Crossref 3. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF. Aggression in humans correlates with cerebrospinal fluid amine metabolites . Psychiatry Res . 1979;1:131-139.Crossref 4. Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK. Aggression, suicide, and serotonin: relationships to CSF amine metabolites . Am J Psychiatry . 1982;139:741-746. 5. Coccaro EF, Siever LJ, Klar H, Maurer G, Cochrane K, Cooper TB, Mohs RC, Davis KL. Serotonergic studies in affective and personality disorder patients: correlates with suicidal and impulsive aggressive behavior . Arch Gen Psychiatry . 1989;46:587-599.Crossref 6. Moss HB, Yao JK, Panzak GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse . Biol Psychiatry . 1990;28:325-338.Crossref 7. O'Keane V, Moloney E, O'Neill H, O'Connor A, Smith C, Dinan TG. Blunted prolactin responses to D-fenfluramine in sociopathy: evidence for subsensitivity of central serotonergic function . Br J Psychiatry . 1992;160:643-646.Crossref 8. Stoff DM, Pollock L, Vitiello B, Behar D, Bridger WH. Reduction of 3H--imipramine binding sites on platelets of conduct disordered children . Neuropsychopharmacology . 1987;1:55-62.Crossref 9. Birmaher B, Stanley M, Greenhill L, Twomey J, Gavrilescu A, Rabinovich H. Platelet imipramine binding in children and adolescents with impulsive behavior . J Am Acad Child Adolesc Psychiatry . 1990;29:914-918.Crossref 10. Marazziti D, Rotondo A, Presta S, Panioli-Guadagnucci ML, Palego L, Conti L. Role of serotonin in human aggressive behavior . Aggress Behav . 1993;9:347-353.Crossref 11. Coccaro EF, Gabriel S, Siever LJ. Buspirone challenge: preliminary evidence for a role for central 5-HT-1a receptor function in impulsive aggressive behavior in humans . Psychopharmacol Bull . 1990;26:393-405. 12. Limson R, Goldman D, Roy A, Lamparski D, Ravitz B, Adinoff B, Linnoila M. Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls . Arch Gen Psychiatry . 1991;48:437-441.Crossref 13. Bernstein DP, Handlesman L. The neurobiology of substance abuse and personality disorders . In: Ratey JJ, ed. Neuropsychiatry of Behavior Disorders . Cambridge, Mass: Blackwell Science, Inc; 1995:120-148. 14. MJP, Rapoport JL, Hamberger S, Hibbs E, Potter WZ, Lenane M, Brown GL. CSF metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents . Arch Gen Psychiatry . 1990;47:419-462.Crossref 15. Brown CS, Kent TA, Bryant SG, Gevedon RM, Campbell JL, Felthous AR, Barratt ES, Rose RM. Blood platelet uptake of serotonin in episodic aggression . Psychiatry Res . 1989;27:5-12.Crossref 16. Eichelman B. Animal and evolutionary models of impulsive aggression . In: Stein D, Hollander E, eds. Impulsive Aggression and Disorders of Impulse Control .New York, NY: John Wiley & Sons Inc; 1995:59-69. 17. Sheard M, Marini J, Bridges C, Wapner A. The effect of lithium on impulsive aggressive behavior in man . Am J Psychiatry . 1976;133:1409-1413. 18. Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder: alprazolam, carbamazepine, trifluoperazine, and tranylcypromine . Arch Gen Psychiatry . 1988;45:111-119.Crossref 19. Silver JM, Yudofsky SC. Propranolol in the treatment of chronically hospitalized violent patients . In: Shagass C, Josiassen RC, Bridger WH, Weiss KJ, Stoft D, Simpson GM, eds. Biological Psychiatry . New York, NY: Elsevier Science Inc; 1986:174-176. 20. Teicher MH, Glod CA, Aaronson ST, Gunter PA, Schatzberg AF, Cole JO. Open assessment of the safety and efficacy of thioridazine in the treatment of patients with borderline personality disorder . Psychopharmacol Bull . 1989;25:535-549. 21. Norden MJ. Fluoxetine in borderline personality disorder . Prog Neuropsychopharmacol Biol Psychiatry . 1989;13:885-893.Crossref 22. Cornelius JR, Soloff PH, Perel JM, Ulrich RF. Fluoxetine trial in borderline Personality disorder . Psychopharmacol Bull . 1990:26:151-154. 23. Coccaro EF, Astill JL, Herbert J, Schut A. Fluoxetine treatment of impulsive aggression in DSM-III-R personality disorder patients . J Clin Psychopharmacol . 1990;10:373-375.Crossref 24. Markovitz PJ, Calabrese JR, Schulz SC, Meltzer HY. Fluoxetine in borderline and schizotypal personality disorder . Am J Psychiatry . 1991;148:1064-1067. 25. Kavoussi RJ, Liu J, Coccaro EF. An open trial of sertraline in personality disordered patients with impulsive aggression . J Clin Psychiatry . 1994;55:137-141. 26. Fava M, Rosenbaum JF, Pava JA, McCarthy MK, Steingard RJ, Bouffides E. Anger attacks in unipolar depression, 1: clinical correlates and response to fluoxetine treatment . Am J Psychiatry . 1993;150:1158-1163. 27. Heiligenstein JH, Coccaro EF, Potvin JH, Beasley CM, Dornseif BE, Mascia DN. Fluoxetine not associated with increased violence or aggression in controlled clinical trials . Ann Clin Psychiatry . 1992;4:285-295.Crossref 28. Salzman C, Wolfson AN, Schatzberg A, Looper J, Henke R, Albanese, Schwartz J, Miyawaki E. Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder . J Clin Psychopharmacol . 1995;15:23-29.Crossref 29. Perry KW, Fuller RW. Effect of fluoxetine on serotonin and dopamine concentration in microdialysis fluid from rat striatium . Life Sci . 1992;50:1683-1690.Crossref 30. Fuller RW. Minireview: uptake inhibitors increase extracellular serotonin concentration measures by brain microdialysis . Life Sci . 1994;55:163-167.Crossref 31. Blier P, de Montigny C, Chaput Y. Modifications of the serotonin system by antidepressant treatments: implication for the therapeutic response in major depression . J Clin Psychopharmacol . 1987;7:24S-35S.Crossref 32. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised . Washington, DC: American Psychiatric Press; 1987. 33. Coccaro EF, Harvey PD, Kupsaw-Lawrence E, Herbert JL, Bernstein DP. Development of neuropharmacologically based behavioral assessments of impulsive aggressive behavior . J Neuropsychiatry Clin Neurosci . 1991;3:S44-S51. 34. Brown GL, Goodwin FK. Diagnostic, clinical and personality characteristics of aggressive men with low CSF 5-HIAA . Clin Neuropharmacol . 1984;7:S408-S409.Crossref 35. Coccaro EF, Kavoussi RJ, Sheline YI, Lish JD, Csernansky JG. Impulsive aggression in personality disorder: correlates with 3H-paroxetine binding in the platelet . Arch Gen Psychiatry . 1996;53:531-536.Crossref 36. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodologic study . Arch Gen Psychiatry . 1982;39:879-883.Crossref 37. Klein DN, Ouimette PC, Kelly HS, Ferro T, Riso LP. Test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study . Am J Psychiatry . 1994;151:1043-1047. 38. Spitzer RL, Endicott J. Schedule for Affective Disorders and Schizophrenia . New York, NY: New York State Psychiatric Institute; 1978. 39. Pfohl B, Zimmerman, M. Structured Interview for the Diagnosis of DSM-III-R Personality Disorders . Ames: University of Iowa College of Medicine; 1989. 40. Guy W. ECDEU Manual for Psychopharmacology. Washington, DC: Superintendent of Documents, US Government Printing Office; 1976. US Dept of Health, Education, and Welfare publication ADM 76-338. 41. DeLongis A, Folkman S, Lazarus RS. The impact of daily stress on health and mood: psychological and social resources as mediators . J Pers Soc Psychol . 1988;54:486-495.Crossref 42. Suckow RS, Chang M, Cooper TB. A sensitive and selective liquid chromatographic method using fluorescence detection for plasma fluoxetine and norfluoxetine . Clin Chem . 1992;38:1756-1761. 43. Sheard MH, Marini JL. Treatment of human aggressive behavior: four case studies of the effect of lithium . Compr Psychiatry . 1978;19:37-45.Crossref 44. Depue RA, Spoont MR. Conceptualizing a serotonin trait: a behavioral dimension of constraint . Ann N Y Acad Sci . 1986;487:47-62.Crossref 45. Coccaro EF. Psychopharmacologic studies in patients with personality disorder: review and perspective . J Pers Disord . (Spring) 1993(suppl):181-192. 46. Molina VA, Gobaille S, Mandel P. Effects of serotonin-mimetic drugs on mousekilling behavior . Aggress Behav . 1986;12:201-211.Crossref 47. Cornelius JR, Soloff PH, Perel JM, Ulrich RF. Continuation pharmacotherapy of borderline personality disorder with haloperidol and phenelzine . Am J Psychiatry . 1993;150:1843-1848. 48. Stone MH. The role of pharmacotherapy in the treatment of patients with borderline personality disorder . Psychopharmacol Bull . 1989;25:564-571. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of General Psychiatry American Medical Association

Fluoxetine and Impulsive Aggressive Behavior in Personality-Disordered Subjects

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References (54)

Publisher
American Medical Association
Copyright
Copyright © 1997 American Medical Association. All Rights Reserved.
ISSN
0003-990X
eISSN
1598-3636
DOI
10.1001/archpsyc.1997.01830240035005
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Abstract

Abstract Background: Evidence of an inverse relationship between central serotonergic (serotonin [5-hydroxytryptamine]) system function and impulsive aggressive behavior has been accumulating for more than 2 decades. If so, pharmacological enhancement of serotonin activity should be expected to reduce impulsive aggressive behavior in subjects in whom this behavior is prominent. Methods: A double-blind, placebo-controlled trial of the selective serotonin-uptake inhibitor fluoxetine hydrochloride was conducted in 40 nonmajor-depressed, nonbipolar or schizophrenic, DSM-III-R personality—disordered individuals with current histories of impulsive aggressive behavior and irritability. Measures included the Overt Aggression Scale—Modified for Outpatients, Clinical Global Impression Rating of Improvement, and several secondary measures of aggression, depression, and anxiety. Results: Fluoxetine, but not placebo, treatment resulted in a sustained reduction in scores on the lrritability and Aggression subscales of the Overt Aggression Scale—Modified for Outpatients that was first apparent during months 2 and 3 of treatment, respectively. Fluoxetine was superior to placebo in the proportion of "responders" on the Clinical Global Impression Rating of Improvement: first at the end of month 1, and then finally demonstrating a sustained drug-placebo difference from the end of month 2 through the end of month 3 of treatment. These results were not influenced by secondary measures of depression, anxiety, or alcohol use. Conclusion: Fluoxetine treatment has an antiaggressive effect on impulsive aggressive individuals with DSM-III-R personality disorder. References 1. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK. Low cerebrospinal fluid 5-hydroxyindolacetic acid concentration differentiates impulsive from nonimpulsive violent behavior . Life Sci . 1983;33:2609-2614.Crossref 2. Virkkunen M, Rawlins R, Tokola R, Poland RE, Guidotti A, Nemeroff C, Bissette G, Kalogeras K, Karonen SL, Linnoila M. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers . Arch Gen Psychiatry . 1994;51:20-27.Crossref 3. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF. Aggression in humans correlates with cerebrospinal fluid amine metabolites . Psychiatry Res . 1979;1:131-139.Crossref 4. Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK. Aggression, suicide, and serotonin: relationships to CSF amine metabolites . Am J Psychiatry . 1982;139:741-746. 5. Coccaro EF, Siever LJ, Klar H, Maurer G, Cochrane K, Cooper TB, Mohs RC, Davis KL. Serotonergic studies in affective and personality disorder patients: correlates with suicidal and impulsive aggressive behavior . Arch Gen Psychiatry . 1989;46:587-599.Crossref 6. Moss HB, Yao JK, Panzak GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse . Biol Psychiatry . 1990;28:325-338.Crossref 7. O'Keane V, Moloney E, O'Neill H, O'Connor A, Smith C, Dinan TG. Blunted prolactin responses to D-fenfluramine in sociopathy: evidence for subsensitivity of central serotonergic function . Br J Psychiatry . 1992;160:643-646.Crossref 8. Stoff DM, Pollock L, Vitiello B, Behar D, Bridger WH. Reduction of 3H--imipramine binding sites on platelets of conduct disordered children . Neuropsychopharmacology . 1987;1:55-62.Crossref 9. Birmaher B, Stanley M, Greenhill L, Twomey J, Gavrilescu A, Rabinovich H. Platelet imipramine binding in children and adolescents with impulsive behavior . J Am Acad Child Adolesc Psychiatry . 1990;29:914-918.Crossref 10. Marazziti D, Rotondo A, Presta S, Panioli-Guadagnucci ML, Palego L, Conti L. Role of serotonin in human aggressive behavior . Aggress Behav . 1993;9:347-353.Crossref 11. Coccaro EF, Gabriel S, Siever LJ. Buspirone challenge: preliminary evidence for a role for central 5-HT-1a receptor function in impulsive aggressive behavior in humans . Psychopharmacol Bull . 1990;26:393-405. 12. Limson R, Goldman D, Roy A, Lamparski D, Ravitz B, Adinoff B, Linnoila M. Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls . Arch Gen Psychiatry . 1991;48:437-441.Crossref 13. Bernstein DP, Handlesman L. The neurobiology of substance abuse and personality disorders . In: Ratey JJ, ed. Neuropsychiatry of Behavior Disorders . Cambridge, Mass: Blackwell Science, Inc; 1995:120-148. 14. MJP, Rapoport JL, Hamberger S, Hibbs E, Potter WZ, Lenane M, Brown GL. CSF metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents . Arch Gen Psychiatry . 1990;47:419-462.Crossref 15. Brown CS, Kent TA, Bryant SG, Gevedon RM, Campbell JL, Felthous AR, Barratt ES, Rose RM. Blood platelet uptake of serotonin in episodic aggression . Psychiatry Res . 1989;27:5-12.Crossref 16. Eichelman B. Animal and evolutionary models of impulsive aggression . In: Stein D, Hollander E, eds. Impulsive Aggression and Disorders of Impulse Control .New York, NY: John Wiley & Sons Inc; 1995:59-69. 17. Sheard M, Marini J, Bridges C, Wapner A. The effect of lithium on impulsive aggressive behavior in man . Am J Psychiatry . 1976;133:1409-1413. 18. Cowdry RW, Gardner DL. Pharmacotherapy of borderline personality disorder: alprazolam, carbamazepine, trifluoperazine, and tranylcypromine . Arch Gen Psychiatry . 1988;45:111-119.Crossref 19. Silver JM, Yudofsky SC. Propranolol in the treatment of chronically hospitalized violent patients . In: Shagass C, Josiassen RC, Bridger WH, Weiss KJ, Stoft D, Simpson GM, eds. Biological Psychiatry . New York, NY: Elsevier Science Inc; 1986:174-176. 20. Teicher MH, Glod CA, Aaronson ST, Gunter PA, Schatzberg AF, Cole JO. Open assessment of the safety and efficacy of thioridazine in the treatment of patients with borderline personality disorder . Psychopharmacol Bull . 1989;25:535-549. 21. Norden MJ. Fluoxetine in borderline personality disorder . Prog Neuropsychopharmacol Biol Psychiatry . 1989;13:885-893.Crossref 22. Cornelius JR, Soloff PH, Perel JM, Ulrich RF. Fluoxetine trial in borderline Personality disorder . Psychopharmacol Bull . 1990:26:151-154. 23. Coccaro EF, Astill JL, Herbert J, Schut A. Fluoxetine treatment of impulsive aggression in DSM-III-R personality disorder patients . J Clin Psychopharmacol . 1990;10:373-375.Crossref 24. Markovitz PJ, Calabrese JR, Schulz SC, Meltzer HY. Fluoxetine in borderline and schizotypal personality disorder . Am J Psychiatry . 1991;148:1064-1067. 25. Kavoussi RJ, Liu J, Coccaro EF. An open trial of sertraline in personality disordered patients with impulsive aggression . J Clin Psychiatry . 1994;55:137-141. 26. Fava M, Rosenbaum JF, Pava JA, McCarthy MK, Steingard RJ, Bouffides E. Anger attacks in unipolar depression, 1: clinical correlates and response to fluoxetine treatment . Am J Psychiatry . 1993;150:1158-1163. 27. Heiligenstein JH, Coccaro EF, Potvin JH, Beasley CM, Dornseif BE, Mascia DN. Fluoxetine not associated with increased violence or aggression in controlled clinical trials . Ann Clin Psychiatry . 1992;4:285-295.Crossref 28. Salzman C, Wolfson AN, Schatzberg A, Looper J, Henke R, Albanese, Schwartz J, Miyawaki E. Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder . J Clin Psychopharmacol . 1995;15:23-29.Crossref 29. Perry KW, Fuller RW. Effect of fluoxetine on serotonin and dopamine concentration in microdialysis fluid from rat striatium . Life Sci . 1992;50:1683-1690.Crossref 30. Fuller RW. Minireview: uptake inhibitors increase extracellular serotonin concentration measures by brain microdialysis . Life Sci . 1994;55:163-167.Crossref 31. Blier P, de Montigny C, Chaput Y. Modifications of the serotonin system by antidepressant treatments: implication for the therapeutic response in major depression . J Clin Psychopharmacol . 1987;7:24S-35S.Crossref 32. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised . Washington, DC: American Psychiatric Press; 1987. 33. Coccaro EF, Harvey PD, Kupsaw-Lawrence E, Herbert JL, Bernstein DP. Development of neuropharmacologically based behavioral assessments of impulsive aggressive behavior . J Neuropsychiatry Clin Neurosci . 1991;3:S44-S51. 34. Brown GL, Goodwin FK. Diagnostic, clinical and personality characteristics of aggressive men with low CSF 5-HIAA . Clin Neuropharmacol . 1984;7:S408-S409.Crossref 35. Coccaro EF, Kavoussi RJ, Sheline YI, Lish JD, Csernansky JG. Impulsive aggression in personality disorder: correlates with 3H-paroxetine binding in the platelet . Arch Gen Psychiatry . 1996;53:531-536.Crossref 36. Leckman JF, Sholomskas D, Thompson WD, Belanger A, Weissman MM. Best estimate of lifetime psychiatric diagnosis: a methodologic study . Arch Gen Psychiatry . 1982;39:879-883.Crossref 37. Klein DN, Ouimette PC, Kelly HS, Ferro T, Riso LP. Test-retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study . Am J Psychiatry . 1994;151:1043-1047. 38. Spitzer RL, Endicott J. Schedule for Affective Disorders and Schizophrenia . New York, NY: New York State Psychiatric Institute; 1978. 39. Pfohl B, Zimmerman, M. Structured Interview for the Diagnosis of DSM-III-R Personality Disorders . Ames: University of Iowa College of Medicine; 1989. 40. Guy W. ECDEU Manual for Psychopharmacology. Washington, DC: Superintendent of Documents, US Government Printing Office; 1976. US Dept of Health, Education, and Welfare publication ADM 76-338. 41. DeLongis A, Folkman S, Lazarus RS. The impact of daily stress on health and mood: psychological and social resources as mediators . J Pers Soc Psychol . 1988;54:486-495.Crossref 42. Suckow RS, Chang M, Cooper TB. A sensitive and selective liquid chromatographic method using fluorescence detection for plasma fluoxetine and norfluoxetine . Clin Chem . 1992;38:1756-1761. 43. Sheard MH, Marini JL. Treatment of human aggressive behavior: four case studies of the effect of lithium . Compr Psychiatry . 1978;19:37-45.Crossref 44. Depue RA, Spoont MR. Conceptualizing a serotonin trait: a behavioral dimension of constraint . Ann N Y Acad Sci . 1986;487:47-62.Crossref 45. Coccaro EF. Psychopharmacologic studies in patients with personality disorder: review and perspective . J Pers Disord . (Spring) 1993(suppl):181-192. 46. Molina VA, Gobaille S, Mandel P. Effects of serotonin-mimetic drugs on mousekilling behavior . Aggress Behav . 1986;12:201-211.Crossref 47. Cornelius JR, Soloff PH, Perel JM, Ulrich RF. Continuation pharmacotherapy of borderline personality disorder with haloperidol and phenelzine . Am J Psychiatry . 1993;150:1843-1848. 48. Stone MH. The role of pharmacotherapy in the treatment of patients with borderline personality disorder . Psychopharmacol Bull . 1989;25:564-571.

Journal

Archives of General Psychiatry – American Medical Association

Published: Dec 1, 1997

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