Psychopharmacology

, Volume 176, Issue 3–4, pp 451–458 | Cite as

Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression

  • Antonia S. New
  • Monte S. Buchsbaum
  • Erin A. Hazlett
  • Marianne Goodman
  • Harold W. Koenigsberg
  • Jenni Lo
  • Lisa Iskander
  • Randall Newmark
  • Jesse Brand
  • Karen O’Flynn
  • Larry J. Siever
Original Investigation

Abstract

Rationale

Impulsive aggressive personality disordered patients have been shown to have decreased relative glucose metabolism in orbito-frontal cortex and anterior cingulate gyrus compared with normal subjects. In addition, patients with impulsive aggression have an attenuation of symptoms with selective serotonin reuptake inhibitor (SSRI) treatment.

Objectives

The goals of the present study were to attempt to replicate the finding of improvement in impulsive aggression in borderline personality disorder with SSRIs and to investigate the specific cortical areas modified by medication, which might underlie the observed clinical improvement using 18FDG-PET.

Methods

Ten impulsive aggressive patients with borderline personality disorder were imaged with 18F-deoxyglucose positron emission tomography at baseline and after receiving fluoxetine at 20 mg/day for 12 weeks. Anatomical MRIs were coregistered to PET and relative metabolic rates were obtained in 39 Brodmann areas.

Results

Brodmann areas 11 and 12 in the orbito-frontal cortex showed significant increases in relative metabolic rate. Significant clinical improvement was also observed as assessed by the Overt Aggression Scale-Modified.

Conclusions

These changes are consistent with a normalizing effect of fluoxetine on prefrontal cortex metabolism in impulsive aggressive disorder.

Keywords

Serotonin reuptake inhibitor Intermittent explosive disorder Functional brain imaging 

Notes

Acknowledgements

This project was supported by a grant from Eli Lilly and Co. This work was also supported in part by a grant (5-M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources, at the NIH. The authors thank Vivian Mitropoulou, administrative director of the GCRC, for her support of this project and Mary Corsey for technical assistance. The research conducted complied with the laws and standards of the United States of America, and guidelines of the IRB at Mount Sinai.

References

  1. Anderson SW, Bechara A, Damasio H, Tranel D, Damasio AR (1999) Impairment of social and moral behavior related to early damage in human prefrontal cortex. Nat Neurosci 2:1032–1037CrossRefPubMedGoogle Scholar
  2. Baxter LR Jr, Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, Alazraki A, Selin CE, Ferng HK, Munford P (1992) Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry 49:681–689PubMedGoogle Scholar
  3. Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr (1998) FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder Psychiatry Res 84:1–6Google Scholar
  4. Brody AL, Saxena S, Stoessel P, Gillies LA, Fairbanks LA, Alborzian S, Phelps ME, Huang SC, Wu HM, Ho ML, Ho MK, Au SC, Maidment K, Baxter LR Jr (2001) Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Arch Gen Psychiatry 58:631–640CrossRefPubMedGoogle Scholar
  5. Buchsbaum MS, Wu J, Siegel B, Hackett E, Trenary M, Abel L, Reynolds C (1997) Effect of sertraline on regional metabolic rate in patients with affective disorder. Biol Psychiatry 41:15–22PubMedGoogle Scholar
  6. Buchsbaum MS, Nenadic I, Hazlett EA, Spiegel-Cohen J, Fleischman MB, Akhavan A, Silverman JM, Siever LJ (2002) Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder. Schizophr Res 54:141–150CrossRefPubMedGoogle Scholar
  7. Buss AH, Durkee A (1957) An inventory for assessing different kinds of hostility. J Consult Psychol 21:343–348Google Scholar
  8. Coccaro EF, Kavoussi RJ (1997) Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry 54:1081–1088PubMedGoogle Scholar
  9. Coccaro EF, Harvey PD, Kupsaw-Lawrence E, Herbert JL, Bernstein PD (1991) Development of neuropharmacologically based behavioral assessments of impulsive aggressive behavior. J Neuropsychiatr Clin Neurosci 3:S44–S51PubMedGoogle Scholar
  10. Coccaro EF, Kavoussi RJ, Trestman RL, Gabriel SM, Cooper TB, Siever LJ (1996) Hormonal responses to meta-chlorophenylpiperazine (m-CPP) undiminished by acute m-CPP pretreatment. Psychiatry Res 62:139–145CrossRefPubMedGoogle Scholar
  11. Coccaro E, Kavoussi R, Berman M, Lish J (1998) Intermittent explosive disorder-revised: development, reliability, and validity of research criteria. Comp Psychiatry 39:368–376PubMedGoogle Scholar
  12. Cohen J (1969) Statistical power analysis for the behavioral sciences. Academic, New York, p 99, Table 3.4.1Google Scholar
  13. Critchley HD, Simmons A, Daly EM, Russell A, van Amelsvoort T, Robertson DM, Glover A, Murphy DG (2000) Prefrontal and medial temporal correlates of repetitive violence to self and others. Biol Psychiatry 47:928–934CrossRefPubMedGoogle Scholar
  14. FBI (1999) Uniform crime reporting. Federal Bureau of Investigation, Washington D.C.Google Scholar
  15. First M, Spitzer R, Gibbon M, Williams J (1996) Structured clinical interview for axis I disorders—patient edition. Biometrics Research, New York State Psychiatric Institute, New York, N.Y.Google Scholar
  16. George DT, Rawlings RR, Williams WA, Phillips MJ, Fong G, Kerich M, Momenan R, Umhau JC, Hommer D (2004) A select group of perpetrators of domestic violence: evidence of decreased metabolism in the right hypothalamus and reduced relationships between cortical/subcortical brain structures in position emission tomography. Psychiatry Res 130:11–25CrossRefPubMedGoogle Scholar
  17. Hazlett EA, Buchsbaum MS, Mohs RC, Speigel-Cohen J, Wei TC, Azueta R, Haznedar MM, Singer MB, Shihabuddin L, Luu-Hsia C, Harvey PD (1998) Age-related shift in brain region activity during successful memory performance. Neurobiol Aging 19:437–445CrossRefPubMedGoogle Scholar
  18. Hirono N, Mega MS, Dinov ID, Mishkin F, Cummings JL (2000) Left frontotemporal hypoperfusion is associated with aggression in patients with dementia. Arch Neurol 57:861–866CrossRefPubMedGoogle Scholar
  19. Horwitz B, Swedo SE, Grady CL, Pietrini P, Schapiro MB, Rapoport JL, Rapoport SL (1991) Cerebral metabolic pattern in obsessive compulsive disorder: altered intercorrelations between regional rates of glucose utilization. Psychiatry Res 40:221–237CrossRefPubMedGoogle Scholar
  20. Juhasz C, Behen ME, Muzik O, Chugani DC, Chugani HT (2001) Bilateral medial prefrontal and temporal neocortical hypometabolism in children with epilepsy and aggression. Epilepsia 42:991–1001CrossRefPubMedGoogle Scholar
  21. Kavoussi RJ, Liu J, Coccaro EF (1994) An open trial of sertraline in personality disordered patients with impulsive aggression. J Clin Psychiatry 55:137–141Google Scholar
  22. Kennedy SH, Evans KR, Kruger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ (2001) Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 158:899–905PubMedGoogle Scholar
  23. Mayberg HS, Brannan SK, Mahurin RK, Jerabek PA, Brickman JS, Tekell JL, Silva JA, McGinnis S, Glass TG, Martin CC, Fox PT (1997) Cingulate function in depression: a potential predictor of treatment response. Neuroreport 8:1057–1061PubMedGoogle Scholar
  24. Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA (2000) Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 48:830–843Google Scholar
  25. New AS, Hazlett E, Buchsbaum MS, Goodman M, Reynolds D, Mitropoulou V, Sprung L, Shaw J, RB, Koenigsberg HW, Platholi J, Silverman J, Siever L (2002) Blunted prefrontal cortical 18fluorodeoxyglucose positron emission tomography response to meta-chloropiperazine in impulsive aggression. Arch Gen Psychiatry 59:621–629CrossRefPubMedGoogle Scholar
  26. Pfohl B, Blum N, Zimmerman M (1996) Structured clinical interview for DSM-IV. American Psychiatric Association, Washington D.C.Google Scholar
  27. Raine A (1993) Features of borderline personality and violence. J Clin Psychol 49:277–281PubMedGoogle Scholar
  28. Raine A, Buchsbaum M, Stanley J, Lottenberg S, Abel L, Stoddard J (1994) Selective reductions in prefrontal glucose metabolism in murderers. Biol Psychiatry 36:365–373CrossRefPubMedGoogle Scholar
  29. Raine A, Buchsbaum M, LaCasse L (1997) Brain abnormalities in murderers indicated by positron emission tomography. Biol Psychiatry 42:495–508CrossRefPubMedGoogle Scholar
  30. Raine A, Meloy JR, Bihrle S, Stoddard J, LaCasse L, Buchsbaum MS (1998a) Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers. Behav Sci Law 16:319–332CrossRefPubMedGoogle Scholar
  31. Raine A, Phil D, Stoddard J, Bihrle S, Buchsbaum M (1998b) Prefrontal glucose deficits in murderers lacking psychosocial deprivation. Neuropsychiatr Neuropsychol Behav Neurol 11:1–7Google Scholar
  32. Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR Jr (2003) Differential brain metabolic predictors of response to paroxetine in obsessive-compulsive disorder versus major depression. Am J Psychiatry 160:522–532CrossRefPubMedGoogle Scholar
  33. Siever LJ, Buchsbaum M, New AS, Spiegel-Cohen J, Wei T, Hazlett E, Sevin E, Nunn M, Mitropoulou V (1999) d,l-Fenfluramine response in impulsive personality disorder assessed with 18F-deoxyglucose positron emission tomography. Neuropsychopharmacology 20:413–423CrossRefPubMedGoogle Scholar
  34. Soderstrom H, Tullberg M, Wikkelso C, Ekholm S, Forsman A (2000) Reduced regional cerebral blood flow in non-psychotic violent offenders. Psychiatry Res 98:29–41CrossRefPubMedGoogle Scholar
  35. Soderstrom H, Hultin L, Tullberg M, Wikkelso C, Ekholm S, Forsman A (2002) Reduced frontotemporal perfusion in psychopathic personality. Psychiatry Res 114:81–94CrossRefPubMedGoogle Scholar
  36. Soderstrom H, Sjodin AK, Carlstedt A, Forsman A (2004) Adult psychopathic personality with childhood-onset hyperactivity and conduct disorder: a central problem constellation in forensic psychiatry. Psychiatry Res 121:271–280CrossRefPubMedGoogle Scholar
  37. Soloff PH, Meltzer CC, Becker C, Greer PJ, Kelly TM, Constantine D (2003) Impulsivity and prefrontal hypometabolism in borderline personality disorder. Psychiatr Res Neuroimaging 123:153–163CrossRefGoogle Scholar
  38. Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI, Rapoport JL, Grady CL (1992) Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy. Arch Gen Psychiatry 49:690–694PubMedGoogle Scholar
  39. Van Elst LT, Woermann FG, LeMieux L, Thompson PJ, Trimble MR (2000) Affective aggression in patients with temporal lobe epilepsy: a quantitative MRI study of the amygdala. Brain 123: 234–243CrossRefPubMedGoogle Scholar
  40. Volkow ND, Tancredi L (1987) Neural substrates of violent behavior: a preliminary study with positron emission tomography. Br J Psychiatry 151:668–673PubMedGoogle Scholar
  41. Volkow ND, Tancredi L, Grant C, Gillespie H, Valentine A, Mulani N, Wang GJ, Hollister L (1995) Brain glucose metabolism in violent psychiatric patients: a preliminary study. Psychiatry Res 61:243–253CrossRefPubMedGoogle Scholar
  42. Woods RP, Mazziotta JC, Cherry SR (1993) MRI-PET registration with automated algorithm. J Comput Assist Tomogr 17:536–546PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Antonia S. New
    • 1
    • 2
  • Monte S. Buchsbaum
    • 2
  • Erin A. Hazlett
    • 2
  • Marianne Goodman
    • 1
  • Harold W. Koenigsberg
    • 1
  • Jenni Lo
    • 1
  • Lisa Iskander
    • 1
  • Randall Newmark
    • 2
  • Jesse Brand
    • 2
  • Karen O’Flynn
    • 1
  • Larry J. Siever
    • 1
  1. 1.Psychiatry Service-Mount Sinai School of Medicine and the Bronx VA Medical CenterBronxUSA
  2. 2.Neuroscience PET Laboratory, Department of PsychiatryMount Sinai School of MedicineNew YorkUSA

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