Abstract

The proposed studies are designed to evaluate 5-hydroxytryptophan transporter (5-HTT) binding of [S11C] McN5652 in midbrain and 5-HT2a receptor binding of [S11C] MDLIOO9O7 in orbital frontal cortex in 40 patients with impulsive aggressive personality disorders and 40 normal volunteer controls controlling for gender, age, season of the year, and other clinical/demographic variables. It is hypothesized that 5-HTT binding will be reduced in the impulsive aggressive personality disorder patients compared to normal controls, while 5-HT2a receptor binding will be increased in impulsive aggressive personality disorder patients compared to normal controls. These proposed studies would be the first to explicitly evaluate these components of the serotonergic system In vivo in impulsive aggressive personality disorder patients, but build on a large body of data regarding serotonergic abnormalities in impulsive aggression.
The specific aims of this proposal are to: I) Identify and clinically characterize 40 impulsive/aggressive personality disorder patients (20 males, 20 females) as defined by DSM-lV criteria in Methodsas well as 40 normal volunteer control subjects (20 males, 20 females) over four years, 2) Measure [S11C] McN5652binding by Positron Emission Tomography (PET) scan in the midbrain region of the impulsive aggressive personality disorder patients and the normal control comparison group, 3) Measure binding of [S11C] MDLIOO9O7 by PET scan in orbital frontal cortex of impulsive/aggressive personality disorder patients and the normal control comparison group. Secondary analyses include the correlation of ratings of impulsive aggression in the impulsive personality disorder cohort in relation to both the 5-HTT binding and the 5-HT2a receptor binding and the correlation of specific 5-HiT and 5-Hi2a receptor binding with polymorphisms of the 5-HTT and 5-HT2a receptor respectively obtained through other funding. The proposed study will enable a better understanding of the character of serotonergic dysfunction in impulsive/aggression.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH063875-04
Application #
6931203
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Meinecke, Douglas L
Project Start
2002-08-01
Project End
2008-02-29
Budget Start
2005-08-01
Budget End
2008-02-29
Support Year
4
Fiscal Year
2005
Total Cost
$416,836
Indirect Cost

  Institution

Name
Mount Sinai School of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029

  Publications

van de Giessen, Elsmarieke; Rosell, Daniel R; Thompson, Judy L et al. (2014) Serotonin transporter availability in impulsive aggressive personality disordered patients: a PET study with [11C]DASB. J Psychiatr Res 58:147-54
Perez-Rodriguez, M Mercedes; Weinstein, Shauna; New, Antonia S et al. (2010) Tryptophan-hydroxylase 2 haplotype association with borderline personality disorder and aggression in a sample of patients with personality disorders and healthy controls. J Psychiatr Res 44:1075-81
Rosell, Daniel R; Thompson, Judy L; Slifstein, Mark et al. (2010) Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry 67:1154-62
Look, Amy E; Flory, Janine D; Harvey, Philip D et al. (2010) Psychometric properties of a short form of the Affective Lability Scale (ALS-18). Pers Individ Dif 49:187-191
Stanley, Barbara; Siever, Larry J (2010) The interpersonal dimension of borderline personality disorder: toward a neuropeptide model. Am J Psychiatry 167:24-39
McCloskey, Michael S; New, Antonia S; Siever, Larry J et al. (2009) Evaluation of behavioral impulsivity and aggression tasks as endophenotypes for borderline personality disorder. J Psychiatr Res 43:1036-48
Flory, Janine D; Yehuda, Rachel; Grossman, Robert et al. (2009) Childhood trauma and basal cortisol in people with personality disorders. Compr Psychiatry 50:34-7
Siever, Larry J (2008) Neurobiology of aggression and violence. Am J Psychiatry 165:429-42
Flory, Janine D; Xu, Ke; New, Antonia S et al. (2007) Irritable assault and variation in the COMT gene. Psychiatr Genet 17:344-6
Flory, Janine D; Harvey, Philip D; Mitropoulou, Vivian et al. (2006) Dispositional impulsivity in normal and abnormal samples. J Psychiatr Res 40:438-47

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