Despite the wealth of data supporting the hypothesis that central pre- synaptic serotonin (5-HT) function is reduced in male patients with suicidal and/or impulsive aggressive behaviors, little is conclusively known concerning the relationship between these behaviors and indices of post-synaptic or overall (""""""""integrated"""""""" or """"""""net"""""""") 5-HT function. Moreover, since little is known regarding the relationships among different putative indices of 5-HT function, our understanding of how to best interpret these data is limited. Finally, since few studies of central 5-HT activity and impulsive aggressive behavior in female subjects have been performed, little is known regarding these issues in women and the possibility of a gender difference in these relationships remains to be tested. In order to address these issues we propose to conduct three parallel studies which assess the relationship between central 5-HT function and suicidal and impulsive aggressive behavior in a psychiatric and in a normal control population. We propose to examine three indices of central 5-HT function in male and female patients with DSM-III-R personality disorder (PD) and in age and sex matched normal controls. These indices include: a) lumbar CSF concentrations of 5-HIAA as an index of """"""""pre-synaptic"""""""" 5-HT activity; b) PRL responses to the direct post-synaptic 5-HT agonist m- chlorophenylpiperazine (m-CPP) as an index of """"""""post-synaptic"""""""" receptor function; and c) PRL responses to the 5-HT releasing/uptake-inhibiting agent d-fenfluramine (d-FEN) as an index of integrated """"""""pre-/post-synaptic"""""""" function). We have chosen to study personality disorder patients as the experimental group because suicidal and impulsive aggressive behaviors exist across a wide continuum in this group and because of previous data which indicate that PD patients consistently demonstrate inverse relationships between indices of central 5-HT function and both suicidal and impulsive aggressive behavior. Based upon previous work, we hypothesize that: a) the proposed indices of central 5-HT function will be intercorrelated; b) CSF 5-HIAA concentrations (5-HT """"""""pre-synaptic"""""""") and PRL responses to both m-CPP (5-HT """"""""post- synaptic"""""""") and d-FEN (5-HT """"""""integrated pre-/post-synaptic"""""""") will be inversely related to suicidal and impulsive aggressive in behaviors in both male and female PD patients; and c) relationships between the PRL response to d-FEN, as an index of """"""""integrated pre-/post-synaptic"""""""" index of 5-HT function, and those observed between the above behavioral variables will be stronger than those observed with either CSF 5-HIAA 95-HT """"""""pre-synaptic"""""""") or the PRL response to m-CPP (""""""""post-synaptic"""""""").

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH046948-03
Application #
3386770
Study Section
Psychopathology and Clinical Biology Research Review Committee (PCB)
Project Start
1991-04-01
Project End
1995-03-31
Budget Start
1993-04-01
Budget End
1994-03-31
Support Year
3
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
Puhalla, Alexander A; McCloskey, Michael S; Brickman, Lauren J et al. (2016) Defense styles in Intermittent Explosive Disorder. Psychiatry Res 238:137-142
Fanning, Jennifer R; Meyerhoff, Jonah J; Lee, Royce et al. (2014) History of childhood maltreatment in intermittent explosive disorder and suicidal behavior. J Psychiatr Res 56:10-7
Fettich, Karla C; McCloskey, Michael S; Look, Amy E et al. (2014) Emotion regulation deficits in intermittent explosive disorder. Aggress Behav :
Marseille, Robert; Lee, Royce; Coccaro, Emil F (2012) Inter-relationship between different platelet measures of 5-HT and their relationship to aggression in human subjects. Prog Neuropsychopharmacol Biol Psychiatry 36:277-81
Coccaro, Emil F (2011) Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Compr Psychiatry 52:119-25
Dakwar, Elias; Popii, Marias; Coccaro, Emil F (2011) Lifetime history of cigarette smoking associated with aggression and impulsivity in both healthy and personality disordered volunteers. J Pers Disord 25:645-55
Lee, Royce; Coccaro, Emil F (2010) Plasma homovanillic acid correlates inversely with history of childhood trauma in personality disordered and healthy control adults. J Neural Transm (Vienna) 117:1327-34
Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J (2010) Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology 35:435-44
Coccaro, Emil F; Lee, Royce; Kavoussi, Richard J (2010) Inverse relationship between numbers of 5-HT transporter binding sites and life history of aggression and intermittent explosive disorder. J Psychiatr Res 44:137-42
Almeida, Marcela; Lee, Royce; Coccaro, Emil F (2010) Cortisol responses to ipsapirone challenge correlate with aggression, while basal cortisol levels correlate with impulsivity, in personality disorder and healthy volunteer subjects. J Psychiatr Res 44:874-80

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