This proposal, entitled """"""""PTSD and drug dependence: neuroimaging of reward circuitry"""""""" is a response to NIDA Request for R01 Applications (#DA-04-001; Stress and Drug Abuse: Epidemiology, Etiology, Prevention and Treatment). The primary goal of this proposal is to investigate brain reward function as a potential neuropathological basis for substance use disorders (SUDs) comorbidity in posttraumatic stress disorder (PTSD). Basic neuroscience and clinical findings suggest that brain reward circuitry is altered by chronic stress exposure in ways that may be important for facilitating SUDs. We hypothesize that: 1) functionally impaired brain reward mechanisms may comprise a neural substrate underlying core PTSD symptoms of reduced reactivity to natural rewarding stimuli or emotional numbing and that 2) this neural substrate is further altered by the presence of comorbid SUDs. The proposed project is designed to test these hypotheses integrating functional magnetic resonance imaging, psychopharmacology and cognitive psychology to empirically measure reward responses in PTSD, cocaine dependence, PTSD with comorbid cocaine dependence and in health. The proposed experiments have already been successfully performed in separate cohorts of healthy volunteers and piloted in PTSD subjects with and without cocaine dependence. The published data and preliminary results suggest unique patterns of hemodynamic responses in the nucleus accumbens (NAc) and related structures during reward processing along with PTSD-related abnormalities in performance on a behavioral probe of reward function. Three distinct experimental paradigms to be used in this project include a) low doses of an FDA-approved euphorigenic drug, morphine, which can be safely administered to drug-naive subjects, b) social reward in the form of visual processing of attractive faces and c) monetary incentive stimuli incorporated into a gambling task. We expect to find that in PTSD patients the magnitude of the NAc's activation in response to the three rewarding stimuli will be smaller relative to healthy controls, but larger than in individuals with comorbid PTSD and cocaine dependence. This research plan will provide important leads for understanding and preventing the development of SUDs in the context of chronic stress exposure or PTSD. Furthermore our project may offer insights on the pathogenesis of emotional numbing symptoms, which cause severe disability not only in PTSD patients, but also in those suffering from other neuropsychiatric conditions such as SUDs, schizophrenia and major depression.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA017959-04
Application #
7237891
Study Section
Special Emphasis Panel (ZDA1-KXN-G (05))
Program Officer
Grant, Steven J
Project Start
2004-06-01
Project End
2010-05-31
Budget Start
2007-06-01
Budget End
2010-05-31
Support Year
4
Fiscal Year
2007
Total Cost
$385,610
Indirect Cost
Name
Mclean Hospital
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Elman, Igor; Gurvits, Tamara V; Tschibelu, Evelyne et al. (2013) Neurological soft signs in individuals with pathological gambling. PLoS One 8:e60885
Elman, Igor; Becerra, Lino; Tschibelu, Evelyne et al. (2012) Yohimbine-induced amygdala activation in pathological gamblers: a pilot study. PLoS One 7:e31118
Moulton, Eric A; Elman, Igor; Pendse, Gautam et al. (2011) Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images. J Neurosci 31:3795-804
Elman, Igor; Zubieta, Jon-Kar; Borsook, David (2011) The missing p in psychiatric training: why it is important to teach pain to psychiatrists. Arch Gen Psychiatry 68:12-20
Elman, Igor; Tschibelu, Evelyne; Borsook, David (2010) Psychosocial stress and its relationship to gambling urges in individuals with pathological gambling. Am J Addict 19:332-9
Elman, Igor; Lowen, Steven; Frederick, Blaise B et al. (2009) Functional neuroimaging of reward circuitry responsivity to monetary gains and losses in posttraumatic stress disorder. Biol Psychiatry 66:1083-90
Yamamoto, Rinah; Ariely, Dan; Chi, Won et al. (2009) Gender differences in the motivational processing of babies are determined by their facial attractiveness. PLoS One 4:e6042
Elman, Igor; Chi, Won H; Gurvits, Tamara V et al. (2008) Impaired reproduction of three-dimensional objects by cocaine-dependent subjects. J Neuropsychiatry Clin Neurosci 20:478-84
Hopper, James W; Pitman, Roger K; Su, Zhaohui et al. (2008) Probing reward function in posttraumatic stress disorder: expectancy and satisfaction with monetary gains and losses. J Psychiatr Res 42:802-7
Rott, D; Langleben, D D; Elman, I (2008) Cocaine decreases plasma insulin concentrations in non-diabetic subjects: a randomized double-blind study. Diabet Med 25:510-1

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