Major depression is a significant independent risk factor for the development of ischemic heart disease and is a potentially lethal comorbid condition in post-myocardial infarction patients. The pathophysiology that links major depression to the occurrence of heart disease is not known. Preliminary observations indicate that platelet reactivity is increased in depression, which implies that depressed patients may be prone to thrombus formation, hence at increased risk for catastrophic cardiac events. There are considerable data indicating that the serotonergic system is altered in depression, both in the central nervous system (CNS) and in the platelets. In the periphery, the most notable and consistently replicated observation of serotonergic alteration is an increased B max for the serotonin-2A (5-HT2A) receptor on the platelets of depressed individuals. The platelet 5-HT2A receptor plays a central role in platelet reactivity and thrombus formation, and may be involved in regulating the expression of platelet specific genes in megakaryocytes, the cells from which platelets are derived. While not tested directly, the overarching hypothesis for this proposal is that major depression adversely increases platelet reactivity, which leads to increased risk of developing heart disease. The principal hypotheses that will be tested are that: 1) Platelets from depressed patients are produced in a """"""""upregulated"""""""" state, with increased amounts of a number of transcripts that encode platelet specific genes, the result being the platelets are more reactive and prone to thrombus formation. 2) The platelet serotonergic system, in particular the 5-HT2A receptor, is altered in depression which in turn contributes to the increased platelet reactivity observed in depression, and the relevant alteration may occur in the megakaryocytes. 3) Alterations in the concentration of one or more humoral factors (interleukins, cytokines, stress hormones) orchestrate the alterations in platelet reactivity and serotonergic functioning observed in depression. Patients suffering from major depression will be recruited and their condition treated. Their platelets will be sampled before and after treatment and the amounts of transcripts that encode platelet reactivity molecules will be measured. The circulating concentration of three hormones, cortisol, interleukin-1 and interleukin-6 will be measured before and after treatment, and correlated to platelet reactivity.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Wilde, David B
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Emory University
Schools of Medicine
United States
Zip Code
Garlow, Steven J; Dunlop, Boadie W; Ninan, Philip T et al. (2012) The combination of triiodothyronine (T3) and sertraline is not superior to sertraline monotherapy in the treatment of major depressive disorder. J Psychiatr Res 46:1406-13
Purselle, David C; Heninger, Michael; Hanzlick, Randy et al. (2009) Differential association of socioeconomic status in ethnic and age-defined suicides. Psychiatry Res 167:258-65
Boone, Ericka M; Hawks, Brian W; Li, Wei et al. (2008) Genetic regulation of hypothalamic cocaine and amphetamine-regulated transcript (CART) in BxD inbred mice. Brain Res 1194:1-7
Garlow, Steven J; Purselle, David C; Heninger, Michael (2007) Cocaine and alcohol use preceding suicide in African American and white adolescents. J Psychiatr Res 41:530-6
Garlow, Steven J; Boone, Ericka; Kinkead, Becky et al. (2006) Genetic analysis of the hypothalamic neurotensin system. Neuropsychopharmacology 31:535-43
Garlow, Steven J; Purselle, David; Heninger, Michael (2005) Ethnic differences in patterns of suicide across the life cycle. Am J Psychiatry 162:319-23
Garlow, Steven J; Boone, Ericka; Li, Wei et al. (2005) Genetic analysis of the hypothalamic corticotropin-releasing factor system. Endocrinology 146:2362-8
Garlow, Steven J; Purselle, David; D'Orio, Barbara (2003) Cocaine use disorders and suicidal ideation. Drug Alcohol Depend 70:101-4
Garlow, Steven J (2002) Age, gender, and ethnicity differences in patterns of cocaine and ethanol use preceding suicide. Am J Psychiatry 159:615-9
Garlow, Steven J; D'Orio, Barbara; Purselle, David C (2002) The relationship of restrictions on state hospitalization and suicides among emergency psychiatric patients. Psychiatr Serv 53:1297-300