This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Several lines of evidence suggest that dysfunction of serotonin neurotransmission predisposes individuals to alcohol dependence and contributes to the maintenance of excessive alcohol consumption. A variety of studies have provided evidence that serotonin neurotransmission is reduced in the brain of alcohol-dependent subjects and alcohol-preferring animals. Alcohol-dependent populations have a high lifetime suicide rate, and alcoholism is one of two psychiatric disorders most frequently found in suicidal cases. Furthermore, major depression is a frequent co-morbid condition among individuals with alcohol dependence, and suicidal behavior and depression have also been linked to alterations in serotonin. It remains unclear what neurochemical substrate or mechanism is responsible for the deficit in serotonin neurotransmission in alcohol dependence or if serotonergic regulation is further diminished in alcohol-dependent subjects with major depression that exhibit suicidal behavior. This research will test the hypothesis that there is a deficit in serotonin neurotransmission in midbrain serotonin neurons in suicide subjects diagnosed with alcohol-dependence and major depression relative to non-suicide, non-depressed alcohol-dependent and normal control subjects which is caused by an alteration in one or more key neuronal regulators of serotonin biosynthesis. We will further examine gene and protein expression of several serotonin molecules including tryptophan hydroxylase, 5-HT(1A) receptors and specific serotonin transcription factors in the dorsal and median raphe nucleus of human postmortem specimens of two alcohol-use subject groups, a major depression group and a normal control subject group. The goals of this proposal are to understand the biochemical mechanisms underlying the deficiency in serotonin neurotransmission specifically in subjects committing suicide with alcohol dependence and co-morbid major depression. Given the seriousness, lethality and devastating consequences associated with suicidal behavior in alcohol-dependent populations, understanding the neurobiological mechanisms contributing to such harmful behavior in alcohol-dependent individuals may offer clues for developing new treatment strategies and possible avenues to prevent suicidal behavior in alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR017701-05
Application #
7381918
Study Section
Special Emphasis Panel (ZRR1-RI-A (01))
Project Start
2006-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
5
Fiscal Year
2006
Total Cost
$143,933
Indirect Cost
Name
University of Mississippi Medical Center
Department
Psychiatry
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
Greening, Leilani; Stoppelbein, Laura; Cheek, Kara (2017) Racial/ethnic disparities in the risk of posttraumatic stress disorder symptoms among mothers of children diagnosed with cancer and Type-1 diabetes mellitus. Psychol Trauma 9:325-333
Stoppelbein, Laura; McRae, Elizabeth; Greening, Leilani (2017) A Longitudinal Study of Hardiness as a Buffer for Posttraumatic Stress Symptoms in Mothers of Children with Cancer. Clin Pract Pediatr Psychol 5:149-160
Ginley, Meredith K; Bagge, Courtney L (2017) Psychiatric heterogeneity of recent suicide attempters: A latent class analysis. Psychiatry Res 251:1-7
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Stewart, Courtney; Yu, Yue; Huang, Jun et al. (2016) Effects of high intensity noise on the vestibular system in rats. Hear Res 335:118-127
Duncan, Jeremy W; Zhang, Xiao; Wang, Niping et al. (2016) Binge ethanol exposure increases the Krüppel-like factor 11-monoamine oxidase (MAO) pathway in rats: Examining the use of MAO inhibitors to prevent ethanol-induced brain injury. Neuropharmacology 105:329-340
Fisher, Lauren B; Overholser, James C; Dieter, Lesa (2015) Methods of committing suicide among 2,347 people in Ohio. Death Stud 39:39-43
Duncan, Jeremy; Wang, Niping; Zhang, Xiao et al. (2015) Chronic Social Stress and Ethanol Increase Expression of KLF11, a Cell Death Mediator, in Rat Brain. Neurotox Res 28:18-31
Stoppelbein, Laura; Greening, Leilani (2015) A longitudinal study of the role of cortisol in posttraumatic stress disorder symptom clusters. Anxiety Stress Coping 28:17-30
Johnson, Shakevia; Duncan, Jeremy; Hussain, Syed A et al. (2015) The IFN?-PKR pathway in the prefrontal cortex reactions to chronic excessive alcohol use. Alcohol Clin Exp Res 39:476-84

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