Internet and Psychiatry
  • Home
    • Editorials
    • Research news
    • Research papers
    • Interviews with eminent psychiatrists
    • Ten years ago
    • Fifteen years ago
  • Topics
    • Alcohol and Drug Abuse
    • Anxiety Disorders
    • Biomedical Science
    • Compulsive gambling
    • Disaster Medicine
    • Education
    • General Medicine
      • Acupuncture
      • Physical medicine and Rehabilitation
    • Human Rights
    • Interviews with eminent psychiatrists
    • Mood Disorders
      • Bipolar Disorder
      • Depression
      • Seasonal Affective Disorder
    • Neurological Disorders
    • Other Psychiatric Disorders
    • Posttraumatic Stress Disorder
    • Sexual Behavior
  • Books
    • Comorbidity of Depression and Alcohol Use Disorders
    • “Immigration and Mental Health” chapter abstracts
    • “Internet and Suicide” chapter abstracts
    • “Neurobiology of PTSD” chapter abstracts
    • “Suicidal Behavior in Alcohol…” chapter abstracts
    • “Suicide in the Military” chapter abstracts
    • “Terror and Suicide” chapter abstracts
    • “War and Suicide” chapter abstracts
  • Editors
    • Leo Sher, M.D.
    • Alexander Vilens, M.S.
  • Guests
    • Distinguished Guests
    • Our Contributors
  • Reflections
    • Poetry
    • Quotes

Alcohol and Drug Abuse

Effects of Acute Plasma Tryptophan Depletion on Serotonin Receptor Binding Using PET in Healthy Controls: Implications for Alcoholic Brain Disease

February 7, 2009

W. A. Williams1; R. E. Carson3; A. Heinz2; J. Bjork5; M. Enoch4; C. Geyer5; R. Rawlings5; D. Hommer5; D. Goldman4; P. Herscovitch6
1. Psychiatry, Yale Univ, New Haven, CT, USA.
2. Psychiatry, Humboldt Univ, Berlin, Germany.
3. PET Center, Yale Univ, New Haven, CT, USA.
4. Lab Neurogenetics, NIAAA, Bethesda, MD, USA.
5. Lab Clinical Studies, NIAAA, Bethesda, MD, USA.
6. PET Dept, NIH, Bethesda, MD, USA

Alcohol dependence (AD) is an etiologically heterogeneous syndrome determined by a complex interaction of genetic and environmental factors. We propose to investigate monoamine dysfunction in alcoholic patients by using acute tryptophan (TRP) depletion (ATD) and PET imaging.

Differences in 5-HT turnover (synthesis, metabolism, and release) in alcoholics may be involved in reinforcing responses to ethanol and alcohol seeking behaviors. To examine this question, we first studied 5-HT turnover and 5-HT1A receptor occupancy in healthy volunteers. We report the results of the first 5 subjects in this cohort. We hypothesize that diminished 5-HT release following ATD leads to decreased competition for 5-HT1A receptors by endogenous 5-HT, and greater 5-HT1A receptor binding of the radioligand [18F]FCWAY, a 5-HT1A receptor antagonist. ATD lowers brain 5-HT synthesis and release by decreasing plasma and brain TRP concentration. We administered a TRP-deficient amino acid mixture to acutely lower plasma TRP, the precursor for 5-HT synthesis. In humans, ATD decreases plasma TRP concentration, with a nadir occurring approximately 5 to 6 hr after drink administration. 5-hydroxyindoleacetic acid (5-HIAA), the principal metabolite of 5-HT and a neurochemical marker of neuronal 5-HT metabolism, also decreases.

[18F]FCWAY PET studies with concurrent CSF/plasma sampling were performed in 5 healthy volunteers, in a within-subject repeated measures design. The baseline PET scan was done before ATD on day 1. The active condition scan was done on day 2, 16 hr after ATD. The day 2 scan corresponds to the CSF 5-HIAA nadir. [18F]FCWAY was synthesized by the method of Lang. Dynamic scans were acquired over 2 hours on a GE Advance tomograph (3D mode; 6 mm resolution) following iv. bolus administration of 5 mCi of tracer. IMAGE PROCESSING. Dynamic PET images were motion-corrected, and converted to functional images of distribution volume (DV) using the metabolite-corrected arterial input function. Each subject’s MR image was registered to a Talairach template and this transformation was applied to the PET DV images. Cortical and subcortical regions of interest (ROIs), including the raphe, were drawn on structural MR images.

ROI analysis corrected for the free-fraction (f1) parent compound was performed. Comparing the day1 to day 2 scans, we found significant decreases in 5 subjects in 10 brain regions. The largest decrease, 25%, was localized to the raphe (p=0.023). The difference in f1, day1 vs day2, was -11.3% (p=0.012). In the raphe, there was a strong correlation (r=0.823) between day1 and day2 DV data, with intersubject variability being much greater than intrasubject variability.

Our data show a measurable effect of ATD on FCWAY/5-HT1A brain receptor binding. There were significant regional decreases in 5-HT1A receptor occupancy, post-ATD. This effect is opposite the hypothesized decrease in synaptic 5-HT/ligand receptor competition. We postulate that acute reduction in 5-HT turnover leads to a compensatory decrease in 5-HT1A auto- and hetero- receptor density. These effects may combine to produce lower FCWAY binding after ATD. It is unclear whether receptor density in other sub-cortical and cortical regions is behaving similarly. However, lower brainstem 5-HT1A receptor density could account for the marked reduction in FCWAY binding seen in the raphe. These findings in healthy subjects may have important implications for the pathophysiology of acute and chronic alcohol dependence.

Related Posts

Alcohol and Drug Abuse /

Low testosterone in a young combat veteran with dual diagnosis and suicidal behavior: a case study

Alcohol and Drug Abuse /

Alcohol and drug use among adolescents: an educational overview

Alcohol and Drug Abuse /

The impact of cigarette excise taxes on smoking cessation rates from 1994 to 2010 in Poland, Russia, and Ukraine

‹ CNS Serotonergic Functioning, Alcohol, Genotype X by Rearing Interactions and Violence Using a Nonhuman Primate Model › Dysregulation of the Hypothalamic-Pituitary-Adrenal Axis in Alcohol-Dependent Self-Administering Rats

Editorials

  • Suicide in combat veterans
  • Navigating ethical dilemmas in genetic testing for Huntington’s Disease
  • Loneliness: Surgeon General Dr. Murthy’s warning
  • Intranasal esketamine ought to be more widely available

Research Papers

  • COVID-19 mortality in Europe and the ’Iron Curtain’ between East and West
  • Examination of depressive signs and symptoms among 803 University students in seven Universities and Colleges. Hungary, Romania, Serbia.
  • Examination of spirituality and the dimensions of spirituality among 803 students in seven different Universities. Hungary, Romania and Serbia.
  • Examination of depressive signs and symptoms among 932 students in eight different secondary schools in Hungary

Research News

  • Regular sleep patterns are more important to health and longevity than spending eight hours in bed
  • Age and antisuicidal effect of lithium
  • Obesity is associated with increased risk for psychiatric disorders
  • The effect of multivitamin supplementation on memory in older adults

Latest News

  • Suicide rates in the United States in 2022
  • Suicide rates in the United States in 2001-2021
  • Leading world experts on suicide. Expertscape, the January 9, 2023, report
  • Best universities in the world

Interviews with eminent psychiatrists

  • Interview with Professor Shih-Ku Lin
  • Interview with Professor Masahito Fushimi
  • Interview with Professor Maurizio Pompili
  • Interview with Professor Marco Sarchiapone

Ten Years Ago

  • Combined dexamethasone suppression-corticotrophin-releasing hormone stimulation test in medication-free individuals with major depression and healthy controls
  • Plasma testosterone levels in bipolar suicide attempters
  • Teaching medical professionals and trainees about suicide prevention
  • Suicidal ideation in depressed patients with or without comorbid posttraumatic stress disorder treated with selective serotonin reuptake inhibitors

Back to Top

  • About
  • Contact
  • Privacy Policy
  • Terms and Conditions
Copyright © 2023 AVCalc LLC. All rights reserved worldwide.