MedPath

Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT

Conditions
Bipolar Disorder
Registration Number
NCT01237158
Lead Sponsor
University of Sao Paulo
Brief Summary

Background: The pathophysiological mechanisms of bipolar disorder are not completely clarified and several hypothesis have already been formulated including the role of monoamines, gama amino butyric acid (GABA) and glutamate. GABA is the main inhibitory neurotransmitter while glutamate is the main excitatory neurotransmitter. Genes that play a role in GABA metabolism and in the activity of GABA neurons are very important to understand the GABA function, once they affect neurodevelopment and its dysfunctions may predispose to neuropsychiatric diseases. The two genes that are going to be study in this project are glutamic acid decarboxylase (GAD1) and reelin (Reln). The enzyme glutamic acid descarboxylase (GAD67) metabolizes glutamate in GABA in the pre synaptic neuronal regions and is coded by the gene GAD1. Reelin is secretory serine protease with dual roles in mammalian brain: embryologically, it guides neurons and radial glial cells to their corrected positions in the developing brain; in adult brain, Reelin is involved in a signaling pathway which underlies neurotransmission, memory formation and synaptic plasticity. Magnetic resonance spectroscopy (MRS) studies on bipolar disorder show a number of alterations in cerebral level of GABA and glutamate in different cerebral areas when compared to healthy subjects and other mood disorders. Objective: Investigate in bipolar patients and healthy controls the association of GAD1 and Reln single nucleotide polymorphisms(SNP) and cerebral levels of GABA/glutamate on MRS. Methods: 70 symptomatic bipolar I patients medication free and 70 healthy controls are going to be genotyped for GAD1 and Reln SNPs and GABA/glutamate MRS.

Key words: GAD1, GAD67, bipolar, GABA, Glutamate, Reelin, Rln, Spectroscopy.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
140
Inclusion Criteria
  • Bipolar disorder type I diagnose (DSM-IV criteria)
  • Medication free (4 last weeks)
Exclusion Criteria
  • heavy smokers
  • cannabis use
  • recent alcohol abuse (14 days)

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
association between GABA/glutamate brain levels and GAD1 polymorphismssingle evaluation
Secondary Outcome Measures
NameTimeMethod
association between GABA/glutamate brain levels and Reelin polymorphismssingle evaluation

Trial Locations

Locations (1)

Institute of Psychiatry HCFMUSP

🇧🇷

Sao Paulo, Brazil

© Copyright 2025. All Rights Reserved by MedPath