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

The recruitment status of this study is unknown because the information has not been verified recently.

Verified October 2010 by University of Sao Paulo.
Recruitment status was Recruiting

Sponsor:

Collaborator:

Fundação de Amparo à Pesquisa do Estado de São Paulo

Information provided by:

University of Sao Paulo

ClinicalTrials.gov Identifier:

NCT01237158

First received: November 8, 2010

Last updated: August 15, 2011

Last verified: October 2010

History of Changes

Purpose

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.

Condition
Bipolar Disorder

Study Type:	Observational
Study Design:	Observational Model: Case Control Time Perspective: Cross-Sectional
Official Title:	Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder

Drug Information available for: Glutamic Acid

U.S. FDA Resources

Further study details as provided by University of Sao Paulo:

Primary Outcome Measures:

association between GABA/glutamate brain levels and GAD1 polymorphisms [ Time Frame: single evaluation ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

association between GABA/glutamate brain levels and Reelin polymorphisms [ Time Frame: single evaluation ] [ Designated as safety issue: No ]

Estimated Enrollment:	140
Study Start Date:	October 2010
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Groups/Cohorts
healthy controls
bipolar disorder type I

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes
Sampling Method:	Probability Sample

Study Population

Bipolar Disorder Patients

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01237158

Contacts

Contact: Marcio G Soeiro-de-Souza, MD

mgss@usp.br

Locations

Brazil
Institute of Psychiatry HCFMUSP	Recruiting
Sao Paulo, Brazil
Contact: Marcio G Soeiro-de-Souza, MD mgss@usp.br
Principal Investigator: Marcio G Soeiro-de-Souza, MD

Sponsors and Collaborators

University of Sao Paulo

Fundação de Amparo à Pesquisa do Estado de São Paulo

More Information

Additional Information:

Related Info This link exits the ClinicalTrials.gov site

Publications:

Tost H, Lipska BK, Vakkalanka R, Lemaitre H, Callicott JH, Mattay VS, Kleinman JE, Marenco S, Weinberger DR. No effect of a common allelic variant in the reelin gene on intermediate phenotype measures of brain structure, brain function, and gene expression. Biol Psychiatry. 2010 Jul 1;68(1):105-7.

Straub RE, Lipska BK, Egan MF, Goldberg TE, Callicott JH, Mayhew MB, Vakkalanka RK, Kolachana BS, Kleinman JE, Weinberger DR. Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry. 2007 Sep;12(9):854-69. Epub 2007 May 1.

Responsible Party:	Ricardo Alberto Moreno, University of Sao Paulo
ClinicalTrials.gov Identifier:	NCT01237158 History of Changes
Other Study ID Numbers:	nov 2010
Study First Received:	November 8, 2010
Last Updated:	August 15, 2011
Health Authority:	Brazil: SISNEP (National committee for ethics in research)

Keywords provided by University of Sao Paulo:

GAD1,
GAD67,
bipolar,
GABA,
Glutamate,

Reelin,
Rln,
Spectroscopy
euthymic bipolar I patients

Additional relevant MeSH terms:

Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders

ClinicalTrials.gov processed this record on May 22, 2013

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