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

Bipolar Disorder Clinical Trial

— SPECGENE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01237158
• Other study ID #: nov 2010
• Status: Recruiting
• Phase: N/A
• First received: November 8, 2010
• Last updated: August 15, 2011
• Start date: October 2010

Study information

• Verified date: October 2010
• Source: University of Sao Paulo
• Contact: Marcio G Soeiro-de-Souza, MD
• Email: mgss[@]usp.br
• Is FDA regulated: No
• Health authority: Brazil: SISNEP (National committee for ethics in research)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 35 Years

Eligibility

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

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Bipolar Disorder

Locations

Country	Name	City	State
Brazil	Institute of Psychiatry HCFMUSP	Sao Paulo

Sponsors (2)

Lead Sponsor	Collaborator
University of Sao Paulo	Fundação de Amparo à Pesquisa do Estado de São Paulo

Country where clinical trial is conducted

Brazil, 

References & Publications (2)

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. — View Citation

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. doi: 10.1016/j.biopsych.2010.02.023. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	association between GABA/glutamate brain levels and GAD1 polymorphisms		single evaluation	No
Secondary	association between GABA/glutamate brain levels and Reelin polymorphisms		single evaluation	No

External Links

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