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

NCT01237158 | Unknown DMC

• 1 other identifier: nov 2010
• Study Type: observational
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

Bipolar Disorder

Keywords

GAD1,; GAD67,; bipolar,; GABA,; Glutamate,; Reelin,; Rln,; Spectroscopy; euthymic bipolar I patients

Outcome Measures

Primary Outcomes (1)

• association between GABA/glutamate brain levels and GAD1 polymorphisms

  single evaluation

Secondary Outcomes (1)

• association between GABA/glutamate brain levels and Reelin polymorphisms

  single evaluation

Study Arms (2)

healthy controls

bipolar disorder type I

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Bipolar Disorder Patients

You may qualify if:

• Bipolar disorder type I diagnose (DSM-IV criteria)
• Medication free (4 last weeks)

You may not qualify if:

• heavy smokers
• cannabis use
• recent alcohol abuse (14 days)

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator

Study Sites (1)

Institute of Psychiatry HCFMUSP

São Paulo, Brazil

RECRUITING

Related Publications (5)

• 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.

  PMID: 20434133 BACKGROUND

• 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. doi: 10.1038/sj.mp.4001988. Epub 2007 May 1.

  PMID: 17767149 BACKGROUND

• Scotti-Muzzi E, Chile T, Moreno R, Pastorello BF, da Costa Leite C, Henning A, Otaduy MCG, Vallada H, Soeiro-de-Souza MG. ACC Glu/GABA ratio is decreased in euthymic bipolar disorder I patients: possible in vivo neurometabolite explanation for mood stabilization. Eur Arch Psychiatry Clin Neurosci. 2021 Apr;271(3):537-547. doi: 10.1007/s00406-020-01096-0. Epub 2020 Jan 28.

  PMID: 31993746 DERIVED

• Soeiro-de-Souza MG, Lafer B, Moreno RA, Nery FG, Chile T, Chaim K, da Costa Leite C, Machado-Vieira R, Otaduy MC, Vallada H. The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder. Transl Psychiatry. 2017 Apr 11;7(4):e1086. doi: 10.1038/tp.2017.57.

  PMID: 28398341 DERIVED

• Soeiro-de-Souza MG, Pastorello BF, Leite Cda C, Henning A, Moreno RA, Garcia Otaduy MC. Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study. Int J Neuropsychopharmacol. 2016 Aug 12;19(8):pyw032. doi: 10.1093/ijnp/pyw032. Print 2016 Aug.

  PMID: 27207914 DERIVED

MeSH Terms

Conditions

Bipolar Disorder

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders

Central Study Contacts

Marcio G Soeiro-de-Souza, MD

CONTACT

mgss@usp.br

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 8, 2010
• First Posted: November 9, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2012
• Last Updated: August 16, 2011

Record last verified: 2010-10

Locations

BR (1)