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

Status

UNKNOWN

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT01237158

Acronym

SPECGENE

Enrollment

140

Registered

2010-11-09

Start date

2010-10-31

Completion date

Unknown

Last updated

2011-08-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar Disorder

Keywords

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

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

CROSS_SECTIONAL

Eligibility

Sex/Gender

ALL

Age

18 Years to 35 Years

Healthy volunteers

Yes

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)

Design outcomes

Primary

Measure	Time frame
association between GABA/glutamate brain levels and GAD1 polymorphisms	single evaluation

Secondary

Measure	Time frame
association between GABA/glutamate brain levels and Reelin polymorphisms	single evaluation

Countries

Brazil

Contacts

Primary ContactMarcio G Soeiro-de-Souza, MD

mgss@usp.br

Outcome results