Bipolar DisorderSPECGENENCT01237158
Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT
An observational study of Bipolar Disorder, run by University of Sao Paulo at 1 site in Brazil.
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- How many people
- 140 participants
- Where
- 1 siteBrazil
- Study dates
- Oct 2010to Oct 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Bipolar Disorder Patients
Who may be able to join
- Bipolar disorder type I diagnose (DSM-IV criteria)
- Medication free (4 last weeks)
Who cannot join
- heavy smokers
- cannabis use
- recent alcohol abuse (14 days)
Trial locations and contacts
1 site in 1 country.
Marcio G Soeiro-de-Souza, MD contact
Brazil1 site, 1 recruiting
- Recruiting
Institute of Psychiatry HCFMUSP
São Paulo
Marcio G Soeiro-de-Souza, MD, mgss@usp.br
Marcio G Soeiro-de-Souza, MD
About this study
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
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| healthy controls | Not described | |
| bipolar disorder type I | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
association between GABA/glutamate brain levels and GAD1 polymorphisms
Measured: single evaluation
Secondary outcomes (1)
association between GABA/glutamate brain levels and Reelin polymorphisms
Measured: single evaluation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2010 (estimated)
- Study startOct 2010
- Primary completionOct 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01237158
- Sponsor's protocol ID
- nov 2010
- Acronym
- SPECGENE
- Status last verified
- Oct 2010
- First submitted
- 8 Nov 2010
- Last updated
- 16 Aug 2011
- Results posted
- No
- Data monitoring committee
- Yes
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. doi: 10.1016/j.biopsych.2010.02.023.
PubMed 20434133Straub 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.
PubMed 17767149Scotti-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.
PubMed 31993746Soeiro-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.
PubMed 28398341Soeiro-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.
PubMed 27207914
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Association Study Between GAD1 and Reelin Polymorphisms and GABA/Glutamate MRS in Bipolar Disorder Type 1 and Healthy Controls: SPECGENE PROJECT
- ClinicalTrials.gov ID
- NCT01237158
- Acronym / sponsor ID
- SPECGENE / nov 2010
- Conditions
- Bipolar Disorder
- Keywords
- GAD1,, GAD67,, bipolar,, GABA,, Glutamate,, Reelin,, Rln,, Spectroscopy
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- Oct 2010
- Primary completion
- Oct 2012 (estimated)
- First posted
- 9 Nov 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| healthy controls | – | – |
| bipolar disorder type I | – | – |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Bipolar Disorder Patients
Key inclusion criteria (2 listed)
- Bipolar disorder type I diagnose (DSM-IV criteria)
- Medication free (4 last weeks)
Key exclusion criteria (3 listed)
- heavy smokers
- cannabis use
- recent alcohol abuse (14 days)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
association between GABA/glutamate brain levels and GAD1 polymorphisms
Time frame: single evaluation
1 secondary outcome
association between GABA/glutamate brain levels and Reelin polymorphisms
Time frame: single evaluation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2011.
- Background: PubMed 20434133Tost 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.
- Background: PubMed 17767149Straub 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.
- Derived from this study: PubMed 31993746Scotti-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.
- Derived from this study: PubMed 28398341Soeiro-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.
- Derived from this study: PubMed 27207914Soeiro-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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcio G Soeiro-de-Souza, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bipolar Disorder, run by University of Sao Paulo at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 16 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Marcio G Soeiro-de-Souza, MD (mgss@usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
association between GABA/glutamate brain levels and GAD1 polymorphisms (time frame: single evaluation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01237158, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2011; AzTrials last refreshed its copy on 1 Nov 2026.