Identification of genetic variations that control monoamine and amino acid metabolism in humans, by translating recent genetic findings in non-human primates to a human cohort.
ID
Source
Brief title
Condition
- Mood disorders and disturbances NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Levels of HVA, 5-HIAA and MHPG in CSF will be tested for association with a set
of single nucleotide polymorphisms (SNPs). The DNA region of interest is the
chromosome region that is homologous to the region that was recently found to
be linked with MAM levels in vervet monkeys. Once identified, the effect of
associated polymorphisms on RNA expression of monoamine genes will be
investigated. MAM levels and associated genotypes will be related to specific
behavioral traits, as assessed through validated questionnaires.
Secondary outcome
As a secondary parameter, we will measure CSF amino acid concentrations and
correlate these quantitatively to candidate genotypes and behavioral traits as
assessed with the abovementioned questionnaires.
Background summary
Signaling mediated by monoamines (MA) -such as the neurotransmitters serotonin
(5-HT), norepinephrine (NE) and dopamine (DA)- is thought to be compromised in
many psychiatric disorders. Knowledge of the mechanisms that determine the
levels of monoamines in the brain could increase our insight into the
pathophysiology of many psychiatric diseases, which in turn could be helpful in
developing new effective treatments. The turnover of DA, 5-HT and NE in the
brain may be estimated by measuring their respective metabolites homovanillic
acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and
3-methoxy-4-hyrdoxy-phenylethyleneglycol (MHPG) in cerebrospinal fluid (CSF).
Previous research has shown monoamine metabolites (MAM) in CSF to be party
under influence of genetic factors (Jönsson et al 2004). A recent quantitative
trait locus (QTL) study of MAM concentrations in the CSF of vervet monkeys
found genetic linkage on chromosome 9, which is homologous to human chromosome
10 (Freimer et al 2007).
In addition, previous research has shown that CSF amino acid (such as
glutamate, glycine and aspartate) concentrations is aberrant in depression
(Frye et al 2007).
Study objective
Identification of genetic variations that control monoamine and amino acid
metabolism in humans, by translating recent genetic findings in non-human
primates to a human cohort.
Study design
This study will be a cross-sectional, naturalistic study.
Study burden and risks
Spinal and venous canules are routinely inserted as part of the surgical
procedure. The study will involve the collection and analysis of small amounts
of CSF and venous blood through these existing lines, which does not constitute
an additional risk. Phenotyping will require that subjects fill out online
questionnaires (40-45 minutes) at a time that is convenient for them.
Universiteitsweg 100
Utrecht 3584 CG
NL
Universiteitsweg 100
Utrecht 3584 CG
NL
Listed location countries
Age
Inclusion criteria
Military personnel and civilians referred for surgical procedures under spinal anesthesia whose four grandparents were born in The Netherlands will be included.
Exclusion criteria
Exclusion criteria are: age < 18 and > 58 years old and the use of benzodiazepines shortly before entering the operating theatre.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL23042.041.08 |