Primary objective: - Investigate the effects of childhood maltreatment on basal and stress-induced in vivo metabolite concentrations in the brain measured with 7T-MRS. Secondary objectives: - Correlate the endocrine, autonomic and subjective stress…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
effecten van stress op MRS metabolieten bij jeugdtrauma
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary parameter: Concentrations of glutamate, glutamine, GABA, choline, NAA,
creatine, myoinositol and lactate as measured by 7T-MRS.
Secondary outcome
Secondary parameters:
- Basal and stress-induced levels of cortisol, alpha amylase, and heart rate.
- Perceived stress levels.
- (Epi)genetic variation in a limited number of stress genes.
- Plasma GABA levels
Background summary
Childhood maltreatment has a substantial impact on the brain during a critical
developmental period and is a major risk factor for the development of almost
all psychiatric disorders. However, the neurobiological mechanisms in the brain
underlying these detrimental effects are not well understood. Magnetic
resonance spectroscopy (MRS) non-invasively measures biologically important
molecules in the living brain, yielding quantitative information on
neurotransmitters, energy metabolism, and neuronal integrity. Therefore, this
in vivo technique can probe the neurochemical correlates of childhood
maltreatment. In light of the profound and long-lasting effects of childhood
maltreatment on the stress system, this study integrates neuroimaging with an
experimental stress design. Repeatedly measuring MRS metabolites prior to and
following exposure to acute stress provides a dynamic readout of stress
vulnerability.
Study objective
Primary objective:
- Investigate the effects of childhood maltreatment on basal and stress-induced
in vivo metabolite concentrations in the brain measured with 7T-MRS.
Secondary objectives:
- Correlate the endocrine, autonomic and subjective stress response with
stress-induced changes of MRS metabolites.
- Investigate the association between (epi)genetic variation in stress-related
genes and stress-induced changes in the MRS metabolites.
- Investigate the association between plasma GABA levels and
childhood trauma
Study design
A small monocenter intervention study in healthy male individuals. Two
experimental groups (n=60 each) are formed based on low and high exposure to
childhood maltreatment. MRS levels of various in vivo metabolites are measured
in the brain under basal and acute stress conditions using 7T-MRS. A
between-subject design will be applied and participants will be randomized to
either the stress condition (Trier Social Stress Test, TSST) or a validated
control condition.
Intervention
Stress test or a control test randomized.
o Stress: the Trier Social Stress Test (TSST), an validated and standardized
test to induce psychosocial stress in laboratory settings.
o Control: a validated protocol with no psychosocial stress components.
Study burden and risks
Risks for participants are minimal. Participants are invited to the UMCU two
times with a maximum duration of 3 hours and 50 minutes and sufficient time for
breaks. No direct benefits are present for participants. All participants will
be given a reimbursement of ¤50,- for their cooperation and time, also
potential travel costs will be reimbursed.
- Screening
- Potential participants can fill in questionnaires via a website (General
screening list, MRI screening list, Life Stressor Checklist Revised (LSC-R),
Childhood Trauma Questionnaire (CTQ) en State Trait Anxiety Inventory (STAI).
Identity of the subject will be encoded on this questionnaire, in a way that
the identity can only be known by the researcher. Participants will be
selected, based on their answers on these questionnaires.
- First visit
- Inclusion, collect blood samples, complete several questionnaires, and
perform a first short scan to acquaint subjects with the 7T scanner.
- Total duration: 85 min (of which 15 min in the 7T scanner)
- Second visit
- Two 45 min MRS scans in the 7T scanner before and after either the Trier
Social Stress Test (TSST) or a control protocol.
- Total duration: 145 min (of which 90 min in the 7T scanner)
Regarding a risk analysis, a negligible risk for participants is estimated. The
stress test involves a speech test and/or a short arithmetic test that does not
lead to extreme perceived stress levels. The control protocol also consists of
a speech and/or short arithmetic task, but without the psychosocial stress
components. The stress test has often been applied without any known lasting
disadvantageous effects as reviewed in literature.1 This includes two previous
studies from our group outside the MRI scanner (the CHOICE study [METC 11-222)
and Epistress [METC 11-259]) and an ongoing stress study measuring GABA and
glutamate levels in the 7T-MRI scanner (Columbus study [METC 12-563]) which
show no detrimental effects of the combination of stress and 7T scans and the
feasibility of repeatedly measuring metabolites in the MRI scanner. The scan
protocol will be carried out in accordance with this protocol and protocol
07-235 (*MRI development for 7T (and lower field strengths)*).
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
- Male sex
- Age between 18 and 40 years old
- Either low or high levels of childhood maltreatment
Exclusion criteria
General exclusion criteria:
- Incapability of giving informed consent
- Lack of fluency in the Dutch language or speech impairments
- Irregular sleep/wake rhythm (e.g., regular nightshifts or cross timeline travel).
- Use of medication which might influence the stress response, such as psychotropics, beta blockers, ACE inhibitors and any hormonal treatment.
- Major medical history including history of closed or open head injury.
- Acute minor medical illness within the three weeks prior to testing
- History of any psychiatric, neurological or endocrine disorder including claustrophobia and alcohol abuse or dependence
- Self-reported current smoking in the last 2 weeks
- Self-reported current or past drug use in the last 2 weeks
- Ferrous objects in or around the body according to default checklist present at 7T scanner (version defined by METC protocol 07-235: *MRI development for 7T (and lower field strengths)* ;Acute exclusion criteria on 2nd and 3rd visit:
- Any acute inflammatory disease
- Physical exertion within the last 2 hours
- Drink other than water or any food within the last 2 hours
- Any alcohol use in the last 24 hours
- Positive urine screen on the presence of amphetamines (including MDMA), barbiturates, cannabinoids, benzodiazepines, cocaine and opiates)
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 | NL48847.041.14 |