Primary objective: Investigate the effects of acute stress on resting state and task-induced connectivity in the brain of healthy individuals and unaffected siblings of schizophrenia patients. Secondary objectives: - Correlate the endocrine stress…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
effecten van stress op connectiviteit van het brein
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Task-induced and resting state functional connectivity between the prefrontal
cortex and amygdala
Secondary outcome
- Basal and stress-induced levels of cortisol, alpha amylase, heart rate and
perceived stress levels.
- (Epi)genetic variation in a limited number of stress genes.
Background summary
Stress increases the risk for psychotic symptoms, both in schizophrenia and in
the general population. It is currently unknown how stress causes these
detrimental effects and what the underlying neurobiological mechanisms are. The
overall aim of this study is to investigate how stress affects the brain by
examining functional connectivity.
Recent neuroimaging studies at the UMCU have established impairments of both
structural and functional connectivity in unaffected siblings of schizophrenia
patients. Therefore, this study will also study unaffected siblings of
schizophrenia patients. This provides a unique opportunity to investigate how
acute stress affects connectivity in the vulnerable brain in which connectome
abnormalities are already present.
Repeatedly measuring brain activity with functional MRI (fMRI) allows the
assessment of both the spatial and temporal characteristics of stress on
neuronal connectivity. This is relevant as the effects of stress follow a
distinct temporal pattern. Immediately after stress, catecholamines and fast
(non-genomic) effects of corticosteroids promote instrumental and short-term
behavior. In contrast, in the aftermath of stress, behavior is aimed at
restoring higher cortical functions with more flexible behavior. Investigating
the temporal effects of stress on the brain by repeatedly measuring functional
connectivity patterns can provide a dynamic readout of stress vulnerability.
Study objective
Primary objective: Investigate the effects of acute stress on resting state and
task-induced connectivity in the brain of healthy individuals and unaffected
siblings of schizophrenia patients.
Secondary objectives:
- Correlate the endocrine stress response to resting state and task-induced
functional brain connectivity parameters.
- Investigate the association between (epi)genetic variation in stress-related
genes and stress-related functional connectivity.
Study design
A small monocenter intervention study in healthy individuals (N=40) and
unaffected siblings of schizophrenia patients (N=40). Participants will be
randomized to either the stress condition (Trier Social Stress Test, TSST) or a
validated control condition, resulting in the following 4 groups:
- healthy individuals * control test (N=20)
- healthy individuals * stress test (N=20)
- unaffected siblings * control test (N=20)
- unaffected siblings * stress test (N=20)
Functional connectivity is repeatedly measured in the brain before and after an
experimental stress/control test using fMRI in a 3Tesla scanner.
Intervention
Participants are randomized to either a stress test or a control test.
o Stress: the Trier Social Stress Test (TSST), a 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 duration of approximately 4 hours and sufficient time for breaks.
No direct benefits are present for participants. All participants will be given
a reimbursement of ¤60,- for their cooperation and time. Also potential travel
costs will be reimbursed.
During visit:
- Inclusion, collect a blood and urine sample, complete several questionnaires
- Three MRI scans in the 3T scanner before (1x) and after (2x) either the Trier
Social Stress Test (TSST) or a control protocol.
- Saliva samples
- Total duration: 250 min (of which 65 min in the 3T 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 the MRI scanner.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
- Age between 18 and 55 years old
- 1st degree family member with schizophrenia (unaffected sibling group only)
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
- Current psychiatric, neurological or endocrine disorder including claustrophobia and alcohol abuse or dependence
- Epilepsy in 1st degree family
- Psychiatric illness in 1st degree family (only in healthy control group)
- Self-reported current or past drug use in the last 2 weeks
- Ferrous objects in or around the body according to default checklist present ;Acute exclusion criteria:
- 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 | NL48978.041.14 |