To study the effects of transient severe endogenous stress hormone exposure on the structure and functioning of brains circuitry regulating emotion, and the association with cognition and psychopathological symptoms.
ID
Source
Brief title
Condition
- Hypothalamus and pituitary gland disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
I. What are the (irreversible) effects of M. Cushing on the brain and what is
the correlation with psychopathology and cognition?
It is expected that in patients with treated M. Cushing, abnormalities will be
found in emotion regulation circuitry (parts of the prefrontal cortex,
cingulate cortex, basal ganglia, hippocampus and amygdala) compared with
matched controls.
II. Are there shared and unique structural and functional MRI abnormalities in
patients with treated M. Cushing and in patients with mood and anxiety
disorders?
It is expected that after treatment for M. Cushing, comparable cerebral
impairment with comparable correlates with psychopathology are found as in
patients with mood and anxiety disorders, compared to controls.
III: Are there any effects of common polymorphisms of genes important for the
stress system on the shared and unique functional and structural MRI
abnormalities in patients treated for M Cushing and NESDA participants?
It is expected that certain polymorphisms are associated with more pronounced
variations and more psychopathology in both treated M. Cushing and depression
and anxiety patients, based on a stronger predisposition to dysregulation of
the HPA axis, or a greater sensitivity to the harmful effects of high cortisol
levels.
Secondary outcome
not applicable
Background summary
Cushing's disease (M. Cushing) is a rare disorder characterized by an increased
endogenous production of the stress hormone cortisol, leading to various
physical but also psychological changes. Patients with active M. Cushing show
an increased prevalence of various psychiatric disorders, even after successful
treatment. It is believed that the pathophysiological models of depressive and
anxiety disorders show abnormal activation of the stress axis, which plays a
central role and impact in those areas of the central nervous system that are
very sensitive to changes in cortisol levels, such as the hippocampus, the
amygdala, prefrontal areas and more. Corresponding changes would explain the
similarities in psychopathology. If this is correct, M. Cushing is a unique
human model to gain more insight into the role and contribution of transient
abnormal stress hormone exposure in the pathophysiology of depressive and
anxiety disorders, particularly at the level of emotion-regulating brain
circuits. This has not been done systematically before.
Study objective
To study the effects of transient severe endogenous stress hormone exposure on
the structure and functioning of brains circuitry regulating emotion, and the
association with cognition and psychopathological symptoms.
Study design
Patients with treated M. Cushing follow the same structural and functional MRI
scanning protocol as previously investigated members of the MRI study of the
Netherlands Study on Depression and Anxiety (NESDA). The data are analyzed
according to NESDA.
Study burden and risks
The burden of the participants consists of the MRI scan (1 hour), preparation,
questionnaires and saliva collection (1 hour). In total the study will take 2
hours to complete. An MRI scan is accompanied by loud noise. All participants
are provided with appropriate hearing protection. There are no expected risks
in participating in this MRI study.
Albinusdreef 2
2333 ZA Leiden
NL
Albinusdreef 2
2333 ZA Leiden
NL
Listed location countries
Age
Inclusion criteria
- men and women between 18 and 55 years of age
- patients treated for M. Cushing by transsphenoidal surgery with or without additional radiotherapy
- adequately substituted
- patients should be prepared and well informed about the study
- patients should sign the informed consent
Exclusion criteria
- difficulty to understand the Dutch language
- history of contusio cerebri
- presence of non-endocrinological impairments which could influence brainstructure or function
- chronic misuse of alcohol or drugs
- medication (other than suppletion) that could influence perfusion or cognition and can not be stopped two days before the scan takes place, with exclusion of SSRI in stable dossage
- contraindications for MRI, such as metal implants, heart arrhythmia, claustrophobia etc.
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 | NL34912.058.10 |