To evaluate two biomarker tests (characterized by an activated inflammatory response system (IRS) as reflected by an aberrant monocyte gene expression signature and/or a disturbed metabolism of tryptophan) by comparing patients with BD with healthy…
ID
Source
Brief title
Condition
- Autoimmune disorders
- Ancillary infectious topics
- Manic and bipolar mood disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentages of patients and controls with positively expressed genes in the
monocytes and aberrant tryptophan parameters (positive/aberrant being defined
as over one standard deviation of the level found in healthy controls).
Secondary outcome
Gene polymorphism determination and the various cytokine and S100 and BDNF
determinations on the collected blood cells and HPA axis activity.
Determine microglia activation in brain using PET.
Background summary
Bipolar disorder (BD) with a lifetime prevalence of 2% is characterized by
episodic pathologic disturbances in mood ranging from extreme elation (mania)
to severe depression. There is no (biological) diagnostic marker for BD.
Nevertheless, several findings have been found to be associated with BD:
hypothalamic-pituitary-adrenal (HPA) axis disturbances; a higher frequency of
autoimmune diseases; an increase of pro-inflammatory monocyte/macrophage
cytokines; a pro-inflammatory gene signature in the circulating monocytes (and
a PDE4B associated pro-inflammatory signature); an activated inflammatory
response system (IRS) and glucocorticoid insensitivity with a linkage between
an activated IRS, disturbances in the tryptophan metabolism, and immune
activation of microglia cells in brain.
Study objective
To evaluate two biomarker tests (characterized by an activated inflammatory
response system (IRS) as reflected by an aberrant monocyte gene expression
signature and/or a disturbed metabolism of tryptophan) by comparing patients
with BD with healthy controls (as well as other cohorts of MOODINFLAME, i.e.
patients with major depressive disorder and with post-partum mood disorders and
with individuals at risk for the development of BD, i.e. children of a parent
with BD and unaffected (discordant) co-twins from a twin with BD).
Study design
Een crosssectionele casus-controle studie.
Study burden and risks
Participants will undergo an extensive psychiatric interview, will be asked to
complete various questionnaires, will be asked to consent with reviewing
existing medical records, will deliver 50 ml of blood, and will undergo a
dexamethason suppression test (DST). The study provides no benefits for the
participants with exception of the discovery of possible unexpected findings
during the interview and or via the blood test. If such finding is relevant for
the participant, in mutual arrangement his/her treating physician will be
informed about this finding.
The study has no risks, with the exception of a minimal risk associated with
the taking of a single blood sample.
The small number of patients/volunteers that give additional approval to
receive a PET scan, will be exposed to a small to intermediate radiation risk
and small risk by arterial cannulation of the radial artery. From this cannula
160ml blood will be withdrawn in the course of 1 hour with no detrimental
effects to be expected.
Hanzeplein 1
9713 GZ Groningen
NL
Hanzeplein 1
9713 GZ Groningen
NL
Listed location countries
Age
Inclusion criteria
Patients:
18-65 years
Both male and female
Bipolar I disorder or Bipolar II disorder
Preferentially euthymic (IDS-C <22 and YMRS <12)
No other primary major psychiatric diagnosis (e.g. primary psychotic disorder, schizo-affective disorder, primary anxiety disorder)
No current severe alcohol or other substance use disorder, needing treatment in a specialized setting
No alcohol or other substance dependence in the last year
No current or recent (last 4 weeks) severe infectious or inflammatory disease
No known current uncontrolled systemic disease (e.g. LE, RA)
No known major uncontrolled metabolic disorder (e.g. diabetes, hyper- or hypothyroidism, Cushing disease of Addison disease)
No known other significant uncontrolled somatic/organic/neurological disorder which may cause/affect mood
No current or recent (last month) use of somatic medication which may affect mood or the immune system (e.g. corticoids, anti-inflammatory drugs, immune suppressive drugs)
Women: Not pregnant or recent (<6 months) delivery
Informed consent
Healthy controls:
To be collected at same site
Age matched (within 5 years)
Gender matched
Sampling time matched (within 6 months)
18-65 years
Both male and female
No relevant present psychopathology
No major axis I disorder, e.g. MDD, bipolar disorder, psychotic disorder, schizo-affective disorder, anxiety disorder, alcohol or other substance dependence (lifetime)
For women: No prior PP depression/psychosis
No current alcohol or other substance use disorder
No current or recent (last 4 weeks) severe infectious or inflammatory disease
No known current uncontrolled systemic diseases (e.g. LE, RA)
No known major uncontrolled metabolic disorder (e.g. uncontrolled diabetes, hyper- or hypothyroidism, Cushing disease of Addison disease)
No known other significant somatic/organic/neurological disorder which may cause/affect mood
No current or previous psychiatric treatment/medication
No current or recent (last month) use of somatic medication which may affect mood or the immune system (e.g. corticoids, anti-inflammatory drugs, immune suppressive drugs)
Not pregnant or recent (<6 months) delivery
Informed consent
For PET imaging with MRI: No magnetizable metal in body, no pregnancy, adequate birth contol, no current use of benzodiazepines, no use of anticoagulants, and additional informed consent
Exclusion criteria
See inclusion criteria
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 | NL26374.042.09 |