Study A: Show BP patients similar progression in brain volume change compared to schizophrenia patients. If so, can the progressive change in BP patients also be explained by genetic factors?Study B: Show BP patients and their non-bipolar cotwins…
ID
Source
Brief title
Condition
- Manic and bipolar mood disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Study A: Change in brain volume (sMRI) or gray/white matter density (Voxelbased
morphometry)
Study B: Change in immunology parameters
Study C: Fractional anisotropy and magnetisation transfer ratio
Study D: Genotype and gene expression data
All studies: Baseline values or parameters which might intervene with the main
study parameter (age, gender, years of education, symptoms, level of
functioning, medication intake, life events)
Secondary outcome
n/a
Background summary
Family and twin studies in bipolar disorder (BP) have established the
importance of genetic factors in etiology of the illness. Moreover, BP shows
high point estimates of heritability in liability to the illness, i.e. ~85%.
Recently, we finished data collection of a large cohort op BP twin pairs. The
purpose of collecting a BP twin cohort was two-fold. First, patients show
structural brain abnormalities, but whether the abnormalities are due to
genetic factors or disease related (non-genetic) factors remains largely
unknown. Therefore, an MRI study was performed (study A). Secondly, the
prevalence of thyroid dysfunction is higher in patients with mood disorder than
in the general population. Therefore, blood samples were acquired to determine
parameters involved in the immune system (study B). Currently, this is the
largest BP twin cohort worldwide.
Earlier, we carried out a longitudinal study in monozygotic (MZ) and dizygotic
(DZ) twin pairs concordant or discordant for schizophrenia. Because of the
apparent genetic overlap, and the overlap in phenotypic characteristics it is
of particular interest to conduct a longitudinal study of our BP twin sample
and compare the data to the results of the prospective study of schizophrenia
twins.
We propose to carry out 4 studies, using the earlier collected bipolar disorder
(BP) twin cohort of our department. In addition, we ask affected and unaffected
siblings of these twin pairs to participate as well.
Study A: A longitudinal MRI study
Study B: A longitudinal study on neuroimmune parameters
Study C: A cross-sectional study into MRI measures that focus on integrity and
connectivity in white matter structures.
Study D: A cross-sectional study into gene expression levels in discordant MZ
twin pairs. Moreover, genetic information will be available to investigate the
effect of genotype on brain volume (change) in BP twins.
Study objective
Study A: Show BP patients similar progression in brain volume change compared
to schizophrenia patients. If so, can the progressive change in BP patients
also be explained by genetic factors?
Study B: Show BP patients and their non-bipolar cotwins progression in TPO-Abs
and other neuroimmune parameters compared to normal controls. If so, can the
progressive change also be explained by genetic factors?
Study C: Since our baseline measures show a genetic contribution to the white
matter volume abnormalities in BP we hypothesis that abnormal values of
fractional anisotropy and magnetisation transfer ratio will also be influenced
by the genetic risk to develop BP.
Study D-genotyping: What is the effect of genotype on brain volume (change) in
BP, schizophrenia and healthy twin pairs, regarding specificity to diagnosis?
Study D-gene expression: Is there differential gene expression within
discordant MZ twin pairs with either BP or SZ and are can these expression
patterns explain discordancy?
Study design
Study A and B: longitudinal twin design
Study C and D: cross-sectional extended twin design
Study burden and risks
A magnetic resonance imaging (MRI) scan session of approximately 50 minutes
will be performed: MRI is a non-invasive technique, so there is no need for
special preparation for the subject. There are no known risks associated with
the MRI acquisition and the data are solely used for research purposes.
However, structural cerebral pathology may be noticed. If medical treatment is
indicated, the subject will be notified.
From each participant a small amount (4 x 10 ml) of EDTA blood will be taken,
by means of a venapuncture. On request, the skin can be locally anesthetized
prior to the venapuncture. If the participant refuses the puncture, a cotton
swab of buccal mucosa can be taken. Since the number of blood samples is
limited and the samples are small, the burden for participating subjects is
expected to be negligible.
No immediate benefits are to be expected from participation in this study for
the subjects. In the long run, increased understanding of the aetiology and
pathophysiology of psychiatric illness in general and schizophrenia and bipolar
disorder in particular, may contribute to diagnosis, early detection and/or
prediction of treatment outcome.
Heidelberglaan 100
3584 CX utrecht
NL
Heidelberglaan 100
3584 CX utrecht
NL
Listed location countries
Age
Inclusion criteria
Study A+B (longitudinal):
participation at baseline;Study A+B+C+D (cross-sectional)
New bipolar twin pairs
1) Part of a monozygotic or dizygotic twin pair
2) At least one twin has a diagnoses (life time) of Bipolar Disorder I or Bipolar Disorder II (DSM-IV criteria)
3) No history of drug or alcohol dependency (DSM-IV criteria) for the last half year
4) No history of Cognitive Disorder (DSM-IV criteria)
5) No history of serious neurological illness
6) No severe medical illness
7) Age between 18 and 60 years;New healthy control twin pairs
1) Part of a monozygotic or dizygotic twin pair
2) No history of axis I psychiatric disorder (DSM-IV criteria), on the basis of a SCID interview (Modules A-G)
3) No history of axis II personality disorder (DSM-IV criteria), on the basis of SIDP-V
4) No first degree relative with a history of specific axis I psychiatric disorder (DSM-IV criteria), on the basis of a FIGS interview
5) No history of drug or alcohol dependency (DSM-IV criteria) for the last half year
6) No history of serious neurological illness
7) No severe medical illness
8) Age between 18 and 60 years;Siblings
1) full sibling of an included twin pair
2) No history of axis I psychiatric disorder (DSM-IV criteria), on the basis of a SCID interview (Modules A-G)
3) No history of axis II personality disorder (DSM-IV criteria), on the basis of SIDP-V
4) No history of drug or alcohol dependency (DSM-IV criteria) for the last half year
5) No history of serious neurological illness
6) No severe medical illness
7) Age between 18 and 60 years
Exclusion criteria
Did not give written informed consent
2) Ferrous objects in or around the body (e.g. braces, glasses, pacemaker, metal fragments)
3) Drug or alcohol abuse over a period of six months prior to the experiment
4) History of closed-head injury
5) History of neurological illness or endocrinological dysfunction
6) Claustrophobia
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 | NL20509.041.08 |