Objectives1. Are there differences in brain structures in bipolar twin pairs compared to their (healthy) co-twins and healthy control twin pairs?2. If there are changes in brain volume, will these changes differ across a 5 year interval between…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Psychiatrische stoornissen: Bipolar Disorder (Manisch-Depressiviteit)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Volume changes across time: Volume change within subjects, in patients as
well as in (healthy) co-twins and healthy control twin pairs. This means the
difference in brain volumes for T0 and T5 (in years).
Secondary outcome
- Diagnosis. Do patients have more and larger structural brain abnormalities
compared to healthy control twin pairs, but also compared to their (healthy)
co-twin.
- Zygosity: Do patients have more and larger structural brain abnormalities
compared to healthy control twin pairs and is there a difference between mono-
and dizygotic twin pairs.
- Sexe. Is there a difference in structural brain abnormalities between males
and females.
Background summary
Bipolar Disorder (BD) is a common, severe, and often life-threatening condition
with a lifetime prevalence of about 1-2 percent. Symptoms during a depression
include a persistent sad mood; loss of interest or pleasure in activities that
were once enjoyed; significant change in appetite or body weight; difficulty
sleeping or oversleeping; physical slowing or agitation; loss of energy;
feelings of worthlessness or inappropriate guilt; difficulty thinking or
concentrating; and recurrent thoughts of death or suicide. Patients in a manic
episode show abnormally and persistently elevated (high) mood or irritability
occurring with at least three of the following: overly-inflated self-esteem;
decreased need for sleep; increased talkativeness; racing thoughts;
distractibility; increased goal-directed activity or physical agitation; and
excessive involvement in risky behaviors or activities (e.g., unwise spending
sprees, reckless driving, sexual affairs).
Family and twin studies in BD have established the importance of genetic
factors in the aetiology of the illness. Environmental are also of great
importance, given that the concordance rate among monozygotic twin pairs is
approximately 70%. However, the precize interaction between genetic
vulnerability for BD (genotype) and environmental factors remains unknown.
There is evidence that there are structural brain abnormalities in BD. However,
relatively little MRI research has been performed (as compared to
schizophrenia) and the results are sometimes inconsistent for brain structures.
The most pronounced abnormalities show an increase of lateral ventricular
volume, a decrease of gray matter in the prefrontal cortex and an enlargement
of the amygdala.
The prevalance of thyroid dysfunction is higher in patients with mooddisorders
than in the general population. Previous research indicates that autoimmune
thyroiditis with increased TPO-Abs levels seems to be a marker which is related
to the genetic vulnerability to develop bipolar disorder rahter than to the
disease process itself.
Furthermore, there is increasing evidence that the immune system, in close
interaction with the central nervous system and the endocrine system, plays a
rol in the pathophysiology of bipolar disorder.
Study objective
Objectives
1. Are there differences in brain structures in bipolar twin pairs compared to
their (healthy) co-twins and healthy control twin pairs?
2. If there are changes in brain volume, will these changes differ across a 5
year interval between bipolar twin pairs, their (healthy) co-twins and healthy
control twin pairs?
3. Investigate whether the structural brain changes during a 5 year interval in
twin pairs concordant and discordant for bipolar disorder are mediated by
genetic and/or environmental factors.
4. Investigate whether white matter disparities as detected by DTI and MTR
imaging are mediated by genetic and/or environmental factors.
5. Since the same MRI protocol is used for both the schizophrenia and the BP
twin pairs, we can compare the results and find out whether there are
differences between both patient groups.
6. Is there a connection between structural changes in brain anatomy and
(certain) genes?
7. Are there differences in TPO-Abs levels in bipolar twin pairs compared to
their (healthy) co-twins, their healthy siblings and healthy control twin pairs?
8. If there are changes in TPO-Abs levels, will these changes differ across a 5
year interval between bipolar twin pairs, their (healthy) co-twins and healthy
control twin pairs?
9. Investigate whether the TPO-Abs levels changes during a 5 year interval in
twin pairs concordant and discordant for bipolar disorder are mediated by
genetic and/or environmental factors.
10. Is there a connection between TPO-Abs levels and (certain) genes?
11. Are there differences in neuroimmmune parameters or organ-specific
antibodies in bipolar twin pairs compared to their (healthy) co-twins, their
healthy siblings and healthy control twin pairs?
12. If there are changes in neuroimmmune parameters or organ-specific
antibodies, will these changes differ across a 5 year interval between bipolar
twin pairs, their (healthy) co-twins and healthy control twin pairs?
13. Investigate whether the neuroimmmune parameters or organ-specific
antibodies changes during a 5 year interval in twin pairs concordant and
discordant for bipolar disorder are mediated by genetic and/or environmental
factors.
14. Is there a connection between neuroimmmune parameters or organ-specific
antibodies and (certain) genes?
Study design
The research will be performed in a double blind study design. All subjects are
coded, this accounts for the questionaires and interviews as well as the MRI
scan.
The subjects will be asked to fill in some questionaires, and participate in a
couple of interviews e.g. to determine how the severity of the symptoms.
Also, an abbreviated version of the WAIS IQ test will be performed to get an
idea of the average IQ of the subjects.
Furthermore, a small bloodsample will be taken. This will be used to determine
zygosity, to assess functioning of the pancreas and autoimmune levels, and for
future objectives in genetics.
The MRI scan will be used to acquire the volumes of several brain structures.
The DTI and MTI scan (both are made during the MRI sequence) will be used to
detect and quantify white matter abnormalities.
Study burden and risks
It is of great importance to know which brain structures are involved in
bipolar disorder, and if these changes are progressive (or not) across time and
have a genetic background or if they are more influenced by environmental
factors.
There are no risk concerning this research project.
For the follow-up measurements subjects will be occupied for approximately3-4
hours. First, interviews and questionaires will be held. Second, a blood sample
will be taken. Subsequently, there will be a break before starting with the MRI
scan.
The same activities are applied for the new subjects. However, the
questionaires and interviews will be more extensive, because no background
information is yet available.
It will also be possible to spread the study over two days, to decrease any
pressure.
Some questionaires can be filled in at home, others have to be held at the UMC
Utrecht. This will take approximately 2-2.5 hours. The scan will take 45
minutes.
Subjects can also stop at moment if they find the examination too exhausting.
Heidelberglaan 100
POBox 85060, 3508 AB Utrecht
Nederland
Heidelberglaan 100
POBox 85060, 3508 AB Utrecht
Nederland
Listed location countries
Age
Inclusion criteria
Patients:
1) Part of a monozygotic or dizygotic twin pair
2) For monozygotic twin pairs at least one twin (MZ concordant and MZ discordant) and for dizygotic twin pairs only one twin (DZ discordant) has a diagnoses (life time):
- Bipolar Disorder I or Bipolar Disorder II (DSM-IV criteria)
- For the interview and blood sample: not in a acute (hypo)manic or major depressive episode
3) Age between 18 and 60 years;Healthy controls:
1) Part of a monozygotic or same-sex dizygotic twin pair
2) Matched to patient groups on age, sex and zygosity
3) Age between 18 and 60 years
Exclusion criteria
Patients:
1) No history of drug or alcohol dependency (DSM-IV criteria) for the last half year
2) No history of Cognitive Disorder (DSM-IV criteria)
3) No history of serious neurological illness
4) No severe medical illness
Healthy controls:
1) No history of specific axis I psychiatric disorder (DSM-IV criteria), on the basis of a SCID interview (Modules A-G)
2) No history of axis II personality disorder (DSM-IV criteria), on the basis of SIDP-V
3) No first degree relative with a history of specific axis I psychiatric disorder (DSM-IV criteria), on the basis of a FIGS interview
4) No history of serious neurological illness
5) No severe medical illness
6) No history of drug or alcohol dependency (DSM-IV criteria) for the last half year
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 | NL12339.041.06 |