Improvement of diagnosis of major depressive and bipolar disorder: an fMRI-study.

BACKGROUND:
The study concerns the diagnosis of major depressive disorder (MDD) and bipolar disorder (BD). Early differentiation between both disorders is very important, since treatments differ, and providing the wrong therapy is associated with prolonged illness duration and recurrence. However, when a patient presents with a major depressive episode (MDE), diagnosis is often unclear due to the fact that:

1. Clinical characteristics of MDE in both disorders do not clearly discriminate;

2. Retrospective assessment of a (hypo)manic episode is usually equivocal, and;

3. (Hypo)manic episodes may occur long after the first MDE.
Current diagnostivc tools (i.e., questionnaires and interviews) are rather insensitive, rendering a diagnostic grey zone of false negative diagnosis for BD. Therefore additional diagnostic procedures are required. At best, this could be procedures to identify disease specfic brain processes (biomarkers). Since findings from recent affective neuropsychological and fMRI studies indicate differences in emotional processing between MDD and BD, these instruments are promising candidates for detecting such biomarkers. Until now, only two studies directly compared MDD and depressed BD with healthy controls (HC). Furthermore, in most studies medication use was allowed, which may have been an iimportant confounder. To investigate the value of neuropsychological testing and/or fMRI for diagnosis, new studies and replications of earlier research of these biomarkers are needed, preferably in direct comparisons of unmedicated MDD and BD patients versus HC.
OBJECTIVE:
We aim to:

1. Improve differential diagnosis of recurrent MDD and BD by investigating biomarkers at a neuropsychological and neurobiological level;

2. Investigate whether affective neuropsychological testing can be used as a diagnostic tool for MDD and BD;

3. Investigate wether fMRI can be used for this purpose.
DESIGN:
The study is a cross sectional study with proscpective follow up for a period of 2.5 years in an outpatient population.
STUDY POPULATION:
We will investigate three subject groups: 20 MDD, 20 BD I, and 40 HC. Patients will be medication free, aged 20-60 years, currently moderately to severly depressed, with a history of at least 2 MDEs. HC will be matched on sex, age, handedness and years of education.
PRIMARY OUTCOME:
We will compare performance on the neuropsychological task between MDD, BD I and HC, measured by reponse time, number of omissions and number of errors. The same outcomes will be examined for the neuroimaging tasks. We will compare brain responses of fMRI tasks relative to control conditions between MDD, BD and HC. We will compare responses in predefined ventral and dorsal brain regions (dorsolateral prefrontal cortex (PFC), ventral PFC, orbitofrontal, limbic and subcortical regions).
RISKS AND BENEFITS:
There is no immediate advantage for the participants. All depresed patients will be offered treatment according to treatment guidelines. On the other hand, the study is neither very burdensome, nor does it carry a major health risk.

By detection of disease specific deviations in emotion processing in unipolar vs bipolar patients, affective neuropsychological tests and fMRI could be used to discriminate between both affective disorders.

1. Intake and scan session (within 1 week);

2. Follow up for 30 months: telephone contact every 6 months.

1. Questionnaire;

2. Psychiatric interview;

3. Affective neuropsychological testing;

4. fMRI;

5. Venapunction.