An Imaging and Cognition Study of Positive Valence Systems in Psychotic Syndromes

The Research Domains Criteria (RDoC) initiative aims to identify more valid
dimensions, spanning multiple biological and psychological levels, to advance
basic understanding of mental disorders and their treatments. One of the core
components of RDoC is focused on reward circuits and behavior. Reward circuitry
is central to the formulation of the RDoC Positive Valence Systems (PVS)
domain, which has been linked to diverse psychiatric disorders including
schizophrenia and bipolar disorder.
There is consensus that schizophrenia (SCZ) and bipolar disorder (BP) share
substantial genetic risk and multiple overlapping phenotypic variations at the
levels of corticostriatal brain circuits, cognitive functions, and behavior.
Yet, it remains unknown precisely whether reward circuitry and behaviour is
similar.

To examine the PVS domain, and in particular reward circuits and behaviour, in
large genetically informative cohorts comprising 500 individuals (including 125
SCZ patients, 125 BP patients, 125 relatives and 125 controls) already
ascertained in the Netherlands. Using functional MRI (fMRI) we aim to
characterize the neural correlates of the ventral striatum of the reward
circuit during the Monetary Incentive Delay (MID) task in relation to
diagnostic category and symptom dimensions. In addition, we aim to characterize
the PVS system using 3 online assessments. "

The primary objective is to identify differences in ventral striatum (VS)
activity during reward anticipation between 125 patients with SCZ, 125 patients
with BP and 125 controls.

The secondary objectives are:
1. to characterize the neural correlates of the VS of the reward circuit in
relation to symptom dimensions in 250 patients, 125 relatives and 125 controls
2. to identify differences in VS activity during reward anticipation in
relatives of patients as compared with patients and controls
3. to identify differences in the other three primary PVS components (reward
valuation, effort valuation, Action Selection/Decision Making ), assessed using
an online tool, between patients, relatives and controls.

This is an observational study.

Study participation involves one visit to the Erasmus MC which will take
approximately 5.5 hours in total. At the Erasmus MC, the participant will
conduct an online cognitive assessment (1 hour) and will be interviewed
(patients: to assess current state and lithium, lamotrigine and clozapine
response, 45 minutes; relatives and controls: to assess psychiatric symptoms,
30 minutes). In addition, we ask for a fecal sample for biobanking, we measure
height, weight and blood pressure, a blood sample will be drawn (8 ml in 2 EDTA
tubes). Blood samples will be taken from the participating subjects and stored
at the biobank of the Erasmus MC. On request, the skin can be locally
anesthetized prior to the venapuncture. Since the amount and number of blood
samples is limited, the burden for participating subjects is expected
negligible. Participants are asked to fill out questionnaires on current
demographic and clinical situation, lithium and lamotrigine reponse,
motivational behaviour and personality (1 hour, these questionnaires can be
filled out from home). In addition, a magnetic resonance imaging (MRI) scan
session will be performed (1 hour). Technically MRI is a non-invasive technique
(i.e., nothing is inserted into the body). However, the CCMO marked MRI as an
invasive technique to heighten the safety regulations. There are no known risks
associated with MRI acquisition, so there is no need for special preparation
for the subject on top of the Erasmus MC standard procedure. The data are
primarily used for research purposes. However, a radiologist will provide a
neurodiagnostic evaluation. When the specialist finds that medical treatment is
indicated, then the subject will be notified. Also, subjects may become anxious
during the scan. The subject can communicate this by means of a push button,
and he/she will be taken out of the scanner.
The risk assessment for participation to this study is minimal. Subjects will
experience no direct benefits from our study. In the long run, increased
understanding of the etiology and pathophysiology of SCZ and BP may contribute
to diagnosis, early detection, and/or prediction of treatment outcome.