Genetic, Imaging, and Cognition study of Positive Valence Systems in Psychotic Syndromes

In this project, individuals with schizophrenia or bipolar disorder, their first-degree relatives and individuals without psychotic or mood disorder were asked to participate in either an MRI study or an online study.

MRI study

Participants are invited to visit the Erasmus MC (department of Child and Adolescent Psychiatry/Psychology). During the visit they underwent MRI scanning. During scanning they performed the Monetary Incentive Delay task. In addition, this task, but also the EEfRT task and a social and non-social Bandit task were administered while participants were seated behind a computer. Moreover, a psychiatric interview, symptom severity questionnaires, information on neuroleptic medication use, and a self-report measure allowing the assessment of anticipatory and consummatory pleasure were administered.

A total of 278 participants are included in the project (138 patients, 63 first degree relatives, and 77 controls).

Online study

Participants received an email with a link to online questionnaires on severity of psychiatric symptom, neuroleptic medication use and a self-report measure allowing the assessment of anticipatory and consummatory pleasure. In addition, the same task as described in the MRI study were administered online.

A total of 322 participants (197 patients, 81 relatives and 54 controls) enrolled in the study and complete at least one part of the full online protocol. From the majority of the participants extensive clinical and cognitive data has been obtained in earlies studies, i.e. the GROUP study and Bipolar Genetics.

Our aims are three-fold:

1. Develop, validate, and complete online and/or in-laboratory screening of PVS. We will examine and test: (a) the trait covariation of the primary PVS components in the overall cohort; (b) heritability of the primary and new derived PVS measures; (c) associations of PVS measures with specific candidate gene variants proposed in prior studies, and with polygenic risk profiles derived from large genome-wide studies.
2. Conduct detailed characterization of reward circuit responses using functional MRI (fMRI) during the Monetary Incentive Delay (MID) task. Analyses will focus on the ventral striatal (VS) and ventromedial prefrontal cortex (vmPFC) responses to anticipation and receipt of reward.
3. Using the data acquired in Aim 2, we will derive response profiles from the PVS cognitive tests that possess greatest concurrent validity with respect to individual differences in neural circuit function (i.e., optimal cognitive indicators of VS and vmPFC responsivity seen on fMRI), and then examine how those newly generated indicators perform in analyses paralleling those of Aim 1. These analyses will determine if the new circuit-validated phenotypes are: (1) more or less heritable, (2) more or less associated with candidate gene variants and PVS, compared to the original behavioral measures extracted prior to knowledge of their associations with neural circuit responses.

The project is funded by the National Institute of Mental Health (NIMH).

Internal collaborations

MRI acquisition parameters were developed in collaboration with the Erasmus MC department of Radiology and Nuclear Medicine.

External collaborations

The project is a collaboration with the University of California Los Angeles (UCLA). Many of the participants were recruited from existing cohorts (i.e. the GROUP study and Bipolar Genetics) that are hosted by the University Medical Center Utrecht (UMCU).