New tests to measure drug effects on psychological functioning

In addition to the NeuroCart®, the legacy neurophysiological test battery used by CHDR for more than three decades, there is a need for function tests to measure domains of psychological functioning. The Biomarker Engineering and Analytics (BEA) group and Psychiatry group use the Research Domain Criteria (RDoC) developed by the US National Institute of Mental Health (NIMH). Clinical Scientist Soma Makai-Bölöni: 'The Psychiatry group mainly studies mood disorders. The tests we developed address the ‘reward responsiveness’ domain and the 'reception of facial recognition' subdomain, which are both relevant in assessing depression. Facial recognition, for example, is based on the fact that in a negative mood, one will more likely interpret a facial expression as a negative emotion.’

'The GET measures how much effort a person is willing to exert for a given level of reward,' explains Ingrid van den Heuvel, Clinical Research Engineer at the BEA group. In this case, the effort is squeezing a hand dynamometer. At the beginning of each test, participants are asked to squeeze with maximum force. During testing, the participant receives options where a certain effort is rewarded by a small amount of money (‘Are you willing to give 80% of your maximum effort for five cents?’).

Patients with mood disorders often are less willing to make an effort and do not respond much to rewards. 'We are particularly interested in the extent to which outcomes change after the administration of drugs with an effect on mood disorders, such as ketamine,' says Van den Heuvel.

A first test of the GET’s sensitivity to drug effects was recently conducted in an internal study where study participants were given a well-known benzodiazepine or placebo. Van den Heuvel: ‘A benzodiazepine would not have been our first choice, but the opportunity arose to add the GET to a study that was already planned for another goal. We hope it shows some effect, positive or negative.’ The results of this study are currently being analysed.

In the FERT, study participants are shown images of a face for half a second. The face may express an emotion, such as anger or happiness, or it can be neutral. Van den Heuvel: 'We have morphed the images so that they are gradations between neutral and a clearly visible emotion. Using buttons with labels of emotions, the study participant has to quickly indicate whether it is a neutral face or which of the six emotions is visible’. Like with the GET, the main aim is to make drug effects objectively visible. An initial series of tests with colleagues showed that there was a learning effect if the same limited set of faces was used each time, so now the researchers are using a larger set of faces. The FERT was first used in a pharmacological context in the same benzodiazepine study where the GET was used. ‘Our main objective was to study the sensitivity of the test to pharmacological effects, but we also wanted to assess the repeatability of the modified tests’, says Van den Heuvel.

The concept for both the GET and the FERT was developed elsewhere.  Van den Heuvel and her colleagues developed the tests as they are now for application by CHDR: 'We developed our own set-ups and we are now validating them, tweaking them if necessary. I hope our efforts will be rewarded, and we will indeed be able to measure drug effects, supporting the clinical development of novel drugs.'