Deficits or abnormalities in reward processing are present in a number of psychiatric disorders. The overarching objective of the study is to conduct initial validation work towards optimising three experimental tasks - which have previously been shown to be sensitive to reward processing deficits - for future use in clinical trials.

This initial validation work has the primary objective to uncover group differences in task outcome measures between healthy control participants, participants with Major Depressive Disorder (MDD) and participants with schizophrenia (SZ) using statistical analyses. This may provide some indications for the use of these tasks as clinically-relevant biomarkers.

Primary aims include:

(i) comparing the investigator's endpoint means and distributions to those in previously published data; (ii) replication of previously-reported differences between MDD/SZ vs. healthy control participants, and, (iii) exploring the relationship between task endpoints and subjective participant- and clinician-rated report of reward-related constructs (e.g. anhedonia, negative symptoms).

General:

1. Be able to provide signed and dated informed consent for study participation.
2. Be male or female, aged between 20 and 55 years, inclusive.
3. Be able to read, write, and speak the language in which psychometric tests are provided, with acceptable visual and auditory acuity (corrected if necessary).
4. Unless otherwise stated, CNS medications to treat symptoms of MDD or SZ and other stable CNS conditions requiring medication is permitted in the MDD and SZ groups, provided the daily dose of medication has not been changed by more than +/- 30% in the last 4 weeks before the start of the study, and is not expected to change by a larger fraction while participating in the study.

MDD

Participants must:

1. Have a primary Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnosis of MDD, confirmed by the result of the MINI interview conducted by the site at screening. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder or specific phobia may be included.
2. Meet the DSM-5 criteria for a current Major Depressive Episode, with the current depressive episode not having lasted longer than 6 months.
3. If undergoing treatment, be currently treated with an antidepressant approved in this protocol for at least 4 continuous weeks. Psychological treatments (e.g., Cognitive Behaviour Therapy, Interpersonal Psychotherapy, Psychodynamic Psychotherapy etc.) are all permitted in this study regardless of frequency and duration.

SZ

Subjects must:

1. Have a primary diagnosis of schizophrenia according to the Statistical Manual of Mental Disorders 5th edition (DSM-5), confirmed by the result of the MINI interview conducted by the site at screening. Subjects with a diagnosis of comorbid Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder or specific phobia may be included.
2. Dose of antipsychotics not exceeding the equivalent of 6 mg risperidone.

A sample of 37 completed individuals with MDD, 37 completed individuals with SZ, and a maximum of 80 healthy volunteers (without a neurological or psychiatric disorder) who will not differ on age or gender.

The RTOC clinical study has received funding from Boehringer Ingelheim International GmbH, H. Lundbeck, Janssen Pharmaceutica, Blackthorn Therapeutics, and F. Hoffmann-La Roche Ltd. All individual data will be made available to these parties.