Validating Reward-related Biomarkers (RTOC)

Study Overview
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Brief Summary
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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).

Official Title
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Validating Reward-related Biomarkers to Facilitate Development of New Treatments for Anhedonia and Reward Processing Deficits in Schizophrenia and Major Depressive Disorder

Conditions
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Schizophrenia, Depression, Motivation, Anhedonia, Physical, Anhedonia, Social, Negative Symptoms With Primary Psychotic Disorder

Intervention / Treatment
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* Behavioral: Self-rating Questionnaires
* Behavioral: Measures of Reward processing/reinforcement learning
* Behavioral: Additional Schizophrenia-specific Questionnaires and Interviews


Participation Criteria
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Eligibility Criteria
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General: Be able to provide signed and dated informed consent for study participation. Be male or female, aged between 20 and 55 years, inclusive. Be able to read, write, and speak the language in which psychometric tests are provided, with acceptable visual and auditory acuity (corrected if necessary). 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: 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. Meet the DSM-5 criteria for a current Major Depressive Episode, with the current depressive episode not having lasted longer than 6 months. 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: 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. Dose of antipsychotics not exceeding the equivalent of 6 mg risperidone.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HV<br>Humans aged 20-55 without a diagnosis of a psychiatric and neurological disorder. | Behavioral: Self-rating Questionnaires<br>* Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al. 1995) Quick Inventory of Depressive Symptomatology (QIDS; 16 items) Behavioral avoidance/inhibition Scales (BIS/BAS)<br>Behavioral: Measures of Reward processing/reinforcement learning<br>* Grip Strength Effort Task (Reddy et al. 2015; in combination with EEG) Doors (Gambling) task (Foti and Hajcak 2009; in combination with EEG) Reinforcement Learning/Working Memory task (Collins et al. 2017; no EEG)<br>|
| SZ<br>Humans aged 20-55 with a primary Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnosis of Schizophrenia. | Behavioral: Self-rating Questionnaires<br>* Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al. 1995) Quick Inventory of Depressive Symptomatology (QIDS; 16 items) Behavioral avoidance/inhibition Scales (BIS/BAS)<br>Behavioral: Measures of Reward processing/reinforcement learning<br>* Grip Strength Effort Task (Reddy et al. 2015; in combination with EEG) Doors (Gambling) task (Foti and Hajcak 2009; in combination with EEG) Reinforcement Learning/Working Memory task (Collins et al. 2017; no EEG)<br>Behavioral: Additional Schizophrenia-specific Questionnaires and Interviews<br>* Positive and Negative Syndrome Scale (PANSS: Kay et al. 1987) Brief Negative Symptom Scale (BNSS; Kirkpatrick et al. 2011)<br>|
| MDD<br>Humans aged 20-55 with a primary Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnosis of MDD. | Behavioral: Self-rating Questionnaires<br>* Snaith-Hamilton Pleasure Scale (SHAPS; Snaith et al. 1995) Quick Inventory of Depressive Symptomatology (QIDS; 16 items) Behavioral avoidance/inhibition Scales (BIS/BAS)<br>Behavioral: Measures of Reward processing/reinforcement learning<br>* Grip Strength Effort Task (Reddy et al. 2015; in combination with EEG) Doors (Gambling) task (Foti and Hajcak 2009; in combination with EEG) Reinforcement Learning/Working Memory task (Collins et al. 2017; no EEG)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grip effort outcome | Percentage of hard task choices at different reward levels | Day 1 | 
| Doors task outcome | Feedback negativity, an event-related potential (ERP) at approximately 300ms after feedback presentation indicating a favourable versus unfavourable outcome in paradigms in which the participant loses or wins money. | Day 1 | 
| RL/WM task outcome | Accuracy as function of set size (difficulty) | Day 1 |