Effort and Antidepressant Study Test

Effort and Antidepressant Study Test

The aim of this study is to investigate the behavioural effects and neural correlates of increasing serotonin levels in healthy volunteers, through a 7-day course of the SSRI escitalopram, on an effort-based decision-making task measuring self-benefiting and prosocial behaviours.

This study investigates the mechanisms behind motivation and apathy, focusing on how effort is dedicated to both self-benefiting and prosocial actions. Diminished motivation, often manifesting as apathy, is associated with poor health outcomes and is common in neurological disorders like Parkinson's, Alzheimer's, and small vessel cerebrovascular disease (SVD). While brain regions like the dorsal anterior cingulate cortex (dACC), dorsomedial prefrontal cortex (dmPFC), and anterior insula (AI) are known to regulate motivation in reward-based decision-making for personal gain, prosocial motivation remains underexplored. Prosocial behaviour involves actions that benefit others and contribute to physical and psychological well-being. Recent studies suggest unique neural activity in the anterior cingulate gyrus (ACCg) during prosocial actions, differing from self-benefiting behaviour.

To the best of our knowledge, there is no prior evidence on how SSRIs might influence prosocial motivation or its neural correlates. This study will address this gap by examining SSRI effects on effort-based prosocial decision-making, potentially identifying novel insights into the neural mechanisms underlying motivation for prosocial behaviour.

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the research
• Aged 18 to 40 years
• Sufficient knowledge of English language to understand and complete study tasks
• Right-handed

Exclusion Criteria:

• Current or past probable diagnosis of psychiatric illness, according to DSM-5 criteria requiring intervention by a healthcare professional, including but not limited to psychosis, bipolar disorder, major depression, OCD, PTSD, substance abuse disorder or any eating disorder
• Current or past diagnosis of any significant personality disorder (e.g., borderline personality disorder) according to self-report
• Diagnosis of attention deficit hyperactive disorder or autistic spectrum disorder that impairs daily functioning, requires pharmacotherapy or in the opinion of the study medic would affect the scientific integrity of the study
• Current use of medication that might interact with the effects of escitalopram or affect the scientific integrity of the study
• Previous suicide attempt or previous prolonged period (eg., > 5 days) of thought to end life
• Known contraindication to escitalopram including: past allergic reaction to escitalopram or any other medicines, diagnosis of angle-closure glaucoma, or current use of any other medication whose use interacts with escitalopram (according to BNF guidance) e.g. associated with prolonged QT-interval
• Any other current or past medical conditions which in the opinion of the study medic may interfere with the safety of the participant or the scientific integrity of the study including epilepsy/seizures, brain injury, hepatic or renal disease, diabetes, severe gastro-intestinal problems, Central Nervous System (CNS) tumours, neurobiological conditions
• First-degree relative with a diagnosis of schizophrenia-spectrum or other psychotic disorder, or bipolar disorder
• Severely underweight (BMI<17) or very obese (BMI>40) in a manner that renders them unsuitable for the study in the opinion of the study medic
• Heavy use of cigarettes (smoke>20 cigarettes per day)
• Heavy use of caffeine (drink>4 x 250 ml cups/cans of coffee/energy drinks per day)
• Lactose intolerance (due to the study involving administration of a lactose placebo tablet)
• Pregnancy (as determined by urine pregnancy test taken during the Part 2 screening visit), breast feeding or plans to become pregnant
• Past history of dependence on illicit substances or regular illicit substances use within the previous three months
• Evidence of current or past harmful use of alcohol
• Previous participation in a study involving the tasks used in this study or involving use of escitalopram in the last year in the Department of Psychiatry (University of Oxford)
• Physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging.
• Participant is unlikely to comply with the clinical study protocol or is unsuitable for any other reason, in the opinion of the investigator
• Not suitable for MRI neuroimaging, e.g., difficulty remaining still for duration of scan
• Any MRI contraindications outlined in FMRIB 3 Tesla scanning safety form