Apathy
Conditions
Keywords
Atomoxetine, Apathy, Motivation, Reward Processing
Brief summary
This study investigates how increasing noradrenaline levels with atomoxetine affects motivation and information processing relevant to apathy. Apathy, characterised by low motivation and reduced goal-directed behaviour, is common across neuropsychiatric disorders and is associated with poorer outcomes. Atomoxetine, a noradrenaline reuptake inhibitor, has been shown to influence effort, reward learning, and decision-making; however, its effects on cognitive processes relevant to apathy remain unclear. This study will investigate how pharmacologically increasing noradrenaline levels with atomoxetine affects different components of motivation altered in apathy, including reward processing, effort-based decision-making, goal-directed behaviour, and learning. In a within-subject, double-blind, placebo-controlled, randomised study, forty healthy participants with varying levels of apathy will complete a computerised task battery after receiving a single dose of atomoxetine (40 mg) and placebo. Validated tasks assessing motivation, reward learning, decision-making, goal-directed behaviour, and information processing will be used to examine whether and how atomoxetine influences motivation-related cognitive processes.
Interventions
DRUGAtomoxetine
Acute (single dose) of Atomoxetine (40mg). Oral administration. Atomoxetine is FDA approved for the treatment of ADHD in adults and children.
OTHERPlacebo
Sucrose pillules will be encapsulated in an opaque capsule (identical to the experimental drug).
Sponsors
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Intervention model description
In a within-subject, double-blind, placebo-controlled, randomised study, forty healthy participants with varying levels of apathy will complete a computerised task battery after receiving a single dose of atomoxetine (40 mg) and placebo. Participants will complete two visits, 21 to 30 days apart.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age: 18-45 * Good physical health * Willing and able to give informed consent to participate in the study * Sufficient knowledge of English language to understand and complete the study tasks
Exclusion criteria
* Current DSM-5 axis-I diagnosis (based on SCID results at screening) or history of a severe psychological disorder such as psychotic disorder, bipolar disorder, alcohol or substance abuse, or post-traumatic stress disorder * Previous or current extended period of persistent thoughts about ending one's life (longer than 5 days) or previous suicide attempt * Clinical diagnosis of attention deficit hyperactivity disorder (ADHD) or on the waiting list for assessment * Any intake of CNS-medication in the last 6 weeks (including as part of another study) * Any current intake of blood pressure or other heart medication, including beta blockers * Any current or previous medical condition or medication intake (last month) of any medication that, in the opinion of the study medic, may interfere with the safety of the participant or the scientific integrity of the study. * Severely underweight (BMI \<17) or very obese (BMI \>40), OR otherwise deemed unsuitable for the study due to weight-related concerns at the discretion of the study medic * History of cardiovascular, cerebrovascular disease * Breathing or lung-related illnesses, significant liver or kidney problems, or severe gastrointestinal conditions. * High blood pressure (defined as repeated measurements of blood pressure where either the systolic or the diastolic blood pressure, or both, are at or above 140/90 mmHg (https://doi.org/10.1093/eurheartj/ehy339) * History of recurrent rashes or history of allergic reactions to relevant substances (atomoxetine, placebo treatment) * Significant physical (including visual and auditory) or language impairment that would make complying with the study protocol challenging. * History of palpitations with sudden onset and offset, * History of fainting on exertion or in response to fright or loud noise * Family history of sudden death in a first-degree relative under 40 years of age * Women: pregnancy (as determined by a urine test), breast-feeding * Significant consumption of caffeine (more than about 6 cups of strong coffee per day), nicotine (more than 5 cigarettes per day, or equivalent amount), alcohol (more than two pints of beer a day or equivalent) * Participation in a study that involves the use of medication in the past 3 months * Participation in another study using similar tasks in the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effort-based choice behaviour during the Mental Effort Task | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo | Change in the acceptance rate of offers requiring varying levels of cognitive effort for reward, measured during the Mental Effort Task. Higher acceptance rates indicate greater willingness to exert cognitive effort for reward. |
| Effort-based choice behaviour during the Apple Gathering Task | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in the acceptance rate of offers requiring varying levels of physical effort for reward, measured during the Apple Gathering Task. Higher acceptance rates indicate greater willingness to exert effort for reward. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reinforcement learning under working memory load task behavioural performance | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in behavioural performance, measured as the proportion of optimal choices across low and high working memory load conditions. |
| Reinforcement learning under working memory load task parameter estimate | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in participant-specific learning rate parameter estimate derived from computational modelling of learning and working memory task performance across low and high working memory load conditions. |
| Affective Go/No-Go Task Behavioural Performance | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in behavioural performance, (response time; accuracy) on the Affective Go/No-Go Task. |
| Reward sensitivity computational parameter estimates from effort-based decision-making tasks. | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in participant-specific parameter estimates of reward sensitivity derived from computational modelling of performance on the Apple Gathering Task and Mental Effort Task. |
| Effort sensitivity computational parameter estimates from effort-based decision-making tasks. | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Change in participant-specific effort sensitivity parameter derived from computational modelling of performance on the Apple Gathering Task and Mental Effort Task. |
| Prior goal precision on the Goal Priors Assay Task | During the post-dose task battery, approximately 2-3 hours after single dose of atomoxetine or placebo. | Estimated prior goal precision derived from the relationship between estimation error (difference between estimated and actual ball landing position) and performance error (difference between actual ball landing position and target position). Higher values indicate greater weighting of prior beliefs relative to sensory evidence. |
Countries
United Kingdom
Contacts
CONTACTMarta M Radzikowska, MSc
CONTACTEva Periche-Tomas, PhD
PRINCIPAL_INVESTIGATORCatherine J Harmer, DPhil
University of Oxford
Outcome results
None listed