Losartan and Social Processing

While renin-angiotensin mechanisms have been implicated in physiological disease, such as hypertension and stroke, the discovery of a local brain renin-angiotensin system (RAS) in the 1970s brought into question whether the RAS may play a role in psychiatric disorders too. Recent work has supported this link, with several studies reporting RAS influence on aversive learning, stress response to traumatic stimuli, and fear extinction.

Despite these promising results, studies have yet to fully explore the influence of the RAS and losartan on social processes. It is plausible that the RAS may be involved in social functioning, as recent work reported that losartan reduces sensitivity to social punishment in healthy volunteers. Such an effect of losartan may have broad relevance for psychopathology, as impairment to social functioning is present across a range of psychiatric disorders.

In this double-blind, randomized between-group study, the investigators will examine the effects of a single dose of losartan (50mg) versus placebo on social processing in N=68 healthy volunteers. Following a one-hour waiting period, participants will complete a set of computer tasks investigating social processes reported to be sensitive to psychopathology. Specifically, participants will complete the Approach Avoidance Task which assesses social approach and avoidance behaviour in response to various facial expressions via joystick movement, the Interpretation Inflexibility Task which evaluates cognitive flexibility in a social context, the Social Learning Trust Game which evaluates social learning through a trust game between participant investors and realistic trustees, and Cyberball, which probes response to social rejection. Results from this study will provide more insight on the potential role of the RAS in social cognitive processing in humans, which could lead to an improved mechanistic understanding of emotional disorders that are marked by social impairment.

Inclusion criteria

• Willing and able to provide informed consent
• Aged 18-50 years
• Sufficient written and spoken English skills to understand what the study involves, and to complete the questionnaires
• Non- or light-smoker (5 cigarettes a day, if vaping: less than 50 puffs)
• BMI between 18 - 30

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
• First-degree family member with severe psychiatric illness (including psychosis, bipolar disorder, unipolar psychotic depression).
• CNS-medication last 6 weeks (including as part of another study)
• Current blood pressure or other heart medication, including aliskiren and beta blockers)
• Diagnosis of intravascular fluid depletion or dehydration
• History of angioedema
• Impaired kidney function (based on self-report)
• Very low blood pressure (defined as repeated (at least three consecutive measurements) measures of blood pressure under standardised conditions where either the systolic or the diastolic blood pressure or both are below 90/50 mmHg (in accordance with established standard definitions)
• Lifetime history of epilepsy or other neurological disorder, as established by a professional diagnosis (e.g. autism, ADHD)
• Lifetime history of systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study
• Significant loss of hearing that is not corrected with a hearing device
• Women: pregnancy (as determined by a urine test, if the participant's pregnancy status is unknown during the in-person visit), breast-feeding