Rationale: Poor social functioning may contribute to major depressive disorder (MDD). Poor serotonin function may also contribute to MDD. Recent research suggests that serotonin plays a role in regulating human social behaviour. Therefore it would be intriguing to investigate the role of serotonin in regulating the quality of everyday social interactions in a population at risk for MDD. Human social behaviour can be reliably assessed in everyday life using Ecological Momentary Assessment (EMA).

Objective: This study aims to investigate how an experimental increase in serotonin influences social functioning in healthy adults with a first-degree family member diagnosed with MDD. The primary goal is to investigate the role of serotonin in regulating everyday social behaviour, measured using EMA. This will be done using oral supplementation with tryptophan, the amino acid precursor of serotonin. Secondary goals are to determine how this experimental manipulation influences people's feelings as well as their perceptions of other's social behaviour following interpersonal events, and social cognitions at the end of the day. An exploratory goal is to investigate if these effects are moderated by genes thought to be involved in MDD.

The primary hypothesis to be tested is that tryptophan will reduce quarrelsome behaviour.

Inclusion Criteria:

• Age 18-65 years
• At least one first-degree family member with MDD
• Willingness to cooperate; to sign written informed consent

Exclusion Criteria:

• Any current or past MDD or other mood disorder as determined by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID)
• Any current anxiety disorder, psychotic disorder, substance use disorder, eating disorder, or somatoform disorder as determined by SCID
• Any contraindication for the use of tryptophan, i.e. pregnancy, diabetes, cancer or a history of cancer, a history of any scleroderma-like condition, evidence of achlorhydria, upper bowel malabsorption, or irritation of the urinary bladder
• Current use of psychotropic medications including medications for psychiatric problems (e.g., antidepressants such as Mono Amine Oxidase inhibitors and fluoxetine) or migraines
• Not speaking Dutch fluently