Affiliation:
1. Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet
2. University Hospital Rigshospitalet
Abstract
Abstract
The serotonin 2A receptor (5HT2AR) and personality factors indexing stress coping mechanisms are implicated in the pathophysiology of depression. Cross-sectional studies performed in individuals with high familial risk for depression suggest that the coupling between 5-HT2AR and the inward-directed facets of neuroticism may be associated with a risk for depression. This study aimed to build a risk model for first-episode depression in healthy individuals based on serotonergic and personality biomarkers and utilizing up to 19 years of longitudinal data on depression. Such a model could have potential implications for identifying high-risk individuals for early preventative interventions. In this study, 131 healthy volunteers completed an [18F]altanserin positron emission tomography scan to measure 5-HT2AR binding and personality assessment of neuroticism, as part of research studies conducted between 2000-2008. Following study participation, information on future diagnoses of depression was obtained until 2019 from the Danish National Health Registers. Cause-specific Cox regression was used to investigate the hypothesis that neocortical 5-HT2AR binding in interaction with the inward-directed facets of neuroticism (neuroticisminward) would be associated with a risk of developing depression. The study found a significant positive interaction between neocortical 5HT2AR binding and neuroticisminward (p=0.018) such that individuals with high 5-HT2AR binding and high neuroticisminward scores had the highest risk for developing depression. In conclusion, the study provides a novel risk model for first-episode depression. Healthy individuals who have the personality phenotype of high neuroticisminward along with the serotonergic phenotype of high 5-HT2AR binding may be at the greatest risk for developing depression in the future.
Publisher
Research Square Platform LLC
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