Fear of Negative Evaluation and Depression: How are They Related and Do Brain Structures Play a Mediating Role?

Background: The fear of negative evaluation (FNE) is a core feature of social anxiety disorder (SAD), a highly prevalent and impairing disorder, and has been linked to depressive symptoms. However, the relationship between FNE and depressive symptoms within families genetically enriched for social anxiety remained until now unexplored. Additionally, the potential role of brain structures in this association has not yet been investigated. Therefore, the study aimed to investigate the relationship between FNE and depressive symptoms in a sample enriched for social anxiety. Furthermore, we investigated whether volumes of the amygdala, hippocampus, putamen, and pallidum play a role in this relationship. Methods: The study used data from the Leiden Family Lab study on Social Anxiety Disorder (LFLSAD), the first multigenerational study designed to identify neurocognitive endophenotypes of social anxiety. Participants included members of two generations from nine families genetically...Show moreBackground: The fear of negative evaluation (FNE) is a core feature of social anxiety disorder (SAD), a highly prevalent and impairing disorder, and has been linked to depressive symptoms. However, the relationship between FNE and depressive symptoms within families genetically enriched for social anxiety remained until now unexplored. Additionally, the potential role of brain structures in this association has not yet been investigated. Therefore, the study aimed to investigate the relationship between FNE and depressive symptoms in a sample enriched for social anxiety. Furthermore, we investigated whether volumes of the amygdala, hippocampus, putamen, and pallidum play a role in this relationship. Methods: The study used data from the Leiden Family Lab study on Social Anxiety Disorder (LFLSAD), the first multigenerational study designed to identify neurocognitive endophenotypes of social anxiety. Participants included members of two generations from nine families genetically enriched for social anxiety. Using a cross-sectional design, self-report questionnaires assessed FNE and depressive symptoms, while structural MRI scans measured the volumes of the bilateral amygdala, hippocampus, putamen, and pallidum. Correlation and mediation analyses were performed to investigate the associations between FNE, depressive symptoms, and brain volumes. Results: SAD was highly prevalent in the sample (n = 133), with (sub)clinical SAD cases identified in 39.6% of generation 1 and in 36.5% of generation 2. Furthermore, FNE was significantly and positively associated with depressive symptoms (p < .001). However, no significant associations were found between FNE and volumes of the bilateral amygdala, hippocampus, putamen, or pallidum (p > .00625). Conclusion: The findings suggest that higher levels of FNE are associated with higher levels of depressive symptoms in individuals from families genetically enriched for social anxiety. However, no evidence was found for a mediating role of the volumes of the amygdala, hippocampus, putamen, and pallidum. The results emphasize the need for future research, with longitudinal designs and larger sample sizes, to explore the relationship between FNE and depression, and alternative mechanisms underlying this relationship. This could contribute to the development of targeted interventions for individuals at risk for social anxiety, FNE, and depression.Show less

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Fear of Negative Evaluation and Depression: How are They Related and Do Brain Structures Play a Mediating Role?