Universiteit Leiden

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Research project

Profiling Endophenotypes in Social Anxiety Disorder – a family study

The key question addressed in this family study is whether the psychophysiological and neurocognitive abnormalities often reported in SAD patients are heritable and can thus be found in family members of SAD patients as well. Determination of heritability of these deficiencies is essential for endophenotyping. A successful delineation of endophenotypes will facilitate the investigation of gene-environment interactions, which will be the subsequent phase in this research program.

Duration
2013 - 2021

Social anxiety disorder (SAD) is characterized by an intense fear of social or performance situations due to expected personal scrutiny. SAD is a common anxiety disorder with an early onset, long course and lifetime prevalence rates are estimated between 7-13% [1]. Since 70% of those individuals diagnosed with SAD will develop a comorbid psychiatric disorder (e.g., depression) in their lifetime [2], it is imperative to identify reliable risk factors that aid in early detection of SAD, as well as the development of prevention/intervention methods.

Our research is guided by the idea that reliable risk factors for SAD can be determined by studying endophenotypes in multigenerational families. We focus on neurocognitive endophenotypes that should set the stage for a reliable approach to discover the genetic architecture of SAD. Profiling (neurocognitive) endophenotypes is a necessary step to enhance the power to detect reliable candidate genes associated with psychiatric disorders [3]. Endophenotypes are highly heritable, manifest in the affected individual whether or not the illness is active, and can be found in non-affected family members at a higher rate than in the general population [4]. Profiling SAD endophenotypes should therefore offer an interesting vantage point to understand the disorder’s pathophysiology and its genetic architecture, ultimately facilitating medical and psychological interventions to alleviate symptoms in SAD patients.

The design of the study is a multigenerational family study, having the potential to yield heritability patterns of neurocognitive markers of psychiatric disorders. Twelve patients with social anxiety disorder (targets) will be enrolled in the study, including their children, spouse, siblings and their spouses and children (at least 8 members per family). Since adolescence is considered to be the critical period for the development of SAD, the target’s children should be between 8-21 years of age. Targets should be within the 25-to-55 year age range. Measurements include MRI, EEG, a diagnostic interview and questionnaires.

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