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Fear and anxiety are conceptualized as responses to acute or potential threat, respectively. Adult twin studies found substantial interplay between genetic and environmental factors influencing fear disorders (phobias) and anxiety disorders. Research in children, however, has largely examined these factors independently. Thus, there exists a substantial knowledge gap regarding the underlying etiologic structure of these closely-related constructs during development. Symptom counts for five fear (criticism, the unknown, death, animal, medical) and four anxiety (generalized, panic, separation, social) dimensions were obtained for 373 twin pairs ages 9-14. Multivariate twin modeling was performed to elucidate the genetic and environmental influences distributed amongst these dimensions. The best fitting model contained one genetic, two familial environmental, and two unique environmental factors shared between fear and anxiety symptoms plus dimension-specific genetic and unique environmental factors. Although several environmental factors were shared between fear and anxiety dimensions, one latent factor accounted for genetic influences across both domains. While adult studies find somewhat distinct etiological differences between anxiety and phobic disorders, the current results suggest that their relative genetic and environmental influences are not as clearly demarcated in children. These etiological distinctions are more nuanced, likely contributing to the highly diffuse symptom patterns seen during development.

The modulation of the startle response (SR) by threatening stimuli (fear-potentiated startle; FPS), is a proposed endophenotype for disorders of the fearful-fearlessness spectrum. FPS has failed to show evidence of heritability, raising concerns. However, the metrics used to index FPS – and, importantly, other conditional phenotypes that are dependent on a baseline – may not be suitable for the approaches used in genetic epidemiology studies. Here we evaluated multiple metrics of FPS in a population-based sample of pre-adolescent twins (N = 569 from 320 twin pairs, M(age) = 11.4) who completed a fear-conditioning paradigm with airpuff-elicited SR on two occasions (~1 month apart). We applied univariate and multivariate biometric modeling to estimate the heritability of FPS using several proposed standardization procedures. This was extended with data simulations to evaluate biases in heritability estimates of FPS (and similar metrics) under various scenarios. Consistent with previous studies, results indicated moderate test-retest reliability (r = .59) and heritability of the overall SR (h(2) = 34%) but poor reliability and virtually no unique genetic influences on FPS when considering a raw or standardized differential score that removes baseline SR. Simulations demonstrated that the use of differential scores introduces bias in heritability estimates relative to jointly analyzing baseline SR and FPS in a multivariate model. However, strong dependency of FPS on baseline levels make unique genetic influences virtually impossible to detect regardless of methodology. These findings indicate that FPS and other conditional phenotypes may not be well-suited to serve as endophenotypes unless such co-dependency can be disentangled.