The cognitive anxiety sensitivity treatment (CAST) in anxiety prevention - Focus on separation anxiety and interoception.

Given the high prevalence and considerable clinical and societal burden of anxiety disorders, preventive measures are urgently warranted to reduce their incidence and overall healthcare impact. Anxiety sensitivity (AS) - a key element in learning theories of anxiety disorders in the context of interoceptive conditioning - constitutes a malleable risk factor of particularly panic disorder and separation anxiety, which share developmental, nosological, epidemiological and pathomechanistic characteristics. The computer-assisted 'Cognitive Anxiety Sensitivity Treatment' (CAST) targeting interoceptive anxiety symptoms (cf. Schmidt et al., 2014) was translated, intensified and culturally adapted to German and evaluated in a sample of 105 healthy adult volunteers with elevated AS (mean ASI-3: 29.5) applying a randomized design. Success of the intervention was measured as a function of AS and separation anxiety (ASA-27) ∼6 weeks (T1) and ∼6 months (T2) after the intervention. As compared to waitlist, CAST resulted in a significant reduction of AS at both T1 and T2. Separation anxiety was not directly reduced by the intervention, but decreased mediated by a decline in AS. A composite interoceptive score capturing changes in sensitivity to respiratory symptoms during the baseline therapist-accompanied CAST session was shown to be predictive of overall response at T1. In sum, CAST-German Version was successfully established as an effective intervention reducing AS, while at the same time indirectly decreasing separation anxiety. A composite interoceptive score predicting treatment response might aid in further delineating risk markers informing targeted preventive interventions for anxiety disorders.

Serotonergic influence on depressive symptoms and trait anxiety is mediated by negative life events and frontal activation in children and adolescents.

Depression and anxiety are common in childhood and adolescence. Even though cardinal symptoms differ, there is a considerable overlap regarding the pathogenic influence of serotonergic innervation, negative life experience, disturbed emotion perception/affect regulation, and impaired neural functioning in the fronto-limbic circuit. In this study, we examined the effect of the 5-HTTLPR/rs25531 genotype on depressive symptoms and trait anxiety under the consideration of the amount of negative life events in healthy children and adolescents (N = 389). In a subsample of 49 subjects, we performed fMRI to add fronto-limbic brain activation as a second interacting factor. Across all subjects, negative life events moderated the influence of the 5-HTTLPR/rs25531 genotype on both depressive symptoms and trait anxiety. In the fMRI subsample, 5-HTTLPR/rs25531 S + S/LG + S/LA + LGLA + LGLG genotype-associated left middle frontal gyrus (MFG) activation mediated the influence of 5-HTTLPR/rs25531 genotype on depressive symptoms, however, only in combination with negative life events. Genetic influence on trait anxiety was predominantly mediated by negative life events; only LALA genotype-specific activation in the right MFG worked as a mediator in combination with negative life events. The present findings hint towards distinct mechanisms mediating the influence of 5-HTTLPR/rs25531 genotype on depressive symptoms and anxiety, with negative life events playing a crucial role in both phenotypes. With regard to depressive symptoms, however, this influence was only visible in combination with MFG activation, whereas, in anxiety, it was independent of brain activation.