Resumen de Biological traits and neurophysiological substrates of anxiety and somatic symptoms
Anxiety is an emotion state that involves behavioural, psychological and physiological changes. Importantly at its excessive expression, anxiety is usually approached as a mind-body multisystem condition specifically characterized by feelings of tension, worried thoughts and physical changes that can lead to significant distress. The aetiology of anxiety disorders (ADs) still remains unclear. However clinical and neurophysiological studies have described some important predisposing factors. Accordingly trait anxiety, body awareness and interoception have been widely used as vulnerability traits and potential markers for hypochondriasis, anxiety and somatization. In addition several brain regions have a key role in the development and maintenance of ADs, mostly those conferring the so called emotional brain (e.g.: amygdala, anterior cingulate cortex, insula and hippocampus). Besides Joint Hypermobility Syndrome (JHS), which is an inherited generalized collagen condition associated with abnormal autonomic reactivity, has shown to be a risk factor for developing ADs. Importantly, recent findings have point out a possible association between body awareness and JHS as well as specific brain regions that are likely to mediate the clinical expression of anxiety through JHS. In order to better understand the aetiology of anxiety and somatic symptoms and thus help improving the treatment of ADs, we explore biological traits and neurophysiological substrates of anxiety and somatic symptoms in a general population with different ranges of joint hypermobility (JH) as well as different ranges of non-clinical anxiety. Hence we conducted two different studies to: (1) explore the association between body awareness, sate anxiety and JH and (2) identify neural correlates of JH and trait/social anxiety. In the first study, all participants underwent a clinical examination for hypermobility, undertook tests of interoceptive sensitivity and completed questionnaire measures of state anxiety and body awareness. Also, some participants performed an emotional processing task during fMRI. In the second study, all participants were assessed with a structured clinical examination for hypermobility, completed validated questionnaire measures of anxiety tendency (i.e.: trait and social anxiety) and underwent a functional emotional paradigm using fMRI techniques. Results showed that state anxiety negatively correlates with the attention regulation subscale and the trusting body sensations subscale of the body awareness self-reported measure. Also state anxiety positively correlated with higher accuracy of interoceptive sensitivity. JH was associated with higher state anxiety and demonstrated higher interoceptive accuracy than non-JH. Still, our mediation analysis revealed that interoceptive sensitivity mediated the association found between JH and state anxiety. Likewise, JH individuals were found to present a discrete but stronger neural reactivity to affective stimuli in brain areas known to be involved in emotional processing (particularly in anxiety) and interoception (i.e.: insula, brainstem), when compared to non-hypermobile participants. Results also show a significant association between trait anxiety and social anxiety, and between trait anxiety and JH. Our ROI analyses showed no associations with BOLD signals and the anxiety measures. However when studying JH scores, ROI analyses showed a positive association between BOLD signals in the hippocampus as a response to crying faces compared to neutral faces. Additionally, the whole brain analysis showed that hypermobility scores were positively associated with an increased BOLD signal in some other key affective processing areas, such as the middle and anterior cingulate cortex, the fusiform gyros, the parahippocampal region, the orbitofrontal cortex and the cerebellum. We present the first neuroimaging study of the relationship between anxiety tendencies (state-trait anxiety, social anxiety and hypermobility) that also examines interoceptive sensitivity in a non-clinical sample. Our findings have the potential to increase our understanding of the mechanisms through which vulnerability to anxiety disorders and somatic symptoms arises in people with trait anxiety, enhanced interoception and/or JH.
