HPA axis, respiration and the airways in stress—A review in search of intersections

Given clear connections between respiratory distress and subjective anxiety, it is not surprising that respiratory psychophysiologists have been interested in the psychobiology of anxiety. Given parallel links between anxiety and stress, it is not surprising that the hypothalamic-pituitary adrenal (HPA) stress system has also been a focus in anxiety research. However, despite extensive work in respiratory psychophysiology and stress neuroendocrinology - and evidence that these systems are jointly dysregulated in anxiety disorders - direct studies of their interactions are rare. This paper reviews evidence for scientific intersections, providing an overview of the HPA axis, its psychobiology, and shared neural substrates for HPA and respiratory control. We examine HPA hormone effects on respiration, immune/inflammatory mediators, and lung maturation. We also examine respiratory/dyspnea effects on HPA axis. There are clear points of intersection in the neuroscience of respiration and stress. Given the importance of both systems to an organism's ability to survive and adapt in challenging and changing environments, further study of their interactions is needed.     

Extending the clinical phenotype of SPTAN1: From DEE5 to migraine,epilepsy, and subependymal heterotopias without intellectual disability

Mutations in SPTAN1 gene, encoding the nonerythrocyte αII-spectrin, are responsible for a severe developmental and epileptic encephalopathy (DEE5) and a wide spectrum of neurodevelopmental disorders, as epilepsy with or without intellectual disability (ID) or ID with cerebellar syndrome. A certain genotype–phenotype correlation has been proposed according to the type and location of the mutation. Herein, we report three novel cases with de novo SPTAN1 mutations, one of them associated to a mild phenotype not previously described. They range from (1) severe developmental encephalopathy with ataxia and a mild cerebellar atrophy, without epilepsy; (2) moderate intellectual disability, severe language delay, ataxia and tremor; (3) normal intelligence, chronic migraine, and generalized tonic–clonic seizures. Remarkably, all these patients showed brain MRI abnormalities, being of special interest the subependymal heterotopias detected in the latter patient. Thus we extend the SPTAN1-related phenotypic spectrum, both in its radiological and clinical involvement. Furthermore, after systematic analysis of all the patients so far reported, we noted an excess of male versus female patients (20:9, p = 0.04), more pronounced among the milder phenotypes. Consequently, some protection factor might be suspected among female carriers, which if confirmed should be considered when establishing the pathogenicity of milder genetic variants in this gene.