In this chapter, we critically reviewed findings suggesting the existence of two psychopathological dimensions: apprehension/fear and somatic concern/somatisation. The complex interplay between environment, genetics, endocrine and immune systems, and brain circuitries underlying these two dimensions is discussed, with a specific focus on relevance in terms of trans-diagnostic expression. Furthermore, starting with the data presented in Chap. 2, we provide evidence of a clear expression of these two dimensions across traditional diagnostic boundaries, further highlighting the need for a dimensional approach to psychiatric syndromes. Finally, we describe some clinical cases that in our clinical experience might represent an important portrait of a real-word scenario in which these theoretical notions could be applied. Starting with these considerations, an overview of the potential implication for treatment is provided.