Structural brain abnormalities in patients with severe health anxiety: A cross-sectional MRI study

Background: Severe health anxiety (HA) is characterized by a persistent preoccupation with one's health and excessive fear of having or acquiring a serious illness. HA is understudied and its structural implications on the brain are largely unknown. Here, we wanted to investigate whether key structures of the fear processing network affected in anxiety disorders i.e., the amygdala, thalamus and prefrontal cortex, are also implicated in HA, and explore potentially distinct abnormalities. Methods: 22 patients with severe HA and 22 matched healthy controls were investigated with structural MRI. Using the FreeSurfer processing pipeline, we assessed group differences in the volumes of the amygdala, thalamus, and cerebral white matter, as well as the thickness of the medial orbitofrontal cortex. Additionally, exploratory whole-brain surface-based analyses were performed, along with post-hoc analyses of individual thalamic nuclei. Results: Compared to controls, patients with HA had significant increases in bilateral whole thalamus volumes (left η²ₚ = 0.096, p = 0.048; right η²ₚ = 0.256, p < 0.001), decreases in the left medial orbitofrontal cortex thickness (η²ₚ = 0.102, p = 0.041), and increases in global cerebral white matter volume (left η²ₚ = 0.105, p = 0.038; right η²ₚ = 0.136, p < 0.018). Larger volumes of the right ventromedial thalamic nuclei (r = 0.652, p = 0.002) were associated with stronger HA symptoms. No significant group differences were found in the bilateral amygdala. Conclusion: Our findings suggest gray matter alterations in the thalamus and medial orbitofrontal cortex as shared features of HA and anxiety disorders. The correlation between symptom severity and a distinct thalamic subregion, alongside absent amygdala differences, may indicate features that differentiate HA from other anxiety disorders.