Treatment-refractory chronic depression in a CADASIL patient with a symptom-free somatic course: a case report

Abstract

Listen

Translate article

Depressive disorders are very common psychiatric disorders that are usually well treatable. However, special attention is required if the depressive symptoms do not improve despite guideline-compliant treatment and if brain structural changes can be detected on neuroimaging.We report on a genetically newly diagnosed 63-year-old patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with a two-decade course of severe affective symptoms in the absence of classical somatic disease characteristics although we found a pathogenic variant in the EGFr 4 domain of the NOTCH3 protein.CADASIL is a rare inherited disease of the small cerebral vessels which is caused by mutations in the NOTCH3 gene. The disease typically begins in young adulthood and is characterized by ischemic strokes, migraine-like headaches, psychiatric disturbance, and cognitive decline. Pathogenic variants in NOTCH3 EGFr domains 1-6 are associated with a more severe somatic phenotype. Our case report highlights the phenotypic heterogeneity of CADASIL with only psychiatric symptoms despite mutation within EGFr domain 4; therefore, CADASIL should be considered in the presence of affective disorders, lack of response to antidepressants and typical MR changes.