Limbic and Frontal Cortical Degeneration Is Associated with Psychiatric Symptoms in PINK1 Mutation Carriers

Background: Mutations in the PINK1 gene can cause Parkinson's disease and are frequently associated with psychiatric symptoms that might even precede motor signs. Methods: To determine whether specific gray matter degeneration of limbic and frontal structures might be liable to different psychiatric symptoms in PINK1 mutation carriers, observer-independent voxel-based morphometry was applied to high-resolution magnetic resonance images of 14 PINK1 mutation carriers from a large German family and 14 age- and gender-matched healthy control subjects. Results: Psychiatric diagnoses in PINK1 mutation carriers comprised major depression without psychotic symptoms and schizophrenia-spectrum, panic, adjustment, and obsessive-compulsive personality disorders. As hypothesized, the categorical comparison between all PINK1 mutation carriers and control subjects demonstrated atrophy of limbic structures, especially the hippocampus and parahippocampus. More specifically, multiple regression analysis considering all psychiatric subscores simultaneously displayed different frontal (prefrontal, dorsolateral, and premotor cortex) and limbic (parahippocampus and cingulate) degeneration patterns. The duration of the psychiatric disease was also correlated with the extent of limbic and frontal gray matter volume decrease. Conclusions: Our results support the hypothesis that limbic and frontal gray matter alterations could explain various psychiatric symptoms observed in PINK1 mutation carriers. Factors determining individual susceptibility to degeneration of certain brain areas remain to be elucidated in future studies.