Pathoanatomic correlates of psychiatric symptoms in PINK1 mutation carriers

Objectives: Mutations in the PINK1 gene can cause parkinsonism and are frequently associated with psychiatric symptoms that may even precede motor symptoms and signs. The aim of the present voxel-based morphometric (VBM) MRI study was to determine whether different psychiatric symptoms in PINK1 mutation carriers (Pmc) are associated with specific structural gray matter volume (GMV) changes.

Methods: We compared structural MR images of 14 Pmc (major depression [N=5], schizophrenia-spectrum disorders [N=4], panic disorder [N=2], adjustment disorder [N=2] and obsessive compulsive personality disorder [N=2]) and 14 age- and sex-matched healthy controls. MR images were preprocessed and analyzed with SPM2 (Wellcome Department of Cognitive Neurology, London, UK) and VBM. Based on previous morphometric data in psychiatric patients, we hypothesized reduced GMV mainly in limbic and frontal structures. Canonical contrasts were calculated between Pmc and controls. Negative correlations between GMV and psychiatric scores were performed using the regression algorithms. Following our a-priori-hypothesis, small volume corrections with a sphere of 10mm were applied. The WFU PickAtlas was used as anatomical reference.

Results: The categorical comparison between 14 Pmc and controls revealed a decrease in GMV within the limbic hippocampus and parahippocampal gyrus. Categorical comparisons between the psychiatric subgoups and controls showed a significant decrease in GMV of the parahippocampal gyrus in the schizophrenia-spectrum and adjustment disorder subgroups. Wheras for the obsessive-compulsive personality disorder subgroup mostly a GMV decrease was found in frontal structures (dorsolateral and prefrontal cortex, right insula) and in the cingulate gyrus.

Multiple regression analysis considering all psychiatric subscores displayed degeneration patterns including frontal (prefrontal, dorsolateral and premotor cortex) and limbic (parahippocampus and cingulate) structures. The correlation with duration of the psychiatric disease yielded a degeneration pattern involving also limbic and frontal structures.

Conclusion: Various psychiatric disorders representing different phenotypes of a single mutation in PINK1 are associated with distinct patterns of GMV degeneration. The nature of the diversity of the psychiatric symptoms and the underlying individual susceptibility to GMV degeneration in Pmc remains unknown and needs to be elucidated in further studies.