title: Neuropsychiatric symptoms in Parkinson's disease: fronto-striatal atrophy contributions.
abstract: BACKGROUND
  Neuropsychiatric symptoms (NPS) in Parkinson's disease (PD) have been mostly attributed to neurotransmitter imbalances. However, recent findings suggest that gray matter atrophy also contributes to NPS in PD. We contrast PD patients with different levels of NPS, who are well-matched for dopaminergic medication levels and disease stage, to identify the fronto-striatal gray matter atrophy areas associated with NPS in PD.
  
  
  METHODS
  Fifty mild, non-demented PD patients were included. We median-split the group via a neuropsychiatric screening tool (Cambridge Behavioural Inventory-Revised), which resulted in higher vs. lower NPS groups (n = 25 in each group). Using T1 brain scans acquired on a 3 Tesla MRI scanner, voxel-based morphometry analysis was applied to characterize the pattern of fronto-striatal gray matter atrophy associated with elevated NPS.
  
  
  RESULTS
  We found that the higher NPS group was characterized by greater atrophy in the prefrontal cortex, but not striatal areas. This was further corroborated by a post-hoc analysis cross-correlating the severity of NPS with gray matter loss across the whole PD group, which revealed that atrophy in the orbitofrontal cortex and frontal pole was specifically associated with elevated NPS.
  
  
  CONCLUSIONS
  Prefrontal cortex atrophy in PD has an additional effect to dopamine replacement therapy on the generation of NPS in these patients. These findings are an important step towards the delineation of atrophy vs. neurochemical imbalance in PD, and the results emphasize the importance of considering interactions between prefrontal atrophy and neurochemical dysfunction in the genesis of neuropsychiatric symptoms in PD.
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: C
authors.initials: C
authors.lastname: O'Callaghan
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Shine
authors.affiliation: Brain and Mind Research Institute, University of Sydney, Sydney, Australia.
authors.forename: S J G
authors.initials: SJ
authors.lastname: Lewis
authors.affiliation: Neuroscience Research Australia, Sydney, Australia; Department of Clinical Neurosciences, Cambridge University, Cambridge, UK. Electronic address: mh755@medschl.cam.ac.uk.
authors.forename: M
authors.initials: M
authors.lastname: Hornberger
mesh_terms: D000368:Aged; D001284:Atrophy / Q000473:pathology; D003342:Corpus Striatum / Q000473:pathology; D003704:Dementia / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000473:pathology* / Q000523:psychology*; D017397:Prefrontal Cortex / Q000473:pathology*
keywords: Fronto-striatal; Magnetic resonance imaging; Neuropsychiatric; Parkinson's disease; Voxel-based morphometry