title: Limbic and frontal cortical degeneration is associated with psychiatric symptoms in PINK1 mutation carriers.
abstract: 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.
authors.affiliation: Department of Neurology, University of Luebeck, Luebeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Reetz
authors.forename: Rebekka
authors.initials: R
authors.lastname: Lencer
authors.forename: Susanne
authors.initials: S
authors.lastname: Steinlechner
authors.forename: Christian
authors.initials: C
authors.lastname: Gaser
authors.forename: Johann
authors.initials: J
authors.lastname: Hagenah
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.forename: Dirk
authors.initials: D
authors.lastname: Petersen
authors.forename: Norman
authors.initials: N
authors.lastname: Kock
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Binkofski
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008032:Limbic System / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D001523:Mental Disorders / Q000150:complications / Q000235:genetics / Q000473:pathology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019636:Neurodegenerative Diseases / Q000150:complications / Q000235:genetics / Q000473:pathology; D009460:Neurologic Examination / Q000379:methods; D011494:Protein Kinases / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase