| 1 | J. Neurol. Neurosurg. Psychiatr. 2007 May 78: 532-5 |
|---|---|
| PMID | 17202228 |
| Title | Co-occurrence of affective and schizophrenia spectrum disorders with PINK1 mutations. |
| Abstract | To investigate a possible association of mutations in the PTEN-induced putative kinase 1 (PINK1) gene with psychiatric disorders in a large family with monogenic parkinsonism. 20 members of a family (4 homozygous, 11 heterozygous and 5 non-mutation carriers) were investigated for the presence of psychiatric disorders using the structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); information on three additional heterozygous mutation carriers was obtained according to the family history research diagnostic criteria. We found predominantly affective and schizophrenia spectrum disorders in 11 (61%) of the 18 mutation carriers and in 1 (20%) of the 5 mutation-negative cases. First, affective and psychotic symptoms may be part of the phenotypic spectrum or even the sole manifestation of PINK1 mutations. Second, patients with familial movement disorders associated with psychiatric conditions may serve as a valuable study population to explore (genetic) causes of neuropsychiatric disease. |
| SCZ Keywords | schizophrenia |
| 2 | Parkinsonism Relat. Disord. 2008 Aug 14: 465-70 |
| PMID | 18342564 |
| Title | Autosomal dominant dopa-responsive parkinsonism in a multigenerational Swiss family. |
| Abstract | To describe a large family with autosomal dominant parkinsonism. Seven genes are directly implicated in autosomally inherited parkinsonism. However, there are several multigenerational large families known with no identifiable mutation. Family members were evaluated clinically, by history and chart review. Genetic investigation included SCA2, SCA3, UCHL1, SNCA, LRRK2, PINK1, PRKN, PGRN, FMR1 premutation, and MAPT. The proband underwent brain fluorodopa PET (FD-PET) scan, and one autopsy was available. Eleven patients had a diagnosis of Parkinson's disease (PD), nine women. Mean age of onset was 52 with tremor-predominant dopa-responsive parkinsonism. Disease progression was slow but severe motor fluctuations occurred. One patient required subthalamic nucleus deep-brain stimulation with a good motor outcome. One patient had mental retardation, schizophrenia and became demented, and another patient was demented. Three patients and also two unaffected subjects had mild learning difficulties. All genetic tests yielded negative results. FD-PET showed marked asymmetric striatal tracer uptake deficiency, consistent with PD. Pathological examination demonstrated no Lewy bodies and immunostaining was negative for alpha-synuclein. Apart from a younger age of onset and a female predominance, the phenotype was indistinguishable from sporadic tremor-predominant PD, including FD-PET scan results. As known genetic causes of autosomal dominant PD were excluded, this family harbors a novel genetic defect. |
| SCZ Keywords | schizophrenia |
| 3 | Mov. Disord. 2008 Jul 23: 1461-5 |
| PMID | 18546294 |
| Title | Familial Parkinsonism with digenic parkin and PINK1 mutations. |
| Abstract | To clarify the genetic correlation between parkin and PINK1, we screened for PINK1 mutations in 175 parkinsonism patients with parkin mutations. We detected two sibling pairs and one sporadic patient carrying both parkin and PINK1 mutations. The age at onset of Parkinsonism of patients with the digenic mutations was lower than that of patients with the same parkin mutation alone. In addition, two of three patients carrying both parkin and PINK1 mutations had schizophrenia. These findings indicate that PINK1 mutation might modify parkin mutation-positive Parkinsonism, and PINK1 mutations might be associated with psychiatric disorders. |
| SCZ Keywords | schizophrenia |
| 4 | Biol. Psychiatry 2008 Aug 64: 241-7 |
| PMID | 18261714 |
| Title | Limbic and frontal cortical degeneration is associated with psychiatric symptoms in PINK1 mutation carriers. |
| Abstract | Mutations in the PINK1 gene can cause Parkinson's disease and are frequently associated with psychiatric symptoms that might even precede motor signs. 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. 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. 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. |
| SCZ Keywords | schizophrenia |
| 5 | Mol. Genet. Genomics 2015 Apr 290: 585-92 |
| PMID | 25354644 |
| Title | Common variants of the PINK1 and PARL genes do not confer genetic susceptibility to schizophrenia in Han Chinese. |
| Abstract | schizophrenia is a prevalent psychiatric disorder with a complex etiology. Mitochondrial dysfunction has been frequently reported in schizophrenia. Phosphatase and tension homologue-induced kinase 1 (PINK1) and presenilin-associated rhomboid-like protease (PARL) are mitochondrial proteins, and genetic variants of these two genes may confer genetic susceptibility to schizophrenia by influencing mitochondrial function. In this study, we conducted a two-stage genetic association study to test this hypothesis. We genotyped 4 PINK1 and 5 PARL genetic variants and evaluated the potential association of the 9 SNPs with schizophrenia in two independent case-control cohorts of 2510 Han Chinese individuals. No positive association of common genetic variants of the PINK1 and PARL genes with schizophrenia was identified in our samples after Bonferroni correction. Re-analysis of the newly updated Psychiatric Genetics Consortium (PGC) data sets confirmed our negative result. Intriguingly, one PINK1 SNP (rs10916832), which showed a marginally significant association in only Hunan samples (P = 0.032), is associated with the expression of a schizophrenia susceptible gene KIF17 according to the expression quantitative trait locus (eQTL) analysis. Our study indicated that common genetic variants of the PINK1 and PARL genes are unlikely to be involved in schizophrenia. Further studies are essential to characterize the role of the PINK1 and PARL genes in schizophrenia. |
| SCZ Keywords | schizophrenia |