Frequency and risk factors of rebound after fingolimod discontinuation - A retrospective study.

BACKGROUND: Fingolimod (FTY) rebound, a phenomenon of unexpectedly severe disease activity following FTY discontinuation, has been reported to occur in 5-43 % of patients. Only a few larger cohorts have been analyzed. We aimed to determine the frequency and risk factors of FTY rebound in our hospital district in Southern Finland with a population of 1.7 million. METHODS: We searched the Finnish MS-register for patients who were previous or current users of FTY for at least 6 months by November 2020. We assessed medical records and collected basic demographic data for the whole cohort. Criteria for a rebound were: (i) the most severe relapse in patient's history and an increase of at least 2 EDSS points during the relapse occurring within 6 months from FTY cessation, or (ii) more than one relapse within 6 months after FTY discontinuation, this being the highest relapse rate observed during the patient's lifetime. RESULTS: Among 3496 MS patients, we found 331 patients ever starting FTY and 283 of them had used FTY for at least 6 months. Among these 283 patients we discovered a total of 114 discontinuation events in 110 patients. Of the discontinuations, 32 (28 %) were followed by a relapse: 20 (17.5 %) were ordinary relapses not fulfilling rebound criteria, and 12 (10.5 %) were rebounds. The median time to an ordinary relapse and rebound were similar: 8.5 weeks (range 1.3-23) and 9.9 weeks (range 5.9-15.9), respectively. The rebound group was younger at diagnosis (p = 0.034) and had used FTY for a longer time (p = 0.048) before discontinuation compared to the group without a relapse. After discontinuation, rebound group had lower lymphocyte values as compared to both ordinary relapse group (p = 0.027) and no-relapse group (p = 0.006) and neutrophil to lymphocyte ratio (NLR) was increased compared to the no-relapse group (p = 0.019). CONCLUSION: In this study, 10.5 % of patients experienced a rebound, which is similar to the frequencies (10.3-12.5 %) obtained in other larger studies with >100 discontinuations. Relapses of any severity occurred in 28 % of patients discontinuing FTY, and therefore initiation of subsequent disease modifying therapies should occur promptly after discontinuation. Younger age at diagnosis, longer exposure to FTY and lower lymphocyte count as well as higher NLR after discontinuation were identified as risk factors for a rebound. The differences in blood leukocytes indicate that rebound might be a distinct pathophysiological phenomenon compared to an ordinary relapse.

Primary familial brain calcification linked to deletion of 5' noncoding region of SLC20A2.

OBJECTIVES: Primary familial brain calcification (PFBC) is a rare neurological disease often inherited as a dominant trait. Mutations in four genes (SLC20A2, PDGFB, PDGFRB, and XPR1) have been reported in patients with PFBC. Of these, point mutations or small deletions in SLC20A2 are most common. Thus far, only one large deletion covering entire SLC20A2 and several smaller, exonic deletions of SLC20A2 have been reported. The aim of this study was to identify the causative gene defect in a Finnish PFBC family with three affected patients. MATERIALS AND METHODS: A Finnish family with three PFBC patients and five unaffected subjects was studied. Sanger sequencing was used to exclude mutations in the coding and splice site regions of SLC20A2, PDGFRB, and PDGFB. Whole-exome (WES) and whole-genome sequencing (WGS) were performed to identify the causative mutation. A SNP array was used in segregation analysis. RESULTS: Copy number analysis of the WGS data revealed a heterozygous deletion of ~578 kb on chromosome 8. The deletion removes the 5' UTR region, the noncoding exon 1 and the putative promoter region of SLC20A2 as well as the coding regions of six other genes. CONCLUSIONS: Our results support haploinsufficiency of SLC20A2 as a pathogenetic mechanism in PFBC. Analysis of copy number variations (CNVs) is emerging as a crucial step in the molecular genetic diagnostics of PFBC, and it should not be limited to coding regions, as causative variants may reside in the noncoding parts of known disease-associated genes.

Intrafamilial clinical variability in individuals carrying the CHCHD10 mutation Gly66Val.

OBJECTIVES: Mutations in the CHCHD10 gene, which encodes a mitochondrially targeted protein, have emerged as an important cause of motor neuron disease and frontotemporal lobar degeneration. The aim of this study was to assess the clinical variability in a large family carrying the p.Gly66Val mutation of the CHCHD10 gene. This mutation has recently been reported to cause late-onset spinal muscular atrophy (SMAJ) or sensorimotor axonal Charcot-Marie-Tooth neuropathy (CMT2) in the Finnish population. MATERIALS AND METHODS: Nine affected members of an extended Finnish pedigree were included in the study. Detailed clinical and neurophysiological examinations were performed. The CHCHD10 p.Gly66Val mutation was examined by Sanger sequencing. RESULTS: The heterozygous p.Gly66Val mutation was present in all affected individuals from whom a DNA sample was available. The clinical phenotype varied from proximal sensorimotor neuropathy to spinal muscular atrophy and in one case resembled motor neuron disease ALS at its early stages. The age of onset varied from 30 to 73 years. CONCLUSIONS: Our data demonstrate that even within the same family, the p.Gly66Val variant can cause variable phenotypes ranging from CMT2-type axonal neuropathy to spinal muscular atrophy, which may also present as an ALS-like disease. The spectrum of CHCHD10-related neuromuscular disease has widened rapidly, and we recommend keeping the threshold for genetic testing low particularly when dominant inheritance or mitochondrial pathology is present.

Association of parental communication deviance with offspring's psychiatric and thought disorders. A systematic review and meta-analysis.

Elevated number of parental Communication Deviance (CD) has been connected with psychiatric and thought disorders in their offspring. However, no earlier systematic efforts have been made to review this issue. The aim of this study was to survey the existing literature systematically and perform a meta-analysis of this association. A literature search for published and unpublished observational studies on the association of parental Communication Deviance with psychopathology in the offspring was conducted. Multiple electronic databases were searched (from 1960 to 2012) and the reference lists of the resulting publications were scanned. The findings were pooled using random effect meta-analysis. A total of 19 relevant papers were found and accessed. The results showed that a high level of parental CD is associated with schizophrenia spectrum disorders in the offspring. A large overall effect size (0.79) was found in the meta-analysis. No meta-analysis could be performed on the association of parental CD with an offspring's thought disorders, but the results suggest that such an association may exist. Parental Communication Deviance is associated with schizophrenia spectrum disorders in the offspring. High parental CD could be treated as an indicator of a risk of developing a schizophrenia spectrum disorder, at least among high-risk groups.

Doppler ultrasound examination of multiple sclerosis patients and control participants: inter-observer agreement and association with disease.

OBJECTIVE: Chronic cerebrospinal venous insufficiency (CCSVI) has been proposed as a major risk factor for multiple sclerosis (MS). The aim of this study was to assess inter-observer agreement between two ultrasound examiners and to compare findings in MS patients and control participants. METHODS: A prospective, blinded, controlled study of MS patients diagnosed within 2 years (MS ≤ 2, n = 39), patients diagnosed more than 10 years ago (MS > 10, n = 43) and age- and sex-matched control participants (n = 40). Ultrasound examinations were performed by two independent examiners. CCSVI criteria 1, 3, 4 and 5 as proposed by Zamboni were explored: (1) reflux in the internal jugular (IJV) and vertebral veins (VV), (3) IJV cross-sectional area (CSA) ≤0.3 cm(2), (4) absence of flow in IJV and VV, and (5) reverted postural control of venous outflow. RESULTS: Criteria 1, 4 and 5 were met in less than 10% of the MS patients and control participants as studied by both examiners. The level of inter-observer agreement was poor for all parameters except assessment of the CSA of IJV at the thyroid level. Findings meeting CCSVI criterion 3 (CSA ≤ 0.3 cm(2)) were observed in 18/40 (45%) of the control participants, in 24/37 (65%) of MS ≤ 2 patients (p = 0.09 vs. control participants) and in 30/43 (70%) of the MS > 10 patients (p = 0.022 vs. control participants). CONCLUSIONS: The feasibility of the CCSVI criteria for common use is questionable because of low inter-observer agreement. Small-calibre IJVs meeting the CCSVI criterion 3 appear common in both Finnish control participants and MS patients, but the clinical significance of this finding is questionable.

The stability of severe thought disorders and mature thinking.

The aim of this study was to investigate whether severe formal thought disorders and mature thinking are stable among adoptees (=187) drawn from the Finnish adoptive family study of schizophrenia. A group of 93 adoptees genetically at high risk (HR) and 94 at low risk (LR) for schizophrenia were assessed blindly and reliably using the Index of Primitive Thought (IPT) and the Index of Integration (IOI). Two assessments of the IPT and the IOI were performed with the mean interval of 11 years. Comparisons of the IPT and the IOI mean scores were conducted both at baseline and at follow-up between adoptees at low and high genetic risk, gender, and psychiatric status. The main result was that the IOI as well as the IPT of the adoptees at the initial assessment predicted the IOI and the IPT estimated at follow-up, thus indicating the stability of severe formal thought disorders and mature thinking over time. The stability of IOI or IPT was not related to genetic risk, gender or psychiatric status or their interactions.

DARS2 mutations in mitochondrial leucoencephalopathy and multiple sclerosis.

BACKGROUND: Leucoencephalopathy with brain stem and spinal cord involvement and high brain lactate (LBSL) was first defined by characteristic magnetic resonance imaging and spectroscopic findings. The clinical features include childhood or juvenile onset slowly progressive ataxia, spasticity, and dorsal column dysfunction, occasionally accompanied by learning difficulties. Mutations in DARS2, encoding mitochondrial aspartyl-tRNA synthetase, were recently shown to cause LBSL. The signs and symptoms show some overlap with the most common leucoencephalopathy of young adults, multiple sclerosis (MS). OBJECTIVE: To clarify the molecular background of LBSL patients in Finland, and to look for DARS2 mutations in a group of MS patients. METHODS: Clinical evaluation of LBSL patients, DARS2 sequencing and haplotype analysis, and carrier frequency determination in Finland. RESULTS: All eight LBSL patients were compound heterozygotes for DARS2 mutations: all carried R76SfsX5 change, seven had M134_K165del, and one had C152F change. Axonal neuropathy was found in five of the eight patients. The carrier frequencies of the R76SfsX5 and M134_K165del mutations were 1:95 and 1:380, respectively. All patients shared common European haplotypes, suggestive of common European LBSL ancestors. No enrichment of the two common DARS2 mutations was found in 321 MS patients. CONCLUSION: All LBSL patients were compound heterozygotes, which suggests that DARS2 mutation homozygosity may be lethal or manifest as a different phenotype. The authors show here that despite identical mutations the clinical picture was quite variable in the patients. Axonal neuropathy was an important feature of LBSL. DARS2 mutations cause childhood-to-adolescence onset leucoencephalopathy, but they do not seem to be associated with MS.

Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis.

Multiple sclerosis (MS) is a complex disorder of the central nervous system, causing inflammation, demyelination and axonal damage. A limited number of genetic risk factors for MS have been identified, but the etiology of the disease remains largely unknown. For the identification of genes regulating neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a linkage analysis in an advanced intercross line (AIL). We thereby redefine the Eae18b locus to a 0.88 Mb region, including a cluster of chemokine genes. Further, we show differential expression of Ccl2, Ccl11 and Ccl11 during EAE in rat strains with opposite susceptibility to EAE, regulated by genotype in Eae18b. The human homologous genes were tested for association to MS in 3841 cases and 4046 controls from four Nordic countries. A haplotype in CCL2 and rs3136682 in CCL1 show a protective association to MS, whereas a haplotype in CCL13 is disease predisposing. In the HLA-DRB1* 15 positive subgroup, we also identified an association to a risk haplotype in CCL2, suggesting an influence from the human leukocyte antigen (HLA) locus. We further identified association to rheumatoid arthritis in CCL2, CCL8 and CCL13, indicating common regulatory mechanisms for complex diseases.

Interferon regulatory factor 5 (IRF5) gene variants are associated with multiple sclerosis in three distinct populations.

BACKGROUND: IRF5 is a transcription factor involved both in the type I interferon and the toll-like receptor signalling pathways. Previously, IRF5 has been found to be associated with systemic lupus erythematosus, rheumatoid arthritis and inflammatory bowel diseases. Here we investigated whether polymorphisms in the IRF5 gene would be associated with yet another disease with features of autoimmunity, multiple sclerosis (MS). METHODS: We genotyped nine single nucleotide polymorphisms and one insertion-deletion polymorphism in the IRF5 gene in a collection of 2337 patients with MS and 2813 controls from three populations: two case-control cohorts from Spain and Sweden, and a set of MS trio families from Finland. RESULTS: Two single nucleotide polymorphism (SNPs) (rs4728142, rs3807306), and a 5 bp insertion-deletion polymorphism located in the promoter and first intron of the IRF5 gene, showed association signals with values of p<0.001 when the data from all cohorts were combined. The predisposing alleles were present on the same common haplotype in all populations. Using electrophoretic mobility shift assays we observed allele specific differences in protein binding for the SNP rs4728142 and the 5 bp indel, and by a proximity ligation assay we demonstrated increased binding of the transcription factor SP1 to the risk allele of the 5 bp indel. CONCLUSION: These findings add IRF5 to the short list of genes shown to be associated with MS in more than one population. Our study adds to the evidence that there might be genes or pathways that are common in multiple autoimmune diseases, and that the type I interferon system is likely to be involved in the development of these diseases.

Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease.

OBJECTIVE: Dysfunction of mitochondrial DNA polymerase gamma (POLG) has been recently recognized as an important cause of inherited neurodegenerative diseases. We have reported dominant and recessive inheritance of parkinsonism, mitochondrial myopathy, and premature amenorrhea in five ethnically distinct families with POLG1 mutations. This prompted us to carry out a detailed analysis of the coding region and intron-exon boundaries of POLG1 in Finnish patients with idiopathic sporadic Parkinson disease (PD) and in nonparkinsonian controls. METHODS: The coding region of POLG1 was analyzed in 140 Finnish patients with PD and their 127 spouses as age- and ethnically matched controls. Further, we analyzed the intragenic CAG-repeat region of POLG1 in 126 additional patients with nonparkinsonian neurologic disorders and in 516 Finnish population controls. RESULTS: We found clustering of rare variants of the POLG1 CAG-repeat, encoding a polyglutamine tract, in Finnish patients with idiopathic PD as compared to their spouses (p = 0.003; OR 3.01, 95% CI 1.35 to 6.71), population controls (p = 0.001; OR 2.45, 95% CI 1.45 to 4.14), and patients with nonparkinsonian neurologic disorders (p = 0.05, OR 1.98, 95% CI 0.97 to 4.05). We found several amino acid substitutions, none of them associating with PD. These included a previously parkinsonism-associated POLG variant Y831C, found in one patient with PD, but also in five controls, suggesting that it is a neutral amino acid polymorphism. CONCLUSIONS: Our results suggest that POLG polyglutamine tract variants should be considered as a predisposing genetic factor in idiopathic sporadic Parkinson disease.

Mapping susceptibility gene locus for IgA deficiency at del(18)(q22.3-q23); report of familial cryptic chromosome t(18q; 10p) translocations.

This study presents a clinical report of the Finnish chromosome t(18q; 10p) translocation family with an overview of eight other selected immunoglobulin A (IgA)-deficient 18q deletion (18q-) patients from seven published articles. The family members show features common to 18q- syndrome such as mental retardation, multiple facial dysmorphism, foot/hand deformities, abnormal myelination of brain white matter, and a spectrum of immunological/infectious disorders including IgA deficiency (IgAD). Genotype-phenotype correlation study of the unbalanced t(18q-; 10p+) translocation family members and other 18q- syndrome reports led to definition of a potential susceptibility gene locus for IgAD at distal region of 18q22.3-q23 between markers D18S812-18qter. The haplo-insufficiency of the 18q22.3-q23 gene region is suggested to be a cause of the IgAD phenotype in 18q- individuals. This 7 Mb IgAD critical region shows significant association with susceptibility region for celiac disease that is frequently connected to IgAD.

BDNF tagging polymorphisms and haplotype analysis in sporadic Parkinson's disease in diverse ethnic groups.

Experimental and clinical data suggest that genetic variations in brain-derived neurotrophic factor (BDNF) gene may affect risk for Parkinson's disease (PD). We performed a case-control association analysis of BDNF in three independent Caucasian cohorts (Greek, North American, and Finnish) of PD using eight tagging SNPs and five constructed haplotypes. No statistically significant differences in genotype and allele frequencies were found between cases and controls in all series. A relatively rare BDNF haplotype showed a trend towards association in the Greek (p=0.02) and the Finnish (p=0.03) series (this haplotype was not detected in the North American series). However, given the large number of comparisons these associations are considered non-significant. In conclusion, our results do not provide statistically significant evidence that common genetic variability in BDNF would associate with the risk for PD in the Caucasian populations studied here.

Association of tau haplotype-tagging polymorphisms with Parkinson's disease in diverse ethnic Parkinson's disease cohorts.

BACKGROUND: The overlap in the clinical and pathological features of tauopathies and synucleinopathies raises the possibility that the tau protein may be important in Parkinson's disease (PD) pathogenesis. Several MAPT polymorphisms that define the tau H1 haplotype have been investigated for an association with PD with conflicting results; however, two meta-analyses support an association between haplotype H1 and PD. METHODS: In this study, we recruited 508 patients and 611 healthy controls from Greek, Finnish and Taiwanese populations. We examined the possible genetic role of variation within MAPT in PD using haplotype-tagging single polymorphisms (SNPs) in these ethnically different PD populations. RESULTS: We identified a moderate association at SNP rs3785883 in the Greek cohort for both allele and genotype frequency (p = 0.01, p = 0.05, respectively) as well as for SNP rs7521 (genotype p = 0.02) and rs242557 (p = 0.01 genotypic, p = 0.04 allelic) in the Finnish population. There were no significant differences in genotype or allele distribution between cases and controls in the Taiwanese cohort. CONCLUSION: We failed to demonstrate a consistent association between the MAPT H1 haplotype (delineated by intron 9 ins/del) and PD in three ethnically diverse populations. However, the data presented here suggest that subhaplotypes of haplotype H1 may confer susceptibility to PD, and that either allelic heterogeneity or different haplotype composition explain the divergent haplotype results.

Testing association between LRRK2 and Parkinson's disease and investigating linkage disequilibrium.

BACKGROUND: We and others recently identified the gene underlying PARK8 linked Parkinson's disease (PD). This gene, LRRK2, contains mutations that cause an autosomal dominant PD, including a mutation, G2019S, which is the most common PD causing mutation identified to date. Common genetic variability in genes that contain PD causing mutations has previously been implicated as a risk factor for typical sporadic disease. METHODS: We undertook a case-control association analysis of LRRK2 in two independent European PD cohorts using 31 tagging single nucleotide polymorphisms (tSNPs) and five potentially functional SNPs. To assess the structure of this locus in different populations, we have performed linkage disequilibrium (LD) analysis using these variants in a human diversity panel. RESULTS: We show that common genetic variability in LRRK2 is not associated with risk for PD in the European populations studied here. We also show inter-population variability in the strength of LD across this locus. CONCLUSIONS: To our knowledge this is the first comprehensive analysis of common variability within LRRK2 as a risk factor for PD.

Thought Disorder Index: a longitudinal study of severity levels and schizophrenia factors.

BACKGROUND: Thought disturbances are commonly associated with psychiatric disorders, especially schizophrenia. Our aim was to clarify whether thought disorders are only stable at certain severity levels and in the presence of certain schizophrenia factors of the Thought Disorder Index (TDI) scale. Furthermore, we also examined the significance of genetic status and the psychiatric disorder for the persistence of TDI severity levels and factors. METHODS: The thought disorders of 158 adoptees genetically at high-risk or low-risk for schizophrenia participating the Finnish Adoptive Family Study of Schizophrenia were evaluated twice at a mean interval of 11 years. Thought Disorder Index (TDI) was used to assess the severity levels and schizophrenia factors. TDI identifies 23 different items of thinking disturbances, which are weighted along a continuum of severity. RESULTS: Thought disorders at the 0.50 and 0.75 severity levels and idiosyncratic verbalization indicative of the schizophrenia factors turned out to be stable phenomena throughout the follow-up period. The adoptees' genetic or psychiatric status was not associated with the results. CONCLUSIONS: The study shows that the stability of TDI seems to be related to the most severe categories of thought disorders. However, of the specific schizophrenia factors, idiosyncratic verbalization, but not confusion and fluid thinking, showed stability over time. Although idiosyncratic verbalization does not necessarily represent the most severe type of thought disturbance, it turned out relatively stable and we can speculate that idiosyncratic verbalization have some predictive value, too.

Cerebral amyloid angiopathy in a 95+ cohort: complement activation and apolipoprotein E (ApoE) genotype.

There is growing evidence that in Alzheimer's disease (AD) amyloid beta-protein (Abeta) triggers a chronic inflammatory reaction in cerebral amyloid plaques, including complement proteins. Abeta also accumulates cerebrovascularly in age- and AD-associated cerebral amyloid angiopathy (CAA). We investigated complement proteins in CAA in a population-based series using histological and immunohistochemical staining methods. The 74 subjects, aged 95 years or more, had undergone clinical neurological examination and apolipoprotein E (ApoE) genotyping. The brains had been studied for AD post-mortem, allowing us to relate the histopathological findings to clinical and genetic conditions. CAA with congophilic amyloid was found in 36/74 individuals (48.6%). The vascular amyloid deposits immunoreacted with antibodies to Abeta and complements 3d (C3d) and 9 (C9). The positivity in complement stains increased with growing severity of CAA (P = 0.001). The presence of CAA associated with ApoE epsilon4 (P = 0.0005) and overrepresentation of epsilon4 among those with moderate or severe vs. mild CAA (P = 0.03) was demonstrated. The presence of CAA associated with dementia (P = 0.01), which was contributed by both epsilon4+ (P = 0.02) and epsilon4- (P = 0.06) subjects. Our study shows that complement proteins are deposited in the affected vessels in Abeta-associated CAA. They may solely represent the cerebral Abeta- burden associated to inflammatory stimuli, or signal a contribution in the clearance of cerebral Abeta, thereby contributing to the events associated with evolution of clinical dementia. Our results demonstrate a strong association between CAA and ApoE epsilon4 as well as dementia and suggest that the contribution of CAA to dementia is largely independent of ApoE epsilon4.

How useful is [123I]beta-CIT SPECT in clinical practice?

OBJECTIVE: To assess the accuracy and clinical usefulness of [(123)I]beta-CIT (2beta-carbomethoxy-3beta-(4-iodophenyl)tropane) SPECT in the differential diagnosis of Parkinson's disease. SUBJECTS: 185 consecutive patients with symptoms of movement disorder were studied. The diagnoses were Parkinson's disease (92), essential tremor (16), vascular parkinsonism (15), various Parkinson plus syndromes (P+) (12), dementia with Lewy bodies (DLB) (5), dystonia (5), drug induced movement disorder (12), and other diagnoses (8). A reference group (psychogenic parkinsonism) comprised 20 subjects with complaints suggesting extrapyramidal disease but with no unequivocal signs on clinical examination and no abnormalities on brain imaging. RESULTS: beta-CIT uptake was significantly lower in the whole striatum as well as separately in the putamen and in the caudate nucleus in Parkinson's disease than in the reference group or in drug induced movement disorder, essential tremor, or dystonia. The uptake of beta-CIT in the vascular parkinsonism group was heterogeneous and mean beta-CIT uptake fell between the reference group and the Parkinson's disease group. In the P+ and DLB groups the striatal uptake ratios overlapped those of the Parkinson's disease group. CONCLUSIONS: [(123)I]beta-CIT SPECT may not be as useful a tool in the clinical differential diagnosis of Parkinson's disease as was previously believed, but it was 100% sensitive and specific for the diagnosis in younger patients (age <55 years). In older patients (age >55 years) specificity was substantially lower (68.5%). This differential specificity reflected the different distribution of differential diagnostic disorders (P+, DLB, vascular parkinsonism) in the older and younger age groups.

Stability of Thought Disorder Index among high-risk and low-risk adoptees in the Finnish adoptive family study of schizophrenia.

The aim of the study was to evaluate whether thought disorders are stable, trait-like features specific to subjects who have a genetic liability to schizophrenia or a psychiatric disorder. The thought disorders of adoptees genetically at high risk (HR) or low risk (LR) for schizophrenia from the Finnish adoptive family study of schizophrenia were evaluated twice at a mean interval of 11 years, using the sum of the Thought Disorder Index (TDI) scores on the Rorschach (TD(R)). At the initial assessment, the mean TD(R) scores of women were significantly higher than those of men, while no association between genetic risk and psychiatric status or their interactions with the TD(R) scores at baseline were found. The main finding was that the initial TD(R) scores statistically significantly predicted the TD(R) scores at follow-up, thus indicating the stability of thought disorder over time. However, neither genetic or psychiatric status nor gender or any interaction between these variables associated with TD(R) at follow-up.

SNCA multiplication is not a common cause of Parkinson disease or dementia with Lewy bodies.

The authors recently have shown that triplication of the alpha-synuclein gene (SNCA) can cause Parkinson disease (PD) and diffuse Lewy body disease within the same kindred. The authors assessed 101 familial PD probands, 325 sporadic PD cases, 65 patients with dementia with Lewy bodies, and 366 neurologically normal control subjects for SNCA multiplication. The authors did not identify any subjects with multiplication of SNCA and conclude this mutation is a rare cause of disease.