Brain microstructural changes and cognitive function in non-demented essential tremor patients: a diffusion tensor imaging study.

BACKGROUND: Essential tremor (ET) is disease with both motor and non-motor features. Notable among the non-motor features is cognitive impairment. While this impairment has been attributed to cortico-thalamo-cerebellar pathway pathology, it is likely that a more complicated involvement of brain structures underlies cognitive function in ET. OBJECTIVE: To evaluate the brain microstructural changes of both white matter and grey matter in ET using region of interest based diffusion tensor imaging (DTI), and to correlate these changes with cognitive function assessed during detailed neuropsychological testing. METHOD: Thirty-five non-demented ET patients with a range of cognitive function (Clinical Dementia Rating = 0-0.5, mean age = 57.5 ± 16.7 years, age range = 23-76 years) underwent a comprehensive neuropsychological evaluation and brain magnetic resonance imaging, including DTI. DTI findings were reported as fractional anisotropy, average diffusion coefficient, these values were evaluated for 32 ROIs. Cognitive domains included attention, visuospatial functions, executive function, verbal memory, visual memory, and language. Domain Z-scores were calculated each cognitive domain and compared for each brain region. RESULTS: Microstructural changes in prefrontal cortical areas (dorsolateral, ventrolateral), paralimbic and limbic structures (posterior cingulate cortex, precuneus, hippocampus), basal ganglia (substantia nigra, putamen, caudate nucleus) and white matter bundles (corpus callosum, anterior thalamic radiation, longitudinal fasciculus, frontooccipital fasciculus, etc.) correlated with specific domains of cognitive function in ET patients. CONCLUSION: These data suggest that not only the cerebello thalamocortical pathway, but numerous other brain structures are related to level of cognitive performance and possibly underlie cognitive dysfunction in ET.

Cognition in non-demented Parkinson's disease vs essential tremor: A population-based study.

OBJECTIVES: Patients with Parkinson's disease (PD) and essential tremor (ET) have a higher risk of cognitive impairment than age-matched controls. Only a few small studies (11-18 subjects per group) have directly compared the cognitive profile of these conditions. Our aim was to compare the cognitive profile of patients with these two conditions to each other and to healthy individuals in a population-based study of non-demented participants. MATERIALS AND METHODS: This investigation was part of the NEDICES study, a survey of the elderly in which 2438 dementia-free participants underwent a short neuropsychological battery. We used nonparametric techniques to evaluate whether there are differences and/or a gradient of impairment across the groups (PD, ET, and controls). Also, we performed a head-to-head comparison of ET and PD, adjusting for age and education. RESULTS: Patients with PD (N=46) and ET (N=180) had poorer cognition than controls (N=2212). An impaired gradient of performance was evident. PD scored lower than ET, and then each of these lower than controls, in memory (P<.05) and verbal fluency (P<.001) tasks. When we compared PD and ET, the former had lower scores in verbal fluency (P<.05), whereas the later had a poorer cognitive processing speed (P<.05). CONCLUSIONS: This large population-based study demonstrates that both conditions influence cognitive performance, that a continuum exists from normal controls to ET to PD (most severe), and that although deficits are in many of the same cognitive domains, the affected cognitive domains do not overlap completely.

Genetic analysis of ten common degenerative hereditary ataxia loci in patients with essential tremor.

BACKGROUND: To investigate the association of repeat expansion size in 10 common degenerative hereditary ataxia genes with essential tremor. These genes were spinocerebellar ataxia (SCA)-1 (ATXN1), SCA-2 (ATXN2), SCA-3 (ATXN3), SCA-6 (CACNA1A), SCA-7 (ATXN7), SCA-8 (ATXN8OS), SCA-10 (ATXN10), SCA-12 (PPP2R2B), SCA-17 (TBP) and dentatorubral-pallidolysian atrophy (DRPLA) (ATN1). METHODS: Genetic analysis of repeat size in 10 degenerative hereditary ataxia loci was performed in 323 essential tremor patients and 299 controls enrolled at Columbia University. To test for differences in the allele distribution between patients and controls, a CLUMP analysis was performed. RESULTS: None of the essential tremor patients had a repeat expansion in the intermediate or pathogenic range. Significant differences in the distribution of repeats in the 'normal' range for SCA2 and SCA8 (both p ≤ 0.02) were observed between essential tremor patients and controls. CONCLUSIONS: Our study suggests that pathogenic repeat expansions in SCA loci are not associated with essential tremor.

Challenges in essential tremor genetics.

The field of essential tremor (ET) genetics remains extremely challenging. The relative lack of progress in understanding the genetic etiology of ET, however, does not reflect the lack of a genetic contribution, but rather, the presence of substantial phenotypic and genotypic heterogeneity. A meticulous approach to phenotyping is important for genetic research in ET. The only tool for phenotyping is the clinical history and examination. There is currently no ET-specific serum or imaging biomarker or defining neuropathological feature (e.g., a protein aggregate specific to ET) that can be used for phenotyping, and there is considerable clinical overlap with other disorders such as Parkinson's disease (PD) and dystonia. These issues greatly complicate phenotyping; thus, in some studies, as many as 30-50% of cases labeled as "ET" have later been found to carry other diagnoses (e.g., dystonia, PD) rather than ET. A cursory approach to phenotyping (e.g., merely defining ET as an "action tremor") is likely a major issue in some family studies of ET, and this as well as lack of standardized phenotyping across studies and patient centers is likely to be a major contributor to the relative lack of success of genome wide association studies (GWAS). To dissect the genetic architecture of ET, whole genome sequencing (WGS) in carefully characterized and well-phenotyped discovery and replication datasets of large case-control and familial cohorts will likely be of value. This will allow specific hypotheses about the mode of inheritance and genetic architecture to be tested. There are a number of approaches that still remain unexplored in ET genetics, including the contribution of copy number variants (CNVs), 'uncommon' moderate effect alleles, 'rare' variant large effect alleles (including Mendelian and complex/polygenic modes of inheritance), de novo and gonadal mosaicism, epigenetic changes and non-coding variation. Using these approaches is likely to yield new ET genes.

Genetic analysis of FMR1 repeat expansion in essential tremor.

We performed an association analysis of Fragile X mental retardation 1 (FMR1) CGG repeats in 321 essential tremor (ET) cases and 296 controls at Columbia University. In addition to analyzing the allele distribution (10-49 CGG repeats) in the entire sample, we also performed a screen for ET cases with the FMR1 premutation allele (55-200 CGG repeats), and evaluated an association between ET and FMR1 alleles that included gray zone alleles (41-54 CGG repeats). CGG premutation alleles and gray zone alleles were rare in ET cases, and we found no evidence for association of premutation or gray zone alleles with ET. These data suggest that FMR1 CGG repeats are not a genetic risk factor for ET.

Prevalence and correlates of rest tremor in essential tremor: cross-sectional survey of 831 patients across four distinct cohorts.

BACKGROUND AND PURPOSE: Essential tremor (ET) is amongst the most commonly encountered neurological disorders. Its hallmark feature is kinetic tremor. However, other tremors may also occur in ET patients, creating considerable diagnostic confusion amongst treating physicians. Hence, characterizing the prevalence and clinical accompaniments of these other tremors is of value. Surprisingly, there are few data on the prevalence of rest tremor in ET patients, and even fewer data on the clinical correlates of such tremor. METHODS: Eight hundred and thirty-one patients in four distinct settings (population, genetics study, study of environmental epidemiology, brain bank) underwent a detailed videotaped neurological examination that was reviewed by a senior movement disorders neurologist. Rest tremor was evaluated in several positions (seated, standing, lying down). RESULTS: The prevalence of rest tremor whilst seated or standing was lowest in the population-based setting (1.9%), highest in the brain bank study (46.4%) and intermediate in the remaining two settings (9.6% and 14.7%, respectively). Rest tremor was restricted to the arms and was not observed in the legs. Rest tremor was associated with older age, longer disease duration (in some studies), greater tremor severity and, to some extent, the presence of cranial tremors. CONCLUSIONS: Rest tremor can be a common clinical feature of ET. Its prevalence is highly dependent on the setting in which patients are evaluated, ranging from as low as 1% to nearly 50%. Rest tremor seems to emerge as a clinical feature with advancing disease. The anatomical substrates for this type of tremor remain unknown at present.

Reduced body mass index in essential tremor: a study of 382 cases and 392 matched controls.

BACKGROUND AND PURPOSE: There is mounting evidence that essential tremor (ET) is a neurodegenerative disease. Reduced body mass index (BMI) is a clinical feature of many neurodegenerative diseases, yet there has been little documentation of BMI in patients with ET. METHODS: Essential tremor cases and controls were enrolled in a study of the environmental epidemiology of ET at Columbia University Medical Center. Weight and height were measured using a standard protocol; BMI was weight (kg) divided by height (m(2)). Daily calorie count (kcal) was calculated using the Willett Semi-Quantitative Food Frequency Questionnaire. Tremor severity was assessed with a clinical rating scale (total tremor score, range 0-36). RESULTS: The 382 ET cases and 392 controls were similar with respect to age, gender and other demographic variables. BMI was lower in ET cases than controls [26.7 ± 5.0 (median = 26.2) vs. 27.7 ± 5.6 (median = 26.7), P = 0.03] despite the fact that the daily caloric intake was marginally higher in ET cases than controls (P = 0.09). In ET cases, BMI was not associated with tremor severity (Spearman's r = -0.02, P = 0.66) but, among younger onset ET cases, longer tremor duration was associated with lower BMI (Spearman's r = -0.14, P = 0.049). CONCLUSIONS: The observed lower BMI in ET is consistent with the neurodegenerative hypothesis of ET. The data also suggest that some mechanism other than decreased daily caloric intake or an involuntary movement-related increased burning of calories is likely to account for this case-control difference.

The microtubule associated protein tau H1 haplotype and risk of essential tremor.

BACKGROUND AND PURPOSE: Two recent studies investigated the association of the microtubule associated protein tau (MAPT) H1 haplotype, a known risk factor for neurodegenerative disease including progressive supranuclear palsy and Parkinson's disease (PD), with essential tremor (ET). METHODS: To confirm this association in a different population the distribution of allele and genotype frequencies for the MAPT H1/H2 tagging single-nucleotide polymorphism (SNP) rs1052553 in ET cases and controls enrolled in a clinical-epidemiological study of ET at Columbia University was analyzed. RESULTS: Overall, no association was observed between ET and the MAPT H1 haplotype. The analysis was also restricted to clinical subtypes including early-onset (≤40 years of age), Ashkenazi Jewish ancestry, white non-Ashkenazi, or ET cases with a 'definite' or 'probable/possible' diagnosis; none of these stratified analyses showed evidence of association with ET. A meta-analysis of the H1/H2 tagging SNP rs1052553 in published data sets and the H1 haplotype with risk for ET in the current study was also performed and did not find evidence for association. CONCLUSIONS: The inconsistent reports of association of MAPT H1 in three emerging studies (our own and two published studies) may reflect sampling issues and/or clinical heterogeneity in these populations.

Is there a one-way street from essential tremor to Parkinson's disease? Possible biological ramifications.

There is considerable evidence for an association between essential tremor (ET) and Parkinson's disease (PD), although the topic remains somewhat controversial. An important issue, not previously addressed, is what seems to be the unidirectional nature of the relationship (ET→ET + PD and not PD→PD + ET). The aims of this review are (i) to discuss the evidence for and against a unidirectional relationship and (ii) to discuss the implications of such a unidirectional relationship, if it exists, for disease mechanisms. Evidence 'for' a unidirectional relationship includes (i) abundant clinical anecdotal observation and (ii) clinical and epidemiological studies. Evidence 'against' is theoretical rather than empirical. Overall, the evidence 'for' is stronger, although additional studies are needed in order to be certain; for the time being, it might be best to leave this as an open question. The biological ramifications/extensions of such a unidirectional relationship include (i) that the association is causal (i.e., some aspect of ET pathophysiology predisposes an individual to develop PD) and (ii) that some ET cases may have a circumscribed form of Lewy body disease, and the secondary development of PD may represent a spread of those Lewy bodies in the brainstem. The presence and nature of the links between ET and PD are controversial. Further primary data (epidemiological and pathological) are needed to improve understanding of the relationship and its implications for the pathogenesis of both disorders.

Essential tremor 10, 20, 30, 40: clinical snapshots of the disease by decade of duration.

BACKGROUND AND PURPOSE: Essential tremor (ET) is a chronic, progressive neurological disorder in which disease burden may slowly accrue. There are few long-term studies, and the clinical and functional status of patients, with each decade of disease duration, has not been documented in detail. We used cross-sectional data on 335 patients with ET (disease duration 1-81 years) to produce clinical snapshots of the disease at each 10-year milestone (i.e. < 10, 10-19, 20-29, 30-39, ≥ 40 years). We hope these data will be of value in clinical-prognostic settings both to patients and their treating physicians. METHODS: In this cross-sectional, clinical-epidemiological study at Columbia-University Medical Center, each patient underwent a single evaluation, including self-reported measures of tremor-related disability, performance-based measures of function, and neurologist-assessments of tremor type, location and severity. RESULTS: A variety of metrics of tremor severity increased across the 10-year time intervals. By ≥ 40 years duration, one-third of patients had tremor in at least two cranial locations (neck, voice, jaw), and the proportion with high-amplitude tremor reached 20.3% (while drawing spirals), 33.8% (spilling while drinking) and 60.8% (spilling while using a spoon). Yet even in the longest tremor duration group, very few (< 10%) were incapacitated (i.e. completely unable to perform the above-mentioned tasks), and one-third continued to exhibit no cranial tremor. CONCLUSIONS: These data paint a picture of progressive decade-by-decade decline in ET. Yet patients with long disease duration did not relentlessly converge at the same end-stage of severe, functionally incapacitating, diffuse tremor. In this respect, long-duration ET patients presented a heterogeneous picture.

The primary type of tremor in essential tremor is kinetic rather than postural: cross-sectional observation of tremor phenomenology in 369 cases.

BACKGROUND: Essential tremor (ET) is amongst the most commonly misdiagnosed neurological diseases. The current aim was to provide observational data on a basic characteristic of ET, namely, the relative severity of postural to kinetic tremor. METHODS: A total of 369 ET cases were enrolled in a cross-sectional study. Postural tremor scores (0-3) and kinetic tremor scores (0-3) were assigned during a standardized neurological examination. RESULTS: In the vast bulk of cases (~95%), kinetic tremor was more severe than postural tremor. In nearly one-in-three cases (32.8%), the kinetic tremor score was ≥ 1 points higher than the postural tremor score. Conversely, in only a few cases (~5%) was postural tremor even marginally (<1 point) more severe than kinetic tremor, and in no case was the postural tremor score ≥ 1 point higher than the kinetic tremor score. At each postural tremor score, nearly all cases had that amount of kinetic tremor or more. CONCLUSION: The primary type of tremor in ET is kinetic rather than postural. Recognition of the simple, empirical features of tremor phenomenology has potential diagnostic value for practicing clinicians.

Genetic analysis of the FUS/TLS gene in essential tremor.

BACKGROUND AND PURPOSE: Although essential tremor (ET) has a genetic basis, specific genes have not been identified. Recently, in a large ET family (FET1) from Quebec, a non-sense mutation (p.Q290X) in the amyotrophic lateral sclerosis (ALS) gene fused in sarcoma/translated in liposarcoma (FUS/TLS) was identified by exome sequencing. No confirmatory studies have been published. METHODS: Two-hundred and fifty-nine ET cases and 262 controls were enrolled in a study at Columbia University. We performed a comprehensive analysis of the FUS/TLS gene by sequencing all exons in a subsample of 116 ET cases with early-onset (≤40 years) ET. We evaluated an association between ET and SNPs in the FUS/TLS gene by genotyping four haplotype tagging SNPs in all 259 ET cases and 262 controls. Additionally, seven variants associated with ALS, two variants of unknown pathogenicity detected in ALS cases, eight mis-sense variants predicted to be damaging, and six rare variants were genotyped in these 259 ET cases and 262 controls. RESULTS: FUS/TLS mutations previously reported in ALS, the FET1 family, or novel mutations were not found in any of the 116 early-onset ET cases. In the case-control analyses, although the power of the performed associations was limited, no significant association between tagging SNPs in FUS/TLS and ET was observed, and none of the analyzed SNPs showed evidence of association with ET. CONCLUSION: Our study suggests that pathogenic mutations in FUS/TLS are rare in a sample of early-onset ET cases in North America. We did not find evidence that the FUS/TLS gene is a risk factor for ET.

Depressive traits in essential tremor: impact on disability, quality of life, and medication adherence.

BACKGROUND: There is growing study of the psychiatric features of essential tremor. Depressive symptoms occur in a considerable number of patients. Yet their impact, as a primary factor, has received almost no attention. We assessed whether, independent of tremor severity, patients with more depressive symptoms have more perceived tremor-related disability, lower tremor-related quality of life, and poorer compliance with tremor medication. METHODS: On the basis of their Center for Epidemiological Studies Depression Scale score, we stratified 70 essential tremor patients into three groups: 41 with minimal depressive symptoms, 24 with moderate depressive symptoms, and five with severe depressive symptoms. Importantly, the three groups had similar tremor severity on neurological examination. We assessed self-reported tremor-related disability, tremor-related quality of life (Quality of Life in Essential Tremor) (QUEST) score, and medication compliance. RESULTS: Cases with minimal depressive symptoms had the lowest QUEST scores (i.e., highest quality of life), cases with moderate depressive symptoms had intermediate scores, and those with severe depressive symptoms had the highest QUEST scores (i.e., lowest quality of life) (P < 0.001). Depressive symptoms were a stronger predictor of tremor-related quality of life than was the main motor feature of essential tremor (ET) itself (tremor). Self-reported medication compliance was lowest in cases with severe depressive symptoms and highest in cases with minimal depressive symptoms. CONCLUSIONS: The physical disability caused by the tremor of ET has traditionally been regarded as the most important feature of the disease that causes distress, and it has received the most attention in the management of patients with this disease. Our data indicate that this may not be the case.

Color vision: a study of essential tremor cases versus normal controls.

BACKGROUND AND PURPOSE: Patients with essential tremor (ET) and Parkinson's disease (PD) may exhibit overlapping clinical features. Also, a growing number of non-motor features are being documented in ET. Color vision abnormalities, although well known to occur in PD, have not been studied extensively in ET. We assessed color vision in ET cases and controls. We furthermore assessed subgroups of ET cases with clinical features that might link them to PD (i.e., ET cases with a family history of PD, and ET cases with rest tremor) to determine whether these cases had greater color vision abnormalities than ET cases without those features. METHODS: Participants were enrolled in a case-control study at Columbia University Medical Center. Color discrimination testing was performed using the Farnsworth-Munsell 100 Hue test. The total error score (TES) for the hue test was determined. RESULTS: The TES was similar in 55 ET cases and 55 controls (144.6 ± 91.8 vs. 145.6 ± 96.6, P = 0.96). ET cases with rest tremor (n = 8) were similar to ET cases without rest tremor (n = 47) with respect to the TES (117.0 ± 73.4 vs. 149.3 ± 94.4, P = 0.36), as were ET cases with a family history of PD (n = 9) versus without (n = 46) (144.4 ± 57.0 vs. 144.6 ± 97.6, P = 0.996). CONCLUSIONS: Although a number of links exist between ET and PD, and non-motor features have been described in both, a color vision abnormality does not seem to be a feature of ET.

The effects of a novel histamine-3 receptor inverse agonist on essential tremor in comparison to stable levels of alcohol.

Essential tremor (ET) is a common movement disorder. Animal studies show that histaminergic modulation may affect the pathological processes involved in the generation of ET. Histamine-3 receptor inverse agonists (H3RIA) have demonstrated attenuating effects on ET in the harmaline rat model. In this double-blind, three-way cross-over, single-dose, double-dummy study the effects of 25 mg of a novel H3RIA (MK-0249) and a stable alcohol level (0.6 g L(-1)) were compared with placebo, in 18 patients with ET. Tremor was evaluated using laboratory tremorography, portable tremorography and a clinical rating scale. The Leeds Sleep Evaluation Questionnaire (LSEQ) and a choice reaction time (CRT) test were performed to evaluate potential effects on sleep and attention, respectively. A steady state of alcohol significantly diminished tremor as assessed by laboratory tremorography, portable tremorography and clinical ratings compared with placebo. A high single MK-0249 dose was not effective in reducing tremor, but caused significant effects on the LSEQ and the CRT test. These results suggest that treatment with a single dose of MK-0249 does not improve tremor in alcohol-responsive patients with ET, whereas stable levels of alcohol as a positive control reproduced the commonly reported tremor-diminishing effects of alcohol.

Increased number of Purkinje cell dendritic swellings in essential tremor.

BACKGROUND AND PURPOSE: Essential Tremor (ET) is among the most prevalent neurologic disorders. Growing clinical and neuro-imaging evidence implicates cerebellar dysfunction in the pathogenesis of ET and emerging postmortem studies have identified structural changes in the cerebellum, particularly in Purkinje cells. In this study we systematically quantified focal Purkinje cell dendritic swellings (DS) in 20 ET vs. 19 control brains. METHODS: In each brain, a standard parasagittal neocerebellar tissue block was harvested. DS were quantified in one 7-µm thick section stained with Luxol Fast Blue/Hematoxylin and Eosin (LH&E) and one section stained with Bielschowsky method. RESULTS: The number of DS were higher in cases than controls by LH&E (1.50 ± 1.79 vs. 0.05 ± 0.23, P = 0.002) and Bielschowsky methods (2.70 ± 3.10 vs. 0.37 ± 0.50, P = 0.002). The number of DS was correlated with the number of torpedoes and marginally inversely correlated with the number of Purkinje cells. CONCLUSION: The current study documents and quantifies an additional structural abnormality in the ET cerebellum, adding to the growing list of such changes in this disease. The mechanisms that underlie this and other structural changes observed in ET are currently unknown, and they deserve additional exploration.

Update on essential tremor.

Essential tremor (ET) is one of the most common neurological disorders among adults, and is the most common tremor disorder. ET has classically been viewed as a benign monosymptomatic condition. Yet over the past 10 years, a growing body of evidence indicates that this is a progressive condition that is clinically heterogeneous, and may be associated with a variety of different features such as gait abnormalities, parkinsonism, cognitive impairment, dementia, personality disturbances, depressive symptoms, and sensory abnormalities (e.g., mild olfactory dysfunction and hearing impairment). In addition, postmortem studies are showing a pathologically heterogeneous neurodegenerative disease. The emerging view is that ET might be a family of diseases, unified by the presence of kinetic tremor, but further characterized by etiological, clinical and pathological heterogeneity. The diagnosis of ET is clinical and made by history and physical examination. Effective pharmacological treatments for the disorder currently remain limited. Drugs are generally initiated when the tremor begins to interfere with the patient's ability to perform daily activities or when the tremor becomes embarrassing. For severe, medically refractory ET, thalamic ventralis intermedius nucleus deep brain stimulation may lessen tremor and improve function.

Evidence-based guideline update: treatment of essential tremor: report of the Quality Standards subcommittee of the American Academy of Neurology.

BACKGROUND: This evidence-based guideline is an update of the 2005 American Academy of Neurology practice parameter on the treatment of essential tremor (ET). METHODS: A literature review using MEDLINE, EMBASE, Science Citation Index, and CINAHL was performed to identify clinical trials in patients with ET published between 2004 and April 2010. RESULTS AND RECOMMENDATIONS: Conclusions and recommendations for the use of propranolol, primidone (Level A, established as effective); alprazolam, atenolol, gabapentin (monotherapy), sotalol, topiramate (Level B, probably effective); nadolol, nimodipine, clonazepam, botulinum toxin A, deep brain stimulation, thalamotomy (Level C, possibly effective); and gamma knife thalamotomy (Level U, insufficient evidence) are unchanged from the previous guideline. Changes to conclusions and recommendations from the previous guideline include the following: 1) levetiracetam and 3,4-diaminopyridine probably do not reduce limb tremor in ET and should not be considered (Level B); 2) flunarizine possibly has no effect in treating limb tremor in ET and may not be considered (Level C); and 3) there is insufficient evidence to support or refute the use of pregabalin, zonisamide, or clozapine as treatment for ET (Level U).

The relation between depression and parkin genotype: the CORE-PD study.

BACKGROUND: Mutations in parkin are a known genetic risk factor for early onset Parkinson's disease (EOPD) but their role in non-motor manifestations is not well established. Genetic factors for depression are similarly not well characterized. We investigate the role of parkin mutations in depression among those with EOPD and their relatives. METHODS: We collected psychiatric information using the Patient Health Questionnaire and Beck Depression Inventory II on 328 genotyped individuals including 88 probands with early onset PD (41 with parkin mutations, 47 without) and 240 first and second-degree relatives without PD. RESULTS: Genotype was not associated with depression risk among probands. Among unaffected relatives of EOPD cases, only compound heterozygotes (n = 4), and not heterozygotes, had significantly increased risk of depressed mood (OR = 14.1; 95% CI 1.2-163.4), moderate to severe depression (OR = 17.8; 95% CI 1.0-332.0), depression (score ≥ 15) on the Beck Depression Inventory II (BDI-II) (OR = 51.9; 95% CI 4.1-657.4), and BDI-II total depression score (ß = 8.4; 95% CI 2.4-11.3) compared to those without parkin mutations. CONCLUSIONS: Relatives of EOPD cases with compound heterozygous mutations and without diagnosed PD may have a higher risk of depression compared to relatives without parkin mutations. These findings support evidence of a genetic contribution to depression and may extend the phenotypic spectrum of parkin mutations to include non-motor manifestations that precede the development of PD.

Atributos psicométricos de la versión española de la escala de cribado A-TAC para trastornos del espectro autista / Psychometric attributes of the spanish version of A-TAC screening scale for autism spectrum disorders

Introducción: Actualmente debido a la ausencia de marcadores biológicos, el cribado de trastornos del espectro autista (TEA) se centra fundamentalmente en la presencia de alteraciones conductuales caracterizadas por alteraciones en la interacción social y comunicación verbal y no verbal. Objetivo: Evaluar los atributos psicométricos de la versión española de la escala de autismo Autism-Tics, AD/HD and other Comorbidities Inventory (A-TAC), como medida de cribado de TEA. Material y métodos: Se incluyó en el estudio a 140 escolares (43% niños, 57% niñas), de edades comprendidas entre los 6 y los 16 años, con TEA (n = 15), discapacidad intelectual (n = 40), enfermedades psiquiátricas (n = 22), tics (n = 12) y participantes controles (n = 51). Se analizaron los principales atributos psicométricos como la fiabilidad, asunción escalar, la consistencia interna, la precisión y la validez predictiva. Resultados: La consistencia interna de la A-TAC fue alta (α = 0,93) y el error estándar de medida fue adecuado (1,13 [intervalo de confianza del 95%, —1,08 a 3,34]). Las puntuaciones medias de la escala A-TAC fueron más altas en participantes diagnosticados con TEA y discapacidad intelectual comparadas con el resto de participantes (p < 0,001), siendo el área bajo la curva de 0,96 para el grupo de TEA. Conclusión: La subescala de autismo de la escala A-TAC es un instrumento fiable, válido y preciso para el cribado de TEA en la población escolar española (AU)

Background: As there are no biological markers for Autism Spectrum Disorders (ASD), screening must focus on behaviour and the presence of a markedly abnormal development or a deficiency in verbal and non-verbal social interaction and communication. Objective: To evaluate the psychometric attributes of a Spanish version of the autism domain of the Autism-Tics, AD/HD and other Comorbidities Inventory (A-TAC) scale for ASD screening. Material and methods: A total of 140 subjects (43% male, 57% female) aged 6-16, with ASD (n = 15), Mental Retardation (n = 40), Psychiatric Illness (n = 22), Tics (n = 12) and controls (n = 51), were included for ASD screening. The predictive validity, acceptability, scale assumptions, Internal consistency, and precision were analysed. Results: The internal consistency was high (α = 0.93), and the standard error was adequate (1.13 [95% CI, -1.08 a 3.34]). The mean scores of the Autism module were higher in patients diagnosed with ASD and mental disability compared to the rest of the patients (P < 0.001). The area under the curve was 0.96 for the ASD group. Conclusion: The autism domain of the A-TAC scale seems to be a reliable, valid and precise tool for ASD screening in the Spanish school population (AU)