Empathy Mediates the Relations between Working Memory and Perpetration of Intimate Partner Violence and Aggression.

Deficits in executive functioning have been associated with aggressive and violent behavior toward intimate partners. However, it is unclear what specific mechanisms are being affected by cognitive deficits that increase an individual's tendency to become aggressive. The current study examined empathy as a mediating factor between deficits in working memory and perpetration of intimate partner aggression and violence. Men in heterosexual relationships (N = 49) were administered a measure of visual-spatial working memory, and questionnaire measures of head injury and empathy. During a second session, men participated in a conflict discussion with their female partner that was coded for aggressive behavior. Female partners also reported on men's physical and psychological abuse. Working memory was positively related to cognitive and affective empathy, and negatively related to men's physical abuse perpetration and observed aggression during the conflict discussion. The effects of working memory on observed aggression during the conflict were fully mediated by cognitive and affective empathy. Additionally, the effects of working memory on reported physical IPV frequency were fully mediated by affective empathy. Deficits in working memory may decrease men's ability to use empathetic processes, resulting in increased aggression and violence toward their intimate partners. Clinically, incorporating empathy training in battering intervention programs may be helpful, especially among men with deficits in cognitive functioning.

Analysis of common and rare VPS13C variants in late-onset Parkinson disease.

OBJECTIVE: We aimed to study the role of coding VPS13C variants in a large cohort of patients with late-onset Parkinson disease (PD) (LOPD). METHODS: VPS13C and its untranslated regions were sequenced using targeted next-generation sequencing in 1,567 patients with PD and 1,667 controls from 3 cohorts. Association tests of rare potential homozygous and compound heterozygous variants and burden tests for rare heterozygous variants were performed. Common variants were analyzed using logistic regression adjusted for age and sex in each of the cohorts, followed by a meta-analysis. RESULTS: No biallelic carriers of rare VPS13C variants were found among patients, and 2 carriers of compound heterozygous variants were found in 2 controls. There was no statistically significant burden of rare (minor allele frequency [MAF] <1%) or very rare (MAF <0.1%) coding VPS13C variants in PD. A VPS13C haplotype including the p.R153H-p.I398I-p.I1132V-p.Q2376Q variants was nominally associated with a reduced risk for PD (meta-analysis of the tagging SNP p.I1132V [odds ratio = 0.48, 95% confidence interval = 0.28-0.82, p = 0.0052]). This haplotype was not in linkage disequilibrium with the known genome-wide association study top hit. CONCLUSIONS: Our results do not support a role for rare heterozygous or biallelic VPS13C variants in LOPD. Additional genetic replication and functional studies are needed to examine the role of the haplotype identified here associated with reduced risk for PD.

Higher Urine bis(Monoacylglycerol)Phosphate Levels in LRRK2 G2019S Mutation Carriers: Implications for Therapeutic Development.

BACKGROUND: LRRK2 mutations are a common cause of dominantly inherited PD. Previous studies showed decreases in urine levels of didocohexaenoyl (22:6) bis(monoacylglycerol)phosphate in LRRK2-knockout mice and in non-human primates treated with LRRK2 kinase inhibitors. We hypothesized that urine levels of bis(monoacylglycerol)phosphate isoforms will be higher in individuals with a PD-causing gain-of-kinase function mutation, LRRK2 G2019S. The objective of this study was to investigate alterations in urinary phospholipids as biomarkers of LRRK2 mutations and Parkinson's disease status/phenotypes. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to assess 54 bioactive phospholipids in urine from the LRRK2 Cohort Consortium (n = 80). To confirm and extend the findings, urine from an independent LRRK2 cohort from Columbia University Irving Medical Center (n = 116) was used. Both cohorts were composed of LRRK2 G2019S carriers and non-carriers with and without PD. RESULTS: In each cohort, 4 bis(monoacylglycerol)phosphate isoforms (di-18:1-bis[monoacylglycerol]phosphate, didocohexaenoyl [22:6] bis[monoacylglycerol] phosphate, 2,2'-di-22:6-bis[monoacylglycerol]phosphate, and 2,2'-di-18:1-bis[monoacylglycerol]phosphate) were significantly higher (2.5- to 4.3-fold) in G2019S carriers compared with non-carriers. Interestingly, 2,2'-di-18:1-bis(monoacylglycerol)phosphate levels were marginally higher in LRRK2 carriers with PD than in those without PD (P = 0.045). Moreover, increased 2,2' and total di-22:6-bis(monoacylglycerol)phosphate were associated with worse cognitive status assessed by the Montreal Cognitive Assessment (P = 0.0033 and 0.0144, respectively). CONCLUSIONS: The observed association of bis(monoacylglycerol)phosphate isoforms with LRRK2 G2019S mutation, PD status among G2019S carriers, and correlation with cognitive decline suggest the potential use of urinary bis(monoacylglycerol)phosphate isoforms as biomarkers for clinical trials of LRRK2-targeted therapies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Correction: Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Genetic testing for Parkinson disease: current practice, knowledge, and attitudes among US and Canadian movement disorders specialists.

PURPOSE: Genetic testing for Parkinson disease (PD) has not been widely used in clinical practice. In preparation for upcoming precision medicine-designed clinical trials for GBA and LRRK2, we evaluated movement disorders specialists' current practice, knowledge, attitudes, and barriers to genetic testing in PD. METHODS: An anonymous questionnaire was sent to movement disorders specialists at 146 Parkinson Study Group (PSG) sites in the United States (n = 131) and Canada (n = 15) to assess their knowledge and attitudes about genetic testing for PD. RESULTS: One hundred seventy-eight (47.6%) PSG clinicians completed the questionnaire. Forty-one percent of respondents had not referred any PD patients for genetic testing in the last year and >80% reported referring fewer than 11 patients over the same period. Most common reasons for not referring for genetic testing included lack of insurance coverage/cost to the patient and lack of perceived utility. On a scale of 0-100, the mean level of comfort in respondents' own ability to genetically counsel PD patients on GBA and LRRK2 was 52 (SD = 28). Sixty percent of clinicians correctly answered all questions about the inheritance and penetrance of GBA and LRRK2 variants. CONCLUSIONS: There is an urgent need to increase knowledge and reduce practical barriers to genetic counseling and testing in PD.

Graded motor responses in the time course of categorizing atypical exemplars.

The time course of categorization was investigated in four experiments, which revealed graded competitive effects in a categorization task. Participants clicked one of two categories (e.g., mammal or fish) in response to atypical or typical exemplars (e.g., whale or cat) in the form of words (Experiments 1 and 2) or pictures (Experiments 3 and 4). Streaming x, y coordinates of mouse movement trajectories were recorded. Normalized mean trajectories revealed a graded competitive process: Atypical exemplars produced trajectories with greater curvature toward the competing category than did typical exemplars. The experiments contribute to recent examination of the time course of categorization and carry implications for theories of representation in cognitive science.