Semantic clustering on common list-learning tasks: a systematic review of the state of the literature and recommendations for future directions.

INTRODUCTION: On some list-learning tasks, such as the California Verbal Learning Test (CVLT) or Hopkins Verbal Learning Test (HVLT), examinees have the opportunity to group words based on semantically related categories (i.e., semantic clustering). Semantic clustering (SC) is often considered the most efficient organizational strategy and adopting SC is presumed to improve learning and memory. In addition, SC is conceptualized as reflecting higher-order executive functioning skills. Although SC measures have intuitive appeal, to date, there are no comprehensive reviews of the SC literature base that summarize its psychometric utility. In this systematic review, we synthesize the literature to judge the validity of SC scores. METHOD: We conducted a systematic literature search for empirical articles reporting SC from the CVLT and HVLT. We qualitatively described the relationship of SC with other list-learning and cognitive test scores and clinical diagnoses, contrasting SC with serial clustering and total learning scores when possible. RESULTS: SC was inversely correlated with serial clustering. Higher SC was strongly associated with better learning and memory performances. When compared with cognitive tests, SC tended to have the strongest relationships with other memory measures and modest relationships with tests of executive functioning. SC had negligible to small relationships with most other cognitive domains. Traditional memory scores yielded stronger relationships to cognitive test performances than did SC. SC across clinical groups varied widely, but clinical groups tended to use SC less often than healthy comparison groups. CONCLUSION: Our comprehensive review of the literature revealed that SC is strongly related to measures of learning and memory on the CVLT and HVLT and is correlated with a wide range of cognitive functions. SC has been understudied in relevant populations and additional research is needed to test the degree to which it adds incremental validity beyond traditional measures of learning and memory.

Systematic Review of the Psychometric Properties of the Saint Louis University Mental Status (SLUMS) Examination.

OBJECTIVES: This systemic review qualitatively synthesizes existing psychometric support for the Saint Louis University Mental Status (SLUMS) Examination, a cognitive screening measure which presents as a free alternative to other widely used dementia screening measures including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). METHODS: A total of 90 peer-reviewed articles on the SLUMS were identified from PsycINFO and PubMed databases. RESULTS: Sixty-eight records were identified and reviewed by the lead author for eligibility. Studies that included at least one psychometric property of the SLUMS (n = 20) were included in this review. CONCLUSIONS: Support for the SLUMS remains preliminary; however, it appears to have adequate validity, and adequate sensitivity and specificity in detecting cognitive impairment. Numerous shortcomings were identified, including lack of sufficient normative data, information on test-reliability, explored factor structure, and limited application of criterion measures (e.g., imaging studies, biomarkers). Research is needed to establish diverse normative samples and describe the reliability and validity of the SLUMS to strengthen the empirical support for its use. CLINICAL IMPLICATIONS: Until its psychometric properties are better established the SLUMS should be used cautiously when screening for cognitive impairment.

Multidimensional imaging techniques for prediction of treatment response in major depressive disorder.

A large number of studies have attempted to use neuroimaging tools to aid in treatment prediction models for major depressive disorder (MDD). Most such studies have reported on only one dimension of function and prediction at a time. In this study, we used three different tasks across domains of function (emotion processing, reward anticipation, and cognitive control, plus resting state connectivity completed prior to start of medication to predict treatment response in 13-36 adults with MDD. For each experiment, adults with MDD were prescribed only label duloxetine (all experiments), whereas another subset were prescribed escitalopram. We used a KeyNet (both Task derived masks and Key intrinsic Network derived masks) approach to targeting brain systems in a specific match to tasks. The most robust predictors were (Dichter et al., 2010) positive response to anger and (Gong et al., 2011) negative response to fear within relevant anger and fear TaskNets and Salience and Emotion KeyNet (Langenecker et al., 2018) cognitive control (correct rejections) within Inhibition TaskNet (negative) and Cognitive Control KeyNet (positive). Resting state analyses were most robust for Cognitive control Network (positive) and Salience and Emotion Network (negative). Results differed by whether an -fwhm or -acf (more conservative) adjustment for multiple comparisons was used. Together, these results implicate the importance of future studies with larger sample sizes, multidimensional predictive models, and the importance of using empirically derived masks for search areas.

A Quasi-Experimental Analysis of Elementary School Absences and Fine Particulate Air Pollution.

Fine particulate air pollution (PM2.5) has been associated with many adverse health outcomes including school absences. Specifically, a previous study in the Utah Valley area, conducted during a time with relatively high air pollution exposure, found significant positive correlations between school absences and air pollution. We examined the hypothesis that ambient PM2.5 exposures are associated with elementary school absences using a quasi-natural experiment to help control for observed and unobserved structural factors that influence school absences. The Alpine, Provo, and Salt Lake City school districts are located in valleys subject to daily mean PM2.5 concentrations almost twice as high as those in the Park City School District. We used seminonparametric generalized additive Poisson regression models to evaluate associations between absences and daily PM2.5 levels in the 3 districts that were exposed to the most pollution while using Park City absences as a quasi-control. The study covered 3 school years (2011/12-2013/14). School absences were most strongly associated with observed structural factors such as seasonal trends across school years, day-of-week effects, holiday effects, weather, etc. However, after controlling for these structural factors directly and using a control district, a 10 µg/m increase in PM2.5 was associated with an approximately 1.7% increase in daily elementary school absences. Exposure to ambient air pollution can contribute to elementary school absences, although this effect is difficult to disentangle from various other factors.

TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases.

Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.

Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis.

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 x 10(-10), OR = 1.63) and 17q12-21 (P = 1.7 x 10(-10), OR = 1.38).

Intermediate: cognitive phenotypes in bipolar disorder.

BACKGROUND: Intermediate cognitive phenotypes (ICPs) are measurable and quantifiable states that may be objectively assessed in a standardized method, and can be integrated into association studies, including genetic, biochemical, clinical, and imaging based correlates. The present study used neuropsychological measures as ICPs, with factor scores in executive functioning, attention, memory, fine motor function, and emotion processing, similar to prior work in schizophrenia. METHODS: Healthy control subjects (HC, n=34) and euthymic (E, n=66), depressed (D, n=43), or hypomanic/mixed (HM, n=13) patients with bipolar disorder (BD) were assessed with neuropsychological tests. These were from eight domains consistent with previous literature; auditory memory, visual memory, processing speed with interference resolution, verbal fluency and processing speed, conceptual reasoning and set-shifting, inhibitory control, emotion processing, and fine motor dexterity. RESULTS: Of the eight factor scores, the HC group outperformed the E group in three (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity), the D group in seven (all except Inhibitory Control), and the HM group in four (Inhibitory Control, Processing Speed with Interference Resolution, Fine Motor Dexterity, and Auditory Memory). LIMITATIONS: The HM group was relatively small, thus effects of this phase of illness may have been underestimated. Effects of medication could not be fully controlled without a randomized, double-blind, placebo-controlled study. CONCLUSIONS: Use of the factor scores can assist in determining ICPs for BD and related disorders, and may provide more specific targets for development of new treatments. We highlight strong ICPs (Processing Speed with Interference Resolution, Visual Memory, Fine Motor Dexterity) for further study, consistent with the existing literature.

European population genetic substructure: further definition of ancestry informative markers for distinguishing among diverse European ethnic groups.

The definition of European population genetic substructure and its application to understanding complex phenotypes is becoming increasingly important. In the current study using over 4,000 subjects genotyped for 300,000 single-nucleotide polymorphisms (SNPs), we provide further insight into relationships among European population groups and identify sets of SNP ancestry informative markers (AIMs) for application in genetic studies. In general, the graphical description of these principal components analyses (PCA) of diverse European subjects showed a strong correspondence to the geographical relationships of specific countries or regions of origin. Clearer separation of different ethnic and regional populations was observed when northern and southern European groups were considered separately and the PCA results were influenced by the inclusion or exclusion of different self-identified population groups including Ashkenazi Jewish, Sardinian, and Orcadian ethnic groups. SNP AIM sets were identified that could distinguish the regional and ethnic population groups. Moreover, the studies demonstrated that most allele frequency differences between different European groups could be controlled effectively in analyses using these AIM sets. The European substructure AIMs should be widely applicable to ongoing studies to confirm and delineate specific disease susceptibility candidate regions without the necessity of performing additional genome-wide SNP studies in additional subject sets.

Analysis of East Asia genetic substructure using genome-wide SNP arrays.

Accounting for population genetic substructure is important in reducing type 1 errors in genetic studies of complex disease. As efforts to understand complex genetic disease are expanded to different continental populations the understanding of genetic substructure within these continents will be useful in design and execution of association tests. In this study, population differentiation (Fst) and Principal Components Analyses (PCA) are examined using >200 K genotypes from multiple populations of East Asian ancestry. The population groups included those from the Human Genome Diversity Panel [Cambodian, Yi, Daur, Mongolian, Lahu, Dai, Hezhen, Miaozu, Naxi, Oroqen, She, Tu, Tujia, Naxi, Xibo, and Yakut], HapMap [ Han Chinese (CHB) and Japanese (JPT)], and East Asian or East Asian American subjects of Vietnamese, Korean, Filipino and Chinese ancestry. Paired Fst (Wei and Cockerham) showed close relationships between CHB and several large East Asian population groups (CHB/Korean, 0.0019; CHB/JPT, 00651; CHB/Vietnamese, 0.0065) with larger separation with Filipino (CHB/Filipino, 0.014). Low levels of differentiation were also observed between Dai and Vietnamese (0.0045) and between Vietnamese and Cambodian (0.0062). Similarly, small Fst's were observed among different presumed Han Chinese populations originating in different regions of mainland of China and Taiwan (Fst's <0.0025 with CHB). For PCA, the first two PC's showed a pattern of relationships that closely followed the geographic distribution of the different East Asian populations. PCA showed substructure both between different East Asian groups and within the Han Chinese population. These studies have also identified a subset of East Asian substructure ancestry informative markers (EASTASAIMS) that may be useful for future complex genetic disease association studies in reducing type 1 errors and in identifying homogeneous groups that may increase the power of such studies.

Camera perspective bias in videotaped confessions: evidence that visual attention is a mediator.

Several experiments have demonstrated a camera perspective bias in evaluations of videotaped confessions: videotapes with the camera focused on the suspect lead to judgments of greater voluntariness than alternative presentation formats. The present research investigated potential mediators of this bias. Using eye tracking to measure visual attention, Experiment 1 replicated the bias and revealed that changes in camera perspective are accompanied by corresponding changes in duration of fixation on the suspect and interrogator. A path analysis indicated that visual attention partially mediated the bias, with at least one additional factor independently contributing to it. A proposed second factor was changes in available visual content that naturally coincide with alterations in camera perspective. Experiment 2 directly manipulated observers' focus and thus more conclusively established visual attention as one mediator of the camera perspective bias. Together the two experiments provide plausible evidence that differences in visual content may also mediate the bias.

Analysis and application of European genetic substructure using 300 K SNP information.

European population genetic substructure was examined in a diverse set of >1,000 individuals of European descent, each genotyped with >300 K SNPs. Both STRUCTURE and principal component analyses (PCA) showed the largest division/principal component (PC) differentiated northern from southern European ancestry. A second PC further separated Italian, Spanish, and Greek individuals from those of Ashkenazi Jewish ancestry as well as distinguishing among northern European populations. In separate analyses of northern European participants other substructure relationships were discerned showing a west to east gradient. Application of this substructure information was critical in examining a real dataset in whole genome association (WGA) analyses for rheumatoid arthritis in European Americans to reduce false positive signals. In addition, two sets of European substructure ancestry informative markers (ESAIMs) were identified that provide substantial substructure information. The results provide further insight into European population genetic substructure and show that this information can be used for improving error rates in association testing of candidate genes and in replication studies of WGA scans.