Judith R. O'Jile

Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS): Evidence for Impairment and Heritability of Neurocognitive Functioning in Families of Schizophrenia Patients

OBJECTIVE Neurocognitive impairments in schizophrenia are well replicated and widely regarded as candidate endophenotypes that may facilitate understanding of schizophrenia genetics and pathophysiology. The Project Among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) aims to identify genes underlying liability to schizophrenia. The unprecedented size of its study group (N=1,872), made possible through use of a computerized neurocognitive battery, can help further investigation of the genetics of neurocognition. The current analysis evaluated two characteristics not fully addressed in prior research: 1) heritability of neurocognition in African American families and 2) relationship between neurocognition and psychopathology in families of African American probands with schizophrenia or schizoaffective disorder. METHOD Across eight data collection sites, patients with schizophrenia or schizoaffective disorder (N=610), their biological relatives (N=928), and community comparison subjects (N=334) completed a standardized diagnostic evaluation and the computerized neurocognitive battery. Performance accuracy and response time (speed) were measured separately for 10 neurocognitive domains. RESULTS The patients with schizophrenia or schizoaffective disorder exhibited less accuracy and speed in most neurocognitive domains than their relatives both with and without other psychiatric disorders, who in turn were more impaired than comparison subjects in most domains. Estimated trait heritability after inclusion of the mean effect of diagnostic status, age, and sex revealed significant heritabilities for most neurocognitive domains, with the highest for accuracy of abstraction/flexibility, verbal memory, face memory, spatial processing, and emotion processing and for speed of attention. CONCLUSION Neurocognitive functions in African American families are heritable and associated with schizophrenia. They show potential for gene-mapping studies.

Can we improve the clinical assessment of working memory? An evaluation of the Wechsler Adult Intelligence Scale–Third Edition using a working memory criterion construct

Working memory is the cognitive ability to hold a discrete amount of information in mind in an accessible state for utilization in mental tasks. This cognitive ability is impaired in many clinical populations typically assessed by clinical neuropsychologists. Recently, there have been a number of theoretical shifts in the way that working memory is conceptualized and assessed in the experimental literature. This study sought to determine to what extent the Wechsler Adult Intelligence Scale–Third Edition (WAIS–III) Working Memory Index (WMI) measures the construct studied in the cognitive working memory literature, whether an improved WMI could be derived from the subtests that comprise the WAIS–III, and what percentage of variance in individual WAIS–III subtests is explained by working memory. It was hypothesized that subtests beyond those currently used to form the WAIS–III WMI would be able to account for a greater percentage of variance in a working memory criterion construct than the current WMI. Multiple regression analyses (n = 180) revealed that the best predictor model of subtests for assessing working memory was composed of the Digit Span, Letter–Number Sequencing, Matrix Reasoning, and Vocabulary. The Arithmetic subtest was not a significant contributor to the model. These results are discussed in the context of how they relate to Unsworth and Engles (2006, 2007) new conceptualization of working memory mechanisms.

Sensation Seeking and Risk Behaviors in Young Adults With and Without a History of Head Injury

Research has demonstrated a relation between sensation seeking and risky behavior as well as an association between risky behavior and the occurrence of head injury. This study assessed sensation seeking in young adults with and without a history of head injury by administration of the Sensation Seeking Scale (SSS), the Driver Risk Index (DRI), and the MacAndrews Scale of the Minnesota Multiphasic Personality Inventory (MMPI). There was a significant difference between the groups for the Thrill and Adventure Seeking Subscale of the SSS and the MacAndrews Scale of the MMPI, with head-injured participants scoring higher. Gender differences were seen in both groups for subscales of the SSS, with men scoring higher. Significant correlations were found for head-injured participants between the DRI and the Boredom Susceptiblity Subscale of the SSS, suggesting that as knowledge of risk increased for these participants, so did their preferences for risky behaviors. However, non-head-injured participants indicated a lower interest in risky behaviors as their knowledge of risk increased.

Convergent patterns of association between phenylalanine hydroxylase variants and schizophrenia in four independent samples

Recessive mutations in the phenylalanine hydroxylase (PAH) gene predispose to phenylketonuria (PKU) in conjunction with dietary exposure to phenylalanine. Previous studies have suggested PAH variations could confer risk for schizophrenia, but comprehensive follow‐up has not been reported. We analyzed 15 common PAH “tag” SNPs and three exonic variations that are rare in Caucasians but common in African‐Americans among four independent samples (total n = 5,414). The samples included two US Caucasian cohorts (260 trios, 230 independent cases, 474 controls), Bulgarian families (659 trios), and an African‐American sample (464 families, 401 controls). Analyses of both US Caucasian samples revealed associations with five SNPs; most notably the common allele (G) of rs1522305 from case–control analyses (z = 2.99, P = 0.006). This SNP was independently replicated in the Bulgarian cohort (z = 2.39, P = 0.015). A non‐significant trend was also observed among African‐American families (z = 1.39, P = 0.165), and combined analyses of all four samples were significant (rs1522305: χ2 = 23.28, 8 d.f., P = 0.003). Results for rs1522305 met our a priori criteria for statistical significance, namely an association that was robust to multiple testing correction in one sample, a replicated risk allele in multiple samples, and combined analyses that were nominally significant. Case–control results in African‐Americans detected an association with L321L (P = 0.047, OR = 1.46). Our analyses suggest several associations at PAH, with consistent evidence for rs1522305. Further analyses, including additional variations and environmental influences such as phenylalanine exposure are warranted.

Attenuating Demographic Influences on Verbal Fluency and Animal Naming in a Psychiatric Sample

Measures of verbal fluency are common additions to neuropsychological evaluations. Due to the literature demonstrating the impact of demographic variables on these measures, corrective norms have recently been published. However, these norms have yet to be cross-validated. This study sought to cross-validate these norms in a racially diverse psychiatric sample. In addition, this study sought to evaluate the utility of Wide Range Achievement Test, 3rd Edition (WRAT3) Reading Recognition and Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Vocabulary in attenuating the effect of demographic variables on these measures of verbal fluency. Results supported the utility of Gladsjo et al.s (1999) norms. Further analysis revealed that both WRAT3 Reading Recognition and WAIS-III Vocabulary scores also attenuated the impact of demographic variables on these measures and accounted for more of the variance. Together, these results suggest that, although the demographically corrected norms adequately attenuate the impact of these variables, norms corrected for WRAT3 Reading Recognition or WAIS-III Vocabulary may account for more of the variance and therefore might be more appropriate and universally applicable.