Neil B. Edwards

Post-Traumatic Stress Disorder in Young Children: A Reaction to Purported Sexual Abuse

Abstract This paper reviews systematically gathered data on a group of 10 young children, aged 2 to 6 years, who were evaluated and treated for post-traumatic stress disorder (PTSD) after reported sexual abuse in a daycare setting. These children developed symptoms consistent with a DSM-III-R classification of PTSD as well as Terrs descriptions of type II (repeated abuse) disorders. Discussion of Terrs classification is presented and, in addition, some significant sex differences are explored.

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.

Hospital Violence: Site, Severity, and Nurses' Preventive Training

A sample of 663 nurses was surveyed about exposure to violence at the work site; 243 (37%) had faced violence. Hospitals with low response rates to the questionnaire reported less assault, yet the violence admitted to was described as more deadly. More nurses at public than private hospitals had obtained some training to handle potentially violent situations. Serious assault was negatively related to amount of training. At the public psychiatric hospital, violent acts were most frequent, but the rate of deadly violence (e.g., rape, use of knives or guns, etc.) was lowest. The need to train staffs at general as well as psychiatric hospitals was discussed.

Project among African-Americans to explore risks for schizophrenia (PAARTNERS): Recruitment and assessment methods

The Project among African-Americans to Explore Risks for Schizophrenia (PAARTNERS) is a multi-site, NIMH-funded study that seeks to identify genetic polymorphisms that confer susceptibility to schizophrenia among African-Americans by linkage mapping and targeted association analyses. Because deficits in certain dimensions of cognitive ability are thought to underlie liability to schizophrenia, the project also examines cognitive abilities in individuals affected by schizophrenia and their extended family members. This article describes PAARTNERS study design, ascertainment methods and preliminary sample characteristics. We aim to recruit a sample of 1260 African-American families, all of whom have at least one proband with schizophrenia or schizoaffective disorder. The data collection protocol includes a structured Diagnostic Interview for Genetic Studies, Family Interview for Genetic Studies, focused neurocognitive assessment, medical records review, and the collection of blood or buccal cells for genetic analyses. We have currently completed study procedures for 106 affected sib-pair, 457 case-parent trio and 23 multiplex families. A total of 289 probands have completed the best estimate final diagnosis process and 1153 probands and family members have been administered the computerized neuropsychological battery. This project lays the foundation for future analysis of cognitive and behavioral endophenotypes. This novel integration of diagnostic, neurocognitive and genetic data will also generate valuable information for future phenotypic and genetic studies of schizophrenia.

A psycho-behavioral model of genital herpes recurrence

To develop a model of how stress and other psychosocial constructs may interact to explain recurrences of genital herpes, assessments of major and minor life stress, locus of control, arousal or stimulation seeking, and social support were given to 153 university students (33% male; 67% female) who were seropositive for genital herpes. Retrospective and concurrent indices of illness vulnerability were evaluated. Serum levels of thymosin-alpha-1, a peptide sensitive to psychosocial stress, were measured at the beginning of the study. A causal model suggested by previous research was not supported by the data. An alternate model showed that psychosocial stress did not affect herpes recurrence directly, but instead predisposed subjects to more generalized illnesses, which in turn mediated recurrences. Social support increased rather than decreased the likelihood of illness vulnerability, thus increasing the risk of recurrence. Higher levels of both arousal seeking and external locus of control increased illness vulnerability but moderated the likelihood of herpes recurrence. Higher levels of thymosin-alpha-1 were related to greater illness vulnerability but this peptide was not associated with psychosocial stress as originally predicted. Additional construct validation of the role of illness vulnerability in increasing the risk of herpes recurrence is recommended.

Evaluation of HLA Polymorphisms in Relation to Schizophrenia Risk and Infectious Exposure

BACKGROUND Genome-wide association studies (GWAS) implicate single nucleotide polymorphisms (SNPs) on chromosome 6p21.3-22.1, the human leukocyte antigen (HLA) region, as common risk factors for schizophrenia (SZ). Other studies implicate viral and protozoan exposure. Our study tests chromosome 6p SNPs for effects on SZ risk with and without exposure. METHOD GWAS-significant SNPs and ancestry-informative marker SNPs were analyzed among African American patients with SZ (n = 604) and controls (n = 404). Exposure to herpes simplex virus, type 1 (HSV-1), cytomegalovirus (CMV), and Toxoplasma gondii (TOX) was assayed using specific antibody assays. RESULTS Five SNPs were nominally associated with SZ, adjusted for population admixture (P < .05, uncorrected for multiple comparisons). These SNPs were next analyzed in relation to infectious exposure. Multivariate analysis indicated significant association between rs3130297 genotype and HSV-1 exposure; the associated allele was different from the SZ risk allele. CONCLUSIONS We propose a model for the genesis of SZ incorporating genomic variation in the HLA region and neurotropic viral exposure for testing in additional, independent African American samples.

Students' self-ratings of stress in medical school: a replication across 20 months

We replicated the essential results of a prior study on the capacity of the BAROMAS scales to reflect stress in medical school as perceived by students. As before, subjective stress was high at the start of medical school, and when facing the exams prerequisite to entry into clinical clerkships. On most measures, stress was lowest when the second year began (i.e. after having passed the first). Once again, most test-retest reliabilities (significant rs ranged from 0.24 to 0.66 for confidence ratings at 12- and 20-months after entry) were moderate.

Students' self-ratings of subjective stress across 30 months of medical school

Abstract A first study of the capacity of the BAROMAS scales to reflect stress as perceived by normals was conducted with a large sample of medical students. Unlike individual administration with clinical patients, the data were gathered in groups. Measures obtained at entry, and after 30 months of school from the same students disclosed significant temporal stability on all scales but low to moderate in degree (rs ranged from 0.28 to 0.68 for confidence ratings). Significant changes were found on five of the nine scales, all indicating that self-efficacy was higher after surviving 2 1 2 yr of school than at entry. Measures taken at six time points from various students suggested that sequential patterns were as follows: subjective stress was highest at the start of medical school and just before exams; stress was lowest at the end of 30 months, and at the onset of the second year after successfully passing the prior year; ratings obtained immediately after the National Board Exams, 23 months past entry, were intermediate. The results appeared plausible and in reasonably good agreement with advance expectations.

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.

Principal Components of Heritability From Neurocognitive Domains Differ Between Families With Schizophrenia and Control Subjects

Objective: Various measures of neurocognitive function show mean differences among individuals with schizophrenia (SZ), their relatives, and population controls. We use eigenvector transformations that maximize heritability of multiple neurocognitive measures, namely principal components of heritability (PCH), and evaluate how they distribute in SZ families and controls. Methods: African-Americans with SZ or schizoaffective disorder (SZA) (n = 514), their relatives (n = 1092), and adult controls (n = 300) completed diagnostic interviews and computerized neurocognitive tests. PCH were estimated from 9 neurocognitive domains. Three PCH, PCH1–PCH3, were modeled to determine if status (SZ, relative, and control), other psychiatric covariates, and education were significant predictors of mean values. A small-scale linkage analysis was also conducted in a subset of the sample. Results: PCH1, PCH2, and PCH3 account for 72% of the genetic variance. PCH1 represents 8 of 9 neurocognitive domains, is most highly correlated with spatial processing and emotion recognition, and has unadjusted heritability of 68%. The means for PCH1 differ significantly among SZ, their relatives, and controls. PCH2, orthogonal to PCH1, is most closely correlated with working memory and has an unadjusted heritability of 45%. Mean PCH2 is different only between SZ families and controls. PCH3 apparently represents a heritable component of neurocognition similar across the 3 diagnostic groups. No significant linkage evidence to PCH1–PCH3 or individual neurocognitive measures was discovered. Conclusions: PCH1 is highly heritable and genetically correlated with SZ. It should prove useful in future genetic analyses. Mean PCH2 differentiates SZ families and controls but not SZ and unaffected family members.