Mark Opler

Electromagnetic field exposure induces rapid, transitory heat shock factor activation in human cells

Stimulation of human promyelocytic HL60 cells by a 60Hz magnetic field at normal growth temperatures results in heat shock factor 1 activation and heat shock element binding, a sequence of events that mediates the stress‐induced transcription of the stress gene HSP70 and increased synthesis of the stress response protein hsp70kD. Thus, the events mediating the electromagnetic field–stimulated stress response appear to be similar to those reported for other physiological stresses (e.g., hyperthermia, heavy metals, oxidative stress) and could well be the general mechanism of interaction of electromagnetic fields with cells. J. Cell. Biochem. 66:482–488, 1997.

Prenatal Exposure to Lead, δ-Aminolevulinic Acid, and Schizophrenia : Further Evidence

Background A previously conducted study of prenatal lead exposure and schizophrenia using δ-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959–1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life. Objectives In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959–1966). Using similar methods, in this study we found results that suggest a comparable association in this cohort. Methods We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education. Results The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 μg/dL of blood Pb was 1.92 (95% confidence interval, 1.05–3.87; p = 0.03). Conclusion Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders.

Is lead exposure in early life an environmental risk factor for Schizophrenia? Neurobiological connections and testable hypotheses.

Schizophrenia is a devastating neuropsychiatric disorder of unknown etiology. There is general agreement in the scientific community that schizophrenia is a disorder of neurodevelopmental origin in which both genes and environmental factors come together to produce a schizophrenia phenotype later in life. The challenging questions have been which genes and what environmental factors? Although there is evidence that different chromosome loci and several genes impart susceptibility for schizophrenia; and epidemiological studies point to broad aspects of the environment, only recently there has been an interest in studying gene × environment interactions. Recent evidence of a potential association between prenatal lead (Pb(2+)) exposure and schizophrenia precipitated the search for plausible neurobiological connections. The most promising connection is that in schizophrenia and in developmental Pb(2+) exposure there is strong evidence for hypoactivity of the N-methyl-d-aspartate (NMDA) subtype of excitatory amino acid receptors as an underlying neurobiological mechanism in both conditions. A hypofunction of the NMDA receptor (NMDAR) complex during critical periods of development may alter neurobiological processes that are essential for brain growth and wiring, synaptic plasticity and cognitive and behavioral outcomes associated with schizophrenia. We also describe on-going proof of concept gene-environment interaction studies of early life Pb(2+) exposure in mice expressing the human mutant form of the disrupted in schizophrenia 1 (DISC-1) gene, a gene that is strongly associated with schizophrenia and allied mental disorders.

Fetal Environment and Schizophrenia

Schizophrenia and related disorders are adult-onset illnesses with no definitively established risk factors. Several studies report that exposures to infection and nutritional deprivation during early development may elevate the risk of later developing schizophrenia, specifically during the prenatal period. Preliminary evidence implicates lead exposure as well, suggesting that chemical exposures during early development may constitute a new class of risk factors for schizophrenia that has not been adequately investigated. Exposure to lead is given as an example of a chemical agent for which some effects have been described throughout the life course on both general neurodevelopmental outcomes and now on a specific psychiatric diagnosis. Findings from prospectively collected birth cohorts are offered as examples of both innovations in methodology and opportunities for future generations of investigators.

Biological and technical variables in myc expression in HL60 cells exposed to 60 Hz electromagnetic fields

Abstract The purpose of the present report is two-fold: first, to find an explanation for the inability of two groups of investigators, Lacy-Hulbert et al. and Saffer and Thurston [A. Lacy-Hulbert, R. Wilkins, T.R. Hesketh, J.C. Metcalfe, No effect of 60Hz electromagnetic fields on MYC or β-actin expression in human leukemic cells, Radiation Res. 144 (1995) 9–17; J.D. Saffer, S.J. Thurston, Short exposures to 60 Hz magnetic fields do not alter MYC expression in HL60 cells or Daudi cells, Radiation Res. 144 (1995) [18–25], to replicate our results, and second, to examine the broader issues involved in in vitro studies and replication in bioelectromagnetics. Replication experiments mandate that the precise cell type population be used and that the experimental protocol (i.e., exposure system, conditions of exposure, techniques for extraction and measurement) be followed exactly . By this criterion, the reported experiments of Lacy-Hulbert et al. and Saffer and Thurston were not replications. In this paper, we present replication experiments that again show a significant increase in c- myc transcript levels, although at a lower level. We also introduce variations from our protocol that were used in the reported ‘replication’ experiments. A major departure from the original experiments was use of different populations of HL60 cells; American Type Culture Collection (ATCC) as opposed to the original Columbia University Cancer Center (CUCC). The growth characteristics and responses to 12-0-tetra-decanoylphorbol-13-acetate (TPA) of the two cell populations showed significantly different reactivities. In line with these characteristics, c- myc increased in CUCC cells and did not increase in ATCC cells when stimulated by EM fields. We also compared other differences in protocol: SDS/phenol and guanidine/phenol RNA extraction procedures, the stability/variability of two housekeeping genes, β-2 μglobulin and GaPDH, as internal standards, sham-exposed controls versus inactive coil and double-wound coils versus single-wound coils. In all experiments, cell were shielded within mu metal containers during exposures. The shielding in one of the ‘replication’ studies, Lacy-Hulbert et al.s, suggest that both experimental and control cells, which were side by side in the apparatus, were exposed to EM fields.

High glycemic index diet as a risk factor for depression: analyses from the Women’s Health Initiative

BACKGROUND The consumption of sweetened beverages, refined foods, and pastries has been shown to be associated with an increased risk of depression in longitudinal studies. However, any influence that refined carbohydrates has on mood could be commensurate with their proportion in the overall diet; studies are therefore needed that measure overall intakes of carbohydrate and sugar, glycemic index (GI), and glycemic load. OBJECTIVE We hypothesized that higher dietary GI and glycemic load would be associated with greater odds of the prevalence and incidence of depression. DESIGN This was a prospective cohort study to investigate the relations between dietary GI, glycemic load, and other carbohydrate measures (added sugars, total sugars, glucose, sucrose, lactose, fructose, starch, carbohydrate) and depression in postmenopausal women who participated in the Womens Health Initiative Observational Study at baseline between 1994 and 1998 (n = 87,618) and at the 3-y follow-up (n = 69,954). RESULTS We found a progressively higher dietary GI to be associated with increasing odds of incident depression in fully adjusted models (OR for the fifth compared with first quintile: 1.22; 95% CI: 1.09, 1.37), with the trend being statistically significant (P = 0.0032). Progressively higher consumption of dietary added sugars was also associated with increasing odds of incident depression (OR for the fifth compared with first quintile: 1.23; 95% CI: 1.07, 1.41; P-trend = 0.0029). Higher consumption of lactose, fiber, nonjuice fruit, and vegetables was significantly associated with lower odds of incident depression, and nonwhole/refined grain consumption was associated with increased odds of depression. CONCLUSIONS The results from this study suggest that high-GI diets could be a risk factor for depression in postmenopausal women. Randomized trials should be undertaken to examine the question of whether diets rich in low-GI foods could serve as treatments and primary preventive measures for depression in postmenopausal women.

Public Stigma Associated With Psychosis Risk Syndrome in a College Population: Implications for Peer Intervention

OBJECTIVES This study compared stigma associated with the psychosis risk label and diagnostic labels for nonpsychotic and psychotic mental disorders among young adult peers. METHODS Urban college respondents (N=153) read an experimental vignette describing a young adult experiencing prodromal symptoms who was randomly assigned a diagnostic label (major depression, generalized anxiety disorder, schizophrenia, or psychosis risk with and without accurate information about the psychosis risk label) and answered questions about stigma toward the individual in the vignette. RESULTS Compared with labels for nonpsychotic disorders, schizophrenia elicited more negative stereotyping and the at-risk label invoked greater social distance and less willingness to help. Any increased social distance appeared to be reduced by accurate information about the at-risk state. No differences in stigma were found for the psychosis risk and schizophrenia labels. CONCLUSIONS The psychosis risk label alone appeared to evoke greater status loss and discrimination. Accurate information may minimize some stigmatizing attitudes among college peers.

Tetrachloroethylene exposure and risk of schizophrenia: Offspring of dry cleaners in a population birth cohort, preliminary findings

Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia.

Prenatal stress and affective disorders in a population birth cohort.

Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit‐Calderon R, Opler M, Friedlander Y, Malaspina D. Prenatal stress and affective disorders in a population birth cohort. 
Bipolar Disord 2012: 00: 000–000.

Later paternal age and sex differences in schizophrenia symptoms

OBJECTIVE Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-à-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. METHOD Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age > or = 35). RESULTS Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. CONCLUSION The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia.