Matthew R. Marler

Low level lead exposure in the prenatal and early preschool periods: Early preschool development☆

The hypothesis that low level lead exposure in the fetal and early preschool years is related to neuropsychological deficit was examined in a prospective study of child development. We also tested the hypothesis of reverse causality, i.e., that lead level is a function of prior developmental status. Fetal lead exposure was measured in maternal and cord blood while preschool lead level was measured in venous blood samples at ages six months, two years and three years. These blood lead measures (PbB) were related to concurrent and ensuing scores on developmental measures at six months, one year, two years, and three years. With statistical control of covariate measures (age, sex, race, birth weight, birth order, gestational exposure to other toxic substances, maternal intelligence, and several indicators of the quality of the caretaking environment) as well as potentially confounding risk factors (gestational exposure to alcohol and other toxic substances), most statistically significant associations of PbB with concurrent and later development were completely attenuated. Effects of lead exposure, significant or not, were not consistent in direction. In reverse-causality analyses, PbB was not related significantly to prior measures of developmental retardation or acceleration. It was concluded that the relationship of lead level and measures of development in these early years was primarily a function of the dependence of each on the quality of the caretaking environment.

Circadian rhythm of vital signs, norepinephrine, epinephrine, thyroid hormones, and cortisol in schizophrenia

Changes in the circadian rhythmicity in vital signs, catecholamines, thyroid hormones, and cortisol have been observed in psychiatric disorders, most notably in depression. With respect to schizophrenia, the literature is scanty. We report here on the circadian parameter estimates of the vital signs, epinephrine, norepinephrine, triiodothyronine, thyroxine, thyroid stimulating hormone, and cortisol in the blood of 34 healthy subjects, 89 drug-free schizophrenic patients, and 25 neuroleptic-treated schizophrenic patients. The analyses are based on the cosine model to fit the experimental data. The circadian profiles of heart rate, blood pressure, and oral temperature are similar among schizophrenic patients and healthy subjects. Neuroleptic-treated patients have significantly higher MESORs (the daily mean) of serum norepinephrine and epinephrine than healthy subjects. The TSH MESOR is significantly lower in schizophrenic patients; the MESOR of triiodothyronine also shows a tendency to be nonsignificantly lower in schizophrenic patients compared with control subjects. The circadian serum thyroxine and cortisol profiles are similar in the three groups. The data show that the circadian profiles of vital signs in drug-free chronic schizophrenic patients who are not chronically hospitalized are similar to those of healthy subjects and that the increase in serum catecholamines and the apparent lowering in some thyroid indices might induce a down-regulation in the noradrenergic receptor system that could contribute to the pathophysiology of schizophrenia.

Hyperdopaminergia in schizophreniform psychosis: A chronobiological study

Circadian rhythm abnormalities have been described in various psychiatric disorders, but they have not received much attention in studies of schizophrenia and schizophreniform psychosis. The present study used the cosine model to determine the circadian patterns of amino acids, dopamine, and prolactin concentrations, which were analyzed over a 24-hour period in serum of healthy subjects, drug-free schizophrenic patients, and neuroleptic-treated schizophrenic patients. The mesor (the daily mean) of phenylalanine was lower in drug-free schizophrenic women than in healthy women. The mesors of the ratio of phenylalanine or tyrosine to competing amino acids were similar in healthy subjects and patients. The ratio of phenylalanine/competing amino acids showed a phase advance (i.e., earlier onset of the time of highest concentration) in drug-free patients compared with healthy subjects. Schizophrenic patients displayed a higher dopamine mesor than healthy subjects. Female drug-free schizophrenic patients had lower prolactin mesors and lower amplitudes (i.e., half of the total predictable change in rhythm) than healthy women. Compared with healthy subjects, schizophrenic patients showed a phase advance of circadian prolactin concentrations. Neuroleptics raised the prolactin mesor and amplitudes but did not elicit any phase change in amino acids, dopamine, or prolactin. These data confirm the indirect pharmacologic evidence of increased dopaminergic activity in schizophrenic patients that relates to dopamines precursors and to the neuroendocrine regulation of prolactin.

Size and Cognitive Development in the Early Preschool Years

The interrelationships of measures of weight, length, and head circumference from birth through age three years with measures of cognitive development from six months through three years are generally positive in direction. The consistency of the relationship remained apparent after control of potentially relevant confounding variables.

Personality pathology in bulimics versus controls

The Millon Clinical Multiaxial Inventory (MCMI) was administered to 37 bulimic women, as well as 32 female general psychiatric outpatients and 30 normal women in order to assess contrasts in prevalence of various types of personality pathology among the three groups. Bulimic women displayed significantly greater pathology on scales measuring dependent and avoidant characteristics. However, they were not significantly different from female psychiatric outpatients with regard to most types of personality pathology. Results are discussed within the framework of previous literature on personality characteristics and disorders within the bulimic population.

Lead-related Birth Defects: Some Methodological Issues

In the course of reviewing our findings on the topic of foetal lead effects, several methodological problems are noted. The first is the effective measurement and control of important confounding variables. In our studies, we demonstrated that failure to consider the effect of foetal lead exposure with the effects of maternal use of alcohol and cigarettes during pregnancy can lead to discrepant findings in the association of lead exposure and the gestational age, birth weight, length and head circumference of the neonate. We also demonstrated that similar discrepancies in findings for the size measurements might follow from failure to consider parental size. Similarly, the association of lead level and neonatal anomalies might be a function of failure to obtain adequate measurements of maternal alcohol use and to control for this confounding condition in statistical models. The second concern is the effect of adjusting cord blood lead (PbB) data for haematocrits. We demonstrated that effect sizes tend to be reduced when PbB corrected for haematocrits is used in place of uncorrected values. Although the haematocrit measure in our data was correlated with cord PbB, it did not appreciably alter a previously reported association of foetal lead exposure and neonatal status.

Circadiane Rhythmik von Catecholaminen, Melatonin und hypophysaren Hormonen bei schizophrenen Patienten

Veranderungen circadianer Rhythmen werden bei psychiatrischen Erkrankungen beobachtet (Aschoff et al. 1967, Halberg 1967, Kraepelin 1913, Wehr und Goodwin 1984). So ist beispielsweise der Schlaf-Wach-Zyklus bei depressiven Patienten gestort (Papousek 1975). Schlafstorungen konnen auch dem Beginn einer psychotischen Episode schizophrener Patienten vorangehen (van Kammen et al. 1989). Circadiane Studien zur Schizophrenie sind vergleichsweise selten. Es gibt jedoch Hinweise dafur, das die circadianen Profile monoaminerger Metaboliten bei schizophrenen Patienten verandert sind (Halaris 1987). Bei ursprunglich Medikamenten-freien Patienten reduziert die Behandlung mit Fluphenazin die Plasmakonzentration von Homovanillinsaure (HVA) und hebt den 24-Stunden-Rhythmus auf (Doran et al. 1990). Es gibt wenig Information daruber, ob Neuroleptika die circadianen Profile anderer Parameter beeinflussen, ahnlich, wie dies von Antidepressiva bekannt ist (Wehr und Wirz-Justice 1982). Um einige der aufgeworfenen Fragen zu beantworten, untersuchten wir die circadianen Serumkonzentrations-Profile von Catecholaminen, Melatonin und hypophysaren Hormonen bei gesunden Probanden und schizophrenen Patienten.