Lynn Singer

Prenatal exposure to cocaine (PCE) may alter areas of the brain dense with monoamine receptors such as the prefrontal cortex and negatively affect cognitive processes implicated in executive function (EF). This study investigated the effects of PCE on EF at 12 and 15years. EF was examined in 189 PCE and 183 non-cocaine exposed (NCE) children who were primarily African American and of low socioeconomic status. Caregivers rated their child on the Behavior Rating Inventory of Executive Function (BRIEF) at ages 12 and 15. The BRIEF includes two summary scales and eight subscales: Behavioral Regulation Index (BRI) (Inhibit, Shift, and Emotion) and Metacognition Index (MI) (Monitor, Working Memory, Plan/Organize, Organization of Materials and Task Completion). Two additional measures were included at age 15 (BRIEF Self-Report and the CANTAB Stockings of Cambridge (SOC)). Girls with PCE were perceived by caregivers to have more behavioral regulation problems at age 12 (p<0.005) and more metacognitive problems at age 12 (p<0.003) than NCE females, but there was no association for males. PCE girls improved in behavioral regulation (p<0.05) and metacognition (p<0.04) from 12 to 15years compared to NCE girls based on caregiver report. By self-report PCE was associated with problems of inhibition (p<0.006). Girls with PCE performed more poorly on number of moves to complete the SOC, requiring planning and problem solving, than NCE girls. Prenatally cocaine exposed girls were perceived by caregivers as having problems of behavioral regulation, and by self-report, inhibitory control problems. Girls with PCE also performed more poorly on a task of planning and problem solving at age 15 which corresponded to caregiver report at age 12. Early assessment and remediation of these weaknesses in girls may improve school performance and behavior associated with poor EF.

s / Drug and Alcohol Dependence 140 (2014) e86–e168 e151 Active vaccination inhibits the acquisition of methamphetamine self-administration in rats Michelle L. Miller1, A.Y. Moreno2, S. Aarde1, K. Creehan1, K. Janda2, Michael A. Taffe1 1 Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, United States 2 Chemistry, Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, United States Aims: d-Methamphetamine (METH) addiction is a serious public health concern for which successful treatment remains elusive. Immunopharmacotherapy has been shown to attenuate locomotor and thermoregulatory effects ofMETH. The aimof the current study was to investigate whether active vaccination against METH could alter intravenous METH self-administration in rats. Methods: Male Sprague-Dawley rats (N=24) were vaccinated with either a candidate anti-METH vaccine (MH6) or a control keyhole-limpet hemocyanin conjugate vaccine (KLH). Effects of vaccination on the acquisition of METH self-administration under 0.1mg/kg/inf and across a range of doses of METH (0, 0.01, 0.05, 0.20mg/kg/inf) during steady-state responding were investigated. Results: Active vaccination inhibited the acquisition of METH self-administration under the 0.1mg/kg/inf dose condition, with 66% of the MH6-vaccinated rats compared to 100% of the controls reaching criteria, and produced transient and dose-dependent effects on self-administration during the maintenance phase. Conclusions: These data demonstrate that active immunopharmacotherapy for METH inhibits the acquisition of METH selfadministration. Financial support: Supported by NIH/NIDA grant #DA024705. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.426 Behavioral adjustment in prenatally cocaine-exposed adolescents Meeyoung O. Min1, S. Minnes1, E.J. Short2, S. Yoon1, L.T. Singer3 1 Applied Social Sciences, Case Western Reserve University, Cleveland, OH, United States 2 Psychology, Case Western Reserve University, Cleveland, OH, United States 3 Environmental Health, Case Western Reserve University, Cleveland, OH, United States Aims: To assess differences in self-reported behavioral adjustment in prenatally cocaine exposed (PCE) andnon-cocaine exposed (NCE) adolescents at ages 12 and 15 years. Methods: Adolescents (N=371; 189 PCE, 182 NCE), primarily African-American and low socioeconomic status, were prospectively enrolled in a longitudinal study at birth (92% retention). The Youth Self-Report (YSR) was used to assess behavioral adjustment. A mixed model repeated measures analysis was used, controlling for covariates including other prenatal drug exposures and lead. Results: Adolescents with PCE reported greater externalizing problems (adjusted mean± SE: 49.9±0.78 vs. 47.3±0.76 at 12; 52.6±0.86 vs. 50.2±0.84 at 15) than NCE adolescents (p< .02) after control for covariates. PCE adolescents reported increased inattention at 15 year (59.4±0.68 vs. 57.3±0.67; p< .03) compared to NCE adolescents. No PCE effect on internalizing problems was found. All externalizing, internalizing, and attention problem scores increased from 12 to 15 years. Girls reported a greater increase in externalizing and internalizing problems from 12 to 15 years than boys. Greater maternal psychological distress was related to higher internalizing problems (p= .03). Greater parental monitoring was related to fewer externalizing problems; greater family conflict was related to more externalizing and attention problems;andgreaterviolenceexposurewas related tomoreexternalizing and internalizing problems. Prenatal marijuana exposure was related to inattention (p< .02). Marginal effects of prenatal alcohol on internalizing behavior (p= .07) and blood lead on inattention (p= .051) were found. Conclusions: PCE is related to externalizing problems and inattention in adolescence. Interventions focusing on strengthening parental monitoring and decreasing family conflict and violence exposure may be promising in reducing behavioral problems among high risk adolescents with PCE. Financial support: National Institute onDrug AbuseGrant R0107957. http://dx.doi.org/10.1016/j.drugalcdep.2014.02.427 Executive function in children with prenatal cocaine exposure at 12 and 15 years Sonia Minnes1, Meeyoung O. Min1, E. Short3, M. Wu1, S. Yoon1, Lynn Singer2 1 Applied Social Sciences, Case Western Reserve University, Cleveland, OH, United States 2 School of Medicine, Case Western Reserve University, Cleveland, OH, United States 3 Psychology, Case Western Reserve University, Cleveland, OH, United States Aims: To examine between and within group differences in executive function (EF) in prenatally cocaine exposed (PCE) and non-cocaine exposed (NCE) children at 12 and 15 years of age. Methods: Three hundred seventy (188 PCE, 182 NCE), primarily African American, low socioeconomic status children participated in a prospective, longitudinal study. The Behavior Rating Inventory of Executive…

Publisher Summary This chapter discusses prenatal drug exposure and mental retardation. Prenatal exposure to cocaine is a behavioral teratogen. The early “rush to judgement” that occurred with crack cocaine can be replaced by sound research. As is evident from studies of cocaine exposure, even in cases where no birth defects are obvious, long-term follow-up may be needed to detect and ameliorate neurobehavioral effects. At both the individual and the societal levels, even in situations where etiology and pathogenesis are well-known, developmental disorders such as mental retardation do not emerge as a result of a single factor or at a single point in development. Neither a prenatal teratogenic environment nor a postnatal rearing environment model of development following prenatal cocaine exposure has total explanatory power. At each stage in development, the human brain is uniquely susceptible to exposure of teratogenic compounds. It is also readily apparent that prevention and treatment of conditions arising from exposure to teratogenic substances will be largely dictated by the stage or stages in which the exposure occurs. The chapter discusses several drawbacks of the traditional etiological classification of mental retardation—prenatal, perinatal, or postnatal.

L'emploi de criteres de diagnostic et des instruments d'evaluation et de quantification, nos connaissances du fonctionnement cellulaire et moleculaire, ont permis des progres notables de la recherche psychiatrique biologique. Mais les insuffisances methodologiques persistent du fait de la complexite de l'objet d'etude: la vie mentale de l'homme et ses anomalies. Actuellement la psychiatrie biologique risque d'etre dans une impasse, si elle ne change pas ses orientations, et si les protagonistes, les psychiatres cliniciens, et les chercheurs biologistes, ne reconnaissent pas leurs handicaps respectifs et ne cooperent pas de facon continue et etroite. La formation approfondie a la recherche devra etre exigee des psychiatres qui participent a ces etudes

In this study, actual hospital total joint expenditures were analyzed, and the effect of decreased length of stay on these actual costs was determined. Expenditures were stratified per hospital and accounting conventions into fixed and variable costs. Hospital costs associated with 15 index knee arthroplasty procedures from fiscal years 1992, 1993, and 1994 were analyzed. Expenditures were standardized to inflation-controlled 1994 dollars. Average length of stay for knee arthroplasty procedures decreased 30% during this period (range, 8.7-6.1 days). Also, expenditures for total knee arthroplasty decreased only 13% (range, $17,415-$15,200) in inflation-controlled 1994 dollars. Using inflation-controlled dollars, analysis of variable costs revealed a continued rise of $278 during this period. Therefore, essentially all the cost reductions achieved were in the fixed component of cost allocated to each patient. Length of stay reductions, although beneficial, did not reduce hospital variable expenses significantly. Expenditure reductions were most exclusively in fixed costs. However, the overall total fixed hospital costs were largely unchanged. Thus, it is necessary to decrease variable costs (implant and supply costs) to significantly reduce hospital expenditures.

The study aims to describe developmental outcomes from a longitudinal prospective cohort (Cleveland study) of prenatally cocaine-exposed (CE) infants. Two hundred eighteen CE and 197 nonexposed infants were enrolled at birth and followed through mid-adolescence. Birth CE status was determined by interview and biologic measures. Multiple demographic, drug, and environmental correlates were controlled. Standardized, normative, reliable measures of fetal growth, intelligence quotient (IQ), behavior, executive function, and language were given at each age and risk for substance misuse assessed in adolescence. A subset of children received volumetric magnetic resonance imaging (MRI) at 7 years and functional MRI at 14 years. The effect of CE was determined through multiple regression analyses controlling for confounders. Cocaine exposed had significant negative effects on fetal growth, attention, executive function, language, and behavior, while overall IQ was not affected. CE had signif...

While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% c...

In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice. To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding. The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750-1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050-3,300 kJ/L, 22-24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) >/= 50% energy from human milk before hospital discharge (>/= 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119). PFF-T infants weighed approximately…

Maternal cocaine use during pregnancy can affect the infant directly through toxic effects or indirectly through cocaine's influence on maternal psychological status. We followed 160 cocaine exposed and 56 nonexposed infants and their mothers identified at birth through interview and/or urine screen. Although cocaine exposure defined the groups, infant exposure to alcohol, marijuana, and tobacco was allowed to vary. Infants were 99% African American and poor. All mothers completed the Brief Symptom Inventory (BSI) and infants were given the Bayley Scales of Mental (MDI) and Motor (PDI) Development at a mean corrected age of 17 ± 8 months. Both MDIs (94 ± 17 vs. 103 ± 16) and PDIs (101 ± 16 vs. 108 ± 12) were lower for cocaine exposed infants. Psychological distress was greater in cocaine using mothers. Hierarchical multiple regression was used to assess the relative effects of gestational age, maternal psychological distress, and cocaine and polydrug exposure on infant outcomes....