Joseph L Jacobson

University of Cape Town, Kaapstad, Western Cape, South Africa

Are you Joseph L Jacobson?

Claim your profile

Publications (199)741.07 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Children with fetal alcohol spectrum disorders (FASD) may exhibit craniofacial dysmorphology, neurobehavioral deficits, and reduced brain volume. Studies of cortical thickness in FASD have yielded contradictory findings, with 3 reporting thicker cerebral cortex in frontal and temporal brain regions and 2 showing thinner cortex across multiple regions. All 5 studies included subjects spanning a broad age range, and none have examined continuous measures of prenatal alcohol exposure. We investigated the relation of extent of in utero alcohol exposure to cortical thickness in 78 preadolescent children with FASD and controls within a narrow age range. A whole-brain analysis using FreeSurfer revealed no significant clusters where cortical thickness differed by FASD diagnostic group. However, alcohol dose/occasion during pregnancy was inversely related to cortical thickness in 3 regions-right cuneus/pericalcarine/superior parietal lobe, fusiform/lingual gyrus, and supramarginal/postcentral gyrus. The effect of prenatal alcohol exposure on IQ was mediated by cortical thickness in the right occipitotemporal region. It is noteworthy that a continuous measure of maternal alcohol consumption during pregnancy was more sensitive than FASD diagnosis and that the effect on cortical thickness was most evident in relation to a measure of maternal binge drinking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Cerebral Cortex 06/2015; DOI:10.1093/cercor/bhv131 · 8.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A large proportion of Inuit children in Arctic Quebec are adopted in accordance with traditional Inuit customs. In contrast to adoptions in Southern Canada and the United States, the child is adopted at birth and by a close family member; he or she knows who his or her biological parents are, and will typically have contact with them. Studies of other populations have reported an increased incidence of behavior problems in adopted compared with nonadopted children. This study examined the actual extent of the increase in the number of behavior problems seen in Inuit children adopted in accordance with traditional customs. In a prospective longitudinal study conducted in the Canadian Arctic (n = 46 adopted and 231 nonadopted children), prenatal and familial variables were documented at birth and at school age (M = 11.3 years). Behavior problems were assessed on the Teacher Report Form of the Child Behavior Checklist. Adopted children lived in more economically disadvantaged families, but their caregivers were less prone to depression, domestic violence, or alcohol abuse compared with those of the nonadopted children. The adoption status was not related to the teacher's report of attention problems, externalizing or internalizing behaviors, after controlling for confounders. Despite less favorable socioeconomic circumstances, a higher extent of behavioral problems was not seen at school age in Inuit children adopted at birth by a family member. Psychosocial stressors associated with adoption are more likely to be responsible for an association with higher levels of childhood behavior problems rather than adoption per se. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    American Journal of Orthopsychiatry 05/2015; 85(3):250-258. DOI:10.1037/ort0000071 · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies using the California Verbal Learning Test‐Children's Version (CVLT‐C) to examine effects of heavy prenatal alcohol exposure on verbal learning and memory have reported impaired information acquisition (i.e., encoding), rather than retrieval, as the primary mechanism underlying learning and memory impairment. We administered the CVLT‐C to 2 independent cohorts to determine whether (i) effects on encoding are also seen at moderate exposure levels, using both categorical (diagnostic/exposure group) and continuous exposure measures; (ii) these deficits are specific or secondary to alcohol‐related impairment in IQ; (iii) effects on retrieval can be detected over and above effects on initial encoding; and (iv) effects on learning are attributable to less efficient learning strategy use.
    Alcoholism Clinical and Experimental Research 04/2015; 39(4):724-32. DOI:10.1111/acer.12671 · 3.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Number processing deficits are frequently seen in children prenatally exposed to alcohol. Although the parietal lobe, which is known to mediate several key aspects of number processing, has been shown to be structurally impaired in fetal alcohol spectrum disorders (FASD), effects on functional activity in this region during number processing have not previously been investigated. This fMRI study of 49 children examined differences in activation associated with prenatal alcohol exposure in five key parietal regions involved in number processing, using tasks involving simple addition and magnitude comparison. Despite generally similar behavioral performance, in both tasks greater prenatal alcohol exposure was related to less activation in an anterior section of the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the angular gyrus during the magnitude comparison task.
    04/2015; 43. DOI:10.1016/j.nicl.2015.03.023
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fetal alcohol spectrum disorders (FASD) are characterized by a range of neurodevelopmental deficits that result from prenatal exposure to alcohol. These can include cognitive, behavioural, and neurological impairment, as well as structural and functional brain damage. Eyeblink conditioning (EBC) is among the most sensitive endpoints affected in FASD. The cerebellar peduncles, large bundles of myelinated nerve fibers that connect the cerebellum to the brainstem, constitute the principal white matter element of the EBC circuit. Diffusion tensor imaging (DTI) is used to assess white matter integrity in fibre pathways linking brain regions. DTI scans of 54 children with FASD and 23 healthy controls, mean age 10.1 ± 1.0 years, from the Cape Town Longitudinal Cohort were processed using voxelwise group comparisons. Prenatal alcohol exposure was related to lower fractional anisotropy (FA) bilaterally in the superior cerebellar peduncles and higher mean diffusivity (MD) in the left middle peduncle, effects that remained significant after controlling for potential confounding variables. Lower FA and higher MD in these regions were associated with poorer EBC performance. Moreover, effects of alcohol exposure on EBC decreased significantly after inclusion of these DTI measures in regression models, suggesting that these white matter deficits partially mediate the relation of prenatal alcohol exposure to EBC. The associations of greater alcohol consumption with these DTI measures are largely attributable to greater radial diffusivity, possibly indicating poorer myelination. Thus, these data suggest that fetal alcohol-related deficits in EBC are attributable, in part, to poorer myelination in key regions of the cerebellar peduncles. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 03/2015; DOI:10.1002/hbm.22785 · 6.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although prenatal methylmercury exposure has been linked to poorer intellectual function in several studies, data from two major prospective, longitudinal studies yielded contradictory results. Associations with cognitive deficits were reported in a Faroe Islands cohort, but few were found in a study in the Seychelles Islands. It has been suggested that co-exposure to another contaminant, polychlorinated biphenyls (PCBs), may be responsible for the positive findings in the former study and that co-exposure to nutrients in methylmercury-contaminated fish may have obscured and/or protected against adverse effects in the latter. To determine the degree to which co-exposure to PCBs may account for the adverse effects of methylmercury and the degree to which co-exposure to docosahexaenoic acid (DHA) may obscure these effects in a sample of Inuit children in Arctic Québec. IQ was estimated in 282 school-age children from whom umbilical cord blood samples had been obtained and analyzed for mercury and other environmental exposures. Prenatal mercury was related to poorer estimated IQ after adjustment for potential confounding variables. The entry of DHA into the model significantly strengthened the association with mercury, supporting the hypothesis that beneficial effects from DHA intake can obscure adverse effects of mercury exposure. Children with cord mercury ≥ 7.5 μg/L were four times as likely to have an IQ score below 80, the clinical cut-off for borderline intellectual disability. Co-exposure to PCBs did not alter the association of mercury with IQ. To our knowledge, this is the first study to document an association of prenatal mercury exposure with poorer performance on a school-age assessment of IQ, a measure whose relevance for occupational success in adulthood is well established. This association was seen at levels in the range within which many U.S. children of Asian American background are exposed.
    Environmental Health Perspectives 03/2015; DOI:10.1289/ehp.1408554 · 7.03 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives. We examined the relation of household crowding to food insecurity among Inuit families with school-aged children in Arctic Quebec. Methods. We analyzed data collected between October 2005 and February 2010 from 292 primary caregiver-child dyads from 14 Inuit communities. We collected information about household conditions, food security, and family socioeconomic characteristics by interviews. We used logistic regression models to examine the association between household crowding and food insecurity. Results. Nearly 62% of Inuit families in the Canadian Arctic resided in more crowded households, placing them at risk for food insecurity. About 27% of the families reported reducing the size of their children's meals because of lack of money. The likelihood of reducing the size of children's meals was greater in crowded households (odds ratio = 3.73; 95% confidence interval = 1.96, 7.12). After we adjusted for different socioeconomic characteristics, results remained statistically significant. Conclusions. Interventions operating across different levels (community, regional, national) are needed to ensure food security in the region. Targeting families living in crowded conditions as part of social and public health policies aiming to reduce food insecurity in the Arctic could be beneficial. (Am J Public Health. Published online ahead of print January 20, 2015: e1-e11. doi:10.2105/AJPH.2014.302290).
    American Journal of Public Health 01/2015; 105(3):e1-e11. DOI:10.2105/AJPH.2014.302290 · 4.23 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Classical eyeblink conditioning (EBC), an elemental form of learning, is among the most sensitive indicators of fetal alcohol spectrum disorders. The cerebellum plays a key role in maintaining timed movements with millisecond accuracy required for EBC. Functional MRI (fMRI) was used to identify cerebellar regions that mediate timing in healthy controls and the degree to which these areas are also recruited in children with prenatal alcohol exposure. fMRI data were acquired during an auditory rhythmic/non-rhythmic finger tapping task. We present results for 17 children with fetal alcohol syndrome (FAS) or partial FAS, 17 heavily exposed (HE) nonsyndromal children and 16 non- or minimally exposed controls. Controls showed greater cerebellar blood oxygen level dependent (BOLD) activation in right crus I, vermis IV-VI, and right lobule VI during rhythmic than non-rhythmic finger tapping. The alcohol-exposed children showed smaller activation increases during rhythmic tapping in right crus I than the control children and the most severely affected children with either FAS or PFAS showed smaller increases in vermis IV-V. Higher levels of maternal alcohol intake per occasion during pregnancy were associated with reduced activation increases during rhythmic tapping in all four regions associated with rhythmic tapping in controls. The four cerebellar areas activated by the controls more during rhythmic than non-rhythmic tapping have been implicated in the production of timed responses in several previous studies. These data provide evidence linking binge-like drinking during pregnancy to poorer function in cerebellar regions involved in timing and somatosensory processing needed for complex tasks requiring precise timing.
    12/2014; 275. DOI:10.1016/j.nicl.2014.12.016
  • Sandra W. Jacobson, Joseph L. Jacobson
    Clinical Neurophysiology 12/2014; DOI:10.1016/j.clinph.2014.04.016 · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Because of their geographical location and traditional lifestyle, Canadian Inuit children are highly exposed to polychlorinated biphenyls (PCBs) and lead (Pb), environmental contaminants that are thought to affect fetal and child growth. We examined the associations of these exposures with the fetal and postnatal growth of Inuit children. Methods We conducted a prospective cohort study among Inuit from Nunavik (Arctic Québec). Mothers were recruited at their first prenatal visit; children (n=290) were evaluated at birth and at 8–14 years of age. Concentrations of PCB 153 and Pb were determined in umbilical cord and child blood. Weight, height and head circumference were measured at birth and during childhood. Results Cord blood PCB 153 concentrations were not associated with anthropometric measurements at birth or school age, but child blood PCB 153 concentrations were associated with reduced weight, height and head circumference during childhood. There was no association between cord Pb levels and anthropometric outcomes at birth, but cord blood Pb was related to smaller height and shows a tendency of a smaller head circumference during childhood. Interpretation Our results suggest that chronic exposure to PCBs during childhood is negatively associated with skeletal growth and weight, while prenatal Pb exposure is related to reduced growth during childhood. This study is the first to link prenatal Pb exposure to poorer growth in school-age children.
    Environmental Research 10/2014; 134:17–23. DOI:10.1016/j.envres.2014.06.023 · 3.95 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prenatal alcohol exposure (PAE) is known to have severe, long-term consequences for brain and behavioral development already detectable in infancy and childhood. Resulting features of fetal alcohol spectrum disorders include cognitive and behavioral effects, as well as facial anomalies and growth deficits. Diffusion tensor imaging (DTI) and tractography were used to analyze white matter (WM) development in 11 newborns (age since conception <45 weeks) whose mothers were recruited during pregnancy. Comparisons were made with nine age-matched controls born to abstainers or light drinkers from the same Cape Coloured (mixed ancestry) community near Cape Town, South Africa. DTI parameters, T1 relaxation time, proton density and volumes were used to quantify and investigate group differences in WM in the newborn brains. Probabilistic tractography was used to estimate and to delineate similar tract locations among the subjects for transcallosal pathways, cortico-spinal projection fibers, and cortico-cortical association fibers. In each of these WM networks, the axial diffusivity was the parameter that showed the strongest association with maternal drinking. The strongest relations were observed in medial and inferior WM, regions in which the myelination process typically begins. In contrast to studies of older individuals with PAE, fractional anisotropy did not exhibit a consistent and significant relation with alcohol exposure. To our knowledge, this is the first DTI-tractography study of prenatally alcohol exposed newborns. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
    Human Brain Mapping 09/2014; 36(1). DOI:10.1002/hbm.22620 · 6.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: OBJECTIVES: Inuit in Canada experience alarming levels of food insecurity, but nutritional and physiological consequences are poorly documented, especially in school-age children. The objective of this study was to assess the relation of food insecurity to iron deficiency and stature in school-aged Inuit children from Nunavik (Northern Quebec). METHODS: Food insecurity, iron deficiency, and stature were assessed in a cohort of children. Food insecurity was determined by interviewing the children’s mothers. Multiple logistic regression was used to evaluate the association of food insecurity to iron deficiency and short stature. We defined short stature as a height in the lowest tertile for age and sex, based on Canadian growth charts. The relation of food insecurity to height (cm) was analyzed with a general linear model. Statistical models controlled for age, sex, normal/overweight/obese status, prenatal lead exposure and postnatal polychlorinated biphenyls exposure. RESULTS: Half of the children (49.7%, n=145) were food insecure, while one third were iron depleted, 12.6% had anaemia, and 8.7% had iron-deficiency anaemia. The multivariate odds ratio of anaemia was 1.82 (95% CI: 0.97, 3.42, p=0.06) for food-insecure children. Prevalence of short stature was 18.7%. Food-insecure children were an average of 2 cm shorter (95% CI: -0.48, -3.17) than food-secure children (p<0.01). CONCLUSION: In this population, food-insecure children have greater burdens of nutritional deficiencies and slower linear growth. Considering the high prevalence of food insecurity among Inuit children in Nunavik, nutritional deficiencies and adverse effects on development should be carefully monitored.
    Canadian journal of public health. Revue canadienne de santé publique 08/2014; 105(4):e233-e238. · 1.02 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background / Purpose: Prenatal methamphetamine exposure has been associated with neuropsychological, behavioural and cognitive alterations, but few neuroimaging studies have been performed to investigate neurostructural effects. No MRI studies have been done previously in neonates with prenatal methamphetamine exposure. This study aimed to investigate, by means of MRI, the potential volumetric changes in the caudates of neonates who had been exposed to methamphetamine in utero . Main conclusion: Increasing methamphetamine exposure was strongly associated with reduced caudate volumes in neonates. This supports the hypothesis that prenatal methamphetamine exposure induces long-lasting changes in dopamine-rich areas of the brain.
    20th Annual Meeting of the Organization for Human Brain Mapping (OHBM) 2014; 08/2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prenatal cigarette smoke exposure (PCSE) has been linked to problems in behavioral inhibition and attention deficit hyperactivity disorder in children in several epidemiological studies. We used event-related potentials (ERPs) to examine the effects of PCSE on neural correlates of inhibitory control of behavior. In a prospective longitudinal study on child development in the Canadian Arctic, we assessed 186 Inuit children (mean age=11.3years) on a visual Go/No-go response inhibition paradigm. PCSE was assessed through maternal recall. Potential confounders were documented from a maternal interview, and exposure to neurotoxic environmental contaminants was assessed from umbilical cord and child blood samples. PCSE was not related to behavioral performance on this simple response inhibition task. Nevertheless, this exposure was associated with smaller amplitudes of the N2 and P3 components elicited by No-go stimuli, suggesting an impairment in the neural processes underlying response inhibition. Amplitude of the No-go P3 component was also inversely associated with behavioral measures of externalizing problems and hyperactivity/impulsivity in the classroom. This study is the first to report neurophysiological evidence of impaired response inhibition in school-aged children exposed to tobacco smoke in utero. Effects were found on ERP components associated with conflict processing and inhibition of a prepotent response, indicating neurophysiological deficits that may play a critical role in the attention and behavior problems observed in children with PCSE.
    Neurotoxicology and Teratology 06/2014; DOI:10.1016/j.ntt.2014.06.003 · 3.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Due to their geographic location and traditional diet, rich in seafood and marine mammals, the Inuit living in Arctic Quebec are exposed to high amounts of pollutants, including organochlorine pesticides (OCPs). While the adverse developmental effects of these pesticides on child cognitive functions are well known, the effects of developmental exposure to OP on sensory processes have not been investigated. The aim of this longitudinal study was to assess the effects of prenatal and childhood exposure to 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (p,p'-DDT) and its major metabolite 1,1,-dichloro-2,2-bis(p-chlorophenyl)ethylene (p,p'-DDE), on visual processing in Inuit children in Nunavik (Arctic Québec). p,p'-DDT and p,p'-DDE concentrations were determined from umbilical cord and 5- and 11-year plasma samples. Visual evoked potentials (VEPs) were successfully recorded in 150 children at four contrast levels (95%, 30%, 12%, and 4%). Hierarchical multiple regressions were conducted to determine the association between p,p'-DDT, or p,p'-DDE, exposure and VEPs while controlling for the effects of various confounders, including fish nutrients and other contaminants. p,p'-DDE measured in umbilical cord plasma was significantly related to the amplitude of the N150 response at the lowest contrast (4%). In addition, 5-year p,p'-DDE plasma concentration was significantly associated with decreased N75 amplitude. These findings indicate that p,p'-DDE exposure, both pre- and postnatally, during early childhood is associated with visual processing impairment later in life.
    NeuroToxicology 05/2014; 44. DOI:10.1016/j.neuro.2014.04.009 · 3.05 Impact Factor
  • S. W. Jacobson, N. Dodge, J. L. Jacobson
    Neurotoxicology and Teratology 05/2014; 43:86-87. DOI:10.1016/j.ntt.2014.04.037 · 3.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Prenatal alcohol exposure is responsible for a broad range of brain structural malformations, which can be studied using magnetic resonance imaging (MRI). Advanced MRI methods have emerged to characterize brain abnormalities, but the teratogenic effects of alcohol on cortical morphology have received little attention to date. Twenty-four 9-year-old children with fetal alcohol spectrum disorders (9 with fetal alcohol syndrome, 15 heavy exposed nonsyndromal children) and 16 age-matched controls were studied to assess the effect of alcohol consumption during pregnancy on cortical morphology. An automated method was applied to 3D T1-weighted images to assess cortical gyrification using global and regional sulcal indices and two region-based morphological measurements, mean sulcal depth and fold opening. Increasing levels of alcohol exposure were related to reduced cortical folding complexity, even among children with normal brain size, indicating a reduction of buried cortical surface. Fold opening was the strongest anatomical correlate of prenatal alcohol intake, indicating a widening of sulci in all regions that were examined. These data identify cortical morphology as a suitable marker for further investigation of brain damage associated with prenatal alcohol exposure. Hum Brain Mapp 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 05/2014; 35(5). DOI:10.1002/hbm.22327 · 6.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Reductions in brain volumes represent a neurobiological signature of fetal alcohol spectrum disorders (FASD). Less clear is how regional brain tissue reductions differ after normalizing for brain size differences linked with FASD and whether these profiles can predict the degree of prenatal exposure to alcohol. To examine associations of regional brain tissue excesses/deficits with degree of prenatal alcohol exposure and diagnosis with and without correction for overall brain volume, tensor-based morphometry (TBM) methods were applied to structural imaging data from a well-characterized, demographically homogeneous sample of children diagnosed with FASD (n = 39, 9.6–11.0 years) and controls (n = 16, 9.5–11.0 years). Degree of prenatal alcohol exposure was significantly associated with regionally pervasive brain tissue reductions in: (1) thalamus, midbrain, and ventromedial frontal lobe, (2) superior cerebellum and inferior occipital lobe, (3) dorsolateral frontal cortex, and (4) precuneus and superior parietal lobule. When overall brain size was factored out of the analysis on a subject-by-subject basis, no regions showed significant associations with alcohol exposure. FASD diagnosis was associated with a similar deformation pattern, but few of the regions survived FDR correction. In data-driven independent component analyses (ICA) regional brain tissue deformations successfully distinguished individuals based on extent of prenatal alcohol exposure and to a lesser degree, diagnosis. The greater sensitivity of the continuous measure of alcohol exposure compared with the categorical diagnosis across diverse brain regions, underscores the dose dependence of these effects. The ICA results illustrate that profiles of brain tissue alterations may be a useful indicator of prenatal alcohol exposure when reliable historical data are not available and facial features are not apparent.
    04/2014; 5. DOI:10.1016/j.nicl.2014.04.001
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study characterized human cerebellar activity during eyeblink classical conditioning (EBC) in children and adults using functional magnetic resonance imaging (fMRI). During fMRI, participants were administered delay conditioning trials, in which the conditioned stimulus (a tone) precedes, overlaps, and coterminates with the unconditioned stimulus (a corneal airpuff). Behavioral eyeblink responses and brain activation were measured concurrently during two phases: pseudoconditioning, involving presentations of tone alone and airpuff alone, and conditioning, during which the tone and airpuff were paired. Although all participants demonstrated significant conditioning, the adults produced more conditioned responses (CRs) than the children. When brain activations during pseudoconditioning were subtracted from those elicited during conditioning, significant activity was distributed throughout the cerebellar cortex (Crus I-II, lateral lobules IV-IX, and vermis IV-VI) in all participants, suggesting multiple sites of associative learning-related plasticity. Despite their less optimal behavioral performance, the children showed greater responding in the pons, lateral lobules VIII, IX, and Crus I, and vermis VI, suggesting that they may require greater activation and/or the recruitment of supplementary structures to achieve successful conditioning. Correlation analyses relating brain activations to behavioral CRs showed a positive association of activity in cerebellar deep nuclei (including dentate, fastigial, and interposed nuclei) and vermis VI with CRs in the children. This is the first study to compare cerebellar cortical and deep nuclei activations in children versus adults during EBC. Hum Brain Mapp, 2013. © 2013 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2014; 35(4). DOI:10.1002/hbm.22261 · 6.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Animal models have demonstrated fetal alcohol-related disruptions in neuroendocrine function in the hypothalamic–pituitary–gonadal axis and downstream effects on pubertal development and sexual behavior in males and females, but little is known about these effects in humans. This study examined whether prenatal alcohol exposure is associated with alterations in testosterone during adolescence and whether it affects timing of pubertal development.Methods The sample consisted of 265 African American adolescents from the Detroit Longitudinal Cohort Study for whom testosterone and/or pubertal development data were available. Subjects were offspring of women recruited at their first prenatal clinic visit to over represent moderate-to-heavy alcohol use, including a 5% random sample of low-level drinkers/abstainers. Mothers were interviewed at every prenatal visit about their alcohol consumption using a timeline follow-back approach and about their smoking and drug use and sociodemographic factors. At age 14 years, adolescents provided salivary samples, which were analyzed for testosterone (pg/ml), self-reported Tanner stages for pubertal development, and age at menarche (females).ResultsPrenatal alcohol exposure was related to elevated testosterone concentrations for males and females but not to changes in Tanner stages or age at menarche, after controlling for confounders. In regression models stratified by alcohol exposure, the expected relation between testosterone and pubic hair development was seen among males with light-to-no prenatal alcohol exposure, but not among those with moderate-to-heavy prenatal alcohol exposure. This interaction between testosterone and prenatal alcohol exposure was confirmed in multivariable models including an alcohol exposure group × testosterone interaction term and potential confounders.Conclusions This study is the first to show a relation between prenatal alcohol exposure and increased testosterone during adolescence and evidence of decreased testosterone responsiveness in tissues related to pubertal development in humans. Further studies examining androgen receptor expression and other hormonal and cellular factors affecting pubertal development may reveal important mechanisms underlying these teratogenic effects of alcohol exposure.
    Alcoholism Clinical and Experimental Research 04/2014; 38(6). DOI:10.1111/acer.12395 · 3.31 Impact Factor

Publication Stats

8k Citations
741.07 Total Impact Points

Institutions

  • 2010–2015
    • University of Cape Town
      • • Department of Human Biology
      • • Faculty of Health Sciences
      Kaapstad, Western Cape, South Africa
    • University of Rochester
      • Department of Clinical and Social Sciences in Psychology
      Rochester, New York, United States
    • University of British Columbia - Vancouver
      • Department of Pediatrics
      Vancouver, British Columbia, Canada
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 1984–2015
    • Wayne State University
      • • Department of Psychiatry and Behavioral Neurosciences
      • • Department of Obstetrics and Gynecology
      • • Department of Psychology
      Detroit, Michigan, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2007
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2006
    • Indiana University Bloomington
      Bloomington, Indiana, United States
  • 2005
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 1985
    • University of Michigan
      Ann Arbor, Michigan, United States