Vulnerable periods during the development of the nervous system are sensitive to environmental insults because they are dependent on the temporal and regional emergence of critical developmental processes (i.e., proliferation, migration, differentiation, synaptogenesis, myelination, and apoptosis). Evidence from numerous sources demonstrates that neural development extends from the embryonic period through adolescence. In general, the sequence of events is comparable among species, although the time scales are considerably different. Developmental exposure of animals or humans to numerous agents (e.g., X-ray irradiation, methylazoxymethanol, ethanol, lead, methyl mercury, or chlorpyrifos) demonstrates that interference with one or more of these developmental processes can lead to developmental neurotoxicity. Different behavioral domains (e.g., sensory, motor, and various cognitive functions) are subserved by different brain areas. Although there are important differences between the rodent and human brain, analogous structures can be identified. Moreover, the ontogeny of specific behaviors can be used to draw inferences regarding the maturation of specific brain structures or neural circuits in rodents and primates, including humans. Furthermore, various clinical disorders in humans (e.g., schizophrenia, dyslexia, epilepsy, and autism) may also be the result of interference with normal ontogeny of developmental processes in the nervous system. Of critical concern is the possibility that developmental exposure to neurotoxicants may result in an acceleration of age-related decline in function. This concern is compounded by the fact that developmental neurotoxicity that results in small effects can have a profound societal impact when amortized across the entire population and across the life span of humans.

Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models.

Goal constructs in psychology: Structure, process, and content.

Research on attention-deficit/hyperactivity disorder (ADHD), a highly prevalent and controversial condition, has, for the most part, been descriptive and atheoretical. The imperative to discover the genetic and environmental risk factors for ADHD is motivating the search for quantifiable intermediate constructs, termed endophenotypes. In this selective review, we conclude that such endophenotypes should be solidly grounded in the neurosciences. We propose that three such endophenotypes — a specific abnormality in reward-related circuitry that leads to shortened delay gradients, deficits in temporal processing that result in high intrasubject intertrial variability, and deficits in working memory — are most amenable to integrative collaborative approaches that aim to uncover the causes of ADHD.

Neuroscience of attention-deficit/hyperactivity disorder: the search for endophenotypes.

Recent reports show that fewer adolescents believe that regular cannabis use is harmful to health. Concomitantly, adolescents are initiating cannabis use at younger ages, and more adolescents are using cannabis on a daily basis. The purpose of the present study was to test the association between persistent cannabis use and neuropsychological decline and determine whether decline is concentrated among adolescent-onset cannabis users. Participants were members of the Dunedin Study, a prospective study of a birth cohort of 1,037 individuals followed from birth (1972/1973) to age 38 y. Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. Neuropsychological testing was conducted at age 13 y, before initiation of cannabis use, and again at age 38 y, after a pattern of persistent cannabis use had developed. Persistent cannabis use was associated with neuropsychological decline broadly across domains of functioning, even after controlling for years of education. Informants also reported noticing more cognitive problems for persistent cannabis users. Impairment was concentrated among adolescent-onset cannabis users, with more persistent use associated with greater decline. Further, cessation of cannabis use did not fully restore neuropsychological functioning among adolescent-onset cannabis users. Findings are suggestive of a neurotoxic effect of cannabis on the adolescent brain and highlight the importance of prevention and policy efforts targeting adolescents.

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Persistent cannabis users show neuropsychological decline from childhood to midlife

This month, the Clinical Practice Guideline (CPG) column reviews the recently published guideline, Treating Tobacco Use and Dependence. This set of recommendations is available in a quick reference format and a more comprehensive clinician's guide that includes detailed information on the methodology and references used to develop the guidelines. Both are available in electronic and hard copy versions through a variety of sources, including the National Guidelines Clearinghouse, the Centers for Disease Control and Prevention, and the National Cancer Institute.

Treating tobacco use and dependence.

Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana.

Aspects of neurobehavioral development were examined in 133 36-month- and 130 48-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been previously ascertained and who have been assessed since birth. Parallelling earlier observations made with this sample at 12 and 24 months, prenatal exposure to cigarette smoking was significantly associated with poorer language development and lower cognitive scores at both 36 and 48 months after statistically controlling for confounding factors. Relatively low levels of maternal alcohol consumption, which had measurable effects at 24 and 36 months, no longer had significant relationships with outcome variables at 48 months of age. At 48 months, significantly lower scores in verbal and memory domains were associated with maternal marijuana use after adjusting for confounding variables. This negative relationship is the first reported association beyond the neonatal stage, and may represent a long-term effect of the drug upon complex behavior that, at a younger age, had not developed and/or could not be assessed.

36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol.

Cognitive and receptive language development were examined in 135 60-month-old and 137 72-month-old children for whom prenatal exposure to marijuana, cigarettes, and alcohol had been ascertained. Discriminant Function analysis revealed an association between prenatal cigarette exposure and lower cognitive and receptive language scores at 60 and 72 months. This paralleled and extended observations made with this sample at annual assessments at 12 to 48 months of age. Unlike observations made at 48 months, prenatal exposure to marijuana was not associated with the cognitive and verbal outcomes. Relatively low levels of maternal alcohol consumption did not have significant relationships with the outcome variables. The importance of assessing subtle components rather than global cognitive and language skills to detect potential behavioral teratogenic effects of the drugs being examined is discussed.

Barbara Watkinson

Papers

Differential effects on cognitive functioning in 13- to 16-year-olds prenatally exposed to cigarettes and marihuana.

36- and 48-month neurobehavioral follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol.

60- and 72-month follow-up of children prenatally exposed to marijuana, cigarettes, and alcohol: cognitive and language assessment.

Neurocognitive consequences of marihuana--a comparison with pre-drug performance.

A follow-up study of attentional behavior in 6-year-old children exposed prenatally to marihuana, cigarettes, and alcohol