Elsevier

Neurotoxicology and Teratology

Volume 33, Issue 1, January–February 2011, Pages 129-136
Neurotoxicology and Teratology

The effects of prenatal marijuana exposure on delinquent behaviors are mediated by measures of neurocognitive functioning

https://doi.org/10.1016/j.ntt.2010.07.006Get rights and content

Abstract

We hypothesized that there would be an association between prenatal marijuana exposure (PME) and delinquency and that the effects of PME on neurocognitive development would mediate this association. Mothers and offspring enrolled in a longitudinal study of the effects of prenatal substance exposure on child development, were interviewed from the fourth prenatal month through 14 years. There were 580 mother/child dyads at the 14-year phase. A standardized protocol assessed psychological, neurocognitive, social, environmental, and demographic characteristics, and substance use at each phase. The Self Report Delinquency scale (Loeber et al., 1998) and the Child Behavior checklist (Achenbach, 1991) delinquency subscale were combined to represent delinquent behavior. First trimester PME was used as a dichotomous variable, daily use versus all other use. Offspring of heavier marijuana users were significantly more likely to report delinquent behavior at age 14. The odds ratio for delinquency among those who were exposed to one or more joints per day during gestation was 1.76 (C.I. 1.05  2.96). PME significantly predicted child depressive symptoms and attention problems at age 10, after controlling for other significant covariates. Child depressive symptoms and attention problems at age 10 significantly predicted delinquency at 14 years. Theassociation between PME and delinquent behavior at 14 years was mediated by depressive symptoms and attention problems in the offspring at 10 years.

Introduction

Marijuana is the most commonly used illegal substance during pregnancy. In the 1999 National Survey on Drug Use and Health [66], almost 3% of pregnant women reported marijuana use in the past month. In the Maternal Health Practices and Child Development (MHPCD) study, this rate was much higher: 30% of a sequential cohort of 1360 women from a hospital-based prenatal clinic reported using marijuana in their first trimester. Thus, although the rates vary by demographic characteristics such as race, maternal age, and socioeconomic status, use of marijuana during pregnancy is prevalent [12]. In spite of this, little is known about the long-term effects of prenatal marijuana exposure (PME).

Studies in laboratory animals have demonstrated the importance of the endocannabinoid system (ECS) in the developing fetal brain. Endocannabinoid receptors and are found in the fetal brain as early as the 14th week of gestation [9]. During fetal development, the ECS plays an important role in the development of neuronal connectivity [24], [33], [34] and intercellular signaling [54]. The concern with PME lies in the fact that the endocannabinoid receptors interact with exogenous substances such as ∆9-tetrahydrocannabinol (THC), a component of cannabis/marijuana [39]. Prenatal exposure to THC can lead to changes in the ECS, resulting in effects on the fetus such as disruption of the position, postsynaptic target selectivity, and differentiation of the developing axons [6], [7]. Over the long-term, these changes result in deficits in physical, cognitive, emotional, social, and motor functioning in the offspring that last into adulthood [18], [33], [53], [55], [69].

Changes in CNS functioning are seen in human studies as well. The Maternal Health Practices and Child Development (MHPCD) study is a longitudinal cohort study of PME. In the MHPCD cohort, PME affected sleep continuity and organization at birth [62] and at age 3. We found an association with lower efficiency and maintenance, more awake time, and a higher number of arousals [14], which are indications of early subtle differences in brain development. At 3 years [15], we found effects of PME on the composite score, and the short-term memory and verbal reasoning subscales of the Stanford Binet Intelligence Scale [67]. At the same age, Griffith et al. [31] also found a relation between PME and abstract/visual reasoning in a cohort of poly-substance users. In the Ottawa Prenatal Prospective Study (OPPS), PME was associated with significantly lower scores on the verbal and memory domains of the McCarthy Scales of Children's Abilities at 4 years [25]. At 6 years in the MHPCD study, there was a significant nonlinear relationship between marijuana exposure and child intelligence. Use of one or more joints of marijuana per day was associated with lower composite, short-term memory, quantitative, and verbal reasoning scores, depending on the trimester of exposure [29]. In the OPPS, there were no significant effects of PME on IQ at 5–6 or 9–12 years of age [27], [56].

In the pre-teen and adolescent phases of the MHPCD study, we measured development using neuropsychological assessments. At 6 years, PME predicted more errors of commission on a Continuous Performance Test (CPT), a measure of impulsivity [40]. At age 10, there were significant associations between PME and attention, hyperactivity, and impulsivity [28] and memory deficits [61] on the design memory and the screen score of the WRAML [63]. At age 10 in the MHPCD study, exposed offspring also had significantly higher rates of depression and anxiety [30], [42]. At age 14 [73], adolescents with PME did less well on the coding, block design, and mazes tests on the WISC-II [70]. The OPPS also found deficits in cognitive development [27], attention [26], and executive functioning [25] that were associated with PME as the offspring matured.

These deficits on the neuropsychological assessments are indicators of subtle changes in CNS functioning. They are also risk factors for other consequences, including problem behaviors. In this analysis, we will focus on the association between PME and delinquent behaviors. We will also extend this analysis to identify which of the neuropsychological outcomes may mediate the subsequent development of problem behaviors.

In an earlier analysis [28], we demonstrated an association between PME and delinquent behaviors at age 10, using the Child Behavior Checklist (CBCL) [1], a maternal report. We dichotomized PME, defining heavy exposure as exposure to an average of 1 or more joints/day. Twenty-six percent of the offspring with this level of exposure in the first trimester scored above the clinical cut-point of the CBCL compared to 13% who had no PME and 15% among those with exposures of less than 1 joint/day. The relative risk for delinquency, given heavy PME, was 2.4 (CI: 1.3–4.5; p < .01). PME was not related to any of the other subscales on the CBCL. In this same analysis, we also showed that attention, as measured by the SNAP [57], was significantly predicted by first trimester PME and was significantly correlated with delinquency. Using structural equation modeling, we tested the effect of adding attention to the model on the significant association between PME and delinquency. When attention was added, the association between PME and delinquency was no longer significant. In the OPPS cohort O'Connell & Fried [56] also found a significant association between PME and conduct problems at 6 to 9 years.

In another analysis of MHPCD data [41], we used configural frequency analyses, and found that there were three pathways to delinquency: 1) 3-year temperament predicted 10-year temperament, which predicted delinquency; 2) 3-year IQ predicted 10-year IQ, which predicted psychological problems and subsequently delinquency, and 3) behavior problems at age 3 predicted behavior problems at 10 years, which predicted, in turn, peer use, offspring substance use, and then delinquency. This analysis also identified the correlates of delinquency at age 10 including race, gender, anxiety, substance use, perceived substance use of peers, IQ, and shyness. PME was correlated with delinquency, prenatal tobacco and alcohol use were not. In a related analysis, we demonstrated that deficits in mental flexibility, the ability to switch from one task to another, and attention measured at 10 years of age predicted delinquent behavior in offspring at age 16 [43].

In other research, measures of memory [46] and executive function [4], [11], [72] have been identified as correlates or predictors of delinquency, as have attention deficits [50], hyperactivity when combined with disruptive behaviors [51], impulsivity [47], aggression [22], [44], [45], [57], [58], [59], and intelligence [47]. A study by Ellickson et al. [21] found that violent teenagers were more likely to have mental health problems than nonviolent youth. Others have reported higher levels of depression and anxiety in delinquent versus non-delinquent ninth graders [71]. Multiple social and psychological factors also predict the occurrence of delinquency among early adolescents including social class, race, gender, abuse and neglect, and parental factors including education, socioeconomic status, and mental illness [11], [19], [23], [46], [47], [64], [68].

Thus, we have previously demonstrated an association between PME and delinquency in childhood that was mediated by attention. In addition, we have identified correlates of delinquency and pathways to delinquency. These analyses only addressed part of the picture, however. The paper of Goldschmidt et al. [28] addressed the effects of 10-year attention on 10-year delinquency and the paper of Leech et al. [41] only included PME as a covariate in the analyses.

In this and other research, however, we have found that PME predicts multiple outcomes, using many different levels of measurement. The outcomes can be defined as those that are more proximal to brain functioning, including neuropsychological assessments, mood, attention, impulsivity, and activity, and those that are more distal from brain functioning, including problem behaviors. Our over-arching hypothesis is that the proximal effects of PME will mediate the more distal outcomes.

This analysis is an exploration of the relations between PME, neurocognitive deficits, and delinquent behaviors. We hypothesized that: 1) PME will predict each of the proposed mediators, 2) PME will predict a higher rate of delinquent behavior, 3) each of the proposed mediators will predict delinquency, and 4) the proposed mediators will attenuate the association between PME and delinquency. The neurocognitive domains that we have found to be associated with PME by age 10 included depressive symptoms, attention, activity, impulsivity, learning and memory, and IQ.

The Human Subjects Review Board at the University of Pittsburgh approved the protocols for each study phase.

Section snippets

Study design

The MHPCD project is a longitudinal study of the long-term effects of exposure to marijuana or alcohol during gestation. Woman who were at least 18 years of age were recruited from a prenatal clinic. A sequential sample of 1360 women who were in their fourth gestational month was interviewed. The refusal rate was 15%. Two study cohorts were selected from the original cohort of 1360 women. First, all women who used marijuana at least twice a month in the first trimester, and the next woman

Results

This study began in 1982. At the first trimester, 73% of the women had completed high school, 62% earned less than $400 per month. Their median age was 22 years (range 18–42), 30% of the women were primigravidous, 54% were African American, and 68% were not married. On average, marijuana use was 0.4 joints/day (range 0–9), alcohol use was 0.6 drinks/day (range 0–8.5), and the number of cigarettes was 7.8/day (range 0–50). Eleven percent of the women reported illicit drug use other than marijuana,

Discussion

In this paper, we report a significant association between PME and delinquency in exposed adolescents. The odds ratio for delinquency among those who are exposed to one or more joints per day during the first trimester was 1.76, which means that the odds of a heavily-exposed adolescent being delinquent are nearly double those of adolescents who were not exposed or who were exposed to lesser amounts.

While this association is important in itself, we felt that it would be more informative to

Conclusion

In summary, we have demonstrated that there is a significant effect of PME on the rate of delinquency in adolescence. The relation between PME and delinquent behavior is mediated by the effects of marijuana on depressive symptoms and partially mediated by attention deficits in the exposed offspring. The pathway from PME to delinquency, which is mediated by depressive symptoms and attention deficits, provides several potential points for intervention. Intervention to stop marijuana use during

Conflict of interest

Nothing declared.

Acknowledgement

We would like to acknowledge Dr. Vincent Smeriglio who was the Project Officer for our research grants for many years. Dr. Smeriglio was always available for questions or advice. He was helpful when things didn't go well, and supportive and excited when they did. Thank you Vince for your kindness, your wisdom, and your wonderful sense of humor.

This research was supported by a grant from the National Institute on Drug Abuse (DA03874), N. Day, P.I.

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