Journal of Undergraduate Research
Volume 5, Issue 9 - June 2004
The Effects of Prenatal Cocaine Exposure on Cerebellar Vermis Size and Symptoms of Attention-Deficit Hyperactivity Disorder
Elisabeth Gentry
INTRODUCTION
The fact that Attention-Deficit Hyperactivity Disorder (ADHD) has become a significant problem in recent years is well-documented (Anderson, Polcari, Lowen, Renshaw, & Teicher, 2002; Mostofsky, Reiss, Lockhart, & Denckla, 1998; Wilens, Biederman, & Spencer, 2002). According to the Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition (DSM-IV) (American Psychiatric Association, 1994), ADHD is characterized by symptoms of hyperactivity, impulsivity, and inattentiveness.
Although labeled as a disorder, ADHD is not a disease but rather a collection of symptoms that seem to occur together and have been documented in the literature. One defining symptom of ADHD is the deficiency of executive functioning. Individuals with the disorder have increased binding at the dopamine receptors in the brain (Wilens et al., 2002). The cerebellar vermis, which is the area where dopamine transporters are located, has been found to be reduced in size (Bussing, Grudnik, Mason, Wasiak, & Leonard, 2002).
Effects of Maternal Cocaine Use
One substance that affects the dopamine transporters of the
brain is cocaine. Since cocaine easily crosses the placenta and has
access to the fetal brain while in utero, it has been suggested that
many neurodevelopmental defects would be apparent in exposed offspring
(Nassogne, Evrard, & Courtoy, 1998). Low birth weight is one adverse
effect of prenatal cocaine exposure (PCE). Many pregnant women who use
cocaine give birth to underweight babies even at normal gestation times
(Dow-Edwards, Chasnoff, & Griffith, 1992; Snodgrass, 1994). Interestingly,
low birth weight is also associated with ADHD. Therefore, it is reasonable
to expect that there will be a higher rate of ADHD symptoms among prenatally
exposed children.
Study Purpose and Hypotheses
This study tested the following hypotheses: (1) that the cocaine-exposed children demonstrate more attention-deficit symptoms as reflected in caregiver reports and a standardized test of attention than the non-exposed children, (2) that the cocaine-exposed children have smaller posterior-inferior vermis volumes than the non-exposed children, and (3) that a negative relation exists between the size of the posterior-inferior vermis and reported symptoms of ADHD and scores on the test of attention.ext here.
METHODS
Participants
In the present study 34 children (19 exposed/15 controls) were
examined from an original cohort of 308 already enrolled in an existing
study at the University of Florida. Originally the mothers of the children
who tested positive on urine screening for cocaine use and those who
admitted use in private interviews were asked to have their child participate
in a longitudinal developmental study (Eyler, Behnke, Conlon, Woods,
& Wobie, 1998). From a pool of non-users who also consented to the
study, 154 were matched to the cocaine users on level of socioeconomic
status (SES), racial/ethnic group membership, and number of previous
births.
Since birth, each child has been followed for 10 years and behavioral data collected at multiple intervals. A subset of children at age 10 was chosen to receive MRI scanning. Exposed and unexposed groups were balanced by gender and high or low IQ as measured by the WISC-III.
Measures
Behavioral data collection. For this study, three different
standardized measurement tools were used for evaluating three separate
aspects of the children’s lives. It has been noted that home environment
has a significant impact on developmental outcome and therefore the
Home Observation for Measurement of the Environment (HOME; Caldwell
& Bradley, 1984) was administered at ages 5 and 7. These ratings
were obtained by trained interviewers during routine interviews with
the caregivers in their homes. Second, Achenbach’s Child Behavior
Checklist (CBCL) was administered at child age 5 and age 7. Both kindergarten
and second grade teacher and primary caregiver reports were collected
(Warner, 2003).
Finally, the Letter Cancellation task (LC), which assesses visual scanning, motor speed and activation and inhibition of repetitive motor responses was administered at ages 5 and 7. Number of errors and time to completion were recorded for each individual. The age 7 time to completion data were analyzed for this study since it is the most recent data and should be more reflective of current attention abilities at the time of the MRI scan at age 10.
Additionally, SES as obtained using the Hollingshead Index, head circumference measurements at birth, maternal alcohol consumption (average number of ounces of alcohol consumed per day during pregnancy), and maternal tobacco use (average number of cigarettes smoked per day during pregnancy) were all separately and interactively analyzed. Race was not analyzed because over 75% were African American.
Neuroimaging and Measurement. At age 10 the 34 participants underwent Magnetic Resonance Imaging (MRI) scans in a 3T Siemens Allegra head scanner at the McKnight Brain Institute. The parameters for the scan which was taken in the axial plane parallel to the AC-PC axis were: repetition time (TR): 2150ms; echo time (TE): 438ms; flip angle: 8°; field of view (FOV): 25; matrix = 176 x 256. The images were processed in programs written in PV Wave (Visual Numeris, Boulder CO) so as to be viewed and measured on a computer screen. Each brain scan was measured by two trained researchers, blinded to any personal information related to the scan. For each slice, measuring 1 mm in thickness, the anterior, posterior-superior, and posterior-inferior lobules of the cerebellum were measured consecutively. Additionally, total brain volume was measured in order to adjust vermis measurements for overall brain size. All data were analyzed using the Statistical Package for the Social Sciences (SPSS). T tests were used to test for differences between the cocaine exposed and control groups. Pearson r’s were calculated to determine if there was an association between behavioral and anatomical measures. The significant alpha level was defined as p<.05.
RESULTS
Demographic variables and IQ regarding the children with prenatal cocaine exposure and the non-exposed children are listed in Table 1. Hypothesis one was partially supported. Although the cocaine exposed children did not perform less accurately on the letter cancellation task (see Table 2), they did take longer to complete the task than the controls (M=56.05s vs. M=48.27s). One control did not complete the task and had a score well outside the range of the other children. A t-test excluding this value revealed that the children with prenatal cocaine exposure did take significantly longer to complete the letter cancellation task than the non-exposed group, t(31) = 2.3, p<.05.
Other significant differences between the exposed and non-exposed children were that head circumference at birth was significantly smaller in the children with prenatal cocaine exposure (M=34.51) than the children without exposure (M=35.48), t(32)=2.08, p<.05. A negative correlation with the amount of cocaine exposure was found (r=-.454, p<.01). In the present study, there were no differences in brain volumes between the two groups which suggests the children with prenatal cocaine exposure caught up by age 10. Maternal alcohol use was also significantly higher in the cocaine-using group, t(32)=1.82, p<.01, as was maternal tobacco use, t(32)=2.13, p<.05. These findings have already been reported for the original sample, but it is important to note that the findings remain significant for this much smaller sample.
The second hypothesis was not supported. No significant differences were found among any of the structures between the two groups (see tables 3 & 4). The third hypothesis was also not supported. There were no significant correlations between any brain measure and any of the symptoms of ADHD. Interestingly, the HOME score also did not differ between the groups.
Table 1
Demographic VariablesVariable Age WISC III Full Scale IQ SES
Table 2
Variables for Current StudyVariable LC Age 7 (sec) CBCL Externalizing Score age 7 CBCL Internalizing Score age 7 HOME total score age 7 Head circumference at birth (cm) Maternal Alcohol Use (oz./day) Maternal Tobacco Use (cigarettes/day)
Table 3
Cerebellar MeasurementsPosterior Inferior Vermis Left* Right** Total*** Posterior Superior Vermis Left* Right** Total*** Left Hemisphere Volume Right Hemisphere Volume Total Volume * % left hemisphere volume, ** % right hemisphere volume, *** % of total brain volume
Table 4
Asymmetry Coefficients (positive numbers indicate left greater than right)Posterior Inferior Vermis Posterior Superior Vermis Total Brain
DISCUSSION
Our first hypothesis, that children with prenatal cocaine exposure would perform significantly poorer on the CBCL and letter cancellation task, was not strictly supported. However, when one extreme case was removed from analysis of the letter cancellation task data, we found that the children with prenatal cocaine exposure took significantly longer to complete the task. Additionally, the letter cancellation data in full still shows a slightly higher, though not significant, tendency for ADHD symptoms in children with prenatal exposure over non-exposed. No similar findings were apparent for the CBCL.
Our second study hypothesis was also not supported. Cerebellar vermis volumes and total brain volumes of prenatally exposed children did not differ significantly from controls. However, the present study does show that 27% of the non-exposed children and 58% of the children with prenatal cocaine exposure demonstrated leftward asymmetry for the cerebellar vermis. This indicates a slight trend for leftward asymmetry of children with prenatal exposure.
Our third study hypothesis was also not supported since no effects of cerebellar vermis size on symptoms of ADHD were found. Although this study does not show strong indications that children with prenatal cocaine exposure are more prone to ADHD symptoms, they did tend to take longer on the letter cancellation task. Perhaps prenatal cocaine exposure affects a different area of the brain, eventually leading to similar external symptoms of ADHD as those children with ADHD but no prenatal exposure.
CONCLUSION
Based on these findings, it appears that prenatal cocaine exposure may not be as harmful as once thought. The exposed and control groups demonstrated almost identical brain volumes indicating cocaine did not hinder their neurological development. Their IQ scores as well as performances on the CBCL and letter cancellation task are equivalent across groups. This study did not support the notion that prenatally exposed and non-exposed children differ in symptoms of ADHD or cerebellar vermis size. Additionally, cerebellar vermis size did not predict symptoms of ADHD in either group. It is quite possible that since these children are still young their brain structures that may be affected by maternal cocaine use are not mature enough to show any abnormalities. Further studies could use more sensitive imaging techniques such as Diffusion Tensor Imaging to examine other brain structures as well.
The study was funded by the National Institute on Drug Abuse, grant number DA05854, and a University Scholars Program Scholarship.
ACKNOWLEDGEMENTS
I would like to thank Christiana Leonard, Ph.D., Fonda Davis Eyler, Ph.D., and Marylou Behnke, M.D. for their unyielding help, patience, and support throughout this project. Additionally, I would like to thank Dr. Eyler and Dr. Behnke for allowing me access to their data. I would also like to acknowledge the invaluable help of Tamara Duckworth Warner, Ph.D. for her advice on analysis of data.
REFERENCES
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