How may cannabis affect neurodevelopment when exposed in the womb?

In a recent study published in Nature Mental Health, researchers investigated whether prenatal cannabis exposure (PCE) is related to variations in brain development, which may partially mitigate the relationship between PCE and increased psychopathology throughout early adolescence.

Background

PCE has been related to mental health problems in teenagers, although the underlying neurobiological pathways are unclear. Studies report increased cannabis usage during pregnancy despite warnings from health agencies and professional groups. Unfavorable birth outcomes include low weight at birth and premature delivery.

However, emerging research shows that PCE among humans is related to behavioral consequences such as increased psychopathological illness and worse cognition. Understanding cannabis usage safety during gestation and its effects on neonatal health is critical.

About the study

In the present longitudinal study, researchers examined the relationship between PCE and maternal understanding of pregnancy. They anticipated that children with prenatal exposure to cannabis would have stronger relationships with cannabis exposure after their mothers were aware of their pregnancy. They additionally investigated whether brain measurements were related to psychopathology through early teenage years and whether brain differences partially explained these associations.

The researchers examined the Adolescent Brain Cognitive Development (ABCD) Study data, which included 11,875 youngsters. They studied 16,641 findings among 10,186 individuals with complete data for one or more neuroimaging modalities. Participants included 373 with prenatal cannabis exposure before the mother’s awareness of gravidity (pre-knowledge only) and 195 cannabis-exposed prior to and post-pregnancy awareness.

The researchers calculated the relationship between the significant prenatal cannabis exposure-brain correlations and the 13 indicators of psychiatric health previously related to prenatal cannabis exposure in this population, which included measures of psychotic-like experiences, social issues, attention problems, and aggressive behavior.

The researchers used several brain measures, including rs-fMRI, DTI, and RSI. The rs-fMRI measurements included subcortical and cortical connections, thickness, surface area, volume, and sulci depth. The DTI and RSI models were used to analyze diffusion-weighted information from cortical white matter, gray matter, and tracts of white matter.

The study participants completed the 21-item Prodromal Questionnaire—Brief Child Version (PQ-BC) and submitted saliva samples. The researchers genotyped the samples and used principal components analysis (PCA) to determine the individuals’ genetic backgrounds. They created polygenic scores (PGSs) for cannabis use disorder based on summary statistics from recent genome-wide association research.

The researchers used mediation analyses to investigate whether brain metrics at baseline mediated the relationship between prenatal cannabis exposure and psychopathology at one year and if brain metrics at two years mediated the associations at three years.

They used linear mixed-effects regression models to analyze the data, taking into account covariates such as pubertal status, income, race, histories of mental disorders, substance usage problems among family members, parental education, prenatal non-cannabis substance exposure, and pregnancy risk variables. Pregnancy risk factors included intended pregnancy, usage of prenatal vitamin supplementation, the mother’s age at childbirth, and weeks of gestation at maternal awareness of pregnancy.

Results

The study found that PCE is associated with white and gray matter variations in the parietal and frontal cortices, striatal resting-state connectivity, and tracts of white matter. The heterogeneity in pars triangularis diffusion measurements and forceps minor contributes to the link between PCE and attention deficit hyperactivity disorder (ADHD) symptoms.

PCE and brain metrics have somewhat confined relationships, with reduced mean and transverse diffusivity in right-sided pars triangularis cortex gray matter and more total diffusion and restricted directional diffusivity in forceps minor. The relationships were attributed to more profound effects in the pre-awareness group, although areas with pre-knowledge effects did not demonstrate links with psychopathologies in later analyses.

Post-hoc analysis indicated that relationships were significant with additional pregnancy-related factors despite increasing missingness, restricting studies to the baseline wave of data collection, and a smaller number of covariates.

The findings support the concept that the potential effects of PCE on brain development may overlap with the effects of self-administered cannabis usage. The team found indirect relationships between prenatal exposure and psychopathology significant using brain metrics, and the cross-sectional associations remained significant throughout time.

Conclusion

Overall, the study findings indicated that PCE-related abnormalities in brain development may increase sensitivity to poor mental health in early adolescence. The study found that PCE is related to variations in brain growth, which may partially explain the link between PCE and increased psychopathology throughout early adolescence.

Future research that incorporates enhanced assessment of prenatal cannabis exposure and recruits familial populations with disparate exposures may produce more profound effects and more insight into the causal processes behind these correlations. Significant brain measurements were linked to psychopathology in early adolescence, including externalizing-related measures, social issues, and self-reporting of psychotic-like symptoms.