How does exposure to cannabis in the womb affect neurodevelopment?

In a recently published study, Nature Mental HealthResearchers investigated whether prenatal cannabis exposure (PCE) is associated with variations in brain development, which may partially buffer the relationship between PCE and increased psychopathology in early adolescence.

background

PCE has been linked to mental health problems in teenagers, but the underlying neurobiological pathways are unknown. Studies have shown that cannabis use during pregnancy is on the rise, despite warnings from health organizations and expert groups. Unfavorable birth outcomes include low birth weight and premature birth.

However, emerging research indicates that PCE in humans is associated with behavioral outcomes, including increased psychopathology and impaired cognitive performance. Understanding the safety of cannabis use during pregnancy and its impact on neonatal health is important.

About the Research

In this longitudinal study, the researchers investigated the relationship between PCE and mothers' understanding of pregnancy. They predicted that children who were exposed to cannabis prenatally would have a stronger association with cannabis exposure after their mothers learned of their pregnancy. They also explored whether brain measures were associated with psychopathology through the early teenage years and whether brain differences might partially explain these associations.

Researchers examined data from the Adolescent Brain, Cognitive and Development (ABCD) Study, which included 11,875 adolescents. They examined 16,641 findings from 10,186 subjects who had complete data from one or more neuroimaging modalities. Participants included 373 who were exposed to prenatal cannabis before their mothers knew they were pregnant (pre-knowledge only) and 195 who were exposed to cannabis both before and after they knew they were pregnant.

The researchers calculated significant correlations between prenatal cannabis exposure and the brain and 13 indices of mental health that have previously been associated with prenatal cannabis exposure in this population, including measures of psychotic-like experiences, social problems, attention problems, and aggressive behavior.

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

Study participants completed the 21-item Prodromal Symptom Questionnaire-Short Pediatric Version (PQ-BC) and provided saliva samples. The researchers genotyped the samples and used principal component analysis (PCA) to determine individuals' genetic backgrounds. The researchers created a polygenic score (PGS) for cannabis use disorder based on summary statistics from recent genome-wide association studies.

The researchers used mediation analyses to explore whether brain measures at baseline mediated the relationship between prenatal cannabis exposure and psychopathology one year later, and whether brain measures at two years later mediated the association three years later.

They analyzed the data using linear mixed-effects regression models, taking into account covariates such as adolescent status, income, race, history of psychiatric disorders, substance use problems in the family, parental education, prenatal exposure to non-cannabis substances, and pregnancy risk variables, including planned pregnancy, use of prenatal vitamin supplements, maternal age at delivery, and number of weeks pregnant when the mother became aware of her pregnancy.

result

This study found that PCE was associated with parietal and frontal cortical white and gray matter variability, striatal resting-state connectivity, and white matter pathways. Diffusion measures of the pars triangularis and forceps minor heterogeneity contribute to the association between PCE and symptoms of attention-deficit hyperactivity disorder (ADHD).

The associations between PCE and brain indices were somewhat limited, with reduced mean and lateral diffusivity in right pars triangular cortical grey matter, and higher total diffusivity and restricted directional diffusivity in forceps minor. These associations were driven by more pronounced effects in the pre-recognition group, but regions with pre-recognition effects did not show associations with psychopathology in subsequent analyses.

Post hoc analyses showed that associations with additional pregnancy-related factors were significant despite increased missing values, limiting the study to the baseline wave of data collection, and a reduced number of covariates.

The findings support the notion that potential effects of PCE on brain development may overlap with the effects of self-administered cannabis use. Using brain metrics, the research team found significant indirect associations between prenatal exposure and psychopathology, with cross-sectional associations remaining significant through time.

Conclusion

Overall, the findings suggest that abnormalities in brain development associated with PCE may increase susceptibility to poor mental health in early adolescence. This study found that PCE is associated with variations in brain growth, which may partially explain the association between PCE and increased psychopathology in early adolescence.

Future studies incorporating enhanced assessments of prenatal cannabis exposure and including differentially exposed family populations may provide deeper effects and greater insight into the causal processes behind these correlations.Significant brain measures were associated with early adolescent psychopathology, including externalizing-related measures, social problems, and self-reports of psychosis-like symptoms.