Schizophrenia is a serious mental health disorder that is characterized by psychosis, making it difficult for a person to tell what is real. It impacts about one per cent of the Canadian population and is linked to major health challenges, including a shorter life span.
Many factors can increase the risk of developing schizophrenia, such as prenatal environmental conditions (for example, malnutrition or drug exposure), family history, childhood trauma and growing up in an urban environment.
However, there are still no reliable biomarkers that can predict early risk. This is important because early diagnosis leads to better treatment and outcomes for patients. Researchers are now looking at the placenta as a possible source of early indicators of schizophrenia risk.
The placenta-brain axis
The placenta can “record” what happens during pregnancy and can reflect both healthy and unhealthy conditions for the baby. This idea is known as the placenta-brain axis, which suggests that when the placenta is negatively affected, brain development may also be harmed in both the short and long term.
Large clinical studies have shown that in pregnancies resulting in low birth weight babies, certain genetic markers in the placenta are changed. These markers are strongly linked to a higher risk of schizophrenia and other negative behavioural outcomes (for example, autism, impaired cognition) in children.
There is also strong evidence connecting cannabis use during pregnancy to harmful effects on a child’s brain development, including a higher risk of schizophrenia. This is especially concerning in Canada, where cannabis was legalized in 2018. Since then, cannabis use during pregnancy has increased, with the highest reported rate of 24 per cent among pregnant teens (ages 13 to 19 years).
Although prenatal cannabis use is known to be associated with low birth weight, it is not well understood whether cannabis exposure affects the same placental biomarkers linked to schizophrenia. My laboratory, which has experience studying the effects of drug exposure during pregnancy, explored this question in a study published in Biology of Reproduction in January.
THC exposure
As a professor in the Department of Obstetrics and Gynaecology at the Schulich School of Medicine and Dentistry at Western University, I worked with my research team and collaborators, including master of science student Andrea Kocsis, Enzo Perez Valenzuela, Ph.D., David Natale, Ph.D., and Steven Laviolette, Ph.D. to investigate whether THC (the main psychoactive component of cannabis) changes these known placental schizophrenia markers.
First, we used a preclinical rodent model in which pregnant animals were given edible THC mixed with Nutella. We found that both male and female offspring exposed to THC showed reduced prepulse inhibition early in life. Prepulse inhibition is a psychological test commonly used when diagnosing schizophrenia in humans. Specifically, the prepulse inhibition test measures sensorimotor gating — the brain’s ability to filter out irrelevant stimuli — by observing how a weak, preceding stimulus (prepulse) reduces the startle response to a subsequent loud noise (pulse).
More importantly, we discovered that the placentae of these THC-exposed offspring showed increases in several human placental markers linked to schizophrenia risk.
We then tested whether this also occurs in a human cell culture model. We found that isolated human placental cells treated short-term (24 hours) with THC showed similar increases in these schizophrenia-related genes in these cells.
Identifying risks
This study has important clinical implications. Although stopping cannabis use during pregnancy is always recommended, it can be difficult for many people due to social or habitual dependence. As a result, some children are exposed to cannabis before birth without having any choice.
By identifying cannabis-specific placental markers linked to schizophrenia, there is potential to reduce negative behavioural outcomes early in life through psychological or dietary interventions. Since schizophrenia is usually diagnosed between ages 16 and 30, being able to identify risk at birth would be extremely valuable. Moreover, testing the placenta after delivery could become a practical way to assess schizophrenia risk.
Further research is needed to understand whether other components of cannabis, such as cannabidiol (CBD), also affect neurodevelopment or alter these placental markers. It is also imperative to explore whether these markers can help predict other outcomes, including adverse psychological conditions, autism or cognitive impairments.
Additionally, because the pre-conception health and lifestyle of fathers as well as mothers can affect the placenta, it is also possible that consumption of cannabinoids by either parent before pregnancy could affect placental health and increase schizophrenia risk, but this requires further study.
In the meantime, our findings provide important functional evidence for clinicians and regulatory agencies, such as Health Canada, as they continue to make decisions and policies regarding the safety of cannabis use during pregnancy.
Daniel Hardy receives funding from the Canadian Institutes for Health Research (CIHR).
This article was originally published on The Conversation. Read the original article.
