A recent study provides new insights into how maternal and fetal genes contribute to the growth of a baby’s cerebral cortex, the brain’s outer layer responsible for many of its higher functions. Published in Nature Communications, the research not only underscores the genetic variants linked to higher birth weight and an enlarged cerebral cortex but also highlights the influence of environmental factors, such as food availability, on these genetic interactions.
The motivation behind this study was to deepen our understanding of early brain development, which plays a pivotal role in determining cognitive abilities and mental health outcomes later in life. By focusing on the cerebral cortex, the brain region responsible for many higher-order functions such as thought, memory, and decision-making, researchers aimed to dissect the factors contributing to its growth in utero.
“We are interested in early brain development because we know how important it is for future cognitive capacities and mental health. And studying what drives growth of the brain in the womb is one way to start,” explained study author Tomas Paus, a professor at the University of Montreal, scientist in the Research Centre of the Mother and Child Hospital, and co-editor of Digital Ethology: Human Behaviour in Geospatial Context.
“It is important to note that we are able to look for answers to these questions not only by imaging the brain during this period but also by looking at the adult brain – simply because most of the growth of the cerebral cortex is happening in the womb and during the first couple of years after birth. So looking at the brain – the total area of the cerebral cortex (~1,800 cm2) – of a middle-aged person is providing a window into early development, and everything in our genes and environment that influence this early growth.”
To investigate this, the researchers turned to the UK Biobank, a rich biomedical database that includes genetic, health, and demographic information from over half a million participants across the United Kingdom. Specifically, they focused on a subset of participants for whom detailed birth weight data, genetic information, and brain magnetic resonance imaging (MRI) scans were available.
The team first identified genetic variants associated with birth weight by examining both maternal and fetal genes. They distinguished between genes directly influencing the fetus’s birth weight and those affecting the intrauterine environment, thereby influencing fetal growth indirectly.
For the fetal aspect, they found genes linked to insulin action to be pivotal, highlighting insulin’s role in growth and energy regulation. Maternally, genes that enhance the cell’s ability to detoxify emerged as significant, underscoring the mother’s environmental and physiological influence on fetal development.
With these genetic markers in hand, the researchers then turned to the MRI scans to measure the surface area of the cerebral cortex. By applying sophisticated imaging analysis techniques, they were able to quantify the cortical surface area in thousands of adults, providing a window back into the critical periods of brain development in the womb and early life.
The analysis yielded several key findings. First, they confirmed a positive association between higher birth weight and a larger cortical surface area, underscoring the link between overall fetal growth and brain development. More intriguingly, they discovered that the genetic variants in both the mother and baby associated with birth weight were also linked to the size of the cerebral cortex.
Further analysis revealed that the relative importance of maternal and fetal genetic variants in determining cortical size could vary based on external conditions, notably food availability. This was dramatically illustrated by examining individuals born during or shortly after the Dutch famine of 1944-45.
In individuals born during or shortly after this period, maternal genes associated with detoxification had a more pronounced effect on the growth of the cerebral cortex. This suggests that under conditions of food scarcity, the ability to detoxify, potentially linked to the mother’s ability to process and eliminate toxins, becomes more crucial for fetal brain development.
Interestingly, the researchers observed that this pattern of relationships between maternal detoxification genes and cortical growth seemed to reemerge in the children of those exposed to famine, hinting at a potential transgenerational transmission of these effects.
Paus told PsyPost he was surprise by “the fact that different sets of ‘birthweight’ genes relate to the cortical growth depending on when the person was born, namely during WWII or ~10 years later. We interpreted this finding as reflecting differences in food availability, scarce during the war and abundant later.”
“We were also quite surprised to see that the same pattern of this relationship reemerged about 20 years later, hinting at possible transgenerational transmission of this possible effect of environment (food availability).”
The findings highlight that the “healthy growth of the baby during pregnancy also means health growth of their brains,” Paus explained. “We must do what we can to ensure that all pregnant women have access to healthy food and free health care.”
The study, while groundbreaking, is not without its limitations. For instance, while it robustly links birth weight and cortical growth to specific genetic and environmental factors, the observational nature of the study and its reliance on historical data mean that direct causal relationships are difficult to establish. Moreover, the potential for transgenerational effects, suggested by the findings, opens up new avenues for exploration but requires more direct evidence to be fully understood.
“As with any observational study, we cannot make any causal inferences,” Paus said. “And, of course, we do not know what the pregnant mothers ate – remember, they were pregnant with the persons we studied many years earlier, as far back as during WWII.”
Future research will aim to build on these findings, exploring ways to optimize brain growth during pregnancy, Paus said. “And – if this was not possible in some cases for whatever reason – finding ways we can compensate for a suboptimal growth later in childhood so that we can maximize cognitive abilities of the child and minimize the risk of mental illness later in life.”
The study, “Intrauterine growth and the tangential expansion of the human cerebral cortex in times of food scarcity and abundance,” was authored by Daniel E. Vosberg, Igor Jurisica, Zdenka Pausova, and Tomáš Paus.
