Can baby teeth be used to identify children at risk of mental health disorders later in life?

12 November 2021
4 min read

An investigation led by researchers at Massachusetts General Hospital (MGH) and published in JAMA Network Open has revealed that the thickness of growth marks in primary teeth may help identify children at risk for depression and other mental health disorders later in life.

Senior author Erin C. Dunn, ScD, MPH, is a social and psychiatric epidemiologist and an investigator in MGH’s Psychiatric and Neurodevelopmental Genetics Unit. She studies the effects of childhood adversity, which research suggests is responsible for up to one-third of all mental health disorders. Indeed, the investigation report explains, “Children’s exposure to prenatal and perinatal maternal psychosocial stressors, such as psychopathological symptoms, stressful life events, and neighbourhood disadvantage, can impact brain health across the life course. In addition to nearly doubling the risk of a mental health disorder, maternal psychosocial stress can become biologically embedded in children, resulting in lifelong physiological and neurobiological disruptions.”

As such, Erin was interested in uncovering whether there are specific periods during a child’s development when exposure to adversity is particularly harmful – however, scientists lack an effective tool for measuring this. Whilst asking people about painful experiences from their childhood is an option, it is vulnerable to poor recall and a reluctance to share painful memories. Detailed prenatal medical reports are often unavailable, posing another challenge. As a result, the report explains that “there is a need for novel measurement tools that can objectively, as well as inexpensively and noninvasively, provide information (beyond self-reports) about children’s exposure to prenatal maternal stress and social support.”

The investigation centres on the neonatal line (NNL) – a tooth-based marker. Whilst work has recently been done on whether teeth can be used as biomarkers of early-life adversity and subsequent mental health risk, Erin wanted to investigate the extent to which measures of maternal psychosocial stress, a major form of early-life adversity, can also associated with tooth-based markers – specifically, the NNL.

The report explains, “The NNL has been used in anthropology for decades to distinguish between prenatal and postnatal enamel and characterize the overall stress of the birth process. One of the most prominent stress lines in teeth, the NNL has previously been investigated in conjunction with certain prenatal and perinatal factors, including maternal health and delivery characteristics. Notably, stressful prenatal and perinatal conditions, such as complicated delivery, longer duration of delivery, and preterm births, have been associated with wider NNLs.

“Although the NNL is an established anthropological marker of stressful gestational events, it remains unknown whether it could act as a biomarker of prenatal and perinatal psychosocial stress in modern paediatric populations. A handful of nonhuman primate studies suggest exposure to psychosocial stressors during early life, such as separation from the mother or social group or death of a sibling, may coincide with the presence of postnatal stress lines. However, this possibility has yet to be systematically investigated in humans. We describe what is, to our knowledge, the first study to characterize the association between maternal psychosocial factors and any tooth-based measure in living humans.

“In this study, we tested the hypothesis that children exposed to common prenatal and perinatal maternal stressors (stressful life events, maternal psychopathological symptoms and diagnoses, and neighbourhood disadvantage) display wider NNLs—indicative of more stressful conditions—than unexposed children. We also tested the hypothesis that children exposed to protective effects (greater social support for the mother) display narrower NNLs, even after controlling for physiological confounders.”

To test the hypothesis, Erin and two co-lead authors—postdoctoral research fellow Rebecca V. Mountain, PhD, and data analyst Yiwen Zhu, MS, who were both in the Psychiatric and Neurodevelopmental Genetics Unit at the time of the study—led a team that analysed “70 primary teeth collected from 70 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, population-based birth cohort in Bristol, England, beginning in the 1990s and designed to increase understanding of the genetic and environmental factors associated with disease across the life course”. Specifically, the teeth collected were canines of five-to seven-year-old’s that had naturally fallen out.

The report discusses their method, “We examined four types of prenatal and perinatal maternal psychosocial factors: prenatal stressful life events, psychopathological history and symptoms, neighbourhood disadvantage, and prenatal and perinatal social support. These factors were chosen because they represent prominent determinants of child health during the prenatal and perinatal periods. Data were self-reported from mailed-in questionnaires, which mothers completed during and shortly after pregnancy.

“Race and ethnicity were measured as a binary variable (White vs non-White) in the study because the study sample in Avon, UK, was homogeneous, with predominantly White participants. While we recognize the importance of reporting racial and ethnic differences, a more refined categorization was not analytically feasible given our limited sample size.”

Media outlet Eureka Alert summaries the findings, “Several clear patterns emerged. Children whose mothers had lifetime histories of severe depression or other psychiatric problems, as well as mothers who experienced depression or anxiety at 32 weeks of pregnancy, were more likely than other kids to have thicker NNLs. Meanwhile, children of mothers who received significant social support shortly after pregnancy tended to have thinner NNLs. These trends remained intact after the researchers controlled for other factors that are known to influence NNL width, including iron supplementation during pregnancy, gestational age (the time between conception and birth) and maternal obesity.”

“There are several possible mechanisms through which maternal psychosocial stress may become biologically embedded in offspring’s teeth,” the report explains.

“For instance, maternal cortisol responses may influence enamel formation via insulin-like growth factors (IGFs). Cortisol increases following chronic psychosocial stress, decreasing IGF production in the hard tissues. Both IGF-1 and IGF-2 are involved in amelogenesis and positively associated with enamel production. Increased maternal cortisol production, as a result of psychosocial stress, may reduce IGF production in offspring. Higher maternal cortisol levels could likewise decrease amelogenesis during the perinatal period and result in a wider NNL. Conversely, enhanced social support may decrease maternal cortisol levels, possibly producing an inverse effect from psychosocial stress and therefore resulting in a narrower NNL.”

The report discusses, “Should these results be replicated in larger samples, they could have important implications for future intervention programs. Children naturally begin exfoliating teeth around 6 years of age. With more than half of mental health disorders diagnosed by early adolescence, early intervention around this time is critical and can have lifelong benefits. Children’s exfoliated teeth could be collected from paediatricians or dentists during routine check-ups and sent to specialized laboratories for analysis. As is commonly done with other biospecimens during annual physical examinations, these teeth could be examined to detect adverse exposures that would be otherwise difficult to assess. In turn, the results could help identify children at risk and direct them toward evidence-based intervention programs, long before the onset of mental health symptoms.”

The researchers at MGH conclude, “The findings of this cohort study suggest that perinatal psychosocial factors may show novel associations with the NNL. Future studies should attempt to replicate and validate this finding and investigate the links between tooth-based characteristics and child health outcomes. Such research could lay the groundwork for targeted intervention strategies to identify at-risk children and prevent future mental health disorders years before the onset of symptoms.”