Depression in Pregnancy May 'Age' Children's Brains

Fran Lowry

November 21, 2016

Higher levels of maternal depressive symptoms prenatally and postpartum have been linked to the thinning of the cerebral cortex in young children, new research shows.

The findings suggest that maternal depression in pregnancy could adversely affect a child's brain development, underscoring the importance of treating depression in pregnant women, lead author Catherine Lebel, PhD, University of Calgary, Alberta, Canada, told Medscape Medical News.

"We found an association between brain structure in the kids and maternal depressive symptoms, so, while we cannot say the depressive symptoms cause this, there is definitely something different structurally in the brains of kids whose moms were more depressed," Dr Lebel said.

Dr Catherine Lebel

"We know that prenatal and postpartum depression in moms has negative consequences for kids in terms of things like behavior and learning, and in fact, the kids have higher risks of mental health problems themselves, so the brain structure is of interest because it can tell us a little bit about potential mechanisms, help us understand why maternal depression is associated with such outcomes in kids," she said.

The study was published in the December issue of Biological Psychiatry.

More Mature Brain Structure

The investigators studied 52 women for whom Edinburgh Postnatal Depression Scale (EPDS) scores were available during each trimester of pregnancy and at 3 months postpartum. Their children underwent MRI at age 2.6 to 5.1 years.

The investigators examined associations between maternal depressive symptoms and MRI measures of cortical thickness and white matter structure in the children.

They found that cortical thickness in two areas of the right hemisphere was negatively correlated with second trimester maternal depressive symptoms, after controlling for the child's age, sex, gestational age, and weight at birth, as well as maternal postsecondary education.

One region was located in the right inferior frontal area and included much of the pars opercularis and pars triangularis and small sections of the precentral and rostral middle frontal areas.

The other region was located in the middle and superior temporal regions and included small sections of the inferior temporal and supramarginal areas.

Correlations with second trimester EPDS scores remained strong after controlling for postpartum EPDS scores. Depressive symptoms during the first and third trimesters were not significantly related to cortical thickness.

In addition, structural patterns in the children's white matter were different.

"These types of changes suggest to us that the children whose mums were more depressed have a more mature pattern of brain structure. Their gray matter was thinner, and we know that with age, gray matter becomes thinner. So it looks like the kids whose mums were more depressed have this premature pattern of brain structure, almost like their brains are developing too soon," said Dr Lebel.

"Brain development is obviously a complicated process, and there is very likely a narrow window for an optimal time for stages of development to occur. Our findings may indicate that with brains developing almost a little bit too soon, these children are losing flexibility and adaptability that other kids might have.

"When you are young, your brain can learn more easily than when you are old. It's more plastic, so it's easy to learn new things, new languages, new skills, compared to being an older child or an adult. If you close that window too early, kids may lose out," she said.

Dr Lebel added that most of the women did not have major depression.

"Most of these women would not be diagnosed with depression. They were typical women with a typical pregnancy, and we still saw this association. We cannot prove causation; we are looking at an association, but certainly I think these results highlight the importance of monitoring mental health and treating it and really supporting women to help them maintain optimal mental health during pregnancy as well as post partum," she said.

"There is a lot of focus on postpartum depression, but prenatal depression exists, and it is actually quite common, and we have shown here that it is actually associated with children's brain structures. The finding highlights that prenatal is a very important stage to consider as well," Dr Lebel added.

Critical Time

In an accompanying editorial, Amalia Londono Tobon, MD, from the Yale Child Study Center, New Haven, Connecticut, and colleagues note that current neuroscience suggests that one of the most vulnerable times for a person's mental health might be while the individual is still in utero.

"A range of critical neurodevelopmental processes are taking place during this time, including neurogenesis, cell migration, and synaptogenesis. Given the complexity of this process, it is no surprise that small perturbations can lead to significant long-term consequences...," they write.

Prenatal stress may disrupt optimal development and adversely affect the developing brain, they note.

"Accumulating evidence suggests that psychopathology may start even earlier than is commonly acknowledged, and some psychiatric illnesses may need to be redefined as neurodevelopmental disorders.

“Prenatal stress may lead to pathology via various mechanisms, including oxidative damage and epigenetics. A more thorough understanding of these and other mechanisms may lead to unique therapies that can either reverse the damage of prenatal stressors or prevent the damage altogether," they conclude.

"I think that this study could be very important," John H. Krystal, MD, Robert L. McNeil, Jr, Professor of Translational Research and chair, Department of Psychiatry, Yale University School of Medicine, told Medscape Medical News.

Dr John Krystal

"Depression is terribly undertreated in our society. Only about one third of people who are depressed ever receive a diagnosis of depression, and only about a third of people who receive a diagnosis get the treatment that they need," said Dr Krystal, who is also the editor of Biological Psychiatry.

Major Public Health Concern

"Overall, in our society, roughly 1 in 5 people will meet diagnostic criteria for depression in their lifetime. The prevalence of depression in women, overall, is double that of men. Among women who are pregnant or have recently given birth, the rate of depression doubles to roughly four times the rate of depression in men. These statistics suggest that undiagnosed and untreated depression among pregnant women is very common and is a significant public health concern," he said.

"Medical attention has focused on depression during pregnancy and the postpartum period with the aim of alleviating the suffering of mothers and helping them care for their new babies and to function more effectively in their families and in their jobs. We have not considered the impact of maternal depression on the development of the baby," Dr Krystal added.

"This new study of 52 women and their offspring suggests that the greater severity of depression in the third trimester and the postpartum period is associated with thinning of the cerebral cortex in MRI scans in some of the most highly evolved regions of the brain, including the frontal and temporal cortex. These are brain regions that support higher cognitive and social and emotional functions. Other studies suggest that cortical thinning may in some cases be associated with aspects of cognitive function. The study findings raise the possibility that untreated or ineffectively treated depression affected the development of the brain," he said.

A question raised by this study concerns whether treatment of depression with medications might have prevented these alterations in brain development, Dr Krystal noted.

"Only one of the 52 women in this study was treated with antidepressants. We recognize that some antidepressant medications, such as paroxetine or mood stabilizing medications, such as lithium, appear to carry some risk for developmental effects when taken during pregnancy," he said.

"This new study suggests that the risk of developmental impact of maternal antidepressant medications must be weighed against the potential developmental impact of ineffectively treated maternal depression for the offspring.

"There are many forms of treatment for mood disorders that carry limited developmental risk for babies, including psychotherapy, neurostimulation treatments, such as transcranial magnetic stimulation of electroconvulsive therapy, or antidepressant medications that have very little developmental impact," said Dr Krystal.

"The more we look, the more we appreciate the breadth and depth of the destructive impact of depression. That is why we need to make sure that more people are screened for depression, more people [are] referred for effective treatment, and that there are continued effects to study the neurobiology of depression in order to develop safer and more effective treatments for depression," he said.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates – Health Solutions, and the National Institute of Environmental Health Sciences. The editorial was supported by the National Institutes of Health and was produced in collaboration with the National Neuroscience Curriculum Initiative. Dr Lebel and Dr Tobon report no relevant financial relationships. Dr Krystal is editor of Biological Psychiatry.

Biol Psychiatry. 2016;80:859-868, e85-e87. Abstract, Editorial


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