New way to think about brain's link to postpartum depression
Research in animals shows brain's immune system is activated by stress during pregnancy
October 21, 2019
Science Daily/Ohio State University
Chronic stress during pregnancy triggers an immune response in the brain that has potential to alter brain functions in ways that could contribute to postpartum depression, new research in animals suggests.
The study is the first to show evidence of this gestational stress response in the brain, which is unexpected because the immune system in both the body and the brain is suppressed during a normal pregnancy.
The Ohio State University researchers who made the discovery have been studying the brain biology behind postpartum depression for several years, creating depressive symptoms in pregnant rats by exposing them to chronic stress. Chronic stress during pregnancy is a common predictor of postpartum depression, which is characterized by extreme sadness, anxiety and exhaustion that can interfere with a mother's ability to care for herself or her baby.
Stress is known to lead to inflammation, which prompts an immune response to protect against inflammation's harmful effects. Based on what they already know about compromised brain signaling in rats stressed during pregnancy, the scientists suspect the immune cells in the brain responding to stress may be involved. If that's the case, the immune changes may create circumstances in the brain that increase susceptibility to depression.
In unstressed pregnant rats, the normal suppression of the immune system in the body and the brain remained intact throughout pregnancy. In contrast, stressed rats showed evidence of neuroinflammation. The study also showed that the stressed rats' immune response in the rest of their bodies was not active.
"That suggests there's this disconnect between what's happening in the body and what's happening in the brain," said Benedetta Leuner, associate professor of psychology at Ohio State and lead author of the study. She speculated that the signaling changes her lab has seen before in the brain and this immune response are happening in parallel, and may be directly related.
Leuner presented the findings Saturday (Oct. 19, 2019) at the Society for Neuroscience meeting in Chicago.
In this work, rats are exposed to unpredictable and varied stressful events throughout their pregnancies, a practice that adds a component of psychological stress but does not harm the health of the mother or her offspring.
In the stressed animals, the researchers found numerous pro-inflammatory compounds that indicated there was an increase in the number and activity levels of the primary immune cells in the brain called microglia. Their findings also suggested the microglia were affecting brain cells in the process.
Leuner's lab previously determined in rats that chronic stress during pregnancy prevented motherhood-related increases in dendritic spines, which are hair-like growths on brain cells that are used to exchange information with other neurons. These same rats behaved in ways similar to what is seen in human moms with postpartum depression: They had less physical interaction with their babies and showed depressive-like symptoms.
Leuner and colleagues now plan to see whether the brain immune cells activated during gestational stress are responsible for the dendritic spine elimination. They suspect that microglia might be clearing away synaptic material on dendrites.
Leuner has partnered on this research with Kathryn Lenz, assistant professor of psychology at Ohio State, whose work explores the role of the immune system in brain development.
Though pregnancy was known to suppress the body's immune system, Lenz and Leuner showed in a previous study that the same suppression of the immune system happens in the brain during pregnancy -- the number of microglia in the brain decreases.
"By layering gestational stress onto a normal pregnancy, we're finding this normal immunosuppression that should happen during pregnancy doesn't occur, and in fact there's evidence of inflammatory signaling in the brain that could be bad for dendritic spines and synapses," Lenz said. "But we've also found changes in the microglia's appetite. Every characteristic we've looked at in these cells has changed as a result of this stress."
The researchers are now trying to visualize microglia while they're performing their cleanup to see if they are eating synaptic material. They are also manipulating inflammatory changes in the brain to see if that reverses postpartum depression-like behavior in rats.
"We've seen the depressive-like symptoms and neural changes in terms of dendritic spines and synapses, and now we have neuroimmune changes suggesting that those microglia could be contributing to the neural changes -- which we think ultimately underlie the behaviors," Leuner said.
The research was supported by the National Institutes of Health
https://www.sciencedaily.com/releases/2019/10/191021151538.htm
Maternal diet during pregnancy may modulate the risk of ADHD symptoms in children
Association found between omega-6:omega-3 ratio in the umbilical cord and the appearance of ADHD symptoms
March 28, 2019
Science Daily/Barcelona Institute for Global Health (ISGlobal)
The results of a study led by a team from the Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa," suggest that the risk of a child developing symptoms of attention deficit hyperactivity disorder (ADHD) may be modulated by the mother's diet during pregnancy. The study, published in the Journal of Pediatrics, analysed samples of umbilical cord plasma to quantify the levels of omega-6 and omega-3 that reach the fetus. The statistical analysis showed a higher omega-6:omega-3 ratio to be associated with a higher risk of ADHD symptoms at seven years of age.
Omega-6 and omega-3 are long-chain polyunsaturated fatty acids that play a crucial role in the function and architecture of the central nervous system, particularly during the later stages of gestation. These two fatty acids compete for incorporation into cell membranes and are primarily obtained through diet. Since omega-6 and omega-3 have opposing physiological functions -- the former promotes systemic pro-inflammatory states, while the latter promotes anti-inflammatory states -- a balanced intake of these two fatty acids is important. Previous research had shown that children with ADHD symptoms have a higher omega-6:omega-3 ratio.
The authors studied data from 600 children living in four Spanish regions (Asturias, Basque Country, Catalonia and Valencia) who are participating in the INMA Project. They analysed umbilical cord plasma samples and data from questionnaires completed by the children's mothers. ADHD symptoms were assessed using two standard questionnaires: the first completed by the children's teachers at age four years, and the second by their parents at age seven years.
The results showed that, at age seven years, the number of ADHD symptoms increased by 13% per each unit increase in the omega-6:omega-3 ratio in umbilical cord plasma. The study analysed the number of symptoms in the children who met the diagnostic criteria for ADHD (minimum six symptoms) and also in the children with a smaller number of ADHD symptoms. The ratio of the two fatty acids was associated with the number of ADHD symptoms present but not with diagnosis of the disorder, and only in the assessment carried out at seven years of age. The authors suggest that the assessment carried out at four years of age may have been affected by a measurement error because ADHD symptoms reported at early ages may be caused by a neurodevelopmental delay falling within the normal range.
"Our findings are in line with previous studies that established a relationship between the omega-6:omega-3 ratio in mothers and various early neurodevelopmental outcomes," commented Mónica López-Vicente, ISGlobal researcher and lead author of the study.
"Although the association was not clinically significant, our findings are important at the level of the population as a whole," noted López-Vicente. "If a large proportion of the population is exposed to a high omega-6:omega-3 ratio, the distribution for ADHD symptom scores would likely move to the right and the prevalence of extreme values would increase, leading to a negative impact on the community's health costs and productivity."
"This study adds more evidence to the growing body of research on the importance of maternal diet during pregnancy," commented ISGlobal researcher Jordi Júlvez, a co-author of the study. "The nutrient supply during the earliest stages of life is essential in that it programs the structure and function of the organs, and this programming, in turn, has an impact on health at every stage of life. As the brain takes a long time to develop, it is particularly vulnerable to misprogramming. Alterations of this sort could therefore lead to neurodevelopmental disorders."
https://www.sciencedaily.com/releases/2019/03/190328080410.htm