(Updated 09.03.08 and 09.05.08 to include additional links for popular press on epigenetics, scroll down)
This post is about how stress on the parent induces DNA changes in the developing baby.
Birth Scene, oil on paper, possibly French 1800′s (via Wellcome Images)
Southern California (which is, admittedly, an 11 on the dysfunctional scale), seems to be a hot bed of neurological phenotypes. In my orbit there are so many diagnosed with something — addictions, bipolar, OCD, youngish-Parkinson’s, older dementias, mean-and-nastiness, depression, manias, antisocials, of course, obesity — and this just covers my family, friends and neighbors. (Here’s the World Health Organization Mental Health page, with some statistics). Even our lame-duck President is a recovering alcoholic. Rehab biz is booming.
Most people ascribe this to moral failings in society. I’ve previously wondered if there was mass fetal alcohol spectrum from maternal smoking, drinking and drugging in the ’60′s and ’70′s.
But now — I’m thinking in utero epigenetic changes.
Perhaps the 20th century industrialized war machines causing massive stress in wide swaths of the population resulted, a generation or two later, in mass epigenetic changes related to brain biology.
We know that epigenetics play a role in neurological conditions, like autistic spectrum disorder, bipolar, depression and probably others that we haven’t yet connected, like maybe obesity. (Here’s other posts on epigenetics). Could the cause of these epigenetic changes been the in utero environment — particularly a stressed-out mother? Or an older father with epigenetically-loaded sperm?
Recent papers may shed some light on this:
Acute maternal stress during second trimester (here, the Israeli-Arab “Six Day War” in 1967) results in higher incidence of schizophrenia. Malaspina et al., “Acute maternal stress in pregnancy and schizophrenia in offspring: a cohort prospective study,” BMC Psychiatry 8: 71 (08.21.08)doi:10.1186/1471-244X-8-71
Malaspina et al show the second trimester is a particularly vulnerable period: that acute stress – the “Six day war” — resulted in higher incidence of schizophrenia in offspring than if those six days were in the first- or the third-trimester. The second trimester is a period of intense mid-line development – body laterality can get messed up. And schizophrenia does show altered laterality (the paper cited is one example, as far as enzymatic activity as compared to normals).
But even more chronic maternal stress, like that of the Dutch famine of 1945, or the Chinese Famine in 1959-1961has been associated with increased prevalence of schizophrenia of offspring. Among Holocaust survivors, maternal, not paternal, post traumatic stress disorder (PTSD) is correlated with offspring PTSD.
But, what about obesity?
There are in utero epigenetic changes caused by diet. In utero leptin may program adult obesity . So perhaps the children born during the great depression were programmed in utero to only judiciously burn fat. Or, maybe processed foods — something not planned out evolutionarily – threw the fetal metabolic imprinting totally out of whack.
Paternal epigenetics also play a role, but obviously this is from the sperm, unless the father carries the offspring in utero, which has sort of happened. Offspring from older male sperm has increased risk of bipolar, autism, schizophrenia and other conditions. Frans et al., “Advancing Paternal Age and Bipolar Disorder,” Arch Gen Psychiatry. 2008;65(9):1034-1040 (this is the paper for bipolar).
Stress causes epigenetic changes in sperm, and war stress probably put epigenetic changes in the sperm on fast forward. Men who survived the war (pick one, WWII, Korea, Viet Nam, gulf states, Iraq. . . ) perhaps had their youngest children late in life, perhaps resulting in accumulated epigenetic changes.
Are paternal epigenetics related to transient heat? Do Jacuzzi®s or heated car seats have anything to do with autistic spectrum? Even transient high heat from sitting in the jacuzzi can cause DNA changes in sperm DNA. Jacuzzi®s were invented in 1968 — can this be correlated with the uptick in autistic spectrum diagnosis? And, high scrotal heat can result from heated car seats.
At any rate, stress can induce epigenetic changes in the child, and these epigenetic changes can result in a behavioral psychiatric phenotype. Domestic violence during the second trimester of pregnancy seems particularly likely to result in epigenetic changes. Violent neighborhoods, gangs, countries – populations where acute trauma, bad diet, high chronic stress are the new normal — perhaps there are self-segregating populations caused by epigenetic changes.
Ironically, hot tubs and heated car seats in your convertible may also have something to do with heat shocks causing sperm epigenetic changes.
The knowledge that maternal stress affects the fetus has important implications for mental health in a world threatened by acute violence and war. Terrorist acts have stressed whole populations nation-wide, while more locally, hurricanes and earthquakes are recurring stressors in some countries. Smaller communities or individuals can be affected acutely by tornados, episodes of community violence, accidents, bereavement, domestic violence or rape. A significant component of the public burden of mental illness may follow such frights to pregnant women. The subject of intrauterine stress and major psychiatric disorders deserves further scrutiny. Well designed research studies should be aimed at elucidating the pathways to risk and at defining strategies and interventions for prevention.
Additional links to popular press 09.03.08
James Ronan Blog, “Epigenetics and Autism” post, plus links to other posts, and including the links below
“The Ghost in your Genes,” TV show, US Public Broadcasting, landing page
Cogito Interview: Andrew Feinberg, Epigenetics Pioneer
Epigenetics Backgrounder, Johns Hopkins press office (2002, but easily readable)
DNA is not Destiny, Discover Magazine Cover
09.05.08: And one more update related to autistic spectrum disorder and imprinting (in part, intrauterine epigenetics).
Battle of the Sexes May Set the Brain, Christopher Badcock and Bernard Crespi, Nature 2008 (via Scribed)
(This is getting like the situation where you learn a new word and all of a sudden everyone is using it – there are several new papers related to intrauterine epigenetic changes skewing body weight regulation toward obesity which, at least in animal models, are reversible with methylation regulation agents. I’m preparing another post on this one).
[...] Correlates, Second-generation addiction, autistic spectrum, bipolar, schizophrenia, and obesity as artifacts of … Epigenetics explains everything!? Stress meets [...]
Fascinating post. These are some tremendously important questions. Anyone who still argues that there is any hard and fast line between genetics and culture quite clearly has their head buried in the sand. But how can scientists who study the complex interactions between environment, genetics, and behavior when there are so many confounding factors? Stressful perinatal events are extraordinarily likely to have effects far beyond the immediate gestational environment of the developing embryo/infant.
It is going to be vitally important for scientists and social scientists to convincingly demonstrate these links. The “well designed research studies” called for by Malaspina and colleagues are precisely what we need–but how does one design an empirical study that, to be slightly cheeky, controls for everything?
Thanks for this post.
Thanks BB for your thoughtful comments, and your website, “The Banana Peel Project” is terrific — I’m going to spend some time there later.
Your point really cuts to the real issue: how to do nature/nurture studies at all?
Malaspina et al show that the second trimester is the time of most genomic plasticity (if that is part of epigenetics, or imprinting).
I think an interesting question is the larger social question:
Is there a societal impact for children who gestated during war?
20-30 years later, are these grow-up children, (who may have psychiatric illness) otherwise exceptionally creative or intelligent?
Is Israel home to many technological advances because of (or in spite of) the gestational influences?
Are there any other relatively closed populations where there has been a sudden burst of creativity which can be traced to a societal event?
Thanks again BB, Swivelchair
Thank you Neuroanthropology for the cite in your Wednesday Roundup!
http://neuroanthropology.net/2008/09/10/wednesday-round-up-28/
What about the positive effects of stress? Perhaps it promotes curiosity and competitive drive? I’m just sayin’ …
Is this really epigenetics or hormonal changes in the parent/womb. So, for example, it appears that testostorone jolts in the womb, may lead to homosexuality in men/higher testostorone in life (sometimes measured by index finger length).
So if epigenetics is the changing of epigenetic structure, carried forward by environmental events, this just seems the driving of genetic expression, ie, production of proteins, by environmental events.
Mixed Messages from Mom – Maternal Psychological Health Influences Fetal Development
Posted: 05 Dec 2011 04:00 AM PST
Pregnancy is far from a stress-free time of life. But, most mothers try their best to provide a healthy, happy placental home for nine months, knowing that anything she does to or for herself, she does to her growing fetus. The placental environment is sensitive to many foods, drinks, medications, and even activities, and the effects of many of these (think smoking and drinking) have long-term negative consequences. But, in addition to these external influences, internal factors, including psychological health and hormone levels, affect fetal development. A new study to be published in an upcoming issue of Psychological Science claims that, in fact, consistency of maternal mental health is more important in fetal outcomes than whether or not the mother is actually healthy.
The study, whose findings were published early through a press release by the Association for Psychological Science, examined how a mother’s mental state, specifically signs and symptoms of depression, influenced the development of babies, both before and after birth. Interestingly, the babies with the best developmental outcomes were those who grew in a consistent environment. That is, babies whose mothers were healthy both before and after birth and babies whose mothers were depressed both before and after birth had higher developmental scores than babies whose mothers went from healthy to depressed or depressed to healthy during or after birth.
Related studies by the same team of researchers revealed that anxiety during pregnancy, and its related fluctuations in hormones, predicts infant development and temperament. The higher the levels of cortisol, which indicate elevated levels of stress, at different points during pregnancy were significantly associated with negative reactivity and impaired adaptation to stress in infants. Maternal cortisol levels were also related to a more difficult temperament, behavioral and emotional problems, and delayed motor and cognitive development in infants. There is also evidence that cortisol levels during pregnancy result in differences in brain structures in infants.
So, what is a mom to do? Clearly, a lifetime of emotional and psychological connections to her baby begins in the womb, and unstable mental health places the child at risk for developmental, emotional, and cognitive impairment. But, so far, none of these studies have been able to prove if these connections are transient, persistent, or progressive. And, levels of stress and depression are only part of a myriad of conditions and environmental factors that influence development in offspring.
Throughout life, maternal-child interactions are dynamic and influenced by numerous internal and external factors. The current research underscores just how early these interactions start. And, it emphasizes that consistency is key. As the authors note, a cynical interpretation would be to let women who are depressed or anxious stay that way, in order to provide a consistent fetal environment. But, a more pragmatic approach would be to screen mothers-to-be before pregnancy for mental health conditions that may affect their babies later in life. And, monitoring of children at risk for psychological or developmental issues will lead to early intervention and treatment.
Maybe the bottom line is that fetuses should start preparing themselves early for a lifetime of mixed messages from mom.
References
Blair MM, Glynn LM, Sandman CA, & Davis EP (2011). Prenatal maternal anxiety and early childhood temperament. Stress (Amsterdam, Netherlands), 14 (6), 644-51 PMID: 21790468
Buitelaar JK, Huizink AC, Mulder EJ, de Medina PG, & Visser GH (2003). Prenatal stress and cognitive development and temperament in infants. Neurobiology of aging, 24 Suppl 1 PMID: 12829109
Change in mother’s mental state can influence her baby’s development before and after birth. Press release Nov. 9, 2011.
Davis EP, Glynn LM, Schetter CD, Hobel C, Chicz-Demet A, & Sandman CA (2007). Prenatal exposure to maternal depression and cortisol influences infant temperament. Journal of the American Academy of Child and Adolescent Psychiatry, 46 (6), 737-46 PMID: 17513986
Davis EP, & Sandman CA (2010). The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child development, 81 (1), 131-48 PMID: 20331658
de Weerth C, van Hees Y, & Buitelaar JK (2003). Prenatal maternal cortisol levels and infant behavior during the first 5 months. Early human development, 74 (2), 139-51 PMID: 14580753
Huizink AC, Robles de Medina PG, Mulder EJ, Visser GH, & Buitelaar JK (2003). Stress during pregnancy is associated with developmental outcome in infancy. Journal of child psychology and psychiatry, and allied disciplines, 44 (6), 810-8 PMID: 12959490
Sandman CA, Davis EP, Buss C, & Glynn LM (2011). Exposure to Prenatal Psychobiological Stress Exerts Programming Influences on the Mother and Her Fetus. Neuroendocrinology PMID: 21494029
Sandman CA, Davis EP, Buss C, & Glynn LM (2011). Prenatal programming of human neurological function. International journal of peptides, 2011 PMID: 21760821