Neurological Correlates

(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.

Malaspina et al., point out,

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).