A conversation with Dolores Malaspina, M.D., about the generational impact of Holocaust trauma on schizophrenia risk

Jewish children born decades after World War II were found to have greater than double the risk of schizophrenia if their mothers had been older than five when living under Nazi rule, according to a study recently published in the American Journal of Psychiatry.

The study, ‘Schizophrenia in Offspring of Holocaust Survivors: Intergenerational Effects of Preconception Parental Trauma Within the Jerusalem Perinatal Study’ was led in part by Dolores Malaspina, M.D., a pharmacological sciences professor at the Icahn School of Medicine at Mount Sinai.

Malaspina and her colleagues used data from the Jerusalem Perinatal Study and linked them to Israel’s National Psychiatric Registry, which covered 40 years combined.

Malaspina recently sat down with Managed Healthcare Executive to discuss the full study findings and to explain the complexity of intergenerational trauma.

This interview has been edited for length and clarity.

MHE: Can you give an overview of ‘Schizophrenia in Offspring of Holocaust Survivors: Intergenerational Effects of Preconception Parental Trauma Within the Jerusalem Perinatal Study’?

Malaspina: This paper follows earlier work we did that showed fathers' age is a main cause of schizophrenia risk.

Many people have looked at early life course trauma, which makes us ask, ‘What about intergenerational trauma? Could that have an effect?’

Very few studies looking at trauma have such clear and consistent trauma exposure. We studied children who were growing up during Nazi occupation and during the Holocaust, and after the war, they immigrated to Israel. We had 18,000 such fathers and about 15,000 such mothers who came with that exposure.

People tend to think, ‘Schizophrenia is all genetic.’ Well, that idea is what drove the Holocaust, when the Nazis killed almost all people with psychiatric illness.

MHE: What did this study show about schizophrenia risk in the children of survivors?

Malaspina: Our analysis showed that if your schizophrenia or psychiatric illness was attributable to the Holocaust, your children without any trauma were manyfold more likely to have schizophrenia, showing that it’s the evolved circuitry that changes our body and gets transmitted without genes to the next generation, as if evolution were trying to prepare the next generation for what it experienced.

MHE: Were you surprised by the study's findings?

Malaspina: I wouldn't say I was surprised. There was evidence from some animal models that these effects could be lasting, but there was also evidence showing that fathers who had food unavailability had smaller children. So, there was evidence hinting at that kind of effect.

This was really the best demonstration where we had the same exposure. We had the same way of linking to the psychiatric case registry. Other studies have looked to see if the children and grandchildren have some changes in certain molecules that turn genes on or off. That's what we mean by "epigenetic."

MHE: Why was the age of five the baseline for this study?

Malaspina: We examined several ages, and we had the effect overall. But then, when we categorized the ages, we found there really wasn't an effect before age five. I think that has to do with how, if the parents are around, they buffer the trauma as long as they can. But then you can't do that after school age begins and children start maturing, so that lets us know it's not just a prenatal stress effect or nutrition effect. That there really was that age of cognitive awareness when the risk effect began.

MHE: What differences did you observe between maternal and paternal trauma transmission?

Malaspina: I don't think we had a sufficient number of fathers because I do believe it's paternally transmitted as well. But we were very, very careful in this study. We didn't simply find the association. We ruled out everything possible: father's education, his social status, and the same for moms, so we really were taking account of many, many variables, and that weakened the effect in fathers. But it didn't weaken the effect in mothers, and we also have a birth cohort, meaning that for all the people in our study, their moms were followed before pregnancy. So, we know a great deal about the pregnancy itself, and that's very important because pregnancy stress can cause schizophrenia, which we showed in our earlier study, but here the effect of the Holocaust on those women did not get taken away by controlling for other factors.

MHE: Is this increased risk of schizophrenia tied more to biology or environment?

Malaspina: That dichotomy has been discussed for a very long time: nature vs. nurture, but what we know now is that environmental signals in all vertebrates get turned into genetic changes, so genes are turned on or off. You can imagine there are different switches that can control gene expression. What we're more and more sure of is that those exposures are increasing inflammation. Now, there was a time in the ancient evolution of vertebrates when the most common causes of mortality were infections, and our hardware is still more pro-inflammatory when exposed to something. Whether it's childhood trauma or food intolerance, we become more inflammatory. I think the exposure gets turned into a biological signal.

MHE: What is one takeaway you’d like readers to have from this study?

Malaspina: Just because something's running in a family doesn't mean it's due necessarily to their genetics. People who are exposed to trauma really need support, and I think the resolution of traumatic responses is something you need to do for your survival. But it’s also something you do for your family and your species.

We have more and more trauma worldwide, and I think we need to be aware of the intergenerational lasting effects that that trauma has — not just on those who are fighting at the present, but into the future. We need to take that very seriously.