On April 23, Dolores Malaspina, MD, MS, MSPH, published results of a study on marriage duration and how it affects schizophrenia risk in offspring. She found that if a specific man and a woman had a shorter duration of sexual contact before conception, their child would be at a higher risk of developing schizophrenia. The authors write that “offspring born to parents married fewer than two years, equivalent to about one year of pre-pregnancy sexual contact, had a 50 percent increase in risk for schizophrenia.” Children from marriages of 2-4 years had a 30 percent increase in risk.
Marriage duration is not typically indicative of duration of sexual contact; however, this analysis was performed on the children of the 1964-1976 Jerusalem Perinatal Cohort Schizophrenia Study, and the records show that 97 percent of them were born to married couples. At that time, Israel had one of the lowest worldwide rates of out-of-wedlock births, so marriage duration in this population is a reasonable proxy for sexual contact.
Dr. Malaspina has been a psychiatrist for 30 years, and has 300 publications under her belt.
This marriage duration risk factor is independent of established risk factors such as family history of psychiatric disorders and the father’s age at the time of conception. Accounting for the duration of the couple’s sexual contact magnifies the effect of paternal age on offspring risk for schizophrenia, and both factors together explain any effect of later paternal age at marriage. “When older men get married, they are more likely to have babies right away. This could mean that the father’s age at marriage is not a causal factor,” said Dr. Malaspina.
The shorter periods of sexual contact before conception also increase the risk for preeclampsia, a complication during pregnancy that includes high blood pressure, swelling, and high urine protein levels. Dr. Malaspina theorizes that the risk pathway for preeclampsia, which includes prenatal immune activation, could increase the risk for inflammatory conditions such as schizophrenia in offspring. She is working on replicating these findings in other cohorts, and anticipates being able to test if the pathways to schizophrenia include prenatal immune activation.
This is just the latest finding in Dr. Malaspina’s expansive career, which has spanned genetics, zoology, epidemiology, and more. Rather than looking at just symptoms and behavior, her research involves examining the larger picture of the disease, including associated metabolic diseases, physical biomarkers, and gene mutations. She has a track record of thinking outside the box and fostering interdisciplinary collaboration to find pathways to severe mental illnesses, especially schizophrenia. “It’s working across boundaries that really invigorates progress,” she says.
Dr. Malaspina’s particular interest in schizophrenia has to do with the fact that the illness “fundamentally impairs the ability to function—it interferes with social signaling and group selection.” It also comes from her personal experience. She has been on a lifelong quest to understand the underlying factors of schizophrenia ever since her sister, Eileen, was diagnosed in 1971.
The beginning
Her sister’s grades started to slip in her senior year of high school, and she became increasingly paranoid that the neighbors were talking about her and that helicopters were monitoring her activities. She was unable to eat or sleep, and in a constant state of terror. Her family took her to the hospital, where she was diagnosed with schizophrenia. At that time, psychiatrists often blamed the “schizophrenogenic mother” for the disease, meaning that a mother’s cold, domineering, and manipulative personality triggered distrust, resentfulness, and psychosis in her child. This blame on Dr. Malaspina’s mother heaped immense guilt onto her already grieving and distressed family. Deeply affected by this experience, Dr. Malaspina decided to become a scientist and psychiatrist and to devote her career to getting to the bottom of the true causes of this disease.
Career trajectory
She wasted no time. Dr. Malaspina got her MS in zoology and then her MD at Rutgers University. She completed a residency in psychiatry and a clinical research fellowship at Columbia University Medical Center, and at the end of her residency transitioned to independent investigator. Two years later, she was named founding chief of the Schizophrenia Research Unit at the New York State Psychiatric Institute. She stayed at Columbia for 22 years, covering all academic levels: chief resident, research fellow, assistant professor, associate professor, and full professor. In 1998, she received her MS in public health of epidemiology at Columbia. In 2006, she moved to NYU to become the Chair of the Department of Psychiatry, where she founded and directed the Institute of Social and Psychiatric Initiatives (InSPIRES), a multidisciplinary research program.
Breakthroughs
Dr. Malaspina has received nearly continuous NIMH funding throughout her career, and has a collection of scientific discoveries under her belt. She was the first to demonstrate that paternal aging is a predictor of schizophrenia, which has been replicated worldwide. “Some people said it’s just that older men are carrying more genetic risk for schizophrenia, which delayed their childbearing and explains the increased risk of the disease for their offspring,” she said. Her pioneering work on higher paternal age and its correlation with schizophrenia risk stimulated hundreds of follow-up studies confirming the findings, and her new study confirms that older paternal age at marriage is not a risk factor.
Dr. Malaspina also showed hippocampal inflammation in those with schizophrenia, and that olfaction, or the sense of smell, is related to social function. She defined four versions of schizophrenia via gene analysis, showing each subtype had a discrete presentation. She also looked at the effects of the Six Day War of 1967 on pregnancies, and discovered that early pregnancy trauma was a risk factor for schizophrenia in females.
Moving to Mount Sinai
In 2017, Dr. Malaspina moved to Mount Sinai and is now director of the psychosis program Critical Connections. Why Mount Sinai? “The leadership in other institutions is not as aware of the amazing impact that psychiatric disorders have on society,” she said. “I love that Mount Sinai cuts across molecular science, epidemiology, clinical trials, outcomes, and research, and the sheer size and number of scientists working here makes it really special. Also, the new chair, René Kahn, MD, PhD, himself an impressive schizophrenia researcher, had recruited a group of accomplished schizophrenia experts, so it was a wonderful opportunity to work with them.” She adds that Mount Sinai has a fantastic burgeoning genetics department, which is a critical component of her own research. “I hope that we are close to defining specific different pathways to schizophrenia that can lead to precise treatments to prevent and cure the disease, rather than our current ‘one size fits all’ treatment approaches,” she said.
Dr. Malaspina is Professor of Psychiatry, Neuroscience, and Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai, where she is also the Director of the Critical Connections Psychosis Program in collaboration with the Nash Family Department of Neuroscience and the Division of Psychiatric Genomics. Her MS is in zoology, and her MSPH is in epidemiology.