What is the most irrefutable finding that you and your colleagues have made?

Dolores Malaspina, MD, MSPH, interviewed by Norman Sussman, MD
Primary Psychiatry. 2006;13(7):33-36


This interview took place on April 26, 2006, and was conducted by Norman Sussman, MD.






What is the most irrefutable finding that you and your colleagues have made?
The most irrefutable finding is our demonstration that a father’s age is a major risk factor for schizophrenia. We were the first group to show that schizophrenia is linearly related to paternal age and that the risk is tripled for the offspring of the oldest groups of fathers.7 This finding has been born out in every single cohort study that has looked at paternal age and the risk for schizophrenia. The only other finding that has been as consistently replicated in schizophrenia research is that there is an increased risk associated with a family history of schizophrenia. Since only 10% to 15% of schizophrenia cases have a family history, family history does not explain much of the population risk for schizophrenia. However, we think that approximately one third or one quarter of all schizophrenia cases may be attributable to paternal age. Paternal age is the major source of de novo genetic diseases in the human population, which was first described by Penrose8 in the 1950s. He hypothesized that this was due to copy errors that arose in the male germ line over the many cycles of sperm cell replications. These mutations accumulate as paternal age advances. After the Penrose report, medical researchers identified scores of sporadic diseases in the offspring of older fathers, suggesting that these could occur from gene mutations. Particular attention was paid to conditions in last-born children. In the 1960s, an excess of schizophrenia in last-born children was also reported. However, rather than entertaining the main medical hypothesis being explored at that time, the finding of more schizophrenia in later-born children nourished the idea that schizophrenia could be caused by an unavailable mother, soon to be called a schizophenigenic mother, rather than showing its genetic nature. This perception was a result of the unfortunate idea that psychiatric disorders did not have the same types of biologic underpinnings as other chronic diseases prevalent in the United States from the 1940s through the 1970s. Another rationale for those ideas, which I do not fault, was that if schizophrenia was caused by dysfunctional families, perhaps it could be cured with good treatment. Genetic conditions were seen as being too hopeless and off limits in the years following the Nazi genocide.