DOLORES MALASPINA INVESTIGATES CAN DE NOVO MUTATIONS CAUSE SCHIZOPHRENIA

Dolores Malaspina, M.D., M.S.P.H. (Independent Investigator 2001) of New York State Psychiatric Institute, will examine the novel hypothesis that new genetic mutations can cause schizophrenia, and will attempt to define the clinical profile (phenotype) of this type of schizophrenia, known as sporadic schizophrenia (the birth of an affected individual into an unaffected family). This type of schizophrenia has previously been thought to originate from environmental factors that either act independently or interact with latent genes. Dr. Malaspina has conducted two preliminary studies which support the new mutations hypothesis. As a major influence on new mutations in the human gene pool is related to the advancing age of fathers, Dr. Malaspina first examined the relationship of schizophrenia and paternal age. Data showed a strong escalation in schizophrenia risk as the age of the father increased, accounting for over a quarter of the schizophrenia cases. Another of her studies found that fathers of sporadic schizophrenia cases were 5 years older than familial case fathers. If sporadic schizophrenia can originate from new mutations, then neurodevelopmental genes are reasonable candidates. Her study will examine if patients with sporadic schizophrenia, particularly those with fathers older than 35 at birth, show features found in other neurodevelopmental diseases that correlate with paternal age, such as craniofacial abnormalities, nonspecific cognitive deficits and delayed developmental milestones. However, if genes that arise from mutations are inherited by later generations, then some familial cases with a similar illness would not have a paternal age effect. Dr. Malaspina plans to define the clinical profile in sporadic patients associated with paternal age through group comparisons and cluster analysis. If the study is successful, this illness pattern may be useful in gene identification for schizophrenia.