Division of Translational Epidemiology

The aim of the division is to translate human, clinical and epidemiologic observational findings into understanding of mechanisms using modern tools of imaging, genetics and animal models. Funds from the Sackler Serotonin Transporter Project were important in enhancing our collaborations with Drs. Gingrich, Brown, Bruder, Bansal, and Champagne.  The Sackler funds have supported the extension of studies to obtain increased and enriched samples, pilot projects for future development and post-doctoral fellows. These include a continuation of the longitudinal three-generation study of offspring at high and low-risk for major depression (MDD) which includes MRI, EEG, and DNA collection.  We are actively engaged in data collection of the 6th wave of the three generation study and over the last year we have made considerable progress. We have completed 246 structural and functional MRI scans, 101 DTI scans, 303 EEGs collected, 478 DNA samples, and have re-interviewed 407 subjects. The Sackler funds allowed us to collect DNA and clinical data on the full, rather than partial sample in a 30 year follow up. The DTI data previously was not funded in the NIMH grant and only 150 of the 403 interviews were funded by NIMH grant. We now have a far richer data set with this larger sample. We are waiting completion of full data collection and best estimates procedures before analysis of Wave 6. We expect this to be ready for full analysis in November 2015. We have continued to analyze Wave 5 data and have begun examining Wave 6 preliminarily. We are also piloting work on ethnic differences in epigenetics from a study of depressed mothers undergoing treatment and the effect of their remission on their children.

In the Conte Center grant Serotonergic Modulation Influence on Structure, Function, and Behavior, Brown, Sourander, Malm, and colleagues have analyzed the registry data on exposure to SSRIs during pregnancy in Finland and several neuropsychiatric outcomes.  SSRI use in pregnancy was associated with an increased risk of depressive and anxiety disorders in offspring, with a particularly strong effect among the offspring aged 12-14.   SSRI use in pregnancy was also related to certain prenatal outcomes.  No associations were found between SSRIs in pregnancy and autism or attention deficit hyperactivity disorder.  With the help of funding from the Sackler Center to provide partial salary support to Brown, he, with help from the Finnish colleagues, wrote the Project 1 renewal for this grant.  This funding will also be utilized to support other initiatives relevant to the Sackler mission in the Finnish and other birth cohorts.  The Sackler Center also awarded partial salary support to Keely Cheslack-Postava, an epidemiologist and new junior faculty member in Brown’s Unit in Birth Cohort Studies to support research on the Finnish birth cohort, including work in the Conte Center grant.  Dr. Cheslack-Postava will investigate relationships between maternal SSRI exposure, reproductive history, and perinatal events in relation to neuropsychiatric outcomes.  Gingrich, Talati, Brown and Weissman are also developing at collaboration with the Mayo Clinic registry to follow up the findings on the long term effects of in utero exposure to SSRIs.  The Mayo Clinic collaboration provides an opportunity to have more intensive clinical evaluations of offspring exposure to SSRIs.  Brown has also initiated a program of research on prenatal infection and schizophrenia with Sackler investigator Christoph Kellendonk, Sackler award recipient Sarah Canetta, and Ragy Girgis.  Kellendonk, Girgis, and Brown were recently awarded a pilot grant from the Irving Institute to study maternal immune activation and hippocampal function.