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Toxoplasma gondii (T. gondii) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high T. gondii seroprevalence. In 306 OOA with a mean age of 46.1±16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both T. gondii IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n=280] and PHQ-2 [n=26]). Associations between T. gondii IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p=0.045) and current combined anhedonia and dysphoria/hopelessness (p=0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and T. gondii IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for T. gondii-positive individuals at high-risk for SSDV.

Abstract Background Because they are a closed founder population, the Old Order Amish (OOA) of Lancaster County have been the subject of many medical genetics studies. We constructed four versions of Anabaptist Genealogy Database (AGDB) using three sources of genealogies and multiple updates. In addition, we developed PedHunter, a suite of query software that can solve pedigree-related problems automatically and systematically. Methods We report on how we have used new features in PedHunter to quantify the number and expected genetic contribution of founders to the OOA. The queries and utility of PedHunter programs are illustrated by examples using AGDB in this paper. For example, we calculated the number of founders expected to be contributing genetic material to the present-day living OOA and estimated the mean relative founder representation for each founder. New features in PedHunter also include pedigree trimming and pedigree renumbering, which should prove useful for studying large pedigrees. Results With PedHunter version 2.0 querying AGDB version 4.0, we identified 34,160 presumed living OOA individuals and connected them into a 14-generation pedigree descending from 554 founders (332 females and 222 males) after trimming. From the analysis of cumulative mean relative founder representation, 128 founders (78 females and 50 males) accounted for over 95% of the mean relative founder contribution among living OOA descendants. Discussion/Conclusions The OOA are a closed founder population in which a modest number of founders account for the genetic variation present in the current OOA population. Improvements to the PedHunter software will be useful in future studies of both the OOA and other populations with large and computerized genealogies.