Faculty Bibliography

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

The placenta adapts to maternal environment and its alterations may have a lasting impact on child's temperament development. Prenatal stress has been linked to both a downregulation of monoamine oxidase A (MAOA) gene expression in the placenta and to difficult temperament. Capitalizing on an ongoing longitudinal study, we analysed data from 95 mother-child dyads to investigate whether MAOA mediates the association between prenatal stress and infant temperament. Prenatal stress was defined as exposure to Superstorm Sandy (Sandy) during pregnancy. Infant temperament was measured by Infant Behaviour Questionnaire-Revised. MAOA gene expression was quantified in placenta tissue. The Smiling and Laughter subscale score was independently associated with Sandy exposure and MAOA placental gene expression. Mediation analysis confirmed that MAOA expression partially mediated the relationship between Sandy and Smiling and Laughter subscale, suggesting that in utero exposure to Sandy could induce lower frequency of smiling and laughter via downregulation of placental MAOA gene expression. These effects could compromise optimal temperamental trajectory and contribute to risk for psychological problems. Placental epigenetic markers can contribute to a multidimensional model of early intervention for high-risk children.

More than one in every four women in the world experience sexual violence (SV) in their lifetime, most often as teenagers and young adults. These traumatic experiences leave memories in the brain, which are difficult if not impossible to forget. We asked whether women with SV history experience stronger memories of their most stressful life event than women without SV history and if so, whether strength relates to ruminative and trauma-related thoughts. Using the Autobiographical Memory Questionnaire (AMQ), women with SV history (n = 64) reported this memory as especially strong (p < 0.001), remembering more sensory and contextual details, compared to women without SV history (n = 119). They further considered the event a significant part of their personal life story. The strength of the memory was highly correlated with posttraumatic cognitions and ruminative thoughts, as well as symptoms of depression and anxiety (p's < 0.001, n = 183). A third (33%) of the women with SV history were diagnosed with posttraumatic stress disorder (PTSD), but PTSD alone did not account for the increase in memory strength (p's < 0.001). These data suggest that the experience of SV increases the strength of stressful autobiographical memories, which are then reexperienced in everyday life during posttraumatic and ruminative thoughts. We propose that the repeated rehearsal of vivid stressful life memories generates more trauma memories in the brain, making the experience of SV even more difficult to forget.

Background: Chronic illness in children has adverse effects on family members besides the patient and can impact the integrity and function of the family unit. Most previous studies have examined a single disease entity. However, there has been limited assessment comparing the effect of different illnesses on family function.
Method(s): Established patients treated in the pediatric ambulatory Nephrology or DM clinics were included in the study. Their parents were asked to complete the 2-page Pediatric Quality-of-Life Family Impact Module (PedsQL-FIM), version 2.0, a validated survey instrument. Clinical and laboratory data were retrieved from the electronic health record. Data were summarized as mean+/-SD. Disease group and child age were entered as predictors in linear regression analyses with FIM total and subscale scores as outcome variables. Comparisons between groups were assessed using paired t-tests.
Result(s): 96 patients (43 F: 53 M) were evaluated in the Nephrology Clinic and 55 (30 F: 25 M) in the DM Clinic. The mean age of the patients was 13.0+/-3.9 and 10.4+/- 6.3 yr, respectively. Within the KD sample, older age was significantly associated with lower scores on all FIM subscale scores. Gender was not a significant predicator for FIM scores in either disease group. Controlling for age, chronic illness group was a significant predictor of the FIM total and subscale scores. Parents of D patients endorsed significantly lower total FIM scores compared to the KD patients (D 58+/-16; KD 79+/-17 p <0.001) as well as on subscales of physical, emotional, social, and cognitive functioning, communication, worry, daily activities, family relationships, and reports of health-related quality of life (P<0.01).
Conclusion(s): Our findings confirm that chronic illness in childhood adversely affects a wide range of aspects of family function. The impact is greater in older children with KD and varies depending on the disease context. Families with children who have DM manifested greater disturbances than those with children who have isolated KD. Further study is warranted to assess the effects of the underlying renal disease and intensity of medical care and whether there are specific features can be used to identify vulnerable families

Neurotrophins play critical roles in the survival, maintenance and death of neurons. In particular, proneurotrophins have been shown to mediate cell death following brain injury induced by status epilepticus (SE) in rats. Previous studies have shown that pilocarpine-induced seizures lead to increased levels of proNGF, which binds to the p75NTR-sortilin receptor complex to elicit apoptosis. A screen to identify compounds that block proNGF binding and uptake into cells expressing p75 and sortilin identified lithium citrate as a potential inhibitor of proNGF and p75NTR-mediated cell death. In this study, we demonstrate that low, submicromolar doses of lithium citrate effectively inhibited proNGF-induced cell death in cultured neurons and protected hippocampal neurons following pilocarpine-induced SE in vivo. We analyzed specific mechanisms by which lithium citrate afforded neuroprotection and determined that lithium citrate prevented the association and internalization of the p75NTR-sortilin receptor complex. Our results demonstrate a novel mechanism by which low-dose treatments of lithium citrate are effective in attenuating p75NTR-mediated cell death in vitro and in vivo.