Early or Late Gestational Exposure to Maternal Immune Activation Alters Neurodevelopmental Trajectories in Mice: An Integrated Neuroimaging, Behavioral, and Transcriptional Study.

BACKGROUND: Exposure to maternal immune activation (MIA) in utero is a risk factor for neurodevelopmental disorders later in life. The impact of the gestational timing of MIA exposure on downstream development remains unclear. METHODS: We characterized neurodevelopmental trajectories of mice exposed to the viral mimetic poly I:C (polyinosinic:polycytidylic acid) either on gestational day 9 (early) or on day 17 (late) using longitudinal structural magnetic resonance imaging from weaning to adulthood. Using multivariate methods, we related neuroimaging and behavioral variables for the time of greatest alteration (adolescence/early adulthood) and identified regions for further investigation using RNA sequencing. RESULTS: Early MIA exposure was associated with accelerated brain volume increases in adolescence/early adulthood that normalized in later adulthood in the striatum, hippocampus, and cingulate cortex. Similarly, alterations in anxiety-like, stereotypic, and sensorimotor gating behaviors observed in adolescence normalized in adulthood. MIA exposure in late gestation had less impact on anatomical and behavioral profiles. Multivariate maps associated anxiety-like, social, and sensorimotor gating deficits with volume of the dorsal and ventral hippocampus and anterior cingulate cortex, among others. The most transcriptional changes were observed in the dorsal hippocampus, with genes enriched for fibroblast growth factor regulation, autistic behaviors, inflammatory pathways, and microRNA regulation. CONCLUSIONS: Leveraging an integrated hypothesis- and data-driven approach linking brain-behavior alterations to the transcriptome, we found that MIA timing differentially affects offspring development. Exposure in late gestation leads to subthreshold deficits, whereas exposure in early gestation perturbs brain development mechanisms implicated in neurodevelopmental disorders.

Mortality inequality in populations with equal life expectancy: Arriaga's decomposition method in SAS, Stata, and Excel.

PURPOSE: Life expectancy is used to measure population health, but large differences in mortality can be masked even when there is no life expectancy gap. We demonstrate how Arriaga's decomposition method can be used to assess inequality in mortality between populations with near equal life expectancy. METHODS: We calculated life expectancy at birth for Quebec and the rest of Canada from 2005 to 2009 using life tables and partitioned the gap between both populations into age and cause-specific components using Arriaga's method. RESULTS: The life expectancy gap between Quebec and Canada was negligible (<0.1 years). Decomposition of the gap showed that higher lung cancer mortality in Quebec was offset by cardiovascular mortality in the rest of Canada, resulting in identical life expectancy in both groups. Lung cancer in Quebec had a greater impact at early ages, whereas cardiovascular mortality in Canada had a greater impact at older ages. CONCLUSIONS: Despite the absence of a gap, we demonstrate using decomposition analyses how lung cancer at early ages lowered life expectancy in Quebec, whereas cardiovascular causes at older ages lowered life expectancy in Canada. We provide SAS/Stata code and an Excel spreadsheeet to facilitate application of Arriaga's method to other settings.

Suicide mortality gap between Francophones and Anglophones of Quebec, Canada.

PURPOSE: Few studies evaluate language-group differences in suicide mortality. This study assessed the suicide mortality gap between Francophones and Anglophones of Quebec, Canada according to age, sex, method, region and socioeconomic deprivation. METHODS: Suicide decedents were extracted from the Quebec death file for 1989-2007 (N = 24,465). Age- and sex-specific suicide mortality rates were calculated for four periods (1989-1993, 1994-1998, 1999-2003, 2004-2007) for Francophones and Anglophones aged ≥10 years. Age-standardized rates of suicide by method, region, and level of social and material deprivation were calculated for each sex. Rate ratios and rate differences were estimated. RESULTS: Suicide rates for Francophones were two to three times higher than rates for Anglophones, and differences were greatest for adults aged 25-64 years. Francophone males had more than two times the rate of suicide by hanging or firearms than Anglophone males. Francophone females had twice the rate of hanging, poisoning or firearm suicide as Anglophone females, although precision was low. Francophone-Anglophone suicide mortality gaps were higher in urban areas despite lower suicide rates, and varied little across levels of social and material deprivation. CONCLUSIONS: There was a large suicide mortality gap between Francophones and Anglophones of Quebec; especially, among adults aged 25-64 years.

Life expectancy gap between the Francophone majority and Anglophone minority of a Canadian population.

Language is an important determinant of health, but analyses of linguistic inequalities in mortality are scant, especially for Canadian linguistic groups with European roots. We evaluated the life expectancy gap between the Francophone majority and Anglophone minority of Québec, Canada, both over time and across major provincial areas. Arriaga's method was used to estimate the age and cause of death groups contributing to changes in the life expectancy gap at birth between 1989-1993 and 2002-2006, and to evaluate patterns across major provincial areas (metropolitan Montréal, other metropolitan centres, and small cities/rural areas). Life expectancy at birth was greater for Anglophones, but the gap decreased over time by 1.3 years (52% decline) in men and 0.9 years (47% decline) in women, due to relatively sharper reductions in Francophone mortality from several causes, except lung cancer which countered reductions in women. The life expectancy gap in 2002-2006 was widest in other metropolitan centres (men 5.1 years, women 3.2 years), narrowest in small cities/rural areas (men 0.8 years, women 0.7 years), and tobacco-related causes were the main contributors. Only young Anglophones <40 years in small cities/rural areas had mortality higher than Francophones, resulting in a narrower gap in these areas. Differentials in life expectancy favouring Anglophones decreased over time, but varied across areas of Québec. Tobacco-related causes accounted for the majority of the current life expectancy gap.