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      Severe bereavement stress during the prenatal and childhood periods and risk of psychosis in later life: population based cohort study

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          Abstract

          Objective To examine the risk of psychosis associated with severe bereavement stress during the antenatal and postnatal period, between conception to adolescence, and with different causes of death.

          Design Population based cohort study.

          Setting Swedish national registers including births between 1973 and 1985 and followed-up to 2006.

          Participants In a cohort of 1 045 336 Swedish births (1973-85), offspring born to mothers exposed to severe maternal bereavement stress six months before conception or during pregnancy, or exposed to loss of a close family member subsequently from birth to 13 years of age were followed until 2006. Admissions were identified by linkage to national patient registers.

          Main outcome measures Crude and adjusted odds ratios for all psychosis, non-affective psychosis, and affective psychosis.

          Results Maternal bereavement stress occurring preconception or during the prenatal period was not associated with a significant excess risk of psychosis in offspring (adjusted odds ratio, preconception 1.24, 95% confidence interval 0.96 to 1.62; first trimester 0.95, 0.58 to1.56; second trimester 0.79, 0.46 to 1.33; third trimester 1.14, 0.78 to 1.66). Risks increased modestly after exposure to the loss of a close family member from birth to adolescence for all psychoses (adjusted odds ratio 1.17, 1.04 to 1.32). The pattern of risk was generally similar for non-affective and affective psychosis. Thus estimates were higher after death in the nuclear compared with extended family but remained non-significant for prenatal exposure; the earlier the exposure to death in the nuclear family occurred in childhood (all psychoses: adjusted odds ratio, birth to 2.9 years 1.84, 1.41 to 2.41; 3-6.9 years 1.47, 1.16 to 1.85; 7-12.9 years 1.32, 1.10 to 1.58) and after suicide. Following suicide, risks were especially higher for affective psychosis (birth to 2.9 years 3.33, 2.00 to 5.56; 6.9 years 1.84, 1.04 to 3.25; 7-12.9 years 2.68, 1.84 to 3.92). Adjustment for key confounders attenuated but did not explain associations with risk.

          Conclusions Postnatal but not prenatal bereavement stress in mothers is associated with an increased risk of psychosis in offspring. Risks are especially high for affective psychosis after suicide in the nuclear family, an effect that is not explained by family psychiatric history. Future studies are needed to understand possible sources of risk and resilience so that structures can be put in place to support vulnerable children and their families.

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          Most cited references36

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          The adaptive significance of maternal effects

          T Mousseau (1998)
          Recently, the adaptive significance of maternal effects has been increasingly recognized. No longer are maternal effects relegated as simple `troublesome sources of environmental resemblance' that confound our ability to estimate accurately the genetic basis of traits of interest. Rather, it has become evident that many maternal effects have been shaped by the action of natural selection to act as a mechanism for adaptive phenotypic response to environmental heterogeneity. Consequently, maternal experience is translated into variation in offspring fitness.
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            Adult health outcomes of childhood bullying victimization: evidence from a five-decade longitudinal British birth cohort.

            The authors examined midlife outcomes of childhood bullying victimization.
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              Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems.

              Stress-related variation in the intrauterine milieu may impact brain development and emergent function, with long-term implications in terms of susceptibility for affective disorders. Studies in animals suggest limbic regions in the developing brain are particularly sensitive to exposure to the stress hormone cortisol. However, the nature, magnitude, and time course of these effects have not yet been adequately characterized in humans. A prospective, longitudinal study was conducted in 65 normal, healthy mother-child dyads to examine the association of maternal cortisol in early, mid-, and late gestation with subsequent measures at approximately 7 y age of child amygdala and hippocampus volume and affective problems. After accounting for the effects of potential confounding pre- and postnatal factors, higher maternal cortisol levels in earlier but not later gestation was associated with a larger right amygdala volume in girls (a 1 SD increase in cortisol was associated with a 6.4% increase in right amygdala volume), but not in boys. Moreover, higher maternal cortisol levels in early gestation was associated with more affective problems in girls, and this association was mediated, in part, by amygdala volume. No association between maternal cortisol in pregnancy and child hippocampus volume was observed in either sex. The current findings represent, to the best of our knowledge, the first report linking maternal stress hormone levels in human pregnancy with subsequent child amygdala volume and affect. The results underscore the importance of the intrauterine environment and suggest the origins of neuropsychiatric disorders may have their foundations early in life.
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                Author and article information

                Contributors
                Role: professor
                Role: doctoral student
                Role: research associate
                Role: professor
                Role: postdoctoral research associate
                Role: professor
                Role: postdoctoral research assistant
                Role: associate professor
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2014
                2014
                21 January 2014
                : 348
                : f7679
                Affiliations
                [1 ]Centre for Women’s Mental Health, Manchester Academic Health Sciences Centre, Institute of Brain Behaviour and Mental Health, University of Manchester, Manchester, UK
                [2 ]The Cathie Marsh Centre for Census and Survey Research, University of Manchester, Manchester, UK
                [3 ]Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
                [4 ]Imprints Center for Genetic and Environmental Life Course Studies, Mailman School of Public Health and New York State Psychiatric Institute, Columbia University, NY City, NY, USA
                [5 ]Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
                Author notes
                Correspondence to: K M Abel kathryn.abel@ 123456manchester.ac.uk
                Article
                abek015022
                10.1136/bmj.f7679
                3898661
                24449616
                7ea98e96-ce00-4bc2-9d98-8d3b577ce7ef
                © Abel et al 2014

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/.

                History
                : 16 December 2013
                Categories
                Research

                Medicine
                Medicine

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