Higher Risk of Offspring Schizophrenia Following Antenatal Maternal Exposure to Severe Adverse Life Events

Khashan, Ali S.; Abel, Kathryn M.; McNamee, Roseanne; Pedersen, Marianne Giørtz; Webb, Roger T.; Baker, Philip N.; Kenny, Louise C.; Mortensen, Preben Bo

doi:10.1001/archgenpsychiatry.2007.20

Cited by 501 publications

(369 citation statements)

References 36 publications

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“…A male, but not female, fetus exposed during the second trimester of gestation to the stress of the 1940 invasion of The Netherlands had increased risk of schizophrenia later in life (van Os and Selten, 1998). This relationship between prenatal exposure to maternal psychosocial stress and risk for schizophrenia in male, but not female, offspring has been replicated in another study, but with first trimester exposure (Khashan et al, 2008). Although there are likely multiple factors contributing to sex differences in disease, sex-specific responses to fetal antecedents occurring during gestational sensitive windows may promote differences in programming trajectories that underlie such disease biases.…”

Section: Knowledge Gained By Including Sabv In Studies Of Neurodevelomentioning

confidence: 73%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

124

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The inclusion of sex as a biological variable in research is absolutely essential for improving our understanding of disease mechanisms contributing to risk and resilience. Studies focusing on examining sex differences have demonstrated across many levels of analyses and stages of brain development and maturation that males and females can differ significantly. This review will discuss examples of animal models and clinical studies to provide guidance and reference for the inclusion of sex as an important biological variable relevant to a Neuropsychopharmacology audience.

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Section: Knowledge Gained By Including Sabv In Studies Of Neurodevelomentioning

confidence: 73%

Sex as a Biological Variable: Who, What, When, Why, and How

Bale

Epperson

2016

Neuropsychopharmacol

124

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“…Studies on schizophrenia (13) indicated that the first trimester was the most vulnerable period, but studies on other endpoints suggested that the time window of susceptibility was in late pregnancy (12;35). Our findings suggest that exposure to severe stress during late pregnancy may have a greater influence on fetal brain development.…”

Section: Discussionmentioning

confidence: 99%

Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark

Olsen

Vestergaard

et al. 2010

Eur Child Adolesc Psychiatry

172

131

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Severe prenatal stress exposure has been found to increase the risk of neuropsychiatric conditions like schizophrenia. We examined the risk of Attention-deficit/hyperactivity disorder (ADHD) in the offspring following prenatal maternal bereavement, as a potential source of stress exposure. We conducted a nationwide population-based cohort study including all 1 015 912 singletons born in Denmark from 1987 to 2001. A total of 29 094 children were born to women who lost a close relative during pregnancy or up to one year before pregnancy. These children were included in the exposed cohort and other children were in the unexposed cohort. We used Cox regression to estimate hazard ratios for ADHD, defined as the first-time ADHD hospitalization or first-time ADHD medication after 3 years of age. Boys born to mothers who were bereaved by unexpected death of a child or a spouse, had a 72% increased risk of ADHD (Hazard ratio [HR]=1.72, 95% confidence interval [CI]=1.09-2.73). Boys born to mothers who lost a child or a spouse during 0-6 months before pregnancy and during pregnancy had a HR of 1.47 (95%CI=1.00-2.16) and 2.10 (95% CI =1.16-3.80), respectively. Our findings suggest that prenatal maternal exposure to severe stress may increase the risk of ADHD in the offspring.Key words Attention-deficit/hyperactivity Disorder (ADHD); stress; bereavement; fetal programming; child psychiatry.Ms No. ECAP-D-09-00192R2, Prenatal stress and ADHD, 04042010 3, LiAttention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorders (1;2). This disease causes a number of adverse academic and vocational conditions in children, and exerts stress to the affected families and economic burden on society (3). The disorder has a substantial genetic component but epidemiological studies suggest that environmental factors operating in early life most likely contribute to the disease risk (3-5). Evidence from animal studies suggests that maternal stress during pregnancy may affect fetal neurodevelopment (6;7). One of the underlying mechanisms is termed as 'fetal programming', which occurs when the normal pattern of fetal development is disrupted by an abnormal stimulus or insult at critical time points (6;8). Excessive glucocorticoids following stress in pregnant mothers may have such a programming effect on brain development (6-9). In epidemiological studies, prenatal stress has been linked to congenital malformations (10), cerebral palsy (11), and psychiatric disorders including schizophrenia(12;13). Anxiety during pregnancy has been associated with ADHD phenotypical behavior in the offspring (14;15) but no published studies have evaluated the association between prenatal stress and the risk of ADHD.We hypothesized that prenatal stress had a programming effect on brain development (16-18) and could increase the risk of ADHD in childhood. We examined this hypothesis in a cohort study based on data from several nationwide registers in Denmark.Bereavement is a severe life event known to induce stress (...

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“…The prenatal stress/schizophrenia association has been examined in several different ways. Death of spouse 31,32 and experience of catastrophic events, such as war 33 and nuclear explosion, 34 have been found to increase the risk of schizophrenia among those exposed. van Os and Selten 33 found an increased relative risk (RR) of schizophrenia (RR 1.28) among those in the Netherlands who were in their first or second trimester during the Nazi invasion in May 1940, and Malaspina and colleagues 35 found that those in their second month of gestation during the 1967 Arab-Israel War (Six-Day War) also had an increased risk of schizophrenia.…”

Section: Prenatal Stressmentioning

confidence: 99%

“…The association was present after accounting for both maternal depression and measures of fetal well-being at the time of the birth. Khashan and colleagues 32 found that death or serious illness of a relative during the first trimester was associated with an increased risk of developing schizophrenia, even when several potential confounders were controlled for. This partially replicates the classic finding of Huttunen and Niskanen.…”

Section: Prenatal Stressmentioning

confidence: 99%