Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia

Mortensen, Preben Bo; Pedersen, Carsten Bøcker; Westergaard, Tine; Wohlfahrt, Jan; Ewald, Henrik; Mors, Ole; Andersen, Per Kragh; Melbye, Mads

doi:10.1056/nejm199902253400803

Cited by 722 publications

(527 citation statements)

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“…Maternal immune activation is considered to be an etiological factor in schizophrenia based on epidemiological studies of influenza infection in mothers of schizophrenia patients, and an increased incidence of schizophrenia among winter births [125][126][127] . This has been modelled in rodents by infecting pregnant animals with viruses or by administration of the bacterial endotoxin lipopolysaccharide (LPS).…”

Section: Maternal Immune Activationmentioning

confidence: 99%

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Gottschalk

Sarnyai

Guest

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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Psychiatric symptoms are subjective by nature and tend to overlap between different disorders. The modelling of a neuropsychiatric disorder therefore faces challenges because of missing knowledge of the fundamental pathophysiology and a lack of accurate diagnostics. Animal models are used to test hypotheses of aetiology and to represent the human condition as close as possible to increase our understanding of the disease and to evaluate new targets for drug discovery. In this review, genetic and neurodevelopmental animal models of schizophrenia are discussed with respect to behavioural and neurophysiological findings and their association with the clinical condition. Only specific animal models of schizophrenia may ultimately lead to novel diagnostic approaches and drug discovery. We argue that molecular biomarkers are important to improve animal to human translation since behavioural readouts lack the necessary specificity and reliability to assess human psychiatric symptoms.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50 Keywords: Translational research, neuropsychiatry, genetic, neurodevelopment, animal model, schizophrenia. ResumoSintomas psiquiátricos são subjetivos por natureza e tendem a se sobrepor entre diferentes desordens. Sendo assim, a criação de modelos de uma desordem neuropsiquiátrica encontra desafios pela falta de conhecimento dos fundamentos da fisiopatologia e diagnósticos precisos. Modelos animais são usados para testar hipóteses de etiologia e para representar a condição humana tão próximo quanto possível para aumentar nosso entendimento da doença e avaliar novos alvos para a descoberta de drogas. Nesta revisão, modelos animais genéticos e de neurodesenvolvimento de esquizofrenia são discutidos com respeito a achados comportamentais e neurofisiológicos e sua associação com a condição clínica. Somente modelos animais específicos de esquizofrenia podem, em último caso, levar a novas abordagens diagnósticas e descoberta de drogas. Argumentamos que biomarcadores moleculares são importantes para aumentar a tradução de animais a humanos, já que faltam a especificidade e a fidelidade necessárias às leituras comportamentais para avaliar sintomas psiquiátricos humanos.Gottschalk MG, et al. / Rev Psiq Clín. 2013;40(1):41-50

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Section: Maternal Immune Activationmentioning

confidence: 99%

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Gottschalk

Sarnyai

Guest

et al. 2012

Arch. Clin. Psychiatry (São Paulo)

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“…There is substantial evidence associating winter birth with increased risk of non-deficit or type I schizophrenia, which makes up around 85% of cases (Boyd et al, 1986;Gallagher et al, 1999;McGrath and Welham, 1999;Mortenson et al, 1999;Messias et al, 2004). There is some evidence that those born autumn have the lowest risk of developing multiple sclerosis, whereas those born in spring have an increased risk (James, 1995;Willer et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Seasonal variation of nutrient intake in pregnancy: effects on infant measures and possible influence on diseases related to season of birth

Watson

McDonald

2007

Eur J Clin Nutr

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Objectives: To determine, firstly, if there was any seasonal effect on nutrient intake during pregnancy and birth measures, secondly, if there was any relationship between maternal nutrient intake and infant birth measures according to season and thirdly, to consider the hypothesis that seasonal change in nutrient intake during pregnancy might affect health in later life of some women's offspring. Design: Pilot study to determine number of days required to characterize group intake followed by a prospective cohort study. Setting: Patients attending a city ante-natal clinic in the lower North Island, New Zealand. Subjects: A total of 214 healthy mostly European pregnant women volunteers, entering the second trimester of pregnancy, of whom 10 miscarried and seven withdrew. Methods: Subjects were visited in months 4 and 7 of pregnancy, and months 2, 6 and 12 after birth. Height, weight and skinfolds were measured and questionnaires to determine personal details administered at these times. Subjects recorded 8 days of weighed diets in both the fourth and seventh month. Health records were used to supply infant measures. Results: Significant (Pp0.05) seasonal variations in fat, carbohydrate, vitamin C and D, B vitamins, b-carotene, sodium, potassium, calcium, phosphorous, sulfur, sodium, chloride, zinc and selenium intakes were found. No significant 'main effect' difference in gestational age, infant birthweight, and head circumference was found with season. However, there were significant interactions (Pp0.05) for each birth season between birth measures and specific maternal nutrients at months 4 and 7 of pregnancy. Conclusion: The significant seasonal variations in nutrient intake in pregnant women, and significant influence of nutrient intake on birth measures in different seasons, suggests seasonal nutrient variation may also affect fetal development at a cellular level. This supports our hypothesis that the development of conditions related to season of birth, including schizophrenia, multiple sclerosis, type I diabetes and longevity, may be influenced by seasonal variation in nutrient intake during pregnancy.

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“…Maternal infection with influenza virus in the second trimester of pregnancy causes a major disorder incidence (Mednick et al 1988;O'Callaghan et al 1991;Adams et al 1993). In addition, a seasonal effect has been also documented, with more persons born in the late winter and early spring months developing schizophrenia (Torrey et al 1977;Mortensen et al 1999).Release of cytokines by cells from the immune system is a hallmark in the response to infection. Accumulating experimental and clinical evidence suggest the involvement of cytokines in CNS development and function as well as in many pathological conditions (Plata-Salamán 1991;Otero and Merrill 1994;Rothwell and Hopkins 1995;Raber et al 1998;Zao and Schwartz 1998).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

Borrell

Vela²,

Arévalo-Martı́n³

et al. 2002

Neuropsychopharmacology

280

191

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Increasing evidence associates schizophrenia with prenatal exposure to infection. Impaired ability to "gate out" sensory and cognitive information is considered to be a central feature of schizophrenia and is manifested, among others, in disrupted prepulse inhibition (PPI) of the acoustic startle reflex. We analyzed the effect of a prenatal immune challenge-peripheral administration of bacterial endotoxin lipopolysaccharide (LPS) to pregnant female rats-upon PPI and immune function in adult offspring. Prenatal LPS treatment disrupted PPI which was reversed by antipsychotics. Serum levels of interleukin-2 and interleukin-6 were increased. In addition, histopathological features in brain areas related with PPI circuitry were observed. These results illustrate the critical influence of prenatal immune events upon adult CNS functioning in association with the putative role of the immune system in (Braff et al. 1978;Kumari et al. 1999). A well-established sensorimotor gating paradigm is the prepulse inhibition (PPI) of the startle response. PPI refers to the reduction in startle reactivity toward an intense pulse stimulus when it is shortly preceded by a weak prepulse stimulus (Hoffman and Ison 1980). It is thought that the prepulse response activates an inhibitory process that attenuates or "gates" the startle response. Because identical stimulus parameters can be used for animal and human studies, it is considered that animal models of PPI disruption represent a promising way to study the neural mechanisms underlying sensorimotor gating dysfunction (Swerdlow et al. 1994(Swerdlow et al. , 1999Swerdlow and Geyer 1998) and as a screening test for potential antipsychotics (Swerdlow et al. 1994;Depoortere et al. 1997). In fact, antipsychotics remove PPI deficits in schizophrenic patients (Kumari et al. 1999;Weike et al. 2000). Nevertheless, it must be taken into consideration that deficiency of PPI has been reported in other selected neuropsychiatric disorders where inability to inhibit movements is involved (Huntington's disease (Swerdlow et al. 1995 Tourette's syndrome (Castellanos et al. 1996)), where inability to control attentional and cognitive processes is involved (obsessive-compulsive disorder (Swerdlow et al. 1993)), or where anxiety and exaggerated startle occur (posttraumatic stress disorder (Grillon et al. 1996)). The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. Neurodevelopmental theories of schizophrenia postulate that the psychopathology of schizophrenia may derive from alterations of brain organization secondary to defective ontogenesis (Weinberger 1996;Raedler et al. 1998). A causal relationship pertaining to disturbed brain ontogenesis and schizophrenia comes from epidemiological studies that have identified several risk factors that, acting during pregnancy, increase the incidence of the disease in offspring. Maternal infection with influenza virus in the second trimester of preg...

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Effects of Family History and Place and Season of Birth on the Risk of Schizophrenia

Abstract: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis.

Cited by 722 publications

References 19 publications

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

Seasonal variation of nutrient intake in pregnancy: effects on infant measures and possible influence on diseases related to season of birth

Prenatal Immune Challenge Disrupts Sensorimotor Gating in Adult Rats Implications for the Etiopathogenesis of Schizophrenia

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