RESUMO
OBJECTIVES: Pregnant women exposed to an acute traumatic event are thought to produce offspring with an increased incidence of affective disorders. It is not known whether there are specific times in pregnancy which confer increased vulnerability, or if psychosocial stress alone can increase the incidence of affective disorders in offspring. We examined the relationship of the timing of an acute psychosocial threat during pregnancy to the incidence of affective disorders in offspring using data from a large birth cohort. METHODS: Using data on 90079 offspring born in Jerusalem in 1964-1976 and linked to Israel's psychiatric registry, we constructed proportional hazards models to evaluate the link between gestational age during the Arab-Israeli war of June 1967 and incidence of mood disorders. RESULTS: Those in their first trimester of fetal development during the war were more likely to be admitted to hospitals for any mood disorders [relative risk (RR) = 3.01, 95% confidence interval (CI): 1.68-5.39, p = 0.0002]; for bipolar disorder the risk was doubled (RR = 2.44, 95% CI: 0.996-5.99, p = 0.054) and for all 'other' mood disorders the risk was tripled (RR = 3.61, 95% CI: 1.68-7.80, p = 0.001). Mood disorders were also increased in offspring whose mothers had been in the third month of pregnancy in June of 1967 (RR = 5.54, 95% CI: 2.73-11.24, p < 0.0001). CONCLUSIONS: A time-limited exposure to a severe threat during early gestation may be associated with an increased incidence of affective disorders in offspring. The third month of fetal development was a moment of special vulnerability.
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Transtornos do Humor/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adulto , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Israel/epidemiologia , Masculino , Transtornos Mentais/epidemiologia , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Gravidez , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Sistema de Registros , Fatores de RiscoRESUMO
Global decreases in DNA methylation, particularly in repetitive elements, have been associated with genomic instability and human cancer. Emerging, though limited, data suggest that in white blood cell (WBC) DNA levels of methylation, overall or in repetitive elements, may be associated with cancer risk. We measured methylation levels of three repetitive elements [Satellite 2 (Sat2)], long interspersed nuclear element-1 (LINE-1) and Alu) by MethyLight, and LINE-1 by pyrosequencing in a total of 282 breast cancer cases and 347 unaffected sisters from the New York site of the Breast Cancer Family Registry (BCFR) using DNA from both granulocytes and total WBC. We found that methylation levels in all markers were correlated between sisters (Spearman correlation coefficients ranged from 0.17 to 0.55). Sat2 methylation was statistically significantly associated with increased breast cancer risk [odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.09-4.03; for each unit decrease in the natural log of the methylation level, OR = 2.12, 95% CI = 0.88-5.11 for the lowest quartile compared with the highest quartile]. These associations were only observed in total WBC but not granulocyte DNA. There was no association between breast cancer and LINE-1 and Alu methylation. If replicated in larger prospective studies, these findings support that selected markers of epigenetic changes measured in WBC, such as Sat2, may be potential biomarkers of breast cancer risk.
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Neoplasias da Mama/genética , Metilação de DNA , Leucócitos , Sequências Repetitivas de Ácido Nucleico , Biomarcadores Tumorais/análise , Neoplasias da Mama/sangue , Feminino , Humanos , Leucócitos/ultraestrutura , Sistema de Registros , Fatores de Risco , IrmãosRESUMO
The effect of a family history of schizophrenia on the risk for this disorder in the offspring has rarely been examined in a prospective population cohort accounting for the sex of the proband and the first-degree relatives, and certainly not with respect to later paternal age. The influence of affected relatives on offspring risk of schizophrenia was estimated using Cox proportional hazards regression in models that accounted for sex, relation of affected first degree relatives and paternal age in the prospective population-based cohort of the Jerusalem Perinatal Schizophrenia Study. Of all first-degree relatives, an affected mother conferred the highest risk to male and female offspring among the cases with paternal age <35 years, however, female offspring of fathers ≥35 years with an affected sister had the highest risk (RR = 8.8; 95% CI = 3.9-19.8). The risk seen between sisters of older fathers was fourfold greater than the risk to sisters of affected females of younger fathers (RR = 2.2, 95% CI 0.7-6.7). The test for interaction was significant (P = 0.03). By contrast, the risk of schizophrenia to brothers of affected males was only doubled between older (RR = 3.3, 95% 1.6-6.6) and younger fathers (RR = 1.6, 95% CI 0.7-3.5). The most striking finding from this study was the very large increase in risk of schizophrenia to sisters of affected females born to older fathers. The authors speculate that the hypothesized paternally expressed genes on the X chromosome might play some role in these observations.
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Morbidade , Idade Paterna , Esquizofrenia/epidemiologia , Irmãos , Adolescente , Adulto , Criança , Família , Feminino , Humanos , Israel , Masculino , Risco , Esquizofrenia/etiologia , Adulto JovemRESUMO
OBJECTIVE: The purpose of this study was to examine the association between preeclampsia and cancer incidence. STUDY DESIGN: The Jerusalem Perinatal Study is a population-based cohort of all births to 41,206 residents of Western Jerusalem from 1964-76. Cancer incidence to 2004 was assessed by linkage of the cohort with the Israel Cancer Registry. Cox's proportional hazards models were constructed to estimate the hazard ratio for cancer among women who had had preeclampsia. RESULTS: Preeclampsia was associated with a 1.23-fold increased risk of cancer at all sites, a 37% increased risk of breast cancer, and more than a doubling of ovarian cancer risk. Analysis by morphologic condition yielded significantly increased risks for malignancies that were classed as cystic mucinous and serous (relative risk, 1.96; 95% CI, 1.00-3.83) and for ductal, lobular, and medullary carcinomas (relative risk, 1.40; 95% CI, 1.07-1.83). No differential association was observed by sex of offspring. CONCLUSION: Our study suggests that the previously described protective effect of preeclampsia on cancer is not universal.
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Neoplasias da Mama/epidemiologia , Neoplasias Ovarianas/epidemiologia , Pré-Eclâmpsia/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Coortes , Feminino , Humanos , Incidência , Israel/epidemiologia , Masculino , Neoplasias Ovarianas/etiologia , Gravidez , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
OBJECTIVE: Increased incidence of schizophrenia is observed among some immigrant groups in Europe, with the offspring of immigrants, ie "second-generation" immigrants particularly vulnerable. Few contemporary studies have evaluated the risk of schizophrenia among second-generation immigrants in other parts of the world. METHODS: We studied the incidence of schizophrenia in relation to parental immigrant status in a population-based cohort of 88 829 offspring born in Jerusalem in 1964-1976. Parental countries of birth were obtained from birth certificates and grouped together as (1) Israel, (2) Other West Asia, (3) North Africa, and (4) Europe and industrialized countries. Cox proportional hazards methods were used in adjusting for sex, parents' ages, maternal education, social class, and birth order. RESULTS: Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. Incidence of schizophrenia was not increased among second-generation immigrants in this birth cohort, neither overall nor by specific group. CONCLUSIONS: The difference in risk of schizophrenia among second-generation immigrants in Europe and in this Israeli birth cohort suggests that the nature of the immigration experience may be relevant to risk, including reasons for migration, the nature of entry, and subsequent position in the host country for immigrants and their offspring. Minority status may be of importance as, in later studies, immigrants to Israel from Ethiopia had increased risk of schizophrenia.
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Emigrantes e Imigrantes/estatística & dados numéricos , Esquizofrenia/epidemiologia , Adulto , Estudos de Coortes , Estudos Transversais , Emigrantes e Imigrantes/psicologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Incidência , Israel , Acontecimentos que Mudam a Vida , Masculino , Gravidez , Modelos de Riscos Proporcionais , Sistema de Registros , Risco , Esquizofrenia/diagnóstico , Fatores SocioeconômicosRESUMO
Although it is known that schizophrenia is associated with social class, controversy exists as to the nature of this association. The authors studied the incidence of schizophrenia in relation to social class at birth in a population-based cohort of 88,829 offspring born in Jerusalem in 1964-1976. They constructed a six-point scale to index social class, based on paternal occupation at the time of birth, with each of 108 occupations being ranked by mean education. Cox proportional hazards methods were used in adjusting for sex, parents' ages, duration of marriage and birth order. Linkage with Israel's Psychiatric Registry identified 637 people admitted to psychiatric care facilities with schizophrenia-related diagnoses, before 1998. There was no gradient of risk for schizophrenia associated with social class at birth; however, offspring of fathers in the lowest social class showed a modest increase in risk (adjusted Relative Risk = 1.4; 95% Confidence interval = 1.1-1.8, P = 0.002). These data suggest that in contrast to many other health outcomes, there is not a continuous gradient for increasing schizophrenia with decreasing social class of origin. Instead, a modest increase in risk for schizophrenia was observed only for those born at the bottom of the social ladder.
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Pais , Esquizofrenia/epidemiologia , Classe Social , Adulto , Estudos de Coortes , Intervalos de Confiança , Escolaridade , Feminino , Humanos , Israel/epidemiologia , Masculino , Modelos de Riscos Proporcionais , Medição de Risco , Esquizofrenia/economia , Esquizofrenia/genética , EspanhaRESUMO
The California Institute for Regenerative Medicine has formed a group of clinics called the Alpha Stem Cell Clinics Network. Its goal is to accelerate clinical trials of stem cell-based therapies for diseases with unmet medical needs. In this report, we describe our experience in establishing an Alpha Stem Cell Clinic at City of Hope. Implementation and integration of the clinic into the existing institutional structures required collaboration and cooperation with clinical trial units, nursing administration, and creation of new positions. The highlight of this process and the centerpiece to our success has been the definition of the role of the "hybrid nurse," a person with nursing competencies in both clinical care and research. Stem Cells Translational Medicine 2018;7:6-10 Abstract Video Link: https://youtu.be/WOeZrNyXkGU.
Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Enfermagem/métodos , Medicina Regenerativa/métodos , Pesquisa com Células-Tronco , Educação em Enfermagem , Humanos , Transplante de Células-TroncoRESUMO
BACKGROUND: Childhood trauma is emerging as a risk factor for schizophrenia, but its mechanism with respect to etiology is unknown. One possible pathway is through leucocyte telomere length (LTL) shortening, a measure of cellular aging associated with trauma. This study examined early trauma and LTL shortening in schizophrenia and considered sex effects. METHODS: The early trauma inventory (ETI) was administered to 48 adults with DSM-5 schizophrenia and 18 comparison participants. LTL was measured using qPCR. OUTCOMES: Cases had significantly more global trauma (F=4.10, p<0.01) and traumatic events (F=11.23, p<0.001), but case and control groups had similar LTL (1.91±0.74 and 1.83±0.62: p=0.68). The association of early trauma and LTL differed by sex in cases and controls (Fisher's R: Z<0.05). Significant negative associations were shown in male cases and, conversely, in female controls. For example, physical punishment was associated LTL shortening in males' cases (r=-0.429, p<01). Only female controls showed significant telomere shortening in association with early trauma. INTERPRETATION: This data confirms the substantial excess of early trauma among schizophrenia cases. There were significant sex-differences in the relationship of the trauma to LTL, with only male cases showing the expected shortening. There were converse sex effects in the control group. Mean LTL was notably similar in cases and controls, despite the trauma-related shortening in male cases, cigarette smoking, older age and chronic illness of the cases. Factors may lengthen LTL in some schizophrenia cases. The converse sex differences in the cases are consistent with findings defective sexual differentiation in schizophrenia, consistent with other findings in the field.
Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Trauma Psicológico/metabolismo , Esquizofrenia/metabolismo , Encurtamento do Telômero , Adulto , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores SexuaisRESUMO
Tetrachloroethylene is a solvent used in dry cleaning with reported neurotoxic effects. Using proportional hazard methods, we examined the relationship between parental occupation as a dry cleaner and risk for schizophrenia in a prospective population-based cohort of 88,829 offspring born in Jerusalem from 1964 through 1976, followed from birth to age 21-33 years. Of 144 offspring whose parents were dry cleaners, 4 developed schizophrenia. We observed an increased incidence of schizophrenia in offspring of parents who were dry cleaners (RR=3.4, 95% CI, 1.3-9.2, p=0.01). Tetrachloroethylene exposure warrants further investigation as a risk factor for schizophrenia.
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Filhos Adultos/psicologia , Poluentes Atmosféricos/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Esquizofrenia/induzido quimicamente , Solventes/toxicidade , Tetracloroetileno/toxicidade , Adulto , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Israel , Masculino , Gravidez , Estudos Prospectivos , Fatores de Risco , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologiaRESUMO
OBJECTIVE: Recent studies have shown increased maternal mortality rates after hypertensive disorders of pregnancy (HDP), but the reasons for this increase remain unclear. This study examines the relationship between elevated prepregnancy body mass index (BMI), HDP, and postpregnancy mortality. STUDY DESIGN: Data came from a 1975-1976 subset (n = 13,722 women) of a population-based cohort. Multiple logistic regression was used to examine the risk of HDP by BMI; age-adjusted Cox proportional hazards models were used to examine survival rates. RESULTS: Overweight (BMI, 25-29.9 kg/m2) and obesity (BMI, > or = 30 kg/m2) were associated with increased HDP (odds ratio [OR], 2.82; 95% confidence interval [CI], 2.40-3.31 and OR, 5.51; 95% CI, 4.15-7.31]) and decreased survival (hazard ratio [HR], 1.42; 95% CI, 1.10-1.83 and HR, 2.43; 95% CI, 1.61-3.68), compared with normal weight (BMI, 18.5-24.9 kg/m2). HDP was significantly associated with increased mortality rates for women who survived > 15 years (HR, 1.94; 95% CI, 1.42-2.67]; HR adjusted for BMI, 1.65; 95% CI, 1.19-2.79]). A greater increase in risk of death after HDP was seen in the overweight women (HR, 1.86; 95% CI, 1.07-3.20) and obese women (HR, 2.90; 95% CI, 1.28-6.58), compared with normal weight women (HR, 1.26; 95% CI, 0.74-2.14). CONCLUSION: Elevated prepregnancy BMI is associated with increased risk of HDP, which are in turn is associated with increased long-term maternal mortality rates. This association between HDP and mortality rates increases with elevated prepregnancy BMI.
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Hipertensão Induzida pela Gravidez/epidemiologia , Índice de Massa Corporal , Feminino , Humanos , Hipertensão Induzida pela Gravidez/mortalidade , Hipertensão Induzida pela Gravidez/fisiopatologia , Mortalidade Materna , Razão de Chances , Gravidez , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de SobrevidaRESUMO
The causal mechanism underlying the well-established relation between advancing paternal age and schizophrenia is hypothesized to involve mutational errors during spermatogenesis that occur with increasing frequency as males age. Point mutations are well known to increase with advancing paternal age while other errors such as altered copy number in repeat DNA and chromosome breakage have in some cases also been associated with advancing paternal age. Dysregulation of epigenetic processes may also be an important mechanism underlying the association between paternal age and schizophrenia. Evidence suggests that advancing age as well as environmental exposures alter epigenetic regulation. Errors in epigenetic processes, such as parental imprinting can have serious effects on the offspring both pre- and postnatally and into adulthood. This article will discuss parental imprinting on the autosomal and X chromosomes and the alterations in epigenetic regulation that may lead to such errors.
Assuntos
Epigênese Genética/genética , Idade Paterna , Esquizofrenia/genética , Envelhecimento/fisiologia , Cromossomos Humanos X/genética , Metilação de DNA , Meio Ambiente , HumanosRESUMO
Pyrethroid pesticides were applied via ground spraying to residential neighborhoods in New York City during July-September 2000 to control mosquito vectors of West Nile virus (WNV). Case reports link pyrethroid exposure to asthma exacerbations, but population-level effects on asthma from large-scale mosquito control programs have not been assessed. We conducted this analysis to determine whether widespread urban pyrethroid pesticide use was associated with increased rates of emergency department (ED) visits for asthma. We recorded the dates and locations of pyrethroid spraying during the 2000 WNV season in New York City and tabulated all ED visits for asthma to public hospitals from October 1999 through November 2000 by date and ZIP code of patients' residences. The association between pesticide application and asthma-related emergency visits was evaluated across date and ZIP code, adjusting for season, day of week, and daily temperature, precipitation, particulate, and ozone levels. There were 62,827 ED visits for asthma during the 14-month study period, across 162 ZIP codes. The number of asthma visits was similar in the 3-day periods before and after spraying (510 vs. 501, p = 0.78). In multivariate analyses, daily rates of asthma visits were not associated with pesticide spraying (rate ratio = 0.92; 95% confidence interval, 0.80-1.07). Secondary analyses among children and for chronic obstructive pulmonary disease yielded similar null results. This analysis shows that spraying pyrethroids for WNV control in New York City was not followed by population-level increases in public hospital ED visit rates for asthma.
Assuntos
Asma/etiologia , Inseticidas/efeitos adversos , Controle de Mosquitos , Piretrinas/efeitos adversos , Febre do Nilo Ocidental/prevenção & controle , Adolescente , Adulto , Poluentes Atmosféricos/efeitos adversos , Asma/terapia , Criança , Pré-Escolar , Serviço Hospitalar de Emergência/estatística & dados numéricos , Estudos Epidemiológicos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Cidade de Nova Iorque , Estações do Ano , População Urbana , Vírus do Nilo Ocidental/patogenicidadeRESUMO
Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.
RESUMO
BACKGROUND: In the 20th century, catatonia was usually deemed a subtype of schizophrenia. Recently, the nature and classification of catatonia are being reconsidered. This study is the first to describe catatonia using prospectively collected data and to examine how catatonic schizophrenia differs from, or resembles, other types of schizophrenia. METHODS: Data were analyzed in a cohort of 90,079 offspring followed from birth till ages 29-41 years. Proportional hazards models were used, calculating time to first psychiatric hospital admission, to compare risk factors for catatonic schizophrenia vs "other schizophrenia." RESULTS: Of 568 cases of schizophrenia, 43 (7.6%) had catatonic schizophrenia. The sexes were equally at risk for catatonic schizophrenia in contrast to other schizophrenia, for which the incidence was higher in males (1.70, 1.42-2.03, P < .0001). Advancing paternal age had no influence on the risk of catatonic schizophrenia in contrast to other schizophrenia, in which the risk to offspring of fathers age 35+ was 1.27 (1.03-1.57, P = .03) compared with those of younger fathers. Those with catatonic schizophrenia were somewhat more likely to have older mothers (aged 35+) (relative risk = 2.14, 0.85-5.54) while maternal age was not related to other schizophrenia. Both were equally affected by parental history of schizophrenia. Patients with catatonia were significantly more likely to attempt suicide (P = .006). CONCLUSION: Patients with catatonic schizophrenia show a somewhat different profile of risk factors from those with other types of schizophrenia in this cohort and are more likely to attempt suicide. This lends some support to the hypothesis that catatonic schizophrenia may have a distinct etiology.
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Esquizofrenia Catatônica/epidemiologia , Esquizofrenia Catatônica/etiologia , Esquizofrenia/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Idade Materna , Idade Paterna , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais , Tentativa de Suicídio/estatística & dados numéricosRESUMO
Lower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry. We measured global DNA methylation in total white blood cell (WBC) and granulocyte DNA by two different methods, the [ ( 3) H]-methyl acceptance assay and the luminometric methylation assay (LUMA). Global methylation levels were only modestly correlated between sisters discordant for breast cancer (Spearman correlation coefficients ranged from -0.08 to 0.24 depending on assay and DNA source). Using conditional logistic regression models, women in the quartile with the lowest DNA methylation levels (as measured by the [ ( 3) H]-methyl acceptance assay) had a 1.8-fold (95% CI = 1.0-3.3) higher relative association with breast cancer than women in the quartile with the highest DNA methylation levels. When we examined the association on a continuous scale, we also observed a positive association (odds ratio, OR = 1.3, 95% CI = 1.0-1.7, for a one unit change in the natural logarithm of the DPM/µg of DNA). We observed no association between measures by the LUMA assay and breast cancer risk. If replicated in prospective studies, this study suggests that global DNA methylation levels measured in WBC may be a potential biomarker of breast cancer risk even within families at higher risk of cancer.
Assuntos
Neoplasias da Mama/genética , Metilação de DNA , DNA/sangue , Leucócitos/metabolismo , Adulto , Neoplasias da Mama/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , New York/epidemiologia , Sistema de Registros , IrmãosRESUMO
BACKGROUND: Paternal age related schizophrenia (PARS) has been proposed as a subgroup of schizophrenia with distinct etiology, pathophysiology and symptoms. This study uses a k-means clustering analysis approach to generate hypotheses about differences between PARS and other cases of schizophrenia. METHODS: We studied PARS (operationally defined as not having any family history of schizophrenia among first and second-degree relatives and fathers' age at birth ≥ 35 years) in a series of schizophrenia cases recruited from a research unit. Data were available on demographic variables, symptoms (Positive and Negative Syndrome Scale; PANSS), cognitive tests (Wechsler Adult Intelligence Scale-Revised; WAIS-R) and olfaction (University of Pennsylvania Smell Identification Test; UPSIT). We conducted a series of k-means clustering analyses to identify clusters of cases containing high concentrations of PARS. RESULTS: Two analyses generated clusters with high concentrations of PARS cases. The first analysis (N=136; PARS=34) revealed a cluster containing 83% PARS cases, in which the patients showed a significant discrepancy between verbal and performance intelligence. The mean paternal and maternal ages were 41 and 33, respectively. The second analysis (N=123; PARS=30) revealed a cluster containing 71% PARS cases, of which 93% were females; the mean age of onset of psychosis, at 17.2, was significantly early. CONCLUSIONS: These results strengthen the evidence that PARS cases differ from other patients with schizophrenia. Hypothesis-generating findings suggest that features of PARS may include a discrepancy between verbal and performance intelligence, and in females, an early age of onset. These findings provide a rationale for separating these phenotypes from others in future clinical, genetic and pathophysiologic studies of schizophrenia and in considering responses to treatment.
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Análise por Conglomerados , Idade Paterna , Esquizofrenia/diagnóstico , Psicologia do Esquizofrênico , Adulto , Idade de Início , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Fatores de Risco , Esquizofrenia/classificação , Esquizofrenia/etiologia , Esquizofrenia/genéticaRESUMO
Epigenetics holds promise to explain some puzzles concerning the risk and course of psychiatric disorders. Epigenetic information is essential as a set of operating instructions for the genome, which is heritable with DNA. The epigenetic regulation of gene expression can plausibly be influenced by the environment of one's ancestors, prenatal exposures, and by early life events. Some epigenetic mechanisms may alter neurophysiology throughout life by programming gene expression, perhaps in anticipation of certain life experiences. These epigenetic signals are only meta-stable and may be perturbed by stochastic events, errors, or by environmental toxins. This introduction considers the possibility that epigenetic change that may occur as paternal age advances or during fetal adversity may be causally related to the susceptibility for schizophrenia.
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Epigênese Genética/genética , Impressão Genômica/genética , Esquizofrenia/genética , HumanosRESUMO
Schizophrenia has been linked to advanced paternal age, but the explanation is unknown. We questioned whether the incidence of schizophrenia would be related to male reproductive capacity, as reflected in the time taken to conceive. We measured the incidence of schizophrenia in relation to time to conception in a sub-group of 12,269 in the Jerusalem cohort whose mothers, interviewed post-partum, reported that the pregnancy had been intended. Compared with those conceived in less than 3 months, the unadjusted relative risks (RR) of schizophrenia associated with conception-waits of 3-5, 6-11 and 12+ months were 1.10 (95% confidence interval, 0.62-1.94), 1.41 (0.79-2.52) and 1.88 (1.05-3.37) with p for trend=0.035. This trend was attenuated somewhat by adjusting for paternal age, and was observed more strongly in offspring of fathers aged 30+ (p=.010). These findings suggest that factors associated with fecundability, either male or female, may contribute to the risk of schizophrenia.
Assuntos
Gravidez , Efeitos Tardios da Exposição Pré-Natal , Risco , Esquizofrenia/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Idade Paterna , Estudos Retrospectivos , Psicologia do Esquizofrênico , Adulto JovemRESUMO
OBJECTIVE: Advanced paternal age is consistently associated with an increased risk for schizophrenia, accounting for up to a quarter of cases in some populations. If paternal age-related schizophrenia (PARS) involves a distinct etiopathology, then PARS cases may show specific characteristics, vis-à-vis other schizophrenia cases. This study examined if PARS exhibits the symptom profile and sex differences that are consistently observed for schizophrenia in general, wherein males have an earlier onset age and more severe negative symptoms than females. METHOD: Symptoms were assessed at baseline (admission) and during medication-free and treatment phases for 153 inpatients on a schizophrenia research unit, 38 of whom fulfilled operationally defined criteria for PARS (sporadic cases with paternal age > or = 35). RESULTS: Males and females with PARS had the same age at onset and a similar preponderance of negative symptoms, whereas the other (non-PARS) cases showed the typical earlier onset age and more severe negative symptoms in males. When medications were withdrawn, PARS cases showed significantly worse symptoms than non-PARS cases (higher total PANSS scores and positive, activation, and autistic preoccupation scores). However these symptoms globally improved with antipsychotic treatment, such that the differences between the PARS and other schizophrenia cases receded. CONCLUSION: The lack of sex differences in the age at onset and the greater severity of medication-free symptoms bolster the hypothesis that PARS has a distinct etiopathology. It also suggests that female sex does not exert a protective effect on the course of PARS, as it may in other forms of schizophrenia.