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Short duration of marriage at conception as an independent risk factor for schizophrenia

Malaspina, Dolores; Kranz, Thorsten; Kleinhaus, Karine; Daboul, Sulaima; Rothman, Karen; Gilman, Caitlin; Getz, Mara; Harlap, Susan; Friedlander, Yechiel
Short duration of marriage (DoM) is a risk factor for preeclampsia that is also related to the risk for schizophrenia. This analysis examined the risk for schizophrenia associated with DoM and its independence from parental psychiatric disorders, parental ages and fathers' age at marriage.
PMID: 30857873
ISSN: 1573-2509
CID: 3747822

Prenatal x-ray exposure may increase risk of schizophrenia: Results from the Jerusalem perinatal cohort schizophrenia study

Gross, Raz; Hamid, Hamada; Harlap, Susan; Malaspina, Dolores
The purpose of this article is to determine the risk of schizophrenia in offspring of women exposed to x-ray radiation during pregnancy. The risk of schizophrenia was evaluated using cohort data collected in The Jerusalem Perinatal Study. The cohort of 92,408 births from 1964 to 1976 was linked to Israel's National Psychiatric Registry of all individuals hospitalized for psychiatric conditions. Cross-tabulations were analyzed for development of schizophrenia in offspring of mothers who were exposed to an x-ray procedure during the first four months of pregnancy. Relative risks (RRs) were estimated using proportional hazards models, adjusted for male sex, paternal age, family psychiatric history, and social class. The adjusted RRs for schizophrenia spectrum associated with maternal x-rays in months 3 and 4 were, respectively, 2.97 (0.94-9.35) and 1.23 (0.39-3.87). Among 80 cases with narrowly defined schizophrenia (ICD-10 = F20) maternal x-rays in months 3 and 4 were associated, respectively, with adjusted RRs of 3.08 (0.75-12.6, based on 2 cases), and 2.04 (0.64-6.46, 3 cases). Offspring of mothers exposed to x-ray radiation during the third and fourth months of pregnancy may have an increased risk of developing schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved)
PSYCH:2018-53492-002
ISSN: 1557-9328
CID: 4373272

Live birth sex ratios and father's geographic origins in Jerusalem, 1964-1976

Groeger, J; Opler, M; Kleinhaus, K; Perrin, M C; Calderon-Margalit, R; Manor, O; Paltiel, O; Conley, D; Harlap, S; Malaspina, D
OBJECTIVE: To examine whether ancestry influenced sex ratios of offspring in a birth cohort before parental antenatal sex selection influenced offspring sex. METHODS: We measured the sex ratio as the percent of males according to countries of birth of paternal and maternal grandfathers in 91,459 live births from 1964 to 1976 in the Jerusalem Perinatal Study. Confidence limits (CI) were computed based on an expected sex ratio of 1.05, which is 51.4% male. RESULTS: Of all live births recorded, 51.4% were male. Relative to Jewish ancestry (51.4% males), significantly more males (1,761) were born to Muslim ancestry (54.5, 95% CI = 52.1-56.8, P = 0.01). Among the former, sex ratios were not significantly associated with paternal or maternal age, education, or offspring's birth order. Consistent with a preference for male offspring, the sex ratio decreased despite increasing numbers of births over the 13-year period. Sex ratios were not affected by maternal or paternal origins in North Africa or Europe. However, the offspring whose paternal grandfathers were born in Western Asia included fewer males than expected (50.7, 50.1-51.3, P = 0.02), whether the father was born abroad (50.7) or in Israel (50.8). This was observed for descendents of paternal grandfathers born in Lebanon (47.6), Turkey (49.9), Yemen & Aden (50.2), Iraq (50.5), Afghanistan (50.5), Syria (50.6), and Cyprus (50.7); but not for those from India (51.5) or Iran (51.9). The West Asian group showed the strongest decline in sex ratios with increasing paternal family size. CONCLUSIONS: A decreased sex ratio associated with ancestry in Western Asia is consistent with reduced ability to bear sons by a subset of Jewish men in the Jerusalem cohort. Lower sex ratios may be because of pregnancy stress, which may be higher in this subgroup. Alternatively, a degrading Y chromosome haplogroup or other genetic or epigenetic differences on male germ lines could affect birth ratios, such as differential exposure to an environmental agent, dietary differences, or stress. Differential stopping behaviors that favor additional pregnancies following the birth of a daughter might exacerbate these lower sex ratios.
PMCID:5432402
PMID: 27901293
ISSN: 1520-6300
CID: 2329332

Cohort Profile: The Jerusalem Perinatal Family Follow-Up Study

Lawrence, Gabriella M; Siscovick, David S; Calderon-Margalit, Ronit; Enquobahrie, Daniel A; Granot-Hershkovitz, Einat; Harlap, Susan; Manor, Orly; Meiner, Vardiella; Paltiel, Ora; Kwok, Pui-Yan; Friedlander, Yechiel; Hochner, Hagit
PMCID:5841635
PMID: 26163255
ISSN: 1464-3685
CID: 1668572

Grand multiparity and reproductive cancer in the Jerusalem Perinatal Study Cohort

Paltiel, Ora; Tajuddin, Salman M; Polanker, Yelena; Yazdgerdi, Shoshanah; Manor, Orly; Friedlander, Yechiel; Harlap, Susan; Calderon-Margalit, Ronit
OBJECTIVES: Grand multiparity is associated with reduced mortality from reproductive cancers. We aimed to separate the components of mortality, by measuring incidence of and survival after reproductive cancer onset in grand multiparous compared to other parous women. STUDY DESIGN: We linked data from the population-based Jerusalem Perinatal Study Cohort, which included women aged 13-55 who delivered 1964-1976, with Israel's National Cancer Registry. We compared breast and gynecologic cancer risk and all-cause survival following a cancer diagnosis, among grand multiparae (GMPs = parity 5+, n = 8,246) versus women with parity 1-4 (n = 19,703), adjusting for reproductive and demographic variables. RESULTS: Grand multiparae were at significantly lower risk of breast cancer than others (adjusted hazard ratio (HRadj) = 0.62, 95 % confidence interval (CI) 0.54-0.71), after controlling for age at first birth, education, and other covariates. This reduction was greater among GMPs whose first birth occurred after age 30 (p-interaction = 0.0001) and for cancer occurring before age 50 years (p = 0.002). In contrast, GMPs were at greater risk of death than women with parity <5, following a breast cancer diagnosis (HRadj = 1.69, CI 1.39-2.1). Ovarian, uterine, and cervical cancer incidence did not differ between the groups, but survival was reduced for GMPs with uterine cancer (HRadj = 2.48, CI 1.22-5.03). CONCLUSION: Reduced reproductive cancer mortality reported among GMPs masks two opposing phenomena: decreased breast cancer risk and poorer survival after breast and uterine cancers. The latter unfavorable outcome suggests that tumors in GMPs may be particularly aggressive, having perhaps escaped protective mechanisms conferred by parity. This finding calls for heightened clinical attention in this group.
PMID: 26669321
ISSN: 1573-7225
CID: 1953532

Socioeconomic disparities in breast cancer incidence and survival among parous women: findings from a population-based cohort, 1964-2008

Goldberg, Mandy; Calderon-Margalit, Ronit; Paltiel, Ora; Abu Ahmad, Wiessam; Friedlander, Yechiel; Harlap, Susan; Manor, Orly
BACKGROUND: Socioeconomic position (SEP) has been associated with breast cancer incidence and survival. We examined the associations between two socioeconomic indicators and long-term breast cancer incidence and survival in a population-based cohort of parous women. METHODS: Residents of Jerusalem who gave birth between 1964-1976 (n = 40,586) were linked to the Israel Cancer Registry and Israel Population Registry to determine breast cancer incidence and vital status through mid-2008. SEP was assessed by husband's occupation and the woman's education. We used log ranks tests to compare incidence and survival curves by SEP, and Cox proportional hazard models to adjust for demographic, reproductive and diagnostic factors and assess effect modification by ethnic origin. RESULTS: In multivariable models, women of high SEP had a greater risk of breast cancer compared to women of low SEP (Occupation: HR 1.18, 95 % CI 1.03-1.35; Education: HR 1.39, 95 % CI 1.21-1.60) and women of low SEP had a greater risk of mortality after a breast cancer diagnosis (Occupation: HR 1.33, 95 % CI 1.04-1.70; Education: HR 1.37, 95 % CI 1.06-1.76). The association between education and survival was modified by ethnic origin, with a gradient effect observed only among women of European origin. Women of Asian, North African and Israeli origin showed no such trend. CONCLUSIONS: SEP was associated with long-term breast cancer incidence and survival among Israeli Jews. Education had a stronger effect on breast cancer outcomes than occupation, suggesting that a behavioral mechanism may underlie disparities. More research is needed to explain the difference in the effect of education on survival among European women compared to women of other ethnicities.
PMCID:4653946
PMID: 26585765
ISSN: 1471-2407
CID: 1848762

Telomere length, family history, and paternal age in schizophrenia

Malaspina, Dolores; Dracxler, Roberta; Walsh-Messinger, Julie; Harlap, Susan; Goetz, Raymond R; Keefe, David; Perrin, Mary C
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.
PMCID:4113273
PMID: 25077175
ISSN: 2324-9269
CID: 1090242

Prenatal stress and affective disorders in a population birth cohort

Kleinhaus, Karine; Harlap, Susan; Perrin, Mary; Manor, Orly; Margalit-Calderon, Ronit; Opler, Mark; Friedlander, Yehiel; Malaspina, Dolores
Kleinhaus K, Harlap S, Perrin M, Manor O, Margalit-Calderon R, Opler M, Friedlander Y, Malaspina D. Prenatal stress and affective disorders in a population birth cohort. Bipolar Disord 2012: 00: 000-000. (c) 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. 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.
PMID: 23339677
ISSN: 1398-5647
CID: 213772

Catatonic Schizophrenia: A Cohort Prospective Study

Kleinhaus K; Harlap S; Perrin MC; Manor O; Weiser M; Harkavy-Friedman JM; Lichtenberg P; Malaspina D
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
PMCID:3283154
PMID: 20693343
ISSN: 1745-1701
CID: 139506

Olfactory processing, sex effects and heterogeneity in schizophrenia

Malaspina D; Goetz R; Keller A; Messinger JW; Bruder G; Goetz D; Opler M; Harlap S; Harkavy-Friedman J; Antonius D
INTRODUCTION: Smell identification deficits are associated with negative symptoms in schizophrenia, particularly in males. Far less information is known about the relationship of odor detection sensitivity (acuity) and negative symptoms in schizophrenia, and currently there is a dearth in sex-stratified research specifically examining odor sensitivity and smell identification. METHODS: Fifty-eight individuals with schizophrenia and 42 healthy comparison subjects were assessed on tests of odor sensitivity, smell identification and cognition. Negative symptoms were assessed with the Positive and Negative Syndrome Scale and the Schedule for the Deficit Syndrome. RESULTS: In healthy males, increased odor detection sensitivity predicted better smell identification scores. In contrast, male schizophrenia patients showed a significant inverse relationship, in which increased odor sensitivity predicted lower smell identification scores. Odor sensitivity and smell identification were unrelated in both schizophrenia and healthy females. Olfactory processing was strongly linked to negative symptoms, but the relationships differed by sex. Emotional expression deficits were related to odor detection hypersensitivity in female patients, whereas smell identification deficits predicted these emotional deficits in male cases. CONCLUSION: Sex differences in olfactory functioning were identified in healthy subjects and in schizophrenia patients. Smell identification was related to negative symptoms in males with schizophrenia, whereas odor detection sensitivity predicted these features in females. Sex differences should be considered in future analyses that employ odor stimuli for neuropsychiatric research
PMCID:3288877
PMID: 22177347
ISSN: 1573-2509
CID: 150613