Childhood exposure to ionizing radiation to the head and risk of schizophrenia.

While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.

Effect of socioeconomic status and parents' education at birth on risk of schizophrenia in offspring.

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.

Incidence of schizophrenia among second-generation immigrants in the jerusalem perinatal cohort.

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.

Impaired reading comprehension and mathematical abilities in male adolescents with average or above general intellectual abilities are associated with comorbid and future psychopathology.

Research indicates that persons with learning disorders often suffer from psychopathology. We assessed current and future psychopathology in male adolescents with discrete impairments in reading comprehension (IRC) or arithmetic abilities (IAA) but with average or above-average general intellectual abilities. Subjects were a population-based cohort of 174,994 male adolescents screened by the Israeli Draft Board with average or above-average intellectual abilities but with low scores (8.6th and 10th lowest percentile respectively) on reading or arithmetic tests. They were compared with adolescents who scored in the 10th percentile and above on these tests (comparison group). Relative to the comparison group, male adolescents with IRC, IAA, or IRC and IAA (0.69%), had poorer scores on most behavioral assessments and higher prevalence of current psychopathology: 4.2% (comparison group), 8.0% (IRC), 7.0% (IAA), and 9.8% (IRC and IAA). Adolescents with IRC were also at increased risk for later hospitalization for schizophrenia (hazard ratios = 1.8, 95% confidence interval: 1.3-2.6). Male adolescents with average and above-average general intellectual abilities but with IRC or IAA are more likely to have current and future psychopathology. Impairments in intellectual functioning and abnormal behaviors leading to mental illnesses may share common neurobiological substrates. The results support screening male adolescents with learning disorders for psychopathology.

Social and cognitive functioning, urbanicity and risk for schizophrenia.

BACKGROUND: Previous work suggests that the association between urbanicity and schizophrenia may be greatest in those with pre-existing vulnerability. AIMS: To test for synergism in risk of schizophrenia between population density and a combined exposure of poor premorbid social and cognitive functioning. METHOD: For 371 603 adolescent males examined by the Israeli Draft Board on social and cognitive functioning, data on population density of place of residence and later hospitalisation for schizophrenia were obtained from population-based registries. RESULTS: There was an interaction between population density (five levels) and poor premorbid social and cognitive functioning (interaction chi(2)=4.6, P=0.032). The adjusted increase in cumulative incidence associated with one unit change in population density was 0.10% in the vulnerable group (95% CI 0.019-0.18, P=0.015), nine times larger than that in the non-vulnerable group (0.011%, 95% CI 0.0017-0.020, P=0.021). CONCLUSIONS: Risk of schizophrenia may increase when people with a genetic liability to the disorder, expressed as poor social and cognitive functioning, need to cope with city life.

Premorbid behavioral and intellectual functioning in schizophrenia patients with poor response to treatment with antipsychotic drugs.

INTRODUCTION: Approximately one third of schizophrenia patients show partial or no response to pharmacotherapy. Despite intensive investigations, the phenomenological and biological characteristics of such patients are far from elucidated. This study examined the premorbid behavioral and intellectual functioning of schizophrenia patients who showed poor response to antipsychotic treatment. METHOD: One hundred twenty-nine schizophrenia patients who showed poor response to treatment were ascertained from a national register and matched by gender, age and education to 129 patients who showed adequate response. The groups were compared on premorbid measures of behavioral and intellectual functions. RESULTS: As a group, treatment-resistant male patients had significantly lower (worse) social functioning [p=0.002], and individual autonomy [p<0.0001] scores before the onset of the illness compared to treatment non-resistant patients. Male and female treatment-resistant patients did not differ from non-resistant patients in premorbid intellectual functioning [p>0.1]. CONCLUSIONS: Low premorbid social functioning and individual autonomy, but not intellectual functioning, could serve as predictors of poor treatment response in schizophrenia.

Tetrachloroethylene exposure and risk of schizophrenia: offspring of dry cleaners in a population birth cohort, preliminary findings.

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.

The impact of human rights advocacy, mental health legislation and psychiatric reform on the epidemiology of involuntary psychiatric hospitalizations.

Several years ago, the Ministry of Health published a report on the epidemiology of involuntary psychiatric hospitalizations. Many developments (advances in human rights advocacy, mental health legislation and the nascent Psychiatric Reform) have occurred in the mental health field in Israel since 1990 when the earlier report was released. Those favorable developments in mental health care were thought to have the capacity to modify the admission rates. We explored several parameters to check the hospitalization patterns (eg, by demographic factors, diagnosis) and found no substantial modifications. The case for an analytic study was clearly established.

Maternal household crowding during pregnancy and the offspring's risk of schizophrenia.

BACKGROUND: Animal models of schizophrenia suggest a link between maternal crowding during pregnancy and increased risk of the offspring to develop physiological, developmental, and behavioral abnormalities that are comparable to those observed in schizophrenia. We tested the hypothesis that a similar link is present in humans. METHOD: We investigated whether prenatal exposure to household crowding was associated with the risk of schizophrenia in a sub-cohort of the Jerusalem Perinatal Study (JPS) consisting 11,015 individuals born between 1964 and 1976. During these years mothers participated in face to face interviews in early pregnancy. The prenatal and birth data, including the number of rooms and individuals living in the mothers' household, was cross-linked with the Israel Psychiatric Registry by ministry personnel. RESULTS: 104 schizophrenia cases were identified in the cohort. Offspring who, while in utero, their mother resided in a household with five or more individuals had RR of 1.47 (95% CI: 0.99-2.16, p=0.05) to develop schizophrenia, compared to those whose mother resided with four or fewer individuals. However, when adjusted for paternal age, the RR was reduced to 1.18 (95% CI: 0.76-1.84, p=0.46). The number of rooms in the household and the household crowding during pregnancy did not significantly impact the offspring's risk to develop schizophrenia. CONCLUSION: The link between maternal household crowding during pregnancy and the offspring's risk of schizophrenia was explained primarily by the impact of paternal age. The authors discuss the results in view of findings from animal and human studies.

Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National Hospitalization Registry compared with RDC diagnoses based on SADS-L.

OBJECTIVE: The Israeli National Psychiatric Hospitalization Registry is a nationwide list of all psychiatric hospitalizations in the country and has been widely used as a source of data for psychiatric research. This study assessed the sensitivity of the diagnosis of psychotic disorders ( International Statistical Classification of Diseases, 10th Revision [ ICD-10 ] F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) in the Registry. METHOD: Registry discharge diagnoses of psychotic disorders ( ICD-10 F20.0-F29.9) and schizophrenia ( ICD-10 F20.0-F20.9) were compared with research diagnoses derived from best-estimate procedures based on Research Diagnostic Criteria (RDC) using structured clinical research interviews, hospital records, and family information. RESULTS: Out of 169 patients meeting RDC for psychotic disorder, 150 also had a diagnosis of psychotic disorders in the Registry, yielding a sensitivity of 0.89. Re-running this analysis for the narrow definition of schizophrenia identified 94 patients who were diagnosed with schizophrenia using RDC; 82 of those patients also had a diagnosis of schizophrenia in the Registry, yielding a sensitivity of 0.87. CONCLUSION: In 87% to 89% of cases with psychotic disorders or with schizophrenia, Registry diagnoses agreed with RDC diagnoses, a rate of agreement comparable with those of other, similar registries. Because a large number of analyses derived from this and similar national registries will be published in the coming years, this constitutes relevant information.

Cancer in schizophrenia: is the risk higher or lower?

Studies exploring the relationship between schizophrenia and cancer have shown conflicting results. Our study explores this association in three Jewish-Israeli population groups defined by their continent/place of birth (Israel, Europe-America, and Africa-Asia). The identification of the patients was made through the linkage of the nationwide psychiatric and cancer registries. The incidence of cancer in patients diagnosed with schizophrenia was compared with the incidence in the general population. The results showed that the cancer standardized incidence ratios (SIRs) for all sites were significantly lower among men and women with schizophrenia, 0.86 [95% confidence interval (CI) 0.80-0.93] and 0.91 (95% CI 0.85-0.97), respectively. This reduced overall risk was clearest for those born in Europe-America, both men (SIR 0.85, 95% CI 0.74-0.97) and women (SIR 0.86, 95% CI 0.77-0.94). Among women diagnosed with schizophrenia, the SIR was statistically higher for cancer in the breast among those born in Asia-Africa (1.37, 95% CI 1.12-1.63) and in the corpus uteri among the Israel-born (2.75, 95% CI 1.69-3.81) than among their counterparts in the general population. Lung cancer was significantly higher in men born in Asia-Africa diagnosed with schizophrenia than in the respective comparison population group (1.58, 95% CI 1.13-2.2). Our findings, and those of the literature, justify conducting a multinational study that includes identification of cancer-related risk factors among patients with schizophrenia and their families, and information on the use of psychotropic medications. This effort may clarify an epidemiological puzzle that remains outstanding.

Body mass index and future schizophrenia in Israeli male adolescents.

BACKGROUND: Compared with the general population, individuals suffering from schizophrenia are more likely to be overweight, a finding attributed to the effect of antipsychotic medications, poor nutrition, and sedentary lifestyle. As evidence accumulates indicating that some aspects of the illness manifest before the onset of psychosis and establishment of the diagnosis, it has been suggested that increased weight, like other metabolic dysfunctions, might precede active illness. METHOD: Data on height and weight of 203,257 male adolescents assessed by the Israeli Draft Board, and followed for 2-6 years for later hospitalization for schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry, were analyzed. RESULTS: From the entire cohort, 309 (0.15%) were later hospitalized for schizophrenia (ICD-10). After removing adolescents with evidence of illness before or within 1 year of the Draft Board assessment, 204 future schizophrenia patients were available for analysis. Compared with the rest of the cohort, future schizophrenia patients had lower body mass indexes (21.24 +/- 3.3 kg/m2 vs. 21.77 +/- 3.5 kg/m2; F = 4.682, df = 1, p = .03) and weighed slightly but significantly less (64.2 +/- 11.6 kg vs. 66.3 +/- 12.0 kg; F = 6.615, df = 1, p = .01). The mean height of the future patients did not differ significantly from the mean height of the remaining cohort (173.63 +/- 6.7 cm vs. 174.40 +/- 6.9 cm; F = 2.520, df = 1, p = .112). When reanalyzing the data, controlling for physical activity and socioeconomic status, the differences between the groups remained significant. CONCLUSION: Before the onset of illness, future schizophrenia patients are not heavier compared with their peers. This implies that the increased weight of patients with schizophrenia is related to illness effects, including the effects of antipsychotic medication.

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: a historical-prospective cohort study.

OBJECTIVE: The prevalence of cigarette smoking among schizophrenia patients is significantly higher than in the general population; this may reflect self-medication of symptoms and/or adverse effects of neuroleptics. The authors examined the prevalence of cigarette smoking in apparently healthy adolescents later hospitalized for schizophrenia. METHOD: Each year, a random sample of male Israeli military recruits, who have been screened and found not to be suffering from major psychopathology, complete a smoking questionnaire. Through the Israeli National Psychiatric Hospitalization Case Registry, 14,248 of these adolescents were followed to determine later psychiatric hospitalization. RESULTS: Of the 14,248 adolescents assessed, 4,052 (28.4%) reported smoking at least one cigarette a day. Over a 4-16-year follow-up, the prevalence of schizophrenia in the entire cohort was 0.3% (N=44). Smokers were at greater risk for later schizophrenia; the adjusted relative risk was 1.94, and the 95% confidence interval (CI) was 1.05-3.58. The number of cigarettes smoked was significantly associated with the risk for schizophrenia. Compared to nonsmokers, adolescents who smoked 1-9 cigarettes/day were 1.38 times (95% CI=0.48-4.00) as likely to be hospitalized later for schizophrenia, and adolescents who smoked 10 cigarettes/day or more were 2.28 times (95% CI=1.19-4.34) as likely; the latter difference was statistically significant. CONCLUSIONS: Taken together with the existing data on abnormalities in nicotinic transmission in patients and their relatives, this higher prevalence of smoking in future schizophrenia patients, before the onset of their illness, might indicate that impaired nicotinic neurotransmission is involved in the pathophysiology of schizophrenia.

Self-reported drug abuse in male adolescents with behavioral disturbances, and follow-up for future schizophrenia.

BACKGROUND: The prevalence of illicit drug abuse in persons with schizophrenia is greater then in the general population and has been attributed to self-medication of the symptoms of the illness; however, limited data indicate that drug abuse is already prevalent before the manifestation of psychosis, consistent with the possibility that drug abuse might be associated with increased risk for schizophrenia. METHODS: The Israeli Draft Board screens the entire, unselected population of 16- to 17-year-old male adolescents for behavioral or personality disturbances. In a cohort of 270,000 male adolescents screened, 50,413 adolescents were suspected of having behavioral or personality disturbances and were questioned about drug use and abuse. These adolescents were followed for hospitalization for schizophrenia using a national, population-based psychiatric hospitalization registry; 268 of 50,413 (.5%) were hospitalized for schizophrenia over the following 5-11 years. RESULTS: The prevalence of self-reported drug abuse in adolescents later hospitalized for schizophrenia was 12.4%, compared with 5.9% prevalence of drug abuse in adolescents not later hospitalized; adjusted RR = 2.016, 95% confidence interval: 1.309-3.104. CONCLUSIONS: In this cohort of male adolescents with behavior disturbances, these results further support the hypothesis that drug abuse may be associated with increased risk for future schizophrenia.

No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel.

AIM: Maternal stress during pregnancy is a possible risk factor for schizophrenia in the offspring. Using data from the Israel Psychiatric Registry we examined the impact of wars in Israel. METHOD: Retrospective birth cohort study. RESULTS: Relative risks for cohorts exposed to Six-Day War and Yom Kippur War were 0.98 (95% CI: 0.85-1.13) and 1.00 (0.86-1.16). CONCLUSION: The evidence for maternal stress as a risk factor for schizophrenia remains insufficient.