Daniella Nahon

Acute maternal stress in pregnancy and schizophrenia in offspring: A cohort prospective study

Schizophrenia has been linked with intrauterine exposure to maternal stress due to bereavement, famine and major disasters. Recent evidence suggests that human vulnerability may be greatest in the first trimester of gestation and rodent experiments suggest sex specificity. We aimed to describe the consequence of an acute maternal stress, through a follow-up of offspring whose mothers were pregnant during the Arab-Israeli war of 1967. A priori, we focused on gestational month and offsprings sex.MethodIn a pilot study linking birth records to Israels Psychiatric Registry, we analyzed data from a cohort of 88,829 born in Jerusalem in 1964–76. Proportional hazards models were used to estimate the relative risk (RR) of schizophrenia, according to month of birth, gender and other variables, while controlling for fathers age and other potential confounders. Other causes of hospitalized psychiatric morbidity (grouped together) were analyzed for comparison.ResultsThere was a raised incidence of schizophrenia for those who were in the second month of fetal life in June 1967 (RR = 2.3, 1.1–4.7), seen more in females (4.3, 1.7–10.7) than in males (1.2, 0.4–3.8). Results were not explained by secular or seasonal variations, altered birth weight or gestational age. For other conditions, RRs were increased in offspring who had been in the third month of fetal life in June 1967 (2.5, 1.2–5.2), also seen more in females (3.6, 1.3–9.7) than males (1.8, 0.6–5.2).ConclusionThese findings add to a growing literature, in experimental animals and humans, attributing long term consequences for offspring of maternal gestational stress. They suggest both a sex-specificity and a relatively short gestational time-window for gestational effects on vulnerability to schizophrenia.

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.

Gender differences in premorbid cognitive performance in a national cohort of schizophrenic patients

Despite significant research, there are still inconsistent findings regarding gender differences in cognitive performance in individuals already diagnosed with schizophrenia; studies have found that males suffering from schizophrenia are more, less or equally impaired compared with females. Gender differences in cognitive performance in individuals suffering from schizophrenia may be influenced by gender differences in premorbid cognitive performance; the very few and very small N studies published indicated that males have a poorer pre-morbid cognitive performance than females. This study examined the gender differences in premorbid cognition, utilizing cognitive assessments performed on female and male adolescents before induction into military service. The Israeli Draft Board Registry, which contains cognitive assessments equivalent to IQ scores on 16-18 year old Israeli adolescents, was linked with the Israeli National Psychiatric Hospitalization Case Registry, which records all psychiatric hospitalizations in the country. Scores on premorbid cognitive performance in schizophrenia were examined in 90 female-male case pairs matched for school attended as a proxy for socio-economic status. The mean age of first hospitalization was 20. 1+/-1.8 years of age for males and 19.6+/-1.8 years of age for females. A repeated-measures ANCOVA with age of first hospitalization and years of formal education as covariates, and controlling for gender differences in cognitive performance in healthy adolescents, revealed a significant difference in pre-morbid cognitive performance between males and females on all four cognitive measures [F(1,87)=8.07, P=0.006] with females scoring lower (worse) than males. In this national cohort, pre-morbid cognition was poorer in female, compared with male, adolescents who will suffer from schizophrenia in the future, a result consistent with some, but not all, similar studies. These results may be valid only for patients with first hospitalization around age 20. Hence, gender differences in premorbid cognition should be taken into account when assessing gender differences in cognition in 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.

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.

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.

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.

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.

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.

Higher rates of cigarette smoking in male adolescents before the onset of schizophrenia: A historical-prospective cohor 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.