Refractive errors and schizophrenia

BackgroundRefractive errors (myopia, hyperopia and amblyopia), like schizophrenia, have a strong genetic cause, and dopamine has been proposed as a potential mediator in their pathophysiology. The present study explored the association between refractive errors in adolescence and schizophrenia, and the potential familiality of this association.MethodsThe Israeli Draft Board carries a mandatory standardized visual accuracy assessment. 678,674 males consecutively assessed by the Draft Board and found to be psychiatrically healthy at age 17 were followed for psychiatric hospitalization with schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Sib-ships were also identified within the cohort.ResultsThere was a negative association between refractive errors and later hospitalization for schizophrenia. Future male schizophrenia patients were two times less likely to have refractive errors compared with never-hospitalized individuals, controlling for intelligence, years of education and socioeconomic status [adjusted Hazard Ratio = .55; 95% confidence interval .35–.85]. The non-schizophrenic male siblings of schizophrenia patients also had lower prevalence of refractive errors compared to never-hospitalized individuals.ConclusionsPresence of refractive errors in adolescence is related to lower risk for schizophrenia. The familiality of this association suggests that refractive errors may be associated with the genetic liability to schizophrenia.     

Dysthymia in male adolescents is associated with increased risk of later hospitalization for psychotic disorders: a historical-prospective cohort study

Aim: Retrospective studies indicate that patients with psychotic disorders and schizophrenia often suffer from depressive symptoms before the onset of psychosis. In a historical‐prospective design, we studied the association between dysthymia in adolescence and later hospitalization for psychotic disorders and schizophrenia. Methods: The Israeli Draft Board screens the entire, unselected population of 16–17 years old male adolescents for psychiatric disorders. These adolescents were followed for hospitalization for psychotic disorders and schizophrenia using the Israeli National Psychiatric Hospitalization Case Registry. Of 275 705 male adolescents screened, 1267 (0.5%) were hospitalized for psychotic disorders (International Classification of Diseases [ICD]‐10 20.0–29.9), and 757 (0.3%) were hospitalized for schizophrenia (ICD‐10 20.0–20.9) over the next 1–10 years. Results: Of 275 705 male adolescents screened, 513 (0.2%) were diagnosed as suffering from dysthymia by the Draft Board. Of these adolescents, 10/513 (2.0%) were later hospitalized for psychotic disorders (including schizophrenia, HR = 3.967, 95%CI (confidence intervals): 2.129–7.390), and 4/513 (0.8%) were later hospitalized for schizophrenia (HR = 2.664, 95%CI: 0.997–7.116). Conclusions: In this population‐based cohort of male adolescents, dysthymia was associated with increased risk for future psychotic disorders. Dysthymia in some adolescents might be a prodromal symptom, while in others it might be a risk factor for later psychosis. Clinicians assessing dysthymic adolescents should be aware that these symptoms might be part of the prodrome.     

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.     

Premorbid intra-individual variability in intellectual performance and risk for schizophrenia: a population-based study

BACKGROUND: Some, but not most, schizophrenia patients have below-average intelligence years before they manifest psychosis. However, it is not clear if those whose intelligence falls within-normal-range nevertheless have cognitive abnormalities. We examined the association between intra-individual variability in intellectual performance and risk for schizophrenia in individuals with normal IQ. METHODS: 555,326 adolescents, mandatory assessed by the Israeli Draft Board were followed up over 8 to 17 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Data were available on 4 intelligence sub-tests, and on behavioral and psychosocial variables. Variability was computed from the variance of the four intelligence tests' standardized scores. RESULTS: There was a significant monotonic association between increased intra-individual variability in intellectual performance and risk of schizophrenia in individuals with within-normal-range IQ. Individuals with the highest variability were 3.8 times more likely to have schizophrenia [95%CI: 2.32-6.08; p < 0.0001] compared with individuals with the lowest variability. This association held after controlling for the effects of potential confounders. CONCLUSIONS: Despite within-normal-range premorbid IQ, apparently healthy adolescents who will later on manifest schizophrenia, nevertheless have cognitive abnormalities such as increased variability across intellectual tasks, possibly related to frontal lobe abnormalities.     

Longitudinal association between epilepsy and schizophrenia:A population-based study

A large number of studies have reported an association between epilepsy and major psychiatric conditions. This study investigated the association between epilepsy and later schizophrenia, utilizing a historical-prospective, population-based design. Of the 861,062 17-year-old male adolescents consecutively screened by the Israeli Draft Board and found free of major mental illness, 0.06% suffered from severe, treatment-refractory epilepsy, 0.25% had treated, controlled epilepsy, and 0.16% had a history of seizures which had abated 5 or more years prior to screening. Hospitalization for schizophrenia was ascertained through the Israeli National Psychiatric Hospitalization Case Registry, with an average follow-up of 9.6 ± 1.0 years (range: 1.0–10.0 years). Risk of hospitalization was calculated using Cox regression analyses, compared to socioeconomic-adjusted risk of hospitalization in the general population of male adolescents. Among adolescents whose epilepsy was nonresponsive to medication, the adjusted risk of hospitalization was significantly increased for schizophrenia (HR = 3.89, 95% CI = 1.75–89.67). Male adolescents with successfully treated epilepsy were not at increased risk for schizophrenia.Male adolescents with severe, treatment-refractory epilepsy are at increased risk of later schizophrenia. Future studies attempting to understand the biology of this association might focus on this subset of patients, and these patients should be monitored for the appearance of psychosis.     

Self-report of family functioning and risk for psychotic disorders in male adolescents with behavioural disturbances

Objective: Previous studies indicate that a poor family environment might affect vulnerability for the later manifestation of psychotic illness. The current study aims to examine family functioning prior to the onset of psychosis. Method: Subjects were 42 948, 17‐year old males with behavioural disturbances who were asked about the functioning of their family by the Israeli Draft Board. Data on later psychiatric hospitalizations were obtained from a National Psychiatric Hospitalization Registry. Results: Poorer self‐reported family functioning was associated with greater risk for later hospitalization for psychosis [adjusted hazard ratio (HR) = 1.16, 95% CI = 1.05–1.27], with a trend in the same direction for schizophrenia (adjusted HR = 1.1, 95% CI = 0.98–1.24). Conclusion: In male adolescents with behavioural disturbances, perceived poorer family functioning is associated with increased risk for non‐affective psychotic disorders and schizophrenia. These data do not enable us to determine if perceived familial dysfunction increases vulnerability for psychosis, if premorbid behavioural abnormalities disrupt family life, or neither.     

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.     

Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents.

OBJECTIVE: Subtle behavioral and intellectual abnormalities are often present in apparently healthy adolescents who later develop schizophrenia. The authors investigated whether these abnormalities can predict vulnerability for schizophrenia before the first psychotic manifestation. METHOD: The study consisted of linking the Israeli Draft Board Registry with the National Psychiatric Hospitalization Case Registry. The draft board tests measure intelligence, social functioning, organizational ability, interest in physical activity, and individual autonomy. Patients (N = 509) were compared to nonpatients, i.e., adolescents not appearing in the National Psychiatric Registry (N = 9,215), matched to patients by age, gender, and school attended at time of testing. RESULTS: Healthy male adolescents who were later hospitalized for schizophrenia had significantly lower test scores on all measures than adolescents not reported to the National Psychiatric Registry. The strongest predictors for schizophrenia were deficits in social functioning, organizational ability, and intellectual functioning. When patients were compared to matched nonpatients, the prediction model had a 75% sensitivity, a 100% specificity, a positive predictive value of 72%, and an overall rate of correct classification of 87.5%. Applied to the Israeli Draft Board Registry, the model yielded a sensitivity of 74.7%, a validated specificity of 99.7%, and a positive predictive value of 42.7%. CONCLUSIONS: This study demonstrated that simple assessment tools can predict predisposition to schizophrenia in healthy male adolescents. The model's predictive ability does not change as a function of the time elapsed between testing and first hospitalization. This suggests that the model identifies apparently healthy individuals who will manifest the disease later who are not prodromal to psychosis. Easily applied tools allowing early identification of schizophrenia or vulnerability to it may enable early intervention.     

Association between functioning in adolescence prior to first admission for schizophrenia and affective disorders and patterns of hospitalizations thereafter

BACKGROUND: Kraepelin and Blueler suggested that subtle manifestations of schizophrenia are present in some persons for many years before formal diagnosis and that the severity of these is associated with outcomes in schizophrenia. Empirical support for this hypothesis comes primarily from small samples using retrospectively collected data. AIMS: We tested this hypothesis, for the first time, using a population-based cohort. METHOD: The Israeli Draft Board Registry, which contains measures of intellectual and behavioral functioning for the unselected population of 17-year-olds, was merged with the National Psychiatric Hospitalization Case Registry that contains data on all psychiatric hospitalizations. The database was used to identify adolescents assessed by the draft board at least 1 year prior to their first hospitalization for schizophrenia (n=996) or affective disorder (n=335). RESULTS: Poorer social functioning and organizational ability prior to first admission were associated with more days per year in the hospital for the male schizophrenia group. There were no significant correlations between days per year in the hospital and any of the behavioral functioning measures for the affective group. Among females the higher the previous level of intellectual functioning the fewer the days per year in the hospital in both the schizophrenia group and affective groups. For males no such correlations were evident. The comparisons between patients who had one as opposed to more than one admission found that in both diagnostic groups female patients with one admission had higher pre-first hospitalization intellectual functioning. CONCLUSIONS: Gender and disease specific premorbid deficits have may have differential prognostic value for outcomes in schizophrenia and affective disorders.     

Effects of season of birth on autism spectrum disorders: fact or fiction?

OBJECTIVE: This study attempted to examine the relationship between month and season of birth and risk for autism spectrum disorders. METHOD: The cohort included all Jewish individuals born in Israel over 5 consecutive years (N=311,169) and assessed by the Israeli Draft Board as part of the mandatory assessment of eligibility for military service conducted at age 17. The outcome of autism spectrum disorders was ascertained from the Draft Board Medical Registry, which contains information about medical and psychiatric disorders for this population of adolescents. RESULTS: There was no association between month or season of birth and the prevalence of autistic spectrum disorders. CONCLUSIONS: The findings from this historical, population-based cohort study do not support an association between season of birth and autistic spectrum disorders.     

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.     

Accuracy of self-reported premorbid functioning in schizophrenia

BACKGROUND: Information on premorbid functioning is often based on patients recalling their past. Premorbid functioning is relevant as it is associated with treatment response and other outcomes. The extent to which memory impairments of persons with schizophrenia may bias such reporting has not been investigated. The purpose of the current study was to assess the extent to which persons with schizophrenia might exhibit biased reporting relative to controls. METHODS: Seventy males with schizophrenia or schizoaffective disorder and 51 males with no psychiatric symptoms participated in the study. Contemporaneous and retrospective reports from a behavioral functioning assessment conducted as part of the Israeli Draft Board were compared. This assessment routinely administered to all 17 years old males in the country assesses social functioning, individual autonomy, organizational ability, physical activity and functioning in structured environments. We compared the groups on the Draft Board behavioral measures at age 17 and at re-assessment. We also examined the relationship between symptom severity, neuropsychological performance and differences between age 17 and current behavioral assessment scores. RESULTS: In a repeated measures MANCOVA of the five measures there was no overall significant difference in accuracy of reporting between persons with schizophrenia and those without. Both groups showed a slight tendency to glorify their past. Consistency of reporting was not significantly correlated with neuropsychological performance or levels of psychotic symptoms. CONCLUSIONS: We found that when reporting on personal and social functioning during teen age years persons with schizophrenia report with the same level of consistency as persons without schizophrenia. This suggests that self-report of premorbid functioning of persons with schizophrenia can be trusted as being reasonably accurate.     

Association between nonpsychotic psychiatric diagnoses in adolescent males and subsequent onset of schizophrenia

BACKGROUND: Nonpsychotic psychiatric symptoms may occasionally herald the later development of schizophrenia. This study followed a population-based cohort of adolescents with nonpsychotic, non-major affective psychiatric disorders to ascertain future hospitalization for schizophrenia. METHODS: Results of the medical and mental health assessments on 124 24416- to 17-year-old males screened by the Israeli draft board were cross-linked with the National Psychiatric Hospitalization case registry, which contains data on all psychiatric hospitalizations in the country, during a 4- to 8-year-long follow-up through age 25 years. In the cohort, 9365 adolescents were assigned a nonpsychotic, non-major affective diagnosis by the draft board. RESULTS: After excluding 167 adolescents who were hospitalized before or up to 1 year after the draft board assessment, 1.03% of the adolescents assigned a nonpsychotic, non-major affective psychiatric diagnosis, compared with only 0.23% of the adolescents without any psychiatric diagnosis, were later hospitalized for schizophrenia. Of the patients with schizophrenia, 26.8%, compared with only 7.4% in the general population, had been assigned a nonpsychotic, non-major affective psychiatric diagnosis in adolescence (overall odds ratio [OR], 4.5; 95% confidence interval [CI], 3.6-5.6), ranging from OR, 21.5 (95% CI, 12.6-36.6) for schizophrenia spectrum personality disorders to OR, 3.6 (95% CI, 2.1-6.2) for neurosis. CONCLUSION: These results reflect the relatively common finding of impaired functioning in patients later hospitalized for schizophrenia and the relatively low power of these disorders in predicting schizophrenia.     

A population-based cohort study of premorbid intellectual,language, and behavioral functioning in patients with schizophrenia,schizoaffective disorder,and nonpsychotic bipolar disorder

OBJECTIVE: The premorbid intellectual, language, and behavioral functioning of patients hospitalized for schizophrenia, schizoaffective disorder, or nonpsychotic bipolar disorder was compared with that of healthy comparison subjects. METHOD: The Israeli Draft Board Registry, which contains measures of intellectual, language, and behavioral functioning for the unselected population of 16- to 17-year-olds, was merged with the National Psychiatric Hospitalization Case Registry, which contains diagnoses for all patients with psychiatric hospitalizations in Israel. The database was used to identify adolescents with no evidence of illness at their draft board assessment who were later hospitalized for nonpsychotic bipolar disorder (N=68), schizoaffective disorder (N=31), or schizophrenia (N=536). The premorbid functioning of these subjects was compared to that of nonhospitalized individuals matched for age, gender, and school attended at the time of the draft board assessment. The diagnostic groups of hospitalized subjects were also compared. RESULTS: Relative to the comparison subjects, subjects with schizophrenia showed significant premorbid deficits on all intellectual and behavioral measures and on measures of reading and reading comprehension. Subjects with schizophrenia performed significantly worse on these measures than those with a nonpsychotic bipolar disorder, who did not differ significantly from the comparison subjects on any measure. Subjects with schizoaffective disorder performed significantly worse than the comparison subjects only on the measure of nonverbal abstract reasoning and visual-spatial problem solving and performed significantly worse than subjects with nonpsychotic bipolar disorder on three of the four intellectual measures and on the reading and reading comprehension tests. CONCLUSIONS: The results support a nosologic distinction between nonpsychotic bipolar disease and schizophrenia in hospitalized patients.     

Validity of the premorbid adjustment scale

Background: The aim of the current study was to test the predictive and concurrent validity of the Premorbid Adjustment Scale (PAS) by comparing it with another similar but more elaborate retrospective measure and with data collected during late adolescence. Methods: We compared PAS late adolescence scores (age 16-18 years) of 91 males with schizophrenia or schizoaffective disorder with data on behavior collected in adolescence, before the first psychotic episode as part of standardized Draft Board screening, and with the same measure readministered during adulthood and modified to collect the same data again retrospectively. Results: The correlation of the PAS social withdrawal and social relations items with the social behavior scale of the Draft Board were .76 and .80, respectively, for the concurrent ratings and .52 and .53, respectively, for the data collected at age 17 years. The correlation of the PAS school achievements and school adjustment items with the functioning in structured environments scale of the Draft Board were .71 and .72, respectively, for the concurrent ratings and .43 and .47, respectively, for the data collected at age 17 years. Conclusions: Our results support the predictive and concurrent validity of the PAS and the validity of self-reported data on premorbid functioning in persons with schizophrenia.     

Cognitive performance in schizophrenia patients assessed before and following the first psychotic episode

BACKGROUND: The purpose of this historical prospective study was to follow the cognitive impairment in schizophrenia from the premorbid period until shortly after the onset of the first psychotic episode within the same subjects. METHODS: Forty-four first episode schizophrenia patients were enrolled in the study. Their cognitive performance was assessed as part of the Israeli Draft Board aptitude assessments at ages 16-17, when all were found to be in good mental health (first assessment) and again, following the manifestation of the first psychotic episode (second assessment). Forty-four healthy comparisons were also enrolled and tested twice, at the same ages as the patients. Both times, the assessments included four subtests assessing abstract reasoning (Raven Progressive Matrices-R), mental speed and concentration (Otis-R), verbal reasoning (Similarities-R), and mathematical abilities (Arithmetic-R). RESULTS: A within group analysis did not reveal statistically significant changes between the first and the second assessment among the schizophrenia patients on any measure. However, a between group comparison of changes showed that relative to the healthy comparisons, schizophrenia patients deteriorated on the RPM-R (p=0.021) and Otis-R (p<0.001), but not on the Similarities-R and Arithmetic-R. Schizophrenia patients performed worse than comparisons in all four subtests on the first and second assessments (all p<0.01). CONCLUSIONS: The results indicate that most of the cognitive impairment exhibited by first-episode schizophrenia patients precedes the first psychotic episode. A decline between ages 16 and 17 and the onset of psychosis is evident in some but not all cognitive functions.     

Admissions, length of stay, and medication use among women in an acute care state psychiatric facility

OBJECTIVE: Despite growing numbers of elderly persons with serious mental illness such as schizophrenia, little research has been conducted on the manifestation of serious mental illness in later life, and our understanding of the mental health care needs of this population is limited. This study examined length of stay and medication use among women age 50 and older admitted to an acute care state psychiatric facility. METHODS: A computerized record search for all women discharged from a large urban state psychiatric facility over a one-year period was undertaken. Demographic and resource utilization data, including total length of stay and pharmacy utilization, were obtained from the hospital database. RESULTS: The database search produced the records of 564 women, with a mean age of 37.5 years. Women constituted 60 percent of patients over age 50. The mean length of stay was 16.1 days for the entire group; for women under age 50 (N=492), mean length of stay was 15 days, and for women age 50 and older (N=72), it was 23.1 days (p=. 01). Among those age 50 and older, 58.3 percent had a diagnosis of schizophrenia or schizoaffective disorder, compared with only 38 percent of those under age 50. CONCLUSIONS: Our data suggest that women constitute the majority of patients over age 50 in a state psychiatric facility and that they have longer stays than younger women.     

Parental mental health after the accidental death of a son during military service: 23-year follow-up study

We prospectively studied parental mental health after suddenly losing a son in a military training accident. Parents (N = 32) were interviewed at 1, 2 and 23 years after the death of their son. The General Health Questionnaire and Expanded Texas Inventory of Grief were self-reported at 1, 2, 5, and 23 years; the Inventory of Complicated Grief was self-reported at 23 years. We observed a high prevalence of psychiatric disorders at 1- and 2-year follow-ups (57% and 45%, respectively), particularly major depression (43% and 31%, respectively). Only one mental disorder was diagnosed at the 23-year follow-up. Grief and psychological distress were highest at 1- and 2-year follow-ups. Spouses exhibited a high concordance of psychological distress. Mothers reported more intense grief reactions than did fathers. The loss of a son during military service may have a substantial impact on parental mental health particularly during the first 2 years after death. Spouses' grief can be interrelated and may contribute to their psychological distress.