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.     

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.     

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.     

Self-reported mental health difficulties and subsequent risk for schizophrenia in females: a 5-year follow-up cohort study

BACKGROUND: Patients with schizophrenia often report a history of premorbid mild to severe psychological distress. We investigated the association between self-reported mental health difficulties and later psychiatric hospitalization for schizophrenia. METHODS: 13,357 females aged 17, mandatory assessed by the Israeli Draft Board were followed up over 5 years for psychiatric hospitalization by means of the Israeli National Psychiatric Hospitalization Case Registry. Seventeen females, judged healthy at Draft Board assessment, were hospitalized for schizophrenia or schizoaffective disorder over the follow-up period. RESULTS: There was a significant monotonic association between increasing self-reported mental health difficulties (psychological distress and increasing need for psychological counseling) and prevalence of schizophrenia [odds ratios over four levels: 1.56; 95% CI:1.04 to 2.34; chi2 (1) = 4.62, p = 0.03], after controlling for low IQ, immigration, SES, and presence of psychiatric disorders at age 17. Increasing severity of self-reported mental health difficulties was related to earlier age of first hospitalization [r = -0.48, p = 0.05]. CONCLUSIONS: Increased undifferentiated self-reported mental health difficulties are associated with increased risk of later hospitalization for schizophrenia prior to age 23 in females. This may reflect the prodromal phase of the illness.     

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.     

Premorbid functioning in a national population of male twins discordant for psychoses

OBJECTIVE: The goal of the current study was to compare premorbid behavioral and cognitive functioning between co-twins discordant for psychotic disorder and between these pairs of twins and pairs of twins with no psychotic disorders. METHOD: The authors linked data from the Israeli Draft Board Registry, which contains cognitive and behavioral assessments of all 16-17-year-old male Israeli twins, with data from the National Psychiatric Hospitalization Case Registry. Pairs of male twins who were healthy at the time of testing but discordant for psychoses later on were compared with one another and with pairs of healthy male twins. RESULTS: The affected twins performed significantly worse than healthy twins on measures of individual autonomy, social functioning, and physical activity and nonsignificantly worse on measures of abstract reasoning. There were no significant differences in cognitive or behavioral scores between the co-twins who did or did not develop psychotic disorders. CONCLUSIONS: The authors conclude that these findings underscore the familial nature of behavioral and cognitive deficits antecedent to psychoses.     

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.     

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.     

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.     

Premorbid functioning in schizophrenia: relation to baseline symptoms, treatment response, and medication side effects

Impaired premorbid functioning prior to the onset of acute psychosis has frequently been noted in schizophrenia. This study examined retrospectively the premorbid status of patients in their first episode of psychosis in order to determine relationships with baseline symptoms, treatment response, and medication side effects. One hundred eleven schizophrenic and schizoaffective patients participating in a large prospective study of first episode schizophrenia were evaluated with the Premorbid Adjustment Scale (PAS). Premorbid functioning in males became progressively worse over time. Deficit state patients exhibited worse premorbid functioning. A third of patients exhibited sustained poor premorbid functioning. At various developmental stages, lower "sociability and withdrawal" scores correlated with increased time to treatment response, more severe negative symptoms, increased drug-induced parkinsonism, and deterioration of premorbid functioning. Various mean PAS scores predicted susceptibility to tardive dyskinesia. Our findings suggest that prior to acute psychosis onset there are certain behavioral precursors reflected in premorbid functioning that may predict subsequent illness manifestations. Measures of premorbid functioning indicate that disease pathogenesis is manifest, albeit more subtly, prior to presentation of first psychotic symptoms.     

Correlates of substance misuse in patients with first-episode schizophrenia and schizoaffective disorder.

OBJECTIVE: To identify factors associated with substance misuse in first-episode patients with schizophrenia or schizoaffective disorder. METHOD: Twenty-seven patients with a past or current history of substance misuse were compared with 91 patients with no history of misuse on demographic and psychopathological measures before being treated for their first episode of psychosis, and on cognitive measures after 6 months of treatment. RESULTS: There were no statistically significant differences between groups for sex, schizophrenia subtype, marital status, education, family history of schizophrenia, course of illness, age of onset, baseline symptoms, time to treatment response, medication side effects, attention span, memory and executive functioning. However, dual diagnosis patients were found to have a higher parental social class, better premorbid cognitive functioning, higher IQ and better language skills. CONCLUSION: First-episode patients with a history of substance misuse have higher intellectual functioning, which may be associated with higher premorbid socioeconomic status and cognitive functioning.     

Differential patterns of premorbid academic and social deterioration in patients with schizophrenia

Schizophrenia is a neurodevelopmental disorder that is characterized by a number of behavioral abnormalities that are present prior to onset. These premorbid abnormalities may serve as unique markers for the disorder. The current study examines academic and social functioning prior to schizophrenia onset in a group of 58 males diagnosed with schizophrenia. The pattern of deterioration for social and academic functioning was examined across three age periods including childhood, early adolescence, and late adolescence, using the retrospective Premorbid Adjustment Scale (PAS). Results indicated that while increasing deterioration was present for both social and academic adjustment across age periods, there was a significant difference in deterioration between academic and social functioning (p<.05) during late adolescence, with greater deterioration in academic functioning. Results of the current study suggest that premorbid academic functioning is particularly susceptible to deterioration during late adolescence, with accelerating deterioration as schizophrenia onset becomes imminent. When considered together with results from other studies, the present findings suggest that deterioration in premorbid academic functioning from early to late adolescence may be a unique premorbid marker for 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.     

Cognitive performance of male adolescents is lower than controls across psychiatric disorders: a population-based study

OBJECTIVE: Psychiatric patients, as well as humans or experimental animals with brain lesions, often concurrently manifest behavioral deviations and subtle cognitive impairments. This study tested the hypothesis that as a group, adolescents suffering from psychiatric disorders score worse on cognitive tests compared with controls. METHOD: As part of the assessment for eligibility to serve in the military, the entire, unselected population of 16-17-year old male Israelis undergo cognitive testing and screening for psychopathology by the Draft Board. We retrieved the cognitive test scores of 19 075 adolescents who were assigned any psychiatric diagnosis, and compared them with the scores of 243 507 adolescents without psychiatric diagnoses. RESULTS: Mean test scores of cases were significantly poorer then controls for all diagnostic groups, except for eating disorders. Effect sizes ranged from 0.3 to 1.6. CONCLUSION: As group, adolescent males with psychiatric disorders manifest at least subtle impairments in cognitive functioning.     

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.     

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.     

The relationship of premorbid functioning to illness course in schizophrenia and psychotic mood disorders during two years following first hospitalization

Studies suggest that better premorbid functioning is associated with better outcomes in chronic schizophrenia. Yet first admission studies, which are more appropriate to examine this, are less conclusive. Also, little attention has been given to whether these findings hold for other psychoses. We examined the relationship of premorbid functioning using the Premorbid Adjustment Scale and outcomes in first admission psychoses (schizophrenia, N = 177; bipolar disorder, N = 106; major depression, N = 68) in the Suffolk County-wide mental health project. Poor premorbid functioning was associated with worse outcomes in all three diagnostic groups. Specifically, it was associated with more negative symptoms early in the course of illness, less improvement in negative symptoms, poorer overall clinical functioning, and poorer social functioning. Consistent with new epidemiological research, early assessment of premorbid functioning could provide an avenue for targeted interventions that might improve outcomes.     

Differential patterns of premorbid social and academic deterioration in deficit and nondeficit schizophrenia

Numerous studies indicate that social dysfunction is associated with negative symptoms of schizophrenia during the chronic phase of illness. However, it is unclear whether social abnormalities exist during the premorbid phase in people who later develop schizophrenia with prominent negative symptoms, or whether social functioning becomes progressively worse in these individuals from childhood to late adolescence. The current study examined differences in academic and social premorbid functioning in people with schizophrenia meeting criteria for deficit (i.e., primary and enduring negative symptoms) (DS: n = 74) and non-deficit forms of schizophrenia (ND: n = 271). Premorbid social and academic functioning was assessed for childhood, early adolescence, and late adolescence developmental periods on the Premorbid Adjustment Scale (PAS). Results indicated that both DS and ND participants showed deterioration in social and academic functioning from childhood to late adolescence. However, while ND schizophrenia demonstrated greater deterioration of academic compared to social premorbid functioning from childhood to late adolescence, the DS group exhibited comparable deterioration across both premorbid domains, with more severe social deterioration than the ND group. Findings suggest that people with DS show poorer social premorbid adjustment than those with ND as early as childhood, and are particularly susceptible to accelerated deterioration as the onset of schizophrenia becomes imminent. Thus, poor premorbid social adjustment and significant social deterioration from childhood to adolescence may be a hallmark feature of people who later go on to develop prominent negative symptoms and a unique marker for the DS subtype of schizophrenia.