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Original Article |

Self-reported Attenuated Psychotic Symptoms as Forerunners of Severe Mental Disorders Later in Life FREE

Nomi Werbeloff, PhD; Marjan Drukker, PhD; Bruce P. Dohrenwend, PhD; Itzhak Levav, MD; Rinat Yoffe, MA; Jim van Os, MD, PhD; Michael Davidson, MD; Mark Weiser, MD
[+] Author Affiliations

Author Affiliations: Department of Psychiatry, Sheba Medical Center, Tel Hashomer (Drs Werbeloff, Davidson, and Weiser), Division of Mental Health Services, Ministry of Health, Jerusalem (Dr Levav and Ms Yoffe), and Department of Psychiatry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv (Drs Davidson and Weiser), Israel; Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, European Robotics Research Network, Maastricht University Medical Centre, Maastricht, the Netherlands (Drs Drukker and van Os); Department of Psychiatry, Mailman School of Public Health, Columbia University, New York State Psychiatric Institute, New York (Dr Dohrenwend); and Department of Psychosis Studies, Institute of Psychiatry, King's College London, King's Health Partners, London, England (Dr van Os).


Arch Gen Psychiatry. 2012;69(5):467-475. doi:10.1001/archgenpsychiatry.2011.1580.
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Context It has been suggested that attenuated psychotic symptoms (APSs) reported by people who do not have psychotic disorders signal risk for later severe mental illness.

Objective To investigate this suggestion using follow-up assessments of hospitalization for clinical diagnoses of nonaffective psychotic and other psychiatric disorders.

Design Longitudinal cohort study of self-reported APSs with outcome assessment of severe mental illness obtained through linkage with a national hospitalization case registry.

Setting Israel.

Participants A stratified full probability sample of 4914 persons aged 25 to 34 years who were screened for psychopathology in the 1980s.

Main Outcome Measure Subsequent psychiatric hospitalization was ascertained using the psychiatric hospitalization registry, with a mean follow-up of 24 years.

Results After removing subjects with diagnosable psychotic disorders at baseline, 57.2% of the remaining sample reported at least 1 weak (infrequent) APS and 14.3% reported at least 1 strong (frequent) APS in the year preceding the assessment. Self-reported APSs predicted risk of later hospitalization for nonaffective psychotic disorders, mostly during the 5 years after baseline (adjusted odds ratio = 4.31; 95% CI, 2.21-8.41; positive predictive value = 1.27%; population attributable risk fraction = 33%). Also, APSs increased the risk of later hospitalization for other psychiatric disorders, albeit to a lesser extent (adjusted odds ratio = 2.21; 95% CI, 1.02-4.82).

Conclusions Self-reported APSs signal risk for later nonaffective psychotic disorders but are not clinically useful as predictors. The difference between these population-based data and the high-risk literature in terms of the positive predictive value (1% vs 10%, respectively) and the time window of transition (5 years vs 12 months, respectively) can be attributed to the selective enrichment strategies that produce high-risk samples.

Figures in this Article

It has long been recognized that schizophrenia-like pathology is also expressed at attenuated levels in individuals with schizotypal or schizoid personality traits,1 and mild attenuated paranoid delusional thinking and auditory hallucinations are observed in up to 30% of the general population.2 There is consistent evidence that these attenuated psychotic symptoms (APSs) may be construed as an expression of liability for schizophrenia and related disorders,39 just as higher but borderline abnormal levels of blood pressure or glucose express higher liability for metabolic and cardiovascular disease.10 This interpretation is supported by studies showing a link between APSs and nonaffective psychotic3,1114 and, to a lesser extent, other psychiatric disorders.15,16

Doubt may be expressed about the validity of these findings, however, as the measurements of psychotic disorders at follow-up in these studies were mostly based on lay-interviewer assessments using instruments such as the Composite International Diagnostic Interview,17 which is not an optimal instrument for the diagnosis of psychotic disorders.1820 As hospitalization is a more conservative outcome measure, we assessed clinical outcomes of self-reported APSs during 24 years by linkage to a nationwide psychiatric hospitalization case registry,21,22 hence reducing the possibility of false-positive outcomes. We hypothesized the following: (1) APSs would be strongly associated with an increased risk of later hospitalization for nonaffective psychotic disorder; (2) this association would be pres ent but weaker for other psychiatric hospitalizations; and (3) APSs would interact with social functioning, major depressive disorder, anxiety, exposure to trauma, and cannabis use11,13,2328 in models predicting risk of later hospitalization for nonaffective psychotic disorders.

The association between APSs and subsequent psychiatric hospitalization was examined by merging data from an epidemiological study conducted in Israel in the 1980s with data from the National Psychiatric Hospitalization Case Registry. After receiving approval from the local ethics committee, these databases were linked in 2007 using the national identification number (analogous to the US Social Security number) as the linking variable. For subjects who participated in the epidemiological study and appeared in the hospitalization registry, dates of hospitalizations and discharge diagnoses were added to the file. Individuals who had a discharge diagnosis of nonaffective psychotic disorder (International Statistical Classification of Diseases, 10th Revision [ICD-10 ] codes F20.0-F29.9) at any hospitalization were considered clinically diagnosed as having a psychotic disorder.

To preserve subjects' confidentiality, the national identification number was removed before the linked file was transferred to the investigators.

EPIDEMIOLOGICAL STUDY

This study used data from a 2-stage epidemiological study of mental disorders among young adults in a 10-year birth cohort (1949-1958) conducted in Israel in the 1980s.29,30 As part of the original study's goal to compare the risk of selected disorders in socioeconomically contrasting ethnic groups, a sample of 19 000 Israel-born individuals was drawn from the population registry and screened for father's continent of origin (North Africa or Europe) and level of education. This was done to balance socioeconomic status within advantaged and disadvantaged ethnic groups by oversampling disadvantaged subjects from North African origin with high educational level and advantaged subjects of European origin with low educational level. Based on sex, education, ethnicity, and year of birth, 5200 subjects were selected.

This sample was screened and diagnosed for psychotic and other psychiatric disorders in 2 stages. During the screening stage, 4914 subjects (94.5%) were interviewed using a Hebrew version of the Psychiatric Epidemiology Research Interview (PERI), a well-validated screening tool.26,31,32 Data were not obtained for 286 subjects (5.5%). Of these, approximately 2.0% had already been hospitalized for schizophrenia at least once; 160 (2.4%) died after age 15 years, of whom approximately 2.5% had been hospitalized for schizophrenia. An additional 334 subjects (6.4%) had migrated and data regarding psychiatric illness were unavailable. The mean (SD) age at the time of the interview was 29.4 (3.1) years; 49.6% were men. Subjects reaching predetermined cutoff values on the PERI,26 unable to complete the screening interview, or suspected of having a history of psychiatric illness were referred for a clinical diagnostic (second) stage (n = 2643) along with 416 of the “negatives” from the first stage to control for false-negatives. From this subsample, 2741 subjects (90.8%) were interviewed by psychiatrists using a modified lifetime version of the Schedule for Affective Disorders and Schizophrenia–Israel to arrive at a Research Diagnostic Criteria (RDC)33 diagnosis. The Schedule for Affective Disorders and Schizophrenia–Israel also included an assessment of the best level of social functioning during the 5 years preceding the interview, rated on a scale of 1 (superior) to 7 (grossly inadequate). The mean (SD) time from the screening stage (PERI) to the second stage (Schedule for Affective Disorders and Schizophrenia–Israel) was 1.1 years (11.5 months) (range, 0-4.5 years).

SELF-REPORTED APSs

Self-reports of APSs were assessed using the 13-item false beliefs and perceptions subscale of the PERI. Subjects were asked whether they had experienced APSs, and the frequency of each symptom during the past year was recorded on a 5-item Likert scale with the following scores: 0 indicates never; 1, rarely; 2, sometimes; 3, often; and 4, very often. The scale includes questions assessing core APSs such as delusions, hallucinations, and bizarre thinking; feeling possessed; feeling dissolved; feeling that thoughts are not one's own; and beliefs of mind control. An example of a typical question is, “Have you felt that your mind was dominated by external forces that you had no control over?” The PERI false beliefs and perceptions subscale is based on criteria similar to that of the CIDI psychosis section (version 1.1), the favored instrument in similar studies13,23,34,35 (eAppendix and eTable 1). The PERI screening scales, including the false beliefs and perceptions subscale, were tested for reliability and criterion validity and were calibrated against known cases of psychiatric disorders in a pilot research project in Israel.26

NONSPECIFIC PSYCHOLOGICAL DISTRESS

Nonspecific psychological distress was assessed using the PERI demoralization subscale,36 which includes 27 items drawn from 8 subscales: anxiety, sadness, psychophysiological symptoms, perceived physical symptoms, low self-esteem, hopelessness or helplessness, confused thinking, and dread. Each symptom is scored on a 5-point Likert scale, ranging from a score of 0, indicating never or not at all like you, to a score of 4, indicating very often or very much like you. The total score is obtained by calculating the mean of the 27 items. In the analyses, a dichotomous variable split around the median value of the distribution was used.

BASELINE DIAGNOSES OF NONAFFECTIVE PSYCHOTIC DISORDERS, ALCOHOLISM, MAJOR DEPRESSIVE DISORDER, AND ANXIETY DISORDERS

Psychiatric diagnoses of RDC-probable and RDC-definite disorders37 were taken from the second stage of the study.30,33 These included nonaffective psychotic disorders (including schizophrenia), alcoholism, major depressive disorder, and anxiety disorders (including panic disorder, generalized anxiety disorder, obsessive-compulsive disorder, and phobic disorder).

CANNABIS USE

Lifetime use of cannabis (including single or rare use) was recorded based on self-report in the screening interview. Subjects were asked whether they had ever used marijuana or hashish. Answers were coded as yes or no.

EXPOSURE TO TRAUMA

Self-report of exposure to trauma was based on data from the screening stage. This included self-report of exposure to war or terrorism or having been a prisoner of war.

NATIONAL PSYCHIATRIC HOSPITALIZATION CASE REGISTRY

The National Psychiatric Hospitalization Case Registry21,22 is a complete listing of all psychiatric hospitalizations in the country, including psychiatric hospitals, day hospitals, and psychiatric units in general hospitals, using ICD discharge diagnoses assigned by a board-certified psychiatrist. Reporting is regularly monitored to ensure accuracy. A study comparing RDC diagnoses with registry diagnoses found that the sensitivity of the registry diagnosis of nonaffective psychotic disorders was 0.89, and that of schizophrenia was 0.87.21,22

STUDY POPULATION

Of the 4914 subjects who participated in the screening interview, 172 had a subsequent psychiatric hospitalization, 87 (1.8%) of whom were hospitalized at least once for a nonaffective psychotic disorder (ICD-10 codes F20.0-F29.9). During the follow-up, 169 cohort members had died and were thus excluded from the analysis. In addition, we removed the following subjects from the analyses: (1) those with missing data on the PERI false beliefs and perceptions subscale; (2) those diagnosed as having a psychotic disorder during the Schedule for Affective Disorders and Schizophrenia–Israel interview; (3) those hospitalized in psychiatric facilities prior to or within a year after the PERI assessment (and hence might have been in the prodromal stages of their first psychotic episode); and (4) those with missing data on diagnosis from the hospitalization registry (Figure 1). The final sample included 4587 subjects.

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Figure 1. Study population. RDC indicates Research Diagnostic Criteria.

During the follow-up period (mean [SD] time from PERI interview to first hospitalization or to date of merger in 2007, 23.8 [1.9] years), 22 individuals (0.5%) were identified in the National Psychiatric Hospitalization Case Registry as having been later hospitalized at least once for a nonaffective psychotic disorder (ICD-10 codes F20.0-F29.9; including diagnoses of schizophrenia [n = 15], schizoaffective disorder [n = 4], and psychotic disorder not otherwise specified [n = 3]). The reason for this relatively low rate of nonpsychotic disorders (0.5%) in the analytic sample is that most subjects with these disorders had already manifested their illness at the time of the epidemiological study and hence were excluded from this analysis, which focuses on the risk associated with APSs in subjects not diagnosed as having a concurrent psychotic illness. Thirty-four subjects (0.7%) were identified as having been hospitalized for other disorders, including drug use, personality disorders, affective disorders, anxiety disorders, and organic mental disorders.

STATISTICAL ANALYSIS

All analyses were performed using Stata version 10 statistical software (StataCorp LP). The data were weighted to estimate the rates of APSs in the original population from which the cohort sample was drawn. All numbers shown represent the actual number of subjects, whereas the percentages are weighted.

To assess the effect of baseline reports of APSs on later hospitalization, we created a mean APS score for each subject (for more details, see the eAppendix). We examined whether this mean APS score was influenced by age, origin, marital status, and other demographic variables. The mean APS score was then used in a logistic regression model to predict later hospitalization for nonaffective psychotic and other psychiatric disorders. In the next step, a logistic regression analysis looking at the presence of any APS in the past year and risk of later hospitalization for a nonaffective psychotic or other psychiatric disorder was performed.

As in previous studies,12,14,34 separate scores were defined for weak (occurring rarely or sometimes) and strong (occurring often or very often) APSs. Logistic regression analyses were performed to examine the association between no APSs (n = 1187), weak APSs (n = 2595), or strong APSs (n = 766) at baseline and hospitalization for nonaffective psychotic or other psychiatric disorders by 2007. Associations were expressed as odds ratios (ORs)38 and 95% CIs, presented before and after adjustment for age, sex, education, and ethnicity.

To examine linear effects, the number of weak or strong APSs was then entered into logistic regression analyses examining their association with hospitalization for nonaffective psychotic or other psychiatric disorders.

The population attributable fraction, or the proportion of admissions that could be prevented if APSs were removed from the population assuming causality, was calculated from the OR, ie, [(OR − 1)/OR] × prevalence of exposure in the cases,39 as were the positive predictive values (PPVs; probability of the outcome given exposure).

To study the pattern of transition from APS to hospitalization over time, Kaplan-Meier survival graphs were constructed for hospitalization for nonaffective psychotic or other psychiatric disorders as a function of baseline APS.

Finally, we estimated the interaction between social functioning, major depressive disorder, anxiety disorders, alcoholism, cannabis use, and exposure to trauma (factors that may increase the probability of transition from APS to psychotic disorder) on the one hand and the presence of any APS (weak or strong) on the other in the model predicting psychotic hospitalization. The statistical method for assessing interactions was similar to that applied previously4043 in that effects were expressed on the additive scale (ie, as a risk difference rather than a risk ratio) using risk difference regression in Stata statistical software, which fits generalized linear models estimating risk differences.44,45 The statistical significance of the interactions was assessed by the Wald test.46 After calculation of the interaction term, effect sizes of APSs stratified by level of moderator variables were calculated from the model using the appropriate linear combinations with the Stata LINCOM command. A sensitivity analysis modeling interactions on the multiplicative scale was performed as well.

BASELINE DEMOGRAPHIC CHARACTERISTICS AND APSs

The weighted mean (SD) age of the sample in 2007 was 53.7 (2.8) years; 50.2% were male. Of the sample, 57.2% reported at least 1 weak APS and 14.3% reported at least 1 strong APS in the year before the baseline assessment.

At baseline, the mean APS score was higher in younger individuals, subjects of North African origin, cannabis users, those who were single or divorced, and those who were unemployed (Table 1). A significant negative correlation was found between the mean APS score and years of education (r = −0.16; P < .001), indicating that APSs share some demographic patterns and risk factors with schizophrenia.2,47 There was a substantial positive correlation between the mean APS score and the level of nonspecific psychological distress (r = 0.56; P < .001), confirming previous work.15,27

Table Graphic Jump LocationTable 1. Distribution of Mean Ratings of Psychotic Experiences According to Demographic Variables
PREDICTION OF HOSPITALIZATION FOR NONAFFECTIVE PSYCHOTIC DISORDERS

To assess the effect of APSs on later hospitalization with no assumptions regarding the way in which APSs should be modeled, we examined the association using the mean scores of the PERI false beliefs and perceptions subscale. Higher mean levels of APS scores significantly increased the risk of later hospitalization for nonaffective psychotic disorder (OR = 3.60; 95% CI, 1.93-6.70), indicating that with every unit increase in the mean APS score, there was more than a 3-fold increase in the risk of later hospitalization for nonaffective psychotic disorder. This association remained stable when adjusting for age, sex, education, and ethnicity (OR = 4.31; 95% CI, 2.21-8.41).

Also, APSs were associated with increased risk for later hospitalization with an ICD-10 diagnosis of narrowly defined schizophrenia (ICD-10 codes F20.0-F20.9) (OR = 4.13; 95% CI, 2.21-7.71; adjusted OR = 5.35; 95% CI, 2.67-10.70). To increase power, for the remainder of the article we use hospitalization for all nonaffective psychotic disorders as the outcome of interest.

When using the dichotomous yes or no variable for the presence or absence of any APS, the regression model also showed increased association between the presence of any APS in the past year and risk of later hospitalization for a nonaffective psychotic disorder (OR = 4.64; 95% CI, 1.04-20.70; adjusted OR = 4.70; 95% CI, 1.05-21.06).

When examining the linear effects of the number of weak (possible range, 0-13) and strong (possible range, 0-13) APSs, a greater number of weak APSs (OR = 1.29; 95% CI, 1.09-1.53; adjusted OR = 1.30; 95% CI, 1.10-1.54) or strong APSs (OR = 1.35; 95% CI, 1.09-1.67; adjusted OR = 1.41; 95% CI, 1.10-1.82) significantly increased the risk of later hospitalization for a nonaffective psychotic disorder. This indicates that with every additional weak or strong APS, there was a 30% or 41% increase, respectively, in the risk of later hospitalization for a psychotic disorder.

Analysis with the 3-level variable representing no APS, any weak APS, or any strong APS revealed a monotonic dose-response association between the strength of the APS and risk of hospitalization for nonaffective psychotic disorder (Table 2).

Table Graphic Jump LocationTable 2. Psychotic Experiences and Association With Later Hospitalization for Nonaffective Psychotic Disordersa

In terms of population attributable risk, 36.0% (weak APS) and 33.0% (strong APS) of the hospitalizations for nonaffective psychotic disorder could be attributed, assuming causality, to the existence of APSs in the population at baseline. The PPV was 0.51% for weak APSs and 1.27% for strong APSs. The PPV was low for all individual APSs in the PERI, although some symptoms displayed higher values, particularly strong APSs of paranoia (“feeling that people wish to harm you”; PPV = 4.0%), delusional mood (“feeling that something odd is going on”; PPV = 3.5%), and thought withdrawal (“feeling that your thoughts are taken away”; PPV = 3.5%).

PREDICTION OF HOSPITALIZATION FOR OTHER PSYCHIATRIC DISORDERS

Higher mean APS ratings significantly increased the risk of later hospitalization for other psychiatric disorders (OR = 3.00; 95% CI, 1.57-5.73; adjusted OR = 2.21; 95% CI, 1.02-4.82). Examining linear effects of the number of weak and strong APSs on predicting later hospitalization for other psychiatric disorders revealed nonsignificant effects in the same direction. Analysis with the 3-level variable representing no APS, weak APS, or strong APS did not show a significant association between exposure to APS and other psychiatric hospitalizations (Table 3).

Table Graphic Jump LocationTable 3. Psychotic Experiences and Association With Later Hospitalization for Nonpsychotic Disordersa

The Kaplan-Meier survival curves for later hospitalization for nonaffective psychotic disorders showed that the increased risk associated with strong APSs was apparent mostly in the first 5 years after baseline (Figure 2A), whereas for other psychiatric disorders the risk incurred by APSs was more spread out during a period of 5 to 15 years (Figure 2B).

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Figure 2. Kaplan-Meier survival curves of strong psychotic experiences and hospitalization for nonaffective psychotic (A) or other, nonpsychotic (B) disorders. APSs indicates attenuated psychotic symptoms.

INTERACTIONS BETWEEN APSs AND OTHER VARIABLES ON RISK OF LATER PSYCHOTIC HOSPITALIZATION

Significant interactions were apparent between poor social functioning (χ21 = 5.85; P = .02) and anxiety disorders (χ21 = 9.29; P = .002) at baseline and the presence of any APS in predicting later nonaffective psychotic hospitalizations, suggesting that subjects with APSs and poor social functioning or an anxiety disorder are more prone to hospitalization for nonaffective psychotic disorders. No significant interaction was found between APSs and major depressive disorder, cannabis use, alcoholism, or exposure to trauma, but all interactions were in the hypothesized direction (eTable 2). No interactions were significant on the multiplicative scale, although trends were in a direction similar to that of the findings on the additive scale.

APSs AND LATER SEVERE MENTAL DISORDERS

Among the 4587 subjects sampled from a 10-year birth cohort of young adults and followed up for 24 years, 14.3% of the subjects reported at least 1 strong APS at baseline, but only 0.5% were hospitalized and clinically diagnosed as having a nonaffective psychotic disorder at follow-up. This discrepancy between APSs and clinical diagnoses of nonaffective psychotic disorder is similar to that reported by van Os et al48 in the Netherlands Mental Health Survey and Incidence Study (0.4% had nonaffective psychotic disorder; 18% reported APSs) and Kendler et al20 in the National Comorbidity Survey in the United States (0.7% had a clinical diagnosis; 28% reported APSs). Taken together, these findings confirm that in the general population, APSs are much more prevalent than clinically diagnosed psychotic disorders.

A dose-response relationship was observed, with risk for hospitalization increasing with an increasing number of APSs. This is consistent with earlier findings13 in which the more APSs there were, the greater the risk was of future psychiatric diagnosis and need for care. This report adds to the existing literature as it is the first to use hospitalization to assess outcome, is based on a birth cohort, and has the longest duration of follow-up. Although some APSs displayed particularly high ORs, the numbers were too small to address the question of whether true differences in predictive value exist as a function of type of APS.

The 95% CIs of weak and strong APSs overlap, suggesting that similar risk is associated with increasing levels of both weak and strong APSs. This may suggest that risk for transition from APSs to psychotic disorder is associated with a threshold effect rather than a linear dose response. Other work, however, is suggestive of a dose-response effect on risk for transition.12,13

Similar to previous reports,3,12 the association was significant between APSs and later psychiatric hospitalization but was much weaker for other psychiatric disorders, indicating that APSs might be general predictors of severe mental illness requiring hospitalization that lack both sensitivity and specificity. However, the Kaplan-Meier survival curve showing that almost all of the hospitalizations for nonaffective psychotic disorders in participants with strong APSs occur within 5 years of the baseline assessment (Figure 2A), while hospitalizations for other, nonpsychotic, psychiatric disorders in participants with strong APSs were spread over 15 years, may indicate some degree of specificity of APSs for nonaffective psychotic disorders.

INTERACTIONS

Given the relatively high attributable risk associated with APSs, it is crucial to learn more about the nature of the association between these nonclinical manifestations and psychotic disorders. One important clue may reside in the finding that the cumulative incidence of later psychotic hospitalization associated with APSs was much higher in respondents with poor social functioning at baseline than in those with normal or high social functioning. This is in line with the centrality of impaired social functioning in schizophrenia49 and with evidence emphasizing deficits in social functioning as increasing risk for later schizophrenia,24,38,40,50,51 suggesting that a poor outcome of APSs is contingent on the additional presence of poor social functioning.52,53 Most of the subsample assessed for social functioning reached predetermined cutoff values on the PERI26 or had a previously diagnosed psychiatric disorder. Unweighted, they would not be representative of the entire cohort. However, as described in “Methods,” 416 of the subjects (18.3%) who screened negative in the first stage went through the second stage of assessment in the epidemiological study. We included the weighted social functioning scores and rates of psychiatric diagnoses from these 416 “negatives” in the analyses.

The finding that the presence of anxiety disorders at baseline also significantly interacts with APSs in increasing risk of hospitalization for nonaffective psychotic disorders is in line with reports showing a central role for anxiety in relation to the onset of psychotic symptoms such as paranoia.54 The interaction with baseline depression was similarly large, albeit not statistically significant.

There was no indication that the risk of transition to psychotic hospitalization was affected by cannabis use. However, numbers were small and findings were directionally similar to those of social functioning.

The results from the investigations of these interactions should be interpreted with caution, as in all models the variables that made up the interaction (APSs on the one hand and social functioning, cannabis use, major depressive disorder, anxiety disorders, and alcoholism on the other) were significantly associated with each other. In practice, this means that it is difficult to distinguish between moderation (for example, poor social functioning increasing the likelihood of transition from APSs to later psychotic disorder) and mediation (poor social functioning increasing the risk of APSs, which in turn increase the likelihood of transition to psychotic disorder). Nevertheless, both mediation and moderation are important and clinically relevant in this context, and future studies should attempt to distinguish between the two.

IMPLICATIONS ON SCREENING FOR HIGH-RISK STATES

Given the fact that psychotic disorders are usually preceded by sometimes lengthy prodromes, attempts have been made to identify persons with future disorders when they are in the early stages of a psychosis prodrome.55,56 Considerable literature now exists on prodromal clinics that attempt to identify and characterize individuals who will convert to a clinical psychotic disorder in a reasonably short period.57,58 These prodromal clinics focus on individuals with attenuated or transitory psychotic symptoms, family history, and decline in functioning,59 and recent studies reported 12-month cumulative conversion rates of 10%60 and 11%.61

A major and hitherto unresolved issue regarding the interpretation of these studies is that the base risk of transition from APSs to clinically relevant psychotic disorders in the general population was not known. This study is the first with an unambiguous outcome of psychotic disorder, showing that in the general population, the base risk of transition from APSs to nonaffective psychotic disorder is around 1%, or one-tenth of the estimates in the prodromal literature, during a period of 5 years.

Therefore, the difference between this epidemiological study and the high-risk literature in terms of the PPV (1% vs 10%, respectively) and the time window of conversion (5 years vs 12 months, respectively) can be attributed to the selective sampling strategies used when collecting high-risk, prodromal samples. Our data suggest that the predictors identified by the prodromal clinics might not be relevant to individuals with APSs in the general population. However, it should be noted that the transition rate is likely to depend on the severity and type of APS, which may be skewed by inaccuracies in assessment that may arise from the use of lay-administered questionnaires.

LIMITATIONS

Diagnoses of psychotic disorders in this study were drawn from a hospitalization case registry. This could be of limited value if a large proportion of individuals with psychosis were never hospitalized. However, data from additional ongoing analyses of this Israeli cohort by our group (data not shown) indicate that 93% of the subjects diagnosed as having schizophrenia in the second stage of the study were hospitalized at least once during their lifetime. A related study from England62 of never-hospitalized patients with schizophrenia who were receiving outpatient treatment (hence not assessed independently of treatment status as in our epidemiological research) showed that 93.3% of outpatients with schizophrenia were eventually hospitalized at least once in their lifetime.

Although the registry diagnoses are clinical, not research, diagnoses, they are assigned by board-certified psychiatrists who had the benefit of observing the patients throughout 1 or more hospitalizations and had been trained and retrained in the use of the diagnostic criteria of the ICD-10 and DSM-IV. Studies that compared clinical diagnoses of schizophrenia assigned in state hospitals63 with research diagnoses have shown a high degree of concordance, and a previous study by our group comparing registry diagnoses with RDC diagnoses found that the sensitivity of the registry diagnosis of nonaffective psychotic disorders is 0.89, and that of schizophrenia is 0.87.22 In this article, in the interest of increasing power, the main outcome measure was hospitalization for all nonaffective psychotic disorders (ICD-10 codes F20.0-F29.9). However, APSs were also significantly associated with increased risk for later hospitalization for narrowly defined schizophrenia (ICD-10 codes F20.0-F20.9) (adjusted OR = 5.35; 95% CI, 2.67-10.70).

We are also limited by lack of data regarding emigrants. However, recent studies on schizophrenia and emigration argue against the possibility that patients more prone to schizophrenia are more likely to emigrate compared with those less prone to schizophrenia.64

A potential limitation is the age of the population (mean, 29.4 years), and in fact the mean APS score was slightly higher (approximately 0.2 effect sizes) in younger rather than older participants at baseline (Table 1). Doubtlessly, had we performed the baseline assessment at age 12 years and repeated assessments during years of follow-up, we would have a more complete picture of the relationship between APSs and nonaffective psychotic disorder during the life span, which might be different in adolescents and young adults. That being said, in a meta-analysis of APSs, younger age was not associated with the incidence of APSs and (as in this data set) was only weakly associated with prevalence.2,65

Similarly, one might think that the low transition rate of 0.5% is related to the age of the sample. However, we recently conducted a meta-analysis of transition rates in all available general population epidemiological samples, both young and old, and found similar low rates of transition (around 15 times lower than in high-risk samples).66 The limitations notwithstanding, the study has considerable strengths. These include its population-based historical-prospective design, the clinical register follow-up decreasing the danger of false-positive diagnoses generated by lay interviews, minimization of false-negatives caused by nonresponders in interview-based studies, and the ability to exclude all psychotically ill individuals at baseline on the basis of clinical interview.

In summary, self-reported APSs signal risk for later nonaffective psychotic disorder but are not clinically useful as predictors. This relationship between APSs and psychotic disorders is supported by other work showing that APSs are associated with epidemiological risk factors and molecular genetic variation associated with psychotic disorders.67 Ultimately, greater understanding of the molecular and cognitive mechanisms of both APSs and psychotic disorders will lead to identification of clinically relevant biological markers predicting which person with an APS will go on to have a psychotic disorder, hence enabling early identification and intervention in psychotic illness.

Correspondence: Mark Weiser, MD, Department of Psychiatry, Sheba Medical Center, Tel Hashomer, Ramat Gan, 52621, Israel (mweiser@netvision.net.il).

Submitted for Publication: August 25, 2011; accepted October 12, 2011.

Published Online: January 2, 2012. doi:10.1001/archgenpsychiatry.2011.1580. Corrected on February 10, 2012.

Financial Disclosure: None reported.

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Fanous A, Gardner C, Walsh D, Kendler KS. Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives.  Arch Gen Psychiatry. 2001;58(7):669-673
PubMed   |  Link to Article
Hanssen M, Krabbendam L, Vollema M, Delespaul P, van Os J. Evidence for instrument and family-specific variation of subclinical psychosis dimensions in the general population.  J Abnorm Psychol. 2006;115(1):5-14
PubMed   |  Link to Article
Kendler KS, McGuire M, Gruenberg AM, O’Hare A, Spellman M, Walsh D. The Roscommon Family Study, III: schizophrenia-related personality disorders in relatives.  Arch Gen Psychiatry. 1993;50(10):781-788
PubMed   |  Link to Article
Lataster T, Myin-Germeys I, Derom C, Thiery E, van Os J. Evidence that self-reported psychotic experiences represent the transitory developmental expression of genetic liability to psychosis in the general population.  Am J Med Genet B Neuropsychiatr Genet. 2009;150B(8):1078-1084
PubMed   |  Link to Article
Lenzenweger MF, Loranger AW. Detection of familial schizophrenia using a psychometric measure of schizotypy.  Arch Gen Psychiatry. 1989;46(10):902-907
PubMed   |  Link to Article
Vollema MG, Sitskoorn MM, Appels MC, Kahn RS. Does the Schizotypal Personality Questionnaire reflect the biological-genetic vulnerability to schizophrenia?  Schizophr Res. 2002;54(1-2):39-45
PubMed   |  Link to Article
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks: US population data.  Arch Intern Med. 1993;153(5):598-615
PubMed   |  Link to Article
Dominguez MD, Wichers M, Lieb R, Wittchen HU, van Os J. Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study.  Schizophr Bull. 2011;37(1):84-93
PubMed   |  Link to Article
Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H. Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study.  Arch Gen Psychiatry. 2000;57(11):1053-1058
PubMed   |  Link to Article
Hanssen M, Bak M, Bijl R, Vollebergh W, van Os J. The incidence and outcome of subclinical psychotic experiences in the general population.  Br J Clin Psychol. 2005;44(pt 2):181-191
PubMed   |  Link to Article
Welham J, Scott J, Williams G, Najman J, Bor W, O’Callaghan M, McGrath J. Emotional and behavioural antecedents of young adults who screen positive for non-affective psychosis: a 21-year birth cohort study.  Psychol Med. 2009;39(4):625-634
PubMed   |  Link to Article
Varghese D, Scott J, Welham J, Bor W, Najman J, O’Callaghan M, Williams G, McGrath J. Psychotic-like experiences in major depression and anxiety disorders: a population-based survey in young adults.  Schizophr Bull. 2011;37(2):389-393
PubMed   |  Link to Article
Yung AR, Buckby JA, Cosgrave EM, Killackey EJ, Baker K, Cotton SM, McGorry PD. Association between psychotic experiences and depression in a clinical sample over 6 months.  Schizophr Res. 2007;91(1-3):246-253
PubMed   |  Link to Article
World Health Organization.  Composite International Diagnostic Interview (CIDI), Version 1.0. Geneva, Switzerland: World Health Organization; 1990
Anthony JC, Folstein M, Romanoski AJ, Von Korff MR, Nestadt GR, Chahal R, Merchant A, Brown CH, Shapiro S, Kramer M, Gruenberg EM. Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis: experience in eastern Baltimore.  Arch Gen Psychiatry. 1985;42(7):667-675
PubMed   |  Link to Article
Helzer JE, Robins LN, McEvoy LT, Spitznagel EL, Stoltzman RK, Farmer A, Brockington IF. A comparison of clinical and diagnostic interview schedule diagnoses: physician reexamination of lay-interviewed cases in the general population.  Arch Gen Psychiatry. 1985;42(7):657-666
PubMed   |  Link to Article
Kendler KS, Gallagher TJ, Abelson JM, Kessler RC. Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample: the National Comorbidity Survey.  Arch Gen Psychiatry. 1996;53(11):1022-1031
PubMed   |  Link to Article
Levav I, Grinshpoon A. Mental health services in Israel.  Int Psychiatry. 2004;4:10-14
Weiser M, Kanyas K, Malaspina D, Harvey PD, Glick I, Goetz D, Karni O, Yakir A, Turetsky N, Fennig S, Nahon D, Lerer B, Davidson M. Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National Hospitalization Registry compared with RDC diagnoses based on SADS-L.  Compr Psychiatry. 2005;46(1):38-42
PubMed   |  Link to Article
Cougnard A, Marcelis M, Myin-Germeys I, De Graaf R, Vollebergh W, Krabbendam L, Lieb R, Wittchen HU, Henquet C, Spauwen J, van Os J. Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? a psychosis proneness-persistence model.  Psychol Med. 2007;37(4):513-527
PubMed   |  Link to Article
Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents.  Am J Psychiatry. 1999;156(9):1328-1335
PubMed
Krabbendam L, Myin-Germeys I, Hanssen M, de Graaf R, Vollebergh W, Bak M, van Os J. Development of depressed mood predicts onset of psychotic disorder in individuals who report hallucinatory experiences.  Br J Clin Psychol. 2005;44(pt 1):113-125
PubMed   |  Link to Article
Shrout PE, Dohrenwend BP, Levav I. A discriminant rule for screening cases of diverse diagnostic types: preliminary results.  J Consult Clin Psychol. 1986;54(3):314-319
PubMed   |  Link to Article
van Rossum I, Dominguez MD, Lieb R, Wittchen H-U, van Os J. Affective dysregulation and reality distortion: a 10-year prospective study of their association and clinical relevance.  Schizophr Bull. 2011;37(3):561-571
PubMed   |  Link to Article
van Os J, Kapur S. Schizophrenia.  Lancet. 2009;374(9690):635-645
PubMed   |  Link to Article
Dohrenwend BP, Levav I, Shrout PE, Schwartz S, Naveh G, Link BG, Skodol AE, Stueve A. Socioeconomic status and psychiatric disorders: the causation-selection issue.  Science. 1992;255(5047):946-952
PubMed   |  Link to Article
Levav I, Kohn R, Dohrenwend BP, Shrout PE, Skodol AE, Schwartz S, Link BG, Naveh G. An epidemiological study of mental disorders in a 10-year cohort of young adults in Israel.  Psychol Med. 1993;23(3):691-707
PubMed   |  Link to Article
Dohrenwend BP. “The problem of validity in field studies of psychological disorders” revisited.  Psychol Med. 1990;20(1):195-208
PubMed   |  Link to Article
Dohrenwend BP, Shrout PE, Egri G, Mendelsohn FS. Nonspecific psychological distress and other dimensions of psychopathology: measures for use in the general population.  Arch Gen Psychiatry. 1980;37(11):1229-1236
PubMed   |  Link to Article
Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia.  Arch Gen Psychiatry. 1978;35(7):837-844
PubMed   |  Link to Article
Hanssen MS, Bijl RV, Vollebergh W, van Os J. Self-reported psychotic experiences in the general population: a valid screening tool for DSM-III-R psychotic disorders?  Acta Psychiatr Scand. 2003;107(5):369-377
PubMed   |  Link to Article
van Os J, Hanssen M, Bijl RV, Vollebergh W. Prevalence of psychotic disorder and community level of psychotic symptoms: an urban-rural comparison.  Arch Gen Psychiatry. 2001;58(7):663-668
PubMed   |  Link to Article
Roberts RE, Vernon SW. Usefulness of the PERI demoralization scale screen for psychiatric disorder in a community sample.  Psychiatry Res. 1981;5(2):183-193
PubMed   |  Link to Article
Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders. 3rd ed. New York: Research Assessment and Training Unit, New York State Psychiatric Institute; 1981
Yung AR, Phillips LJ, Yuen HP, Francey SM, McFarlane CA, Hallgren M, McGorry PD. Psychosis prediction: 12-month follow up of a high-risk (“prodromal”) group.  Schizophr Res. 2003;60(1):21-32
PubMed   |  Link to Article
Hennekens CH, Buring JE. Epidemiology in Medicine. Toronto, ON: Little Brown & Co; 1987
Addington J, Addington D. Patterns of premorbid functioning in first episode psychosis: relationship to 2-year outcome.  Acta Psychiatr Scand. 2005;112(1):40-46
PubMed   |  Link to Article
Krabbendam L, Myin-Germeys I, De Graaf R, Vollebergh W, Nolen WA, Iedema J, van Os J. Dimensions of depression, mania and psychosis in the general population.  Psychol Med. 2004;34(7):1177-1186
PubMed   |  Link to Article
Spauwen J, Krabbendam L, Lieb R, Wittchen HU, van Os J. Evidence that the outcome of developmental expression of psychosis is worse for adolescents growing up in an urban environment.  Psychol Med. 2006;36(3):407-415
PubMed   |  Link to Article
van Os J, Hanssen M, Bak M, Bijl RV, Vollebergh W. Do urbanicity and familial liability coparticipate in causing psychosis?  Am J Psychiatry. 2003;160(3):477-482
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Hardin JW, Cleves MA. Generalized linear models: extensions to the binominal family: seb29.  Stata Tech Bull. 1999;50:21-25
Wacholder S. Binomial regression in GLIM: estimating risk ratios and risk differences.  Am J Epidemiol. 1986;123(1):174-184
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Clayton D, Hills M. Wald tests. In: Clayton D, Hills M, eds. Statistical Models in Epidemiology. Oxford, England: Oxford University Press; 1993:101-102
Polanczyk G, Moffitt TE, Arseneault L, Cannon M, Ambler A, Keefe RS, Houts R, Odgers CL, Caspi A. Etiological and clinical features of childhood psychotic symptoms: results from a birth cohort.  Arch Gen Psychiatry. 2010;67(4):328-338
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van Os J, Hanssen M, Bijl RV, Ravelli A. Strauss (1969) revisited: a psychosis continuum in the general population?  Schizophr Res. 2000;45(1-2):11-20
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American Psychiatric Association.  Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000
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Rabinowitz J, Reichenberg A, Weiser M, Mark M, Kaplan Z, Davidson M. Cognitive and behavioural functioning in men with schizophrenia both before and shortly after first admission to hospital: cross-sectional analysis.  Br J Psychiatry. 2000;177:26-32
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Murray RM, Sham P, van Os J, Zanelli J, Cannon M, McDonald C. A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder.  Schizophr Res. 2004;71(2-3):405-416
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Kaymaz N, van Os J. Murray et al (2004) revisited: is bipolar disorder identical to schizophrenia without developmental impairment?  Acta Psychiatr Scand. 2009;120(4):249-252
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Freeman D. Suspicious minds: the psychology of persecutory delusions.  Clin Psychol Rev. 2007;27(4):425-457
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Marshall M, Rathbone J. Early intervention for psychosis.  Cochrane Database Syst Rev. 2006;(4):CD004718
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Yung AR, McGorry PD. The prodromal phase of first-episode psychosis: past and current conceptualizations.  Schizophr Bull. 1996;22(2):353-370
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van Os J, Delespaul P. Toward a world consensus on prevention of schizophrenia.  Dialogues Clin Neurosci. 2005;7(1):53-67
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Bosanac P, Patton GC, Castle DJ. Early intervention in psychotic disorders: faith before facts?  Psychol Med. 2010;40(3):353-358
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Olsen KA, Rosenbaum B. Prospective investigations of the prodromal state of schizophrenia: assessment instruments.  Acta Psychiatr Scand. 2006;113(4):273-282
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Cannon TD, Cadenhead K, Cornblatt B, Woods SW, Addington J, Walker E, Seidman LJ, Perkins D, Tsuang M, McGlashan T, Heinssen R. Prediction of psychosis in youth at high clinical risk: a multisite longitudinal study in North America.  Arch Gen Psychiatry. 2008;65(1):28-37
PubMed   |  Link to Article
Ruhrmann S, Schultze-Lutter F, Salokangas RK, Heinimaa M, Linszen D, Dingemans P, Birchwood M, Patterson P, Juckel G, Heinz A, Morrison A, Lewis S, von Reventlow HG, Klosterkötter J. Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study.  Arch Gen Psychiatry. 2010;67(3):241-251
PubMed   |  Link to Article
Geddes JR, Kendell RE. Schizophrenic subjects with no history of admission to hospital.  Psychol Med. 1995;25(4):859-868
PubMed   |  Link to Article
Pulver AE, Carpenter WT, Adler L, McGrath J. Accuracy of the diagnoses of affective disorders and schizophrenia in public hospitals.  Am J Psychiatry. 1988;145(2):218-220
PubMed
Selten JP, Cantor-Graae E, Kahn RS. Migration and schizophrenia.  Curr Opin Psychiatry. 2007;20(2):111-115
PubMed   |  Link to Article
Linscott RJ, van Os J. Systematic reviews of categorical versus continuum models in psychosis: evidence for discontinuous subpopulations underlying a psychometric continuum: implications for DSM-V, DSM-VI, and DSM-VII Annu Rev Clin Psychol. 2010;6:391-419
PubMed   |  Link to Article
Kaymaz N, Lataster T, Lieb R, Wittchen HU, Werbeloff N, Weiser M, van Os J, Drukker M. The case of the missing evidence: do psychotic experiences predict clinical outcomes in unselected population-based samples? a systematic review and meta-analysis, enriched with new results.  Psychol Med. 2011;In press
Stefanis NC, Trikalinos TA, Avramopoulos D, Smyrnis N, Evdokimidis I, Ntzani EE, Ioannidis JP, Stefanis CN. Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level.  Biol Psychiatry. 2007;62(7):784-792
PubMed   |  Link to Article

Figures

Place holder to copy figure label and caption
Graphic Jump Location

Figure 1. Study population. RDC indicates Research Diagnostic Criteria.

Place holder to copy figure label and caption
Graphic Jump Location

Figure 2. Kaplan-Meier survival curves of strong psychotic experiences and hospitalization for nonaffective psychotic (A) or other, nonpsychotic (B) disorders. APSs indicates attenuated psychotic symptoms.

Tables

Table Graphic Jump LocationTable 1. Distribution of Mean Ratings of Psychotic Experiences According to Demographic Variables
Table Graphic Jump LocationTable 2. Psychotic Experiences and Association With Later Hospitalization for Nonaffective Psychotic Disordersa
Table Graphic Jump LocationTable 3. Psychotic Experiences and Association With Later Hospitalization for Nonpsychotic Disordersa

References

Sadock BJ, Sadock VA. Synopsis of Psychiatry: Behavioral Sciences, Clinical Psychiatry. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2007
van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis proneness-persistence-impairment model of psychotic disorder.  Psychol Med. 2009;39(2):179-195
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Chapman LJ, Chapman JP, Kwapil TR, Eckblad M, Zinser MC. Putatively psychosis-prone subjects 10 years later.  J Abnorm Psychol. 1994;103(2):171-183
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Fanous A, Gardner C, Walsh D, Kendler KS. Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives.  Arch Gen Psychiatry. 2001;58(7):669-673
PubMed   |  Link to Article
Hanssen M, Krabbendam L, Vollema M, Delespaul P, van Os J. Evidence for instrument and family-specific variation of subclinical psychosis dimensions in the general population.  J Abnorm Psychol. 2006;115(1):5-14
PubMed   |  Link to Article
Kendler KS, McGuire M, Gruenberg AM, O’Hare A, Spellman M, Walsh D. The Roscommon Family Study, III: schizophrenia-related personality disorders in relatives.  Arch Gen Psychiatry. 1993;50(10):781-788
PubMed   |  Link to Article
Lataster T, Myin-Germeys I, Derom C, Thiery E, van Os J. Evidence that self-reported psychotic experiences represent the transitory developmental expression of genetic liability to psychosis in the general population.  Am J Med Genet B Neuropsychiatr Genet. 2009;150B(8):1078-1084
PubMed   |  Link to Article
Lenzenweger MF, Loranger AW. Detection of familial schizophrenia using a psychometric measure of schizotypy.  Arch Gen Psychiatry. 1989;46(10):902-907
PubMed   |  Link to Article
Vollema MG, Sitskoorn MM, Appels MC, Kahn RS. Does the Schizotypal Personality Questionnaire reflect the biological-genetic vulnerability to schizophrenia?  Schizophr Res. 2002;54(1-2):39-45
PubMed   |  Link to Article
Stamler J, Stamler R, Neaton JD. Blood pressure, systolic and diastolic, and cardiovascular risks: US population data.  Arch Intern Med. 1993;153(5):598-615
PubMed   |  Link to Article
Dominguez MD, Wichers M, Lieb R, Wittchen HU, van Os J. Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study.  Schizophr Bull. 2011;37(1):84-93
PubMed   |  Link to Article
Poulton R, Caspi A, Moffitt TE, Cannon M, Murray R, Harrington H. Children's self-reported psychotic symptoms and adult schizophreniform disorder: a 15-year longitudinal study.  Arch Gen Psychiatry. 2000;57(11):1053-1058
PubMed   |  Link to Article
Hanssen M, Bak M, Bijl R, Vollebergh W, van Os J. The incidence and outcome of subclinical psychotic experiences in the general population.  Br J Clin Psychol. 2005;44(pt 2):181-191
PubMed   |  Link to Article
Welham J, Scott J, Williams G, Najman J, Bor W, O’Callaghan M, McGrath J. Emotional and behavioural antecedents of young adults who screen positive for non-affective psychosis: a 21-year birth cohort study.  Psychol Med. 2009;39(4):625-634
PubMed   |  Link to Article
Varghese D, Scott J, Welham J, Bor W, Najman J, O’Callaghan M, Williams G, McGrath J. Psychotic-like experiences in major depression and anxiety disorders: a population-based survey in young adults.  Schizophr Bull. 2011;37(2):389-393
PubMed   |  Link to Article
Yung AR, Buckby JA, Cosgrave EM, Killackey EJ, Baker K, Cotton SM, McGorry PD. Association between psychotic experiences and depression in a clinical sample over 6 months.  Schizophr Res. 2007;91(1-3):246-253
PubMed   |  Link to Article
World Health Organization.  Composite International Diagnostic Interview (CIDI), Version 1.0. Geneva, Switzerland: World Health Organization; 1990
Anthony JC, Folstein M, Romanoski AJ, Von Korff MR, Nestadt GR, Chahal R, Merchant A, Brown CH, Shapiro S, Kramer M, Gruenberg EM. Comparison of the lay Diagnostic Interview Schedule and a standardized psychiatric diagnosis: experience in eastern Baltimore.  Arch Gen Psychiatry. 1985;42(7):667-675
PubMed   |  Link to Article
Helzer JE, Robins LN, McEvoy LT, Spitznagel EL, Stoltzman RK, Farmer A, Brockington IF. A comparison of clinical and diagnostic interview schedule diagnoses: physician reexamination of lay-interviewed cases in the general population.  Arch Gen Psychiatry. 1985;42(7):657-666
PubMed   |  Link to Article
Kendler KS, Gallagher TJ, Abelson JM, Kessler RC. Lifetime prevalence, demographic risk factors, and diagnostic validity of nonaffective psychosis as assessed in a US community sample: the National Comorbidity Survey.  Arch Gen Psychiatry. 1996;53(11):1022-1031
PubMed   |  Link to Article
Levav I, Grinshpoon A. Mental health services in Israel.  Int Psychiatry. 2004;4:10-14
Weiser M, Kanyas K, Malaspina D, Harvey PD, Glick I, Goetz D, Karni O, Yakir A, Turetsky N, Fennig S, Nahon D, Lerer B, Davidson M. Sensitivity of ICD-10 diagnosis of psychotic disorders in the Israeli National Hospitalization Registry compared with RDC diagnoses based on SADS-L.  Compr Psychiatry. 2005;46(1):38-42
PubMed   |  Link to Article
Cougnard A, Marcelis M, Myin-Germeys I, De Graaf R, Vollebergh W, Krabbendam L, Lieb R, Wittchen HU, Henquet C, Spauwen J, van Os J. Does normal developmental expression of psychosis combine with environmental risk to cause persistence of psychosis? a psychosis proneness-persistence model.  Psychol Med. 2007;37(4):513-527
PubMed   |  Link to Article
Davidson M, Reichenberg A, Rabinowitz J, Weiser M, Kaplan Z, Mark M. Behavioral and intellectual markers for schizophrenia in apparently healthy male adolescents.  Am J Psychiatry. 1999;156(9):1328-1335
PubMed
Krabbendam L, Myin-Germeys I, Hanssen M, de Graaf R, Vollebergh W, Bak M, van Os J. Development of depressed mood predicts onset of psychotic disorder in individuals who report hallucinatory experiences.  Br J Clin Psychol. 2005;44(pt 1):113-125
PubMed   |  Link to Article
Shrout PE, Dohrenwend BP, Levav I. A discriminant rule for screening cases of diverse diagnostic types: preliminary results.  J Consult Clin Psychol. 1986;54(3):314-319
PubMed   |  Link to Article
van Rossum I, Dominguez MD, Lieb R, Wittchen H-U, van Os J. Affective dysregulation and reality distortion: a 10-year prospective study of their association and clinical relevance.  Schizophr Bull. 2011;37(3):561-571
PubMed   |  Link to Article
van Os J, Kapur S. Schizophrenia.  Lancet. 2009;374(9690):635-645
PubMed   |  Link to Article
Dohrenwend BP, Levav I, Shrout PE, Schwartz S, Naveh G, Link BG, Skodol AE, Stueve A. Socioeconomic status and psychiatric disorders: the causation-selection issue.  Science. 1992;255(5047):946-952
PubMed   |  Link to Article
Levav I, Kohn R, Dohrenwend BP, Shrout PE, Skodol AE, Schwartz S, Link BG, Naveh G. An epidemiological study of mental disorders in a 10-year cohort of young adults in Israel.  Psychol Med. 1993;23(3):691-707
PubMed   |  Link to Article
Dohrenwend BP. “The problem of validity in field studies of psychological disorders” revisited.  Psychol Med. 1990;20(1):195-208
PubMed   |  Link to Article
Dohrenwend BP, Shrout PE, Egri G, Mendelsohn FS. Nonspecific psychological distress and other dimensions of psychopathology: measures for use in the general population.  Arch Gen Psychiatry. 1980;37(11):1229-1236
PubMed   |  Link to Article
Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia.  Arch Gen Psychiatry. 1978;35(7):837-844
PubMed   |  Link to Article
Hanssen MS, Bijl RV, Vollebergh W, van Os J. Self-reported psychotic experiences in the general population: a valid screening tool for DSM-III-R psychotic disorders?  Acta Psychiatr Scand. 2003;107(5):369-377
PubMed   |  Link to Article
van Os J, Hanssen M, Bijl RV, Vollebergh W. Prevalence of psychotic disorder and community level of psychotic symptoms: an urban-rural comparison.  Arch Gen Psychiatry. 2001;58(7):663-668
PubMed   |  Link to Article
Roberts RE, Vernon SW. Usefulness of the PERI demoralization scale screen for psychiatric disorder in a community sample.  Psychiatry Res. 1981;5(2):183-193
PubMed   |  Link to Article
Spitzer RL, Endicott J, Robins E. Research Diagnostic Criteria (RDC) for a Selected Group of Functional Disorders. 3rd ed. New York: Research Assessment and Training Unit, New York State Psychiatric Institute; 1981
Yung AR, Phillips LJ, Yuen HP, Francey SM, McFarlane CA, Hallgren M, McGorry PD. Psychosis prediction: 12-month follow up of a high-risk (“prodromal”) group.  Schizophr Res. 2003;60(1):21-32
PubMed   |  Link to Article
Hennekens CH, Buring JE. Epidemiology in Medicine. Toronto, ON: Little Brown & Co; 1987
Addington J, Addington D. Patterns of premorbid functioning in first episode psychosis: relationship to 2-year outcome.  Acta Psychiatr Scand. 2005;112(1):40-46
PubMed   |  Link to Article
Krabbendam L, Myin-Germeys I, De Graaf R, Vollebergh W, Nolen WA, Iedema J, van Os J. Dimensions of depression, mania and psychosis in the general population.  Psychol Med. 2004;34(7):1177-1186
PubMed   |  Link to Article
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Supplemental Content

Werbeloff N, Drukker M, Dohrenwend BP, Levav I, Yoffe R, van Os J, Davidson M, Weiser M. Self-reported attenuated psychotic symptoms as forerunners of severe mental disorders later in life. Arch Gen Psychiatry. Published online January 2, 2012. doi:10.1001/archgenpsychiatry.2011.1580.

eAppendix. Elaboration of Methods section: APS variables created for the statistical analyses

eTable 1. Comparison of CIDI psychosis items with the PERI false beliefs and perceptions subscale

eTable 2. Moderating effect of social functioning, major depressive disorder, alcoholism*, cannabis use and exposure to trauma** on the association between psychotic experiences and hospitalization for nonaffective psychotic disorder (weighted)

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