What is the relative importance of self reported psychotic symptoms in epidemiological studies? Results from the ESEMeD Catalonia Study

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1 Available online at Schizophrenia Research 102 (2008) What is the relative importance of self reported psychotic symptoms in epidemiological studies? Results from the ESEMeD Catalonia Study Susana Ochoa a,, Josep Maria Haro a, Juan Vicente Torres a, Alejandra Pinto-Meza a, Concepció Palacín a, Mariola Bernal a, Traolach Brugha b, Bibiana Prat a, Judith Usall a, Jordi Alonso c, Jaume Autonell a a Sant Joan de Déu-Serveis de Salut Mental, Fundació Sant Joan de Déu., Dr. Pujades, 42, Sant Boi de Llobregat, Barcelona, CIBERSAM Spain b General Hospital of Leicester, University of Leicester, Gwendolen Road, Leicester LE5 4PW c Health Services Research Unit, IMIM-Hospital del Mar, Passeig Marítim, 25-29, CIBERESP Spain Received 27 December 2007; received in revised form 4 April 2008; accepted 8 April 2008 Available online 20 May 2008 Abstract Different prevalence of non-affective psychosis has been reported in general population surveys. The objectives of this study were to describe lifetime prevalence of non-affective psychosis in Catalonia, Spain; and to analyze the use of the CIDI psychosis module as a screening instrument for psychotic disorders. As part of the ESEMeD project in Catalonia, 1645 respondents were assessed with the CIDI. Respondents who scored positively to any of the CIDI psychosis screen questions, who had been hospitalised for a psychiatric reason or had received antipsychotic medication were re-assessed with the SCID-I by a clinician. The results showed that 11.18% people of the sample had lifetime self reported psychotic symptoms using the CIDI. After a clinical interview with the SCID-I, between 0.85 and 2.37% of the sample had a psychotic disorder, and 0.48% 1.58% had schizophrenia. The most frequent reported psychotic symptoms in individuals without a psychotic disorder were those related with hearing or seeing something missing during a bereavement period. Experiencing mind control, feeling that your mind was being controlled by strange forces, experiencing attempts of communications (CIDI questions) and taking medication were the items that discriminate between non-affective psychosis cases and negatives. Only experiencing mind control was associated with psychotic disorders in a logistic regression analysis. The main conclusions are that the use of lay-administered interviews should only be used as a screening instrument in the detection of psychosis in general population surveys because the majority of self reported psychotic symptoms have not been found to be associated with a psychotic disorder Elsevier B.V. All rights reserved. Keywords: Prevalence; Psychosis; Schizophrenia; Epidemiology 1. Introduction Corresponding author. Research and Developmental Unit, Sant Joan de Déu-Serveis de Salut Mental, C/Dr. Pujades, 42, Sant Boi de Llobregat, Barcelona, Spain. Tel.: x address: sochoa@sjd-ssm.com (S. Ochoa). Many authors have postulated that lifetime prevalence of schizophrenia and non-affective psychosis is around 1% and little variation is observed across countries, cultural groups, and gender (Mueser and McGurk, 2004) /$ - see front matter 2008 Elsevier B.V. All rights reserved. doi: /j.schres

2 262 S. Ochoa et al. / Schizophrenia Research 102 (2008) However, in Goldner et al. (2002) systematic review, they identified 18 studies that estimated the prevalence of schizophrenia and found that, in fact, the results showed significant heterogeneity. Differences have been reported according to participants' gender, geographical area (e.g. rural or urban) and country (e.g. developed or developing). For example, recent studies have reported more men with schizophrenia than women (Andia et al., 1995; Usall et al., 2001). Some authors (Mortensen et al., 1999; Van Os et al., 2003, 2004) have also found that prevalence of psychosis was higher in urban areas. Moreover, others factors as older paternal age, prenatal complications and winter birth have been described as an increased risk of schizophrenia as suggested by McGrath (2007). Overall prevalence in Goldner et al. (2002) review resulted in a figure around 0.55%, similar to previous prevalence studies. In the last decade, epidemiological studies using questionnaires administered by lay interviewers have allowed recruited larger samples of population. Many of these instruments include questions to assess psychotic symptoms, and the information obtained depends on the instrument used (Spengler and Wittchen, 1988). It is thus appealing to use this method to estimate the prevalence of schizophrenia and non-affective psychosis in the general population. Several of these studies have found very high prevalence figures of psychotic symptoms in community samples. For example, Kendler et al. (1996) found that 28% of general population answered positively to at least one of the psychosis screening questions. However, in the clinical interview, the rate of non-affective psychosis decreased to only %. In a study by Van Os et al. (2001), assessing a total of 7076 participants from the general population with the Composite International Diagnostic Interview (CIDI) (Cooper et al., 1998), it was found that 17.5% of the population responded positively to at least one of the psychotic symptoms. After a clinician re-interview, the total prevalence of psychosis (affective or non-affective) was 4.2%. Hanssen et al. (2003) in the same study found that the prevalence of non-affective psychosis and affective psychosis (considering DSM-III-R criteria) was 0.4% and 1.1%, respectively. In the United Kingdom, Johns et al. (2004) found that a 5.5% of the respondents to the Psychosis Screening Questionnaire answered positively to at least one of the questions. In summary, prevalence figures for self reported psychotic symptoms using structured interviews are high while the frequency of individuals fulfilling criteria for schizophrenia (Bijl et al., 1998a) or non-affective psychosis (Van Os et al., 2001) is low. Other epidemiological surveys have also been carried out using semi-structured clinical diagnostic interviews. The prevalence of psychosis was found to be around 0.4% in Great Britain (Singleton et al., 2001), very similar to findings in Australia (Jablensky et al., 1992). Recently, in Finland, a prevalence of 1.94 was found for non-affective psychosis and of 0.87 for schizophrenia (Perala et al., 2007). These discrepancies highlight the need to clarify what is the real clinical meaning and interpretation of prevalence figures for psychotic symptoms in the general population with the use of lay-administered (self report) interviews in the assessment of prevalence of nonaffective psychosis. The aims of the present study are 1) to describe lifetime prevalence of non-affective psychosis in the general population of Catalonia (Spain) based on the assessment made by clinicians administering the Structured Clinical Interview for DSM-IV Disorders (SCID-I) (First et al., 1996) and compare it with the prevalence of psychotic symptoms as obtained by lay interviewers administering the CIDI; 2) to describe the explanations given by respondents to positive psychotic symptoms reported in the CIDI; and 3) to determine which CIDI items and sociodemographic characteristics could be associate with a diagnosis of non-affective psychosis on the SCID-I. 2. Methods 2.1. Participants The present study is part of the European Study of the Epidemiology of Mental Disorders (ESEMeD). ESEMeD included a cross-sectional face-to-face household interview survey carried out in a representative sample of the non-institutionalized adult population (aged 18 years or older) of Catalonia, Spain. A stratified multistage probability sample without replacement was drawn. In a face-to-face contact, the interviewer approached each selected household. In the households that accepted to participate, the interviewer made a listing of all adults living there. A computer system randomly selected one of them. Overall response rate was 78.6%. A total of 1645 respondents were assessed between June 2001 and July Catalonia, which capital is Barcelona, is an autonomous region of the North-East of Spain with a population of more than seven million people (Idescat, 2007). It is one of the most developed parts of the country. Although inhabitants are also fluent in Spanish, it has its own language, Catalan. The population has around 10% of immigrants from outside Spain.

3 S. Ochoa et al. / Schizophrenia Research 102 (2008) A full description of the sampling and methods of the ESEMeD Spain study has been reported elsewhere (Alonso et al., 2004; Haro et al., 2003) Material A revised version of the Composite International Diagnostic Interview (CIDI 3.0) (Cooper et al., 1998) was administered at home using a computer-assisted interview, designed to facilitate its administration (Andrews and Peters, 1998). The CIDI 3.0 is a comprehensive, fully structured diagnostic interview for the assessment of mental disorders. It provides, by means of computerized algorithms, diagnoses according to the International Classification of Diseases (ICD-10) (ISCDRHP, 1992) and the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) (APA, 1996). The criteria to define a probable psychosis case were based on previous studies (Eaton, 1986). The lifetime diagnosis of probable psychosis was determined if the respondent scored positively to any of the psychosis screening question of the CIDI, or was hospitalised at any time in his/her life for a psychiatric reason or received antipsychotic medication treatment in the past year. We also used the psychotic and associated symptoms module of the research version of the Structured Clinical Interview for DSM-IVAxis I Disorders: SCID-I (First et al., 1996), for assessing people with positive probable psychosis assessed by the CIDI Procedure After CIDI administration, all individuals were asked if they would accept to be re-interviewed. The individuals who accepted were asked to provide their telephone number. Individuals who were positives in psychosis screen were included in the second phase. In this second phase, participants were re-interviewed over the telephone by a clinical psychologist, who administered the SCID-I Psychotic and associated symptoms module. The SCID- I conducted over the telephone is a valid assessment procedure which provides similar results than in-person administration (Cacciola et al., 1999). Moreover, in six cases, SCID-I interviews were conducted in-person after the telephone interview. In the six cases, the diagnostic results were the same in both assessments Statistical analyses The standard errors of prevalence, logistic regression coefficients, and other statistics were estimated taking into account the sample design, by using the Taylor series linearization method. Estimates were weighted to restore full representation of the data, according to the sociodemographic characteristics of the population of Spain and according to the probability of selection for the professional assessment. Individuals were weighted to account for the different probabilities of selection within household and among hard to reach individuals, as well as restore age and gender distribution of the general population. An additional weight was used to adjust for differences in probability of selection into the sample. Associations between responders and non-responders in sociodemographic and clinical characteristics were estimated using the likelihood ratio chi-square statistic with the Rao Scott's correction for complex sampling. The comparison between probable psychosis (CIDI) cases and non-affective psychosis (SCID-I) identified cases was done using the likelihood ratio chi-square statistic with the Rao Scott's correction for complex sampling. Given the small sample size, categories were grouped in those variables with few cases in some categories. The total of CIDI questions asked by responders and non-responders, and by CIDI positive and SCID-I positive were calculated using a general lineal model because the distribution of the sample was not normal. In order to determine which CIDI items and sociodemographic characteristics could be associated to a diagnosis of non-affective psychosis according to the SCID-I assessment, a survey logistic regression with a forward selection method was performed. The dependent variable was the presence or absence of a non-affective psychosis diagnosis according to SCID-I; independent variables included in the model were CIDI items, gender, age (classified into the categories 18 24, 25 34, 35 49, 50 64, and 64+), years of education (categorized as 0 11, 12, 13 15, and +16), marital status, employment status, geographical area, fulfilling criteria for anxiety disorder or mood disorder. The anxiety disorders included were general anxiety disorder, social phobia, specific phobia, agoraphobia and panic disorder. Mood disorders included major depressive episode and dysthymia. All the analyses were performed using the SAS software, version 9 of the SAS System for Windows (SAS, 1999). 3. Results Of the 1645 participants, 189 responded positively to one of the psychosis screening questions, were taking antipsychotic medication, or had been hospitalised for mental health problems. Thus, 11.18% (CI = ) of the individuals were probable psychosis cases according to the CIDI.

4 264 S. Ochoa et al. / Schizophrenia Research 102 (2008) Table 1 Sociodemographic characteristics of the total of the sample, people who were classified as possible psychosis cases in the CIDI and people with an SCID-I diagnosis of non-affective psychosis (number of cases and adjusted proportions) Overall CIDI screen positive SCID-I non-affective psychosis Characteristic N % N % N % Total Sex Male Female Age N Education Marital status Married or living with someone Previously married Never married Geographical area Rural (b10,000) Mid-size urban (10, ,000) Large urban (N10,000) Status Working Student Homemaker Retired Other Any mental disorder No Yes Any mood disorder No Yes Any anxiety disorder No Yes Psychiatric hospital No Yes Taking antipsychotic medication No Yes Results were weighted according to the sex and age distribution of the population of Catalonia.

5 S. Ochoa et al. / Schizophrenia Research 102 (2008) Among the 189 probable psychosis cases, 88 individuals had given consent to be re-interviewed over the telephone and had provided their telephone. The rest, 101 individuals, either did not accept to be reinterviewed or did not provide their telephone. Of the 88 individuals who were the sample of the second phase of the survey, a total of 58 (67%) participants were telephonically re-interviewed; 23 could not be contacted (after at least five telephone call attempts) and 7 refused to be re-interviewed. No differences were observed in sociodemographic and clinical characteristics among participants who were re-interviewed (58 cases) and those who did not (30 cases). The mean number of positive CIDI screen questions in those who were reinterviewed was 1.29 (SD 1.2) and on those who were not re-interviewed 1.23 (DE 1.28) (p=0.7). Among the interviewees, 14 were diagnosed as having non-affective psychosis. Assuming that individuals who did not give consent to be re-interviewed or did not have a telephone (N=101), who could not be interviewed (n=23) or who refused to participate in the telephone interview (n=7) did not have psychosis, the minimum lifetime prevalence of psychosis in the general population of Catalonia (Spain) was 0.85% (95% CI= ). If we assume that people who could not be interviewed and people who did not give consent to be re-interviewed had the same proportion of being psychotic than the people interviewed the prevalence of psychosis was 2.37% (95% CI ). Among participants with psychosis according to SCID-I (n = 14), eight were diagnosed as having schizophrenia and six received other psychosis diagnoses. All participants with schizophrenia were receiving or had received psychiatric or psychological treatment during the year prior to the interview; but none of the individuals with other diagnosis did. Thus, minimum lifetime prevalence of schizophrenia in our sample was 0.48% ( ). Assuming the same distribution of presence of schizophrenia for people who were no re-interviewed or did not give the consent, the prevalence of schizophrenia was 1.58 ( ). Table 1 summarizes the sociodemographic characteristics of the total sample, participants who were classified as probable psychosis cases according to the CIDI, and participants with non-affective psychosis according to SCID-I. The only statistically significant difference between the probable psychosis cases and the non-affective psychosis cases was the sex distribution. While women were more frequent among probable psychosis cases according to the CIDI (61%), there were more men in the group of non-affective psychosis according to SCID (71%). Probable psychosis CIDI cases were younger, had less years of education and lived in large urban areas compared to nonaffective psychosis cases, although any of these differences are statically significant. Among CIDI probable psychosis cases, 53.23% met criteria for another mental disorder: 46.39% presented a mood disorder and 25.45% presented an anxiety disorder. The figures are similar for the nonaffective psychosis cases. Table 2 compares the clinical characteristics of the individuals who scored positively to any of the CIDI psychosis screen questions but were not classified as true non-affective psychosis cases in the SCID with the non-affective psychosis cases. Individuals with nonaffective psychosis had a greater mean screen positive questions (2.11; SD 2.01) compared to those CIDI screen positive who did not have non-affective psychosis diagnosis (mean 0.99; SD 0.77) (pb0.005). Table 2 Comparison of the clinical characteristics of the CIDI screen positive but no non-affective psychosis cases with the non-affective psychosis cases as assessed with the SCID-I Clinical characteristics CIDI screen positive/no nonaffective psychosis SCID-I nonaffective psychosis N % N % Psychiatric hospitalisation ever No Yes Antipsychotic medication in previous year No Yes Saw a vision No Yes Heard voices No Yes Had experienced mind control No Yes Had felt that your mind was being taken by strange forces No Yes Had experienced attempts of communication from strange forces No Yes Had a plot to harm you No Yes

6 266 S. Ochoa et al. / Schizophrenia Research 102 (2008) Table 3 Reasons provided by respondents and assessed by the clinical psychologist regarding why they answered positively the CIDI psychosis questions Explanations to the positive questions of the CIDI Non-affective psychosis SCID-I cases Non-affective psychosis SCID-I negatives N=14 N=44 ps1a. Saw a vision 10 (100%) 20 (100%) True hallucination 10 (100%) Hypnagogic or hipnopompic hallucinations 3 (15%) Bereavement 9 (45%) Fever 2 (10%) Sensation of seeing something 4 (20%) Affective psychosis 1 (5%) Did not answer the question 1 (5%) ps1b. Heard voices 8 (100%) 17 (100%) True hallucination 8 (100%) Hypnagogic or hipnopompic hallucinations 1 (5.9%) Bereavement 4 (23.4%) Sensation of hearing something 11 (64.8%) Affective psychosis 1 (5.9%) ps1c. Had experienced mind control 4 (100%) 2 (100%) Psychotic symptom 4 (100%) Other not psychotic reasons 1 (50%) Not answer the question 1 (50%) ps1d. Had felt that your mind was being taken by 2 (100%) 1 (100%) strange forces Psychotic symptom 2(100%) Other not psychotic reasons 1 (100%) ps1e. Had experienced attempts of communication from 5 (100%) 2 (100%) strange forces Psychotic symptoms 5 (100%) Other not psychotic reasons 2 (100%) ps1f. Had a plot to harm you 3 (100%) 7 (100%) Explanation of psychotic symptoms Psychotic symptoms 3 (100%) Feeling of everything was wrong 3 (43%) Other not psychotic reasons 4 (57.0%) Table 4 Frequency of positive answers in the CIDI psychosis module and the other psychosis screen questions by non-affective psychosis SCID-I diagnosis Questions of the CIDI, services and medication Non-affective psychosis cases Non-affective Psychosis negatives N=14 N=44 ps1a. Saw a vision 10 (66.47%) 20 (42.31%) ps1b. Heard voices 8 (49.94%) 17 (40.41%) ps1c. Had experienced mind control. 4 (34.4%) 2 (1.96%) ps1d. Had felt that your mind was being taken by strange forces 2 (12.5%) 1 (0.98%) ps1e. Had experienced attempts of communication from strange forces 5 (31.54%) 2 (3.97%) ps1f. Had a plot to harm you 3 (16.92%) 7 (12.03%) Was hospitalised overnight for mental health problems 3 (23.24%) 14 (33.91%) Was taking or had taken antipsychotic medication 3 (27.61%) 2 (1.92%) Rao Scott modified likelihood ratio test. b0.001 significant. b0.01 significant. b0.05 significant.

7 S. Ochoa et al. / Schizophrenia Research 102 (2008) Table 5 Factors associated with the presence or absence of a SCID-I nonaffective psychosis diagnosis among people who have punctuated in psychosis by the CIDI (logistic regression analysis) Effect Odds ratio estimate (CI) Urbanity Rural (b10,000) 1 Mid-size urban (10, ,000) 9.62 ( ) Large urban (N100,000) 2.67 ( ) Had experienced mind control No 1 Yes ( ) The explanations given by respondents to positive psychotic symptoms reported in the CIDI are described in Table 3. The decision whether a experience was a true psychotic symptom or not was taken during the SCID interview and was based on the SCID criteria. For the experience of having a vision, the most frequent explanation was having the perception of seeing a family member in the days after the relative died. In the item of hearing voices, the most frequent explanation was hearing a voice in contexts where there was people around (the grandmother calls, someone calls you in the street, at home ). The rest of the screen questions were scored less frequently and most of the answers were not considered to be true psychotic experiences. Table 4 shows the comparison of each of the CIDI questions between participants with and without nonaffective psychosis. The most frequent psychotic experiences among participants with non-affective psychosis were saw a vision (66.5%) and heard voices (49.9%). However, no differences were observed among groups. On the contrary, differences were observed between groups for experiences such as: Have experienced mind control (p b 0.001) ; Have felt that your mind was being taken by strange forces (p b 0.05); and Had experienced attempts of communication from strange forces (p b 0.05). The use of antipsychotic medication was significantly more frequent among the group with non-affective psychosis (p b 0.001). The results of the logistic regression showed that only one item of the CIDI psychosis module ( Had experienced mind control ) was associated to non-affective psychosis diagnosis (Table 5). None of the sociodemographic characteristics were found to be related with nonaffective psychosis diagnosis except for urbanity. 4. Discussion Approximately 11% of adults from Catalonia reported experiences that were compatible with psychotic symptoms. However, the vast majority of them were not truly psychotic symptoms and the prevalence of non-affective psychosis was 0.85%. These results are slightly higher than most prevalence studies of non-affective psychosis (Kendler et al., 1996; Kessler et al., 1995, 2005). This slight difference could be because these studies used SCAN as a screening questionnaire instead of the SCID-I, and SCAN is a more restrictive questionnaire. Some authors have previously reported a high prevalence of self reported psychotic symptoms in the community (Van Os et al., 2003; Kendler et al., 1996; Hanssen et al., 2003; Perala et al., 2007). However, as observed in our results, the endorsement of questions about psychotic symptoms does not qualify for psychotic symptoms when assessed by clinicians. In most of the cases, the symptoms could be explained by other reasons. Certain life situations may facilitate the appearance of hallucinations, for example few days after the death of a close relative (MBBS, 2005). Our results show that more than 45% of the visual and more than 20% of the auditory hallucinations reported appeared few days after the death of a relative or friend. Hallucinations have been described as sensory experiences that occur without external stimulation of the sensorial organ and without voluntary control of the individual (David, 2004). However, this kind of hallucination that appears isolated and during bereavement situations should not be considered as a psychotic symptom; although some authors support some continuity between normal and pathological perceptions (Sanjuan, 2006). However, our findings partially support the continuum theory of psychosis (Van Os and Verdoux, 2003), since there are individuals in the general population that have experiences that are psychotic symptoms and others have experiences that are similar or resemble psychotic symptoms. Although the CIDI specifically indicates that experiences that occur while people are dreaming or halfasleep should not be considered when answering the questions, some of the respondents did explain that the experiences appeared when falling asleep. Ohayon (2000) described that hypnopompic and hypnagogic hallucinations could be present in approximately one fourth of the general population. More than 50% of the individuals reporting psychotic experiences, whether or not confirmed by the clinical interview, met criteria for a non-psychotic mental disorder, especially mood disorder. It is possible that some of them had psychotic symptoms during the mood disorder episode, but in the assessment with SCID-I they did not met criteria for non-affective psychosis. One person who had answered positively the psychotic screen questions suffered from bipolar disorder. Ohayon (2000)

8 268 S. Ochoa et al. / Schizophrenia Research 102 (2008) found that the use of drugs or alcohol, anxiety disorders, bipolar disorders, depressive disorders and organic diseases are sometimes associated with hallucinations. Olfson et al. (2002) found similar results in patients with psychotic symptoms in primary care settings. As we have seen, psychotic symptoms as assessed by CIDI are frequently present in the general population, but when these symptoms are evaluated by a clinician, the vast majority does not qualify for clinically relevant psychotic experiences. Several studies reported consistent similar findings (Van Os et al., 2003; Kendler et al., 1996; Hanssen et al., 2003). The results suggest that the assessment of psychosis in general population surveys requires the participation of mental health professionals, although lay-administered interviews can be used as screening instruments. In improving the performance of lay-administered surveys, Kessler et al. (2005) proposed to record a description of the symptoms in case of a positive response in the CIDI screen question. This description could be later assessed by a clinician. When using this methodology, the prevalence of psychosis was 1.5%, near to the prevalence they found when assessments were done in a clinical interview (0.5%). Given the limitations of the CIDI screen questions, we analyzed factors that could be related to having nonaffective psychosis. Taking antipsychotic medication, having experienced mind control, and having felt that one's mind was being taken by strangers were significantly more frequent in individuals with non-affective psychosis compared to probable psychosis cases with no psychosis diagnosis. Based on the results of the regression analysis, the most important CIDI question was have experienced mind control. Although some other psychosis screen questions were more frequently answered by individuals with a psychotic disorder (for example visual and auditory perceptions), their predictive value was small. Several limitations should be considered when analyzing the results. First, we need to take into account that the final number of cases detected was small given the small original sample size and the inefficiency of finding low prevalence disorders in community surveys. Second, individuals who live in institutions or were hospitalised were not included in the survey. Bijl et al. (1998b) estimated that a 0.05% of the people who suffer schizophrenia live in a hospital. In Catalonia the estimation is similar, and this percentage should be added to the prevalence figure. Moreover, the prevalence of psychosis in prisoners is higher than in general population (Brugha et al., 2005), so we should take into account this data. Third, CIDI screen negatives were not examined with SCID-I, as the cost of assessing sufficient people to estimate false negatives with precision would have been high and the probabilities scarce as suggested by Singleton et al. (2001). Fourth, it could be that individuals who were non-psychotic at the assessment could later develop psychosis. Fifth, the assessments are based on the comments of the respondents, and thus subject to recall bias. Finally, non-response rates may have affected the results. Kessler et al. (2005) suggested that people with mental disorders are more frequently non-responders. If this is true, prevalence rate should be increased, although the size of the bias may be difficult to estimate. In conclusion, we have found that re-interview is necessary to detect individuals with psychotic disorders in general population surveys, including a clinical interview. Some screening questions for psychosis are more predictive of non-affective psychosis and thus they can provide and thus improve the efficiency of the method. Role of funding source This project received the following funding: European Commission (QLG5-CT ; SANCO ); Sanitary Research Funding (FIS 00/ ); Sciences and Technology Ministry (SAF CE); Cat Salut-Servei Català de la Salut (SAMCAT); Spanish Ministry of Health, Instituto de Salud Carlos III, RETICS RD06/0011 (REM-TAP Network); and an unrestricted educational grant by GlaxoSmithKline. The ESEMeD Spain was carried out in coordination with the WHO World Mental Health Survey Initiative ( wmh/). We thank the WMH staff for assistance with instrumentation, fieldwork, and data analysis. These activities were supported by the John D. and Catherine T. MacArthur Foundation, the Pfizer Foundation, the US Public Health Service (1R13MH066849, R01-MH069864, and R01 DA016558), Eli Lilly and Company, GlaxoSmithKline, Ortho-McNeil Pharmaceuticals and the Pan American Health Organization. A complete list of WMH publications can be found at The funding sources had no further role in study design, collection, analysis or interpretation of the data, in the writing of the report or in the decision to submit the paper for publication. Contributors Susana Ochoa wrote the article and made the clinical assessments; Josep Maria Haro, Jordi Alonso and Jaume Autonell, designed the study and wrote the protocol; Juan Vicente Torres and Bibiana Prat, undertook the statistical analysis and AlejandraPinto-Meza, Concepción Palacin, Mariola Bernal, Judith Usall and Traolach Brugha, contributed in the study and managed the literature searches and analysis. All authors contributed to and have approved the final manuscript. 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