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Prevalence of psychotic and non-psychotic disorders in relatives of patients with a first episode psychosis
Schizophrenia Research 114 (2009) 57–63
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Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Prevalence of psychotic and non-psychotic disorders in relatives of patients with a first episode psychosis Kia Faridi a,b,c, Nicole Pawliuk a,c, Suzanne King b,c, Ridha Joober a,b,c, Ashok K. Malla a,b,c,⁎ a b c
Prevention and Early Intervention Program for Psychosis, Montreal, Quebec, Canada Department of Psychiatry, McGill University, Montreal, Quebec, Canada Douglas Mental Health University Institute, Montreal, Quebec, Canada
a r t i c l e
i n f o
Article history: Received 11 August 2008 Received in revised form 29 June 2009 Accepted 6 July 2009 Available online 9 August 2009 Keywords: Schizophrenia First-episode psychosis Family history Familiality
a b s t r a c t Background: Family members of individuals with schizophrenia suffer from elevated rates of schizophrenia-spectrum disorders (SSD) and other forms of psychopathology. However, few studies have examined familial psychopathology in probands with a first episode of psychosis (FEP). We systematically evaluated family history in patients experiencing an affective or nonaffective FEP. Methods: The Family Interview for Genetic Studies was used to obtain diagnostic information on all first- and second-degree relatives of probands admitted to a specialized FEP program. Probands were 94 previously untreated patients suffering from a first-episode of affective or schizophrenia spectrum psychosis, aged 14 to 30. The interview ascertained diagnoses of psychotic disorders, affective disorders, substance-use disorders (SUD), and schizophreniarelated personality disorders. Results: One in five probands (19.1%) had a history of psychosis among their first-degree relatives, while 34.0% had any relative with psychosis. Fewer probands had a family history of SSD (7.4% with a first-degree history and 18.1% with a history among any relatives). Over half (53.2%) of probands had a first-degree relative with Major Depressive Disorder, and 38.3% had a first-degree relative with a SUD. Overall, 69.9% of probands had a first-degree relative with a mental disorder. The proportion of probands with a family history of any of these diagnoses did not vary by proband diagnosis (affective or SS Psychosis), though probands with co-morbid SUD were more likely to have a family history of substance abuse. Conclusions: Diverse psychopathology is commonly present in families of FEP patients and may imply a generalized vulnerability to psychiatric disorders to be greater in such families compared to specific vulnerability to SS or affective psychosis. These findings may also have implications for provision of care for the probands. © 2009 Elsevier B.V. All rights reserved.
1. Introduction The familial nature of schizophrenia is well documented, with the most robust evidence emerging from controlled epidemiologic studies (Kendler et al., 1985, 1993a; Tsuang et al., 1980). It has also been demonstrated that other psychotic disorders tend to aggregate in the families of probands with ⁎ Corresponding author. McGill University, Douglas Mental Health University Institute, 6875 Boul. Lasalle, Montreal, Qc, Canada H4H 1R3. E-mail address: [email protected] (A.K. Malla). 0920-9964/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.07.007
schizophrenia. Kendler used data from the Roscommon Family Study to support the existence of a Schizophrenia Spectrum, consisting of a shared liability between affective psychoses, nonschizophrenic non-affective psychoses, schizotypal and paranoid personality disorders, schizoaffective disorder, and schizophrenia (Kendler et al., 1995). Most studies confirm that affective illnesses do not form part of the Schizophrenia Spectrum (Kendler et al., 1995; Tsuang et al., 1980), though some studies have reported an increased risk of non-psychotic affective illnesses in the relatives of probands with schizophrenia (Chang et al., 2002; Kendler and Gardner, 1997; Kendler et al.,
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1993b; Maier et al., 2002). The increased risk of both psychotic and non-psychotic illness extends to both first-degree and more distant relatives of probands (Maier et al., 2002). Despite this extensive literature regarding family history in schizophrenia, few studies have evaluated family history in patients suffering from a first episode of psychosis (FEP). Aside from the inherent value in extending the body of knowledge regarding family history in psychotic disorders, studying this patient population may hold other advantages. Most clinical family studies of schizophrenia ascertain cases from a more chronic patient population. This entails a selection bias towards more severely ill or treatment resistant cases, as people with milder illness, or people who make a full recovery after a single psychotic episode, would not be part of this population. A FEP population is more likely to include such cases that would later be lost to follow-up and/or cases that would make a full recovery and which therefore would not be ascertained in studies of other clinical populations. Two studies have reported on the proportion of FEP patients with a family history of psychotic disorders. Norman et al. (2007b) recently examined the relationship of family history to a number of clinical characteristics and found that 15.7% of their largely non-affective FEP sample had a firstdegree relative with a schizophrenia spectrum disorder, and that those probands with a family history had a poorer outcome, a lower IQ, and increased rates of EEG abnormalities. Chen et al. (2005) reported that 23.1% of FEP patients in their sample had a family history of a psychotic disorder. While informative, these studies had certain limitations. They both used an instrument that does not systematically identify and evaluate each member of the pedigree and that screens for mental illness by exploring a history of treatment contacts. This method of ascertainment may have led to an underestimation of cases, and does not collect information on the number of unaffected relatives, or their ages, which are important in calculating scores of family loading. Further, both studies examined only probands with non-affective psychosis, and ascertained only psychotic illness among relatives. To our knowledge there are no reports of systematic evaluation of diverse forms of psychopathology in the families of FEP patients. Further, no study has examined family history in extended families including both first- and second-degree relatives of FEP probands. The primary objective of the present study was to add to the literature demonstrating the familial nature of psychotic illnesses by conducting a systematic evaluation of diverse forms of psychopathology in first- and second-degree relatives of patients with a non-affective or affective FEP. These relatives were evaluated for histories of psychotic disorders, affective disorders, psychosis-related personality disorders, and substance use disorders. We hypothesized that a family history of a schizophrenia spectrum disorder (SSD) is more prevalent in probands diagnosed with a SSD compared to probands with an affective psychosis (AP). 2. Methods 2.1. Setting and subjects The sample for this study is drawn from consecutive admissions to the Prevention and Early intervention Program for Psychoses (PEPP-Montreal), a program designed for the
assessment and treatment of all cases of FEP in a defined catchment area. Included patients were aged 14 to 30, suffering from symptoms meeting criteria for a DSM-IV psychotic disorder, and were not previously treated with antipsychotic medications for greater than one month. Exclusion criteria included the inability to speak either English or French; an IQ of less than 70; or an organic brain syndrome. All patients admitted to PEPP-Montreal who met these criteria were approached to take part in the study within the first year of their participation. A total of 195 consecutive admissions were approached, and 94 family history interviews were completed. 2.2. Measures Proband diagnosis was determined by the Structured Clinical Interview for DSM-IV (SCID) (First et al., 2002), administered by trained research assistants soon after entry to PEPP-Montreal. Diagnosis was established through consensus meetings with two senior psychiatrists (A.M. or R.J.). Probands were grouped into diagnostic categories of “Schizophrenia Spectrum Disorder” (Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Delusional Disorder, and Psychosis NOS) and “Affective Psychoses” (Major Depressive Disorder with Psychotic Features or Bipolar Affective Disorder with Psychotic Features). Parental socioeconomic status was assessed with the Hollingshead twofactor index of social position (Miller, 1991). Family history was ascertained by interviewing a firstdegree relative (usually a parent) of the proband, though in ten cases the probands themselves were suitable informants, and in two cases the informant was a sibling and a grandparent, respectively. The interview was conducted by trained research assistants. The informant assisted the interviewer in completing a family tree of the proband's first- and second-degree blood relatives. A structured interview, the Family Interview for Genetic Studies (FIGS) (Maxwell, 1992), was used to first identify potential cases of mental illness in the family tree, and then to systematically determine the diagnoses of psychotic disorders, affective disorders, Cluster A personality disorders, and substance use disorders in these individuals. For each relative, the diagnosis given was rated as to degree of certainty: “Certain” (relative was psychiatrically assessed and the diagnosis clearly made, treatment received); “Probable” (based on symptom profile); and “Reported” (informant reports the diagnosis, but little evidence of compatible symptoms). For the purposes of thisstudy, only “Certain” and “Probable” diagnoses were considered. The diagnoses for the relatives were grouped into a number of overlapping categories. “Schizophrenia Spectrum Disorder” referred to diagnoses of Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Paranoid Personality Disorder, and Schizotypal Personality Disorder. Relatives with Major Depressive Disorder (MDD) with Psychotic Features or Bipolar Affective Disorder (BAD) with Psychotic Features were grouped together as “Affective Psychoses”. A third category, “Any Psychosis”, was applied to any relative who received a diagnosis of SSD, affective psychosis, Delusional Disorder, Brief Psychotic Disorder,
K. Faridi et al. / Schizophrenia Research 114 (2009) 57–63
Psychosis NOS, or any drug-induced psychosis. Additional categories were created for any diagnosis of MDD, any diagnosis of BAD, and any substance-use disorder. These family history data are presented in three different ways. First, we report the proportion of probands with any positive family history of each diagnostic category, either among their first-degree relatives or among any (first- or second-degree) relatives. These data, though they are not age corrected, are presented as they give a clinical sense of the burden of familial illness in PEPP populations. For the diagnostic categories of Schizophrenia Spectrum Disorder and Any Psychosis, we calculated two age-corrected indicators of level of familiality: Morbid Risk (MR) and a Family Loading Score (FLS). The morbid risk is an age-corrected prevalence figure commonly reported in the literature. Morbid Risk was calculated using the Hardy-Weinberg abridged method, in which the prevalence denominator is decreased to account for relatives who remain in the age of risk (counted as 0.5). Morbid Risks were separately calculated for first- and second-degree relatives. Though commonly used, this method of age-correction is imprecise. For this reason, we also calculated a Family Loading score (Verdoux et al., 1996). This parameter accounts for the age of the affected relatives and the pedigree structure to produce a score that indicates the degree of ‘familiality’ for each proband. The calculation was modified from the original protocol to include second-degree relatives. For the purposes of this calculation, the risk of being ill in the presence of ‘familial schizophrenia’ was assumed to be 10% for first-degree relatives; for seconddegree relatives, this risk was assumed to be 3%. 2.3. Data analysis The data were analyzed to examine the rate of positive family history of the above mentioned categories, among first-degree relatives and amongst any relatives (first-degree or second-degree). These were compared by diagnostic status of probands (Schizophrenia Spectrum Disorder (SSD) vs. Affective Psychosis (AP)) using Pearson Chi-square test (or Fisher's exact test when the number of subjects in any cell was less than five). Morbid Risk was compared between groups by means of a chi-square analysis. A two-sided t-test was used to compare Loading Score between groups. 3. Results 3.1. Subjects 94 FIGS interviews were completed yielding diagnostic data on 1484 relatives. Proband diagnoses are listed in Table 1. Probands did not differ from patients who did not participate on any demographic variables or diagnostic categories (Table 2). 3.2. Family history of psychotic illnesses We found that 7 (7.4%) probands had a family history of a Schizophrenia-Spectrum Disorder amongst their first-degree relatives. If both first- and second-degree relatives are considered, 17 (18.1%) probands had a positive family history. For the broader diagnostic category of “Any Psychosis”, nearly
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Table 1 Diagnoses of probands. Diagnosis
n (94)
%
Schizophrenia spectrum disorders Schizophrenia Schizophreniform disorder Schizoaffective disorder Delusional disorder Psychosis NOS Affective psychoses MDD with psychotic features Bipolar disorder with psychotic features
74 36 3 16 4 15 20 4 16
78.7 38.3 3.2 17.0 4.3 16.0 21.3 4.3 17.0
a fifth (18 (19.1%)) of probands had a family history amongst first-degree relatives, while over a third (32 (34.0%)) had a family history of any psychosis amongst first- or seconddegree relatives. There was no significant difference in the rate of a positive family history of SSD, Any Psychosis, or affective psychosis, between SSD and AP probands (Table 3). The Morbid Risk (Table 5) or Loading Score (Table 4) for these categories did not differ between groups. 3.3. Family history of affective illness A history of MDD among first-degree relatives was reported by more than half of the probands (50 (53.2%)), while almost two-thirds (61 (64.9%)) report MDD among first- or second-degree relatives (Table 3). A history of BAD was less common: 7 (7.4%) probands had a history among their first-degree relatives, and 11 (11.7%) had a history among any relative (Table 3). There were no significant differences in the prevalence of family history of affective illness among the proband groups. 3.4. Family history of substance use disorders Overall, 36 (38.3%) probands had a first-degree relative with a substance-use disorder, while 56 (59.6%) probands had a first- or second-degree relative with a substance use disorder (Table 3). There was a trend for probands with a SSD to be more likely to have a history of a SUD among firstdegree relatives compared to probands with an affective psychosis (43.2% in SSD vs. 20% in affective psychosis; χ2 = 3.60; p = 0.058) (Table 3). This difference was less marked when 1st and 2nd degree relatives were considered (63.5% vs. 45.0%, χ2 = 2.24, p = 0.13). Probands who met criteria for a co-morbid diagnosis of SUD were significantly
Table 2 Demographic characteristics of subjects (probands) compared to nonparticipating PEPP patients.
Age at PEPP entry (Mean, (SD)) Male (%) Hollingshead class IV or V (%) Education, greater than 12 years (%) SSD diagnosis (%) Affective psychosis diagnosis (%) Substance-induced psychosis diagnosis (%) Substance use disorder diagnosis (%)
Subjects included
Subjects not included
22.7 (4.0) 67.3 54.4 53.8 78.7 21.3 0 53.8
23.1 (4.0) 71.3 57.4 48.0 82.0 14.6 3.4 55.4
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Table 3 Distribution of family history of psychiatric illness in probands with a FEP. Presence of diagnosis in relatives
Schizophrenia spectrum Any psychosis Affective psychosis Depression Bipolar Substance use disorder
1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree
SSD probands (n = 74)
Affective probands (n = 20)
Overall (n = 94)
n (%)
n (%)
n (%)
4 (5.4%) 14 (18.9%) 13 (17.6%) 25 (33.8%) 7 (9.5%) 7 (9.5%) 40 (54.1%) 48 (64.9%) 5 (6.8%) 7 (9.5%) 32 (43.2%) 47 (63.5%)
3 (15.0%) 3 (15.0%) 5 (25.0%) 7 (35.0%) 1 (5.0%) 1 (5.0%) 10 (50.0%) 13 (65.0%) 2 (10.0%) 4 (20.0%) 4 (20.0%) 9 (45.0%)
7 (7.4%) 17 (18.1%) 18 (19.1%) 32 (34.0%) 8 (8.5%) 8 (8.5%) 50 (53.2%) 61 (64.9%) 7 (7.4%) 11 (11.7%) 36 (38.3%) 56 (59.6%)
χ2
0.010
0.104 0.000
3.600 2.241
p
0.163⁎ 1.00⁎ 0.524⁎ 0.919 1.00⁎ 1.00⁎ 0.747 0.991 0.638⁎ 0.239⁎ 0.058 0.134
⁎Indicates use of Fisher Exact Test. In all other cases, chi-square test was used.
more likely to have a family history of a SUD amongst first- or second-degree relatives compared to probands with no SUD (71.2% vs. 45.2%; χ2 = 6.48, p = 0.011; Table 6). When only first-degree relatives were considered, this difference missed significance (46.2% vs. 28.6%; χ2 = 3.04, p = 0.081). Family history of psychotic or affective disorders did not differ between probands with a secondary diagnosis of SUD and those without such a diagnosis (data not shown).
4. Discussion To our knowledge this is the first study to systematically evaluate the frequency of a family history of a variety of psychiatric disorders among patients presenting for a first episode of psychosis. We found a first-degree family history of schizophrenia-spectrum disorder in a relatively low proportion (5.4%) of probands with SSD compared to previous reports of 15.7% (Norman et al., 2007b) and 21% (Chen et al., 2005) and a similar lower rate when second-degree relatives were included (18.9% in the current sample vs. 27% in Norman et al. (2007a)). However, when a family history of any psychotic disorder is considered, the rates are higher, with 17.6% of probands reporting any psychotic disorder among first-degree relatives, and 33.8% reporting any psychotic disorder among first- or second-degree relatives. The discrepancies in the rates reported in our study and those reported in previous studies of FEP may be partially related to differences in assignment of diagnostic categories within the schizophrenia spectrum. For example, in the present study, 56% of families with a psychosis history had a history of SSD, compared to 93% reported by Chen et al. (2005). The precise
Table 4 Loading scores for psychotic illness categories.
Schizophrenia spectrum Any psychosis Affective psychosis
Proband diagnosis
Loading score
SD
SEM
p
SSD AP SSD AP SSD AP
0.03 0.09 0.60 0.92 − 0.08 0.12
1.29 1.75 1.77 2.44 1.04 1.85
0.15 0.39 0.21 0.55 0.12 0.41
0.862 0.518 0.532
diagnostic process used in the FIGS interview could have led to relatives being less likely to be classified as SSD, and more likely to receive labels of affective psychosis or Psychosis NOS. The rate of a positive family history of schizophrenia spectrum disorder in our first-episode population is lower than studies of subjects with a more long-standing diagnosis of schizophrenia. In the Roscommon study, a first-degree family history of schizophrenia was present in 27 of 173 (15.6%) probands with a non-affective psychosis, while 9.3% of probands with a psychotic affective illness had a family history of schizophrenia (Kendler et al., 1993a (Table 4)). Similar rates of a first-degree family history of non-affective psychosis (15.6% (Alda et al., 1996)) or schizophrenia (15.3% (Shimizu and Kurachi, 1989)) were reported in two studies that examined clinically ascertained probands with schizophrenia. One potential explanation of the lower rates found in the present study is the lower sensitivity of the family history method used in this study compared to the family study method used in the Roscommon study (this limitation is further discussed below). The difference may also result from a difference in our ability to use precise diagnostic labels, resulting in more relatives being diagnosed with ‘psychosis NOS’ in the present sample. However, the difference may also represent a lower rate of schizophrenia in the families of FEP patients, compared to probands with illness of variable duration. Studies of more chronic populations are likely to include a higher proportion of relatively more severe and/or treatment-resistant cases while those with very good outcomes may no longer be in the service system. These more chronic course cases have a heavier family loading for schizophrenia (Joober et al., 2005). A FEP sample may, therefore, be more likely to give a true representation of psychopathology in families of patients suffering from the full range of psychotic illness. Perhaps the most significant finding from our study is that an array of psychiatric disorders was very frequently present in the immediate families of subjects suffering from a FEP. Approximately half had a first-degree relative with depression, 40% had a first-degree relative with a SUD and 20% had a first-degree relative who had experienced some form of a psychotic disorder. Such high rates of non-psychotic and psychotic disorders in families of patients with a FEP may have several implications for the patient or for the care he/she receives. Siblings of people with schizophrenia often have
K. Faridi et al. / Schizophrenia Research 114 (2009) 57–63
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Table 5 Morbid risks for psychotic illness categories. Proband diagnosis
Diagnosis in relatives Schizophrenia spectrum
All probands SSD AP
1st degree 2nd degree 1st degree 2nd degree 1st degree 2nd degree
Any psychosis
BZ
MR
n
BZ
MR
n
BZ
MR
7 17 4 15 3 2
233 882.5 184 679.5 49 203
3.00% 1.93% 2.17% 2.21% 6.12% 0.99%
20 27 14 21 6 6
234.5 883.5 185 680.5 49.5 203
8.53% 3.06% 7.57% 3.09% 12.12% 2.96%
10 1 8 0 2 1
234.5 880 185 677 49.5 203
4.26% 0.11% 4.32% 0.00% 4.04% 0.49%
important care-giver roles, and often experience concerns about their own genetic liability to psychosis (Stalberg et al., 2004). It has been proposed that experiences with psychosis can increase stigma and resistance to coming to treatment or recognizing psychosis, or, alternatively, that family experience may sensitize patient and family to early symptoms, facilitating presentation for treatment (Hambrecht, 1995). The presence of a close family member suffering from depression or a substance-use disorder may be a source of major stress for a patient presenting an obstacle to recovery. The precise impact of a family history of non-psychotic disorders on a patient's presentation and care has not been explored. The frequent presence of a family history of these disorders emphasizes the importance of a thorough assessment of family psychopathology in clinical evaluation of patients with a FEP. In our sample, proband diagnostic category did not impact the frequency of a family history of any of our diagnostic groupings. This is an unexpected finding, as it has previously been reported that a family history of schizophrenia is more common in probands with a schizophrenia spectrum disorder (Kendler et al., 1993a). Our negative finding may represent a lack of statistical power to detect differences, particularly given the smaller proportion of probands with an affective psychosis diagnosis. However, inspection of the data reveals no trends in the expected direction. Another possibility is that, in FEP patients, the proband's symptomatology and diagnosis remains somewhat fluid during the earliest stages of illness; this initial variability in diagnosis could attenuate differences between diagnostic groups. This possibility is supported by Bromet et al. (2005) who found that in FEP patients, a SCID diagnosis at baseline was less predictive of diagnosis at 10 years compared to a SCID diagnosis determined at a later time point. A third possibility is that psychotic disorders share a common vulnerability and that schizophre-
Table 6 Distribution of family history of a SUD in FEP probands. Probands with SUD (n = 52) n (%)
Probands without SUD (n = 42) n (%)
SUD in 24 (46.2%) 12 (28.6%) 1st degree SUD in 37 (71.2%) 19 (45.2%) 1st or 2nd degree
Affective psychosis
n
Overall (n = 94) n (%)
χ2
p
36 (38.3%) 3.04 0.081 56 (59.2%) 6.48 0.011
nia and affective psychosis may not necessarily represent two distinct disease entities (Craddock et al., 2005; Crow, 1990). We found that probands with a concurrent substance-use diagnosis were more likely to have relatives with a substance use diagnosis, in keeping with previous reports (Merikangas et al., 1998; Miles et al., 1998). The strengths of this study include a sample likely to be representative of a clinical FEP population. PEPP-Montreal has a defined catchment area with no competing services and a well defined case identification initiative. It is thus likely that almost all new cases of psychosis within this sector will be referred to PEPP-Montreal. Ascertained cases represent the full spectrum of psychotic diagnosis. We believe that using a FEP clinical group captures aspects of the full spectrum of psychotic illnesses that can be missed when more chronic populations are examined. Given that the familial liability to schizophrenia and other psychiatric disorders is clearly not limited to first-degree relatives, an additional strength of the study is the systematic evaluation of both first- and second-degree relatives using the FIGS interview. Furthermore, this instrument allows a systematic assessment of a broad range of psychopathology that has not commonly been reported in the literature. Limitations of the present study include the use of the Family History method of gathering diagnostic information, rather than individual interviews with all relatives. However, a number of studies have found that the Family History technique is highly specific for diagnosing psychotic disorders (between 99% and 100%), but has only low to moderate sensitivity (Andreasen et al., 1977; Andreasen et al., 1986; Davies et al., 1997; Roy et al., 1996). The Relative Psychiatric History, which is similar to the FIGS, was found to have a moderate sensitivity of 44% for diagnosing “Any psychotic disorder”, but a specificity and positive predictive value of 100% for this diagnostic category (Fogelson et al., 2004). Similarly, Family History Instruments seem to have low- to moderate sensitivity and high specificity in the diagnosis of affective illness and substance use disorders in relatives (Davies et al., 1997; Miles et al., 1998). We are unaware of any studies evaluating the accuracy of Family History information obtained for second-degree relatives. Thus, the FIGS interview is likely to have underestimated the frequency of mental disorders but is unlikely to have misclassified relatives into incorrect diagnostic groups. The relatively young age of the relatives, an inevitable consequence of the young probands who were ascertained, represents another weakness of the present study, as not all
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relatives would themselves have passed through the age of risk for the onset of psychiatric illnesses. The use of the agecorrected Morbid Risk and the Family Loading Score serve to mitigate this factor by accounting for the age of relatives. A larger proportion of SSD probands in this sample may limit comparisons between proband groups. This imbalance is a consequence of considering consecutive admissions to a FEP program and is likely to be representative of clinical FEP populations. The chi-square analysis used in comparison of the proportion of probands with familial psychopathology, and in comparison of Morbid Risks, is robust to mismatches in balance size. The t-test used in comparison of loading scores is more sensitive to such effects, though no significant findings were identified using this test. An additional limitation is the relatively high rate of nonparticipation in this study, with 94 completed FIGS interviews completed out of 195 consecutive admissions approached. Though the subjects and the patients who refused participation did not differ in terms of demographics or diagnostic category, a selection bias may still exist. In conclusion, in an epidemiologically representative sample of FEP patients, the majority had a family history of psychiatric illness in their first-degree relatives, with particularly high rates of MDD and Substance Use Disorders. Though the frequency of a family history of SSD was lower than in other studies, as many as a third of probands did have a family history of some form of psychosis. The frequency of a family history of illness did not differ between probands with a diagnosis of SSD or a diagnosis of AP. A family history of a substance use disorder was more likely among probands with a substance use disorder. Role of funding source This study was supported by a foundation grant from Valorisation de Recherche de Quebec through the Douglas Research Centre. Additional funds were made available through an operating grant from the Fonds de recherche en santé mentale du Québec (FRSQ) (#24501-2041) awarded to Drs. King & Joober (2002–2005). Dr. Faridi is supported in his fellowship by the PEPPMontreal program at the Douglas Mental Health Institute. Dr. Joober is supported by a salary award from the FRSQ. Dr. Malla is supported by the Canada Research Chair Program. None of these funding agencies played any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors Drs. Malla, Joober and King designed the study and wrote the protocol. Dr. Faridi performed the literature searches and analyses, the statistical analysis, and prepared the first draft of the paper. Ms. Pawliuk contributed to the statistical analysis. All authors contributed to and have approved the final manuscript. Conflict of interest None. Acknowledgements The research staff of the Prevention and Early Intervention Program for Psychoses in Montreal assisted with recruitment and assessments. The time and attention of the probands and their families is also appreciated.
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Psychiatric illness in firstdegree relatives of patients with paranoid psychosis, schizophrenia and medical illness. Br. J. Psychiatry 147, 524–531. Kendler, K.S., McGuire, M., Gruenberg, A.M., O'Hare, A., Spellman, M., Walsh, D., 1993a. The Roscommon Family Study. I. Methods, diagnosis of probands, and risk of schizophrenia in relatives.[see comment]. Arch. Gen. Psychiatry 50 (7), 527–540. Kendler, K.S., McGuire, M., Gruenberg, A.M., O'Hare, A., Spellman, M., Walsh, D., 1993b. The Roscommon Family Study. IV. Affective illness, anxiety disorders, and alcoholism in relatives. Arch. Gen. Psychiatry 50 (12), 952–960. Kendler, K.S., McGuire, M., Gruenberg, A.M., Walsh, D., 1995. Examining the validity of DSM-III-R schizoaffective disorder and its putative subtypes in the Roscommon Family Study. Am. J. Psychiatry 152 (5), 755–764. Maier, W., Lichtermann, D., Franke, P., Heun, R., Falkai, P., Rietschel, M., 2002. The dichotomy of schizophrenia and affective disorders in extended pedigrees. Schizophr. Res. 57 (2–3), 259–266. Maxwell, E., 1992. Family Interview for Genetic Studies. National Institute of Mental Health, Intramural Research Program – Clinical Neurogenetics Branch, Washington DC. Merikangas, K.R., Stolar, M., Stevens, D.E., Goulet, J., Preisig, M.A., Fenton, B., Zhang, H., O'Malley, S.S., Rounsaville, B.J., 1998. Familial transmission of substance use disorders. Arch. Gen. Psychiatry 55 (11), 973–979. Miles, D.R., Stallings, M.C., Young, S.E., Hewitt, J.K., Crowley, T.J., Fulker, D.W., 1998. A family history and direct interview study of the familial aggregation of substance abuse: the adolescent substance abuse study. Drug Alcohol Depend. 49 (2), 105–114. Miller D.C., 1991. Hollingshead two-factor index of social position, in (Ed.)^ (Eds.), Hand book of Research Design and Social Measurement. Sage Publications, Inc, Newbury Park, CA, p 353–359. Norman, R.M.G., Malla, A.K., Manchanda, R., 2007a. Delay in treatment for psychosis: its relation to family history. Soc. Psychiatry Psychiatr. Epidemiol. 42 (6), 507–512. Norman, R.M.G., Manchanda, R., Malla, A.K., Harricharan, R., Northcott, S., 2007b. The significance of family history in first-episode schizophrenia spectrum disorder. J. Nerv. Ment. Dis. 195 (10), 846–852.
K. Faridi et al. / Schizophrenia Research 114 (2009) 57–63 Roy, M.A., Walsh, D., Kendler, K.S., 1996. Accuracies and inaccuracies of the family history method: a multivariate approach. Acta Psychiatr. Scand. 93 (4), 224–234. Shimizu, A., Kurachi, M., 1989. Do women without a family history of schizophrenia have a later onset of schizophrenia? Psychiatry Clin. Neurosci. 43 (2), 133–136. Stalberg, G., Ekerwald, H., Hultman, C.M., Stalberg, G., Ekerwald, H., Hultman, C.M., 2004. At issue: siblings of patients with schizophrenia: sibling bond, coping patterns, and fear of possible schizophrenia heredity. Schizophr. Bull. 30 (2), 445–458.
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Tsuang, M.T., Winokur, G., Crowe, R.R., 1980. Morbidity risks of schizophrenia and affective disorders among first degree relatives of patients with schizophrenia, mania, depression and surgical conditions. Br. J. Psychiatry 137, 497–504. Verdoux, H., van Os, J., Sham, P., Jones, P., Gilvarry, K., Murray, R., 1996. Does familiality predispose to both emergence and persistence of psychosis? A follow-up study.[erratum appears in Br J Psychiatry 1996 Jul;169(1):116]. Br. J. Psychiatry 168 (5), 620–626.
Contents lists available at ScienceDirect
Schizophrenia Research j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / s c h r e s
Prevalence of psychotic and non-psychotic disorders in relatives of patients with a first episode psychosis Kia Faridi a,b,c, Nicole Pawliuk a,c, Suzanne King b,c, Ridha Joober a,b,c, Ashok K. Malla a,b,c,⁎ a b c
Prevention and Early Intervention Program for Psychosis, Montreal, Quebec, Canada Department of Psychiatry, McGill University, Montreal, Quebec, Canada Douglas Mental Health University Institute, Montreal, Quebec, Canada
a r t i c l e
i n f o
Article history: Received 11 August 2008 Received in revised form 29 June 2009 Accepted 6 July 2009 Available online 9 August 2009 Keywords: Schizophrenia First-episode psychosis Family history Familiality
a b s t r a c t Background: Family members of individuals with schizophrenia suffer from elevated rates of schizophrenia-spectrum disorders (SSD) and other forms of psychopathology. However, few studies have examined familial psychopathology in probands with a first episode of psychosis (FEP). We systematically evaluated family history in patients experiencing an affective or nonaffective FEP. Methods: The Family Interview for Genetic Studies was used to obtain diagnostic information on all first- and second-degree relatives of probands admitted to a specialized FEP program. Probands were 94 previously untreated patients suffering from a first-episode of affective or schizophrenia spectrum psychosis, aged 14 to 30. The interview ascertained diagnoses of psychotic disorders, affective disorders, substance-use disorders (SUD), and schizophreniarelated personality disorders. Results: One in five probands (19.1%) had a history of psychosis among their first-degree relatives, while 34.0% had any relative with psychosis. Fewer probands had a family history of SSD (7.4% with a first-degree history and 18.1% with a history among any relatives). Over half (53.2%) of probands had a first-degree relative with Major Depressive Disorder, and 38.3% had a first-degree relative with a SUD. Overall, 69.9% of probands had a first-degree relative with a mental disorder. The proportion of probands with a family history of any of these diagnoses did not vary by proband diagnosis (affective or SS Psychosis), though probands with co-morbid SUD were more likely to have a family history of substance abuse. Conclusions: Diverse psychopathology is commonly present in families of FEP patients and may imply a generalized vulnerability to psychiatric disorders to be greater in such families compared to specific vulnerability to SS or affective psychosis. These findings may also have implications for provision of care for the probands. © 2009 Elsevier B.V. All rights reserved.
1. Introduction The familial nature of schizophrenia is well documented, with the most robust evidence emerging from controlled epidemiologic studies (Kendler et al., 1985, 1993a; Tsuang et al., 1980). It has also been demonstrated that other psychotic disorders tend to aggregate in the families of probands with ⁎ Corresponding author. McGill University, Douglas Mental Health University Institute, 6875 Boul. Lasalle, Montreal, Qc, Canada H4H 1R3. E-mail address: [email protected] (A.K. Malla). 0920-9964/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.schres.2009.07.007
schizophrenia. Kendler used data from the Roscommon Family Study to support the existence of a Schizophrenia Spectrum, consisting of a shared liability between affective psychoses, nonschizophrenic non-affective psychoses, schizotypal and paranoid personality disorders, schizoaffective disorder, and schizophrenia (Kendler et al., 1995). Most studies confirm that affective illnesses do not form part of the Schizophrenia Spectrum (Kendler et al., 1995; Tsuang et al., 1980), though some studies have reported an increased risk of non-psychotic affective illnesses in the relatives of probands with schizophrenia (Chang et al., 2002; Kendler and Gardner, 1997; Kendler et al.,
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1993b; Maier et al., 2002). The increased risk of both psychotic and non-psychotic illness extends to both first-degree and more distant relatives of probands (Maier et al., 2002). Despite this extensive literature regarding family history in schizophrenia, few studies have evaluated family history in patients suffering from a first episode of psychosis (FEP). Aside from the inherent value in extending the body of knowledge regarding family history in psychotic disorders, studying this patient population may hold other advantages. Most clinical family studies of schizophrenia ascertain cases from a more chronic patient population. This entails a selection bias towards more severely ill or treatment resistant cases, as people with milder illness, or people who make a full recovery after a single psychotic episode, would not be part of this population. A FEP population is more likely to include such cases that would later be lost to follow-up and/or cases that would make a full recovery and which therefore would not be ascertained in studies of other clinical populations. Two studies have reported on the proportion of FEP patients with a family history of psychotic disorders. Norman et al. (2007b) recently examined the relationship of family history to a number of clinical characteristics and found that 15.7% of their largely non-affective FEP sample had a firstdegree relative with a schizophrenia spectrum disorder, and that those probands with a family history had a poorer outcome, a lower IQ, and increased rates of EEG abnormalities. Chen et al. (2005) reported that 23.1% of FEP patients in their sample had a family history of a psychotic disorder. While informative, these studies had certain limitations. They both used an instrument that does not systematically identify and evaluate each member of the pedigree and that screens for mental illness by exploring a history of treatment contacts. This method of ascertainment may have led to an underestimation of cases, and does not collect information on the number of unaffected relatives, or their ages, which are important in calculating scores of family loading. Further, both studies examined only probands with non-affective psychosis, and ascertained only psychotic illness among relatives. To our knowledge there are no reports of systematic evaluation of diverse forms of psychopathology in the families of FEP patients. Further, no study has examined family history in extended families including both first- and second-degree relatives of FEP probands. The primary objective of the present study was to add to the literature demonstrating the familial nature of psychotic illnesses by conducting a systematic evaluation of diverse forms of psychopathology in first- and second-degree relatives of patients with a non-affective or affective FEP. These relatives were evaluated for histories of psychotic disorders, affective disorders, psychosis-related personality disorders, and substance use disorders. We hypothesized that a family history of a schizophrenia spectrum disorder (SSD) is more prevalent in probands diagnosed with a SSD compared to probands with an affective psychosis (AP). 2. Methods 2.1. Setting and subjects The sample for this study is drawn from consecutive admissions to the Prevention and Early intervention Program for Psychoses (PEPP-Montreal), a program designed for the
assessment and treatment of all cases of FEP in a defined catchment area. Included patients were aged 14 to 30, suffering from symptoms meeting criteria for a DSM-IV psychotic disorder, and were not previously treated with antipsychotic medications for greater than one month. Exclusion criteria included the inability to speak either English or French; an IQ of less than 70; or an organic brain syndrome. All patients admitted to PEPP-Montreal who met these criteria were approached to take part in the study within the first year of their participation. A total of 195 consecutive admissions were approached, and 94 family history interviews were completed. 2.2. Measures Proband diagnosis was determined by the Structured Clinical Interview for DSM-IV (SCID) (First et al., 2002), administered by trained research assistants soon after entry to PEPP-Montreal. Diagnosis was established through consensus meetings with two senior psychiatrists (A.M. or R.J.). Probands were grouped into diagnostic categories of “Schizophrenia Spectrum Disorder” (Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Delusional Disorder, and Psychosis NOS) and “Affective Psychoses” (Major Depressive Disorder with Psychotic Features or Bipolar Affective Disorder with Psychotic Features). Parental socioeconomic status was assessed with the Hollingshead twofactor index of social position (Miller, 1991). Family history was ascertained by interviewing a firstdegree relative (usually a parent) of the proband, though in ten cases the probands themselves were suitable informants, and in two cases the informant was a sibling and a grandparent, respectively. The interview was conducted by trained research assistants. The informant assisted the interviewer in completing a family tree of the proband's first- and second-degree blood relatives. A structured interview, the Family Interview for Genetic Studies (FIGS) (Maxwell, 1992), was used to first identify potential cases of mental illness in the family tree, and then to systematically determine the diagnoses of psychotic disorders, affective disorders, Cluster A personality disorders, and substance use disorders in these individuals. For each relative, the diagnosis given was rated as to degree of certainty: “Certain” (relative was psychiatrically assessed and the diagnosis clearly made, treatment received); “Probable” (based on symptom profile); and “Reported” (informant reports the diagnosis, but little evidence of compatible symptoms). For the purposes of thisstudy, only “Certain” and “Probable” diagnoses were considered. The diagnoses for the relatives were grouped into a number of overlapping categories. “Schizophrenia Spectrum Disorder” referred to diagnoses of Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Paranoid Personality Disorder, and Schizotypal Personality Disorder. Relatives with Major Depressive Disorder (MDD) with Psychotic Features or Bipolar Affective Disorder (BAD) with Psychotic Features were grouped together as “Affective Psychoses”. A third category, “Any Psychosis”, was applied to any relative who received a diagnosis of SSD, affective psychosis, Delusional Disorder, Brief Psychotic Disorder,
K. Faridi et al. / Schizophrenia Research 114 (2009) 57–63
Psychosis NOS, or any drug-induced psychosis. Additional categories were created for any diagnosis of MDD, any diagnosis of BAD, and any substance-use disorder. These family history data are presented in three different ways. First, we report the proportion of probands with any positive family history of each diagnostic category, either among their first-degree relatives or among any (first- or second-degree) relatives. These data, though they are not age corrected, are presented as they give a clinical sense of the burden of familial illness in PEPP populations. For the diagnostic categories of Schizophrenia Spectrum Disorder and Any Psychosis, we calculated two age-corrected indicators of level of familiality: Morbid Risk (MR) and a Family Loading Score (FLS). The morbid risk is an age-corrected prevalence figure commonly reported in the literature. Morbid Risk was calculated using the Hardy-Weinberg abridged method, in which the prevalence denominator is decreased to account for relatives who remain in the age of risk (counted as 0.5). Morbid Risks were separately calculated for first- and second-degree relatives. Though commonly used, this method of age-correction is imprecise. For this reason, we also calculated a Family Loading score (Verdoux et al., 1996). This parameter accounts for the age of the affected relatives and the pedigree structure to produce a score that indicates the degree of ‘familiality’ for each proband. The calculation was modified from the original protocol to include second-degree relatives. For the purposes of this calculation, the risk of being ill in the presence of ‘familial schizophrenia’ was assumed to be 10% for first-degree relatives; for seconddegree relatives, this risk was assumed to be 3%. 2.3. Data analysis The data were analyzed to examine the rate of positive family history of the above mentioned categories, among first-degree relatives and amongst any relatives (first-degree or second-degree). These were compared by diagnostic status of probands (Schizophrenia Spectrum Disorder (SSD) vs. Affective Psychosis (AP)) using Pearson Chi-square test (or Fisher's exact test when the number of subjects in any cell was less than five). Morbid Risk was compared between groups by means of a chi-square analysis. A two-sided t-test was used to compare Loading Score between groups. 3. Results 3.1. Subjects 94 FIGS interviews were completed yielding diagnostic data on 1484 relatives. Proband diagnoses are listed in Table 1. Probands did not differ from patients who did not participate on any demographic variables or diagnostic categories (Table 2). 3.2. Family history of psychotic illnesses We found that 7 (7.4%) probands had a family history of a Schizophrenia-Spectrum Disorder amongst their first-degree relatives. If both first- and second-degree relatives are considered, 17 (18.1%) probands had a positive family history. For the broader diagnostic category of “Any Psychosis”, nearly
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Table 1 Diagnoses of probands. Diagnosis
n (94)
%
Schizophrenia spectrum disorders Schizophrenia Schizophreniform disorder Schizoaffective disorder Delusional disorder Psychosis NOS Affective psychoses MDD with psychotic features Bipolar disorder with psychotic features
74 36 3 16 4 15 20 4 16
78.7 38.3 3.2 17.0 4.3 16.0 21.3 4.3 17.0
a fifth (18 (19.1%)) of probands had a family history amongst first-degree relatives, while over a third (32 (34.0%)) had a family history of any psychosis amongst first- or seconddegree relatives. There was no significant difference in the rate of a positive family history of SSD, Any Psychosis, or affective psychosis, between SSD and AP probands (Table 3). The Morbid Risk (Table 5) or Loading Score (Table 4) for these categories did not differ between groups. 3.3. Family history of affective illness A history of MDD among first-degree relatives was reported by more than half of the probands (50 (53.2%)), while almost two-thirds (61 (64.9%)) report MDD among first- or second-degree relatives (Table 3). A history of BAD was less common: 7 (7.4%) probands had a history among their first-degree relatives, and 11 (11.7%) had a history among any relative (Table 3). There were no significant differences in the prevalence of family history of affective illness among the proband groups. 3.4. Family history of substance use disorders Overall, 36 (38.3%) probands had a first-degree relative with a substance-use disorder, while 56 (59.6%) probands had a first- or second-degree relative with a substance use disorder (Table 3). There was a trend for probands with a SSD to be more likely to have a history of a SUD among firstdegree relatives compared to probands with an affective psychosis (43.2% in SSD vs. 20% in affective psychosis; χ2 = 3.60; p = 0.058) (Table 3). This difference was less marked when 1st and 2nd degree relatives were considered (63.5% vs. 45.0%, χ2 = 2.24, p = 0.13). Probands who met criteria for a co-morbid diagnosis of SUD were significantly
Table 2 Demographic characteristics of subjects (probands) compared to nonparticipating PEPP patients.
Age at PEPP entry (Mean, (SD)) Male (%) Hollingshead class IV or V (%) Education, greater than 12 years (%) SSD diagnosis (%) Affective psychosis diagnosis (%) Substance-induced psychosis diagnosis (%) Substance use disorder diagnosis (%)
Subjects included
Subjects not included
22.7 (4.0) 67.3 54.4 53.8 78.7 21.3 0 53.8
23.1 (4.0) 71.3 57.4 48.0 82.0 14.6 3.4 55.4
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Table 3 Distribution of family history of psychiatric illness in probands with a FEP. Presence of diagnosis in relatives
Schizophrenia spectrum Any psychosis Affective psychosis Depression Bipolar Substance use disorder
1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree 1st degree 1st or 2nd degree
SSD probands (n = 74)
Affective probands (n = 20)
Overall (n = 94)
n (%)
n (%)
n (%)
4 (5.4%) 14 (18.9%) 13 (17.6%) 25 (33.8%) 7 (9.5%) 7 (9.5%) 40 (54.1%) 48 (64.9%) 5 (6.8%) 7 (9.5%) 32 (43.2%) 47 (63.5%)
3 (15.0%) 3 (15.0%) 5 (25.0%) 7 (35.0%) 1 (5.0%) 1 (5.0%) 10 (50.0%) 13 (65.0%) 2 (10.0%) 4 (20.0%) 4 (20.0%) 9 (45.0%)
7 (7.4%) 17 (18.1%) 18 (19.1%) 32 (34.0%) 8 (8.5%) 8 (8.5%) 50 (53.2%) 61 (64.9%) 7 (7.4%) 11 (11.7%) 36 (38.3%) 56 (59.6%)
χ2
0.010
0.104 0.000
3.600 2.241
p
0.163⁎ 1.00⁎ 0.524⁎ 0.919 1.00⁎ 1.00⁎ 0.747 0.991 0.638⁎ 0.239⁎ 0.058 0.134
⁎Indicates use of Fisher Exact Test. In all other cases, chi-square test was used.
more likely to have a family history of a SUD amongst first- or second-degree relatives compared to probands with no SUD (71.2% vs. 45.2%; χ2 = 6.48, p = 0.011; Table 6). When only first-degree relatives were considered, this difference missed significance (46.2% vs. 28.6%; χ2 = 3.04, p = 0.081). Family history of psychotic or affective disorders did not differ between probands with a secondary diagnosis of SUD and those without such a diagnosis (data not shown).
4. Discussion To our knowledge this is the first study to systematically evaluate the frequency of a family history of a variety of psychiatric disorders among patients presenting for a first episode of psychosis. We found a first-degree family history of schizophrenia-spectrum disorder in a relatively low proportion (5.4%) of probands with SSD compared to previous reports of 15.7% (Norman et al., 2007b) and 21% (Chen et al., 2005) and a similar lower rate when second-degree relatives were included (18.9% in the current sample vs. 27% in Norman et al. (2007a)). However, when a family history of any psychotic disorder is considered, the rates are higher, with 17.6% of probands reporting any psychotic disorder among first-degree relatives, and 33.8% reporting any psychotic disorder among first- or second-degree relatives. The discrepancies in the rates reported in our study and those reported in previous studies of FEP may be partially related to differences in assignment of diagnostic categories within the schizophrenia spectrum. For example, in the present study, 56% of families with a psychosis history had a history of SSD, compared to 93% reported by Chen et al. (2005). The precise
Table 4 Loading scores for psychotic illness categories.
Schizophrenia spectrum Any psychosis Affective psychosis
Proband diagnosis
Loading score
SD
SEM
p
SSD AP SSD AP SSD AP
0.03 0.09 0.60 0.92 − 0.08 0.12
1.29 1.75 1.77 2.44 1.04 1.85
0.15 0.39 0.21 0.55 0.12 0.41
0.862 0.518 0.532
diagnostic process used in the FIGS interview could have led to relatives being less likely to be classified as SSD, and more likely to receive labels of affective psychosis or Psychosis NOS. The rate of a positive family history of schizophrenia spectrum disorder in our first-episode population is lower than studies of subjects with a more long-standing diagnosis of schizophrenia. In the Roscommon study, a first-degree family history of schizophrenia was present in 27 of 173 (15.6%) probands with a non-affective psychosis, while 9.3% of probands with a psychotic affective illness had a family history of schizophrenia (Kendler et al., 1993a (Table 4)). Similar rates of a first-degree family history of non-affective psychosis (15.6% (Alda et al., 1996)) or schizophrenia (15.3% (Shimizu and Kurachi, 1989)) were reported in two studies that examined clinically ascertained probands with schizophrenia. One potential explanation of the lower rates found in the present study is the lower sensitivity of the family history method used in this study compared to the family study method used in the Roscommon study (this limitation is further discussed below). The difference may also result from a difference in our ability to use precise diagnostic labels, resulting in more relatives being diagnosed with ‘psychosis NOS’ in the present sample. However, the difference may also represent a lower rate of schizophrenia in the families of FEP patients, compared to probands with illness of variable duration. Studies of more chronic populations are likely to include a higher proportion of relatively more severe and/or treatment-resistant cases while those with very good outcomes may no longer be in the service system. These more chronic course cases have a heavier family loading for schizophrenia (Joober et al., 2005). A FEP sample may, therefore, be more likely to give a true representation of psychopathology in families of patients suffering from the full range of psychotic illness. Perhaps the most significant finding from our study is that an array of psychiatric disorders was very frequently present in the immediate families of subjects suffering from a FEP. Approximately half had a first-degree relative with depression, 40% had a first-degree relative with a SUD and 20% had a first-degree relative who had experienced some form of a psychotic disorder. Such high rates of non-psychotic and psychotic disorders in families of patients with a FEP may have several implications for the patient or for the care he/she receives. Siblings of people with schizophrenia often have
K. Faridi et al. / Schizophrenia Research 114 (2009) 57–63
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Table 5 Morbid risks for psychotic illness categories. Proband diagnosis
Diagnosis in relatives Schizophrenia spectrum
All probands SSD AP
1st degree 2nd degree 1st degree 2nd degree 1st degree 2nd degree
Any psychosis
BZ
MR
n
BZ
MR
n
BZ
MR
7 17 4 15 3 2
233 882.5 184 679.5 49 203
3.00% 1.93% 2.17% 2.21% 6.12% 0.99%
20 27 14 21 6 6
234.5 883.5 185 680.5 49.5 203
8.53% 3.06% 7.57% 3.09% 12.12% 2.96%
10 1 8 0 2 1
234.5 880 185 677 49.5 203
4.26% 0.11% 4.32% 0.00% 4.04% 0.49%
important care-giver roles, and often experience concerns about their own genetic liability to psychosis (Stalberg et al., 2004). It has been proposed that experiences with psychosis can increase stigma and resistance to coming to treatment or recognizing psychosis, or, alternatively, that family experience may sensitize patient and family to early symptoms, facilitating presentation for treatment (Hambrecht, 1995). The presence of a close family member suffering from depression or a substance-use disorder may be a source of major stress for a patient presenting an obstacle to recovery. The precise impact of a family history of non-psychotic disorders on a patient's presentation and care has not been explored. The frequent presence of a family history of these disorders emphasizes the importance of a thorough assessment of family psychopathology in clinical evaluation of patients with a FEP. In our sample, proband diagnostic category did not impact the frequency of a family history of any of our diagnostic groupings. This is an unexpected finding, as it has previously been reported that a family history of schizophrenia is more common in probands with a schizophrenia spectrum disorder (Kendler et al., 1993a). Our negative finding may represent a lack of statistical power to detect differences, particularly given the smaller proportion of probands with an affective psychosis diagnosis. However, inspection of the data reveals no trends in the expected direction. Another possibility is that, in FEP patients, the proband's symptomatology and diagnosis remains somewhat fluid during the earliest stages of illness; this initial variability in diagnosis could attenuate differences between diagnostic groups. This possibility is supported by Bromet et al. (2005) who found that in FEP patients, a SCID diagnosis at baseline was less predictive of diagnosis at 10 years compared to a SCID diagnosis determined at a later time point. A third possibility is that psychotic disorders share a common vulnerability and that schizophre-
Table 6 Distribution of family history of a SUD in FEP probands. Probands with SUD (n = 52) n (%)
Probands without SUD (n = 42) n (%)
SUD in 24 (46.2%) 12 (28.6%) 1st degree SUD in 37 (71.2%) 19 (45.2%) 1st or 2nd degree
Affective psychosis
n
Overall (n = 94) n (%)
χ2
p
36 (38.3%) 3.04 0.081 56 (59.2%) 6.48 0.011
nia and affective psychosis may not necessarily represent two distinct disease entities (Craddock et al., 2005; Crow, 1990). We found that probands with a concurrent substance-use diagnosis were more likely to have relatives with a substance use diagnosis, in keeping with previous reports (Merikangas et al., 1998; Miles et al., 1998). The strengths of this study include a sample likely to be representative of a clinical FEP population. PEPP-Montreal has a defined catchment area with no competing services and a well defined case identification initiative. It is thus likely that almost all new cases of psychosis within this sector will be referred to PEPP-Montreal. Ascertained cases represent the full spectrum of psychotic diagnosis. We believe that using a FEP clinical group captures aspects of the full spectrum of psychotic illnesses that can be missed when more chronic populations are examined. Given that the familial liability to schizophrenia and other psychiatric disorders is clearly not limited to first-degree relatives, an additional strength of the study is the systematic evaluation of both first- and second-degree relatives using the FIGS interview. Furthermore, this instrument allows a systematic assessment of a broad range of psychopathology that has not commonly been reported in the literature. Limitations of the present study include the use of the Family History method of gathering diagnostic information, rather than individual interviews with all relatives. However, a number of studies have found that the Family History technique is highly specific for diagnosing psychotic disorders (between 99% and 100%), but has only low to moderate sensitivity (Andreasen et al., 1977; Andreasen et al., 1986; Davies et al., 1997; Roy et al., 1996). The Relative Psychiatric History, which is similar to the FIGS, was found to have a moderate sensitivity of 44% for diagnosing “Any psychotic disorder”, but a specificity and positive predictive value of 100% for this diagnostic category (Fogelson et al., 2004). Similarly, Family History Instruments seem to have low- to moderate sensitivity and high specificity in the diagnosis of affective illness and substance use disorders in relatives (Davies et al., 1997; Miles et al., 1998). We are unaware of any studies evaluating the accuracy of Family History information obtained for second-degree relatives. Thus, the FIGS interview is likely to have underestimated the frequency of mental disorders but is unlikely to have misclassified relatives into incorrect diagnostic groups. The relatively young age of the relatives, an inevitable consequence of the young probands who were ascertained, represents another weakness of the present study, as not all
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relatives would themselves have passed through the age of risk for the onset of psychiatric illnesses. The use of the agecorrected Morbid Risk and the Family Loading Score serve to mitigate this factor by accounting for the age of relatives. A larger proportion of SSD probands in this sample may limit comparisons between proband groups. This imbalance is a consequence of considering consecutive admissions to a FEP program and is likely to be representative of clinical FEP populations. The chi-square analysis used in comparison of the proportion of probands with familial psychopathology, and in comparison of Morbid Risks, is robust to mismatches in balance size. The t-test used in comparison of loading scores is more sensitive to such effects, though no significant findings were identified using this test. An additional limitation is the relatively high rate of nonparticipation in this study, with 94 completed FIGS interviews completed out of 195 consecutive admissions approached. Though the subjects and the patients who refused participation did not differ in terms of demographics or diagnostic category, a selection bias may still exist. In conclusion, in an epidemiologically representative sample of FEP patients, the majority had a family history of psychiatric illness in their first-degree relatives, with particularly high rates of MDD and Substance Use Disorders. Though the frequency of a family history of SSD was lower than in other studies, as many as a third of probands did have a family history of some form of psychosis. The frequency of a family history of illness did not differ between probands with a diagnosis of SSD or a diagnosis of AP. A family history of a substance use disorder was more likely among probands with a substance use disorder. Role of funding source This study was supported by a foundation grant from Valorisation de Recherche de Quebec through the Douglas Research Centre. Additional funds were made available through an operating grant from the Fonds de recherche en santé mentale du Québec (FRSQ) (#24501-2041) awarded to Drs. King & Joober (2002–2005). Dr. Faridi is supported in his fellowship by the PEPPMontreal program at the Douglas Mental Health Institute. Dr. Joober is supported by a salary award from the FRSQ. Dr. Malla is supported by the Canada Research Chair Program. None of these funding agencies played any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Contributors Drs. Malla, Joober and King designed the study and wrote the protocol. Dr. Faridi performed the literature searches and analyses, the statistical analysis, and prepared the first draft of the paper. Ms. Pawliuk contributed to the statistical analysis. All authors contributed to and have approved the final manuscript. Conflict of interest None. Acknowledgements The research staff of the Prevention and Early Intervention Program for Psychoses in Montreal assisted with recruitment and assessments. The time and attention of the probands and their families is also appreciated.
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