Introduction
Schizophrenia can be a devastating illness, which is associated with huge disability across society (Murray & Lopez, Reference Murray and Lopez1996; World Health Organisation, 2001). This disorder can be associated with poor long-term outcomes (Lang et al. Reference Lang, Kosters, Lang, Becker and Jager2013), reduced life expectancy (Saha et al. Reference Saha, Chant and McGrath2007) and imposes a major financial cost to society, estimated at 460 million euros/annum in Ireland alone (Behan et al. Reference Behan, Kennelly and O’Callaghan2008).
Epidemiology aims to describe illness characteristics, such as demographics and risk factors of disease, with the ultimate aim of intervening to reduce morbidity and mortality (Gordis, Reference Gordis2009). The epidemiology of schizophrenia has been previously described in several international studies. Age of onset usually occurs during late adolescence or early adulthood (Owens et al. Reference Owens, Miller, Lawrie and Johnstone2005; Jones, Reference Jones2013), with an earlier mean age of onset in males (Angermeyer & Kuhn, Reference Angermeyer and Kuhn1988). The peak age of onset distribution occurs between 18 and 30 years for males and females, and there is a second peak later in life for females (American Psychiatric Association, 2000; Kirkbride et al. Reference Kirkbride, Errazuriz, Croudace, Morgan, Jackson, Boydell, Murray and Jones2012). This age of onset distribution suggests that adequate resources should be provided for identifying and treating individuals presenting with psychosis at this young age.
Momentum for delivery of specialised first episode psychosis (FEP) services has increased over the last few decades (McGorry, Reference McGorry2013). FEP services have been introduced in Ireland, and are established in several other countries such as United Kingdom, Australia and Canada. Concurrently, services that specialise in youth mental health have been growing internationally (Birchwood & Singh, Reference Birchwood and Singh2013). This has provided focus for intervention in the young with a view to improving lifelong mental health.
Given that FEP and youth mental health have been identified as an important target for mental health research, the current epidemiological study investigates early psychosis in a youth population. To our knowledge, no previous Irish study has compared characteristics and symptoms between a youth population and an older FEP population. The aim of this exploratory study was to describe characteristics and symptoms in a youth FEP sample, and compare with a sample aged over 25 years. We chose 25 years as a cutoff, as this age has been used for delivery of youth mental health services both in Ireland and internationally (McGorry et al. Reference McGorry, Bates and Birchwood2013). This research is part of a larger project investigating symptomatology, specifically negative symptoms and FEP outcomes (Lyne et al. Reference Lyne, Renwick, Madigan, O’Donoghue, Bonar, Grant, Kinsella, Malone, Turner, O’Callaghan and Clarke2014).
Methods
Study setting and participants
The study was based in the Dublin and East Treatment and Early Care Team (DETECT), an Irish early intervention in psychosis service, located in South Dublin and County Wicklow between February 2005 and January 2012. DETECT receives referrals for all inpatient and outpatient cases of suspected FEP aged 16–65 years within a defined catchment area. The catchment area comprises three geographically defined mental health services serving a population of 390 000. DETECT also receives referrals from St. John of God Hospital, a private inpatient psychiatric facility located within the catchment area, which receives referrals from both within the catchment area and nationally. Proactive efforts are made to identify cases of suspected psychosis within the DETECT catchment area.
Following referral to the service, a Structured Clinical Interview for DSM IV (SCID) assessment was conducted to determine the presence or absence of a psychosis diagnosis (First et al. Reference First, Spitzer, Gibbon and Williams1995). All individuals satisfying criteria for a psychosis diagnosis and with <30 days antipsychotic treatment were eligible for study inclusion. Individuals with learning disability and with psychotic disorder owing to a general medical condition were excluded from the study. In the entire study sample of 437 individuals, 158 (36.2%) individuals were aged 25 years and under, whereas 279 (63.8) individuals were aged over 25 years. The 25 years and under sample will be referred to as the youth sample for the rest of the manuscript. Informed consent was obtained from all study participants and ethics approval was obtained before commencing the study.
Measures
A comprehensive assessment was conducted at first presentation for all study participants. Demographic information was collected, including age, gender, marital status, living status, socioeconomic group, country of birth and working status. SCID assessment also determined the presence or absence of a lifetime diagnosis of substance abuse/dependence, including for alcohol and cannabis abuse. The term substance abuse diagnosis is used throughout the manuscript to refer to individuals with a lifetime substance abuse/dependence diagnosis.
Negative symptoms were measured with the Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, Reference Andreasen1984a), which has been recommended for use in negative symptom research (Kirkpatrick et al. Reference Kirkpatrick, Fenton, Carpenter and Marder2006). Positive symptoms were measured using the Scale for the Assessment of Positive Symptoms (SAPS) (Andreasen, Reference Andreasen1984b). Standardised remission criteria were used to determine the presence of positive and negative symptoms in the sample (Andreasen et al. Reference Andreasen, Carpenter, Kane, Lasser, Marder and Weinberger2005). The Calgary Depression Scale for Schizophrenia was used to measure depressive symptoms, for which a cutoff score of 7 or greater was used to determine the presence or absence of depressive symptoms (Addington et al. Reference Addington, Addington and Maticka-Tyndale1993).
The Beiser Scale was used to determine the first onset of the psychosis prodrome and the first onset of psychosis, in order to determine duration of untreated psychosis (DUP), duration of psychosis prodrome (DP) and duration of untreated illness (DUI) (Beiser et al. Reference Beiser, Erickson, Fleming and Iacono1993). DUP was recorded in months as the duration between first onset of prominent psychotic symptoms and the date of first presentation for treatment. DP was recorded in months as the duration between onset of first noticeable signs and first onset of prominent psychotic symptoms. DUI was recorded in months as the sum of the DP and DUP.
Premorbid adjustment was measured by summing all items of the Premorbid Adjustment Scale (PAS) and dividing by the total possible score for these items (Cannon-Spoor et al. Reference Cannon-Spoor, Potkin and Wyatt1982; van Mastrigt & Addington, Reference van Mastrigt and Addington2002). Higher scores on PAS represent poorer premorbid adjustment. Items from age groups that overlapped with or occurred subsequent to psychosis prodrome onset were excluded to ensure PAS scores were not influenced by psychosis prodrome symptoms.
Inter-rater reliability was conducted for each of the 17 data collectors in the study. Intraclass correlation coefficients (ICC) for SANS global total ranged between 0.67 and 0.99 for SANS (median 0.86, 16 out of 17 raters had ICC of >0.7), between 0.82 and 1.00 for SAPS (median 0.91) and between 0.78 and 1.00 for DUP, DP and DUI (median 0.99). Concordance of SCID diagnosis across raters was >0.82 for all assessors.
Statistical analysis
For the purposes of this study, data were anonymised and SPSS statistical software was used to conduct analyses. Significance level for statistical testing was set at 0.05, and all statistical tests were two-tailed. The Beiser Scale was used to determine first symptom onset (either prodromal or psychosis) by subtracting DUI from age at first presentation. Where DUI data was unavailable (n=17), DUP was used to calculate first symptom onset.
Logarithmic transformations were used to normalise the positively skewed distributions for DP, DUP and DUI for statistical tests. χ 2 test was used to compare categorical characteristics across relevant categories, whereas independent samples t-test was used to compare continuous variables across relevant categories. Variables significantly associated with age category were included as explanatory variables in a binary logistic regression model to assess for confounding. Age category was the binary dependent variable in the model. The variation in the model explained by the dependent variable was ascertained using the Cox and Snell R 2 and the Nagelkerke R 2.
Results
Sample description and first symptom onset
The mean age of the entire sample was 32 years (s.d.=11.6). In all, 40% of the sample was female, 65% were inpatient at first assessment, median DUP was 3 months and median DUI was 12 months.
First symptom onset occurred at age 25 years and under for 46.7% of the entire sample aged 16–65 years. Onset of first symptoms occurred before age 18 years for 9.3% of the entire sample. Of the youth sample, 23.4% experienced first symptoms before the age of 18 years. Figure 1 shows the age at first symptom onset and age at first presentation for the youth sample. Highest percentage of first symptom onset in this age category was in the 17–19 years age category (36.1%).
Age at first symptom onset (prodrome or psychosis) and age at first presentation for treatment in the 25 years and under sample.
Comparison of characteristics across age categories
Comparison of all diagnoses between the youth sample and the over 25 years sample suggested a significant difference (χ 2=22.81, p=0.004). When individual diagnoses were considered, the youth sample had significantly fewer cases of delusional disorder and significantly more cases of substance-induced psychosis (Table 1). In Table 1, the schizophrenia spectrum group included schizophrenia (n=142), schizophreniform disorder (n=43) and schizoaffective disorder (n=6). The substance-induced psychosis group included individuals with substance-induced psychotic disorder (n=50) and substance-induced mood disorder with psychotic features (n=9).
Sample diagnoses
NOS, not otherwise specified.
**Significance level of p<0.01 comparing ⩽25 years and >25 years.
Significant differences in the characteristics of the youth sample included fewer living alone, fewer married, more diagnoses of cannabis abuse, more negative symptoms and shorter DUP (Table 2). Of note, median DUP was 3 months in both the youth sample and the over 25 years sample. In the youth male sample, 28.0% had a diagnosis of cannabis abuse and 35.5% had a diagnosis of any substance abuse.
Comparison of categorical and continuous characteristics at first presentation across age categories
PAS, Premorbid Adjustment Scale; DUP, duration of untreated psychosis; DP, duration of psychosis prodrome; DUI, duration of untreated illness.
Data excluded from table where missing.
*Significance level of 0.05>p>0.01 comparing ⩽25 years and >25 years.
**Significance level of p<0.01 comparing ⩽25 years and >25 years.
The five significantly different characteristics in the youth sample were included as explanatory variables in a binary logistic regression model, with age category as the binary dependent variable. Explanatory variable data was missing for 14 cases leaving 423 cases for the regression analysis. The variation in the model explained by the dependent variable (R 2) was between 23% and 31%. Omnibus test of model coefficients was significant (p<0.001) for the regression model (p-values of <0.05 suggest good model fit). The significance level for the Hosmer–Lemeshow Goodness of Fit Test (p=0.947) was >0.05 (Field, Reference Field2005). Each of the explanatory variables remained significant predictors of age category in the regression analysis (Table 3). When we repeated the regression analysis as a linear regression analysis with the same explanatory variables and with age as a continuous dependent variable, each of the explanatory variables remained significant except for negative symptoms (β=0.75, 95% CI −0.20–3.73, p=0.078).
Logistic regression model with age category as the binary dependent variable (n=423)
OR, odds ratio; DUP, duration of untreated psychosis.
Subanalysis of youth sample
Given the relatively higher prevalence of negative symptoms in the youth sample, we conducted a subanalysis comparing characteristics in a negative symptom (n=78) and no negative symptom group (n=80) in the youth sample. The significant differences in the negative symptom group included fewer working (20.5% v. 46.2%), more with a schizophrenia spectrum diagnosis (70.5% v. 23.8%), poorer premorbid adjustment (mean 0.23 v. 0.16), longer log DUP (mean 0.82 v. 0.46) and longer log DUI (mean 1.29 v. 0.85).
Given the relatively higher prevalence of cannabis abuse diagnosis in the youth sample, we conducted a subanalysis comparing characteristics among individuals with (n=34) and without (n=124) cannabis abuse diagnosis in the youth sample. This subanalysis aimed to determine whether characteristics of youth individuals with cannabis abuse differed from the rest of the youth sample. Significant differences were noted for the cannabis abuse group including more males (88.2% v. 62.1%) and more alcohol abuse diagnoses (32.4% v. 6.5%).
Given that not all individuals with comorbid cannabis abuse diagnosis had a primary diagnosis of substance-induced psychosis (15 out of 34 individuals with cannabis abuse diagnosis had a primary diagnosis of substance-induced psychosis), we conducted a further analysis comparing individuals in the sample with substance-induced psychosis diagnosis (n=32) with the rest of the youth sample (n=126). This subanalysis only showed significantly more cannabis abuse diagnoses (46.9% v. 15.1%) and more alcohol abuse diagnoses (25.0% v. 8.7%) in the substance-induced psychosis sample. When this analysis was repeated excluding affective psychosis (n=32), the substance-induced psychosis sample had significantly fewer negative symptoms (34.4% v. 66.0%), shorter log DUP (mean 0.50 v. 0.77), more cannabis abuse diagnoses (46.9% v. 16.0%) and more alcohol abuse diagnoses (25.0% v. 9.6%).
Discussion
This study described characteristics and symptoms in an FEP sample, comparing a youth sample with a cohort aged over 25 years. Within the youth sample, first onset of symptoms commonly occurred before age 18 years. The youth sample had more substance-induced psychosis diagnoses, more cannabis abuse diagnoses and more negative symptoms at first presentation. The over 25 years sample had more delusional disorder diagnosis, longer DUP, were more likely to be married and more likely to be living alone. Individuals with negative symptoms in the youth sample were less likely to be working, had poorer premorbid adjustment and longer delays to treatment. Individuals with cannabis abuse diagnosis in the youth sample were predominantly male; those with substance-induced psychosis were more likely to have shorter DUP and fewer negative symptoms than the non-affective FEP sample.
The findings of lower likelihood of living alone and being married in the youth sample are intuitive and consistent with previous studies (Subramaniam et al. in press). The finding in relation to marital status likely reflects the age demographic during which marriage occurs, whereas the living status finding could be explained by the younger sample commonly residing with their parents, although we cannot definitively conclude this from our data.
Negative symptoms
Overall, the sample had a high prevalence of negative symptoms, and the youth sample had greater negative symptoms than the over 25 years sample at first presentation. Of note, when the regression analysis was repeated with age as a continuous variable, the relationship between age and negative symptoms was no longer significant. The finding of greater negative symptoms among those with younger age of onset has been reported previously (Clarke et al. Reference Clarke, Whitty, Browne, McTigue, Kamali, Gervin, Kinsella, Waddington, Larkin and O’Callaghan2006); however, the finding requires further study and the reasons for this finding are not fully clear. Those with negative symptoms in the youth sample had poorer premorbid adjustment and longer delays to treatment, both of which could be a contributing factor to negative symptoms (MacBeth & Gumley, Reference MacBeth and Gumley2008; Boonstra et al. Reference Boonstra, Klaassen, Sytema, Marshall, De Haan, Wunderink and Wiersma2012); these individuals were also less likely to be working, which could have impact on their recovery and quality of life (Turner et al. Reference Turner, Browne, Clarke, Gervin, Larkin, Waddington and O’Callaghan2009).
The high prevalence of negative symptoms across all age categories suggests the need for a more intensive approach to treating these symptoms following FEP presentation. This approach could consist of a ‘second wave’ of intervention delivered during the medium term after initial presentation to prevent the progression of negative/cognitive deficits and functional disability (Alvarez-Jimenez et al. Reference Alvarez-Jimenez, Gleeson, Henry, Harrigan, Harris, Killackey, Bendall, Amminger, Yung, Herrman, Jackson and McGorry2012). Possible interventions include cognitive behavioural therapy, cognitive remediation therapy, supported employment and family education, as well as a detailed review of the need for pharmacotherapy strategies such as clozapine.
Substance use and other characteristics
Given the high prevalence of cannabis and other substance use diagnoses in the youth sample, services treating young individuals with FEP, particularly young males, need to be adequately resourced to cater for these needs. The finding of greater cannabis use in those with presentation in youth is consistent with a previous meta-analysis, which suggested a relationship between cannabis use and earlier onset of psychosis (Large et al. Reference Large, Sharma, Compton, Slade and Nielssen2011). It should be noted that this relationship could have several explanations, such as a generally higher rate of cannabis use in young populations, rather than greater cannabis having a causal relationship with younger onset of psychosis. Interpretation of this relationship is further complicated by the possibility that substance-induced psychosis could be a different condition to schizophrenia. This would be supported by our finding of significant differences between the youth sample with substance-induced psychosis and the rest of the youth sample with non-affective psychoses. Ongoing research relating to this should focus on the age of cannabis use onset and the trajectory of psychotic symptoms (Stefanis et al. Reference Stefanis, Dragovic, Power, Jablensky, Castle and Morgan2013).
The substance-induced psychosis youth sample had fewer negative symptoms than the non-affective FEP youth sample, which is consistent with a previous study reporting fewer negative symptoms among individuals with schizophrenia and comorbid substance use disorder (Potvin et al. Reference Potvin, Sepehry and Stip2006). The finding of shorter DUP in the substance-induced psychosis sample could be explained by a more acute presentation following the onset of psychosis owing to substance misuse when compared with the insidious illness onset sometimes associated with schizophrenia.
The finding that not all individuals with cannabis abuse diagnosis had a substance-induced psychosis diagnosis suggests that when considered clinically, cannabis abuse is common among individuals whose psychotic symptoms do not present as being directly related to cannabis abuse. All SCID diagnoses in this study were discussed at consensus clinical meetings attended by a senior psychiatrist. In spite of previous advances in clinical descriptions of illness, the boundaries between some early psychosis diagnoses such as substance-induced psychosis and schizophrenia remain blurred, which is supported by previous findings that up to half of individuals with substance-induced psychosis may eventually develop schizophrenia (Whitty et al. Reference Whitty, Clarke, McTigue, Browne, Kamali, Larkin and O’Callaghan2005; Bromet et al. Reference Bromet, Kotov, Fochtmann, Carlson, Tanenberg-Karant, Ruggero and Chang2011). Future research should aim to improve our understanding diagnostic boundaries in psychosis (Carpenter, Reference Carpenter2014).
Overall, substance abuse did not differ between the youth sample and the over 25 years sample, which may be partly explained by a non-significantly higher alcohol abuse diagnosis in the over 25 years sample. This finding highlights the importance of managing comorbid substance use conditions across all age categories in FEP presentations.
It is estimated that ~40% of people with psychosis will abuse substances at some point in their lifetime (National Institute for Health and Care Excellence, 2011), and our findings suggest that almost 30% satisfy a substance abuse diagnosis at first presentation with psychosis. Comorbid substance abuse can complicate management of FEP for several reasons: substance use can result in psychosis relapse and can increase the challenge for engaging individuals with mental health services. Implementation of guidelines and intensive early management of dual diagnosis presentations may be necessary for management of these complex needs (NICE, 2011).
Onset of FEP symptoms
Major mental disorders commonly have onset in adolescence and early adulthood (Jones, Reference Jones2013), and this study supports that young individuals presenting with FEP commonly have onset of first symptoms before the age of 18 years. In our sample, prodromal and psychotic symptoms were present before age 18 years in 23.4% of the youth sample. This suggests that symptoms are commonly present during the transition from adolescence to adulthood, which needs consideration when delivering services to young individuals with FEP.
Strengths and limitations
Some of the variables collected, such as delays to treatment and premorbid adjustment, may have been subject to recall bias owing to the retrospective nature of their data collection. Multiple raters collected data for the study, which may have introduced measurement bias, although comprehensive training was given to all data collectors before commencement, and median inter-rater reliability was good for all scales. Inter-rater reliability for the SANS was good for most raters, although of note ICC was <0.7 for one rater.
Strengths of the study are that to our knowledge this is the largest epidemiological description of FEP in a youth population in Ireland to date. Validated and reliable scales such as the SCID were used for all participants. The use of face-to-face interview for consecutive inpatient and outpatient FEP presentations is a further study strength.
Conclusions
This description of characteristics and symptoms in a young Irish FEP sample is important, given the lack of previous epidemiological studies conducted on youth samples in Ireland to date (Lynch et al. Reference Lynch, Mills, Daly and Fitzpatrick2006). The findings can inform the ongoing development of services for young people in Ireland. Early intervention strategies play an important role for management of FEP (McGorry, Reference McGorry2013), and our findings suggest the need for adequate resources for management of negative symptoms and substance abuse in early psychosis. It is essential that we continue to evaluate how our services cater for young people with the aim of providing high-quality care for serious mental illness in youth (McNamara et al. Reference McNamara, McNicholas, Ford, Paul, Gavin, Coyne, Cullen, O’Connor, Ramperti, Dooley, Barry and Singh2014).
Acknowledgements
The authors wish to thank all individuals who took part in this study. The authors would also like to acknowledge the input of all clinicians in the referring mental health services. The authors would like to thank Ms Daria Brennan and Ms Felicity Fanning for their contribution to this research. The authors wish to express gratitude to the members of the DETECT early intervention in Psychosis consortium.
This work was funded by the Hospitaller Order of St. John of God and the Health Service Executive. Neither funding body had any further role in the study design, the collection, analysis or interpretation of data, in the writing of the report or in the decision to submit the paper for publication.
Conflicts of Interest
The authors declare they have no conflicts of interest.
