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Adolescent vs. adult onset of a first episode psychosis: Impact on remission of positive and negative symptoms

Schizophrenia Research, Volume 174, Issue 1-3, July 2016, Pages 183 - 188

Abstract

Objective

Adolescent-onset psychosis has traditionally been characterized as a more severe form of psychosis with a poorer prognosis. However, it is still unclear if patients with an adolescent-onset have worse symptom remission outcomes. Symptom remission is the principal clinical outcome known to predict quality of life and social functioning in the long term. The goal of this study is to clarify the influence of age of onset of psychosis on symptom remission in a sample of first-episode psychosis patients.

Method

A total of 246 first-episode psychosis patients were recruited from a specialized early intervention program serving a defined epidemiological catchment area. Age of onset of psychosis (adolescence vs. adulthood) was used as the main predictor, and duration of untreated psychosis (DUP), baseline symptoms, baseline functioning, substance abuse diagnosis, medication adherence and gender were used as covariates in hierarchical regression models predicting the following positive and negative symptom remission outcomes: maximum continuous months in remission and early remission (i.e., occurring in the first three months of follow-up).

Results

After controlling for other variables, onset of psychosis in adulthood and shorter DUP predicted early remission of positive symptoms. This effect was stronger in patients with a diagnosis of a schizophrenia-spectrum disorder. Remission of negative symptoms did not depend on age of onset, and was only predicted by baseline negative symptoms.

Conclusion

Patients with onset of psychosis during adulthood are more likely to achieve early positive symptom remission than those with adolescent onset. This effect might be stronger in patients with a diagnosis of a schizophrenia-spectrum disorder.

Abbreviations: CORS - Circumstances of Onset and Relapse Schedule, DUP - duration of untreated psychosis, LOCF - last observation carried forward, OR - odds ratio, PAS - Premorbid Adjustment Scale, PEPP - Prevention and Early Intervention Program for Psychosis Montreal, RSWG - Remission in Schizophrenia Working Group, SANS - Scale for the Assessment of Negative Symptoms, SAPS - Scale for the Assessment of Positive Symptoms, SCID-IV - Structured Clinical Interview for DSM-IV Axis I Disorders, SOFAS - Social and Occupational Functioning Assessment Scale, β - Standardized Beta Coefficient, VIF - variance inflation factor.

Keywords: First-episode-psychosis, Adolescence, Age at onset, Symptom remission, Multivariable regression.

1. Introduction

An important clinical characteristic associated with the course of psychotic disorders is the age at onset of psychosis. Earlier ages of onset of psychosis are associated with more psychopathology (Langeveld et al., 2012), greater cognitive impairment (Rajji et al., 2009), more early conduct problems (Vinokur et al., 2014), premorbid personality changes (Skokou et al., 2012), and structural brain changes (Burke et al., 2008). Furthermore, adolescent-onset patients often exhibit unfavorable risk factors such as longer duration of untreated psychosis (DUP) (Ballageer et al., 2005), poorer premorbid adjustment (Larsen et al., 2004), and higher rates of substance abuse (Pencer et al., 2005). Thus, adolescent-onset patients are expected to have worse clinical and functional outcomes than those with an adult onset.

Symptom remission is a fundamental clinical outcome by itself (Iyer et al., 2015), that also has prognostic value for social and occupational functioning (Cassidy et al, 2010a and Jordan et al, 2014), higher levels of life satisfaction (Bodén et al., 2009) and paid or voluntary employment (Üçok et al., 2011), better quality of life (Emsley et al., 2007), and better long-term functional and vocational recovery (Alvarez-Jimenez et al., 2012). Thus, assessing the influence of having an adolescent versus an adult onset of psychosis on symptom remission might provide insight on the natural history, clinical evolution, and functional prognosis of a first-episode of psychosis in these two different groups of patients.

Previous studies have examined the influence of age at onset of psychosis as a continuous variable on symptom remission, yielding equivocal findings (Addington and Addington, 2008, Ballageer et al, 2005, Chang et al, 2012, Crumlish et al, 2009, Langeveld et al, 2012, and Verma et al, 2012). Only one previous study has compared adolescent versus adult-onset patients without finding any differences (Schimmelmann et al., 2007). However, to our knowledge, no study has assessed the influence of having an adolescent versus an adult onset of psychosis (as a grouping variable) on symptom remission using a widely accepted definition, or studied related aspects such as length or remission of negative symptoms, while accounting for other established predictors of symptom remission. Separating adolescents and adults may have an additional value considering these groups have different roles, living situations, legal statuses, and are offered services in different parts of the system.

The main goal of this study is to determine the influence of having an adolescent versus an adult onset of psychosis on various aspects of symptom remission while controlling for other known predictive variables. We hypothesized that patients with adolescent-onset psychosis would have poorer symptom remission outcomes — early remission (i.e., occurring in the first three months after initiation of treatment), and number of continuous months in remission — when compared to their adult-onset counterparts. As a secondary objective, we sought to explore the impact of age of onset on symptom remission outcomes separately among individuals with non-affective psychotic disorders, given the known differences in clinical outcomes (Jarbin et al., 2003) and neurobiological changes (Walterfang et al., 2009) between these and individuals with an affective psychotic disorder.

2. Materials and methods

2.1. Participants and setting

Participants were recruited from the Prevention and Early Intervention Program for Psychosis (PEPP), the only specialized early intervention service for patients experiencing a first episode of psychosis in a predominantly urban catchment-area of 400,000 inhabitants in Montreal, Canada. PEPP treats nearly all potential cases of FEP in this catchment area (Anderson et al., 2013), increasing the generalizability of our findings. Further, due to strong linkages with all local health care and community partners, participants who disengage from PEPP and later seek services elsewhere are almost always referred back. PEPP's admission criteria include: a DSM-IV diagnosis of non-affective or affective psychosis not due to an organic brain disorder (e.g. epilepsy); age 14 to 35 years old; IQ of 70 or greater; and no more than one month of prior treatment with antipsychotics. Patients are offered low-dose antipsychotic medication, assertive case-management and psychosocial interventions for two years (Iyer et al., 2015). This study was approved by the appropriate ethics board. All participants granted informed consent.

2.2. Remission definitions

Remission was defined using the Remission in Schizophrenia Working Group (RSWG) criteria, which are based on symptom severity and duration, and are widely accepted (Andreasen et al., 2005). This definition has demonstrated prognostic validity for functional outcome (Jordan et al., 2014) and quality of life (Brissos et al., 2011). Using RSWG severity criteria for every month of follow-up, patients were considered in positive symptom remission if they scored ≤ 2 on all Scale for the Assessment of Positive Symptoms (SAPS) (Andreasen, 1984) global subscales (i.e., hallucinations, delusions, bizarre behavior and formal thought disorder). Patients were considered in negative symptom remission if they scored ≤ 2 on all Scale for the Assessment of Negative Symptoms (SANS) (Andreasen, 1983) global items except ‘attention’ (i.e., affective flattening, alogia, avolition-apathy, anhedonia-asociality). Symptom evaluations were conducted nine times during the two-year treatment period (at entry and months 1, 2, 3, 6, 9, 12, 18, and 24). For the months without an evaluation, information on positive remission was coded from clinical notes. If clinical notes were insufficient, the last observation carried forward (LOCF) technique was used. For negative symptom remission, only the LOCF technique was applied for months without symptom evaluations due to the lower accuracy when scoring negative symptoms from clinical notes. Data were considered valid for analysis if baseline and last month (month 24) evaluations were conducted, and there was no gap of six or more consecutive months of evaluations (thus hindering the application of LOCF). Our previous work has shown these estimates to be 82.9% accurate (Jordan et al., 2014). No significant differences in the percentage of patients with early remission or the number of total or continuous months in remission (positive or negative) were found between cases with complete observations and those for which LOCF was needed (Supplementary Table 1).

Two aspects of remission were considered. The first consisted of the maximum number of continuous months in which the RSWG severity criterion for symptom remission was present. The second reflected the achievement of early remission, defined as attaining the RSWG severity criterion at any month within the first three months after admission. The number of continuous months of symptom remission is arguably a more ecologically valid metric of remission than a categorical metric of whether or not persons were in remission for a specified duration. Early remission has shown stronger predictive value for lower positive symptoms, better global functioning, and better employment stability after five years (Norman et al., 2014). Both variables were independently established for remission of positive and negative symptoms, as the latter represent different psychopathological dimensions (Kumar and Khess, 2012), have different neuroanatomical substrates (Nenadic et al., 2010), and prognostic implications (Milev et al, 2005 and Rosen and Garety, 2005).

2.3. Predictors of remission

Age at onset of psychosis was defined as the age at which the severity and duration of psychotic symptoms met threshold criteria for psychosis using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-IV) (First et al., 2002). It was determined using the Circumstances of Onset and Relapse Schedule (CORS) (Norman et al., 2004), a semi-structured interview administered to patients by a trained evaluator with collateral information from families and medical records. Onset between 14 and 17 years of age was considered ‘adolescent-onset’ psychosis and onset occurring at or after age 18 was considered ‘adult-onset’.

The following ancillary factors that predict symptom remission were included in the analyses: DUP, premorbid adjustment, severity of psychopathology and functional levels upon entry, substance use/abuse diagnosis, medication adherence, and gender (Lambert et al., 2010). DUP was defined as the time (in weeks) from onset of psychosis to the beginning of antipsychotic medication taken either continuously for 30 days or until symptom remission, whichever came earlier. Premorbid functioning was assessed with the Premorbid Adjustment Scale (PAS) (Cannon-Spoor et al., 1982), using a composite score of social and academic dimensions during childhood and early adolescence. Late adolescence and adulthood information was omitted due to the temporal overlap with the period of onset of psychosis. Baseline psychotic symptoms were determined using the SAPS and the SANS. Baseline functioning was determined with the Social and Occupational Functioning Assessment Scale (SOFAS) (Goldman et al., 1992). Modal medication adherence was defined using a validated method (Cassidy et al., 2010b) and dichotomously coded as either good (75–100% compliance) or not (0–74% compliance). Monthly assessments were conducted using several sources, including patients, families and clinical notes. Diagnoses (including baseline substance abuse or dependence) were established using the SCID-IV, administered by a trained interviewer and corroborated by two psychiatrist-researchers. Diagnoses were further clustered into diagnostic categories: Schizophrenia Spectrum Disorders (i.e., schizophrenia, schizophreniform disorder, schizoaffective disorder, psychosis NOS), and affective psychoses (i.e., bipolar or depressive disorders with psychotic features).

2.4. Statistical analyses

Preliminary analyses comprised: 1) comparing participants and non-participants in terms of diagnosis, predictors of remission and demographic characteristics, 2) assessing the normality and multicollinearity of predictor variables, and 3) univariable analyses between predictors and outcome variables examining unadjusted effects. Main analyses were conducted using hierarchical regression models to assess the effect of the category of age at onset (adolescent vs. adult) on the remission outcome variables of interest, while controlling for other known covariates. Categorical outcomes (i.e., achieving early remission of positive or negative symptoms) were analyzed using logistic regression, while continuous outcomes (i.e., maximum number of continuous months in remission of positive or negative symptoms) were estimated using linear regression. The above-mentioned covariates were entered into the first block followed by age of onset in the second block. The same hierarchical model was also tested for the group of schizophrenia spectrum disorder patients.

3. Results

3.1. Demographic and clinical characteristics

Patients who entered PEPP between 2003 and 2012 were considered for inclusion (N = 399). As described earlier, cases were excluded if their data were not valid for analysis (i.e., did not have baseline or month 24 assessments or had more than 6 months of missing data between baseline and month 24). For the positive symptom remission analysis, 153 cases were excluded, yielding 246 valid cases, including 30 in which the LOCF procedure was applied. For the remission of negative symptoms analysis, 184 cases did not have valid data, leaving 215 valid cases, including 82 in which LOCF was used. Table 1 shows the demographic and clinical characteristics of participants and non-participants. The only significant difference is a slightly higher baseline SOFAS score among participants (5 on a 100-point scale).

Table 1 Comparison of demographic variables between participants and non-participants, positive and negative remission analyses (two-year follow-up).

Variables Positive remission analysis Negative remission analysis
Participants Non-participants Sig1. Participants Non-participants Sig1.
Total N 155 91 142 73
Age at entry – mean (SD) 22.89 (± 4.32) 23.4 (± 4.62) 0.38 22.7 (± 4.21) 23.34 (± 4.62) 0.30
Age at onset – mean (SD) 22.21 (± 4.27) 22.55 (± 4.47) 0.55 21.95 (± 4.25) 22.37 (± 4.49) 0.50
Age onset group
 Adolescent – N (%) 28 (18.06%) 13 (14.29%) 0.44 31 (21.83%) 10 (13.70%) 0.15
DUP2 (weeks) – mean (SD) 49.84 (± 95.8) 59.39 (± 134.0) 0.53 50.51 (± 97.5) 59.86 (± 134.7) 0.56
 Median (weeks) 15.00 15.79 14.86 16.36
 Range 0.1–574.0 0.0–1049.4 0.29–574.0 0.14–1011.6
Premorbid adjustment – mean (SD) 0.21 (± 0.14) 0.2 (± 0.12) 0.63 0.22 (± 0.14) 0.22 (± 0.11) 0.96
SAPS global baseline – mean (SD) 11.28 (± 3.08) 12.1 (± 3.78) 0.07 11.49 (± 2.97) 12.29 (± 3.73) 0.09
SANS global baseline – mean (SD) 11.92 (± 4.11) 11.92 (± 4.38) 0.99 12.09 (± 4.18) 12.42 (± 4.59) 0.60
SOFAS global baseline – mean (SD) 43.23 (± 12.69) 38.34 (± 14.37) 0.02* 42.38 (± 12.49) 37.43 (± 14.19) 0.03*
Gender
 Male – N (%) 110 (70.97%) 63 (69.23%) 0.77 102 (71.83%) 54 (73.97%) 0.74
Diagnosis non vs. affective psychosis
 Non-affective Psychosis – N (%) 108 (69.68%) 68 (74.73%) 0.40 98 (69.01%) 53 (72.60%) 0.59
Substance abuse/depend. diagnosis
 Yes – N (%) 89 (57.42%) 46 (58.97%) 0.82 83 (58.45%) 34 (53.97%) 0.55
Medication adherence
 Adherent – N (%) 134 (86.45%) 82 (91.11%) 0.28 128 (90.14%) 68 (95.77%) 0.15
Education (completed high school)
 High-school or higher – N (%) 102 (66.23%) 50 (60.24%) 0.36 91 (64.54%) 41 (61.19%) 0.64
Relationship
 In relationship – N (%) 10 (6.49%) 8 (8.89%) 0.49 10 (7.09%) 8 (10.96%) 0.33

p < 0.05.

DUP: duration of untreated psychosis; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; SOFAS: Social and Occupational Functioning Assessment Scale; 1: Significance was tested with t-tests for continuous variables (e.g., age at entry) and chi-square tests for categorical variables (e.g., Gender). 2: Non-transformed DUP variable. Note: Significant findings are displayed in bold font.

p < 0.1.

⁎⁎ p < 0.01.

⁎⁎⁎ p < 0.001.

3.2. Preliminary analyses

Of the covariates, only DUP was positively skewed and treated with a logarithmic transformation. Pairwise correlations between predictors were calculated. For every pair of predictors with a significant correlation, a variance inflation factor (VIF) was calculated. There were not any VIFs that suggested multicollinearity. The results of univariable regression analyses are outlined in Table 2. The unadjusted data indicate that adult-onset patients had significantly almost 3 times higher odds of achieving early remission of positive symptoms. However, age at onset did not influence other positive or negative remission variables. Longer DUP and higher baseline levels of positive and negative symptoms significantly reduced the odds of achieving early positive and early negative symptom remission. Poorer premorbid adjustment was negatively associated with both early remission of negative symptoms and continuous months in negative symptom remission. There was a significant negative relationship between baseline levels of positive and negative symptoms and the number of continuous months in negative remission. Higher baseline levels of negative symptoms significantly decreased the odds of attaining both positive and negative early symptom remission and predicted a reduction in the number of continuous months in negative remission. Baseline functioning (SOFAS) had a significant positive relationship with the number of continuous months in positive and negative remission and increased the odds of achieving early negative symptom remission. Medication adherence significantly predicted an increase in continuous months in positive remission. The presence of a substance abuse/dependence diagnosis and gender had no significant effect on any remission variable.

Table 2 Positive and negative symptom remission: Univariable Coefficients.

Positive symptom remission Negative symptom remission
Continuous months Early remission Continuous months Early remission
β S.E. OR S.E. β S.E. OR S.E.
DUP (log-transformed) − 0.09 0.29 0.73 ⁎⁎⁎ 0.09 − 0.11 0.30 0.76 ⁎⁎ 0.09
Premorbid adjustment − 0.12 4.36 0.18 1.20 − 0.21 ⁎⁎ 4.20 0.47 1.26
SAPS baseline − 0.06 0.15 0.90 0.04 − 0.14 0.16 0.90 0.05
SANS baseline − 0.12 0.12 0.93 0.03 − 0.28 ⁎⁎⁎ 0.12 0.82 ⁎⁎⁎ 0.04
SOFAS baseline 0.14 0.04 1.01 0.01 0.18 0.04 1.03⁎⁎ 0.01
Substance diagnosis − 0.05 1.05 0.59 0.29 − 0.04 1.06 0.81 0.30
Medication adherence 0.13 1.55 1.10 0.42 − 0.09 1.90 0.43 0.51
Gender (female) 0.07 1.10 1.41 0.31 0.08 1.16 0.68 0.33
Age at onset (adult) 0.08 1.35 2.93⁎⁎ 0.35 0.09 1.32 1.59 0.39

p < 0.1.

p < 0.05.

⁎⁎ p < 0.01.

⁎⁎⁎ p < 0.001.

DUP: duration of untreated psychosis; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; SOFAS: Social and Occupational Functioning Assessment Scale. Please note that higher scores in the Premorbid Adjustment Scale indicate lower adjustment. Note: Significant findings are displayed in bold font.

3.3. Main analyses

3.3.1. Positive symptom remission

The multivariable models for remission of positive symptoms are displayed in Table 3. Including the covariates in the first block revealed that only the effect of log-DUP on early positive remission was significant. Including the age at onset in the second block did not affect the influence of log-DUP on early positive symptom remission, while medication adherence became significant for continuous months in remission. When compared to the univariable model, the effect of age at onset on early remission became stronger and remained at the same significance level, confirming that adult-onset patients have higher odds of early remission, independent of other predictor variables. Both models including the age at onset variable were significant.

Table 3 Positive and negative symptom remission: Main Multivariable Model.

Positive symptom remission Negative symptom remission
Continuous months Early remission Continuous months Early remission
β S.E. OR S.E. β S.E. OR S.E.
Block 1
DUP (log-transformed) − 0.05 0.38 0.73 ⁎⁎ 0.12 − 0.05 0.38 0.78 0.13
Premorbid adjustment − 0.05 4.95 0.26 1.41 − 0.16 4.69 0.33 1.64
SAPS baseline − 0.06 0.21 0.94 0.06 − 0.05 0.22 1.03 0.07
SANS baseline − 0.14 0.18 0.96 0.05 − 0.21 0.17 0.80 ⁎⁎⁎ 0.06
SOFAS baseline 0.07 0.05 1.00 0.02 0.03 0.05 1.01 0.02
Substance diagnosis 0.00 1.30 0.70 0.40 0.01 1.30 0.56 0.44
Medication adherence 0.15 1.91 0.62 0.57 − 0.11 2.11 0.17 ⁎⁎ 0.69
Gender (female) 0.09 1.43 1.46 0.44 0.06 1.41 0.60 0.48
ΔR2 Sig. Cox-Snell Sig. ΔR2 Sig. Cox-Snell Sig.
Block statistics 0.09 0.08 0.11 0.02 0.14 0.01 0.24 0.00
 
Block 2
DUP (log-transformed) − 0.04 0.38 0.74 0.12 − 0.04 0.38 0.78 0.13
Premorbid adjustment − 0.05 4.93 0.31 1.44 − 0.15 4.69 0.33 1.64
SAPS baseline − 0.08 0.21 0.91 0.07 − 0.07 0.22 1.03 0.08
SANS baseline − 0.12 0.18 0.98 0.06 − 0.19 0.17 0.80 ⁎⁎⁎ 0.07
SOFAS baseline 0.08 0.05 1.00 0.02 0.04 0.05 1.01 0.02
Substance diagnosis 0.00 1.30 0.72 0.41 0.01 1.30 0.56 0.44
Medication adherence 0.17 1.91 0.72 0.59 − 0.11 2.11 0.17 ⁎⁎ 0.69
Gender (female) 0.11 1.42 1.62 0.46 0.07 1.41 0.60 0.48
Age at onset (adult) 0.14 1.66 3.32 0.48 0.10 1.54 1.03 0.55
ΔR2 Sig. Cox-Snell Sig. ΔR2 Sig. Cox-Snell Sig.
Block statistics 0.02 0.09 0.15 0.01 0.01 0.22 0.24 0.95
F R2 x2 Cox-Snell F R2 x2 Cox-Snell
Complete model 1.97 0.11 2.56⁎⁎ 0.15 24.4⁎⁎ 0.15 38.2⁎⁎ 0.24

p < 0.1.

p < 0.05.

⁎⁎ p < 0.01.

⁎⁎⁎ p < 0.001.

DUP: duration of untreated psychosis; SANS: Scale for the Assessment of Negative Symptoms; SAPS: Scale for the Assessment of Positive Symptoms; SOFAS: Social and Occupational Functioning Assessment Scale. Please note that higher scores in the Premorbid Adjustment Scale indicate lower adjustment. Note: Significant findings are displayed in bold font.

3.3.2. Negative symptom remission

Table 3 also summarizes the results from the multivariable models for the negative symptom remission variables. When including all predictors except age of onset in the first block, DUP was a significant predictor of early negative remission. The significant influence of baseline negative symptom levels on both negative remission outcomes also persisted, while the effect of baseline positive symptom levels did not. The effect that the baseline level of functioning had on the negative remission variables in the univariable analysis did not persist after controlling for other variables. As in the univariable model, age at onset did not influence any negative remission outcome variables. Both models including the age at onset category variable were significant.

3.4. Analysis only with schizophrenia spectrum disorder patients

Conducting the analysis including only patients with a SSD showed that the influence of age at onset on early remission of positive symptoms became stronger (OR = 4.2; 95% C.I. = 1.3–14.4; p < 0.05), the influence of DUP remained almost unchanged, and the influence of the level of baseline positive symptoms became significant, decreasing the odds for early remission of positive symptoms. The influence of medication adherence on the number of continuous months in positive remission was not significant for this group. In the case of remission of negative symptoms in patients with a SSD, medication adherence remained significant for early remission of negative symptoms, and the effect of age of onset approached statistical significance. The number of continuous months in negative remission was only significantly predicted by positive symptoms at baseline in these patients. These results are completely summarized in Supplementary Table 2.

4. Discussion

This study sought to assess the influence of age at onset of psychosis (before or after 18 years) on various aspects of symptom remission. Given the considerable differences found between adolescent-onset and adult-onset psychosis across multiple clinical and biological domains, we approached age at onset of psychosis as a categorical rather than as a continuous factor. We hypothesized that individuals who develop psychotic symptoms during adolescence would have poorer symptom remission and functional outcomes. After adjusting for other predictors, we found that adolescent-onset patients had significantly decreased odds of achieving early positive symptom remission. Furthermore, the adult-onset group had marginally more months in continuous positive remission. Contrastingly, there were no differences in negative symptom remission between the two groups. To our knowledge, this is the first study assessing the predictive value of the age of onset of psychosis on both positive and negative symptom remission outcomes, using the widely accepted RSWG definition.

The detrimental effect of an adolescent onset of psychosis on early remission of positive symptoms seems stronger for patients with a SSD, as shown by a noticeable change in the odds ratio when analyzing this group alone. The degree of positive symptom psychopathology at baseline became significant, predicting early remission in these patients. Interestingly, adolescent-onset patients with a SSD might also have lower odds for an early remission of negative symptoms, as this relationship approached statistical significance. Other effects were lost, which might have been the result of a loss of statistical power. Given that the change in the results was noticeable but not extreme, and the fact that some of the effects were lost, the differences between SDD and all patients presenting with a psychotic disorder (including those with an affective psychosis) do not seem profound, at least regarding symptom remission.

Previous studies assessing the effect of age as a continuous variable on remission using the RSWG criteria showed mixed results. Chang et al. (2012) found that an increase in age at onset reduced the odds of remission, albeit only controlling for DUP, gender, and early remission. In contrast, after controlling for multiple predictors and demographic characteristics, Verma et al. (2012) did not find an effect of age at onset on symptom remission, but did for functional remission and recovery. Taken together, the current findings support our approach to age at onset (comparing adolescents versus adults) and suggest that considering age as a category also clarifies the influence of other predictors of remission.

The selective way in which the predictors of positive symptom remission clustered with respect to the prediction of the different outcome variables, suggests that the capacity to rapidly achieve remission (i.e., early remission), and the likelihood of remaining in positive remission (i.e., continuous remission), are two separate aspects of this process. The reasons for this difference are unclear and beyond the scope of the present work. However, it can be speculated that since early positive symptom remission depends on age at onset and DUP, this characteristic would depend on factors more closely associated with development, and thus are relatively unmalleable, while the stability of positive remission would be a malleable factor influenced by adherence to pharmacological treatment, among other predictors.

Since other authors have found that early remission of positive symptoms –regardless of age– also predicts better long-term (at five years) functional outcomes (Norman et al., 2014), adolescent-onset patients might be at a higher risk of not attaining therapeutic and functional goals upon returning to standard services after two years of follow-up in an early intervention service. This underscores the need for services that can provide sustained support to these patients. Consistent with previous reports (Simonsen et al., 2010), DUP inversely predicted the odds of attaining early positive remission. However, it had no influence on the stability of positive symptom remission, which was only influenced by medication adherence. The latter was expected since antipsychotic pharmacotherapy primarily controls positive symptoms. Negative symptom levels upon admission emerged as the most consistent predictor of negative symptom remission (early and continuous months), reflecting the tendency of negative symptoms to endure (Malla et al., 1993). Interestingly, after controlling for other variables, female patients did not differ from their male counterparts. This finding goes against the prevailing notion that women have better prognoses across all aspects of the psychotic syndrome (Thorup et al., 2014).

Strengths of the present study are: the implementation of defined and accepted remission criteria, an epidemiological catchment area-derived cohort, and the longitudinal design of the research protocol. Potential limitations of the current study are first, the statistically significant difference in the baseline social and occupational scores between included and excluded participants, indicating that our study sample had somewhat higher levels of functioning than would be expected in an incidence sample. However, participants scored only 5 points more on average that the subjects excluded from the analysis. The SOFAS scale goes from 1 to 100, and is divided in 10 levels of function, suggesting that such difference might not be clinically relevant since a 5 point change does not necessarily imply a major functional change. Second, our additional analyses by diagnostic category were limited by the smaller number of participants with affective psychosis, hampering an analysis only on this group.

In summary, our results show that patients who develop a psychotic disorder before the age of 18 have lower odds of achieving early remission of positive symptoms, whereas the stability of remission of positive symptoms (continuous months) depends primarily on adherence to antipsychotic medication therapy irrespective of age of onset. Negative symptom remission is highly dependent on the level of baseline negative symptoms and global functioning, but not on the age at onset category. As such, a close monitoring of the attainment of early remission of positive symptoms would be particularly meaningful for patients whose onset of psychosis occurs in adolescence, whereas the proactive promotion of medication adherence to achieve remission stability would be critical for all patients regardless of their age. The functional prognostic disadvantage expected in adolescent-onset patients given their lower odds of early positive symptom remission might be mitigated by the integral care offered in an early intervention setting.

Conflicts of Interest

Dr. Iyer is supported by the Fonds de recherche du Québec – Santé, and reports no biomedical financial interests or potential conflicts of interest.

Dr. Malla is supported by the Canada Research Chairs Program funded by the Federal Government of Canada. In addition, Dr. Malla has received research funding and honoraria for conference presentations and participation in advisory boards for the following pharmaceutical industries in the past five years: Otsuka, Lundbeck, Roche, Janssen-Ortho, and Bristol-Myers Squibb.

Dr. Joober is supported by the Fonds de recherche du Québec – Santé. In addition, Dr. Joober sits on the advisory boards and speakers’ bureaus of Pfizer Canada, Janssen Ortho Canada, BMS and Sunovian, Myelin Canada, Otsuka Canada and Perdue Pharmaceuticals; he has received grant funding from AstraZeneca and Lundbeck Canada. He has received honoraria from Janssen Ortho Canada, Shire and from Pfizer Canada for CME presentations and royalties from Henry Stewart talks.

G Jordan MSc is a doctoral student under the supervision of Drs. Malla and Iyer, and funded through a scholarship from the Canadian Institutes of Health Research, and reports no biomedical financial interests or potential conflicts of interest.

F. Veru MD MSc is a doctoral student under the supervision of Drs. Malla and Iyer. F. Veru and supported through a doctoral training award granted by the Fonds de recherche du Québec – Santé, and reports no biomedical financial interests or potential conflicts of interest.

Contributors

F. Veru, S. Iyer, A. Malla, R. Joober, and G. Jordan participated in the conception, design, and planning of the study. F. Veru and G. Jordan undertook the statistical analyses. F. Veru managed the literature searches and analyses, and wrote the first draft of the manuscript. All the authors participated in the drafting of the final manuscript and approved it.

Funding Source

Dr. Iyer is supported by the Fonds de recherche du Québec – Santé.

Dr. Malla is supported by the Canada Research Chairs Program funded by the Federal Government of Canada.

Dr. Joober is supported by the Fonds de recherche du Québec – Santé.

G Jordan MA is a doctoral student under the supervision of Drs. Malla and Iyer, and funded through a scholarship from the Canadian Institutes of Health Research

F. Veru MD MSc is a doctoral student under the supervision of Drs. Malla and Iyer, and supported through a doctoral training award granted by the Fonds de recherche du Québec – Santé.

The funding bodies had no involvement in the design, conduction or analysis of the study.

Acknowledgements

The authors would like to express their gratitude to the participants and their families as well as the PEPP research staff. This research was supported by operating grants from CIHR (#68961) and the Sackler Foundation to Drs. M. Lepage and A. Malla.

Appendix A. Supplementary data

Download file

Supplementary tables.

References

  • Addington and Addington, 2008 J. Addington, D. Addington. Symptom remission in first episode patients. Schizophr. Res.. 2008;106(2):281-285 Crossref
  • Alvarez-Jimenez et al., 2012 M. Alvarez-Jimenez, J. Gleeson, L. Henry, S. Harrigan, M. Harris, E. Killackey, S. Bendall, G. Amminger, A. Yung, H. Herrman. Road to full recovery: longitudinal relationship between symptomatic remission and psychosocial recovery in first-episode psychosis over 7.5 years. Psychol. Med.. 2012;42(03):595-606 Crossref
  • Anderson et al., 2013 K.K. Anderson, R. Fuhrer, N. Schmitz, A.K. Malla. Determinants of negative pathways to care and their impact on service disengagement in first-episode psychosis. Soc. Psychiatry Psychiatr. Epidemiol.. 2013;48(1):125-136 Crossref
  • Andreasen, 1983 N. Andreasen. Scale for the Assessment of Negative Symptoms (SANS). (University of Iowa, 1983)
  • Andreasen, 1984 N. Andreasen. Scale for the Assessment of Positive Symptoms (SAPS). (University of Iowa, 1984)
  • Andreasen et al., 2005 N.C. Andreasen, W.T. Carpenter Jr., J.M. Kane, R.A. Lasser, S.R. Marder, D.R. Weinberger. Remission in schizophrenia: proposed criteria and rationale for consensus. Am. J. Psychiatr.. 2005;162(3):441-449 Crossref
  • Ballageer et al., 2005 T. Ballageer, A. Malla, R. Manchanda, J. Takhar, R. Haricharan. Is adolescent-onset first-episode psychosis different from adult onset?. J. Am. Acad. Child Adolesc. Psychiatry. 2005;44(8):782-789 Crossref
  • Bodén et al., 2009 R. Bodén, J. Sundström, E. Lindström, L. Lindström. Association between symptomatic remission and functional outcome in first-episode schizophrenia. Schizophr. Res.. 2009;107(2):232-237
  • Brissos et al., 2011 S. Brissos, V.V. Dias, V. Balanzá-Martinez, A.I. Carita, M.L. Figueira. Symptomatic remission in schizophrenia patients: relationship with social functioning, quality of life, and neurocognitive performance. Schizophr. Res.. 2011;129(2):133-136 Crossref
  • Burke et al., 2008 L. Burke, C. Androutsos, J. Jogia, P. Byrne, S. Frangou. The Maudsley early onset schizophrenia study: the effect of age of onset and illness duration on fronto-parietal gray matter. Eur. Psychiatry. 2008;23(4):233-236 Crossref
  • Cannon-Spoor et al., 1982 H.E. Cannon-Spoor, S.G. Potkin, R.J. Wyatt. Measurement of premorbid adjustment in chronic schizophrenia. Schizophr. Bull.. 1982;8(3):470 Crossref
  • Cassidy et al., 2010a C.M. Cassidy, R. Norman, R. Manchanda, N. Schmitz, A. Malla. Testing definitions of symptom remission in first-episode psychosis for prediction of functional outcome at 2 years. Schizophr. Bull.. 2010;36(5):1001-1008 Crossref
  • Cassidy et al., 2010b C.M. Cassidy, M. Rabinovitch, N. Schmitz, R. Joober, A. Malla. A comparison study of multiple measures of adherence to antipsychotic medication in first-episode psychosis. J. Clin. Psychopharmacol.. 2010;30(1):64-67 Crossref
  • Chang et al., 2012 W.C. Chang, J.Y. Tang, C.L. Hui, M.M. Lam, S.K. Chan, G.H. Wong, C.P. Chiu, E.Y. Chen. Prediction of remission and recovery in young people presenting with first-episode psychosis in Hong Kong: a 3-year follow-up study. Aust. N. Z. J. Psychiatry. 2012;46(2):100-108 Crossref
  • Crumlish et al., 2009 N. Crumlish, P. Whitty, M. Clarke, S. Browne, M. Kamali, M. Gervin, O. McTigue, A. Kinsella, J.L. Waddington, C. Larkin. Beyond the critical period: longitudinal study of 8-year outcome in first-episode non-affective psychosis. Br. J. Psychiatry. 2009;194(1):18-24 Crossref
  • Emsley et al., 2007 R. Emsley, J. Rabinowitz, R. Medori, E.P.G.W. Group. Remission in early psychosis: rates, predictors, and clinical and functional outcome correlates. Schizophr. Res.. 2007;89(1):129-139 Crossref
  • First et al., 2002 M. First, R. Spitzer, M. Gibbon, J. Williams. Structured clinical interview for DSM-IV-TR axis I disorders, research version, patient edition (SCID-I/P). New York, Biometrics Research (New York State Psychiatric Institute, 2002)
  • Goldman et al., 1992 H.H. Goldman, A.E. Skodol, T.R. Lave. Revising axis V for DSM-IV: a review of measures of social functioning. Am. J. Psychiatry. 1992;149(9):1148-1156
  • Iyer et al., 2015 S. Iyer, G. Jordan, K. MacDonald, R. Joober, A. Malla. Early intervention for psychosis: a Canadian perspective. J. Nerv. Ment. Dis.. 2015;203(5):356-364 Crossref
  • Jarbin et al., 2003 H. Jarbin, Y. Ott, A.L. Von Knorring. Adult outcome of social function in adolescent-onset schizophrenia and affective psychosis. J. Am. Acad. Child Adolesc. Psychiatry. 2003;42(2):176-183 Crossref
  • Jordan et al., 2014 G. Jordan, D. Lutgens, R. Joober, M. Lepage, S.N. Iyer, A. Malla. The relative contribution of cognition and symptomatic remission to functional outcome following treatment of a first episode of psychosis. J. Clin. Psychiatry. 2014;75(6):e566-e572 Crossref
  • Kumar and Khess, 2012 A. Kumar, C. Khess. Factor analysis of positive and negative syndrome scale in schizophrenia: an exploratory study. Indian J. Psychiatry. 2012;54(3):233
  • Lambert et al., 2010 M. Lambert, A. Karow, S. Leucht, B.G. Schimmelmann, D. Naber. Remission in schizophrenia: validity, frequency, predictors, and patients' perspective 5 years later. Dialogues Clin. Neurosci.. 2010;12(3):393
  • Langeveld et al., 2012 J. Langeveld, I. Joa, S. Friis, W. ten Velden Hegelstad, I. Melle, J.O. Johannessen, S. Opjordsmoen, E. Simonsen, P. Vaglum, B. Auestad. A comparison of adolescent-and adult-onset first-episode, non-affective psychosis: 2-year follow-up. Eur. Arch. Psychiatry Clin. Neurosci.. 2012;262(7):599-605 Crossref
  • Larsen et al., 2004 T.K. Larsen, S. Friis, U. Haahr, J.O. Johannessen, I. Melle, S. Opjordsmoen, B.R. Rund, E. Simonsen, P.V. Vaglum, T.H. McGLASHAN. Premorbid adjustment in first-episode non-affective psychosis: distinct patterns of pre-onset course. Br. J. Psychiatry. 2004;185(2):108-115 Crossref
  • Malla et al., 1993 A.K. Malla, R.M. Norman, P. Williamson. Stability of positive and negative symptoms in schizophrenia. Can. J. Psychiatry/La Rev. Can. Psychiatr.. 1993;38(9):617-621
  • Milev et al., 2005 P. Milev, B.-C. Ho, S. Arndt, N.C. Andreasen. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am. J. Psychiatr.. 2005;162(3):495-506 Crossref
  • Nenadic et al., 2010 I. Nenadic, H. Sauer, C. Gaser. Distinct pattern of brain structural deficits in subsyndromes of schizophrenia delineated by psychopathology. NeuroImage. 2010;49(2):1153-1160 Crossref
  • Norman et al., 2004 R. Norman, A. Malla, M. Verdi, L. Hassall, C. Fazekas. Understanding delay in treatment for first-episode psychosis. Psychol. Med.. 2004;34(02):255-266 Crossref
  • Norman et al., 2014 R.M. Norman, R. Manchanda, D. Windell. The prognostic significance of early remission of positive symptoms in first treated psychosis. Psychiatry Res.. 2014;218(1):44-47 Crossref
  • Pencer et al., 2005 A. Pencer, J. Addington, D. Addington. Outcome of a first episode of psychosis in adolescence: a 2-year follow-up. Psychiatry Res.. 2005;133(1):35-43 Crossref
  • Rajji et al., 2009 T. Rajji, Z. Ismail, B. Mulsant. Age at onset and cognition in schizophrenia: meta-analysis. Br. J. Psychiatry. 2009;195(4):286-293 Crossref
  • Rosen and Garety, 2005 K. Rosen, P. Garety. Predicting recovery from schizophrenia: a retrospective comparison of characteristics at onset of people with single and multiple episodes. Schizophr. Bull.. 2005;31(3):735-750 Crossref
  • Schimmelmann et al., 2007 B.G. Schimmelmann, P. Conus, S. Cotton, P.D. McGorry, M. Lambert. Pre-treatment, baseline, and outcome differences between early-onset and adult-onset psychosis in an epidemiological cohort of 636 first-episode patients. Schizophr. Res.. 2007;95(1):1-8 Crossref
  • Simonsen et al., 2010 E. Simonsen, S. Friis, S. Opjordsmoen, E.L. Mortensen, U. Haahr, I. Melle, I. Joa, J.O. Johannessen, T.K. Larsen, J.I. Røssberg. Early identification of non-remission in first-episode psychosis in a two-year outcome study. Acta Psychiatr. Scand.. 2010;122(5):375-383 Crossref
  • Skokou et al., 2012 M. Skokou, A. Katrivanou, I. Andriopoulos, P. Gourzis. Active and prodromal phase symptomatology of young-onset and late-onset paranoid schizophrenia. Rev. Psiquiatr. Salud Ment.. 2012;5(3):150-159 (English Edition)
  • Thorup et al., 2014 A. Thorup, N. Albert, M. Bertelsen, L. Petersen, P. Jeppesen, P. Le Quack, G. Krarup, P. Jørgensen, M. Nordentoft. Gender differences in first-episode psychosis at 5-year follow-up–two different courses of disease? Results from the OPUS study at 5-year follow-up. Eur. Psychiatry. 2014;29(1):44-51 Crossref
  • Üçok et al., 2011 A. Üçok, S. Serbest, P.E. Kandemir. Remission after first-episode schizophrenia: results of a long-term follow-up. Psychiatry Res.. 2011;189(1):33-37
  • Verma et al., 2012 S. Verma, M. Subramaniam, E. Abdin, L. Poon, S. Chong. Symptomatic and functional remission in patients with first-episode psychosis. Acta Psychiatr. Scand.. 2012;126(4):282-289 Crossref
  • Vinokur et al., 2014 D. Vinokur, S. Levine, D. Roe, A. Krivoy, T. Fischel. Age of onset group characteristics in forensic patients with schizophrenia. Eur. Psychiatry. 2014;29(3):149-152 Crossref
  • Walterfang et al., 2009 M. Walterfang, A.G. Wood, D.C. Reutens, S.J. Wood, J. Chen, D. Velakoulis, P.D. McGorry, C. Pantelis. Corpus callosum size and shape in first-episode affective and schizophrenia-spectrum psychosis. Psychiatry Res. Neuroimaging. 2009;173(1):77-82 Crossref

Footnotes

Department of Psychiatry, McGill University, Canada

Douglas Mental Health University Institute, Canada

Prevention and Early Intervention Program for Psychosis (PEPP-Montréal), Canada

Corresponding author at: ACCESS Network Canada, Douglas Mental Health University Institute, 6625, Boul. LaSalle, Montréal, Québec H4H 1R3, Canada.