SEARCH

SEARCH BY CITATION

Keywords:

  • at-risk mental states;
  • early intervention;
  • prodrome;
  • psychosis;
  • quality of life

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Aims

It remains debatable whether early intervention for psychosis is capable of meeting the needs of at-risk subjects. The aims of this study were to describe the actual impact of interventions on subjective difficulties and to explore the factors that may be associated with a poor outcome.

Methods

Participants were help-seeking outpatients at a university hospital who met the Criteria of Prodromal Syndromes. Changes in the symptoms, subjective experience and current insight were assessed using the Scales of Prodromal Symptoms, the Subjective Well-being under Neuroleptics, and the Scale to Assess Unawareness of Mental Disorder, respectively. Global functioning, social functioning and subjective quality of life were evaluated using the Global Assessment of Functioning Scale, the Social Functioning Scale, and the WHO-Quality of Life 26, respectively. These measures were assessed both at baseline and after 1 year.

Results

Forty-six patients agreed to participate. Of the 27 patients who completed the reassessment at the follow-up point, 13 patients (48%) showed little improvement in their positive/negative symptoms, subjective well-being or awareness of their symptoms. Additionally, less severe negative symptoms, more severe general symptoms and lower subjective well-being at baseline significantly predicted a deterioration of positive/negative symptoms after 1 year.

Conclusion

Our findings suggest that the current strategy for reducing psychosis risk based on positive symptoms should be reappraised.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

In the last 15 years, a number of studies have supported the view that the earlier detection and care of psychosis can lead to a better outcome.[1, 2] However, most of these studies were conducted in research settings; thus, the actual effectiveness of early intervention for psychosis remains unclear.[3] One of the issues that such studies have raised is that the diagnostic criteria or primary outcomes focus mainly on the attenuated positive psychotic symptoms.

Attenuated psychotic symptoms or psychotic-like experiences have been commonly found in the general population, and these symptoms or experiences may not necessarily be associated with distress or help-seeking behaviour.[4-6] In a previous study comparing help-seeking patients with the general population, the authors reported that psychosis-like experiences do not significantly contribute to help-seeking behaviour.[7] Attenuated positive symptoms may not always confer subjective difficulties or sufferings; therefore, the current interventions to reduce risk which are focused on the attenuated positive symptoms may not be truly capable of meeting the needs of individuals meeting at-risk criteria.

To date, longitudinal studies on the outcomes of individuals at risk for psychosis have underlined the considerably high rates of remission[8] and the low rates of transition to psychosis.[9, 10] Given that the criteria for remission and transition are based on the attenuated psychotic symptoms, however, it would be doubtful whether or not these outcomes reflect the actual changes in subjective difficulties of individuals at risk for psychosis. Indeed, a large longitudinal study, the North American Prodrome Longitudinal Study (NAPLS), revealed that most individuals who met the at-risk criteria but did not convert to psychosis continued to suffer from lower levels of functioning or disabilities.[11] Additionally, an approach focused predominantly on the low rate of transition to psychotic disorder can obscure individual treatment effects. Subgroups of participants may respond to individual treatments particularly well or particularly poorly as a result of the participants' characteristics or baseline symptom patterns. A recent report on a randomized controlled trial examining the effect of various therapies on young people with a high risk for psychosis concluded that the interventions were equally effective or ineffective.[12] Thus, the effectiveness of interventions for early psychosis should be clarified in clinical settings, regardless of the transition to full-blown psychosis.

We hypothesized that the current strategy, which is focused on the attenuated positive symptoms, cannot sufficiently ameliorate the subjective difficulties of individuals at risk for psychosis, such as their subjective quality of life (QOL), role/social functioning, interpersonal relationships and subjective well-being. We also assumed that some patients would continue to receive treatment because their symptoms had not been relieved.

The aims of this study were: (i) to describe the actual 1-year outcome of individuals with a high risk of psychosis based on comprehensive assessments including subjective QOL, role/social functioning, interpersonal relationships, insight into illness and subjective well-being; and (ii) to clarify the characteristics of patients who continue to receive treatment for over 1 year so as to explore the factors that may lead to a poor outcome, even without a transition to psychosis.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Participants

This study was performed at a university hospital (Toho University) located in a suburb of Tokyo. The participants were eligible for enrolment in the study if they were between the ages of 16 and 40 years and met the Criteria of Prodromal Syndromes (COPS).[13] Patients were excluded from the study if they had: (i) any lifetime DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) diagnosis of any psychotic disorder; (ii) symptoms fully accounted for by an Axis 1 disorder or sequelae arising from drug/alcohol use; or (iii) abuse of alcohol or drugs. All the participants were help-seeking outpatients. Each adult participant provided his or her written informed consent and each minor provided written informed assent in addition to consent from a parent or guardian. Data were collected between June 2007 and October 2009.

Measures

The Structured Interview for Prodromal Syndromes (SIPS)[13] was performed for patients identified as having an ‘at-risk mental state’, including the Scale of Prodromal Symptoms (SOPS). The SOPS items consist of four symptoms: positive symptoms, negative symptoms, disorganized symptoms, and general symptoms, although the COPS focuses upon merely positive symptoms. We used the SIPS/SOPS Japanese version, which we previously reported to have an excellent interrater reliability.[14] The developers of this SIPS/SOPS Japanese version (H. Kobayashi and M. Mizuno) trained the staff to score these tests with accuracy, and the interviews (including the SIPS and the other assessments) were conducted by experienced psychiatrists (K. Morita, K. Takeshi and N. Tsujino).

Changes in subjective experience were assessed using the Subjective Well-being under Neuroleptics Short version (SWNS).[15] The SWNS is a 20-item test that uses a 6-point Likert-type self-rating scale. Naber et al. found a five-factor solution for the scale, which was interpreted as emotional regulation, self-control, mental functioning, social integration and physical functioning. We used the SWNS Japanese version, which has been shown to have a good reliability and validity.[16]

Current insight was measured using the Scale to Assess Unawareness of Mental Disorder (SUMD).[17] The SUMD rates awareness of 20 items was based on a 5-point Likert scale. To assess current insight, we used the 3 global insight items (awareness of mental disorder, awareness of achieved medication effects, and awareness of social consequences of medications) and the 17 subscales (awareness of symptoms).

Global functioning, social functioning and subjective QOL were evaluated using the Global Assessment of Functioning Scale, the Social Functioning Scale, and the WHO-Quality of Life 26, respectively.

These measures were assessed both at baseline and after 1 year. The Institutional Review Board at Toho University approved the study protocol and the procedure for obtaining informed consent.

Interventions

During the follow-up period, all the patients received usual supportive therapy and/or psychotropic medication, with the main aim of reducing the severity of psychotic symptoms. Psychotropic medication included the use of antipsychotics for positive symptoms, anxiolytics for anxiety symptoms, and antidepressants for comorbid depressive symptoms, if necessary. The administration of antipsychotics was generally judged according to the International Clinical Practice Guidelines for Early Psychosis.[18] The nature of the psychological intervention was left to the discretion of the psychiatrist in charge; cognitive therapy, psychoeducation, or family therapy, if used, were thus provided in diverse forms.

Clinical outcome

To determine the factors that may lead to a poor outcome, even without a transition to psychosis, the sample was subsequently split into two groups according to the degree to which either positive or negative symptoms had developed. At the follow-up point, patients with improvements from the baseline in both the SOPS positive and negative symptom scores without transitioning to psychosis were defined as ‘improved’, and patients with no improvements from the baseline in the SOPS positive or negative symptoms or who fulfilled the criteria for psychosis were defined as ‘not improved’. The transition to psychosis was operationally defined using the Presence of Psychotic Symptoms criteria.[13]

Statistical analyses

All the statistical analyses were conducted using the Statistical Package for Social Sciences (SPSS) version 18.0 for Windows (SPSS Inc., Chicago, IL, USA). The baseline variables were compared between the patients who were lost because of attrition and the patients who were followed up after 1 year with the help of Mann–Whitney U-tests for continuous variables and with chi-square tests for categorical variables. Also, clinical variables at baseline were compared between the ‘improved’ group and the ‘not improved’ group using the Mann–Whitney U-tests for continuous variables and the chi-square tests for categorical variables. In addition, we compared clinical outcomes between the ‘improved’ group and the ‘not improved’ group using the analysis of variance, adjusting for age, duration of illness and baseline scores. To explore variables that can predict poor outcomes, multiple linear regression analysis was conducted. For each comparison, a value of P < 0.05 was considered statistically significant without any consideration for multiple comparisons.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

At baseline, 46 treatment-seeking patients who had been clinically diagnosed as having clinical high risk of psychosis agreed to participate in the study and to be assessed. The demographic characteristics of the sample at baseline are presented in Table 1.

Table 1. Demographic characteristics of the sample at baseline (n = 46)
 n%
  1. APS, Attenuated Positive Symptom Group; BIPS, Brief Intermittent Psychosis Group; GAF, Global Assessment of Functioning Scale; GRD, Genetic Risk and Deterioration Group; SD, standard deviation; SFS, Social Functioning Scale; SOPS, Scale of Prodromal Symptoms; SUMD, Scale to Assess Unawareness of Mental Disorder; SWNS, Subjective Well-being under Neuroleptics Short version; WHO-QOL26, WHO-Quality of Life 26.

Female3371.7
Past treatment history2963.0
Family history (any mental illness)1839.1
Married919.5
Employed1941.3
Student1634.8
APS46100.0
BIPS919.6
GRD2145.7
 MeanSD
Age, years23.56.6
Duration of illness, weeks26.024.0
Education, years12.32.5
GAF current54.012.9
SOPS  
Positive symptoms18.94.8
Negative symptoms18.35.8
Disorganized symptoms8.33.7
General symptoms13.14.2
Total58.615.7
SFS  
Withdrawal9.02.6
Interpersonal7.13.1
Pro-social activities13.69.7
Recreation17.16.9
Independence–competence23.36.3
Independence–performance33.56.9
Employment5.13.0
Total107.926.5
SWNS  
Mental functioning10.73.9
Self-control11.63.6
Emotional regulation11.33.8
Physical functioning11.23.0
Social integration10.73.9
Total55.413.2
WHO-QOL26  
Physical domain16.44.4
Psychological domain12.94.3
Social relationship8.02.7
Environmental domain21.65.1
General3.91.5
Total62.814.7
SUMD, current disorder
Item 1-3 (global insight) awareness2.30.9
Item 4-10 (symptom items) awareness1.50.5
Item 4-10 (symptom items) attribution3.00.9

At the 1-year follow-up point, 27 participants (59%) completed the reassessment. Table 2 shows the sample characteristics of these 27 patients and the patients who withdrew from the study, indicating that the withdrawn patients were younger and had a shorter duration of illness, less negative/general symptoms and a higher QOL.

Table 2. Comparisons at baseline between the followed-up patients and the withdrawn patients
 Followed-up (n = 27)Withdrawn (n = 19)Chi-squareP
n %n %  
  1. *P < 0.05; **P < 0.01.

  2. APS, Attenuated Positive Symptom Group; BIPS, Brief Intermittent Psychosis Group; GAF, Global Assessment of Functioning Scale; GRD, Genetic Risk and Deterioration Group; SD, standard deviation; SFS, Social Functioning Scale; SOPS, Scale of Prodromal Symptoms; SUMD, Scale to Assess Unawareness of Mental Disorder; SWNS, Subjective Well-being under Neuroleptics Short version; WHO-QOL26, WHO-Quality of Life 26.

Female1970.31473.70.601.00
Past treatment history2177.8842.10.010.90
Family history (any mental illness)1037.0842.10.120.77
Married725.9210.52.200.33
Employed1140.7842.10.011.00
Student725.9947.42.260.21
APS27100.019100.0
BIPS725.9210.51.680.27
GRD 1659.3526.34.880.04*
 MeanSDMeanSDZP
Age, years25.37.220.94.8−2.160.03*
Duration of illness, weeks30.724.519.221.9−2.080.04*
Education, years12.32.612.32.4−0.230.82
GAF current53.912.754.213.7−0.060.96
SOPS      
Positive symptoms19.63.418.06.3−0.460.65
Negative symptoms20.34.515.36.3−2.69<0.01**
Disorganized symptoms8.73.17.74.4−0.620.54
General symptoms14.72.710.85.0−2.66<0.01**
Total63.310.051.720.1−1.930.05
SFS total103.723.1113.930.4−1.180.24
SWNS total52.010.360.315.6−1.640.10
WHO-QOL26 total58.411.569.516.7−2.310.02*
SUMD, current disorder
Item 1-3 (global insight) awareness2.30.92.41.0−0.450.65
Item 4-10 (symptom items) awareness1.60.51.30.3−2.040.04*
Item 4-10 (symptom items) attribution3.00.93.11.0−0.020.99

During the follow-up period, three patients, or 12% of the followed sample, converted to psychosis: two were diagnosed as having schizophrenia and one was diagnosed as having a schizoaffective disorder. According to the criteria mentioned above, 14 patients were defined as ‘improved’ (in both the SOPS positive and negative symptoms), but 13 patients, including the 3 psychotic cases, were defined as ‘not improved’ (in either the SOPS positive or negative symptoms). Detailed comparisons of these two groups are shown in Table 3, suggesting that although few differences in the clinical variables were found between the two groups at baseline, all the patients in the ‘not improved’ group had past treatment histories and had fewer family members with mental health illness.

Table 3. Comparisons at baseline between the ‘improved’ group and the ‘not improved’ group
 Improved (n = 14)Not improved (n = 13)Chi-squareP
n%n%
  1. *P < 0.05

  2. APS, Attenuated Positive Symptom Group; BIPS, Brief Intermittent Psychosis Group; GAF, Global Assessment of Functioning Scale; GRD, Genetic Risk and Deterioration Group; SD, standard deviation; SFS, Social Functioning Scale; SOPS, Scale of Prodromal Symptoms; SUMD, Scale to Assess Unawareness of Mental Disorder; SWNS, Subjective Well-being under Neuroleptics Short version; WHO-QOL26, WHO-Quality of Life 26.

Female1071.4969.20.160.62
Past treatment history857.113100.07.160.02*
Family history (any mental illness)857.1215.35.040.04*
Married321.4430.83.090.21
Employed750.0430.81.030.27
Student321.4430.80.310.45
APS14100.013100.0
BIPS321.4430.80.310.45
GRD1178.6538.54.490.05
Antipsychotic use321.4323.1<0.010.99
 MeanSDMeanSDZP
Age, years25.98.025.07.3−0.210.84
Duration of illness, weeks34.426.026.723.3−0.950.34
Education, years12.83.411.41.4−0.900.37
GAF current53.211.455.015.6−0.030.98
SOPS      
Positive symptoms19.93.119.03.7−0.320.75
Negative symptoms21.13.719.25.7−1.120.26
Disorganized symptoms9.02.98.03.8−0.620.54
General symptoms14.02.515.32.8−1.270.21
Total64.19.461.512.0−0.560.58
SFS total101.526.8108.419.9−0.210.84
SWNS total50.311.255.311.2−1.290.20
WHO-QOL26 total2.110.42.450.42−1.670.10
SUMD, current disorder      
Item 1-3 (global insight) awareness2.50.92.10.8−1.420.16
Item 4-10 (symptom items) awareness1.50.51.60.5−0.650.52
Item 4-10 (symptom items) attribution2.91.13.10.8−0.650.52

Table 4 shows that ‘not improved ’group demonstrated a decline of the SWNS total score and the SUMD sub-score (awareness of symptoms) over time, even after adjusting for age, duration of illness and baseline scores. Twenty-one (78% of the followed) patients had received antipsychotic medication at the follow-up point (aripiprazole: n = 13; quetiapine: n = 5; perospirone: n = 2; risperidone: n = 1), whereas only six patients (22%) were administered antipsychotic treatment at baseline (quetiapine: n = 2; risperidone: n = 2; aripiprazole: n = 1; perospirone: n = 1) (Table 3).

Table 4. ANOVA for comparing clinical outcomes between the ‘improved’ group and the ‘not improved’ group
 Score difference (T2-T1; mean ± SD)Non-adjustedAdjusted
Variables‘Improved’‘Not improved’FPFP
  1. *P < 0.05; **P < 0.01.

  2. †Adjusted for age, DUI and baseline scores.

  3. T1, baseline, T2, at the follow-up point.

  4. ANOVA, analysis of variance; GAF, Global Assessment of Functioning Scale ; SD, standard deviation; SFS, Social Functioning Scale; SUMD, Scale to Assess Unawareness of Mental Disorder; SWNS, Subjective Well-being under Neuroleptics Short version; WHO-QOL, WHO-Quality of Life.

SWNS total17.5 ± 17.32.4 ± 17.34.8960.037*5.1250.034*
SFS total13.7 ± 21.74.6 ± 15.01.5090.2311.5750.223
GAF19.3 ± 11.612.7 ± 17.41.3630.2543.0580.094
WHO-QOL total3.7 ± 3.81.2 ± 3.92.8550.1041.0240.323
SUMD global insight−0.3 ± 1.00.2 ± 0.90.4840.4940.0050.947
SUMD symptom awareness0.9 ± 0.9−0.1 ± 0.78.6320.008**8.4350.009**
SUMD symptom attribution0.5 ± 1.00.1 ± 0.30.6450.4320.6470.432

Multiple linear regression analysis was used to explore variables at baseline that can predict poorer outcome at the follow-up point (Table 5). Results suggest that less severe negative symptoms, more severe general symptoms, or lower subjective well-being at baseline could significantly predict poorer outcome after 1 year.

Table 5. Multiple linear regression analysis for exploring variables that can predict poor outcome at the follow-up point
VariablesBSEβtP
  1. T1, baseline.

  2. SWNS, Subjective Well-being under Neuroleptics Short version.

Negative symptoms at T1−0.0600.020−0.525−2.9070.008
General symptoms at T10.1740.0390.9154.454<0.001
SWNS total score at T10.0240.0090.5102.6770.014

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References

Our findings are of some clinical relevance when treating help-seeking individuals with the features of early psychosis. The current naturalistic study revealed that quite a few patients (48%) showed little improvement in both their positive/negative symptoms and subjective well-being after having received intervention for over 1 year, regardless of transition to full-blown psychosis. Additionally, nearly half of the entire sample (41%) dropped out of the study within 1 year for any reason. These results suggest that the current early interventions cannot truly meet the subjective needs of individuals at risk for psychosis.

One explanation for the unmet needs among the at-risk patients might be that the early interventions for psychosis in clinical settings tended to favour antipsychotic medication, as seen in the present study. We found that about 80% of the patients who were followed up had received antipsychotic medication at the follow-up point. Although such antipsychotic medication would be generally administered to reduce risks that are focused on the attenuated positive symptoms, the results indicated that poorer outcome could not be significantly predicted by severity of positive symptoms at baseline but less severe negative symptoms, more severe general symptoms, and lower subjective well-being at baseline. This suggests that other symptoms than positive symptoms might be a key to patients' subjective difficulties in their daily lives, possibly shedding new light on early intervention strategies for psychosis; for example, a targeted intervention for affective symptoms might be more effective with regard to the subjective response than interventions for positive symptoms.

In addition, to make matters worse, the off-label use of antipsychotics for psychosis prodrome has presented some ethical issues associated with unexpected adverse effects, social stigmatization and low self-esteem.[19] Given that poor adherence to the initial treatment may hinder an adequate intervention,[20] ethical issues regarding pharmacological intervention during the earliest stage of psychosis cannot be ignored. However, recent clinical research has revealed that not a few clinicians in the community have administered pharmacological interventions, including antipsychotics, to individuals who have attenuated psychotic symptoms but do not meet the criteria for psychosis. A naturalistic study from the Recognition and Prevention program showed that individuals presenting with more severe (but non-psychotic) attenuated positive symptoms were nearly all treated with antipsychotics, often in combination with other agents.[21] The data from the NAPLS demonstrated that 60% of the clinical high-risk sample had a lifetime history of receiving psychotropic medication prior to their entry in the research program.[22] Also, anonymous surveys in Japan and Singapore have indicated that most psychiatrists in the community would treat prepsychotic patients with active management, including antipsychotic medication.[23, 24] Generally, most clinical psychiatrists in the community are likely to overestimate the use of pharmacological intervention, including antipsychotics, for individuals who have attenuated (but non-psychotic) psychotic symptoms. However, as a number of medication-free studies have found, antipsychotic medication does not seem to be an essential component of effective treatment for psychosis, even in patients with established illnesses.

The high dropout rate in the study (41%) may be partially due to this strategy for intervention that was focused on attenuated positive symptoms. The patients who withdrew within the 1-year follow-up period were younger and had shorter duration of illness, less severe negative symptoms/general symptoms, better awareness of symptoms, and higher subjective QOL at baseline than the patients who were followed up. Although the reasons for dropping out are needed to be explored, it is noteworthy that although the withdrawn patients had better clinical characteristics at baseline, there were no significant differences in positive symptom at baseline between the withdrawn patients and the followed patients. This result suggests that adherence to treatment in individuals with clinical high risk of psychosis does not depend on the extent to which interventions are based on the target for reducing positive symptoms.

Other clinical variables may also have some impacts on treatment outcome. Patients in the ‘not improved’ group had past treatment histories and had fewer family members with mental health illness. There are two potential interpretations for this finding. First, it may be that those with family experience of psychiatric illness tended to have effective care or support during the earlier stage of illness. Although previous studies have failed to confirm that family history of psychiatric illness was positively associated with a shorter duration of untreated psychosis,[25-27] families with previous experience of mental health illness may facilitate earlier help seeking through the enhancement of knowledge about potential symptoms and their significance.[25] Second, patients in the ‘not improved’ group may be treatment resistant. These patients would continue to receive treatment because their symptoms had not been relieved, as we hypothesized, partly because the current early interventions were not effective for this type of patients. Another explanation for considerable rate of having past treatment history is the preponderance of women in the present study sample. Several studies showed that women in general are more likely to have a past history of any psychiatric disorder.[28, 29] Given that gender differences may influence the course of illness,[29] our results would be skewed by the predominance of women in this sample.

Our data further suggest that negative symptoms do not appear to have an impact on both clinical outcomes and treatment adherence. Less severe negative symptoms at baseline were found to be associated with withdrawal from treatment and to predict significantly poorer outcomes, contrary to previous findings.[30, 31] These findings are also contrary to our previous expectation that severe negative symptoms would be associated with withdrawal from treatment and poorer outcomes. Rather, it appears that general symptoms play a key role more than negative symptoms for both clinical outcomes and treatment adherence. Whereas less severe general symptoms at baseline were found to be associated with withdrawal from treatment, more severe general symptoms at baseline predict poorer clinical outcomes after 1 year. General symptoms include sleep disturbance, dysphoric mood, motor disturbance and impaired tolerance to normal stress.[13] These symptoms may be directly linked to difficulties in daily living, in other words, subjective difficulties. Therefore, fluctuation of general symptoms should be carefully evaluated as a measure of effectiveness in the treatment.

The present study had some methodological weaknesses. First, an evaluation of the extent of the patients' needs is needed to clarify the relationship between subjective difficulties and help-seeking behaviour. Subjective difficulties would be hard to be evaluated precisely by the objective ratings and thus further development of objective ratings on subjective wellness/difficulties should be needed. Second, a considerable attrition rate was also observed in the current study, as in most prospective studies, but the reason for the high rate of patients lost to attrition remains unclear. Third, the present sample was skewed by both this high attrition rate and high rates of previous treatment with relatively long duration of ‘being well’. Finally, the small number of subjects in this study may certainly limit the generalizability of the findings. A larger sample with a longer period of observation is needed.

Despite these limitations, our findings have important clinical implications. A notable number of patients had a poor outcome with symptomatic deterioration, providing a rational for early intervention for psychosis. However, the current strategy for reducing the risk of psychosis, which is focused on the attenuated positive symptoms, should be reappraised. Further comprehensive longitudinal studies are needed to develop truly needs-based interventions for these at-risk patients.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. References
  • 1
    Bird V, Premkumar P, Kendall T, Whittington C, Mitchell J, Kuipers E. Early intervention services, cognitive-behavioural therapy and family intervention in early psychosis: systematic review. Br J Psychiatry 2010; 197: 350356.
  • 2
    Preti A, Cella M. Randomized-controlled trials in people at ultra high risk of psychosis: a review of treatment effectiveness. Schizophr Res 2010; 123: 3036.
  • 3
    Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev 2011; 15 (6): CD004718.
  • 4
    Hanssen M, Bak M, Bijl R, Vollebergh W, van Os J. The incidence and outcome of subclinical psychotic experiences in the general population. Br J Clin Psychol 2005; 44: 181191.
  • 5
    Dominguez M, Wichers M, Lieb R, Wittchen H. Evidence that onset of clinical psychosis is an outcome of progressively more persistent subclinical psychotic experiences: an 8-year cohort study. Schizophr Bull 2011; 37: 8493.
  • 6
    van Os J, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam L. A systematic review and meta-analysis of the psychosis continuum: evidence for psychosis proneness–persistence–impairment model of psychotic disorder. Psychol Med 2009; 39: 179195.
  • 7
    Kobayashi H, Nemoto T, Murakami M, Kashima H, Mizuno M. Lack of association between psychosis-like experiences and seeking help from professionals: a case-controlled study. Schizophr Res 2011; 132 (2–3): 208212.
  • 8
    Simon AE, Velthorst E, Nieman DH, Linszen D, Umbricht D, de Haan L. Ultra high-risk state for psychosis and non-transition: a systematic review. Schizophr Res 2011; 132: 817.
  • 9
    Haroun N, Dunn L, Haroun A, Cadenhead KS. Risk and protection in prodromal schizophrenia: ethical implications for clinical practice and future research. Schizophr Bull 2006; 32: 166178.
  • 10
    Yung AR, Stanford C, Cosgrave E et al. Testing the ultra high risk (prodromal) criteria for the prediction of psychosis in a clinical sample of young people. Schizophr Res 2006; 84: 5766.
  • 11
    Addington J, Cornblatt BA, Cadenhead KS et al. At clinical high risk for psychosis: outcome for nonconverters. Am J Psychiatry 2011; 168: 800805.
  • 12
    Yung AR, Phillips LJ, Nelson B et al. Randomized controlled trial of interventions for young people at ultra high risk for psychosis: 6-month analysis. J Clin Psychiatry 2011; 72: 430440.
  • 13
    Miller TJ, McGlashan TH, Rosen JL et al. Prodromal assessment with the structured interview for prodromal syndromes and the scale of prodromal symptoms: predictive validity, interrater reliability, and training to reliability. Schizophr Bull 2003; 29: 703715.
  • 14
    Kobayashi H, Nozaki S, Mizuno M. Reliability of the Structured Interview for Prodromal Syndromes Japanese version (SIPS-J). Jpn Soc Psychiat 2006; 15: 168174. (Japanese).
  • 15
    Naber D. A self-rating to measure subjective effects of neuroleptic drugs. Relationships to objective psychopathology, quality of life, compliance and other clinical variables. Int Clin Psychopharmacol 1995; 10: 133138.
  • 16
    Watanabe M, Matsumura H. Reliability and validity of Subjective Well-being under Neuroleptic drug treatment Short form, Japanese version (SWNS-J). Jpn J Clin Psychopharmacol 2003; 6: 905912. (Japanese).
  • 17
    Amador XF, Strauss DH, Yale SA, Flaum MM, Endicott J, Gorman JM. Assessment of insight in psychosis. Am J Psychiatry 1993; 150: 873879.
  • 18
    International Early Psychosis Association Writing Group. International clinical practice guidelines for early psychosis. Br J Psychiatry Suppl 2005; 48: s120124.
  • 19
    Francey SM, Nelson B, Thompson A et al. Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention. Schizophr Res 2010; 119 (1–3): 110.
  • 20
    de Koning MB, Bloemen OJ, van Amelsvoort TA et al. Early intervention in patients at ultra high risk of psychosis: benefits and risks. Acta Psychiatr Scand 2009; 119: 426442.
  • 21
    Cornblatt BA, Lencz T, Smith CW et al. Can antidepressants be used to treat the schizophrenia prodrome? Results of a prospective, naturalistic treatment study of adolescents. J Clin Psychiatry 2007; 68: 546557.
  • 22
    Cannon T, Cadenhead K, Cornblatt B et al. Prediction of psychosis in ultra high risk youth: a multi-site longitudinal study in North America. Arch Gen Psychiatry 2008; 65: 2835.
  • 23
    Tor PC, Lee HY. Comparison of attitudes of psychiatrists vs primary healthcare physicians in Singapore towards At Risk Mental States (ARMS). Ann Acad Med Singapore 2009; 38: 442446.
  • 24
    Tsujino N, Katagiri N, Kobayashi H, Netmoto T, Mizuno M. Recognition and decisions regarding the treatment of early psychosis by Japanese psychiatrists. Clin. Psychiatry 2010; 52: 11511159. (Japanese).
  • 25
    Chen EY, Dunn EL, Miao MY et al. The impact of family experience on the duration of untreated psychosis (DUP) in Hong Kong. Soc Psychiatry Psychiatr Epidemiol 2005; 40: 350356.
  • 26
    Esterbeg M, Compton M. Family history of psychosis negatively impacts age at onset, negative symptoms, and duration of untreated illness and psychosis in first-episode psychosis patients. Psychiatry Res 2012; 197: 2328.
  • 27
    Norman RMG, Malla AK, Manchanda R. Delay in treatment for psychosis: its relation to family history. Soc Psychiatry Psychiatr Epidemiol 2007; 42: 507512.
  • 28
    Cotton SM, Lambert M, Schimmelmann BG et al. Gender differences in premorbid, entry, treatment, and outcome characteristics in a treated epidemiological sample of 661 patients with first episode psychosis. Schizophr Res 2009; 114: 1724.
  • 29
    Chang WC, Tang JY, Hui CL et al. Gender differences in patients presenting with first-episode psychosis in Hong Kong: a three-year follow up study. Aust N Z J Psychiatry 2011; 45: 199205.
  • 30
    Lin A, Wood SJ, Nelson B et al. Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high risk for psychosis. Schizophr Res 2011; 132: 17.
  • 31
    Schlosser DA, Jacobson S, Chen Q et al. Recovery from an at-risk state: clinical and functional outcomes of putatively prodromal youth who do not develop psychosis. Schizophr Bull 2012; 38: 12251233.