Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification.

IMPORTANCE: Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE: To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES: Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION: We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS: Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES: The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS: Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE: There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

Predicting 1-year risk for relapse in patients who have discontinued or continued quetiapine after remission from first-episode psychosis.

OBJECTIVE: Relapse is common among patients with psychotic disorders. Identification of relapse predictors is important for decision regarding maintenance medication. Naturalistic studies often identify medication non-adherence as a dominant predictor. There are relatively few studies for predictors where adherence is already known. It is this situation i.e., discontinuation of medication that predictors will be most useful. We identify predictors for relapse in situations of (i) discontinuation and (ii) continuation of maintenance medication. METHOD: Analysis of relapse predictors is based on a randomized controlled study (n=178) comparing relapse rates between patients who discontinued or continued medication for at least 1 year following first-episode psychosis. Demographic, clinical and neurocognitive variables were assessed at baseline as predictors of relapse within 1 year. RESULTS: Risk of relapse was 79% in the discontinuation group and 41% in the maintenance group. Predictors in the discontinuation group were diagnosis of schizophrenia, poorer semantic fluency performance, and higher blink rate. Predictors in the continuation group were disinhibition soft signs and more general psychopathology symptoms. CONCLUSION: Different predictors of relapse were identified for first episode psychosis patients who discontinued and continued maintenance medication. Neurocognitive dysfunctions are important predictors for both groups. While signs of frontal dysfunction and dopamine hyperactivity predict relapse in the discontinuation group, sign of cognitive disinhibition predicts relapse in the continuation group.

Clinical and cognitive correlates of insight in first-episode schizophrenia.

This study aims to explore the relationship between clinical symptoms and cognitive functions with different insight dimensions in patients with first-episode schizophrenia. Seventy-nine patients were assessed following six months of treatment. Insight was assessed using the abridged version of Scale of Unawareness of Mental Disorder (SUMD). Symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). Cognitive functions were assessed using the Modified Wisconsin Card Sorting Test (MWCST), semantic verbal fluency and the letter-number sequencing (LNS) test from the Wechsler Adult Intelligence Scale (WAIS). Positive, negative and disorganized symptoms were found to be correlated with overall insight and all three general insight dimensions. Only perseverative errors and categories completed of MWCST were correlated with overall insight. Perseverative errors and non-perseverative errors of MWCST were correlated with the awareness of medication effects; perseverative errors of MWCST were also correlated with the awareness of social consequence of the illness. These support the link between poor insight and impaired executive function particularly measured by MWCST. The specific correlation of cognitive functions and different dimensions of insight suggests different underlying mechanism within each dimension of insight. The combined model of symptomatology and cognitive function explained 20.6% to 36.4% of the variance in the lack of insight within the different dimensions. The modest combined relationship of clinical and cognitive function with insight suggests that the exploration of other models in relationship to different insight dimensions is important.

Screening and assessing ideas and delusions of reference using a semi-structured interview scale: a validation study of the Ideas of Reference Interview Scale (IRIS) in early psychosis patients.

BACKGROUND: Ideas and delusions of reference (IOR/DOR) are an important but underrecognized research target. Difficulty in their reliable assessment has been a barrier. A screening and assessment tool incorporating a self-information processing framework, the Ideas of Reference Interview Scale (IRIS), was developed and validated in patients with early psychosis. METHODS: Comprehensive review of IOR/DOR phenomena in the literature and pilot interviews were conducted for scale item development. Self-referential themes were summarized into 15 items. A consecutive sample of 137 outpatients with early psychosis was interviewed using IRIS. Their IOR/DOR experiences were also rated independently by clinicians on the Scale for the Assessment of Positive Symptoms (SAPS) and self-rated using the IOR subscale on the Schizotypal Personality Questionnaire (SPQ). Inter-rater reliability of IRIS was examined in a subsample of 15 participants. RESULTS: IRIS demonstrated good internal consistency (Cronbach's alpha 0.80), inter-rater reliability (intraclass correlation coefficient 0.95), and divergent validity with other symptoms. IRIS correlated satisfactorily with the IOR/DOR item or subscale on SAPS and SPQ (Spearman's rho = 0.71 and 0.47, respectively). DISCUSSION: IRIS provided a reliable high-resolution tool for progressing single-symptom research into IOR/DOR, a potential target feature of schizophrenia. The scale allows future investigation into self-referential processing and detailed phenomenological comparison in different clinical, subclinical, and healthy populations.

Persistent negative symptoms in first-episode schizophrenia: a prospective three-year follow-up study.

BACKGROUND: Negative symptoms are a core feature of schizophrenia. The evolution and trajectory of primary negative symptoms were under-studied. We aimed at evaluating the prevalence and stability of primary negative symptoms, and factors associated with persistent primary negative symptoms in a first-episode sample. METHOD: Ninety-three Hong Kong Chinese aged 18 to 55 years presenting with first-episode schizophrenia-spectrum disorder were studied. Data on premorbid adjustment, socio-demographics, and baseline clinical and cognitive profiles were obtained. Psychopathological and vocational reassessments were conducted at 12, 24 and 36 months. Primary negative symptoms were defined as the presence of clinically significant negative symptoms excluding depression and extra-pyramidal signs. RESULTS: At baseline, 25.8% of subjects exhibited primary negative symptoms. A quarter of patients had their initial primary negative symptoms status retained 12 months after treatment initiation. In both Year 2 and Year 3 of study period, around 70% of subjects had their primary negative symptoms status maintained for 12 months. At the end of three-year follow-up, 23.7% were categorized as having persistent primary negative symptoms. Male sex, unemployment at intake, prolonged duration of untreated psychosis, poorer premorbid academic and social functioning, poorer insight and worse vocational outcome were found to be associated with persistent primary negative symptoms. CONCLUSION: Clinical status of primary negative symptoms in first-episode schizophrenia-spectrum disorder was unstable in the initial year of treatment. Baseline symptom assessment may not reliably predict development of persistent primary negative symptoms. Studying negative symptoms should take into account the longitudinal perspective, especially in the early course of psychotic disorders.

Cost-effectiveness of an early assessment service for young people with early psychosis in Hong Kong.

OBJECTIVE: The Early Assessment Service for Young People with Early Psychosis (EASY) was developed in Hong Kong in 2001 to provide a comprehensive and integrated approach for early detection and intervention for young people suffering from first episode psychosis. The present study examined the cost-effectiveness of the service over a period of 24 months compared to standard care. METHOD: This is a historical control study. Sixty-five patients who presented to the EASY service in 2001 with first episode psychosis were individually matched (on age, sex and diagnosis) with 65 patients who received standard psychiatric care in a precursor service (pre-EASY) between 1999 and 2000. A retrospective cost-effectiveness analysis was conducted over a period of 24 months. The overall average cost of service utilization per patient and the effects on hospitalization rate were compared using bootstrapping analysis. Cost per point improvement in Positive and Negative Syndrome Scale (PANSS) was also computed with sensitivity analysis. Only direct costs were analysed in the current study. RESULTS: There was no significant difference in service utilization between the EASY and pre-EASY standard care groups. The cost-effectiveness acceptability curve, which was used to explore uncertainty in estimates of cost and effects, suggested that there was a probability of at least 94% that the EASY model was more cost-effective than the pre-EASY service in reducing psychiatric inpatient admissions. EASY patients also showed superior results in average cost per unit improvement in PANSS. CONCLUSIONS: EASY is likely to be more cost-effective in improving outcomes, particularly in reducing hospitalization and improving clinical symptoms among young people with first episode psychosis. This study provides a perspective from the east Asian region, and supports further development of similar services, particularly in the local setting. However, further studies with a longer follow up period and larger sample size are required to verify these findings.

Three-year outcome of phase-specific early intervention for first-episode psychosis: a cohort study in Hong Kong.

AIM: Although phase-specific early intervention for first-episode psychosis has been implemented in many different parts of the world, limited medium-term outcome data are available in non-Western populations with relatively low mental health resources. The study aimed to determine the effectiveness of phase-specific early intervention in first-episode psychosis. METHOD: In this cohort study, we compared the 3-year outcome of 700 first-episode psychosis patients who received phase-specific early intervention with that of 700 patients matched for age, sex and diagnosis who received standard psychiatric care prior to early intervention. Using a structured data acquisition procedure, we determined functional outcome, symptom levels, relapse, recovery, suicidal behaviour and service utilization from clinical records. RESULTS: Patients in the early intervention group had longer full-time employment or study (P<0.001), fewer days of hospitalization (P<0.001), less severe positive symptoms (P=0.006), less severe negative symptoms (P =0.001), fewer suicides (P=0.009) and fewer disengagements (P=0.002) than the historical control group. Additionally, more patients in the early intervention group experienced a period of recovery (P=0.001), but the two groups had similar rates of relapse (P=0.08) and durations of untreated psychosis (P=0.72). CONCLUSIONS: The 3-year outcome in phase-specific early intervention compared favourably with that of standard psychiatric care, particularly with respect to functional outcome and reduction in hospitalizations, suicides and disengagements. However, intervention did not appear to reduce the rate of relapse.

Perceptions of relapse risks following first-episode psychosis and attitudes towards maintenance medication: a comparison between nursing and social work professionals.

AIM: Existing clinical guidelines have not yet identified an optimal duration of maintenance antipsychotic drug treatment for stable, remitted first-episode psychosis patients. This study compares the perception of relapse risk and attitudes towards maintenance medication among professionals in nursing and social work fields who have direct clinical experience with first-episode psychosis patients. We explore a perception model that identifies the decision-making factors in the clinical dilemma between relapse and maintenance. METHODS: A specially designed survey addressing perceptions of relapse risk and optimal duration of maintenance treatment was conducted among 63 experienced health-care professionals (30 nurses and 33 social workers) in the field of early psychosis in Hong Kong. RESULTS: Two clinically relevant themes were identified that affected professionals' judgment on the optimal duration of maintenance treatment in stable, remitted first-episode psychosis patients: (i) the remission period; and (ii) professionals' perceptions of relapse risk involved in medication discontinuation. The remission period was a significant predictor of the perceived relapse risk. Compared with social workers, mental health nurses perceived a higher relapse risk for patients before Bonferroni adjustment. CONCLUSIONS: The three key clinical components discussed--remission period, perceived relapse risk and perceived optimal duration of maintenance treatment--are interconnected, collectively influencing health-care professionals' attitudes towards relapse and maintenance for patients. Our study identified differences between the perceptions of nursing and social work professionals, indicating a need for communication and discussion among professional groups in order to arrive at a coherent, efficacious team consensus.

Gender differences in patients presenting with first-episode psychosis in Hong Kong: a three-year follow up study.

OBJECTIVE: The aim of the current study was to investigate gender differences with respect to pre-treatment characteristics, clinical presentation, service utilization and functional outcome in patients presenting with first-episode psychosis. METHODS: A total of 700 participants (men, n = 360; women, n = 340) aged 15 to 25 years consecutively enrolled in a territory-wide first-episode psychosis treatment programme in Hong Kong from July 2001 to August 2003 were studied. Baseline and three-year follow up variables were collected via systematic medical file review. RESULTS: At service entry, men had significantly lower educational attainment (p < 0.01), longer median duration of untreated psychosis (p < 0.001), fewer past suicidal attempts (p < 0.01), more severe negative symptoms (p < 0.05) and fewer affective symptoms (p < 0.01) than women. There was no significant gender difference in age of onset. In three-year follow up, men had more prominent negative symptoms (p < 0.001), fewer affective symptoms (p < 0.01), more violent behaviour and forensic records (p < 0.01), and higher rate of substance abuse (p < 0.01). Women achieved higher levels of functioning than men (Social Occupational Functioning Assessment Scale (SOFAS), p < 0.001) and a significantly higher proportion of women than men engaged in full-time employment or study for at least 12 consecutive months (p < 0.001) in the initial three years after psychiatric treatment. CONCLUSION: Notable gender differences in clinical profiles, illness trajectory and functional outcome were demonstrated in Chinese young people suffering from first-episode psychosis. Differential needs between men and women and hence gender-specific therapeutic strategies should be considered in early intervention service.

Executive function in first-episode schizophrenia: a three-year longitudinal study of an ecologically valid test.

Executive function impairment is a key cognitive deficit in schizophrenia. However, traditional neuropsychological tests of executive function may not be sensitive enough to capture the everyday dysexecutive problems experienced by patients. Additionally, existing literature has been inconsistent about longitudinal changes of executive functions in schizophrenia. The present study focuses on examining the longitudinal change of executive functions in schizophrenia using the Modified Six Elements Test (MSET) that was developed based on the Supervisory Attentional System model and shown to be sensitive to everyday dysexecutive problems. In the present study, MSET performance was assessed in 31 medication-naïve first-episode schizophrenic patients at four times over a period of three years, while the 31 normal controls were assessed once. Patients demonstrated impairment in MSET as compared to controls. Importantly, the MSET impairment persisted from the medication-naïve state to clinical stabilization and the three years following the first psychotic episode though patients improved in a conventional executive test (Modified Wisconsin Card Sorting Test). Performance was not related to intelligence, educational level, symptom changes, age-of-onset, or duration of untreated psychosis. Better MSET performance at medication-naïve state predicted improvement in negative and positive symptoms over the three-year period. These findings may suggest that MSET impairment is a primary deficit in schizophrenia that occurs early in the course of the illness and remains stable irrespective of clinical state for at least three years following the first episode of schizophrenia.

What does recovery from psychosis mean? Perceptions of young first-episode patients.

BACKGROUND: This study explored the experience of first-episode psychosis from the patients' perspective and the meanings they attach to the illness and their recovery. METHOD: A qualitative methodology was used based on a focus group. Audio tapes were transcribed verbatim and three researchers participated in a content analysis that identified four major themes: the meaning of psychosis and psychotic experience; the meaning of recovery; stigma; and having an optimistic view of recovery. DISCUSSION: Participants' view of recovery was broader than that often held by psychiatrists, extending beyond symptom control and medication compliance, and they identified positive features that the experience of illness had brought. Their concerns included the side effects of medication and the fear of their illness being disclosed (to employers, university authorities, acquaintances, etc.) in the face of societal stigma. CONCLUSION: Ideas about what constitutes recovery need to take account of patients' views and experience in order to emphasize therapeutic optimism rather than pessimism, and to inform treatment contexts and the views of medical staff.

Naming psychosis: the Hong Kong experience.

AIM: Schizophrenia translates in Chinese as 'Mind Split Disease' which is heavily stigmatizing. The narrow conceptualization for schizophrenia alone was insufficient, in the context of early detection and intervention for psychosis. The need for an effective Chinese translation for psychotic disorders was imminent upon the launch of the Early Assessment Service for Young People with Psychosis in Hong Kong, where public awareness strategies had to be built upon effective communication of the disorder. METHODS: 'Si Jue Shi Tiao', the new term for psychosis, described 'thought and perceptual dysregulation'. This new terminology and concept was strategically introduced to the local community. RESULTS: The term 'Si Jue Shi Tiao' was taken up well locally and had demonstrated interactions within the Chinese and East Asian communities. The public has taken in the broader concept of psychosis, in contrary to the previous concept of schizophrenia per se. CONCLUSIONS: In Hong Kong, the restrictive view of perceiving psychotic disorders as schizophrenia was broadened upon the introduction of a more embracing, less stigmatizing term 'Si Jue Shi Tiao'. Effective establishment of this term to the local vocabulary allowed a basis for communication as well as public education work. Further evaluation is necessary to determine the effectiveness of the naming and to guide further public awareness strategies.

Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial.

OBJECTIVE: To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment. DESIGN: 12 month randomised, double blind, placebo controlled trial. SETTING: Early psychosis outpatient clinics in Hong Kong. PARTICIPANTS: 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis. INTERVENTIONS: Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred. MAIN OUTCOME MEASURE: Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds. RESULTS: 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; chi(2)=3.20, df=1; P=0.07). CONCLUSION: In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year. Trial registration Clinical trials NCT00334035.

Early intervention for psychosis in Hong Kong--the EASY programme.

AIM: This article aims to describe the Hong Kong experience in developing and implementing an early psychosis programme. METHODS: In 2001, the Early Assessment Service for Young People with Psychosis programme was launched in Hong Kong, providing both educational and service components. Public education includes promotion of timely help-seeking, accessible channels to service and knowledge of psychosis. The 2-year phase-specific intervention includes intensive medical follow-up and individualized psychosocial intervention. The programme has adopted the case-management approach, in which case managers provide protocol-based psychosocial intervention. The programme collaborates with non-governmental organizations and community networks in the provision of rehabilitation service. RESULTS: An average of over 600 young patients enter the programme for intensive treatment each year. Based on preliminary data from a 3-year outcome study, patients in the programme have remarkable reductions in hospital stay accompanied by improvements in vocational functioning. CONCLUSIONS: The results suggested that the programme improved patients' outcome. Additional costs such as extra medical staff and medications may be offset by the shortened hospital stay. Further directions in early intervention are also discussed.

Phenotyping psychosis: room for neurocomputational and content-dependent cognitive endophenotypes?

INTRODUCTION: The endophenotype research strategy aims at reducing complex clinical phenomena to reveal a more tractable mapping to underlying genes. Cognitive dysfunctions have been widely pursued as target endophenotype in schizophrenia. We critically discuss the promise and limitations of this approach. METHODS: Relevant theoretical and empirical issues on genes and behaviour, neurocognitive structure and psychopathology were selectively reviewed and discussed. RESULTS: Some important inherent limitations of the current cognitive endophenotype approach were identified. These include reliance on (1) classic neuropsychology; (2) deficit measures; and (3) a general information processing approach with the use of content-independent, neutral stimuli. As a result, many current cognitive endophenotypes are likely to overlap and converge with general cognitive impairments, which may be shared with other disorders. CONCLUSIONS: We propose three novel directions for further psychosis endophenotype research: (1) in addition to such content-independent computational processes, which operate in a similar way regardless of the stimuli, it is important to consider the potential roles of "content-dependent endophenotypes", which operate on different stimuli in consistently different manners. Advances in cognitive studies suggest there may be evolutionarily important aspects of cognition which are content-dependent. We propose that both content-independent and content-dependent processes should be addressed in psychosis research. (2) In line with the emphasis on content, close attention should be paid to the study of "psychopathological endophenotypes" in addition to cognitive endophenotypes. (3) "Neurocomputational endophenotypes" may be defined by parsing cognitive processes into "subsystems" with specific computational processing algorithms and considering key computational parameters suggested from these models. These potential "neurocomputational endophenotypes" (such as neuronal noise, synaptic learning algorithms) are potentially intermediate variables located between the levels of cognition and neurobiology.

Transition to psychosis: 6-month follow-up of a Chinese high-risk group in Hong Kong.

OBJECTIVES: The identification of individuals at high risk of becoming psychotic within the near future creates opportunities for early intervention before the onset of psychosis. This study sets out to identify a group of symptomatic young people in a Chinese population with the high likelihood of transition to psychosis within a follow-up period of 6 months, and to determine the rate of transition to psychosis in this group. METHOD: Symptomatic individuals with a family history of psychotic disorder, sub-threshold psychotic symptoms or brief transient psychotic symptoms were identified using the operationalized criteria of an 'At Risk Mental State'. The individuals were prospectively assessed monthly on a measure of psychopathology for 6 months. RESULTS: Eighteen out of 62 individuals (29%) made the transition to frank psychosis within a 6 month follow-up period, with the majority occurring within 3 months. In addition, significant differences were found in the intake Positive and Negative Syndrome Scale, Comprehensive Assessment of 'At Risk Mental State' and Global Assessment of Functioning scores between the group that ultimately became psychotic and the group that did not. CONCLUSION: The period of the highest risk of transition to psychosis was within the 3 months after the study began. Thus, distressed youths in our outpatient clinic, who meet the high-risk criteria should be monitored most closely in the initial 3 months, particularly those individuals with high levels of psychopathology and functional decline.