H.P. Yuen

The impact of substance use disorders on clinical outcome in 643 patients with first-episode psychosis.

Objective:u2002 Studies investigating the impact of comorbid substance use disorders (SUD) in psychosis have tended to focus on cross‐sectional data, with few studies examining the effects of substance use course on clinical outcome. The main aim of the present study was to assess the impact of baseline SUD and course of SUD on remission of positive symptoms.

The EPPIC Follow-Up Study of First-Episode Psychosis: Longer-Term Clinical and Functional Outcome 7 Years After Index Admission

OBJECTIVEnTo describe the longer-term clinical and functional outcome of a large, epidemiologic representative cohort of individuals experiencing a first episode of psychosis.nnnMETHODnA naturalistic, prospective follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients, followed between January 1998 and April 2005, at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne, Australia. EPPIC is a frontline public mental health early psychosis program, servicing a geographically defined catchment area with a population of about 800,000 people. The main outcome measures included the Brief Psychiatric Rating Scale, the Schedule for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Global Assessment of Functioning Scale, the Social and Occupational Functioning Assessment Scale, the Quality of Life Scale, and the remission criteria developed by the Remission in Schizophrenia Working Group.nnnRESULTSnFollow-up information was collected on up to 90.0% (n = 651) of the baseline cohort of 723 participants, with 66.9% (n = 484) interviewed. In the last 2 years, 57% of individuals with schizophrenia/schizophreniform, 54% with schizoaffective disorder, 62% with affective psychosis, and 68% with other psychotic disorders reported some paid employment. Depending upon the criteria applied, symptomatic remission at follow-up was observed in 37%-59% of the cohort. Social/vocational recovery was observed in 31% of the cohort. Approximately a quarter achieved both symptomatic remission and social/vocational recovery.nnnCONCLUSIONnThe relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs; however it is premature to draw firm conclusions. There was no control group and there are many differences between the relevant comparison studies and the present one. Although difficult to conduct, large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs.

Mapping the onset of psychosis: The comprehensive assessment of at risk mental states (CAARMS)

OBJECTIVEnRecognizing the prodrome of a first psychotic episode prospectively creates the opportunity of intervention, which could delay, ameliorate or even prevent onset. Valid criteria and a reliable methodology for identifying possible prodromes are needed. This paper describes an instrument, the Comprehensive Assessment of At-Risk Mental States (CAARMS), which has been designed for such a purpose. It has two functions: (i) to assess psychopathology thought to indicate imminent development of a first-episode psychotic disorder; and (ii) to determine if an individual meets criteria for being at ultra high risk (UHR) for onset of first psychotic disorder. This paper describes the pilot evaluation of the CAARMS.nnnMETHODnSeveral methodologies were used to test the CAARMS. First, CAARMS scores in a group of UHR young people and the association between CAARMS scores and the risk of transition to psychotic disorder, were analysed. Second, CAARMS scores in a UHR group were compared to a control group. To assess concurrent validity, CAARMS-defined UHR criteria were compared to the existing criteria for identifying the UHR cohort. To assess predictive validity, the CAARMS-defined UHR criteria were applied to a sample of 150 non-psychotic help-seekers and rates of onset of psychotic disorder at 6-month follow-up determined for the CAARMS-positive (i.e. met UHR criteria) group and the CAARMS-negative (i.e. did not meet UHR criteria) group. The inter-rater reliability of the CAARMS was assessed by using pairs of raters.nnnRESULTSnHigh CAARMS score in the UHR group was significantly associated with onset of psychotic disorder. The control group had significantly lower CAARMS scores than the UHR group. The UHR criteria assessed by the CAARMS identified a similar group to the criteria measured by existing methodology. In the sample of non-psychotic help-seekers those who were CAARMS-positive were at significantly increased risk of onset of psychotic disorder compared to those who were CAARMS-negative (relative risk of 12.44 (95% CI = 1.5-103.41, p = 0.0025)). The CAARMS had good to excellent reliability.nnnCONCLUSIONSnIn these preliminary investigations, the CAARMS displayed good to excellent concurrent, discriminant and predictive validity and excellent inter-rater reliability. The CAARMS instrument provides a useful platform for monitoring subthreshold psychotic symptoms for worsening into full-threshold psychotic disorder.

Treated incidence of first-episode psychosis in the catchment area of EPPIC between 1997 and 2000.

Objective:u2002 To identify the treated incidence of psychosis in catchment of the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia.

Early-onset of symptoms predicts conversion to non-affective psychosis in ultra-high risk individuals

OBJECTIVEnWe examined if age of onset of psychiatric symptoms and/or sex predict conversion to non-affective or affective psychosis in individuals considered to be at ultra-high risk for schizophrenia.nnnMETHODnParticipants (n=86) were offered treatment and monthly follow-up until transition to psychosis, or for 12 months if they did not meet exit criteria for psychotic disorder. Individuals without transition to psychosis at 12-month were reassessed approximately 3 years after the end of the treatment phase. Ultra-high risk was defined by the presence of subthreshold and/or self-limiting psychotic symptoms and/or having a family history of psychotic disorder combined with functional decline. Cox regressions after adjustment for treatment interventions were applied to investigate associations between age of onset, sex, and other baseline measures with progression to psychotic outcomes.nnnRESULTSnEarly age of onset of psychiatric symptoms, in particular onset before age 18 was the only tested variable that significantly predicted non-affective psychosis. Independent significant predictors of affective psychosis were poor functioning, female sex and the presence of a combination of intake criteria (family history of psychosis plus drop in functioning, and attenuated and/or brief limited psychotic symptoms) at baseline.nnnCONCLUSIONSnAge of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals.

Further examination of the reducing transition rate in ultra high risk for psychosis samples: The possible role of earlier intervention

BACKGROUNDnThe rate of transition to psychotic disorder in ultra high risk (UHR) patients has declined in recent cohorts. The reasons for this are unclear, but may include a lead-time bias, earlier intervention, a change in clinical characteristics of cohorts, and treatment changes.nnnAIMSnIn this paper we examined the two possibilities related to reduction in duration of symptoms prior to clinic entry, i.e., lead-time bias and earlier intervention.nnnMETHODnThe sample consisted of all UHR research participants seen at the PACE clinic, Melbourne between 1993 and 2006 (N=416), followed for a mean of 7.5years (the PACE 400 cohort). Duration of symptoms was analysed by four baseline year time periods. Analysis of transition rate by duration of symptoms was restricted to more homogenous sub-samples (pre-1998 and pre-2001) in order to minimize confounding effects of change in patient characteristics or treatments. These cohorts were divided into those with a short and long duration of symptoms using a cut-point approach.nnnRESULTSnDuration of symptoms prior to entry did not reduce significantly between 1993 and 2006 (p=0.10). The group with a short duration of symptoms showed lower transition rates and did not catch up in transition rate compared to the long duration of symptoms group.nnnDISCUSSIONnThese data suggest that, while earlier intervention or lead-time bias do not fully account for the declining transition rate in UHR cohorts, it appears that earlier intervention may have exerted a stronger influence on this decline than length of follow-up period (lead-time bias).

Adjunctive Taurine in First-Episode Psychosis: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVEnTaurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor. It also functions as a neuroprotective agent and has a role in neural development and neurogenesis. The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder.nnnMETHODSn121 patients with first-episode psychosis, aged 18-25 years, attending early intervention services consented to participate in this randomized, double-blind, placebo-controlled trial conducted from January 2007 to May 2009. Patients taking low-dose antipsychotic medication were randomly assigned to receive once-daily taurine 4 g or placebo for 12 weeks. The coprimary outcomes were change in symptomatology (measured by the Brief Psychiatric Rating Scale [BPRS] total score) and change in cognition (measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [MATRICS] Consensus Cognitive Battery composite score) at 12 weeks. Secondary outcomes included tolerability and safety and additional clinical and functioning measures.nnnRESULTSn86 participants (n = 47 taurine; n = 39 placebo) were included in the final analysis. Taurine significantly improved symptomatology measured by the BPRS total score (95% CI, 1.8-8.5; P = .004) and psychotic subscale (95% CI, 0.1-1.5; P = .026) compared to placebo. Additionally, improvements were observed in the Calgary Depression Scale for Schizophrenia (95% CI, 0.1-3.0; P = .047) and Global Assessment of Functioning (95% CI, 0.3-8.8; P = .04) scores. There was no group difference in composite cognitive score (95% CI, -1.7 to 1.0; P = .582). A significant group difference was found on one safety and tolerability item (psychic item 2, asthenia/lassitude/increased fatigability) of the Udvalg for Kliniske Undersogelser, with the taurine group showing a more favorable outcome (P = .006).nnnCONCLUSIONSnAdjunctive taurine did not improve cognition, but it appears to improve psychopathology in patients with first-episode psychosis. The use of taurine warrants further investigation in larger randomized studies, particularly early in the course of psychosis.nnnTRIAL REGISTRATIONnClinicalTrials.gov identifier: NCT00420823.

The Ultra-High-Risk for psychosis groups: Evidence to maintain the status quo

Individuals are considered Ultra-High-Risk (UHR) for psychosis if they meet a set of standardised criteria including presumed genetic vulnerability (Trait), or a recent history of Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS). Recent calls to revise these criteria have arisen from evidence that Trait, APS and BLIPS groups may transition to psychosis at different rates. Concurrently, it has become clear that the UHR status confers clinical risk beyond transition to psychosis. Specifically, most UHR individuals will not develop psychosis, but will experience high rates of non-psychotic disorders, persistent APS and poor long-term functional outcomes. Rather than focus on transition, the present study investigated whether UHR groups differ in their broader clinical risk profile by examining baseline clinical characteristics and long-term outcomes other than transition to psychosis. Four UHR groups were defined: Trait-only, APS-only, Trait+APS, and any BLIPS. Participants (N=702) were recruited upon entry to early intervention services and followed-up over a period of up to 13years (mean=4.53, SD=3.84). The groups evidenced similar symptom severity (SANS for negative symptoms, BPRS for positive and depression/anxiety symptoms) and psychosocial functioning (SOFAS, GAF, QLS) at baseline and follow-up as well as similar prevalence of non-psychotic disorders at follow-up. Our findings demonstrate that UHR groups evidence a similar clinical risk profile when we expand this beyond transition to psychosis, and consequently support maintaining the existing UHR criteria.

The 8 year functional and symptomatic outcome of first episode psychosis (FEP)

This is the Special Issue: Abstracts of the 20th International Congress on Schizophrenia Research 2005This journal issue entitled: Special Issue: Abstracts of the XX International Congress on Schizophrenia Research

NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders—medium-term follow-up and clinical course

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4u2009g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6–12. Mean time to follow-up was 3.4 (medianu2009=u20093.3; SDu2009=u20090.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11–13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.Omega-3: No benefit to those at risk of psychosisOmega-3 fatty acids, when given alongside traditional therapies, provide no extra benefits to patients at high risk of developing psychosis. In attempts to validate a previous clinical trial wherein omega-3 reduced the risk of ultra-high-risk patients transitioning to psychosis, Patrick McGorry, of the National Centre of Excellence in Youth Mental Health, Australia, and his team looked to replicate the findings in a larger cohort. Despite improvements in symptoms seen in a medium-term follow-up of 304 patients after ~3.4 years, no extra benefit or reduced transitioning was seen in those additionally receiving omega-3 fatty acids. The bulk of treatment benefit was seen between 0–12 months, but the data indicate a clear need for ongoing patient care. This study also revealed psychopathology score level, anxiety, and societal functioning to be strong indicators of psychosis transition risk.