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Cardiovascular and metabolic diseases are the leading contributors to the early mortality associated with psychotic disorders. To date, it has not been possible to disentangle the effect of medication and non-medication factors on the physical health of people with a first episode of psychosis (FEP). This study aimed to isolate the effects of antipsychotic medication on anthropometric measurements, fasting glucose and lipids.This study utilized data from a triple-blind randomized placebo-controlled trial comparing two groups of antipsychotic-naïve young people with a FEP who were randomized to receive a second-generation antipsychotic medication (FEP-medication group) or placebo (FEP-placebo group) for 6 months. Twenty-seven control participants were also recruited.Eighty-one participants commenced the trial; 69.1% completed at least 3 months of the intervention and 33.3% completed the full 6 months. The FEP-placebo group gained a mean of 2.4 kg (±4.9) compared to 1.1 kg (±4.9) in the control participants (t = 0.76, p = .45). After controlling for multiple analyses, there was no difference in blood pressure, waist circumference or heart rate between the FEP-placebo group and controls. After 6 months, the FEP medication group had gained 4.1 kg (±4.5), higher than those receiving placebo but not statistically significant (t = 0.8, p = .44). There were no differences in fasting glucose or lipids between the FEP groups after 3 months.While limited by small numbers and high attrition, these findings indicate that some of the metabolic complications observed in psychotic disorders could be attributable to factors other than medication. This emphasizes the need to deliver physical health interventions early in the course of FEP.

Background Ultra high-risk (UHR) criteria were introduced to identify people at imminent risk of developing psychosis. To improve prognostic accuracy, additional clinical and biological risk factors have been researched. Associations between psychotic disorders and infections with Toxoplasma gondii and Herpesviridae have been found. It is unknown if exposure to those pathogens increases the risk of transition to psychosis in UHR cohorts. Methods We conducted a long-term follow-up of 96 people meeting UHR criteria, previously seen at the Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service in Melbourne, Australia. Transition to psychosis was assessed using the Comprehensive Assessment of the At-Risk Mental State (CAARMS) and state public mental health records. The relationship between IgG antibodies to Herpesviridae (HSV-1, HSV-2, CMV, EBV, VZV) and Toxoplasma gondii and risk for transition was examined with Cox regression models. Results Mean follow-up duration was 6.46 (±3.65) years. Participants who transitioned to psychosis (n = 14) had significantly higher antibody titers for Toxoplasma gondii compared to those who did not develop psychosis (p = 0.03). After adjusting for age, gender and year of baseline assessment, seropositivity for Toxoplasma gondii was associated with a 3.6-fold increase in transition hazard in multivariate Cox regression models (HR = 3.6; p = 0.036). No significant association was found between serostatus for Herpesviridae and risk of transition. Conclusions Exposure to Toxoplasma gondii may contribute to the manifestation of positive psychotic symptoms and increase the risk of transitioning to psychosis in UHR individuals.

ObjectiveCognitive impairment occurs in antipsychotic-naïve first-episode psychosis (FEP), but antipsychotics confound interpretation of the longitudinal course of cognition. The primary aim was to disentangle the effects of illness from antipsychotics on cognition over the first 6-months of FEP treatment.MethodsRandomised, triple-blind placebo-controlled trial (Staged Treatment and Acceptability Guidelines in Early Psychosis; STAGES), where cognition was a secondary outcome. Antipsychotic-naïve FEP patients were allocated to receive risperidone/paliperidone (N=38) or placebo (N=40) in addition to intensive psychosocial therapy for 6-months. A healthy control group (N=42) was also recruited. A cognitive battery assessing attention, working memory, processing speed, verbal fluency, cognitive control and verbal paired-associate learning and memory was administered at baseline and 6-months. Twelve- and 24-month follow-up was also conducted.ResultsOver the 6-month trial period, cognitive performance remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. The exception was for verbal paired-associate learning and memory, where a significant group-by-time interaction was observed. The placebo and healthy control groups improved, and the medication group deteriorated on immediate paired-associate recall (p=0.039) and delayed cued recall (p=0.005); effect sizes were medium-to-large. Findings were similar when only trial completers were included in the analysis.ConclusionsRisperidone/paliperidone may cause progression of memory impairment in the early months of FEP. Replication is needed in confirmatory trials. The findings support the need for careful consideration of the risks and benefits of various antipsychotics and the importance of accounting for their cognitive effects in longitudinal research.Trial registrationAustralian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/ ACTRN12607000608460).

ImportancePsychotic illness is associated with anatomically distributed grey matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown.ObjectiveTo test the hypothesis that brain network architecture constrains cross-sectional and longitudinal grey matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicentres from which volume loss spreads.Design, Settings, ParticipantsThis study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naïve first episode psychosis (N=59) and a group of medicated patients within 3 years of psychosis onset (N=121). Late-stage cohorts comprised two independent samples of people with established schizophrenia (N=136 in total). Each patient group had a corresponding matched control group (N=218 in total). A further independent sample of healthy adults (N=346) was used to derive representative structural and functional brain networks for modelling of network-based spreading processes. We additionally examined longitudinal illness-related and antipsychotic-related grey matter changes over 3 and 12 months using a triple-blind randomised placebo-control MRI study of the antipsychotic-naïve patients. All data were collected between April 2008 and January 2020, and analyses were performed between March 2021 and January 2023.Main Outcomes and MeasuresWe used coordinated deformation models to predict the extent of grey matter volume change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicentres of volume loss, we used a network diffusion model to simulate the spread of pathology from different seed regions. Correlations between predicted and empirical spatial patterns of grey matter volume alterations were used to quantify model performance.ResultsIn both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately predicted by coordinated deformation models constrained by structural, rather than functional, network architecture (. 46 52;p< .001) and antipsychotic exposure (r> .50;p< .001). Diffusion modelling consistently identified, across all four datasets, the anterior hippocampus as a putative epicentre of pathological spread in psychosis (all p< .05). Epicentres of longitudinal grey matter loss were apparent posteriorly early in the illness and shifted anteriorly to prefrontal cortex with illness progression.Conclusion and RelevanceOur findings highlight a robust and central role for white matter fibres as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicentre of early brain pathology from which dysfunction may spread to affect connected areas.Key pointsQuestionAre grey matter changes across the psychosis continuum constrained by brain network architecture and are certain regions epicentres of volume loss?FindingsAcross four independent samples spanning different stages of psychotic illness, grey matter alterations are strongly constrained by the underlying architecture of the brain’s axonal pathways and the hippocampus is consistently identified as a putative source from which volume-loss may spread to connected regions.MeaningWhite matter fibres may act as conduits for the spread of pathology across all stages of psychotic illness and medial temporal regions play a critical role in the origins of grey matter reductions.

Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and antipsychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking antipsychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between cognition and physical health in healthy populations, the aim was to explore whether cognition and physical health are associated in FEP, which could inform early physical health interventions for cognition in FEP. Participants were aged 15 to 25 and included 86 individuals experiencing FEP with limited antipsychotic exposure and duration of untreated psychosis of ≤six months, and 43 age- and sex-matched controls. Individuals with FEP performed significantly poorer than controls in most cognitive domains (Cohen's d = 0.38 to 1.59). Groups were similar in metabolic health measures, excluding a significantly faster heart rate in FEP (d = 0.68). Through hierarchical regression analyses, we found that in the overall sample, BMI was negatively related to current IQ after controlling for education and group (FEP/control). Relationships between BMI and cognition were consistent across the FEP and healthy control groups. In FEP, current IQ and working memory were negatively correlated with lipid profiles. Findings suggest that in FEP, impaired cognition is exhibited earlier than physical health problems, and that compared to controls, similar relationships with cognition are demonstrated. Causal pathways and trajectories of relationships between health and cognition in FEP require investigation, especially as antipsychotic medications are introduced. The findings have implications for cognitive and health interventions.

BackgroundAltered functional connectivity (FC) is a common finding in resting-state functional Magnetic Resonance Imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotics may influence the temporal evolution of these disturbances, remains unclear. Here, we scanned first episode psychosis (FEP) patients who were and were not exposed to antipsychotic medication during the first six months of illness at baseline, three months, and 12 months, to characterize how FC changes over time and in relation to medication use.MethodsSixty-two antipsychotic-naïve patients with FEP received either an atypical antipsychotic or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n=27) was also recruited. A total of 202 rs-fMRI scans were obtained across three timepoints: baseline, 3-months and 12-months. Our primary aim was to differentiate patterns of FC in antipsychotic-treated and antipsychotic-naive patients within the first 3 months of treatment, and to examine associations with clinical and functional outcomes. A secondary aim was to investigate long-term effects at the 12-month timepoint.ResultsAt baseline, FEP patients showed widespread functional dysconnectivity in comparison to controls, with reductions predominantly affecting interactions between the default mode network (DMN), limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems, and some of these changes correlated with improved clinical outcomes. Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. At the 12-month follow-up, antipsychotic treatment was associated with a prolonged increase of FC primarily in the DMN and limbic systems.Conclusions and RelevanceAntipsychotic-naïve FEP patients show widespread functional dysconnectivity at baseline, followed by an early normalization of DMN and paralimbic dysfunction in patients receiving a psychosocial intervention only. Antipsychotic exposure is associated with distinct FC changes, principally concentrated on thalamo-cortical and limbic networks.

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signaling or impaired top-down cortical regulation. Here, we used spectral dynamic causal modelling (DCM) of resting-state functional magnetic resonance imaging (fMRI) to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis (FEP) patients and 23 controls and an independent sample of 36 patients with established schizophrenia (SCZ) patients and 100 controls. We found that midbrain and thalamic connectivity were implicated across both patient groups. Dysconnectivity in FEP patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in SCZ patients. In another independent sample of 33 healthy individuals who underwent concurrent fMRI and [18F]DOPA positron emission tomography, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits as those associated with psychotic symptom severity in patients. Our findings thus indicate that subcortical dysconnectivity is salient in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signaling are closely related to striatal dopamine synthesis capacity, which is a robust risk marker for psychosis.

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p

The COVID-19 outbreak may profoundly impact population mental health because of exposure to substantial psychosocial stress. An increase in incident cases of psychosis may be predicted. Clinical advice on the management of psychosis during the outbreak needs to be based on the best available evidence. We undertook a rapid review of the impact of epidemic and pandemics on psychosis. Fourteen papers met inclusion criteria. Included studies reported incident cases of psychosis in people infected with a virus of a range of 0.9% to 4%. Psychosis diagnosis was associated with viral exposure, treatments used to manage the infection, and psychosocial stress. Clinical management of these patients, where adherence with infection control procedures is paramount, was challenging. Increased vigilance for psychosis symptoms in patients with COVID-19 is warranted. How to support adherence to physical distancing requirements and engagement with services in patients with existing psychosis requires careful consideration. Registration details: https://osf.io/29pm4.

Key Points Question Are there different patterns of brain connectivity in antipsychotic-treated and antipsychotic-naive patients with psychosis, and how do these patterns evolve over time? Findings In this secondary analysis of a triple-blind, longitudinal, placebo-controlled, randomized clinical trial in antipsychotic-naive patients, patients showed widespread brain dysconnectivity at baseline relative to healthy controls. Patients treated with therapy and placebo or with therapy and antipsychotics showed evidence of circuit-specific and treatment-specific normalization of connectivity over time. Meaning In this study, some prominent baseline connectivity differences in first-episode psychosis normalized with both psychosocial therapy and placebo early in the illness course, with antipsychotics exerting circuit-specific effects., This secondary analysis of a randomized clinical trial investigates differential patterns of brain connectivity in antipsychotic-treated and antipsychotic-naive patients with psychosis and how these patterns change over time., Importance Altered functional connectivity (FC) is a common finding in resting-state functional magnetic resonance imaging (rs-fMRI) studies of people with psychosis, yet how FC disturbances evolve in the early stages of illness, and how antipsychotic treatment influences these disturbances, remains unknown. Objective To investigate longitudinal FC changes in antipsychotic-naive and antipsychotic-treated patients with first-episode psychosis (FEP). Design, Setting, and Participants This secondary analysis of a triple-blind, randomized clinical trial was conducted over a 5-year recruitment period between April 2008 and December 2016 with 59 antipsychotic-naive patients with FEP receiving either a second-generation antipsychotic or a placebo pill over a treatment period of 6 months. Participants were required to have low suicidality and aggression, to have a duration of untreated psychosis of less than 6 months, and to be living in stable accommodations with social support. Both FEP groups received intensive psychosocial therapy. A healthy control group was also recruited. Participants completed rs-fMRI scans at baseline, 3 months, and 12 months. Data were analyzed from May 2019 to August 2020. Interventions Resting-state functional MRI was used to probe brain FC. Patients received either a second-generation antipsychotic or a matched placebo tablet. Both patient groups received a manualized psychosocial intervention. Main Outcomes and Measures The primary outcomes of this analysis were to investigate (1) FC differences between patients and controls at baseline; (2) FC changes in medicated and unmedicated patients between baseline and 3 months; and (3) associations between longitudinal FC changes and clinical outcomes. An additional aim was to investigate long-term FC changes at 12 months after baseline. These outcomes were not preregistered. Results Data were analyzed for 59 patients (antipsychotic medication plus psychosocial treatment: 28 [47.5%]; mean [SD] age, 19.5 [3.0] years; 15 men [53.6%]; placebo plus psychosocial treatment: 31 [52.5%]; mean [SD] age, 18.8 [2.7]; 16 men [51.6%]) and 27 control individuals (mean [SD] age, 21.9 [1.9] years). At baseline, patients showed widespread functional dysconnectivity compared with controls, with reductions predominantly affecting interactions between the default mode network, limbic systems, and the rest of the brain. From baseline to 3 months, patients receiving placebo showed increased FC principally within the same systems; some of these changes correlated with improved clinical outcomes (canonical correlation analysis R = 0.901; familywise error–corrected P = .005). Antipsychotic exposure was associated with increased FC primarily between the thalamus and the rest of the brain. Conclusions and Relevance In this secondary analysis of a clinical trial, antipsychotic-naive patients with FEP showed widespread functional dysconnectivity at baseline, followed by an early normalization of default mode network and cortical limbic dysfunction in patients receiving placebo and psychosocial intervention. Antipsychotic exposure was associated with FC changes concentrated on thalamocortical networks. Trial Registration ACTRN12607000608460

Background This aims of this study were: (1) to determine the prevalence of co-occurring borderline personality disorder (BPD) in a first-episode psychosis (FEP) sample; (2) to determine differences between patients with and without BPD on demographics, comorbidities and clinical risks and other variables; and (3) to examine whether BPD comorbidity influenced treatment received by patients for FEP during their first 3 months after service entry to a specialist early psychosis service. Methods A file audit was conducted for 100 consecutive admissions to an early psychosis service. Patients with a clinician-rated co-occurring diagnosis of BPD were compared with patients without clinician-rated BPD on a range of variables. Results Twenty-two percent of the FEP sample was diagnosed with co-occurring BPD by clinician ratings. The FEP group with co-occurring BPD was found to be younger, more likely to have other comorbidities, and were at higher risk of suicide and violent behaviour. Group differences were found in treatment received for FEP, whereby patients with co-occurring BPD had poorer access to standard treatment, including guideline concordant antipsychotic medication prescription. Conclusion Young people with co-occurring clinician-rated BPD and FEP experienced greater difficulty accessing standard care for FEP and received relatively different treatment, including different pharmacotherapy, compared with those FEP patients without BPD. There is a need to develop new clinical guidelines and effective treatments for this specific subgroup with early psychosis and co-occurring BPD that take into account interpersonal and “premorbid” aspects of their presenting problems.

Background The prevalence of antibodies to Toxoplasma gondii, a ubiquitous parasitic protozoan causing the infectious disease toxoplasmosis, is increased in patients with psychotic disorders compared to the general population. We have previously shown that antibody titers for T.gondii correlate with the severity of positive symptoms in young people at ultra-high risk (UHR) for psychosis, suggesting that infection with T. gondii may be relevant to the manifestation of psychosis. However, it is unclear if T. gondii antibodies represent a risk factor for psychosis onset or non-psychotic outcome in UHR individuals. The aim of the present study was to examine whether seropositivity for T.gondii is associated with transition to psychosis and other outcomes in young people at UHR for psychosis. Methods The study sample consisted of 96 individuals at UHR for psychosis who were referred to the Personal Assistance and Crisis Evaluation (PACE) clinic in Melbourne, Australia, between 2001 and 2004, consented to optional blood tests for infectious agents and were followed up for up to 10 years after baseline (median (interquartile range) duration of follow-up: 7.15 (3.14 – 7.72) years). Serum IgG antibodies to six viral and parasitic pathogens (Toxoplasma gondii, Herpes Simplex Virus Type 1 and 2, Cytomegalovirus, Epstein Barr Virus, Varicella-Zoster Virus) were measured at baseline. Outcome measures included transition to psychosis, general psychiatric symptomatology and positive psychotic symptoms (BPRS), negative symptoms (SANS), depressive symptoms (HAM-D), anxiety symptoms (HAM-A) and functioning (SOFAS and GAF). Cox proportional hazards regression and linear regression models were used to examine the associations of seropositivity and antibody titers at baseline and transition to psychosis and other outcomes at follow-up. Results A total of 17 individuals (17.7%) were seropositive for Toxoplasma gondii at baseline. The rate of transition to psychosis was higher among seropositive (35.7%) compared to seronegative participants (14.6%), although this was not statistically significant (p=0.101). Antibody titers (IgG) for Toxoplasma gondii were significantly higher at baseline in participants who later transitioned to psychosis (1.34 ± 1.36 vs. 0.79 ± 0.73, p=0.027). Seropositivity for T.gondii IgG at baseline significantly predicted transition to psychosis within the follow-up duration (hazard ratio [HR]=3.61, 95%CI 1.08 – 12.00, p=0.036). Toxoplasma IgG at baseline were significantly associated with higher BPRS scores at follow-up in participants who were seropositive at baseline (Beta=6.38, 95%CI 0.43 – 12.34, p=0.038). No significant associations were found between antibodies to other pathogens and outcome, or between antibodies to Toxoplasma gondii and any other outcomes. Discussion Our findings suggest that the presence of IgG class antibodies for Toxoplasma gondii is associated with a higher risk for psychosis transition in individuals at UHR for psychosis, but not with risk for other long-term outcomes. These observations provide support for the hypothesis that infection with Toxoplasma gondii may be an environmental risk factor for psychosis and suggest that IgG antibodies for Toxoplasma gondii in individuals at UHR for psychosis have prognostic relevance.

Background Neuroimaging studies have found dysconnectivity of frontostriatal circuits across a broad spectrum of psychotic symptoms. However, it is unknown whether dysconnectivity within frontostriatal circuits originates from disrupted bottom-up or top-down control signaling within these systems. Here, we used dynamic causal modelling (DCM) to examine the effective connectivity of frontostriatal systems in first-episode psychosis (FEP). Methods A total of 55 FEP patients (26 males; mean [SD] age = 19.24 [2.89]) and 24 healthy controls (15 males; mean [SD] age = 21.83 [1.93]) underwent a resting-state functional magnetic resonance imaging protocol. Biologically plausible connections between eight left hemisphere regions encompassing the dorsal and ventral frontostriatal systems were modelled using spectral DCM. The regions comprise dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior hippocampus, amygdala, dorsal caudate, nucleus accumbens, thalamus, and the midbrain. Effective connectivity between groups were assessed using a parametric Bayesian model. Associations between effective connectivity parameters and positive symptoms, measured by the Brief Psychiatric Rating Scale positive subscale, was assessed in the patient group in a separate Bayesian general linear model. Results DCM shows evidence for differences in effective connectivity between patients and healthy controls, namely in the bottom-down connections distributed in the frontostriatal system encompassing the hippocampus, amygdala, striatum, and midbrain. Compared to healthy controls, patients also demonstrated increased disinhibition of the midbrain. In patients, positive symptoms are associated with increased top-down connections to the midbrain. Outgoing connection from the midbrain to the nucleus accumbens is also increased in association with positive symptoms. Discussion Aberrant top-down connectivity in the frontostriatal system in patients is consistent with top-down dysregulation of dopamine function in FEP, as dopaminergic activity in the midbrain is proposed to be under the control of higher brain areas. In patients, increased self-inhibition of the midbrain, as well as symptom associations in both ingoing and outgoing connections of this region, are congruous with hyperactivity of the midbrain as proposed by the dopamine dysregulation hypothesis. Here, we demonstrate that mathematical models of brain imaging signals can be used to identify the key disruptions driving brain circuit dysfunction, identifying new targets for treatment.

This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).

This is the first study to explore interpersonal schemata in outpatient youths (age 15–25 years) with early-stage borderline personality disorder (BPD) and auditory verbal hallucinations (AVH). It also aimed to replicate, in a transdiagnostic youth sample, the finding from studies of adults with AVH that negative beliefs about the self and others lead to negative appraisals of voices, which in turn elicits depression. The following 3 groups were compared: youth with BPD+AVH (n = 23), youth with schizophrenia spectrum disorder (SZ) with AVH (SZ+AVH, n = 20), and youths with BPD who did not experience AVH (BPD no AVH, n = 23). The BPD+AVH group reported more negative and fewer positive self schemata than the SZ+AVH group. They also saw themselves as being more socially inferior to others than did the SZ+AVH group, but they did not differ in appraisals of self or others, compared with the BPD no AVH group. In youths with AVH (BPD+AVH, SZ+AVH combined), the indirect effect of beliefs about self or others, via negative appraisals of voices on depression, was not significant. Instead, a significant indirect effect of negative appraisals of voices on depression, via negative beliefs about self, was found. The experience of AVH during adolescence and young adulthood, when the identity is still being formed, might have a more profound effect on the developing self than during later adulthood, when the self is more stable and resilient. Negative self-appraisals might constitute a treatment target for early intervention for youths with distressing voices, including those with BPD.

Advance statements represent a promising but relatively unexplored means to empower young people with first-episode psychosis to actively participate in their own mental health care. This qualitative study explored the use of advance statement’s for young people with first-episode psychosis, as well as their carers and clinicians, and provided actionable feedback on how to better meet the needs and preferences of these key stakeholders and more effectively implement advance statements in clinical settings.

OBJECTIVE This study explored phenomenological aspects of auditory verbal hallucinations (AVH) and other psychotic symptoms among youth with borderline personality disorder (BPD). METHODS Sixty-eight outpatients, aged 15 to 25 years, were categorized into three groups according to their primary Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis and AVH symptom profile; BPD + AVH (n = 23), schizophrenia spectrum disorder (SZ) + AVH (n = 22) and BPD with no AVH (n = 23). RESULTS No differences in AVH were found between BPD + AVH and SZ + AVH. Compared with SZ + AVH, BPD + AVH scored lower on delusions and difficulty in abstract thinking and higher on hostility. BPD + AVH reported more severe self-harm, paranoid ideation, dissociation, anxiety and stress than BPD no AVH. CONCLUSIONS This study replicates, in a sample of youth, the finding from studies of adults that AVH in BPD are indistinguishable from those in SZ, when assessed with the Psychotic Symptom Rating Scales (PSYRATS). Clinicians should specifically enquire about AVH among youth with BPD. When present, AVH appear to be an indicator of a more severe form of BPD.

Aim Up to half of patients with borderline personality disorder report auditory verbal hallucinations that are phenomenologically indistinguishable from those in schizophrenia, occur early in the course of the disorder, and are enduring, distressing and disabling. In clinical practice, this symptom is widely assumed to be unresponsive to treatment with antipsychotic medication and early intervention is rarely offered. The Verbal Experiences Response in Borderline personality disorder to Aripiprazole TrIal Medication (VERBATIM) study aims to be the first controlled trial to investigate the effectiveness of conventional pharmacotherapy for this symptom in this patient group. Method VERBATIM is a 12-week, triple-blind, single-centre, parallel groups randomised controlled trial, with a 27-week follow-up period. Participants between the ages of 15 and 25 years receive either aripiprazole or placebo daily, commencing at 2 mg and increasing to 10 mg by day 15. Further dose escalations (up to 30 mg) may occur, as clinically indicated. This trial was prospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616001192471 on 30/08/2016. Results The primary outcome is severity of auditory verbal hallucinations assessed using the Psychotic Symptom Rating Scale. Secondary outcomes include the severity of general psychopathology, borderline personality pathology, social and occupational functioning and change in brain resting state connectivity. The primary endpoint is week 12 and secondary endpoint is week 39. Conclusion The results will inform treatment decisions for individuals with borderline personality disorder who present with auditory verbal hallucinations.

Aim It is now necessary to investigate whether recovery in psychosis is possible without the use of antipsychotic medication. This study will determine (1) whether a first-episode psychosis (FEP) group receiving intensive psychosocial interventions alone can achieve symptomatic remission and functional recovery; (2) whether prolonging the duration of untreated psychosis (DUP) in a sub-group according to randomisation will be associated with a poorer outcome and thereby establish whether the relationship between DUP and outcome is causative; and (3) whether neurobiological changes observed in FEP are associated with the psychotic disorder or antipsychotic medication. Baseline characteristics of participants will be presented. Methods This study is a triple-blind randomized placebo-controlled non-inferiority trial. The primary outcome is the level of functioning measured by the Social and Occupational Functioning Assessment Scale at 6 months. This study is being conducted at the Early Psychosis Prevention and Intervention Centre, Melbourne and includes young people aged 15 to 24 years with a DSM-IV psychotic disorder, a DUP less than 6 months and not high risk for suicide or harm to others. Strict discontinuation criteria are being applied. Participants are also undergoing three 3-Tesla-MRI scans. Results Ninety participants have been recruited and baseline characteristics are presented. Conclusions Staged treatment and acceptability guidelines in early psychosis will determine whether antipsychotic medications are indicated in all young people with a FEP and whether antipsychotic medication can be safely delayed. Furthermore, the relative contribution of psychotic illness and antipsychotic medication in terms of structural brain changes will also be elucidated. The findings will inform clinical practice guidelines.

Aim: Suicidal behaviours (suicide attempts and suicides) are common among individuals experiencing, or having recently experienced, a first-episode psychosis (FEP). Current interventions for suicidal behaviours are crisis driven and focused on hospital admission of patients at imminent risk of ending their lives. This paper aims to describe ideas for universal, selective and indicated strategies that may complement existing practices to suicide risk management in first-episode patients. Methods: Key findings from the Suicidal Behaviours in FEP Project were used to develop suggested interventions. The project examined the temporal course of suicide risk, common characteristics of suicidal behaviours and predictors of suicidal behaviours in 699 patients with FEP. Results: Key findings included: (i) 12% of FEP cohort engaged in suicidal behaviours during treatment (up to 3 years); (ii) first month of treatment conferred the highest suicide risk; (iii) 64% of suicidal behaviours were overdoses, usually on antipsychotics; (iv) 20% of suicidal behaviours occurred on psychiatric units and all involved hanging/strangulation; (v) most suicidal behaviours were impulsive, precipitated by psychosocial stressors and with serious intent; and (vi) proximal non-suicidal self-injurious behaviour and proximal negative life events were the strongest predictors. Conclusion: Comprehensive approach by mental health services to prevention of suicidal behaviours among first-episode patients could be facilitated by: delineating safe quantities of prescribed medications available to outpatients; regular audits of fixtures on inpatient units; enhancing risk recognition by family members; routinely monitoring suicide risk levels; developing crisis cards with all new FEP patients to facilitate help seeking during distress; and skills training programs targeting distress tolerance, interpersonal effectiveness and problem-solving.

AIM: The aim of this study was to identify the core competencies required of mental health professionals working in the early psychosis field, which could function as an evidence-based tool to support the early psychosis workforce and in turn assist early psychosis service implementation and strengthen early psychosis model fidelity. METHOD: The Delphi method was used to establish expert consensus on the core competencies. In the first stage, a systematic literature search was conducted to generate competency items. In the second stage, a panel consisting of expert early psychosis clinicians from around the world was formed. Panel members then rated each of the competency items on how essential they are to the clinical practice of all early psychosis clinicians. RESULTS: In total, 1023 pieces of literature including textbooks, journal articles and grey literature were reviewed. A final 542 competency items were identified for inclusion in the questionnaire. A total of 63 early psychosis experts participated in 3 rating rounds. Of the 542 competency items, 242 were endorsed as the required core competencies. There were 29 competency items that were endorsed by 62 or more experts, and these may be considered the foundational competencies for early psychosis practice. CONCLUSION: The study generated a set of core competencies that provide a common language for early psychosis clinicians across professional disciplines and country of practice, and potentially are a useful professional resource to support early psychosis workforce development and service reform.

Relative to the general population, people with intellectual disability (ID) are at greater risk of psychosis, with an estimated prevalence of 3%–5%. By definition, ID is associated with significant impairment in adaptive function. Similarly, functional disability is a common residual feature of psychosis. Yet, reports of evidence-based treatment for functional impairment in comorbid ID and psychosis are sparse, with most literature focusing on behavior management. Given that intellectual impairment in ID and psychosis are known to interfere with functional recovery, a treatment that addresses this impairment is paramount. Cognitive adaptation training (CAT) may be a suitable intervention for this purpose, as it is underpinned by the understanding that cognitive abilities play a strong role in community functioning. CAT is a manualized intervention involving the application of multiple external compensatory strategies and environmental supports (e.g., signs, alarms, checklists) that are individually tailo...

Introduction Data from the literature suggests that some first episode psychosis (FEP) patients may recover without antipsychotic medication. There is however no reliable way to identify them. In a previous paper we found, in a cohort of 584 FEP patients, that those consistently refusing medication had poorer pre-morbid functioning, less insight, higher rate of substance use and poorer outcome. However, some medication refusers, had a favourable outcome. The study aim was to identify predictors of good short term outcome despite non-exposure to medication. Methods The Early Psychosis Prevention and Intervention Centre (EPPIC) admitted 786 FEP patients between 1998 and 2000. Data were collected from patients' files using a standardized questionnaire. Data on medication adherence was available in 584 patients. Among the 17.9% of patients who consistently refused medication over the entire treatment phase we compared patients who had a favourable symptomatic and functional outcome with those who did not. Results Among patients who consistently refused medication, 41% achieved symptomatic remission and 33% reached functional recovery. Predictors of symptomatic remission were a better premorbid functioning level, higher education and employment status at baseline. Predictors of functional recovery were a shorter duration of the prodrome phase, less severe psychopathology at baseline and lower cannabis use. Conclusions Despite limitations mainly linked to the fact that non-exposure to antipsychotic medication was based on patient's treatment refusal, this study identified some characteristics which may contribute to the identification of a sub-group of FEP patients who may have good short term outcome without antipsychotic treatment.

Background:Although the experience of stress and associated coping responses are thought to play a role in the onset of schizophrenia and other psychotic disorders, there is little empirical evidence to support such a relationship. The relatively recent development of validated and reliable criteria for identifying young people at “ultra” high-risk (UHR) of psychosis has enabled the process of illness onset to be studied more closely than was previously possible.Method:This longitudinal study compared the experiences of stress and coping between a UHR cohort (N= 143) and a healthy comparison group (HC group,N= 32).Results:The UHR group experienced significantly fewer life events over a 12-month period than the HC group, but there was no difference in the experience of minor events or “hassles”. However, the UHR group reported feeling significantly more distressed by events, felt they coped more poorly and utilized different coping strategies.Conclusions:The appraisals made about stressors differentiated the groups and was associated with differences in coping and distress levels. This suggests that treatment strategies focusing on stress management and enhancing coping skills might be important components of preventive interventions.

Background While antipsychotic medication (AP) is a very effective treatment for positive psychotic symptoms in first-episode psychosis (FEP), it is also associated with risks. These include adverse neurological and metabolic effects and measurable changes in brain structure. APs may even be associated with poorer functional recovery. Due to advances in the detection of, and psychosocial treatments for FEP, it is now ethically feasible to study the relative risks and benefits of offering AP as a first line treatment, and conversely, of withholding it, on a background of comprehensive evidence-based psychosocial care. This non-inferiority design randomised double blind placebo controlled study examines whether a (low-risk) subgroup of people with FEP can recover without AP, and considers the effects on functioning, physical health, cognition, and brain structure of AP versus withholding AP. Methods Young people with FEP were screened for study eligibility and invited to participate if they met stringent inclusion criteria indicating low-risk of harm to self or others, and adequate social support. Hence a large proportion of patients were assumed a priori to be too high risk to withhold antipsychotic medication. Participants were randomly assigned to receive either low dose AP (MIPT group) or placebo (PIPT group) for six months, and all participants received intensive psychosocial treatment. Randomisation was stratified with three levels of DUP and gender creating six cells. Assessments of psychopathology, neurocognitive performance, and neuroimaging occurred regularly until two years after study entry. Results 90 young people were randomised and 81 commenced trial medication. They were 44% male and mean age 18.5 years (SD = 2.7). Thirty-four percent of participants completed the six month medication phase and there were more completers in the placebo group than the medication group. On the primary outcome measure of SOFAS there was significant evidence that the placebo group was not inferior to the medication group (SOFAS: MIPT mean = 61.5, SD = 13.4; PIPT mean = 61.7, SD = 16.8). The two groups were found to be very similar on all psychopathology assessments and measures of functioning at both baseline and following treatment, suggesting that the outcomes of the two treatment regimes were not different with respect to symptoms and functioning. Discussion The results of this study demonstrate that it is feasible and acceptable to conduct AP-free research in carefully selected FEP to examine the risk-benefit ratio of current treatments under carefully controlled conditions that prioritise patient outcomes and safety. Although only one-third of the participants completed the six month trial intervention period, more of those on placebo completed the trial phase and they had higher mean, minimum and maximum time in the experimental intervention phase than those on medication. In addition, there were no differences between the groups on measures of psychopathology and functioning, suggesting that the intensive psychosocial intervention provided to all participants is complementary and may be more important than antipsychotic medication in the early phases of psychotic illness for a subgroup of young people. However this subgroup is very small as a % of total FEP patients treated during the study period. Further analysis of physical health and neuroimaging data and completion of the 24 month follow-up assessments will allow detailed examination of the risk-benefit ratio regarding antipsychotic medication in FEP.

Psychological models of schizophrenia and other psychotic disorders suggest that poor coping responses to life stressors and to symptoms of illness is central to their development and maintenance and influences recovery. These models are widely accepted and inform psychological treatments for psychotic disorders. In this paper, 85 studies that explore how individuals with established psychotic disorders cope with symptoms associated with their illness, and with independent life events and stressors are comprehensively reviewed. Reviewed research included cross-sectional and longitudinal investigations of self-initiated coping. Despite limitations in the existing research, it is concluded that most individuals experiencing psychosis implement at least one strategy to cope with symptoms, and life events and most implement more than one strategy. It appears that having a repertoire of strategies to employ leads to greater effectiveness than simply relying on one strategy. This suggests that treatment strategies that aim to enhance the coping of individuals with psychosis should emphasize the development of a range of coping strategies. It also seems that there is no one coping strategy that is universally effective and situational, or other factors may influence both the choice of coping strategy implemented and its efficacy.

Objective: We 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. Method: Participants (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. Results: Early 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. Conclusions: Age of onset of psychiatric symptoms is the single most important factor associated with conversion to non-affective psychosis in ultra-high risk individuals. (PsycINFO Database Record (c) 2006 APA ) (journal abstract)

With the emerging global focus on early psychosis, indicated prevention in schizophrenia has increasingly become a focus of psychiatric research interests. It has been argued that CBT may have some advantages compared with antipsychotics regarding this issue. According to MEDLINE, EMBASE and Psycinfo two completed randomised controlled trials (RCTs; PACE, Melbourne, Australia; EDIE, Manchester, United Kingdom) and one ongoing RCT with only preliminary results published so far (FETZ, Cologne/Bonn, Germany) on indicated prevention in schizophrenia including manualised and standardised psychological treatment can be identified. The aims of the present paper are to present and discuss the three approaches with regard to (I) inclusion, exclusion and exit criteria, (II) characteristics of interventions and (III) evaluations. All interventions use intake, exclusion and exit criteria, which have been evaluated in prospective follow-along studies. The approaches are based on the general structure and principles of cognitive behavioural therapy which have been developed, applied and evaluated in a wide range of mental health problems. Despite several methodological limitations, the first evaluations indicate some effects with regard to three possible aims of early intervention: (1) improvement of present possible pre-psychotic symptoms, (2) prevention of social decline/stagnation and (3) prevention or delay of progression to psychosis. Even though the first results are promising, we conclude that several ethical issues have to be taken into consideration and further predictive and therapeutic research is needed to judge whether psychological intervention is a realistic option for the treatment of people at risk of psychosis.

Objective: An association between birth and pregnancy complications and the later development of schizophrenia has been described for decades and obstetric complications (OCs) have been proposed as a vulnerability marker for psychosis in line with the neurodevelopmental hypothesis of psychotic disorders. Previous studies of OCs have focused on established schizophrenia. In this study, the association between OCs and the development of psychotic disorder was studied in a group of 74 young people identified as being at very high risk for the first onset of psychosis. Method: The ‘ultra’ high risk (UHR) cohort was identified by the presence of subthreshold psychotic symptoms, or a combination of first-degree relative with a psychotic disorder and recent functional decline. Thirty-eight per cent of the cohort developed an acute psychotic episode over the 12-month period after recruitment. As a component of a larger research study, the level of OCs experienced by the UHR cohort was assessed at intake. Results: Obstetric complicationswere not associated with the later development of psychosis in the UHR group included in this study. Conclusions: This study does not suppor t a role for OCs as a risk factorfor the later development of psychosis; however, we cannot conclude that they should be completely ignored as a candidate risk factor for onset of psychosis. A number of weaknesses of the study suggest that it may be premature to dismiss OCs as a risk factor for the development of psychosis and further research is urged in this area.

While cognitive deficits are frequently reported in psychotic disorders, it is unclear whether these impairments predate the onset of illness and to what extent they are predictive of later transition to psychosis.The authors studied 37 healthy volunteers and 98 symptomatic, help-seeking patients meeting the inclusion criteria of a treatment program for people at ultra-high risk for psychosis. Of the ultra-high-risk patients, 34 (34.7%) developed psychosis over the course of the investigation. Premorbid and current IQ, attention, memory, and executive functioning were measured with instruments including subtests from the Wechsler Memory Scale-Revised (WMS-R). Analyses compared the ultra-high-risk patients who became psychotic, those who did not become psychotic, and the comparison subjects.Overall, the ultra-high-risk subjects had significantly lower performance IQs than the comparison subjects. Further, impairments were also found in the visual reproduction subtest and the verbal memory index (predominantly owing to lower logical memory scores) of the WMS-R that were specific to the ultra-high-risk-patients who developed psychosis. No other memory, attentional, or executive tasks discriminated between any of the groups.These findings suggest that visuospatial processing impairment and some memory deficits were apparent before the full expression of psychotic illness. Cognitive performance on more complex tasks requiring rapid registration and efficient recall may be compromised before development of first-episode psychosis. Further experimental tasks that challenge these cognitive domains are required to clarify the predictive value of these results.

OBJECTIVE: Previous investigation has revealed stable olfactory identification deficits in neuroleptic-naive patients experiencing a first episode of psychosis, but it is unknown if these deficits predate illness onset. METHOD: The olfactory identification ability of 81 patients at ultra-high risk for psychosis was examined in relation to that of 31 healthy comparison subjects. Twenty-two of the ultra-high-risk patients (27.2%) later became psychotic, and 12 of these were diagnosed with a schizophrenia spectrum disorder. RESULTS: There was a significant impairment in olfactory identification ability in the ultra-high-risk group that later developed a schizophrenia spectrum disorder but not in any other group. CONCLUSIONS: These findings suggest that impairment of olfactory identification is a premorbid marker of transition to schizophrenia, but it is not predictive of psychotic illness more generally.

Objectives. Cognitively oriented psychotherapy for early psychosis (COPE) is aimed at facilitating the adjustment of the person, and at preventing or alleviating secondary morbidity in the wake of the first psychotic episode. Design. A total of 80 people participated in the initial trial and completed assessments on a range of outcome measures. Post-treatment assessment results from a non-randomized controlled trial of COPE have been previously reported. The present paper describes the results obtained from 51 patients who attended a follow-up assessment 1 year subsequent to the end-of-treatment assessment. Method. The 51 patients formed three groups: (1) those who were offered and accepted COPE; (2) those who were offered COPE but refused it, and continued to receive other services from the Early Psychosis Prevention and Intervention Centre (EPPIC) (refusal subjects); and (3) those who were offered neither COPE nor any other continuing treatment from EPPIC (control subjects). Results. At 1-year follow-up, there was only one significant difference and this was between the COPE and refusal groups on the Integration/Sealing Over (I/SO) measure (p = .008). End-of-treatment differences were mostly sustained over the 1-year follow-up period. When the complete sample of 80 was considered, there were no differences between the three groups in terms of hospital admissions, community episodes, or time taken to first in-patient re-admission. Conclusions. The study was weakened by the poor follow-up rates in the two control groups. This reduced power to detect differences between groups on the seven major measures. However, the relapse data gathered on the complete set of 80 patients were discouraging and suggest that the present formulation of COPE does not confer any advantage to those patients receiving the therapy over those not receiving the therapy.

Background While there is evidence that some cases of schizophrenia may be associated with microbial infections, the role of microbial agents has not been investigated in people with emerging psychosis. Methods Participants were 105 help seeking ultra-high risk individuals. Psychiatric measures included the Brief Psychiatric Rating Scale and the Scale for the Assessment of Negative Symptoms. Serum IgG antibodies against human herpesviruses and Toxoplasma gondii were determined using immunoassay methods. Multiple linear regression with adjustment for age and sex was applied to test associations between serum antibodies and psychiatric measures. Results Higher levels of serum IgG antibodies against Toxoplasma gondii in Toxoplasma-positive individuals were significantly associated with more severe positive psychotic symptoms. No significant association was observed between antibody levels and psychiatric measures in individuals positive for human herpesviruses. Conclusions In some individuals infection with Toxoplasma gondii may be an environmental factor contributing to the manifestation of positive psychotic symptoms.

Background The identification of people at high risk of becoming psychotic within the near future creates opportunities for early intervention prior to the onset of psychosis to prevent or minimise later ill-health. The present study combines current knowledge about risk factors for schizophrenia with our knowledge of psychotic prodromes in an attempt to identify a group particularly vulnerable to impending psychosis. We wanted to identify people with high likelihood of transition to psychosis within a follow-up period of 12 months, and to determine the rate of transition to psychosis in this group.Method Various state and trait risk factors for psychosis were used alone and in combination to operationally define a putatively high-risk group. Operationalised criteria for onset of psychosis were established. The individuals were assessed monthly on measures of psychopathology for six months.Results Eight out of 20 people made the transition to frank psychosis within a six-month follow-up period. Follow-up of this group is still in progress, and the 12 month transition rate might prove to be higher still.Conclusions We have demonstrated that it is possible to identify individuals with a high likelihood of onset of psychosis within a brief follow-up period. This lays the foundation for early treatment in an attempt to prevent, delay or minimise the severity of first onset of schizophrenia.

BackgroundWe evaluate the impact of a group-based, transitional, psychosocial programme, within a comprehensive service (the Early Psychosis Prevention and Intervention Centre, EPPIC), on recovery from first-episode psychosis.MethodIndividuals using the service (and meeting study criteria) were assessed on a range of symptom and functioning instruments at entry, after 6 weeks and 6 months. Participants received comprehensive case management and services according to their identified needs. Thirty-four people who had attended the group programme were compared at 6 month follow-up with 61 EPPIC patients who had not attended.ResultsThe people attending the group programme had a lower level of premorbid adjustment than the comparison group, and a trend towards exhibiting a higher level of negative symptoms, prior to commencing the group programme. However, at 6 month follow-up, no significant differences were found between the groups.ConclusionsInvolvement in the group programme may have had a positive impact on a subgroup of EPPIC subjects with poor level of premorbid adjustment, by providing a ‘holding pattern’ in the critical period following the emergence of first-onset psychosis, and thus prevented deterioration and the development of disability.

Treating individuals in the prodromal phase preceding a first psychotic episode has long been a goal of clinicians, the aim being to prevent or minimize the harm inflicted by a psychosis. Before embarking on such a preventive approach, it is first necessary to characterize the features of impending psychosis. We have defined a set of criteria, based on various state and trait risk factors, to identify subjects likely to undergo transition to psychosis within a short time. We prospectively followed up 23 subjects fulfilling these criteria. Subjects were assessed monthly on measures of psychopathology for 12 months. Eleven of the 23 subjects (48%) made the transition to frank psychosis in the study period; the majority developed schizophrenia-like psychoses. Aberrant results on measures of psychopathology were found before the onset of psychosis. Our results indicate that it is possible to identify individuals who have a high likelihood of onset of psychosis within a brief follow-up period and that there are detectable mental state changes in this group prior to onset of psychosis. This finding lays the foundation for early treatment in an attempt to prevent, delay or minimize the severity of first psychotic episodes.

Importance The ultra high-risk (UHR) criteria were introduced to prospectively identify patients at high risk of psychotic disorder. Although the short-term outcome of UHR patients has been well researched, the long-term outcome is not known. Objective To assess the rate and baseline predictors of transition to psychotic disorder in UHR patients up to 15 years after study entry. Design Follow-up study of a cohort of UHR patients recruited to participate in research studies between 1993 and 2006. Setting The Personal Assessment and Crisis Evaluation (PACE) clinic, a specialized service for UHR patients in Melbourne, Australia. Participants Four hundred sixteen UHR patients previously seen at the PACE clinic. Main Outcomes and Measures Transition to psychotic disorder, as measured using the Comprehensive Assessment of At-Risk Mental States, Brief Psychiatric Rating Scale/Comprehensive Assessment of Symptoms and History, or state public mental health records. Results During the time to follow-up (2.4-14.9 years after presentation), 114 of the 416 participants were known to have developed a psychotic disorder. The highest risk for transition was within the first 2 years of entry into the service, but individuals continued to be at risk up to 10 years after initial referral. The overall rate of transition was estimated to be 34.9% over a 10-year period (95% CI, 28.7%-40.6%). Factors associated with transition included year of entry into the clinic, duration of symptoms before clinic entry, baseline functioning, negative symptoms, and disorders of thought content. Conclusions and Relevance The UHR patients are at long-term risk for psychotic disorder, with the highest risk in the first 2 years. Services should aim to follow up patients for at least this period, with the possibility to return for care after this time. Individuals with a long duration of symptoms and poor functioning at the time of referral may need closer monitoring. Interventions to improve functioning and detect help-seeking UHR patients earlier also may be indicated.

Objective The ultra-high risk clinical phenotype is associated with substantial distress and functional impairment and confers a greatly enhanced risk for transition to full-threshold psychosis. A range of interventions aimed at relieving current symptoms and functional impairment and reducing the risk of transition to psychosis has shown promising results, but the optimal type and sequence of intervention remain to be established. The aim of this study was to determine which intervention was most effective at preventing transition to psychosis: cognitive therapy plus low-dose risperidone, cognitive therapy plus placebo, or supportive therapy plus placebo. Method A double-blind, randomized, placebo-controlled 12-month trial of low-dose risperidone, cognitive therapy, or supportive therapy was conducted in a cohort of 115 clients of the Personal Assessment and Crisis Evaluation Clinic, a specialized service for young people at ultra-high risk of psychosis located in Melbourne, Australia. Recruitment commenced in August 2000 and ended in May 2006. The primary outcome measure was transition to full-threshold psychosis, defined a priori as frank psychotic symptoms occurring at least daily for 1 week or more and assessed using the Comprehensive Assessment of At-Risk Mental States. Secondary outcome measures were psychiatric symptoms, psychosocial functioning, and quality of life. Results The estimated 12-month transition rates were as follows: cognitive therapy + risperidone, 10.7%; cognitive therapy + placebo, 9.6%; and supportive therapy + placebo, 21.8%. While there were no statistically significant differences between the 3 groups in transition rates (log-rank test P = .60), all 3 groups improved substantially during the trial, particularly in terms of negative symptoms and overall functioning. Conclusions The lower than expected, essentially equivalent transition rates in all 3 groups fail to provide support for the first-line use of antipsychotic medications in patients at ultra-high risk of psychosis, and an initial approach with supportive therapy is likely to be effective and carries fewer risks.

This article describes the Early Psychosis Prevention and Intervention Centre (EPPIC) — an innovative and comprehensive service that attempts to address the needs of older adolescents and young adults experiencing their first episode of psychosis. Some of the key theoretical concepts and philosophical tenets which underpin the service delivery model are adumbrated. Furthermore, the historical antecedents of the current service, and the “successive approximations” approach taken in developing the same, are delineated. Given the evolutionary nature of the program, the perceived future needs and developments are stipulated. © 1994, The Author(s). All rights reserved.

Suicide-related behaviors (suicide attempts and suicides) are common in the early phase of psychotic disorders. Studies have examined risk factors among baseline and historical (i.e., past) variables, yet little is known about recent characteristics that increase suicide risk during treatment for first-episode psychosis (FEP). This study had two aims: first, to determine the relative importance of baseline, past, and recent variables to the prediction of suicide-related behaviors in patients with FEP; second, to identify recent characteristics that exert most influence on suicide risk levels and which could become foci of preventive interventions.This was a case-control study of 180 patients from a cohort entering a specialist FEP service between 1/12/2002 and 30/11/2005. Data for 72 cases and 108 matched controls were obtained via medical record audit. Multivariate logistic regression models assessed the contribution of baseline, past, and recent domains. Suicide attempt or suicide during treatment was the outcome variable.The strongest risk factors for suicide-related behaviors were: baseline depressive symptoms, baseline suicidal ideation/intent, past negative events, past non-suicidal self-injurious behavior, recent negative events, recent depressive symptoms, and recent non-suicidal self-injurious behavior. However, when these were entered into a hierarchical logistic regression model, only recent non-suicidal self-injurious behavior (AOR=72.96, p0.001), and recent negative events (AOR=1.90, p=0.003) remained significant predictors. The final model accurately classified 75.5% of cases and 89.2% of controls, and explained 72.0% of variance in the suicide attempt status.Since recent negative events and recent non-suicidal self-injurious behavior were the strongest predictors of suicide-related behaviors during treatment for FEP, psychiatric services could consider incorporating psychosocial interventions addressing affect regulation, interpersonal effectiveness, stress management and problem solving, alongside case management and pharmacotherapy, to help to reduce the rates of suicide attempts and suicides in first-episode patients.

Aim: Although the different approaches to psychosis research have made significant advances in their own fields, integration between the approaches is often lacking. This paper attempts to integrate a strand of cognitive research in psychotic disorders (specifically, social cognition research) with phenomenological accounts of schizophrenia and other psychotic disorders. Method: The paper is a critical investigation of phenomenological models of disturbed selfhood in schizophrenia in relation to cognitive theories of social cognition in psychotic disorders. Results: We argue that disturbance of the basic sense of self, as articulated in the phenomenological literature, may underlie the social cognition difficulties present in psychotic disorders. This argument is based on phenomenological thinking about self-presence (‘ipseity’) being the primary or most basic ground for the intentionality of consciousness – that is, the directedness of consciousness towards others and the world. A disruption in this basic ground of conscious life has a reverberating effect through other areas of cognitive and social functioning. We propose three routes whereby self-disturbance may compromise social cognition, including dissimilarity, disruption of lived body and disturbed mental coherence. Conclusions: If this model is supported, then social cognition difficulties may be thought of as a secondary index or marker of the more primary disturbance of self in psychotic disorders. Further empirical work examining the relationship between cognitive and phenomenological variables may be of value in identifying risk markers for psychosis onset, thus contributing to early intervention efforts, as well as in clarifying the essential psychopathological features of schizophrenia and other psychotic disorders.

Background Young people with first-episode psychosis (FEP) are at risk of a range of negative outcomes. Specialist FEP services have been developed to provide comprehensive, multi-disciplinary treatment. However, these services are often available for a restricted period and the services that young people may be transferred to are less comprehensive. This represents a risk of drop out from treatment services in a group already considered to be at risk of disengagement. Peer support groups have been shown to improve social relationships among people with psychosis however individual peer support programs have not been tested on young people with first-episode psychosis; nor have they been tested at the point of discharge from services. Methods/design The study is an 18-month randomised controlled trial being conducted at Orygen Youth Health Research Centre in Melbourne, Australia. The aim of the study is to test the feasibility and effects of a 6-month peer support intervention delivered to young people with FEP over the period of discharge. Participants are young people aged 15-24 who are being discharged from a specialist first-episode psychosis treatment centre. There is a 6-month recruitment period. The intervention comprises two hours of contact per fortnight during which peer support workers can assist participants to engage with their new services, or other social and community activities. Participants will be assessed at baseline and post intervention (6 months). Discussion This paper describes the development of a randomised-controlled trial which aims to pilot a peer support program among young people who are being discharged from a specialist FEP treatment centre. If effective, the intervention could lead to benefits not only for participants over the discharge period, but for peer support workers as well. Trial registration The study was registered with the Australian New Zealand Clinical Trials Registry; number: ACTRN12610000241033.

Objective: We aimed to replicate a recent finding of high prevalence of trauma history in patients at ‘ultra-high risk’ (UHR) of psychotic disorder and to investigate whether trauma predicts conversion to psychosis in this population. Method: A consecutive sample of UHR patients was assessed. History of trauma was accessed with the General Trauma Questionnaire. Cox regression models were used to explore relationship between conversion to psychosis and trauma. Results: Of 92 UHR patients nearly 70% had experienced a traumatic event and 21.7% developed psychosis during follow-up (mean 615 days). Patients who had experienced a sexual trauma (36%) were significantly more likely to convert to first-episode psychosis (OR 2.96) after controlling for meeting multiple UHR intake groups. Conclusion: UHR patients have a high prevalence of history of trauma. Previous sexual trauma may be a predictor of onset of psychotic disorder in this population.

In recent years, early intervention services have attempted to identify people with a first episode of psychosis as early as possible, reducing the duration of untreated psychosis and changing the timing of delivery of interventions. The logic of early intervention is based partly on accessing people in a more treatment responsive stage of illness in which psychosocial damage is less extensive, and partly on remediating a putatively active process of neuroprogression that leads to pathophysiological, symptomatic and structural changes, hence improving symptomatic and functional outcomes. However, as in other areas of health care, earlier identification of new patients may mean that different treatment approaches are indicated. The corollary of early detection is that the sequence and complexion of treatment strategies for first episode psychosis has been revaluated. Examples include the minimal effective dosage of antipsychotic medication and the content of psychosocial interventions. With the substantial reductions of DUP now seen in many early psychosis services, based on clinical staging and stepped care principles, it is even possible that the immediate introduction of antipsychotic medication may not be necessary for all first episode psychosis cases, but that potentially safer interventions, which may be more acceptable to many patients, such as comprehensive psychosocial intervention, may constitute effective treatment at least for a subgroup of patients. In this paper, we review this theoretical background and describe a randomised controlled trial currently underway at the Early Psychosis Prevention and Intervention Centre (EPPIC) in Melbourne designed to test outcomes for first episode psychosis patients in response to two different treatments: intensive psychosocial intervention plus antipsychotic medication versus intensive psychosocial intervention plus placebo. This is a theoretically and pragmatically novel study in that it will provide evidence as to whether intensive psychosocial intervention alone is sufficient for a subgroup of first episode psychosis patients in a specialised early intervention service, and provide a test of the heuristic clinical staging model. By experimentally manipulating duration of untreated psychosis, the study will also provide a methodologically strong test of the effect of delaying the introduction of antipsychotic medication, as well as helping to disentangle the effects of antipsychotic medications and the putative neurobiological processes associated with brain changes and symptom profiles in the early phase of psychotic disorders. The study has been carefully crafted to satisfy critical ethical demands in this challenging research domain.