Correlates of substance use in a large naturalistic cohort of young people with early and emerging psychosis.

BACKGROUND: Substance use remains a barrier to recovery for young people accessing early intervention services for psychosis. While correlates of use have been explored in populations experiencing a first episode of psychosis (FEP), sample sizes have been small and less research assesses cohorts at ultrahigh risk of psychosis (UHR). METHODS: This study uses data from a naturalistic cohort including UHR and FEP participants (N = 1252) to elucidate clinical correlates of use in the past 3 months of any illicit substance, amphetamine-type stimulants (ATS), cannabis, and tobacco. Moreover, network analysis based on use of these substances and additionally alcohol, cocaine, hallucinogens, sedatives, inhalants, and opioids was completed. RESULTS: Young people with FEP used substances at significantly higher rates than those at UHR. High concurrence of use was seen between substances. In the FEP group, participants who had used any illicit substance, ATS, and/or tobacco had increased positive symptoms and decreased negative symptoms. Young people with FEP who used cannabis had increased positive symptoms. In the UHR group, participants who had used any illicit substance, ATS, and/or cannabis in the past 3 months showed decreased negative symptoms compared to those who had not. CONCLUSION: A distinct clinical picture of more florid positive symptoms and alleviated negative symptoms seen in those who use substances in the FEP group appears muted in the UHR cohort. Treating young people at UHR in early intervention services represents the earliest opportunity to address substance use early to improve outcomes.

Toxoplasma gondii, Herpesviridae and long-term risk of transition to first-episode psychosis in an ultra high-risk sample.

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.

Predictors of suicide-related behaviors during treatment following a first episode of psychosis: the contribution of baseline, past, and recent factors.

BACKGROUND: 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. METHODS: 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. RESULTS: 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, p<0.001), 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. CONCLUSIONS: 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.

Experience of trauma and conversion to psychosis in an ultra-high-risk (prodromal) group.

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.

Who needs antipsychotic medication in the earliest stages of psychosis? A reconsideration of benefits, risks, neurobiology and ethics in the era of early intervention.

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.

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

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.

Shedding of Escherichia coli O157:H7 in dairy cattle housed in a confined environment following waterborne inoculation.

A study of Escherichia coli O157:H7 transmission and shedding was conducted with bull calves housed in individual pens within a confined environment. For comparative purposes, the numbers and duration of E. coli O157:H7 shedding in naturally infected calves were monitored after a single purchased calf (calf 156) tested positive prior to inoculation. During the next 8 days, the calves in adjacent pens and a pen directly across a walkway from calf 156 began to shed this serotype O157:H7 strain. Five of the eight calves in this room shed this O157:H7 strain at some time during the following 8 weeks. The numbers of E. coli O157:H7 isolates shed in these calves varied from 60 to 10(5) CFU/g of feces, and the duration of shedding ranged from 17 to >31 days. The genomic DNAs from isolates recovered from these calves were indistinguishable when compared by using XbaI digestion and pulsed-field gel electrophoresis. Inoculation of calves with 1 liter of water containing ca. 10(3) to 10(4) CFU of E. coli O157:H7/ml resulted in shedding in 10 of 12 calves (trial 1, 4 of 4 calves; trial 2, 6 of 8 calves). The inoculated calves shed the inoculation strain (FRIK 1275) as early as 24 h after administration. The duration of shedding varied from 18 to >43 days at levels from 10(2) to 10(6) CFU/g of feces. The numbers of doses necessary to initiate shedding varied among calves, and two calves in trial 2 never shed FRIK 1275 after four doses (ca. 10(6) CFU per dose). Results from this study confirm previous reports of animal-to-animal and waterborne dissemination of E. coli O157:H7 and highlight the need for an effective water treatment to reduce the spread of this pathogen in cattle.

Cognitively oriented psychotherapy for early psychosis (COPE): a 1-year follow-up.

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.

Prediction of psychosis. A step towards indicated prevention of schizophrenia.

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.

Cognitively-oriented psychotherapy for early psychosis (COPE). Preliminary results.

BACKGROUND: The present study describes the results of the pilot testing of a therapy we have developed for people with first-episode psychosis. 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. METHOD: Eighty people formed three groups: those who were offered and accepted COPE (COPE subjects); those who refused COPE (refusal subjects); and those who were offered neither COPE nor any other continuing treatment from our service (control subjects). The individuals were assessed prior to, and at the end of, COPE treatment (a 12-month period) on the Integration/Sealing Over, Explanatory Model, Scale for the Assessment of Negative Symptoms, Brief Psychiatric Rating Scale, Quality of Life, SCL-90-R, and Beck Depression Inventory measures. RESULTS: People who received COPE obtained significantly superior scores (P < 0.05) to the control group on four of the seven measures but only significantly out-performed the refusal group on one of the seven measures (P < 0.05). The COPE group performed significantly worse on the BDI than the refusal group (P < 0.05). Effect sizes are also provided for each measure. CONCLUSIONS: There seems to be a place for psychological therapy in this group of people but our results need to be replicated in a more definitive randomised controlled trial and such a study is now in progress.

Group programmes for recovery from early psychosis.

BACKGROUND: We 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. METHOD: Individuals 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. RESULTS: The 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. CONCLUSIONS: Involvement 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.