G.P. Amminger

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

Bechdolf A, Thompson A, Nelson B, Cotton S, Simmons MB, Amminger GP, Leicester S, Francey SM, McNab C, Krstev H, Sidis A, McGorry PD, Yung AR. Experience of trauma and conversion to psychosis in an ultra‐high‐risk (prodromal) group.

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

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

Road to full recovery: Longitudinal relationship between symptomatic remission and psychosocial recovery in first-episode psychosis over 7.5 years

BACKGROUND In recent years there has been increasing interest in functional recovery in the early phase of schizophrenia. Concurrently, new remission criteria have been proposed and several studies have examined their clinical relevance for prediction of functional outcome in first-episode psychosis (FEP). However, the longitudinal interrelationship between full functional recovery (FFR) and symptom remission has not yet been investigated. This study sought to: (1) examine the relationships between FFR and symptom remission in FEP over 7.5 years; (2) test two different models of the interaction between both variables. METHOD Altogether, 209 FEP patients treated at a specialized early psychosis service were assessed at baseline, 8 months, 14 months and 7.5 years to determine their remission of positive and negative symptoms and functional recovery. Multivariate logistic regression and path analysis were employed to test the hypothesized relationships between symptom remission and FFR. RESULTS Remission of both positive and negative symptoms at 8-month follow-up predicted functional recovery at 14-month follow-up, but had limited value for the prediction of FFR at 7.5 years. Functional recovery at 14-month follow-up significantly predicted both FFR and remission of negative symptoms at 7.5 years, irrespective of whether remission criteria were simultaneously met. The association remained significant after controlling for baseline prognostic indicators. CONCLUSIONS These findings provided support for the hypothesis that early functional and vocational recovery plays a pivotal role in preventing the development of chronic negative symptoms and disability. This underlines the need for interventions that specifically address early psychosocial recovery.

Online and Social Networking Interventions for the Treatment of Depression in Young People: A Systematic Review

Background Major depression accounts for the greatest burden of all diseases globally. The peak onset of depression occurs between adolescence and young adulthood, and for many individuals, depression displays a relapse-remitting and increasingly severe course. Given this, the development of cost-effective, acceptable, and population-focused interventions for depression is critical. A number of online interventions (both prevention and acute phase) have been tested in young people with promising results. As these interventions differ in content, clinician input, and modality, it is important to identify key features (or unhelpful functions) associated with treatment outcomes. Objective A systematic review of the research literature was undertaken. The review was designed to focus on two aspects of online intervention: (1) standard approaches evaluating online intervention content in randomized controlled designs (Section 1), and (2) second-generation online interventions and services using social networking (eg, social networking sites and online support groups) in any type of research design (Section 2). Methods Two specific literature searches were undertaken. There was no date range specified. The Section 1 search, which focused on randomized controlled trials, included only young people (12-25 years) and yielded 101 study abstracts, of which 15 met the review inclusion criteria. The Section 2 search, which included all study design types and was not restricted in terms of age, yielded 358 abstracts, of which 22 studies met the inclusion criteria. Information about the studies and their findings were extracted and tabulated for review. Results The 15 studies identified in Section 1 described 10 trials testing eight different online interventions, all of which were based on a cognitive behavioral framework. All but one of the eight identified studies reported positive results; however, only five of the 15 studies used blinded interviewer administered outcomes with most trials using self-report data. Studies varied significantly in presentation of intervention content, treatment dose, and dropout. Only two studies included moderator or clinician input. Results for Section 2 were less consistent. None of the Section 2 studies reported controlled or randomized designs. With the exception of four studies, all included participants were younger than 25 years of age. Eight of the 16 social networking studies reported positive results for depression-related outcomes. The remaining studies were either mixed or negative. Findings for online support groups tended to be more positive; however, noteworthy risks were identified. Conclusions Online interventions with a broad cognitive behavioral focus appear to be promising in reducing depression symptomology in young people. Further research is required into the effectiveness of online interventions delivering cognitive behavioral subcomponents, such as problem-solving therapy. Evidence for the use of social networking is less compelling, although limited by a lack of well-designed studies and social networking interventions. A range of future social networking therapeutic opportunities are highlighted.

Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high-risk individuals.

Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high-risk individuals

Prediction of a single psychotic episode: A 7.5-year, prospective study in first-episode psychosis

BACKGROUND Around 20% of patients who suffer from psychosis will experience a single psychotic episode (SPE), but relatively little is known about the characteristics and predictors for this group of patients. This study sought to: 1) characterise the subgroup of first-episode psychosis (FEP) patients who experienced a SPE over a 7.5-year follow-up; and 2) to identify significant predictors for this subgroup independent of potential confounders. METHODS A representative sample of 413 FEP patients treated at a specialist early psychosis service were assessed at baseline and followed-up for 7.5 years. Binary logistic regression models were employed to investigate univariate and adjusted associations between baseline predictors and experiencing a SPE. Results were adjusted for the influence of known prognostic factors for psychosis. RESULTS Follow-up data was available for 274 participants. Forty-six (16.5%) achieved clinical remission and experienced no recurrence over the follow-up period. Duration of untreated psychosis (DUP) shorter than 60 days (OR=3.89, p=0.007), more rapid response to antipsychotic treatment (OR=0.33, p=0.019) and no parental loss (OR=5.25, p=0.045) significantly predicted a SPE. The association remained significant after controlling for potential confounders. CONCLUSIONS Early treatment (within two months of onset of psychotic symptoms) and social support significantly reduce vulnerability to subsequent psychotic episodes. Future studies need to investigate the interplay between biological factors (i.e. sensitized dopaminergic system), environmental variables (i.e. exposure to trauma, stigma and discrimination), and psychological attributes (i.e. cognitive schemata) in order to elucidate the processes underlying the vulnerability to recurrent psychotic episodes.

Omega-3 fatty acid supplementation changes intracellular phospholipase A2 activity and membrane fatty acid profiles in individuals at ultra-high risk for psychosis

The identification of an ultra-high risk (UHR) profile for psychosis and a greater understanding of its prodrome have led to increasing interest in early intervention to delay or prevent the onset of psychotic illness. In a randomized placebo-controlled trial, we have identified long-chain ω-3 (ω-3) polyunsaturated fatty acid (PUFA) supplementation as potentially useful, as it reduced the rate of transition to psychosis by 22.6% 1 year after baseline in a cohort of 81 young people at UHR of transition to psychosis. However, the mechanisms whereby the ω-3 PUFAs might be neuroprotective are incompletely understood. Here, we report on the effects of ω-3 PUFA supplementation on intracellular phospholipase A2 (inPLA2) activity, the main enzymes regulating phospholipid metabolism, as well as on peripheral membrane lipid profiles in the individuals who participated in this randomized placebo-controlled trial. Patients were studied cross-sectionally (n=80) and longitudinally (n=65) before and after a 12-week intervention with 1.2 g per day ω-3 PUFAs or placebo, followed by a 40-week observation period to establish the rates of transition to psychosis. We investigated inPLA2 and erythrocyte membrane FAs in the treatment groups (ω-3 PUFAs vs placebo) and the outcome groups (psychotic vs non-psychotic). The levels of membrane ω-3 and ω-6 PUFAs and inPLA2 were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA2 activity were in opposite directions in individuals who did (a positive correlation) and who did not (a negative correlation) transition to psychosis. Supplementation with ω-3 PUFA resulted in a significant decrease in inPLA2 activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA2 activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis

Prospective studies have suggested genetic variation in the neuregulin 1 (NRG1) and D-amino-acid oxidase activator (DAOA) genes may assist in differentiating high-risk individuals who will or will not transition to psychosis. In a prospective cohort (follow-up=2.4–14.9 years) of 225 individuals at ultra-high risk (UHR) for psychosis, we assessed haplotype-tagging single-nucleotide polymorphisms (htSNPs) spanning NRG1 and DAOA for their association with transition to psychosis, using Cox regression analysis. Two NRG1 htSNPs (rs12155594 and rs4281084) predicted transition to psychosis. Carriers of the rs12155594 T/T or T/C genotype had a 2.34 (95% confidence interval (CI)=1.37–4.00) times greater risk of transition compared with C/C carriers. For every rs4281084 A-allele the risk of transition increased by 1.55 (95% CI=1.05–2.27). For every additional rs4281084-A and/or rs12155594-T allele carried the risk increased ∼1.5-fold, with 71.4% of those carrying a combination of ⩾3 of these alleles transitioning to psychosis. None of the assessed DAOA htSNPs were associated with transition. Our findings suggest NRG1 genetic variation may improve our ability to identify UHR individuals at risk for transition to psychosis.

Is basic self-disturbance in ultra-high risk for psychosis (‘prodromal’) patients associated with borderline personality pathology?

Research in the phenomenological tradition suggests that the schizophrenia spectrum is characterized by disturbance of the ‘basic’ self, whereas borderline personality disorder involves disturbance of the ‘narrative’ self. The current study investigated this proposal in an ultra‐high risk for psychosis sample.

Transitions Study of predictors of illness progression in young people with mental ill health: study methodology

An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13–24‐year‐olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post‐pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder.