A national evaluation of a multi-modal, blended, digital intervention integrated within Australian youth mental health services.

BACKGROUND: Youth mental health (YMH) services have been established internationally to provide timely, age-appropriate, mental health treatment and improve long-term outcomes. However, YMH services face challenges including long waiting times, limited continuity of care, and time-bound support. To bridge this gap, MOST was developed as a scalable, blended, multi-modal digital platform integrating real-time and asynchronous clinician-delivered counselling; interactive psychotherapeutic content; vocational support; peer support, and a youth-focused online community. The implementation of MOST within Australian YMH services has been publicly funded. OBJECTIVE: The primary aim of this study was to evaluate the real-world engagement, outcomes, and experience of MOST during the first 32 months of implementation. METHOD: Young people from participating YMH services were referred into MOST. Engagement metrics were derived from platform usage. Symptom and satisfaction measures were collected at baseline, 6, and 12 (primary endpoint) weeks. Effect sizes were calculated for the primary outcomes of depression and anxiety and secondary outcomes of psychological distress and wellbeing. RESULTS: Five thousand seven hundred and two young people from 262 clinics signed up and used MOST at least once. Young people had an average of 19 login sessions totalling 129 min over the first 12 weeks of use, with 71.7% using MOST for at least 14 days, 40.1% for 12 weeks, and 18.8% for 24 weeks. There was a statistically significant, moderate improvement in depression and anxiety at 12 weeks as measured by the PHQ4 across all users irrespective of treatment stage (d = 0.41, 95% CI 0.35-0.46). Satisfaction levels were high, with 93% recommending MOST to a friend. One thousand one hundred and eighteen young people provided written feedback, of which 68% was positive and 31% suggested improvement. CONCLUSIONS: MOST is a highly promising blended digital intervention with potential to address the limitations and enhance the impact of YMH services.

Social inclusion, intersectionality, and profiles of vulnerable groups of young people seeking mental health support.

BACKGROUND: headspace centres provide enhanced primary mental healthcare for young people. A priority is to provide services for all young people irrespective of a range of social disadvantages or social exclusion. The aims of this study were to: (i) delineate extent of social inclusion across domains of housing, studying/employment, functioning, alcohol, and other drug use; and (ii) map profiles of young people deemed vulnerable to experiencing additional barriers to accessing services based on their social inclusion domains (e.g., those living in unstable housing, not in employment/education, and/or experiencing intersecting or multiple forms of disadvantage or difficulties), including detailing their clinical characteristics. METHODS: Young people were recruited from five headspace centres. Data relevant to social inclusion were examined. Multivariate logistic regression models were used to determine overlap between vulnerable groups, functional, social, clinical, and behavioural factors. RESULTS: 1107 young people participated, aged 12-25 years (M = 18.1 years, SD = 3.3), most living in stable housing (96.5%) and engaged in studying/employment (84.8%). Specific vulnerabilities were evident in young people with NEET status (15.2%); in unstable accommodation (3.5%); of culturally diverse backgrounds (CALD) (12.2%); living in regional areas (36.1%); and identifying as lesbian, gay, bisexual, transgender, intersex, queer/questioning, and asexual plus (LGBTIQA+; 28.2%). Higher levels of distress, substance use, functional impairment, and lower social support were reported by those who were NEET and/or in unstable housing. LGBTIQA+ status was associated with high distress, depressive symptoms, and suicidal ideation. CONCLUSIONS: Most participants reported good social support, stable housing, and engagement in work or education. Those deemed vulnerable were likely to experience social exclusion across multiple domains and reported more mental health problems. The co-occurrence of mental ill-health and social exclusion highlights the importance of integrated mental healthcare.

The neurophenomenology of early psychosis: An integrative empirical study.

BACKGROUND: The integration of various domains or levels of analysis (clinical, neurobiological, genetic, etc.) has been a challenge in schizophrenia research. A promising approach is to use the core phenomenological features of the disorder as an organising principle for other levels of analysis. Minimal self-disturbance (fragility in implicit first-person perspective, presence and agency) is emerging as a strong candidate to play this role. This approach was adopted in a previously described theoretical neurophenomenological model that proposed that source monitoring deficits and aberrant salience may be neurocognitive/neurobiological processes that correlate with minimal self-disturbance on the phenomenological level, together playing an aetiological role in the onset of schizophrenia spectrum disorders. The current paper presents full cross-sectional data from the first empirical test of this model. METHODS: Fifty ultra-high risk for psychosis patients, 39 first episode psychosis patients and 34 healthy controls were assessed with a variety of clinical measures, including the Examination of Anomalous Self-Experience (EASE), and neurocognitive and neurophysiological (EEG) measures of source monitoring deficits and aberrant salience. RESULTS: Linear regression indicated that source monitoring (composite score across neurocognitive and neurophysiological measures), with study group as an interaction term, explained 39.8% of the variance in EASE scores (R2 = 0.41, F(3,85) = 14.78, p < 0.001), whereas aberrant salience (composite score) explained only 6% of the variance in EASE scores (R2 = 0.06, F(3,85) = 1.44, p = 0.93). Aberrant salience measures were more strongly related to general psychopathology measures, particularly to positive psychotic symptoms, than to EASE scores. DISCUSSION: A neurophenomenological model of minimal self-disturbance in schizophrenia spectrum disorders may need to be expanded from source monitoring deficits to encompass other relevant constructs such as temporal processing, intermodal/multisensory integration, and hierarchical predictive processing. The cross-sectional data reported here will be expanded with longitudinal analysis in subsequent reports. These data and other related recent research show an emerging picture of neuro-features of core phenomenological aspects of schizophrenia spectrum disorders beyond surface-level psychotic symptoms.

Duration of untreated psychosis and neurocognitive functioning in first-episode psychosis: a systematic review and meta-analysis.

BACKGROUND: Previous reviews suggest there is minimal evidence for an association between duration of untreated psychosis (DUP) and neurocognition. This is based on tallied findings of studies with small samples and neurocognition viewed as a single construct. We aimed to conduct a systematic review and meta-analysis examining the association between DUP and individual neurocognitive domains and tests in first-episode psychosis (FEP). METHOD: MOOSE and PRISMA guidelines were followed. Forty-three studies involving 4647 FEP patients were included. For studies providing correlations between DUP and neurocognition, 12 separate meta-analyses were performed based on neurocognitive domains/indices. The influence of demographic/clinical variables was tested using weighted linear meta-regression analyses. RESULTS: The relationship between DUP and most neurocognitive domains/indices was not significant. Longer DUP was associated with a larger cognitive deterioration index, i.e. current minus premorbid intellectual functioning (N = 4; mean ES -0.213, 95% confidence interval (CI) (-0.344 to -0.074), p = 0.003). Findings were homogeneous, with no evidence of publication bias or significant influence from moderators. For studies providing mean and standard deviations for neurocognitive measures and DUP, 20 meta-regressions were performed on individual neurocognitive tests. One significant finding emerged showing that longer DUP was associated with fewer Wisconsin Card Sorting Test-perseverative errors (mean ES -0.031, 95% CI (-0.048 to -0.013), p < 0.001). Exploratory meta-regressions in studies with mean DUP <360 days showed longer DUP was significantly associated with poorer performance on Trail Making Test A and B and higher Full-Scale IQ. CONCLUSION: There may not be a generalised association between DUP and neurocognition, however, specific cognitive functions may be associated with longer DUP or delayed help-seeking.

Cannabis-induced attenuated psychotic symptoms: implications for prognosis in young people at ultra-high risk for psychosis.

BACKGROUND: Cannabis use shows a robust dose-dependent relationship with psychosis risk among the general population. Despite this, it has been difficult to link cannabis use with risk for transitioning to a psychotic disorder among individuals at ultra-high risk (UHR) for psychosis. The present study examined UHR transition risk as a function of cannabis use characteristics which vary substantially between individuals including age of first use, cannabis abuse severity and a history of cannabis-induced attenuated psychotic symptoms (APS). METHOD: Participants were 190 UHR individuals (76 males) recruited at entry to treatment between 2000 and 2006. They completed a comprehensive baseline assessment including a survey of cannabis use characteristics during the period of heaviest use. Outcome was transition to a psychotic disorder, with mean time to follow-up of 5.0 years (range 2.4-8.7 years). RESULTS: A history of cannabis abuse was reported in 58% of the sample. Of these, 26% reported a history of cannabis-induced APS. These individuals were 4.90 (95% confidence interval 1.93-12.44) times more likely to transition to a psychotic disorder (p = 0.001). Greater severity of cannabis abuse also predicted transition to psychosis (p = 0.036). However, this effect was mediated by higher abuse severity among individuals with a history of cannabis-induced APS. CONCLUSIONS: Findings suggest that cannabis use poses risk in a subpopulation of UHR individuals who manifest cannabis-induced APS. Whether this reflects underlying genetic vulnerability requires further study. Nevertheless, findings reveal an important early marker of risk with potentially significant prognostic utility for UHR individuals.

White matter connectivity disruptions in early and chronic schizophrenia.

BACKGROUND: White matter disruptions in schizophrenia have been widely reported, but it remains unclear whether these abnormalities differ between illness stages. We mapped the connectome in patients with recently diagnosed and chronic schizophrenia and investigated the extent and overlap of white matter connectivity disruptions between these illness stages. METHODS: Diffusion-weighted magnetic resonance images were acquired in recent-onset (n = 19) and chronic patients (n = 45) with schizophrenia, as well as age-matched controls (n = 87). Whole-brain fiber tracking was performed to quantify the strength of white matter connections. Connections were tested for significant streamline count reductions in recent-onset and chronic groups, relative to separate age-matched controls. Permutation tests were used to assess whether disrupted connections significantly overlapped between chronic and recent-onset patients. Linear regression was performed to test whether connectivity was strongest in controls, weakest in chronic patients, and midway between these extremities in recent-onset patients (controls > recent-onset > chronic). RESULTS: Compared with controls, chronic patients displayed a widespread network of connectivity disruptions (p < 0.01). In contrast, connectivity reductions were circumscribed to the anterior fibers of the corpus callosum in recent-onset patients (p < 0.01). A significant proportion of disrupted connections in recent-onset patients (86%) coincided with disrupted connections in chronic patients (p < 0.01). Linear regression revealed that chronic patients displayed reduced connectivity relative to controls, while recent-onset patients showed an intermediate reduction compared with chronic patients (p < 0.01). CONCLUSIONS: Connectome pathology in recent-onset patients with schizophrenia is confined to select tracts within a more extensive network of white matter connectivity disruptions found in chronic illness. These findings may suggest a trajectory of progressive deterioration of connectivity in schizophrenia.

A systematic review and meta-analysis of prospective transition from major depression to bipolar disorder.

OBJECTIVE: Some people with major depressive disorder (MDD) may be at a pre-onset stage for bipolar disorder (BD), where early identification or prevention efforts may be feasible. We aimed to identify rates and characteristics predictive of transition to BD in prospective follow-up studies of people with MDD. METHODS: Using a systematic search strategy, we identified studies with a diagnostic ascertainment of MDD and BD of an adequate standard, and where the minimum length of follow-up was 6 months. We examined the incidence and point prevalence of BD and the pooled odds ratios (OR) for baseline predictors. RESULTS: From 5554 unique publications, 56 were included. Nearly a quarter of adults (22.5%) and adolescents with MDD followed up for a mean length of 12-18 years developed BD, with the greatest risk of transition being in the first 5 years. The meta-analysis identified that transition from MDD to BD was predicted by family history of BD (OR = 2.89, 95% CI: 2.01-4.14, N = 7), earlier age of onset of depression (g = -0.33, SE = 0.05, N = 6) and presence of psychotic symptoms (OR = 4.76, 95% CI: 1.79-12.66, N = 5). CONCLUSIONS: Participants with the identified risk factors merit closer observation and may benefit from prevention efforts, especially if outcomes broader than BD are considered.

Predictors of functional status at service entry and discharge among young people with first episode psychosis.

OBJECTIVE: Most patients with first episode psychosis (FEP) are neither studying nor employed (have a poor functional status) when first accessing care. Knowledge of the characteristics of patients with poor functioning and the features influencing functional status over time may pave the way to better treatment. METHOD: A medical file audit was used to collect data on premorbid, entry, treatment and 18-month outcome characteristics on 661 FEP patients who consecutively attended the Early Psychosis Prevention and Intervention Centre, Melbourne, Australia, between 1998 and 2000. Functional status was ascertained using the modified vocational status index and was rated at baseline (poor or good) and according to its evolution over the treatment period (stable good, stable poor, deteriorating or improved functional status). RESULTS: 52.0% of patients had a poor functional status at service entry. They were more likely to be male with a non-affective psychosis. They also had lower levels of premorbid global functioning and education, and were more likely to have self-reported histories of learning disability, forensic issues, traumatic experiences and substance use. At service entry, they had more severe symptoms and poorer global functioning. 37% of these patients maintained a poor functional status at discharge, and 18% of those with a good functional status at service entry experienced a decline. CONCLUSIONS: Although psychosocial interventions might assist a young person with FEP with working towards functional goals, for some, the impact of factors such as ongoing substance use and forensic issues on functional status needs to be addressed.

Early psychosis research at Orygen, The National Centre of Excellence in Youth Mental Health.

BACKGROUND: Specialised early intervention (SEI) programs have offered individuals with psychotic disorders and their families new hope for improving illness trajectories and outcomes. The Early Psychosis Prevention and Intervention Centre (EPPIC) was one of the first SEI programs developed in the world, providing services for young people experiencing their first episode of psychosis. METHODS: We conducted a narrative synthesis of controlled and uncontrolled studies that have been conducted at EPPIC. DISCUSSION: The history of the EPPIC model is first described. This is followed by a discussion of clinical research emerging from EPPIC, including psychopharmacological, psychotherapeutic trials and outcome studies. Neurobiological studies are also described. Issues pertaining to the conduct of clinical research and future research directions are then described. Finally, the impact of the EPPIC model on the Australian environment is discussed.

Divergent effects of first-generation and second-generation antipsychotics on cortical thickness in first-episode psychosis.

BACKGROUND: Whether there are differential effects of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) on the brain is currently debated. Although some studies report that FGAs reduce grey matter more than SGAs, others do not, and research to date is limited by a focus on schizophrenia spectrum disorders. To address this limitation, this study investigated the effects of medication in patients being treated for first-episode schizophrenia or affective psychoses. METHOD: Cortical thickness was compared between 52 first-episode psychosis patients separated into diagnostic (i.e. schizophrenia or affective psychosis) and medication (i.e. FGA and SGA) subgroups. Patients in each group were also compared to age- and sex-matched healthy controls (n = 28). A whole-brain cortical thickness interaction analysis of medication and diagnosis was then performed. Correlations between cortical thickness with antipsychotic dose and psychotic symptoms were examined. RESULTS: The effects of medication and diagnosis did not interact, suggesting independent effects. Compared with controls, diagnostic differences were found in frontal, parietal and temporal regions. Decreased thickness in FGA-treated versus SGA-treated groups was found in a large frontoparietal region (p < 0.001, corrected). Comparisons with healthy controls revealed decreased cortical thickness in the FGA group whereas the SGA group showed increases in addition to decreases. In FGA-treated patients cortical thinning was associated with higher negative symptoms whereas increased cortical thickness in the SGA-treated group was associated with lower positive symptoms. CONCLUSIONS: Our results suggest that FGA and SGA treatments have divergent effects on cortical thickness during the first episode of psychosis that are independent from changes due to illness.

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 (inPLA(2)) 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 inPLA(2) 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 inPLA(2) were significantly related. Some of the significant associations (that is, long-chain ω-6 PUFAs, arachidonic acid) with inPLA(2) 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 inPLA(2) activity. We conclude that ω-3 PUFA supplementation may act by normalizing inPLA(2) activity and δ-6-desaturase-mediated metabolism of ω-3 and ω-6 PUFAs, suggesting their role in neuroprogression of psychosis.

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.

BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

Cognitive deficits in youth with familial and clinical high risk to psychosis: a systematic review and meta-analysis.

OBJECTIVE: It is likely that cognitive deficits are vulnerability markers for developing schizophrenia, as these deficits are already well-established findings in first-episode psychosis. Studies at-risk adolescents and young adults are likely to provide information about cognitive deficits that predate the onset of the illness. METHOD: We conducted meta-analyses of studies comparing familial-high risk (FHR) or ultra-high risk (UHR; n = 2113) and healthy controls (n = 1748) in youth studies in which the mean age was between 15 and 29. RESULTS: Compared with controls, high risk subjects were impaired in each domain in both UHR (d = 0.34-0.71) and FHR (d = 0.24-0.81). Heterogeneity of effect sizes across studies was modest, increasing confidence to the findings of the current meta-analysis (I(2) = 0-0.18%). In both risk paradigms, co-occurrence of genetic risk with attenuated symptoms was associated with more severe cognitive dysfunction. In UHR, later transition to psychosis was associated with more severe cognitive deficits in all domains (d = 0.31-0.49) except sustained attention. However, cognitive impairment has a limited capacity to predict the outcome of high-risk patients. CONCLUSION: Cognitive deficits are already evident in adolescents and young adults who have familial or clinical risk for psychosis. Longitudinal developmental studies are important to reveal timing and trajectory of emergence of such deficits.

Negative psychotic symptoms and impaired role functioning predict transition outcomes in the at-risk mental state: a latent class cluster analysis study.

BACKGROUND: Many research groups have attempted to predict which individuals with an at-risk mental state (ARMS) for psychosis will later develop a psychotic disorder. However, it is difficult to predict the course and outcome based on individual symptoms scores. METHOD: Data from 318 ARMS individuals from two specialized services for ARMS subjects were analysed using latent class cluster analysis (LCCA). The score on the Comprehensive Assessment of At-Risk Mental States (CAARMS) was used to explore the number, size and symptom profiles of latent classes. RESULTS: LCCA produced four high-risk classes, censored after 2 years of follow-up: class 1 (mild) had the lowest transition risk (4.9%). Subjects in this group had the lowest scores on all the CAARMS items, they were younger, more likely to be students and had the highest Global Assessment of Functioning (GAF) score. Subjects in class 2 (moderate) had a transition risk of 10.9%, scored moderately on all CAARMS items and were more likely to be in employment. Those in class 3 (moderate-severe) had a transition risk of 11.4% and scored moderately severe on the CAARMS. Subjects in class 4 (severe) had the highest transition risk (41.2%), they scored highest on the CAARMS, had the lowest GAF score and were more likely to be unemployed. Overall, class 4 was best distinguished from the other classes on the alogia, avolition/apathy, anhedonia, social isolation and impaired role functioning. CONCLUSIONS: The different classes of symptoms were associated with significant differences in the risk of transition at 2 years of follow-up. Symptomatic clustering predicts prognosis better than individual symptoms.

The relationship between subjective sleep disturbance and attenuated psychotic symptoms after accounting for anxiety and depressive symptoms.

BACKGROUND AND HYPOTHESES: Sleep disturbances are increasingly recognized as cooccurring with psychotic symptoms. The potential importance of this relationship is complicated when considering the effects of anxiety and depressive symptoms which commonly present in early-stage illness states. This study aimed to investigate the relationship between self-reported sleep disturbance on the development of attenuated psychotic symptoms (APS) cross-sectionally and longitudinally while adjusting for roles of anxiety and depressive symptoms. DESIGN: Eight-hundred and two help-seeking young people aged 12 to 25 years who engaged with our Australian early intervention services were included in the study (the "Transitions" cohort). Cross sectional mediation and cross-lagged longitudinal (12-month) mediation models were developed with outcomes being different APS domains. RESULTS: Only baseline excessive daytime sleepiness predicted later APS when accounting for previous APS, anxiety and depressive symptomatology. Cross sectionally, self-reported sleep disturbance showed both direct and indirect predictive relationships with all APS domains. Partial mediation through anxiety and depression was shown for unusual thought content, perceptual abnormalities, and disorganised speech, while full mediation through depression was shown for non-bizarre ideas. CONCLUSIONS: The specificity of the relationship between self-reported sleep disturbance on APS highlights the potential for different roles in mechanistic models of psychotic symptom expression. This further indicates the need for further experimental research to illuminate potential causal pathways. Future research should continue to use continuous, symptom level approaches across a range of timeframes to more accurately model the complex dynamics present in the sleep-psychosis relationship.

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.

Has improved treatment contributed to the declining rate of transition to psychosis in ultra-high-risk cohorts?

BACKGROUND: The factors contributing to declining psychotic disorder transition rates in ultra-high-risk populations remain unclear. We examined the contribution of longitudinal changes in standard clinical treatment ('treatment as usual') to this decline. METHOD: An audit was conducted on 105 clinical files of patients who received standard care at a specialised ultra-high-risk service. The session notes of these files were quantified, allowing examination of treatment quantity, targets, psychotherapy, and medication. Differences in these aspects across patients' year of clinic entry were assessed. Variables with significant differences across years were examined using cox regression to assess their contribution to psychosis transition rates. RESULTS: Findings were that, as a function of patients' year of clinic entry, there were increases in: patients' number of sessions, cognitive behavioural therapy (CBT), problem and solving therapy. There was a relationship between baseline year cohort and psychosis transition rate, with lower rates observed in more recent cohorts. When changes in treatment between cohorts were adjusted for, the relationship between baseline year cohort and transition rate disappeared. The relationship between baseline year and transition rate was attenuated most by increases in CBT. CONCLUSION: Changes in standard treatment, particularly increases in CBT, may have contributed to the decline in psychosis risk observed in recent ultra-high-risk cohorts, although these variables do not fully explain this trend. Implications for clinical practice, prediction and intervention research are discussed. Future ultra-high-risk research should investigate the impact of other treatment factors, such as therapeutic alliance.

Improving treatments for psychotic disorders: beyond cognitive behaviour therapy for psychosis.

More effective treatments for people with psychotic disorders are urgently required. Here, we make three suggestions for progress: 1. Targeting the disorders' core phenomenological features ('phenomenological phenotype'), 2. Addressing social disconnection, isolation and loneliness, and 3. Leveraging 'hot' cognitions and using symptom capture approaches that combine psychotherapy with advances in technology and neuroscience.

The psychometric characteristics of the Kessler Psychological Distress Scale (K6) in help-seeking youth: What do you miss when using it as an outcome measure?

This is the first study to describe psychometric properties of the Kessler Psychological Distress Scale (K6) in a large cohort of help-seeking young people presenting to primary mental health care services. The aim was to determine whether the K6 was appropriate for monitoring outcomes in such settings. 1067 young people were recruited from Australian headspace services. We examined dimensionality of the K6, measurement invariance, and how the K6 correlated with the the Patient Health Questionnaire-9 (PHQ-9)and the Generalised Anxiety Disorder-7 Scale (GAD-7). Standardised Response Mean (SRM) and Cohen's d effect size (ES) were used to examine 3-month stability of the K6. The best-fitting model was a two-factor model: (i) nervous and restlessness; and (ii) hopeless, worthless, depressed and effort. Measurement non-invariance was observed for sex and age groups. K6 strongly correlated with the PHQ-9 and GAD-7. The K6 was less sensitive to change compared to these other two measures. There was some support for the K6 being a screener for young people presenting to primary care; however, there issues arise with its use as an outcome measure. These issues include measurement non-invariance, concern about the dimensionality and focus of items, and its sensitivity to change.

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.