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.

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.

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.

The prognostic significance of attenuated psychotic symptoms in help-seeking youth.

BACKGROUND: Recent findings suggest that attenuated psychotic symptoms (APS) might serve as a risk factor for general mental health impairment in help-seeking youth. The current study was designed to test this possibility by examining the prognostic significance of APS in a large cohort of help-seeking youth not selected for psychosis risk. METHOD: 465 youth aged 12-25 referred to general youth mental health services were grouped as either APS + or APS- based on whether or not they met 'ultra high risk' for psychosis APS risk criteria as assessed using the Comprehensive Assessment of At Risk Mental States (CAARMS). They completed clinical assessments at baseline and at 12-month follow-up, measuring a range of psychopathology (depression, anxiety, eating disorders, general psychological distress, substance abuse) and psychosocial functioning. RESULTS: APS + had significantly poorer outcomes at 12-months on a range of clinical variables, even after adjusting for baseline scores and amount of treatment received. However, the APS + group showed greater improvement in functioning at follow-up compared to APS-. CONCLUSION: Attenuated psychotic symptoms are a prognostic indicator of persistent transdiagnostic mental health problems and reduced response to treatment in help-seeking youth over the short term. Hence, it is critical to screen and assess attenuated psychotic symptoms at the primary and secondary mental health services level, especially given that these subclinical symptoms are rarely voluntarily reported.

Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes.

There has been limited research into the predictive value of basic symptoms and their relationship with other psychopathology in patients identified using the 'ultra high risk' (UHR) for psychosis approach. The current study investigated whether basic symptoms, specifically cognitive disturbances (COGDIS), were associated with a greater risk of transition to psychotic disorder and persistent attenuated psychotic symptoms (APS) at medium term follow-up (mean = 3.4 years) in UHR patients, as well as with general psychopathology at baseline. The sample included 304 UHR participants (mean age = 19.12 years) involved in an international multicenter trial of omega-3 fatty acids. UHR individuals who also met the COGDIS criteria (basic symptoms risk criteria) did not have a greater risk of transition than those who met the UHR criteria alone. However, meeting COGDIS risk criteria was associated with a greater likelihood of meeting the UHR attenuated psychotic symptoms risk group (i.e., having persistent attenuated psychotic symptoms) at 12-month follow-up (odds ratio = 1.85; 95% CI = 1.03, 3.32). Greater severity of cognitive basic symptoms was also independently associated with more severe general psychopathology at study entry. The findings do not support the notion that combined risk identification approaches (UHR and basic symptoms) aid in the identification of individuals at greatest risk of psychosis, although this interpretation is limited by the modest transition to psychosis rate (13%) and the time of follow up. However, the findings indicate that basic symptoms may be a clinically useful marker of more severe general psychopathology in UHR groups and risk for persistent attenuated psychotic symptoms.

Dynamic prediction of transition to psychosis using joint modelling.

Considerable research has been conducted seeking risk factors and constructing prediction models for transition to psychosis in individuals at ultra-high risk (UHR). Nearly all such research has only employed baseline predictors, i.e. data collected at the baseline time point, even though longitudinal data on relevant measures such as psychopathology have often been collected at various time points. Dynamic prediction, which is the updating of prediction at a post-baseline assessment using baseline and longitudinal data accumulated up to that assessment, has not been utilized in the UHR context. This study explored the use of dynamic prediction and determined if it could enhance the prediction of frank psychosis onset in UHR individuals. An emerging statistical methodology called joint modelling was used to implement the dynamic prediction. Data from the NEURAPRO study (n = 304 UHR individuals), an intervention study with transition to psychosis study as the primary outcome, were used to investigate dynamic predictors. Compared with the conventional approach of using only baseline predictors, dynamic prediction using joint modelling showed significantly better sensitivity, specificity and likelihood ratios. As dynamic prediction can provide an up-to-date prediction for each individual at each new assessment post entry, it can be a useful tool to help clinicians adjust their prognostic judgements based on the unfolding clinical symptomatology of the patients. This study has shown that a dynamic approach to psychosis prediction using joint modelling has the potential to aid clinicians in making decisions about the provision of timely and personalized treatment to patients concerned.

Exploring the impact of adverse childhood experiences on symptomatic and functional outcomes in adulthood: advances, limitations and considerations.

Exposure to traumatic experiences in childhood is a risk (and potentially causal) factor for the development of a range of adverse physical and mental health conditions. In addition to the onset of clinical disorders, there is emerging evidence that childhood trauma may also be associated with other long-term outcomes, such as the persistence and severity of an individual's symptoms, as well as their long-term social and occupational functioning. However, the reasons for this remain poorly understood. A greater understanding both of the mediators that drive these associations, and those variables that enhance resilience against such damaging experiences may help to inform effective therapeutic interventions. In addition to biological and cognitive measures, there is a need to consider social and environmental factors, such as parental bonding and attachment, when investigating these complex relationships.

Enhancing social functioning in young people at Ultra High Risk (UHR) for psychosis: A pilot study of a novel strengths and mindfulness-based online social therapy.

BACKGROUND: Psychological and pharmacological treatments have been shown to reduce rates of transition to psychosis in Ultra High Risk (UHR) young people. However, social functioning deficits have been unresponsive to current treatments. AIMS: The study aims were to: i) describe the theoretical basis and therapeutic targets of a novel intervention targeting social functioning in UHR young people; and ii) examine its acceptability, safety and preliminary effect on social functioning. METHODS: An international, multidisciplinary team developed a new intervention (MOMENTUM) to improve social functioning in UHR young people. MOMENTUM blends two novel approaches to social recovery: strengths and mindfulness-based intervention embedded within a social media environment, and application of the self-determination theory of motivation. The acceptability and safety of MOMENTUM were tested through a 2-month pilot study with 14 UHR participants. RESULTS: System usage was high, with over 70% of users being actively engaged over the trial. All participants reported a positive experience using MOMENTUM, considered it safe and would recommend it to others. 93% reported it to be helpful. There were large, reliable improvements in social functioning (d = 1.83, p < 0.001) and subjective wellbeing (d = 0.75, p = 0.03) at follow-up. There were significant increases in the mechanisms targeted by the intervention including strengths usage (d = 0.70, p = 0.03), mindfulness skills (d = 0.66, p = 0.04) and components of social support. Social functioning improvement was significantly correlated with indicators of system usage. CONCLUSION: MOMENTUM is engaging and safe. MOMENTUM appeared to engage the hypothesized mechanisms and showed promise as a new avenue to improve social functioning in UHR young people.

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

This study reports a medium-term follow-up of a randomised, double-blind, placebo-controlled trial of omega-3 polyunsaturated fatty acids (PUFA) in ultra-high risk for psychosis (UHR) patients. Primary outcomes of interest were transition to psychosis and symptomatic and functional outcome. A secondary aim was to investigate clinical predictors of medium-term outcome. Three hundred four UHR participants were recruited across 10 specialised early psychosis services in Australia, Asia, and Europe. The intervention consisted of 1.4 g/daily of omega-3 PUFA or placebo, plus up to 20 sessions of cognitive-behavioural case management (CBCM), over the 6-month study period, with participants receiving further CBCM sessions on basis of need between months 6-12. Mean time to follow-up was 3.4 (median = 3.3; SD = 0.9) years. There was a modest increase in transitions between 12-month and medium-term follow-up (11-13%) and substantial improvement in symptoms and functioning between baseline and follow-up, with no differences between the treatment groups. Most improvement had been achieved by end of the intervention. 55% of the sample received mental health treatment between end of intervention and follow-up. Omega-3 PUFA did not provide additional benefits to good quality psychosocial intervention over the medium term. Although most improvement had been achieved by end of intervention the substantial rates of post-intervention mental health service use indicate longer-term clinical need in UHR patients. The post-intervention phase treatment or the longer-term effect of CBCM, or a combination of the two, may have contributed to maintaining the gains achieved during the intervention phase and prevented significant deterioration after this time.

Cannabis use and symptom severity in individuals at ultra high risk for psychosis: a meta-analysis.

OBJECTIVE: We aimed to assess whether individuals at ultra high risk (UHR) for psychosis have higher rates of cannabis use and cannabis use disorders (CUDs) than non-UHR individuals and determine whether UHR cannabis users have more severe psychotic experiences than non-users. METHOD: We conducted a meta-analysis of studies reporting cannabis use in the UHR group and/or positive or negative symptoms among UHR cannabis users and non-users. Logit event rates were calculated for cannabis use, in addition to odds ratios to assess the difference between UHR and controls. Severity of clinical symptoms in UHR cannabis users and non-users was compared using Hedges' g. RESULTS: Thirty unique studies were included (UHR n = 4205, controls n = 667) containing data from cross-sectional and longitudinal studies, and randomised control trials. UHR individuals have high rates of current (26.7%) and lifetime (52.8%) cannabis use, and CUDs (12.8%). Lifetime use and CUDs were significantly higher than controls (lifetime OR: 2.09; CUD OR: 5.49). UHR cannabis users had higher rates of unusual thought content and suspiciousness than non-users. CONCLUSION: Ultra high risk individuals have high rates of cannabis use and CUDs, and cannabis users had more severe positive symptoms. Targeting substance use during the UHR phase may have significant benefits to an individual's long-term outcome.

The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis.

BACKGROUND: When used as an adjunctive with antipsychotics, certain vitamins and minerals may be effective for improving symptomatic outcomes of schizophrenia, by restoring nutritional deficits, reducing oxidative stress, or modulating neurological pathways. METHOD: We conducted a systematic review of all randomized controlled trials (RCTs) reporting effects of vitamin and/or mineral supplements on psychiatric symptoms in people with schizophrenia. Random-effects meta-analyses were used to calculate the standardized mean difference between nutrient and placebo treatments. RESULTS: An electronic database search in July 2016 identified 18 eligible RCTs, with outcome data for 832 patients. Pooled effects showed that vitamin B supplementation (including B6, B8 and B12) reduced psychiatric symptoms significantly more than control conditions [g = 0.508, 95% confidence interval (CI) 0.01-1.01, p = 0.047, I 2 = 72.3%]. Similar effects were observed among vitamin B RCTs which used intention-to-treat analyses (g = 0.734, 95% CI 0.00-1.49, p = 0.051). However, no effects of B vitamins were observed in individual domains of positive and negative symptoms (both p > 0.1). Meta-regression analyses showed that shorter illness duration was associated with greater vitamin B effectiveness (p = 0.001). There were no overall effects from antioxidant vitamins, inositol or dietary minerals on psychiatric symptoms. CONCLUSIONS: There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia. Further research is needed to examine how the benefits of supplementation relate to nutrient deficits and the impact upon underlying neurobiological pathways, in order to establish optimal nutrient formulations for improving clinical outcomes in this population. Future studies should also explore the effects of combining beneficial nutrients within multi-nutrient formulas.

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.

Substance use in youth at risk for psychosis.

BACKGROUND: People with schizophrenia have high rates of substance use which contributes to co-morbidity and premature mortality. Some evidence suggests people at-risk for psychosis have high rates of substance use. We aimed to assess substance use in a help-seeking cohort, comparing those at-risk and not at-risk for psychosis, and to establish any relationship with clinical symptoms. METHOD: Participants were help-seeking youth presenting to mental health services in Sydney and Melbourne. 279 (34.8%) were at-risk for psychosis, and 452 (56.4%) did not meet criteria for a psychotic disorder or risk for psychosis. The excluded individuals were made up of 59 (7.4%) young people who met criteria for a psychotic disorder and 11 (1.4%) who were unable to be evaluated. We assessed the association of substance use involvement with risk status and clinical symptoms using multivariate regression. RESULTS: Individuals at-risk for psychosis had significantly higher tobacco, alcohol and cannabis use than those not at-risk. Multivariate analysis revealed at-risk status was significantly associated with higher alcohol involvement scores when adjusting for age and gender, but no association was found for cannabis or tobacco. At-risk status was no longer associated with alcohol involvement when cannabis or tobacco use was added into the analysis. CONCLUSION: Tobacco smoking, alcohol consumption and cannabis use are common in help-seeking youth, particularly those at-risk for psychosis. It is important to consider co-occurring use of different substances in adolescents. Early substance misuse in this phase of illness could be targeted to improve physical and mental health in young people.

Motivating factors and barriers towards exercise in severe mental illness: a systematic review and meta-analysis.

Exercise can improve clinical outcomes in people with severe mental illness (SMI). However, this population typically engages in low levels of physical activity with poor adherence to exercise interventions. Understanding the motivating factors and barriers towards exercise for people with SMI would help to maximize exercise participation. A search of major electronic databases was conducted from inception until May 2016. Quantitative studies providing proportional data on the motivating factors and/or barriers towards exercise among patients with SMI were eligible. Random-effects meta-analyses were undertaken to calculate proportional data and 95% confidence intervals (CI) for motivating factors and barriers toward exercise. From 1468 studies, 12 independent studies of 6431 psychiatric patients were eligible for inclusion. Meta-analyses showed that 91% of people with SMI endorsed 'improving health' as a reason for exercise (N = 6, n = 790, 95% CI 80-94). Among specific aspects of health and well-being, the most common motivations were 'losing weight' (83% of patients), 'improving mood' (81%) and 'reducing stress' (78%). However, low mood and stress were also identified as the most prevalent barriers towards exercise (61% of patients), followed by 'lack of support' (50%). Many of the desirable outcomes of exercise for people with SMI, such as mood improvement, stress reduction and increased energy, are inversely related to the barriers of depression, stress and fatigue which frequently restrict their participation in exercise. Providing patients with professional support to identify and achieve their exercise goals may enable them to overcome psychological barriers, and maintain motivation towards regular physical activity.

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

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