Study protocol: the development of a randomised controlled trial testing a postcard intervention designed to reduce suicide risk among young help-seekers

<p>Abstract</p> <p>Background</p> <p>Suicidal behaviour and deliberate self harm are common among adolescents. Limited evidence exists regarding interventions that can reduce risk; however research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from services can reduce risk. The aim of the study is to test a postcard intervention among people aged 15-24 who presented to mental health services but are not accepted, yet are at risk of suicide.</p> <p>Methods/design</p> <p>The study is a 3-year randomised controlled trial conducted at Orygen Youth Health Research Centre in Melbourne Australia. Participants are young help-seekers aged 15-24 who are at risk of suicide. Participants will be recruited over a 12 month period. The intervention comprises a regular postcard to be sent monthly for 12 months. The postcard enquires after their well being and includes information regarding individual sources of help and evidence-based self help strategies. Participants are assessed at baseline, 12 and 18 months.</p> <p>Discussion</p> <p>This paper describes the development of a study which aims to reduce suicide risk in a sample of young help-seekers. If effective, this intervention could have significant clinical and research implications for a population who can be hard to treat and difficult to research.</p> <p>Trial Registration</p> <p>The study was registered with the Australian Clinical Trials Registry; number: ACTRN012606000274572.</p

An open label pilot trial of low‐dose lithium for young people at ultra‐high risk for psychosis

Aim: Lithium, even at low doses, appears to offer neuroprotection against a wide variety of insults. In this controlled pilot, we examined the safety (i.e., side‐effect profile) of lithium in a sample of young people identified at ultra‐high risk (UHR) for psychosis. The secondary aim was to explore whether lithium provided a signal of clinical efficacy in reducing transition to psychosis compared with treatment as usual (TAU). Methods: Young people attending the PACE clinic at Orygen, Melbourne, were prescribed a fixed dose (450 mg) of lithium (n = 25) or received TAU (n = 78). The primary outcome examined side‐effects, with transition to psychosis, functioning and measures of psychopathology assessed as secondary outcomes. Results: Participants in both groups were functionally compromised (lithium group GAF = 56.6; monitoring group GAF = 56.9). Side‐effect assessment indicated that lithium was well‐tolerated. 64% (n = 16) of participants in the lithium group were lithium‐adherent to week 12. Few cases transitioned to psychosis across the study period; lithium group 4% (n = 1); monitoring group 7.7% (n = 6). There was no difference in time to transition to psychosis between the groups. No group differences were observed in other functioning and symptom domains, although all outcomes improved over time. Conclusions: With a side‐effect profile either comparable to, or better than UHR antipsychotic trials, lithium might be explored for further research with UHR young people. A definitive larger trial is needed to determine the efficacy of lithium in this cohort

Combining Clinical With Cognitive or Magnetic Resonance Imaging Data for Predicting Transition to Psychosis in Ultra High-Risk Patients:Data From the PACE 400 Cohort

Background: Multimodal modeling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals who are at ultra-high risk. Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in gray matter volume in multiple brain regions identified by magnetic resonance imaging.Methods: In this study, we used Cox proportional hazards regression models to assess the additive predictive value of each modality—cognition, cortical structure information, and the neuroanatomical measure of brain age gap—to a previously developed clinical model using functioning and duration of symptoms prior to service entry as predictors in the Personal Assessment and Crisis Evaluation (PACE) 400 cohort. The PACE 400 study is a well-characterized cohort of Australian youths who were identified as ultra-high risk of transitioning to psychosis using the Comprehensive Assessment of At Risk Mental States (CAARMS) and followed for up to 18 years; it contains clinical data (from N = 416 participants), cognitive data (n = 213), and magnetic resonance imaging cortical parameters extracted using FreeSurfer (n = 231).Results: The results showed that neuroimaging, brain age gap, and cognition added marginal predictive information to the previously developed clinical model (fraction of new information: neuroimaging 0%–12%, brain age gap 7%, cognition 0%–16%).Conclusions: In summary, adding a second modality to a clinical risk model predicting the onset of a psychotic disorder in the PACE 400 cohort showed little improvement in the fit of the model for long-term prediction of transition to psychosis

Impaired mismatch negativity to frequency deviants in individuals at ultra-high risk for psychosis, and preliminary evidence for further impairment with transition to psychosis

© 2018 Elsevier BV. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/Background There is evidence to suggest that people with established psychotic disorders show impairments in the mismatch negativity induced by a frequency-deviant sound (fMMN), and that these impairments worsen with the deterioration of psychotic symptoms. This study aimed to test whether individuals at ultra-high risk (UHR) for psychosis show pre-morbid impairments in fMMN, and if so, whether fMMN continues to deteriorate with transition to psychosis. Method fMMN was recorded in a cohort of UHR individuals (n = 42) and compared to healthy controls (n = 29). Of the 27 UHR participants who returned for a second EEG session, six participants had transitioned to psychosis by 12-month follow-up (UHR-T) and were compared to the 21 participants who did not transition (UHR-NT). Results fMMN amplitude was significantly reduced, relative to healthy controls, in the UHR cohort. Furthermore, UHR-T individuals showed a significant decrease in fMMN amplitude over the period from baseline to post-transition; this reduction was not observed in UHR-NT. Conclusions These results suggest that fMMN is abnormal in UHR individuals, as has repeatedly been found previously in people with established psychotic disorders. The finding that fMMN impairment worsens with transition to psychosis is consistent with the staging model of psychosis; however, caution must be taken in interpreting these findings, given the extremely small sample size of the UHR-T group

Managing deliberate self-harm in young people: An evaluation of a training program developed for school welfare staff using a longitudinal research design

BACKGROUND: Although deliberate self-harm is prevalent among young people, many who engage in deliberate self-harm receive sub-optimal care. Although schools are a well placed setting to support young people who engage in self-harm there are no specific training packages designed to assist school welfare staff to support these young people.The current study aimed to design, deliver and evaluate a training course specifically for school staff. METHODS: The study employed a longitudinal design. Two hundred and thirteen people participated in the training and evaluation. A questionnaire was administered at baseline, immediately after the training and at 6-month follow-up in order to determine if the training led to improvements in confidence when working with young people who self-harm, perceived skill, knowledge of, and attitudes towards people who self harm. RESULTS: Prior to the course, the majority of participants demonstrated relatively high levels of confidence, perceived skill and knowledge of self-harm and endorsed relatively positive attitudes towards people who engage in self-harm. Despite this, significant improvements were observed in terms of increased confidence, increased perceptions of skill along with increased knowledge of deliberate self-harm. These improvements were sustained over the follow-up period. CONCLUSION: The results demonstrated that the provision of specifically designed training can help school welfare staff to feel better equipped to support young people who are engaging in deliberate self-harm

Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial.

BACKGROUND Cognitive impairments are well-established features of psychotic disorders and are present when individuals are at ultra-high risk for psychosis. However, few interventions target cognitive functioning in this population. AIMS To investigate whether omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation improves cognitive functioning among individuals at ultra-high risk for psychosis. METHOD Data (N = 225) from an international, multi-site, randomised controlled trial (NEURAPRO) were analysed. Participants were given omega-3 supplementation (eicosapentaenoic acid and docosahexaenoic acid) or placebo over 6 months. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia (BACS). Mixed two-way analyses of variance were computed to compare the change in cognitive performance between omega-3 supplementation and placebo over 6 months. An additional biomarker analysis explored whether change in erythrocyte n-3 PUFA levels predicted change in cognitive performance. RESULTS The placebo group showed a modest greater improvement over time than the omega-3 supplementation group for motor speed (ηp2 = 0.09) and BACS composite score (ηp2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant (ηp2 = 0.02), but the composite score remained significant (ηp2 = 0.02). Change in erythrocyte n-3 PUFA levels did not predict change in cognitive performance over 6 months. CONCLUSIONS We found no evidence to support the use of omega-3 supplementation to improve cognitive functioning in ultra-high risk individuals. The biomarker analysis suggests that this finding is unlikely to be attributed to poor adherence or consumption of non-trial n-3 PUFAs

Stress hormones and verbal memory in young people over the first 12 weeks of treatment for psychosis

Aims Memory impairment in psychosis may be mediated through detrimental effects of hypothalamic-pituitary-adrenal (HPA) axis function. This study prospectively investigated the relationship between cortisol, sulphate dehydroepiandrosterone (DHEA(S) and cortisol: DHEA(S) ratio and memory in 35 first-episode psychosis (FEP) patients during the first 12 weeks of treatment and 23 healthy controls (HC). Methods Morning blood sampling and tests of attention, working memory and verbal memory occurred at baseline and 12-week follow-up. Results FEP and HC groups did not significantly differ in levels of cortisol, DHEA(S) or their ratio at baseline or over 12-weeks. The FEP group performed significantly below HC on all cognitive measures at baseline and over 12-weeks. Cortisol levels were unrelated to cognition in both groups. At baseline, DHEA(S) was positively associated with attention in HCs, but negatively associated with attention in FEP participants. Change in DHEA(S) was negatively associated with change in memory over 12-weeks in both groups. At 12-weeks, there was a negative correlation between the cortisol: DHEA(S) ratio and attention in both groups. Conclusions These findings are mostly in contrast to findings in chronic schizophrenia. Investigation at different illness phases and over longer-follow-up periods is required to determine the complex relationship between HPA-axis and memory functioning in psychosis

Isolating the impact of antipsychotic medication on metabolic health : secondary analysis of a randomized controlled trial of antipsychotic medication versus placebo in antipsychotic medication naïve first‐episode psychosis (the STAGES study)

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

Characterization and prediction of clinical pathways of vulnerability to psychosis through graph signal processing

Causal interactions between specific psychiatric symptoms could contribute to the heterogenous clinical trajectories observed in early psychopathology. Current diagnostic approaches merge clinical manifestations that co-occur across subjects and could significantly hinder our understanding of clinical pathways connecting individual symptoms. Network analysis techniques have emerged as alternative approaches that could help shed light on the complex dynamics of early psychopathology. The present study attempts to address the two main limitations that have in our opinion hindered the application of network approaches in the clinical setting. Firstly, we show that a multi-layer network analysis approach, can move beyond a static view of psychopathology, by providing an intuitive characterization of the role of specific symptoms in contributing to clinical trajectories over time. Secondly, we show that a Graph-Signal-Processing approach, can exploit knowledge of longitudinal interactions between symptoms, to predict clinical trajectories at the level of the individual. We test our approaches in two independent samples of individuals with genetic and clinical vulnerability for developing psychosis. Novel network approaches can allow to embrace the dynamic complexity of early psychopathology and help pave the way towards a more a personalized approach to clinical care