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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. [ABSTRACT FROM AUTHOR]

Poor vocational engagement is well documented among young people experiencing first-episode psychosis (FEP). The aim of the present study was to establish and compare rates of vocational engagement across young people with first-episode psychosis, depression, and borderline personality pathology. A file audit was used to collect vocational data of young people aged 15-25 entering tertiary mental health treatment in 2011. Rates of vocational engagement were similar across groups, indicating that like those with FEP, young people with depression and borderline personality pathology experience impaired vocational engagement and are in need of targeted vocational interventions. Post hoc analysis indicated that that the depression group had significantly more people who were partially vocationally engaged compared with the psychosis group, suggesting that vocational interventions might need to be targeted differently across different diagnostic groups. Future research should explore risk factors for vocational disengagement across diagnostic groups in order to inform intervention development. [ABSTRACT FROM AUTHOR]

BackgroundThe ACE project involved 62 participants with a first episode of psychosis randomly assigned to either a cognitive behaviour therapy (CBT) intervention known as Active Cognitive Therapy for Early Psychosis (ACE) or a control condition known as Befriending. The study hypotheses were that: (1) treating participants with ACE in the acute phase would lead to faster reductions in positive and negative symptoms and more rapid improvement in functioning than Befriending; (2) these improvements in symptoms and functioning would be sustained at a 1-year follow-up; and (3) ACE would lead to fewer hospitalizations than Befriending as assessed at the 1-year follow-up.MethodTwo therapists treated the participants across both conditions. Participants could not receive any more than 20 sessions within 14 weeks. Participants were assessed by independent raters on four primary outcome measures of symptoms and functioning: at pretreatment, the middle of treatment, the end of treatment and at 1-year follow-up. An independent pair of raters assessed treatment integrity.ResultsBoth groups improved significantly over time. ACE significantly outperformed Befriending by improving functioning at mid-treatment, but it did not improve positive or negative symptoms. Past the mid-treatment assessment, Befriending caught up with the ACE group and there were no significant differences in any outcome measure and in hospital admissions at follow-up.ConclusionsThere is some preliminary evidence that ACE promotes better early recovery in functioning and this finding needs to be replicated in other independent research centres with larger samples. [ABSTRACT FROM AUTHOR]

Background: Social cognitive deficits have been demonstrated in first episode psychosis (FEP) and groups at high risk for developing psychosis but the relative degree of deficit between these groups is unclear. Such knowledge may further our understanding of the importance of these deficits in the development of psychosis. The study aimed to compare the degree of impairment in social cognition in three groups: FEP, those at "ultra high risk" (UHR) for psychosis and healthy controls.Methods: UHR and FEP patients were recruited from an established youth mental health service in Melbourne. Three domains of social cognition were assessed: ToM (hinting task and interpretation of visual jokes); facial and vocal emotion recognition (Diagnostic Assessment of Non Verbal Accuracy); social perception (Mayer-Salovey-Caruso Emotional Intelligence Test - managing emotions branch). Group differences were analysed using Analysis of Covariance with age, gender and IQ as covariates.Results: Data on 30 UHR, 40 FEP and 30 control participants were analysed. FEP patients performed significantly worse on all social cognition tasks compared to controls. For the UHR group, scores were intermediate between FEP and controls for all tasks, but only significantly different to controls for ToM tasks. Effects sizes were largest for the ToM tasks and the emotion recognition task for both patient groups. There were no significant differences between UHR and FEP patients in performance on any of the tasks.Conclusions: Social cognition is generally impaired in FEP patients but there are fewer deficits in a UHR group. Longitudinal research in larger samples is needed to investigate whether social cognition deficits, such as ToM are risk factors in UHR groups for subsequent transition to full-threshold psychosis. [ABSTRACT FROM AUTHOR]

Objective: The current guidelines recommend continuation of antipsychotic medication for a minimum of at least 1 year following a first episode of psychosis (FEP). There have been several trials investigating whether early dose reduction or cessation leads to improved functional outcomes. The aim of this study was to explore the experience of consenting to and participating in a randomized controlled trial (RCT) of antipsychotic medication cessation., Method: Five participants in the Reduce trial-an RCT evaluating early antipsychotic medication dose reduction/cessation following FEP-aged 22-24 years completed a semistructured qualitative interview following the RCT. Interpretive phenomenological analysis was undertaken to understand the key themes., Results: A superordinate theme was derived from interviews: the Liminal Space of FEP and treatment. Themes within the Liminal Space included: rejection versus identification with psychosis, medication as symbolic of illness versus wellness, embodiment of wellness and illness with medication, medication as symbolic of independence versus dependence, discovery of independence when autonomously choosing medication, the Reduce trial offered safety to navigate the liminal space, and self-exploration versus altruism., Conclusions and Implications for Practice: The experience and treatment of FEP involves young people feeling torn between multiple, competing perspectives, demands, and priorities. Participation in an RCT exploring dose reduction provided additional supports contributing to the perception of greater safety to navigate their own experiences of treatment that was appropriate for them. When treatment is experienced as collaborative, involves shared decision making and support, other than medication, young people feel more equipped to navigate the liminal space. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: First-Episode Psychosis (FEP) is a devastating mental health condition that commonly emerges during early adulthood, and is characterised by a disconnect in perceptions of reality. Current evidence suggests that inflammation and perturbed immune responses are involved in the pathology of FEP and may be associated specifically with negative symptoms. Exercise training is a potent anti-inflammatory stimulus that can reduce persistent inflammation, and can improve mood profiles in general populations. Therefore, exercise may represent a novel adjunct therapy for FEP. The aim of this study was to assess the effect of exercise on biomarkers of inflammation, negative symptoms of psychosis, and physiological health markers in FEP., Methods: Seventeen young males (26.67 ± 6.64 years) were recruited from Birmingham Early Intervention in Psychosis Services and randomised to a 6-week exercise programme consisting of two-to-three sessions per week that targeted 60-70 % heart-rate max (HRMax), or a treatment as usual (TAU) condition. Immune T-helper (Th-) cell phenotypes and cytokines, symptom severity, functional wellbeing, and cognition were assessed before and after 6-weeks of regular exercise., Results: Participants in the exercise group (n = 10) achieved 81.11 % attendance to the intervention, with an average exercise intensity of 67.54 % ± 7.75 % HRMax. This led to favourable changes in immune cell phenotypes, and a significant reduction in the Th1:Th2 ratio (-3.86 %) compared to the TAU group (p = 0.014). After the exercise intervention, there was also a significant reduction in plasma IL-6 concentration (-22.17 %) when compared to the TAU group (p = 0.006). IL-8, and IL-10 did not show statistically significant differences between the groups after exercise. Symptomatically, there was a significant reduction in negative symptoms after exercise (-13.54 %, Positive and Negative Syndrome Scale, (PANSS) Negative) when compared to the TAU group (p = 0.008). There were no significant change in positive or general symptoms, functional outcomes, or cognition (all p > 0.05)., Discussion: Regular moderate-to-vigorous physical activity is feasible and attainable in clinical populations. Exercise represents a physiological tool that is capable of causing significant inflammatory biomarker change and concomitant symptom improvements in FEP cohorts, and may be useful for treatment of symptom profiles that are not targeted by currently prescribed antipsychotic medication., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Cognitive impairments are a core feature of first-episode psychosis (FEP) and one of the strongest predictors of long-term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support. However, there are currently no validated screening measures for young people with FEP. CogScreen is a hybrid effectiveness-implementation study which aims to evaluate the classification accuracy (relative to a neuropsychological assessment as a reference standard), test-retest reliability and acceptability of two cognitive screening tools in young people with FEP., Methods: Participants will be 350 young people (aged 12-25) attending primary and specialist FEP treatment centres in three large metropolitan cities (Adelaide, Sydney, and Melbourne) in Australia. All participants will complete a cross-sectional assessment over two sessions including two cognitive screening tools (Screen for Cognitive Impairment in Psychiatry and Montreal Cognitive Assessment), a comprehensive neuropsychological assessment battery, psychiatric and neurodevelopmental assessments, and other supplementary clinical measures. To determine the test-retest reliability of the cognitive screening tools, a subset of 120 participants will repeat the screening measures two weeks later., Results: The protocol, rationale, and hypotheses for CogScreen are presented., Conclusions: CogScreen will provide empirical evidence for the validity and reliability of two cognitive screening tools when compared to a comprehensive neuropsychological assessment. The screening measures may later be incorporated into clinical practice to assist with rapid identification and treatment of cognitive deficits commonly experienced by young people with FEP., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community. In an expected sample of approximately 2000 CHR individuals and 640 matched healthy controls, AMP SCZ will collect clinical, environmental, and cognitive data along with multimodal biomarkers, including neuroimaging, electrophysiology, fluid biospecimens, speech and facial expression samples, novel measures derived from digital health technologies including smartphone-based daily surveys, and passive sensing as well as actigraphy. The study will investigate a range of clinical outcomes over a 2-year period, including transition to psychosis, remission or persistence of CHR status, attenuated positive symptoms, persistent negative symptoms, mood and anxiety symptoms, and psychosocial functioning. The global reach of AMP SCZ and its harmonized innovative methods promise to catalyze the development of new treatments to address critical unmet clinical and public health needs in CHR individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

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., (Copyright © 2023 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS)., Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences., Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS., Conclusions: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Aim: Vitamin D deficiency is prevalent in people with established psychotic disorders, but less is known about vitamin D levels in people with first-episode psychosis (FEP). This study aimed to determine the prevalence of vitamin D deficiency in people with FEP and identify the factors associated with vitamin D status., Methods: This was a prospective cohort study nested within a randomized controlled trial, which included 37 young people with an FEP with minimal antipsychotic medication exposure., Results: Twenty-four percent of participants were vitamin D deficient, and a further 30% were vitamin D insufficient. There was no association between vitamin D and demographic factors or clinical symptoms (positive, negative, general psychopathology and depressive symptoms) or cognition and functioning. However, vitamin D levels were associated with season of sampling., Conclusions: Considering the longer-term adverse effects associated with vitamin D deficiency, it is warranted to ensure this clinical population receives supplementation if indicated., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Aim: Basic self disturbance is a putative core vulnerability marker of schizophrenia spectrum disorders. The primary aims of the Self, Neuroscience and Psychosis (SNAP) study are to: (1) empirically test a previously described neurophenomenological self-disturbance model of psychosis by examining the relationship between specific clinical, neurocognitive, and neurophysiological variables in UHR patients, and (2) develop a prediction model using these neurophenomenological disturbances for persistence or deterioration of UHR symptoms at 12-month follow-up., Methods: SNAP is a longitudinal observational study. Participants include 400 UHR individuals, 100 clinical controls with no attenuated psychotic symptoms, and 50 healthy controls. All participants complete baseline clinical and neurocognitive assessments and electroencephalography. The UHR sample are followed up for a total of 24 months, with clinical assessment completed every 6 months., Results: This paper presents the protocol of the SNAP study, including background rationale, aims and hypotheses, design, and assessment procedures., Conclusions: The SNAP study will test whether neurophenomenological disturbances associated with basic self-disturbance predict persistence or intensification of UHR symptomatology over a 2-year follow up period, and how specific these disturbances are to a clinical population with attenuated psychotic symptoms. This may ultimately inform clinical care and pathoaetiological models of psychosis., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Aim: Cognitive impairments negatively impact the everyday functioning of young people with mental illness. However, no previous study has asked young people (1) how much of a priority cognitive functioning is within mental health treatment, and (2) what types of cognition-focused treatments are most appealing. The current study aimed to address these questions., Methods: Your Mind, Your Choice was a survey-based study involving an Australian sample of young people who were receiving mental health treatment. The survey asked participants to (1) provide demographic and mental health history, (2) rate the importance of 20 recovery domains, including cognition, when receiving mental health treatment, (3) share their experiences of cognitive functioning, and (4) rate their likelihood of trying 14 different behavioural, biochemical, and physical treatments that may address cognitive functioning., Results: Two-hundred and forty-three participants (M age  = 20.07, SD = 3.25, range = 15-25, 74% female) completed the survey. Participants reported that addressing cognitive functioning in mental health care was very important (M = 76.33, SD = 20.7, rated on a scale from 0 = not important to 100 = extremely important), ranking cognition among their top six treatment needs. Seventy percent of participants reported experiencing cognitive difficulties, but less than one-third had received treatment for these difficulties. Compensatory training, sleep interventions and psychoeducation were ranked as treatments that participants were most likely to try to support their cognitive functioning., Conclusions: Young people with mental ill-health commonly experience cognitive difficulties and would like this to be a focus of treatment; however, this need is often unmet and should be a focus of research and implementation., (© 2023 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Introduction: There is limited research into informal support processes amongst young people supporting a peer through a traumatic event and how this process occurs specifically within a rural setting., Objective: The aim of this research was to understand how the contextual environment impacts on the personal and interpersonal processes of rural-based young people supporting a peer who experienced a traumatic event., Design: Qualitative interviews were conducted with 22 young people (aged 14-19), who resided in Gippsland, Victoria, Australia. A substantive theory was developed using Charmaz's (1) Constructivist grounded theory methodology., Findings: Young people who shared responsibility for supporting their peer went back to life as normal and felt connected to their community, whereas young people who maintained sole responsibility, experienced mental health problems, disconnected from their community and felt like an outsider. The contextual environmental factors (i.e., service accessibility, limited transport, and internet blackspots) impacted both negatively and positively on young people's ability to provide support as well as influenced whether they felt safe share responsibility., Discussion: This theory implies that providing pathways to reconnecting with place and community, are essential in guiding young people back to their foundations of support., Conclusion: Integrating these insights can create new service models in rural areas, whilst also creating opportunities to form healthy foundations of support., (© 2023 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Importance: Psychotic illness is associated with anatomically distributed gray matter reductions that can worsen with illness progression, but the mechanisms underlying the specific spatial patterning of these changes is unknown., Objective: To test the hypothesis that brain network architecture constrains cross-sectional and longitudinal gray matter alterations across different stages of psychotic illness and to identify whether certain brain regions act as putative epicenters from which volume loss spreads., Design, Settings, and Participants: This case-control study included 534 individuals from 4 cohorts, spanning early and late stages of psychotic illness. Early-stage cohorts included patients with antipsychotic-naive first-episode psychosis (n = 59) and a group of patients receiving medications within 3 years of psychosis onset (n = 121). Late-stage cohorts comprised 2 independent samples of people with established schizophrenia (n = 136). Each patient group had a corresponding matched control group (n = 218). A sample of healthy adults (n = 356) was used to derive representative structural and functional brain networks for modeling of network-based spreading processes. Longitudinal illness-related and antipsychotic-related gray matter changes over 3 and 12 months were examined using a triple-blind randomized placebo-control magnetic resonance imaging study of the antipsychotic-naive patients. All data were collected between April 29, 2008, and January 15, 2020, and analyses were performed between March 1, 2021, and January 14, 2023., Main Outcomes and Measures: Coordinated deformation models were used to estimate the extent of gray matter volume (GMV) change in each of 332 parcellated areas by the volume changes observed in areas to which they were structurally or functionally coupled. To identify putative epicenters of volume loss, a network diffusion model was used to simulate the spread of pathology from different seed regions. Correlations between estimated and empirical spatial patterns of GMV alterations were used to quantify model performance., Results: Of 534 included individuals, 354 (66.3%) were men, and the mean (SD) age was 28.4 (7.4) years. In both early and late stages of illness, spatial patterns of cross-sectional volume differences between patients and controls were more accurately estimated by coordinated deformation models constrained by structural, rather than functional, network architecture (r range, >0.46 to <0.57; P < .01). The same model also robustly estimated longitudinal volume changes related to illness (r ≥ 0.52; P < .001) and antipsychotic exposure (r ≥ 0.50; P < .004). Network diffusion modeling consistently identified, across all 4 data sets, the anterior hippocampus as a putative epicenter of pathological spread in psychosis. Epicenters of longitudinal GMV loss were apparent in posterior cortex early in the illness and shifted to the prefrontal cortex with illness progression., Conclusion and Relevance: These findings highlight a central role for white matter fibers as conduits for the spread of pathology across different stages of psychotic illness, mirroring findings reported in neurodegenerative conditions. The structural connectome thus represents a fundamental constraint on brain changes in psychosis, regardless of whether these changes are caused by illness or medication. Moreover, the anterior hippocampus represents a putative epicenter of early brain pathology from which dysfunction may spread to affect connected areas.

Background: There is limited research on how supporting a peer through a traumatic event is experienced by adolescents. The aim of this research was to understand the personal and interpersonal processes of adolescents supporting a peer who experienced a traumatic event based on youth definitions., Method: In-depth qualitative interviews were conducted with 22 adolescents aged 14-19, residing in Gippsland, Victoria, Australia. A constructivist grounded theory methodology was used to develop a substantive theory., Results: The substantive theory 'Foundations of Support' was developed which explained the support process phenomena. Specifically, adolescents who had shared responsibility for supporting their peers went back to life as normal, whereas adolescents who maintained sole responsibility experienced mental health problems., Discussion: The 'Foundations of Support' grounded theory highlights the importance of adolescents having strong connections to their trusted others, such as family, friends and community. This theory implies that facilitating connections with positive supports such as place and community are essential in guiding adolescents back to their foundations of support. Without strong connections, adolescents are at risk of maintaining sole responsibility, losing their sense of identity and feeling alienated within their community., (© 2023 The Authors. Australian Journal of Rural Health published by John Wiley & Sons Australia, Ltd on behalf of National Rural Health Alliance Ltd.)

Delivery of neuropsychological interventions addressing the cognitive, psychological, and behavioural consequences of brain conditions is increasingly recognised as an important, if not essential, skill set for clinical neuropsychologists. It has the potential to add substantial value and impact to our role across clinical settings. However, there are numerous approaches to neuropsychological intervention, requiring different sets of skills, and with varying levels of supporting evidence across different diagnostic groups. This clinical guidance paper provides an overview of considerations and recommendations to help guide selection, delivery, and implementation of neuropsychological interventions for adults and older adults. We aimed to provide a useful source of information and guidance for clinicians, health service managers, policy-makers, educators, and researchers regarding the value and impact of such interventions. Considerations and recommendations were developed by an expert working group of neuropsychologists in Australia, based on relevant evidence and consensus opinion in consultation with members of a national clinical neuropsychology body. While the considerations and recommendations sit within the Australian context, many have international relevance. We include (i) principles important for neuropsychological intervention delivery (e.g. being based on biopsychosocial case formulation and person-centred goals); (ii) a description of clinical competencies important for effective intervention delivery; (iii) a summary of relevant evidence in three key cohorts: acquired brain injury, psychiatric disorders, and older adults, focusing on interventions with sound evidence for improving activity and participation outcomes; (iv) an overview of considerations for sustainable implementation of neuropsychological interventions as 'core business'; and finally, (v) a call to action., (© 2023. The Author(s).)

For people living with psychosis, cognitive impairment is common and can have significant impacts for functional recovery, impacting engagement with treatment and quality of life more broadly. There is now strong evidence for the effectiveness of cognition-focused treatments, such as cognitive remediation to improve clinical and functional outcomes for people with psychosis. However, engagement with treatment has been a long-standing issue in mental health care, including for people with psychosis, who often experience difficulties with motivation. While research on clinical effectiveness of cognition-focused treatment is growing, to date there has been little research focused on the implementation of such treatments and it is not clear how best to support uptake and engagement across diverse mental health settings. Implementation science is the study of methods and strategies to promote the adoption, application, and maintenance of evidence-based practices in routine care. To integrate cognition-focused treatments into routine practice, and improve engagement with treatment and the quality and effectiveness of care for people with psychosis, researchers need to embrace implementation science and research. This paper provides a succinct overview of the field of implementation science, current evidence for implementation of cognition-focused treatments for psychosis and practical guidance for using implementation science in clinical research. The future of psychosis research includes multidisciplinary teams of clinical researchers and implementation scientists, working together with providers and consumers to build the evidence that can improve the implementation of cognition-focused treatments.

Background: Studies investigating cognitive impairments in psychosis and depression have typically compared the average performance of the clinical group against healthy controls (HC), and do not report on the actual prevalence of cognitive impairments or strengths within these clinical groups. This information is essential so that clinical services can provide adequate resources to supporting cognitive functioning. Thus, we investigated this prevalence in individuals in the early course of psychosis or depression., Methods: A comprehensive cognitive test battery comprising 12 tests was completed by 1286 individuals aged 15-41 (mean age 25.07, s.d. 5.88) from the PRONIA study at baseline: HC ( N = 454), clinical high risk for psychosis (CHR; N = 270), recent-onset depression (ROD; N = 267), and recent-onset psychosis (ROP; N = 295). Z-scores were calculated to estimate the prevalence of moderate or severe deficits or strengths (>2 s.d. or 1-2 s.d. below or above HC, respectively) for each cognitive test., Results: Impairment in at least two cognitive tests was as follows: ROP (88.3% moderately, 45.1% severely impaired), CHR (71.2% moderately, 22.4% severely impaired), ROD (61.6% moderately, 16.2% severely impaired). Across clinical groups, impairments were most prevalent in tests of working memory, processing speed, and verbal learning. Above average performance (>1 s.d.) in at least two tests was present for 40.5% ROD, 36.1% CHR, 16.1% ROP, and was >2 SDs in 1.8% ROD, 1.4% CHR, and 0% ROP., Conclusions: These findings suggest that interventions should be tailored to the individual, with working memory, processing speed, and verbal learning likely to be important transdiagnostic targets.

The drivers of cognitive change following first-episode psychosis remain poorly understood. Evidence regarding the role of antipsychotic medication is primarily based on naturalistic studies or clinical trials without a placebo arm, making it difficult to disentangle illness from medication effects. A secondary analysis of a randomised, triple-blind, placebo-controlled trial, where antipsychotic-naive patients with first-episode psychotic disorder were allocated to receive risperidone/paliperidone or matched placebo plus intensive psychosocial therapy for 6 months was conducted. A healthy control group was also recruited. A cognitive battery was administered at baseline and 6 months. Intention-to-treat analysis involved 76 patients (antipsychotic medication group: 37; 18.6 Mage [2.9] years; 21 women; placebo group: 39; 18.3 Mage [2.7]; 22 women); and 42 healthy controls (19.2 Mage [3.0] years; 28 women). Cognitive performance predominantly remained stable (working memory, verbal fluency) or improved (attention, processing speed, cognitive control), with no group-by-time interaction evident. However, a significant group-by-time interaction was observed for immediate recall (p = 0.023), verbal learning (p = 0.024) and delayed recall (p = 0.005). The medication group declined whereas the placebo group improved on each measure (immediate recall: p = 0.024; η p 2  = 0.062; verbal learning: p = 0.015; η p 2  = 0.072 both medium effects; delayed recall: p = 0.001; η p 2  = 0.123 large effect). The rate of change for the placebo and healthy control groups was similar. Per protocol analysis (placebo n = 16, medication n = 11) produced similar findings. Risperidone/paliperidone may worsen verbal learning and memory in the early months of psychosis treatment. Replication of this finding and examination of various antipsychotic agents are needed in confirmatory trials. Antipsychotic effects should be considered in longitudinal studies of cognition in psychosis.Trial registration: Australian New Zealand Clinical Trials Registry ( http://www.anzctr.org.au/ ; ACTRN12607000608460)., (© 2023. The Author(s).)

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., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Objective: To develop targeted treatment for young people experiencing mental illness, a better understanding of the biological, psychological, and social changes is required, particularly during the early stages of illness. To do this, large datasets need to be collected using standardized methods. A harmonized data collection protocol was tested in a youth mental health research setting to determine its acceptability and feasibility., Method: Eighteen participants completed the harmonization protocol, including a clinical interview, self-report measures, neurocognitive measures, and mock assessments of magnetic resonance imaging (MRI) and blood. The feasibility of the protocol was assessed by recording recruitment rates, study withdrawals, missing data, and protocol deviations. Subjective responses from participant surveys and focus groups were used to examine the acceptability of the protocol., Results: Twenty-eight young people were approached, 18 consented, and four did not complete the study. Most participants reported positive subjective impressions of the protocol as a whole and showed interest in participating in the study again, if given the opportunity. Participants generally perceived the MRI and neurocognitive tasks as interesting and suggested that the assessment of clinical presentation could be shortened., Conclusion: Overall, the harmonized data collection protocol appeared to be feasible and generally well-accepted by participants. With a majority of participants finding the assessment of clinical presentation too long and repetitive, the authors have made suggestions to shorten the self-reports. The broader implementation of this protocol could allow researchers to create large datasets and better understand how psychopathological and neurobiological changes occur in young people with mental ill-health., (© 2022 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Both psychotic illness and subclinical psychosis-like experiences (PLEs) have been associated with cortico-striatal dysfunction. This work has largely relied on a discrete parcellation of the striatum into distinct functional areas, but recent evidence suggests that the striatum comprises multiple overlapping and smoothly varying gradients (i.e., modes) of functional organization. Here, we investigated two of these functional connectivity modes, previously associated with variations in the topographic patterning of cortico-striatal connectivity (first-order gradient), and dopaminergic innervation of the striatum (second-order gradient), and assessed continuities in striatal function from subclinical to clinical domains. We applied connectopic mapping to resting-state fMRI data to obtain the first-order and second-order striatal connectivity modes in two distinct samples: (1) 56 antipsychotic-free patients (26 females) with first-episode psychosis (FEP) and 27 healthy controls (17 females); and (2) a community-based cohort of 377 healthy individuals (213 females) comprehensively assessed for subclinical PLEs and schizotypy. The first-order "cortico-striatal" and second-order "dopaminergic" connectivity gradients were significantly different in FEP patients compared to controls bilaterally. In the independent sample of healthy individuals, variations in the left first-order "cortico-striatal" connectivity gradient were associated with inter-individual differences in a factor capturing general schizotypy and PLE severity. The presumed cortico-striatal connectivity gradient was implicated in both subclinical and clinical cohorts, suggesting that variations in its organization may represent a neurobiological trait marker across the psychosis continuum. Disruption of the presumed dopaminergic gradient was only noticeable in patients, suggesting that neurotransmitter dysfunction may be more apparent to clinical illness., (© 2023. The Author(s).)

Background: Despite reports of altered brain morphology in established bipolar disorder (BD), there is limited understanding of when these morphological abnormalities emerge. Assessment of patients during the early course of illness can help to address this gap, but few studies have examined surface-based brain morphology in patients at this illness stage., Methods: We completed a secondary analysis of baseline data from a randomised control trial of BD individuals stabilised after their first episode of mania (FEM). The magnetic resonance imaging scans of n = 35 FEM patients and n = 29 age-matched healthy controls were analysed. Group differences in cortical thickness, surface area and gyrification were assessed at each vertex of the cortical surface using general linear models. Significant results were identified at p < 0.05 using cluster-wise correction., Results: The FEM group did not differ from healthy controls with regards to cortical thickness or gyrification. However, there were two clusters of increased surface area in the left hemisphere of FEM patients, with peak coordinates falling within the lateral occipital cortex and pars triangularis., Conclusions: Cortical thickness and gyrification appear to be intact in the aftermath of a first manic episode, whilst cortical surface area in the inferior/middle prefrontal and occipitoparietal cortex is increased compared to age-matched controls. It is possible that increased surface area in the FEM group is the outcome of abnormalities in a premorbidly occurring process. In contrast, the findings raise the hypothesis that cortical thickness reductions seen in past studies of individuals with more established BD may be more attributable to post-onset factors., Competing Interests: Declaration of Competing Interest Dr. Van Rheenen has received grants unrelated to the current study from Club Melbourne, the Henry Freeman Trust, Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation and the Society of Mental Health Research. Professor Berk has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Astra Zeneca, Lundbeck, Merck, Pfizer, and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Lundbeck Merck, Pfizer and Servier. Prof Yücel also received philanthropic donations from the David Winston Turner Endowment Fund, Wilson Foundation, as well as payments in relation to court-, expert witness-, and/or expert review-reports; the funding sources had no role in the design, management, data analysis, presentation, or interpretation and write-up of the data. Professor Pantelis has been on advisory boards for AstraZeneca, Janssen-Cilag, Lundbeck and Servier; and he has received honoraria for talks presented at educational meetings organized by AstraZeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Pfizer and Shire. Prof Cotton, Dr. Dandash, Miss Ringin, Miss Cooper, Dr. Daglas-Georgiou, A/Prof Allott, Dr. Chye, Dr. Suo, Dr. MacNeil, Dr. Hasty, Dr. Hallam, Prof McGorry and Prof Fornito do not have any disclosures., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation. We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET. Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients. Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: Cognitive Adaptation Training (CAT) is a psychosocial intervention with demonstrated effectiveness. However, no validated fidelity instrument is available. In this study, a CAT Fidelity Scale was developed and its psychometric properties, including interrater reliability and internal consistency, were evaluated., Methods: The fidelity scale was developed in a multidisciplinary collaboration between international research groups using the Delphi method. Four Delphi rounds were organized to reach consensus for the items included in the scale. To examine the psychometric properties of the scale, data from a large cluster randomized controlled trial evaluating the implementation of CAT in clinical practice was used. Fidelity assessors conducted 73 fidelity reviews at four mental health institutions in the Netherlands., Results: After three Delphi rounds, consensus was reached on a 44-item CAT Fidelity Scale. After administration of the scale, 24 items were removed in round four resulting in a 20-item fidelity scale. Psychometric properties of the 20-item CAT Fidelity Scale shows a fair interrater reliability and an excellent internal consistency., Conclusions: The CAT fidelity scale in its current form is useful for both research purposes as well as for individual health professionals to monitor their own adherence to the protocol. Future research needs to focus on improvement of items and formulating qualitative anchor point to the items to increase generalizability and psychometric properties of the scale. The described suggestions for improvement provide a good starting point for further development., Competing Interests: None., (© 2022 The Authors.)

Cognitive impairment is a well-documented predictor of transition to a full-threshold psychotic disorder amongst individuals at ultra-high risk (UHR) for psychosis. However, less is known about whether change in cognitive functioning differs between those who do and do not transition. Studies to date have not examined trajectories in intelligence constructs (e.g., acquired knowledge and fluid intelligence), which have demonstrated marked impairments in individuals with schizophrenia. This study aimed to examine intelligence trajectories using longitudinal data spanning an average of eight years, where some participants completed assessments over three time-points. Participants (N = 139) at UHR for psychosis completed the Wechsler Abbreviated Scale of Intelligence (WASI) at each follow-up. Linear mixed-effects models mapped changes in WASI Full-Scale IQ (FSIQ) and T-scores on Vocabulary, Similarities, Block Design, and Matrix Reasoning subtests. The sample showed stable and improving trajectories for FSIQ and all subtests. There were no significant differences in trajectories between those who did and did not transition to psychosis and between individuals with good and poor functional outcomes. However, although not significant, the trajectories of the acquired knowledge subtests diverged between transitioned and non-transitioned individuals (β = -0.12, 95 % CI [-0.29, 0.05] for Vocabulary and β = -0.14, 95 % CI [-0.33, 0.05] for Similarities). Overall, there was no evidence for long-term deterioration in intelligence trajectories in this UHR sample. Future studies with a larger sample of transitioned participants may be needed to explore potential differences in intelligence trajectories between UHR transition groups and other non-psychosis outcomes., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Cognitive deficits are recognized features of depressive disorders in youth aged 12-25. These deficits are distressing, predict functional impairment and limit the effectiveness of psychological therapies. Cognitive enhancement using behavioural, biochemical or physical treatments may be useful in young people with depression, but studies have not been synthesized. The aim was to systematically review the evidence for treatments for objective and subjective cognitive functioning, and their acceptability and functional outcomes in people aged 12-25 with depression., Method: Three electronic databases were searched for articles using pre-specified criteria. Pharmacological treatments were not eligible. Risk of bias was rated using the Cochrane Collaboration's revised risk-of-bias tool. Dual full-text article screening, data extraction and quality ratings were completed., Results: Twelve studies were included for review (median participant age: 20.39 years), five of which were randomized-controlled trials (RCTs). Sample sizes were generally small (median = 23; range: 9-46). Eight studies investigated behavioural treatments including aerobic exercise, cognitive training and education or strategy-based methods. Four studies examined repetitive transcranial magnetic brain stimulation (rTMS). Most behavioural treatments revealed preliminary evidence of improved cognitive function in youth depression. Consent rates were greatest for exercise- and education-based approaches, which may indicate higher acceptability levels. Findings from rTMS trials were mixed, with only half showing cognitive improvement. Functional outcomes were reported by three behavioural treatment trials and one rTMS trial, with functional improvement reported only in the former. Some concern of risk of bias was found in each RCT., Conclusion: Behavioural treatments, such as exercise, cognitive training and education/strategy-focused techniques, show encouraging results and appear to be acceptable methods of addressing cognitive deficits in youth depression based on participation rates. Brain stimulation and biochemical treatments (e.g., nutrient-based treatment) require further investigation., (© 2021 John Wiley & Sons Australia, Ltd.)

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 ( η p 2 = 0.09) and BACS composite score ( η p 2 = 0.21). After repeating the analyses without individuals who transitioned, motor speed was no longer significant ( η p 2 = 0.02), but the composite score remained significant ( η p 2 = 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.