Search

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).)

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).)

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.)

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.

Cognitive impairments in psychosis negatively impact functional recovery and quality of life. Existing interventions for improving cognitive impairment in recent-onset psychosis show inconsistent treatment efficacy, small effects, suboptimal engagement and limited generalizability to daily life functioning. In this perspective we explore how digital technology has the potential to address these limitations in order to improve cognitive and functional outcomes in recent-onset psychosis. Computer programs can be used for standardized, automated delivery of cognitive remediation training. Virtual reality provides the opportunity for learning and practicing cognitive skills in real-world scenarios within a virtual environment. Smartphone apps could be used for notification reminders for everyday tasks to compensate for cognitive difficulties. Internet-based technologies can offer psychoeducation and training materials for enhancing cognitive skills. Early findings indicate some forms of digital interventions for cognitive enhancement can be effective, with well-established evidence for human-supported computer-based cognitive remediation in recent-onset psychosis. Emerging evidence regarding virtual reality is favorable for improving social cognition. Overall, blending digital interventions with human support improves engagement and effectiveness. Despite the potential of digital interventions for enhancing cognition in recent-onset psychosis, few studies have been conducted to date. Implementation challenges affecting application of digital technologies for cognitive impairment in recent-onset psychosis are sustained engagement, clinical integration, and lack of quality in the commercial marketplace. Future opportunities lie in including motivational frameworks and behavioral change interventions, increasing service engagement in young people and lived experience involvement in digital intervention development., Competing Interests: The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© 2022 The Authors.)

Background: Cognitive deficits are associated with poor functional outcomes in individuals recovering from a first episode of psychosis (FEP). Existing treatments that target cognitive deficits in FEP may enhance cognitive function, but improvements to real-world functioning are less consistent. Furthermore, these treatments may not adequately address the personal recovery goals of young people attending FEP services. A novel cognitive strengths-based approach may overcome these shortcomings., Methods: This qualitative study used semi-structured interviews to explore clinicians' (N = 12) perspectives toward the potential development of a cognitive strengths-based assessment or treatment in FEP. The interviews were analysed using thematic analysis., Results: Five higher-order themes emerged: (1) pro-strengths attitude despite unfamiliarity and minimal use, (2) default to a cognitive deficit lens, (3) potential benefits of a cognitive strengths approach, (4) potential risks and barriers, and (5) considerations for successful implementation. While clinicians acknowledged their current deficit approach, they supported implementing a cognitive strengths assessment or treatment and highlighted their potential benefits for the personal recovery needs of young people with FEP., Conclusions: These findings suggest that a deficit-focused approach to cognitive function amongst clinicians may be common practice in FEP services. Nevertheless, a cognitive strengths approach was viewed favourably by clinicians and may represent a novel method of supporting personal recovery. Thus, the design and implementation of a cognitive strengths approach may be worthwhile. Future exploration of other stakeholder perspectives, such as young people with FEP, is essential., (© 2021. The Author(s).)

We aimed to (1) examine decisional capacity for treatment in young people (aged 15 to 25 years) with first-episode psychosis (FEP), Major Depressive Disorder (MDD) and no mental disorder, and (2) determine which theoretically relevant factors are associated with, and predict decisional capacity. We assessed decisional capacity (using MacArthur Competence Assessment Tool-Treatment; MacCAT-T), cognitive abilities, insight and symptom severity in young people with no mental disorder ( n  = 38), MDD ( n  = 38) and FEP ( n  = 18) from inpatient and outpatient services. Most young people with MDD (84.2%) or no mental disorder (86.8%) had adequate decisional capacity to consent to treatment based on recommended cut-off scores, compared with fewer than half of the those with FEP (44.4%). Levels of capacity were not significantly different between young people with MDD and those with no mental disorder ( p  = .861). However, young people with FEP demonstrated significantly poorer decisional capacity than those with no mental disorder ( p  = .006) and MDD ( p  = .009). A hierarchical regression analysis suggested that differences may be better explained by variation in cognitive ability, especially thematic verbal recall. Greater symptom severity and poorer insight were associated with poorer decisional capacity for FEP ( p  = .008 and p  < .001, respectively), but not MDD ( p  = .050 and p  = .805, respectively). Cognitive performance (i.e., predicted IQ, processing speed, mental flexibility and thematic verbal memory) collectively explained 36.6% of the variance in decisional capacity ( p  < .001). Thematic verbal memory was the strongest predictor of decisional capacity ( p  < .001). Supports for memory should be implemented to facilitate involvement in treatment decisions during the early course of illness., Competing Interests: None of the authors have any conflicts to declare., (© 2021 Published by Elsevier Inc.)

Background: The high prevalence of smoking in individuals who are at ultra-high risk (UHR) for psychosis is well known and moderate cognitive deficits have also been found in UHR. However, the association between smoking and cognition in UHR is unknown and longitudinal studies are lacking., Method: A cohort study with 330 UHR individuals and 66 controls was conducted, as part of the European network of national schizophrenia networks studying gene-environment interactions (EU-GEI). At baseline and after 6, 12, and 24 months, smoking behavior was assessed with the Composite International Diagnostic Interview and cognitive functioning with a comprehensive test battery. Linear mixed-effects analyses were used to examine the multicross-sectional and prospective associations between (change in) smoking behavior and cognitive functioning, accounting for confounding variables., Results: At baseline, 53% of UHR and 27% of controls smoked tobacco. Smoking UHR and controls did not significantly differ from nonsmoking counterparts on the tested cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, or reasoning/problem solving) across different assessment times. Neither smoking cessation nor initiation was associated with a significant change in cognitive functioning in UHR., Conclusions: No associations were found between smoking and cognitive impairment in UHR nor in controls. However, the fact that one in every two UHR individuals report daily use of tobacco is alarming. Our data suggest that UHR have fewer cognitive impairments and higher smoking cessation rates compared to patients with first-episode psychosis found in literature. Implications to promote smoking cessation in the UHR stage need further investigation.

Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.

Cognitive impairments are a core feature of first-episode psychosis (FEP), arising before illness onset and antipsychotic exposure. Individuals with chronic psychosis experience poorer physical health while taking antipsychotic medication, but health disparities may be evident at FEP onset, prior to antipsychotic exposure. Given the links between cognition and physical health in healthy populations, the aim was to explore whether cognition and physical health are associated in FEP, which could inform early physical health interventions for cognition in FEP. Participants were aged 15 to 25 and included 86 individuals experiencing FEP with limited antipsychotic exposure and duration of untreated psychosis of ≤six months, and 43 age- and sex-matched controls. Individuals with FEP performed significantly poorer than controls in most cognitive domains (Cohen's d  = 0.38 to 1.59). Groups were similar in metabolic health measures, excluding a significantly faster heart rate in FEP ( d  = 0.68). Through hierarchical regression analyses, we found that in the overall sample, BMI was negatively related to current IQ after controlling for education and group (FEP/control). Relationships between BMI and cognition were consistent across the FEP and healthy control groups. In FEP, current IQ and working memory were negatively correlated with lipid profiles. Findings suggest that in FEP, impaired cognition is exhibited earlier than physical health problems, and that compared to controls, similar relationships with cognition are demonstrated. Causal pathways and trajectories of relationships between health and cognition in FEP require investigation, especially as antipsychotic medications are introduced. The findings have implications for cognitive and health interventions., Competing Interests: MB 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 – all unrelated to this work. In the past 3 years, CP served on an advisory board for Lundbeck, Australia Pty Ltd. He has received honoraria for talks presented at educational meetings organized by Lundbeck. He received a grant from Lundbeck Foundation. His work is funded by grants and fellowship from the National Health & Medical Research Council (NHMRC) of Australia. The authors have declared that there are no conflicts of interest in relation to the subject of this study., (© 2021 The Author(s).)

Background: Subjective cognitive difficulties are common in mental illness and have a negative impact on role functioning. Little is understood about subjective cognition and the longitudinal relationship with depression and anxiety symptoms in young people., Aims: To examine the relationship between changes in levels of depression and anxiety and changes in subjective cognitive functioning over 3 months in help-seeking youth., Method: This was a cohort study of 656 youth aged 12-25 years attending Australian headspace primary mental health services. Subjective changes in cognitive functioning (rated as better, same, worse) reported after 3 months of treatment was assessed using the Neuropsychological Symptom Self-Report. Multivariate multinomial logistic regression analysis was conducted to evaluate the impact of baseline levels of and changes in depression (nine-item Patient Health Questionnaire; PHQ9) and anxiety symptoms (seven-item Generalised Anxiety Disorder scale; GAD7) on changes in subjective cognitive function at follow-up while controlling for covariates., Results: With a one-point reduction in PHQ9 at follow-up, there was an estimated 11-18% increase in ratings of better subjective cognitive functioning at follow-up, relative to stable cognitive functioning. A one-point increase in PHQ9 from baseline to follow-up was associated with 7-14% increase in ratings of worse subjective cognitive functioning over 3 months, relative to stable cognitive functioning. A similar attenuated pattern of findings was observed for the GAD7., Conclusions: A clear association exists between subjective cognitive functioning outcomes and changes in self-reported severity of affective symptoms in young people over the first 3 months of treatment. Understanding the timing and mechanisms of these associations is needed to tailor treatment.

Objective: Cognitive compensatory interventions aim to alleviate psychosocial disability by targeting functioning directly using aids and strategies, thereby minimizing the impact of cognitive impairment. The aim was to conduct a systematic review and meta-analysis of cognitive compensatory interventions for psychosis by examining the effects on functioning and symptoms, and exploring whether intervention factors, study design, and age influenced effect sizes., Methods: Electronic databases (Ovid Medline, PsychINFO) were searched up to October 2018. Records obtained through electronic and manual searches were screened independently by two reviewers according to selection criteria. Data were extracted to calculate estimated effects (Hedge's g) of treatment on functioning and symptoms at post-intervention and follow-up. Study quality was assessed using Cochrane Collaboration's risk of bias tool., Results: Twenty-six studies, from 25 independent randomized controlled trials (RCTs) were included in the meta-analysis (1654 participants, mean age = 38.9 years, 64% male). Meta-analysis revealed a medium effect of compensatory interventions on functioning compared to control conditions (Hedge's g = 0.46, 95% CI = 0.33, 0.60, P < .001), with evidence of relative durability at follow-up (Hedge's g = 0.36, 95% CI = 0.19, 0.54, P < .001). Analysis also revealed small significant effects of cognitive compensatory treatment on negative, positive, and general psychiatric symptoms, but not depressive symptoms. Estimated effects did not significantly vary according to treatment factors (ie, compensatory approach, dosage), delivery method (ie, individual/group), age, or risk of bias. Longer treatment length was associated with larger effect sizes for functioning outcomes. No evidence of publication bias was identified., Conclusion: Cognitive compensatory interventions are associated with robust, durable improvements in functioning in people with psychotic illnesses., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The clinical onset of borderline personality disorder (BPD) usually occurs in young people (aged 12-25 years) and commonly leads to difficulty achieving and maintaining vocational (education and/or employment) engagement. While current psychosocial interventions lead to improvements in psychopathology, they have little effect upon functioning. Individual Placement and Support (IPS) is a client-driven model that assists individuals with severe mental illness to engage with education and/or employment appropriate to their personal goals, and that provides ongoing support to maintain this engagement. The objective of the INdividual Vocational and Educational Support Trial (INVEST) is to evaluate the effectiveness of adding IPS to an evidence-based early intervention programme for BPD, with the aim of improving vocational outcomes., Methods/design: INVEST is a single-blind, parallel-groups, randomised controlled trial (RCT). The randomisation is stratified by gender and age and uses random permuted blocks. The interventions are 39 weeks of either IPS, or 'usual vocational services' (UVS). Participants will comprise 108 help-seeking young people (aged 15-25 years) with three or more DSM-5 BPD features and a desire to study or work, recruited from the Helping Young People Early (HYPE) early intervention programme for BPD at Orygen, in Melbourne, Australia. All participants will receive the HYPE intervention. After baseline assessment, staff who are blind to the intervention group allocation will conduct assessments at 13, 26, 39 and 52 weeks. At the 52-week primary endpoint, the primary outcome is the number of days in mainstream education/employment since baseline. Secondary outcomes include the cost-effectiveness of the intervention, quality of life, and BPD severity., Discussion: Current treatments for BPD have little impact on vocational outcomes and enduring functional impairment is prevalent among this patient group. IPS is a targeted functional intervention, which has proven effective in improving vocational outcomes for adults and young people with psychotic disorders. This trial will investigate whether IPS is effective for improving vocational (employment and educational) outcomes among young people with subthreshold or full-syndrome BPD., Trial Registration: Australian New Zealand Clinical Trials Registry, ID: ACTRN12619001220156 . 13 September 2019.

Background: Specialized early intervention services for first-episode psychosis have been well established in many countries to meet the unique needs of this group. However, with high drop-out rates, these services would benefit from understanding the factors that influence a person's decision to engage with, or disengage from, them. No research has explored the experiences of engagement and disengagement over time, from the perspectives of the person who experienced a first-episode psychosis, their caregiver, and their clinician. This information is crucial to help services better respond to the needs of the people using them. The aim of this study was to understand what causes and maintains periods of disengagement from early intervention services for first-episode psychosis over time., Methods: Using a longitudinal, qualitative approach, young people, their caregivers, and their clinicians were followed through their first year with an early intervention service for first-episode psychosis in Melbourne, Australia. Qualitative interviews were completed between 3-9 weeks, 4-7 months, and 11-15 months after entry to the service (or at discharge if earlier). Trajectory analysis was used to understand the data., Results: Qualitative interviews were conducted with 24 participants (55 interviews). Young people were aged 15-24 years, came from a variety of cultural backgrounds and had various psychotic diagnoses. Three major processes were identified that, over time, led to periods of service disengagement: a mismatch between service model and individual presentation (service mismatch), a lack of shared purpose (aimless engagement), and responses to individual circumstances (reactive disengagement)., Conclusion: Triangulating experiences of engagement across young people, caregivers, and clinicians allows for a comprehensive understanding of what precipitates service disengagement. This study demonstrates how early intervention services for first-episode psychosis are meeting the needs of young people and caregivers, and what areas warrant improvement. The needs of service users and patterns of disengagement vary. In turn, services must be flexible and responsive to individual circumstances. The results of this study recommend that local and international policies move away from diagnostically driven models of care, to better provide an inclusive treatment service for people with transdiagnostic mental health presentations., (Copyright © 2020 Tindall, Simmons, Allott and Hamilton.)

Background: A key component of case-management in early intervention services for first-episode psychosis is engaging a person with the service and building a relationship from which therapy and treatment can be facilitated. The aim of this study was to understand how case-managers at an early intervention service experience the process of engagement and working with varying levels of attendance and participation., Methods: Qualitative interviews were conducted with the case-managers of nine young people treated at an early intervention service for first-episode psychosis within 6 months of treatment entry. Interviews discussed the process of working with the young person and factors that influenced service engagement. Interviews were analyzed using thematic analysis., Results: Case-managers described a range of influences on engagement which were grouped under the themes: young person and caregiver influences on engagement, case-manager influences on engagement, and influences of the early intervention service system on engagement. The experience of engagement was described as relational, however it occurred in the context of broader influences, some of which were unable to be changed or challenged by the case-manager (e.g., resource allocation, models of treatment, young person demographics)., Conclusion: This study illustrates the challenges that case-managers face when working with young people with first-episode psychosis, and the direct influence this has on engagement with treatment. Understanding these challenges and addressing them in policy and service design may lead to improvements in young peoples' recovery from first-episode psychosis and increase case-manager job satisfaction.

The role of nutrition in mental health is becoming increasingly acknowledged. Along with dietary intake, nutrition can also be obtained from "nutrient supplements", such as polyunsaturated fatty acids (PUFAs), vitamins, minerals, antioxidants, amino acids and pre/probiotic supplements. Recently, a large number of meta-analyses have emerged examining nutrient supplements in the treatment of mental disorders. To produce a meta-review of this top-tier evidence, we identified, synthesized and appraised all meta-analyses of randomized controlled trials (RCTs) reporting on the efficacy and safety of nutrient supplements in common and severe mental disorders. Our systematic search identified 33 meta-analyses of placebo-controlled RCTs, with primary analyses including outcome data from 10,951 individuals. The strongest evidence was found for PUFAs (particularly as eicosapentaenoic acid) as an adjunctive treatment for depression. More nascent evidence suggested that PUFAs may also be beneficial for attention-deficit/hyperactivity disorder, whereas there was no evidence for schizophrenia. Folate-based supplements were widely researched as adjunctive treatments for depression and schizophrenia, with positive effects from RCTs of high-dose methylfolate in major depressive disorder. There was emergent evidence for N-acetylcysteine as a useful adjunctive treatment in mood disorders and schizophrenia. All nutrient supplements had good safety profiles, with no evidence of serious adverse effects or contraindications with psychiatric medications. In conclusion, clinicians should be informed of the nutrient supplements with established efficacy for certain conditions (such as eicosapentaenoic acid in depression), but also made aware of those currently lacking evidentiary support. Future research should aim to determine which individuals may benefit most from evidence-based supplements, to further elucidate the underlying mechanisms., (© 2019 World Psychiatric Association.)

It remains unclear whether the onset of psychosis is associated with deterioration in cognitive performance. The aim of this study was to examine the course of cognitive performance in an ultrahigh risk (UHR) cohort, and whether change in cognition is associated with transition to psychosis and change in functioning. Consecutive admissions to Personal Assessment and Crisis Evaluation (PACE) Clinic between May 1994 and July 2000 who had completed a comprehensive cognitive assessment at baseline and follow-up were eligible (N = 80). Follow-up ranged from 7.3 to 13.4 years (M = 10.4 years; SD = 1.5). In the whole sample, significant improvements were observed on the Similarities (P = .03), Information (P < .01), Digit Symbol Coding (P < .01), and Trail Making Test-B (P = .01) tasks, whereas performance on the Rey Auditory Verbal Learning Test (Trials 1-3) declined significantly (P < .01) over the follow-up period. Change in performance on cognitive measures was not significantly associated with transition status. Taking time to transition into account, those who transitioned after 1 year showed significant decline on Digit Symbol Coding, whereas those who did not transition improved on this measure (P = .01; effect size [ES] = 0.85). Small positive correlations were observed between improvements in functioning and improvements in performance on Digit Symbol Coding and Arithmetic (0.24, P = .03 and 0.28, P = .01, respectively). In summary, the onset of psychosis was not associated with deterioration in cognitive ability. However, specific findings suggest that immediate verbal learning and memory, and processing speed may be relevant domains for future risk models and early intervention research in UHR individuals., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Research suggests that young people with major depressive disorder (MDD) experience neurocognitive deficits and that these are associated with poorer functional and clinical outcomes. However, we are yet to understand how young people experience such difficulties. The aim of the current study was to explore the subjective experiences of neurocognitive functioning among young people with MDD., Methods: Semi-structured qualitative interviews were conducted with 11 young people (aged 17-24 years) attending a specialist clinic for youth experiencing moderate-severe depression. Interview transcripts were analysed via Thematic Analysis to identify patterns and themes representing how young people with MDD subjectively experience neurocognitive deficits., Results: Five main themes were identified: (1) experience of neurocognitive complaints; (2) relationship between neurocognitive complaints and depression; (3) impact on functioning; (4) strategies and supports; and (5) neurocognitive complaints and treatment. Overall, young people with MDD commonly experienced a range of subjective neurocognitive complaints. These appeared to have a bidirectional relationship with depressive symptomatology and significantly disrupted vocational, social and independent functioning, and aspects of psychological well-being including self-esteem. Neurocognitive difficulties represented an experiential barrier to psychological therapeutic engagement and were perceived as variably responsive to psychotropic medications, highlighting the need for targeted intervention., Discussion: Neurocognitive difficulties are a common and pervasive experience for young people with MDD, with perceived impacts on depressive symptoms, attitudinal beliefs, everyday functioning and therapeutic engagement. Subjective neurocognitive complaints may therefore contribute to or exacerbate personal challenges faced by young people with MDD and thus, require early identification, consideration in psychological formulation, and treatment. Further research into the mechanisms of neurocognitive impairment in MDD is also needed.

Background: High unemployment is a hallmark of psychotic illness. Individual placement and support (IPS) may be effective at assisting the vocational recoveries of young people with first-episode psychosis (FEP).AimsTo examine the effectiveness of IPS at assisting young people with FEP to gain employment (Australian and Clinical Trials Registry ACTRN12608000094370)., Method: Young people with FEP (n = 146) who were interested in vocational recovery were randomised using computer-generated random permuted blocks on a 1:1 ratio to: (a) 6 months of IPS in addition to treatment as usual (TAU) or (b) TAU alone. Assessments were conducted at baseline, 6 months (end of intervention), 12 months and 18 months post-baseline by research assistants who were masked to the treatment allocations., Results: At the end of the intervention the IPS group had a significantly higher rate of having been employed (71.2%) than the TAU group (48.0%), odds ratio 3.40 (95% CI 1.17-9.91, z = 2.25, P = 0.025). However, this difference was not seen at 12- and 18-month follow-up points. There was no difference at any time point on educational outcomes., Conclusions: This is the largest trial to our knowledge on the effectiveness of IPS in FEP. The IPS group achieved a very high employment rate during the 6 months of the intervention. However, the advantage of IPS was not maintained in the long term. This seems to be related more to an unusually high rate of employment being achieved in the control group rather than a gross reduction in employment among the IPS group.Declaration of interestNone.

Background: The purpose of this study was to examine cognitive functioning in people following first-episode mania relative to a demographically similar healthy control group., Methods: Forty-one patients, who had recently stabilised from a first manic episode, and twenty-one healthy controls, were compared in an extensive cognitive assessment., Results: First-episode mania participants had significantly lower Full-Scale IQ (FSIQ) relative to healthy controls; however, this finding could be driven by premorbid differences in intellectual functioning. There were no significant differences between groups in Verbal IQ (VIQ) and Performance IQ (PIQ). First-episode mania participants performed significantly poorer than healthy controls in processing speed, verbal learning and memory, working memory, and cognitive flexibility with medium-to-large effects. There were no group differences in other measures of cognition., Conclusions: Participants following first-episode mania have poorer global intelligence than healthy controls, and have cognitive difficulties in some, but not all areas of cognitive functioning. This highlights the importance of early intervention and cognitive assessment in the early course of the disorder.

Background: Major depressive disorder (MDD) affects a quarter of adolescents and young adults and is associated with the greatest global burden of disease in this population. There is a growing literature, mostly in adults, showing that significant neurocognitive impairments are common in MDD. It remains unclear whether these impairments are pre-existing trait markers of MDD, state-related impairments that fluctuate with depressive symptoms, or 'scar' impairments that worsen with illness progression. The aim of this study is to provide a conceptual framework for understanding MDD and neurocognitive impairment in adolescence and young adulthood (ages 12-25 years)., Method: Examination of the evidence for neurocognitive deficits as trait, state, and scar features of MDD according to different study designs (family studies, premorbid studies, current depression, remitted depression, and longitudinal studies with repeated assessment) was conducted., Results: The few premorbid and family studies conducted in youth provide equivocal evidence for neurocognitive impairments as trait markers of MDD. The presence of state-based neurocognitive impairment remains unclear as evidence comes mostly from cross-sectional studies. There are a limited, but growing number of longitudinal studies with repeated neurocognitive assessment in youth. Studies that examined neurocognition prior to the onset of MDD and with long-term follow-up provide tentative evidence for neurocognitive scarring., Conclusion: Neurocognitive impairment is a feature of MDD in adolescents and young adults. To better understand the nature, timing, and pattern of impairment, longitudinal studies that examine neurocognition before and after the development of full-threshold MDD, including following recurrence are needed. This knowledge will have important implications for mechanisms, prevention, and treatment of MDD in youth.

There is evidence of cognitive impairment that persists in the remission phase of bipolar disorder; however, the extent of the deficits that occur from the first onset of the disorder remains unclear. This is the first systematic review on cognitive functioning in the early stages of bipolar I disorder. The aim of the study was to identify the patterns and degree of cognitive impairment that exists from first-episode mania. Three electronic databases (MEDLINE, PsycINFO and PubMed) were systematically searched for studies published from January 1980 to June 2014. Eligible studies were separated into two groups: acute and remission. The Newcastle-Ottawa quality assessment scale was utilised to measure the quality of the included studies. A total of seven studies (three acute and four remission), including 230 first-episode mania and 345 healthy control participants, were eligible for the review. The studies in the acute phase only examined aspects of executive functioning, with impairments identified in cognitive flexibility, though not in response inhibition and verbal fluency relative to healthy controls. The most consistent finding during the remission phase was a deficit in working memory, whereas in the other domains, the findings were equivocal. Non-verbal memory and verbal fluency were not impacted in remission from first-episode mania. In conclusion, deficits are present in some but not all areas of cognitive functioning during the early stages of bipolar I disorder. Further research is warranted to understand the longitudinal trajectory of change from first-episode mania.

Personalized medicine is rapidly becoming a reality in today's physical medicine. However, as yet this is largely an aspirational goal in psychiatry, despite significant advances in our understanding of the biochemical, genetic and neurobiological processes underlying major mental disorders. Preventive medicine relies on the availability of predictive tools; in psychiatry we still largely lack these. Furthermore, our current diagnostic systems, with their focus on well-established, largely chronic illness, do not support a pre-emptive, let alone a preventive, approach, since it is during the early stages of a disorder that interventions have the potential to offer the greatest benefit. Here, we present a clinical staging model for severe mental disorders and discuss examples of biological markers that have already undergone some systematic evaluation and that could be integrated into such a framework. The advantage of this model is that it explicitly considers the evolution of psychopathology during the development of a mental illness and emphasizes that progression of illness is by no means inevitable, but can be altered by providing appropriate interventions that target individual modifiable risk and protective factors. The specific goals of therapeutic intervention are therefore broadened to include the prevention of illness onset or progression, and to minimize the risk of harm associated with more complex treatment regimens. The staging model also facilitates the integration of new data on the biological, social and environmental factors that influence mental illness into our clinical and diagnostic infrastructure, which will provide a major step forward in the development of a truly pre-emptive psychiatry., (Copyright © 2014 World Psychiatric Association.)

Improving functional outcome, in addition to alleviating psychotic symptoms, is now a major treatment objective in schizophrenia research. Given the large body of evidence suggesting pharmacological treatments generally have minimal effects on indices of functioning, research has turned to psychosocial rehabilitation programs. Among these, neurocognitive and social cognitive interventions are at the forefront of this field and are argued to target core deficits inherent to the schizophrenia illness. However, to date, research trials have primarily focused on chronic schizophrenia populations, neglecting the early psychosis groups who are often as severely impaired in social and occupational functioning. This theoretical paper will outline the rationale for investigating adjunctive cognitive-based interventions in the early phases of psychotic illness, critically examine the current approach strategies used in these interventions, and assess the evidence supporting certain training programs for improving functional outcome in early psychosis. Potential pathways for future research will be discussed.