Cacciotti-Saija, C., Langdon, R., Ward, P. B., Hickie, I. B., Scott, E. M., Naismith, S. L., Moore, L., Alvares, G. A., Redoblado-Hodge, M. A., Guastella, A. J.

A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis

Social-cognitive deficits contribute to poor functional outcomes in early psychosis; however, no effective pharmacological treatments exist for these problems. This study was the first to investigate the efficacy of an extended treatment of oxytocin nasal spray combined with social cognition training (SCT) to improve social cognition, clinical symptoms, and social functioning in early psychosis. In a double-blind, randomized, placebo-controlled, between-subjects trial, 52 individuals (aged 16-35 years) diagnosed with an early psychosis schizophrenia-spectrum illness were recruited. Participants received oxytocin (24 International Units) or placebo nasal spray twice-daily for 6 weeks, combined with group SCT (2 × 1 hour weekly sessions for 6 weeks). An additional dose of oxytocin was administered before each weekly session. Assessments were conducted at baseline, post-treatment, and at 3-month follow-up. Primary outcomes included the Reading the Mind in the Eyes Test, the Scale for the Assessment of Positive and Negative Symptoms, and the Social Functioning Scale. Secondary outcomes included self-report and behavioral assessments of social cognition, symptom severity, and social functioning. Results showed that on all primary and secondary outcomes, there was no benefit of oxytocin nasal spray treatment in comparison to placebo. Exploratory post hoc analysis suggested that increased use of nasal spray was, however, associated with reductions in negative symptoms in the oxytocin condition only. This study represents the first evaluation of oxytocin treatment for early psychosis. Although results suggest no benefit of oxytocin treatment, results also highlight an urgent need to consider nasal spray delivery and dose-related variables for future clinical trials.; © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected].

Schizophrenia Bulletin, 41(2) : 483-493

Chang, W. C., Chan, G. H. K., Jim, O. T. T., Lau, E. S. K., Hui, C. L. M., Chan, S. K. W., Lee, E. H. M., Chen, E. Y. H.

Optimal duration of an early intervention programme for first-episode psychosis: randomised controlled trial

Background: Numerous early intervention services targeting young people with psychosis have been established, based on the premise that reducing treatment delay and providing intensive treatment in the initial phase of psychosis can improve long-term outcome.; Aims: To establish the effect of extending a specialised early intervention treatment for first-episode psychosis by 1 year.; Method: A randomised, single-blind controlled trial (NCT01202357) compared a 1-year extension of specialised early intervention with step-down care in patients who had all received a 2-year intensive early intervention programme for first-episode psychosis.; Results: Patients receiving an additional year of specialised intervention had better outcomes in functioning, negative and depressive symptoms and treatment default rate than those managed by step-down psychiatric care.; Conclusions: Extending the period of specialised early intervention is clinically desirable but may not be feasible in lower- income countries.; © The Royal College of Psychiatrists 2015.

British Journal of Psychiatry, 206(6) : 492-500

Chaves, C., Marque, C. R., Maia-de-Oliveira, J. P., Wichert-Ana, L., Ferrari, T. B., Santos, A. C., Araujo, D., Machado-de-Sousa, J. P., Bressan, R. A., Elkis, H., Crippa, J. A., Guimaraes, F. S., Zuardi, A. W., Baker, G. B., Dursun, S. M., Hallak, J. E.

Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia

Increasing evidence suggests that the tetracycline antibiotic minocycline has neuroprotective effects and is a potential treatment for schizophrenia. However, the mechanisms of action of minocycline in the CNS remain elusive. The aim of this study was to investigate the effects of minocycline on brain morphology and cerebral perfusion in patients with recent-onset schizophrenia after 12months of a randomized double-blind, placebo-controlled clinical trial of minocycline add-on treatment. This study included 24 outpatients with recent-onset schizophrenia randomized for 12months of adjuvant treatment with minocycline (200mg/d) or placebo. MRI (1.5T) and [99mTc]-ECD SPECT brain scans were performed at the end of the 12-month of trial. Between-condition comparisons of SPECT and MRI brain images were performed using statistical parametric mapping and analyzed by voxel-based morphometry (VBM). Minocycline adjuvant treatment significantly reduced positive and negative symptoms when compared with placebo. The VBM analysis of MRI scans showed that the patients in the placebo group had significant lower gray matter volumes in the midposterior cingulate cortex and in the precentral gyrus in comparison with the patients in the minocycline group. In addition, a decreased ECD uptake in the minocycline condition was observed in fronto-temporal areas. These results suggest that minocycline may protect against gray matter loss and modulate fronto-temporal areas involved in the pathophysiology of schizophrenia. Furthermore, minocycline add-on treatment may be a potential treatment in the early stages of schizophrenia and may ameliorate clinical deterioration and brain alterations observed in this period. (PsycINFO Database Record (c) 2015 APA, all rights reserved) (journal abstract).

Schizophrenia Research, 161(2- 3) : 439-445

Chen, E. Y., Chang, W. C., Chan, S. K., Lam, M. M., Hung, S. F., Chung, D. W., Hui, C. L., Wong, G. H., Au Yang, W. S., Tang, J. Y.

Three-year community case management for early psychosis: a randomised controlled study

Hong Kong Medical Journal, 21 : 23- 26

Conus, P., Berk, M., Cotton, S. M., Kader, L., Macneil, C., Hasty, M. K., Hallam, K., Lambert, M., Murphy, B. P., McGorry, P. D.

Olanzapine or chlorpromazine plus lithium in first episode psychotic mania: An 8-week randomised controlled trial

Background: Treatment strategies for mental disorders may vary according to illness stage. However no data currently exist to guide treatment in first episode psychotic mania. The aim of this study was to compare the safety and efficacy profile of chlorpromazine and olanzapine, as add-on to lithium, in patients with a first episode of psychotic mania, expecting better safety profile and adherence to olanzapine but similar efficacy for both treatments.; Methods: Data from 83 patients were collected in an 8-week randomised controlled trial on clinical variables, side effects, vital signs, and weight. Analyses of treatment differences over time were based on intent-to-treat principles. Kaplan-Meier estimated survival curves were used to analyse time-to-event data and mixed effects models repeated measures analysis of variance were used to determine treatment group differences over time on safety and efficacy measures.; Results: Ethics committee approval to delay informed consent procedure until recovery from the acute episode allowed the inclusion of 83 patients highly representative of those treated in the public sector. Contrary to our hypotheses, safety profile of both medications was similar. A signal for higher rate (P=.032) and earlier occurrence (P=.043) of mania remission was observed in the olanzapine group which did not survive correction for multiple comparisons.; Conclusions: Olanzapine and chlorpromazine have a similar safety profile in a uniquely representative cohort of patients with first episode psychotic mania. The possibility for a greater impact of olanzapine on manic symptoms leading to earlier remission of the episode needs exploration in a large sample.; Copyright © 2015 Elsevier Masson SAS. All rights reserved.

European Psychiatry, 30(8) : 975- 982

Barlati, S., De-Peri, L., Deste, G., Vita, A.

Non-pharmacological interventions in early schizophrenia: Focus on cognitive remediation

Objectives There is a growing body of evidence suggesting that barriers to functional recovery are associated with a host of neurocognitive impairments in both the early and later course of schizophrenia. Given the significant influence of cognitive functions on daily functioning, several cognitive training approaches have been developed to improve cognitive deficits in schizophrenia. Increasing amounts of data suggest that cognitive remediation leads to improvements not only in cognition, but also in functional outcomes of schizophrenia. Some researchers speculate that deficits in cognition are more amenable to remediation during earlier phases of the illness, rather than when chronicity has developed. Despite the widely cited benefits of cognitive remediation in long-term course patients, fewer studies have examined the extent to which cognitive remediation has practical implications in the early stages of schizophrenia. The aim of this paper is to review the available literature on cognitive remediation in the prodromal phase and the early course of schizophrenia. Methods This review summarizes findings of cognitive changes induced in the early course and the prodromal phases of schizophrenia by different cognitive remediation approaches. Electronic searches were performed in the PubMed database, and all the studies published until January 2013 have been taken in account. Controlled studies of cognitive training are discussed in more detail. Results Few studies on the effects of cognitive training programs have been conducted in first episode or in early schizophrenia, and only three studies have been conducted in the prodromal phase of the disease or in subjects at risk for psychosis. The studies available support the usefulness of cognitive remediation when applied in the early course of schizophrenia and in subjects at risk for the disease. Conclusions Although preliminary positive results have been achieved, more empirical research is needed to confirm the efficacy of cognitive remediation in the early course of schizophrenia, and future studies should address the issue of the usefulness of cognitive remediation in the prodromal phases of schizophrenia or in subjects at risk for psychosis.

Journal of Psychopathology, 21(1) : 1-12

Bond, G., Drake, R., Luciano, A.

Employment and educational outcomes in early intervention programmes for early psychosis: A systematic review

Aims: Young adults with early psychosis want to pursue normal roles - education and employment. This paper summarises the empirical literature on the effectiveness of early intervention programmes for employment and education outcomes. Methods: We conducted a systematic review of employment/education outcomes for early intervention programmes, distinguishing three programme types: (1) those providing supported employment, (2) those providing unspecified vocational services and (3) those without vocational services. We summarised findings for 28 studies. Results: Eleven studies evaluated early intervention programmes providing supported employment. In eight studies that reported employment outcomes separately from education outcomes, the employment rate during follow-up for supported employment patients was 49%, compared with 29% for patients receiving usual services. The two groups did not differ on enrolment in education. In four controlled studies, meta-analysis showed that the employment rate for supported employment participants was significantly higher than for control participants, odds ratio = 3.66 [1.93-6.93], p < 0.0001. Five studies (four descriptive and one quasi-experimental) of early intervention programmes evaluating unspecified vocational services were inconclusive. Twelve studies of early intervention programmes without vocational services were methodologically heterogeneous, using diverse methods for evaluating vocational/educational outcomes and precluding a satisfactory meta-analytic synthesis. Among studies with comparison groups, 7 of 11 (64%) reported significant vocational/education outcomes favouring early intervention over usual services. Conclusions: In early intervention programmes, supported employment moderately increases employment rates but not rates of enrolment in education. These improvements are in addition to the modest effects early programmes alone have on vocational/educational outcomes compared with usual services. (PsycINFO Database Record (c) 2015 APA, all rights reserved) (journal abstract).

Epidemiology & Psychiatric Sciences, 24(5) : 446- 457

Fernandez-Gonzalo, S., Turon, M., Jodar, M., Pousa, E., Hernandez-Rambla, C., García, R., Palao, Diego.

A new computerized cognitive and social cognition training specifically designed for patients with schizophrenia/schizoaffective disorder in early stages of illness: A pilot study

People with schizophrenia/schizoaffective disorders at early stages of the illness present cognitive and social cognition deficits that have a great impact in functional outcomes. Cognitive Remediation Therapy (CRT) has demonstrated consistent effect in cognitive performance, symptoms and psychosocial functioning. However, any CRT intervention or social cognition training have been specifically designed for patients in the early stages of psychosis. The aim of this pilot study is to assess the efficacy of a new computerized cognitive and social cognition program for patients with schizophrenia/schizoaffective disorder with recent diagnosis. A comprehensive assessment of clinical, social and non-social cognitive and functional measures was carried out in 53 randomized participants before and after the 4-months treatment. Significant results were observed in Spatial Span Forwards, Immediate Logical Memory and Pictures of Facial Affect (POFA) total score. None of these results were explained by medication, premorbid social functioning or psychopathological symptoms. No impact of the intervention was observed in other cognitive and social cognition outcome neither in clinical and functional outcomes. This new computerized intervention may result effective ameliorating visual attention, logical memory and emotional processing in patients in the early stages of schizophrenia/schizoaffective disorder.; Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Psychiatry Research, 228(3) : 501-509

Czepielewski, L. S., Sodre, L., Souza, A. C. L., Bucker, J., Burke, K. P., Cereser, K. M., Gama, C. S.

Changes in verbal learning of patients with schizophrenia: Results from a randomized, double-blind, placebo-controlled trial of amantadine adjunctive to antipsychotics [letter to editor]

Presents a study which aims to examine the changes in verbal learning of patients with schizophrenia (SZ) by presenting the results from a randomized, double-blind, placebo-controlled trial of amantadine adjunctive to antipsychotics. The present study suggests that amantadine may be a potential adjunctive treatment strategy for improving cognition through learning in recent onset patients with schizophrenia. A small sample size and short follow-up period are limitations of this study. report. However, given the compelling evidence of NMDA receptor role in the pathophysiology of SZ and its possible usefulness as adjunctive drug therapy for this disease, amantadine (AMT) might be a tool for cognitive enhancement through improvement of learning potential. Besides remission of psychotic symptoms, treatments for SZ should ultimately focus on ameliorating functioning and quality of life of patients, what might be reached by increasing cognitive performance. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Schizophrenia Research, 168(1-2) : 571-572

Chen, A., Chibnall, J., Nasrallah, H.

A meta-analysis of placebo-controlled trials of omega-3 fatty acid augmentation in schizophrenia: Possible stage-specific effects

Background: Omega-3 fatty acids have shown promise as an adjunctive treatment for schizophrenia. However, efficacy across studies has been inconsistent. We conducted a meta-analysis of published controlled studies with the goal of detecting different efficacy profiles at various stages of schizophrenia. Methods: An online search was conducted for randomized, double-blind, placebo-controlled clinical trials, and a meta-analysis was conducted. Results: Ten studies met the criteria for inclusion. Among patients in the prodromal phase of schizophrenia, omega-3 supplementation reduced psychotic symptom severity and lowered conversion rates to first-episode psychosis. In patients with first-episode schizophrenia, omega-3 decreased nonpsychotic symptoms, required lower antipsychotic medication dosages, and improved early treatment response rates. Omega-3 had mixed results in patients with stable chronic schizophrenia, with only some patients experiencing significant benefits. Among patients with chronic schizophrenia, use of omega-3 fatty acids both by those experiencing acute exacerbations and those who had discontinued antipsychotic medications resulted in worsening of psychotic symptoms. Conclusions: The data suggest that omega-3 fatty acids may be efficacious in reducing clinical symptoms for patients in the earlier stages of schizophrenia (prodrome and first episode), while producing mixed results for patients in the chronic stages. Based on these results, omega-3 fatty acids would not be recommended for acute exacerbations in patients with chronic schizophrenia nor for relapse prevention after discontinuation of antipsychotics. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Annals of Clinical Psychiatry, 27(4) : 289- 296

Fisher, M., Loewy, R., Carter, C., Lee, A., Ragland, D., Niendam, T., Schlosser, D., Pham, L., Miskovich, T., Vinogradov, S.

Neuroplasticity-based auditory training via laptop computer improves cognition in young individuals with recent onset schizophrenia

Objective: Cognitive deficits that characterize schizophrenia are present in the prodrome, worsen with illness onset, and predict functional outcome. Cognitive dysfunction is thus a critical target for early intervention in young individuals with recent onset schizophrenia. Method: This 2-site double-blind randomized controlled trial investigated cognitive training of auditory processing/verbal learning in 86 subjects with recent onset schizophrenia (mean age of 21 years). Subjects were given laptop computers to take home and were asked to perform 40 hours of training or 40 hours of commercial computer games over 8 weeks. We examined cognitive measures recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS), symptoms, and functioning. We also assessed baseline reward anticipation to index motivational system functioning and measured changes in auditory processing speed after 20 hours of training to assess target engagement. Results: Auditory training subjects demonstrated significant improvements in global cognition, verbal memory, and problem solving compared with those of computer games control subjects. Both groups showed a slight but significant decrease in symptoms and no change in functional outcome measures. Training-induced cognitive gains at posttraining showed significant associations with reward anticipation at baseline and with improvement in auditory processing speed at 20 hours. Conclusion: Neuroscience-informed cognitive training via laptop computer represents a promising treatment approach for cognitive dysfunction in early schizophrenia. An individual's baseline motivational system functioning (reward anticipation), and ability to engage in auditory processing speed improvement, may represent important predictors of treatment outcome. Future studies must investigate whether cognitive training improves functioning and how best to integrate it into critical psychosocial interventions. (PsycINFO Database Record (c) 2015 APA, all rights reserved) (journal abstract).

Schizophrenia Bulletin, 41(1) : 250- 258

De-Maio, M., Graham, P., Vaughan, D., Haber, L., Madonick, S.

Review of international early psychosis programmes and a model to overcome unique challenges to the treatment of early psychosis in the United States

Aim: This article presents a literature review of treatments for first-episode psychosis throughout the world and describes the POTENTIAL (Patient-Oriented Treatment for Early or New onset schizophrenia To Initiate A Long-term recovery) Early Psychosis Programme in detail, explaining the model and the rationale, as well as the uniqueness of the programme.; Methods: An international search was conducted for English articles using PubMed, PsycINFO and PsycARTICLES, as well as the reference lists of published studies and reviews. One article that is currently in press was included, which was not part of the original literature search. Inclusion criteria included any published or in press study focused upon treatment programmes for early psychosis. Out of the 62 articles collected, 27 publications met this criterion and were utilized. In addition to identifying clinical programmes, gaps in treatment for this population were identified.; Results: The primary method in the United States for the treatment of early psychosis is randomized trial for new pharmacological treatments where patients are research subjects. Although there are a multitude of both research and clinical programmes internationally, the few programmes that exist in the United States that focus upon first-episode psychosis are either research based or focus upon prodromal symptoms. Clinical programmes such as the POTENTIAL programme are nearly non-existent.; Conclusions: Although the POTENTIAL programme has been successful both clinically and financially, there are still more strides to be taken to improve upon young adult services. Future development of the programme is continuing with the incorporation of outcome data and outreach into the community.; © 2014 Wiley Publishing Asia Pty Ltd.

Early Intervention in Psychiatry, 9(1) : 1- 11