Eack, S., Newhill, C., Keshavan, M.

Cognitive enhancement therapy improves resting-state functional connectivity in early course schizophrenia

Objective: Cognitive remediation is emerging as an effective psychosocial intervention for addressing untreated cognitive and functional impairments in persons with schizophrenia, and might achieve its benefits through neuroplastic changes in brain connectivity. This study seeks to examine the effects of cognitive enhancement therapy (CET) on fronto-temporal brain connectivity in a randomized controlled trial with individuals in the early course of schizophrenia. Method: Stabilized, early course outpatients with schizophrenia or schizoaffective disorder (N = 41) were randomly assigned to CET (n = 25) or an active enriched supportive therapy (EST) control (n = 16) and treated for 2 years. Functional MRI data were collected annually, and pseudo resting-state functional connectivity analysis was used to examine differential changes in fronto-temporal connectivity between those treated with CET compared with EST. Results: Individuals receiving CET evidenced significantly less functional connectivity loss between the resting-state network and the left dorsolateral prefrontal cortex as well as significantly increased connectivity with the right insular cortex compared to EST (all corrected p < .01). These neural networks are involved in emotion processing and problem-solving. Increased connectivity with the right insula significantly mediated CET effects on improved emotion perception (z' = -1.96, p = .021), and increased connectivity with the left dorsolateral prefrontal cortex mediated CET-related improvements in emotion regulation (z' = -1.71, p = .052). Conclusions: These findings provide preliminary evidence that CET, a psychosocial cognitive remediation intervention, may enhance connectivity between frontal and temporal brain regions implicated in problem-solving and emotion processing in service of cognitive enhancement in schizophrenia. (PsycINFO Database Record (c) 2016 APA, all rights reserved)

Journal of the Society for Social Work and Research, 7(2) : 211- 230

Cheng, S., Schepp, K.

Early intervention in schizophrenia: A literature review

Schizophrenia is a debilitating psychiatric disorder seen across the world. Recently, investigators have witnessed an upsurge in research on the potential benefits of early intervention during the prodromal stage: the sooner people start the treatment at their first psychotic episode, the better outcome on symptom relief and better functioning. This paper aims to critically review and synthesize empirical evidence published between 2005 and 2015 regarding the effectiveness of preemptive interventions on transition rate, symptom severity, depression, anxiety, and function level. Randomized controlled trials were identified in seven different electronic databases and twelve studies were included in this review. Findings indicated that intervention was designed not only for help-seeking individuals, but also for their family members. Also, the applications for psychiatric nursing are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Archives of Psychiatric Nursing, 30(6) : 774- 781

Alvarez-Jimenez, M., O'Donoghue, B., Thompson, A., Gleeson, J., Bendall, S., Gonzalez-Blanch, C., Killackey, E., Wunderink, L., McGorry, P.

Beyond clinical remission in first episode psychosis: Thoughts on antipsychotic maintenance vs. guided discontinuation in the functional recovery era

Treatment guidelines for first episode psychosis (FEP) recommend at least 1 year of antipsychotic treatment following remission; however, in light of some recent research and the preference of some individuals to discontinue their medication sooner, this recommendation can be questioned. The aim of this article is to appraise the current discontinuation studies given our views on how this field should progress. We conducted a review of randomized controlled trials investigating dose-reduction/medication discontinuation compared with treatment maintenance in clinically remitted FEP patients. Seven trials were identified, and these reported a higher rate of relapse in the dose reduction or discontinuation groups. Relapse rates were higher when a lower threshold for relapse was utilized. However, only three studies specified that concurrent psychosocial interventions were also provided, despite an evidence base for these interventions in reducing symptom severity and relapse. Length of follow-up may also be important, as the study with the longest follow-up (7 years), albeit with some methodological shortcomings, found greater functional recovery in the dose-reduction group and that relapse rates between the two groups (dose-reduction vs. maintenance) were equal after 3 years. Finally, in addition to discontinuation or dose reduction, a diagnosis of schizophrenia, a longer duration of illness, and poor premorbid functioning were associated with a greater risk of relapse. Further trials are needed in this area to establish the long-term risk-benefit ratio of antipsychotic medication in FEP. Meanwhile, young people with FEP who do not fulfil criteria for a diagnosis of a schizophrenia disorder, achieve clinical remission for at least 3 months, attain early functional recovery, and have good social support may be possible candidates for discontinuation of antipsychotic medication bolstered by effective psychosocial interventions provided in the context of a specialized FEP service. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

CNS Drugs, 30(5) : 357-368

Chien, W., Thompson, D., Lubman, D., McCann, T.

A randomized controlled trial of clinician-supported problem-solving bibliotherapy for family caregivers of people with first-episode psychosis

Family interventions for first-episode psychosis (FEP) are an integral component of treatment, with positive effects mainly on patients' mental state and relapse rate. However, comparatively little attention has been paid to the effects of family interventions on caregivers' stress coping and well-being, especially in non-Western countries. We aimed to test the effects of a 5-month clinician-supported problem-solving bibliotherapy (CSPSB) for Chinese family caregivers of people with FEP in improving family burden and carers' problem-solving and caregiving experience, and in reducing psychotic symptoms and duration of re-hospitalizations, compared with those only received usual outpatient family support (UOFS). A randomized controlled trial was conducted across 2 early psychosis clinics in Hong Kong, where there might be inadequate usual family support services for FEP patients. A total of 116 caregivers were randomly selected, and after baseline measurement, randomly assigned to the CSPSB or UOFS. They were also assessed at 1-week and 6- and 12-month post-intervention. Intention-to-treat analyses were applied and indicated that the CSPSB group reported significantly greater improvements in family burden and caregiving experience, and reductions in severity of psychotic symptoms and duration of re-hospitalizations, than the UOFS group at 6- and 12-month follow-up. CSPSB produces moderate long-term benefits to caregivers and FEP patients, and is a low-cost adjunct to UOFS. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Schizophrenia Bulletin, 42(6) : 1457- 1466

Chang, W., Kwong, V., Chan, G.,

Prediction of functional remission in first-episode psychosis: 12-month follow-up of the randomized-controlled trial on extended early intervention in Hong Kong

Background: Functional remission (FR) is an intermediate and necessary step toward recovery, but is understudied in first-episode psychosis (FEP). We aimed to examine the rate and predictors of FR in FEP patients in the context of a randomized-controlled trial (RCT) comparing a 1-year extension of early intervention (Extended EI, 3-year EI) with step-down psychiatric care (SC, 2 -year EI). Methods: One hundred sixty Chinese patients were recruited from a specialized EI program for FEP in Hong Kong after they have completed this 2-year EI service, randomly allocated to Extended EI or SC, and followed up for 12 months. Assessments on premorbid adjustment and personality, clinical profiles, functioning, and treatment characteristics were conducted. FR was operationalized as simultaneous fulfillment of attaining adequate functional levels (measured by Social and Occupational Functioning Scale and Role Functioning Scale) and competitive employment at 6 and 12 months. Data analysis was based on 156 subjects who completed follow-up functional assessments. Results: Thirty-one (19.9%) patients achieved FR status. Multivariate binary regression analysis showed that female gender, lower degrees of premorbid schizoid-schizotypal traits, Extended EI treatment condition, lower levels of positive symptoms at intake, and better baseline functioning independently predicted FR. Conclusion: This is the first RCT providing supportive evidence to an extension of EI service beyond 2-year treatment duration on further enhancing the likelihood of FR attainment in FEP. Our findings that only approximately 20% of patients achieved FR indicate an unmet therapeutic need for promoting sustained adequate functional improvement in the early stage of psychotic illness. (PsycINFO Database Record (c) 2017 APA, all rights reserved)

Schizophrenia Research, 173(1-2) : 79- 83

Bergh, S., Hjorthoj, C., Sorensen, H. J., Fagerlund, B., Austin, S., Secher, R. G., Jepsen, J. R., Nordentoft, M.

Predictors and longitudinal course of cognitive functioning in schizophrenia spectrum disorders, 10 years after baseline: The OPUS study

Background Identifying baseline predictors of the long-term course of cognitive functioning in schizophrenia spectrum disorders is important because of associations between cognitive functioning (CF) and functional outcome. Determining whether CF remains stable or change during the course of illness is another matter of interest. Methods Participants from The Danish OPUS Trial, aged 18-45 years, with a baseline ICD-10 schizophrenia spectrum diagnosis, were assessed on psychopathology, social and vocational functioning at baseline, and cognitive functioning 5 (N = 298) and 10 years (N = 322) after baseline. Uni- and multi-variable regression analyses of potential baseline predictors of 10-year CF were performed. Also, changes in CF and symptomatology between 5 and 10 years of follow-up were assessed. Findings Baseline predictors of impaired CF after 10 years included male gender, unemployment, poor premorbid achievement and later age of onset. Having finished high school and receiving early intervention treatment was associated with better CF. Age, growing up with both parents, number of family and friends, primary caregivers education, premorbid social function, negative symptoms, GAF (symptoms, function) and substance abuse, were associated with CF in univariable analyses. Non-participants generally suffered from more severe dysfunction. Longitudinally, amelioration in negative symptoms was associated with improved speed of processing and executive functions. Symptom scores generally improved with time, while scores for all cognitive tests remained stable. Conclusion The current study identifies several robust associations between baseline characteristics and 10-year cognitive outcome. Several other variables were univariably associated with 10-year cognitive outcome. Also, we found evidence for stability of CF over time. Copyright © 2016 Elsevier B.V.

Schizophrenia Research, 175(1-3) : 57- 63

Nuechterlein, K. H., Ventura, J., McEwen, S. C., Gretchen-Doorly, D., Vinogradov, S., Subotnik, Kenneth L

Enhancing cognitive training through aerobic exercise after a first schizophrenia episode: theoretical conception and pilot study

Schizophrenia Bulletin, 42(suppl_1) : S44-S52

Brewer, W. J., Lambert, T. J., Witt, K., Dileo, J., Duff, C., Crlenjak, C., McGorry, P. D., Murphy, B. P.

Intensive case management for high-risk patients with first-episode psychosis: Service model and outcomes

Background: The first episode of psychosis is a crucial period when early intervention can alter the trajectory of the young person's ongoing mental health and general functioning. After an investigation into completed suicides in the Early Psychosis Prevention and Intervention Centre (EPPIC) programme, the intensive case management subprogramme was developed in 2003 to provide assertive outreach to young people having a first episode of psychosis who are at high risk owing to risk to self or others, disengagement, or suboptimal recovery. We report intensive case management model development, characterise the target cohort, and report on outcomes compared with EPPIC treatment as usual. Methods: Inclusion criteria, staff support, referral pathways, clinical review processes, models of engagement and care, and risk management protocols are described. We compared 120 consecutive referrals with 50 EPPIC treatment as usual patients (age 15-24 years) in a naturalistic stratified quasi-experimental real-world design. Key performance indicators of service use plus engagement and suicide attempts were compared between EPPIC treatment as usual and intensive case management, and psychosocial and clinical measures were compared between intensive case management referral and discharge. Findings: Referrals were predominately unemployed males with low levels of functioning and educational attainment. They were characterised by a family history of mental illness, migration and early separation, with substantial trauma, history of violence, and forensic attention. Intensive case management improved psychopathology and psychosocial outcomes in high-risk patients and reduced risk ratings, admissions, bed days, and crisis contacts. Interpretation: Characterisation of intensive case management patients validated the clinical research focus and identified a first episode of psychosis high-risk subgroup. In a real-world study, implementation of an intensive case management stream within a well-established first episode of psychosis service showed significant improvement in key service outcomes. Further analysis is needed to determine cost savings and effects on psychosocial outcomes. Targeting intensive case management services to high-risk patients with unmet needs should reduce the distress associated with pathways to care for patients, their families, and the community. Funding: National Health & Medical Research Council and the Colonial Foundation.

Lancet Psychiatry, 2(1) : 29-37

Calvo, A., Moreno, M., Ruiz-Sancho, A., Rapado-Castro, M., Moreno, C., Sanchez-Gutierrez, T., Arango, C., Mayoral, M.

Psychoeducational group intervention for adolescents with psychosis and their families: A two-year follow-up

Objective: To investigate whether the beneficial effects of a structured, psychoeducational, parallel-group program for adolescents with early-onset psychosis and their families observed immediately after the intervention were maintained 2 years later. Method: The present study examines the longitudinal efficacy of a randomized controlled trial based on a psychoeducational, problem-solving, structured group intervention for adolescents with early-onset psychosis and their families (PE) and compares it with that of a nonstructured group intervention (NS) after a 2-year follow-up. We analyzed whether the differences between PE and NS found after the intervention persisted 2 years later. Intergroup differences in number and duration of hospitalizations, symptoms, and functioning were also assessed. Results: After 2 years of follow-up, we were able to reassess 89% of patients. In the PE group, 13% of patients had visited the emergency department, compared with 50% in the NS group (p = .019). However, no statistically significant differences were found between the groups for negative symptoms or number and duration of hospitalizations. A significant improvement in Positive and Negative Syndrome Scale (PANSS) general symptoms was observed in the PE group. Conclusion: Our psychoeducational group intervention showed sustained effects by diminishing the number of visits to emergency departments 2 years after the intervention. Our findings indicate that this psychoeducational intervention could provide patients with long-lasting resources to manage crises more effectively. (PsycINFO Database Record (c) 2016 APA, all rights reserved) (journal abstract).

Journal of the American Academy of Child & Adolescent Psychiatry, 54(12) : 984-990

Alphs, L., Bossie, C., Mao, L., Lee, E., Starr, H. L.

Treatment effect with paliperidone palmitate compared with oral antipsychotics in patients with recent-onset versus more chronic schizophrenia and a history of criminal justice system involvement

Aim: Long-acting injectable antipsychotics (APs) are not well studied in recent-onset schizophrenia. This exploratory analysis of a study designed to reflect real-world schizophrenia, as defined by patients, interventions and outcomes, compared relative treatment effect between once-monthly paliperidone palmitate (PP) and daily oral APs in patients with recent-onset or chronic illness Methods: This randomized, open-label, event monitoring board-blinded study compared treatment response in subjects with schizophrenia and a history of criminal justice system involvement following treatment with PP or oral APs for 15 months (ClinicalTrials.gov identifier, NCT01157351). Event-free probabilities were estimated using Kaplan-Meier method; hazard ratios (HRs) were estimated using Cox proportional hazard models. This subgroup analysis analysed data by disease duration (=5 (recent-onset) or >5 years (chronic illness) since first psychiatric diagnosis). Results: Seventy-seven subjects met the criteria for recent-onset illness; 365 for chronic illness. HRs (95% CI) for treatment failure for oral APs versus PP were 1.73 (0.87-3.45; P=0.121) for recent-onset and 1.37 (1.02-1.85; P=0.039) for chronic illness.

Early Intervention in Psychiatry, :

Amminger, G. P., Schafer, M. R., Schlogelhofer, M., Klier, C. M., McGorry, P. D.

Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study

Long-chain omega-3 polyunsaturated fatty acids (PUFAs) are essential for neural development and function. As key components of brain tissue, omega-3 PUFAs play critical roles in brain development and function, and a lack of these fatty acids has been implicated in a number of mental health conditions over the lifespan, including schizophrenia. We have previously shown that a 12-week intervention with omega-3 PUFAs reduced the risk of progression to psychotic disorder in young people with subthreshold psychotic states for a 12-month period compared with placebo. We have now completed a longer- term follow-up of this randomized, double-blind, placebo-controlled trial, at a median of 6.7 years. Here we show that brief intervention with omega-3 PUFAs reduced both the risk of progression to psychotic disorder and psychiatric morbidity in general in this study. The majority of the individuals from the omega-3 group did not show severe functional impairment and no longer experienced attenuated psychotic symptoms at follow- up.

Nature Communications, 6 :

Choi, J., Corcoran, C., Dixon, L., Javitt, D. C.

Processing speed training and social functioning in teenagers and young adults at clinical high risk for psychosis [abstract]

Background: Deficits in processing speed (PS) have found to be correlated with social aptitude in CHR cohorts and variably identified as risk markers for psychosis. Among those with attenuated positive symptoms, processing speed has been related to social and role functioning regardless of conversion to Sz. These information processing dysfunctions seem to be upstream to broader, top-down cognitive and social skills. When subprocesses are degraded, the brain must adjust by lengthening space and time integration constants in effort to detect relevant signals. This adaptation comes at a cost since the brain cannot accurately represent details of spatiotemporally complex signals. This results in slowed speed of information processing in a social situation. We examined the feasibility of improving information processing relevant to social situations in CHR, including its sustainability at 2 months, and its association with concurrent social function. Methods: This was a double-blind RC T where 39 CHR participants were randomized to Processing Speed Training (PST) or an active control matched for training format and the same dose and duration of treatment. PST is a tablet-based program that uses pupillometry to continually adjust training parameters for an optimal cognitive load and improve visual scanning efficiency by inhibiting selection of non-essential targets and discriminating figure-ground details. Results: The PST group showed faster motorical and non-motorical PS at post (F [2,35]=5.09, p=.00) and 2 months (F [4,31]=4.49, p=.01). Subsequent results in social functioning at 2 month follow-up showed the PST group reporting better overall social adjustment (F [4,31]=3.72, p=.02) and less anxiety about engaging in new social situations (F [4,31]=3.15, p=.02). Of note, changes in PS from baseline to 2 months were correlated with overall social adjustment (r=.28-.39, p=.00-.02) and social avoidance (r=.29, p=.01) regardless of group assignment. Furthermore, processing speed at baseline predicted social adjustment outcome at 2 mo, even after accounting for variance attributable to group assignment and symptoms (R2=.49, F [4,31]=4.60; p=.01). Conclusion: To our knowledge, this is the first study to test focal cognitive training for PS deficits in a putatively prodromal phase of Sz to address social morbidity. Targeting PS appears to be a promising pathway to improving co-morbidity and mitigating a risk factor for psychosis.

Schizophrenia Bulletin, 41 : S41