Bruno Biagianti

Modeling the role of negative symptoms in determining social functioning in individuals at clinical high risk of psychosis

A priority for improving outcome in individuals at clinical high risk (CHR) is enhancing our understanding of predictors of psychosis as well as psychosocial functioning. Social functioning, in particular, is a unique indicator of risk as well as an important outcome in itself. Negative symptoms are a significant determinant of social functioning in CHR individuals; yet, it is unclear which specific negative symptoms drive functional outcome and how these symptoms function relative to other predictors, such as neurocognition and mood/anxiety symptoms. In a sample of 85 CHR individuals, we examined whether a two-factor negative symptom structure that is found in schizophrenia (experiential vs expressive symptoms) would be replicated in a CHR sample; and tested the degree to which specific negative symptoms predict social functioning, relative to neurocognition and mood/anxiety symptoms, which are known to predict functioning. The two-factor negative symptom solution was replicated in this CHR sample. Negative symptom severity was found to be uniquely predictive of social functioning, above and beyond depression/anxiety and neurocognition. Experiential symptoms were more strongly associated with social functioning, relative to expression symptoms. In addition, experiential symptoms mediated the relationship between expressive negative symptoms and social functioning. These results suggest that experiences of motivational impairment are more important in determining social functioning, relative to affective flattening and alogia, in CHR individuals, thereby informing the development of more precise therapeutic targets. Developing novel interventions that stimulate goal-directed behavior and reinforce rewarding experiences in social contexts are recommended.

Intensive Auditory Cognitive Training Improves Verbal Memory in Adolescents and Young Adults at Clinical High Risk for Psychosis

OBJECTIVE Individuals at clinical high risk (CHR) for psychosis demonstrate cognitive impairments that predict later psychotic transition and real-world functioning. Cognitive training has shown benefits in schizophrenia, but has not yet been adequately tested in the CHR population. METHODS In this double-blind randomized controlled trial, CHR individuals (N = 83) were given laptop computers and trained at home on 40 hours of auditory processing-based exercises designed to target verbal learning and memory operations, or on computer games (CG). Participants were assessed with neurocognitive tests based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative (MATRICS) battery and rated on symptoms and functioning. Groups were compared before and after training using a mixed-effects model with restricted maximum likelihood estimation, given the high study attrition rate (42%). RESULTS Participants in the targeted cognitive training group showed a significant improvement in Verbal Memory compared to CG participants (effect size = 0.61). Positive and Total symptoms improved in both groups over time. CONCLUSIONS CHR individuals showed patterns of training-induced cognitive improvement in verbal memory consistent with prior observations in schizophrenia. This is a particularly vulnerable domain in individuals at-risk for psychosis that predicts later functioning and psychotic transition. Ongoing follow-up of this cohort will assess the durability of training effects in CHR individuals, as well as the potential impact on symptoms and functioning over time. Clinical Trials Number: NCT00655239. URL: https://clinicaltrials.gov/ct2/show/NCT00655239?term=vinogradov&rank=5.

Neural signal during immediate reward anticipation in schizophrenia: Relationship to real-world motivation and function

Amotivation in schizophrenia is a central predictor of poor functioning, and is thought to occur due to deficits in anticipating future rewards, suggesting that impairments in anticipating pleasure can contribute to functional disability in schizophrenia. In healthy comparison (HC) participants, reward anticipation is associated with activity in frontal–striatal networks. By contrast, schizophrenia (SZ) participants show hypoactivation within these frontal–striatal networks during this motivated anticipatory brain state. Here, we examined neural activation in SZ and HC participants during the anticipatory phase of stimuli that predicted immediate upcoming reward and punishment, and during the feedback/outcome phase, in relation to trait measures of hedonic pleasure and real-world functional capacity. SZ patients showed hypoactivation in ventral striatum during reward anticipation. Additionally, we found distinct differences between HC and SZ groups in their association between reward-related immediate anticipatory neural activity and their reported experience of pleasure. HC participants recruited reward-related regions in striatum that significantly correlated with subjective consummatory pleasure, while SZ patients revealed activation in attention-related regions, such as the IPL, which correlated with consummatory pleasure and functional capacity. These findings may suggest that SZ patients activate compensatory attention processes during anticipation of immediate upcoming rewards, which likely contribute to their functional capacity in daily life.

Computerized cognitive training targeting brain plasticity in schizophrenia

Two important paradigm shifts have occurred recently in the field of schizophrenia research. First, we now understand schizophrenia to be a neurodevelopmental disorder, one that is characterized by aberrant patterns of activation and connectivity in cortical and subcortical neural networks that are present before illness onset and that worsen as an individual progresses into later stages of the disease. Second, we now understand that these abnormalities are not immutable and fixed, but instead can respond to interventions targeting brain plasticity, particularly when delivered in the prodromal and early phases of schizophrenia. In this chapter, we will first describe some of the neurocognitive impairments that characterize schizophrenia, highlighting the developmental course of the illness. We will then briefly review salient features of currently available computerized cognitive training programs that target these impairments. Next, we will present an overview of current research findings regarding neurobiological effects of computerized cognitive training in schizophrenia and how these results shed light on the critical neuroplasticity mechanisms that support successful training. Finally, we will present recommendations for future research to optimize computerized cognitive training programs, with an aim to promoting functional recovery.

Potential Benefits of Incorporating Peer-to-Peer Interactions Into Digital Interventions for Psychotic Disorders: A Systematic Review

OBJECTIVE Peer-to-peer interactions and support groups mitigate experiences of social isolation and loneliness often reported by individuals with psychotic disorders. Online peer-to-peer communication can promote broader use of this form of social support. Peer-to-peer interactions occur naturally on social media platforms, but they can negatively affect mental health. Recent digital interventions for persons with psychotic disorders have harnessed the principles of social media to incorporate peer-to-peer communication. This review examined the feasibility, acceptability, and preliminary efficacy of recent digital interventions in order to identify strategies to maximize benefits of online peer-to-peer communication for persons with psychotic disorders. METHODS An electronic database search of PubMed, EMBASE, PsycINFO, Ovid MEDLINE, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database was conducted in February 2017 and yielded a total of 1,015 results. Eight publications that reported data from six independent trials and five interventions were reviewed. RESULTS The technology supporting peer-to-peer communication varied greatly across studies, from online forums to embedded social networking. When peer-to-peer interactions were moderated by facilitators, retention, engagement, acceptability, and efficacy were higher than for interventions with no facilitators. Individuals with psychotic disorders were actively engaged with moderated peer-to-peer communication and showed improvements in perceived social support. Studies involving service users in intervention design showed higher rates of acceptability. CONCLUSIONS Individuals with psychotic disorders value and benefit from digital interventions that include moderated peer-to-peer interactions. Incorporating peer-to-peer communication into digital interventions for this population may increase compliance with other evidence-based therapies by producing more acceptable and engaging online environments.

Feasibility and preliminary efficacy of remotely delivering cognitive training to people with schizophrenia using tablets

Background Limited access to Cognitive Training (CT) for people with schizophrenia (SZ) prevents widespread adoption of this intervention. Delivering CT remotely via tablets may increase accessibility, improve scheduling flexibility, and diminish patient burden. Methods In this reanalysis of data from a larger trial of CT, we compared two samples of individuals with SZ who chose to complete 40 h of CT either on desktop computers in the laboratory (N = 33) or remotely via iPads (N = 41). We examined attrition rates and adherence to training, and investigated whether remote iPad-based CT and in-person desktop-based CT induced significantly different improvements in cognitive and real-world functioning. Results The attrition rate was 36.6%. On average, participants completed 3.06 h of CT per week. There were no significant between-group differences in attrition and adherence to CT requirements. Participants who completed iPad-based CT were significantly younger and had lower symptoms at baseline compared to participants who completed CT on the lab desktops. Controlling for age and symptom severity, rANCOVA showed that iPad-based and desktop-based CT similarly and significantly improved verbal learning and problem solving. Main effects of time, at trend level significance, were evident in global cognition, verbal memory, quality of life, and social functioning. All group by time interactions were non-significant except for verbal memory, where iPad users showed greater gains. Within-group effect sizes for changes in outcomes were in the small range. Conclusion Although underpowered and not randomized, this study demonstrates that delivering CT remotely to people with SZ using tablets is feasible and results in retention rates, adherence, and cognitive and functional outcome improvements that are comparable to those observed when CT is delivered in the laboratory. This has important implications in terms of scalability and dissemination of CT. These results require confirmation in larger samples.

F70. COMPUTERIZED SOCIAL COGNITIVE TRAINING (SCT) IMPROVES COGNITION AND RESTORES FUNCTIONAL CONNECTIVITY IN RECENT ONSET PSYCHOSIS: AN INTERIM REPORT

Abstract Background Neurocognitive impairments are a core and enduring feature of psychosis that continue to persist despite pharmacological interventions. Neurocognitive interventions have emerged as a supplementary treatment option to improve cognition in early psychosis patients. Recently, focus has shifted to using social cognitive training (SCT) as evidence suggests that targeting social cognition may lead to improvements not only in cognition but also in real-world functioning (Horan et al., 2011). This improvement is thought to be mediated by restoration of functional brain activity in patients undergoing neurocognitive interventions, especially associated with medial prefrontal cortex (Hooker et al., 2014). In this study, we report our interim findings of the effects of a 10-hour SCT on cognition and resting-state functional connectivity (rsFC). Our hypothesis was that training would improve cognition and normalize functional connectivity. Methods In this randomized-controlled study, one recent onset psychosis (ROP) patient arm (n=18) underwent a 6-week (10-hour) computerized SCT (Brain HQ, Posit Science, https://www.brainhq.com/), while another naturalistic arm (n=18) received treatment as usual (TAU). Both treatment arms were assessed on a battery of neurocognitive tests and underwent a multimodal imaging protocol, including a 10 min resting-state fMRI, at two timepoints (baseline, T0; follow-up, FU). Seed-based voxel-wise rsFC was performed and individual-level rsFC correlation maps were calculated between the bilateral medial prefrontal cortex (mPFC) and the whole brain. Results The SCT group showed significant improvements in the domain of spatial working memory (p<0.05), processing speed (p<0.05) and resilience to both immediate and delayed memory decline over 6 weeks (p<0.05), as compared to TAU. Comparison of FC between the two measurement time points, suggested increased FC between mPFC and left inferior temporal gyrus (ITG), as well as increased FC between mPFC and left somatosensory area in ROP patients that underwent SCT relative to TAU. Discussion We have shown improvements in processing speed, verbal memory, and spatial working memory that agree with previous studies using computerized cognitive interventions. Moreover, the improvement in the spatial working memory domain was significant in the most demanding test condition with 10 elements - indicative of benefits from the fine-tuning of higher-level executive functions. The neuroimaging results also suggested that the improvements may have been mediated by the improvement of FC in regions typically associated with social cognition and facial recognition (Adolphs et al., 2009). These results are in line with recent studies investigating not only the feasibility of SCT as an intervention, but also the effects on cognition and underlying neural alterations resulting from intensive computerized neurocognitive interventions (Hooker et al., 2012; Nahum et al., 2014; Subramaniam et al., 2014). Future studies using machine learning methods will be necessary to determine functional biomarkers in order to personalize SCT at the individual-level.