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OBJECTIVES: Currently, there are no effective treatments for functional outcomes (i.e., role and social) and negative symptoms for youth at clinical high-risk (CHR) for psychosis. Investigations into possible mechanisms that may contribute to the improvement of functioning and negative symptoms are needed in CHR research to help inform psychosocial treatments. The present study examined whether functioning and negative symptoms were mediated by asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, or attenuated psychotic symptoms (APS) in a large clinical trial. METHODS: CHR participants (n = 203; 104 females; 99 males) were recruited as part of a three-site randomized control trial comparing group cognitive-behavioural social skills training (CBSST) versus a supportive therapy group. Mediation analyses were conducted to test the relationships between treatment group, mediators (asocial beliefs, defeatist beliefs, self-efficacy, maladaptive schemas, anxiety, depression, social cognition, and APS), and outcome (social and role functioning, and negative symptoms). The mediation analyses employed conditional process path analysis via ordinary least squares regression. RESULTS: At the end of treatment, but not 12-month follow-up, more severe APS were found to mediate the impact of treatment on negative symptoms, and social and role functioning. The greater the severity of APS, the less likely that CBSST would result in improvement in negative symptoms and social and role functioning. Many of the other variables showed significant associations with social (less for role) functioning and negative symptoms but did not mediate the effect of treatment on these outcomes at the end of treatment or 12-month follow-up. CONCLUSIONS: There were no significant mediators except for APS at the end of treatment. Since more severe APS may result in participants being unable to fully participate in therapy and thus limit their gains, clinical implications may include offering some individual therapy to prepare these young people to benefit from the group treatment.

BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) affects a significant proportion of the population and is associated with numerous adverse outcomes including lower educational attainment, occupational challenges, increased substance use, and various mental health issues including psychosis. This study examined the demographic, clinical, cognitive, social cognitive, and functional differences between youth at clinical high-risk (CHR) for psychosis with and without comorbid ADHD. METHOD: Data were drawn from the North American Prodrome Longitudinal Studies (NAPLS2 and NAPLS3), which included 764 and 710 CHR individuals, respectively. After applying exclusion criteria, the sample consisted of 271 CHR participants with ADHD and 1118 without ADHD. All data were examined cross-sectionally. RESULTS: Compared with the non-ADHD group, the ADHD group was younger, had more difficulties with role functioning, premorbid functioning, and social cognition, were more likely to have a comorbid learning disorder, and reported less depression symptoms. There were no significant differences between the groups on positive or negative psychotic symptoms, transition rates, adverse events, or other comorbid disorders including substance use and depression. DISCUSSION: Comorbid ADHD is likely not a significant predictor of transition to psychosis among CHR youth; however, those CHR with ADHD may experience symptoms at a younger age than those without and present with a distinct clinical profile.

AIM: Difficulties in social functioning have been observed in youth at clinical high-risk (CHR) of psychosis even in those who do not go on to develop a psychotic illness. Few treatment studies have attempted to improve social functioning in this population. The aim of this study was to conduct a randomized trial comparing the effects of Cognitive-Behavioral Social Skills Training (CBSST) with a supportive therapy (ST). METHODS: Both CBSST and ST were weekly group therapies, delivered over 18 weeks. This was a 2-arm trial with single-blinded ratings and intention-to-treat analyses. Assessments occurred at baseline, end-of-treatment, and 12 months after the baseline assessment. The primary outcome was social and role functioning and defeatist performance attitudes were the secondary outcome. Attenuated positive and negative symptoms, anxiety, depression, self-efficacy, and beliefs about self and others were examined as exploratory outcomes. RESULTS: There were no significant differences between the 2 groups at baseline or either of the 2 follow-ups. However, at follow-ups, in each group there were significant improvements in clinical symptoms. These could not be attributed to group treatment since there was no control or wait-list group. CONCLUSIONS: Since poor social functioning is one of the most observed difficulties in CHR individuals, and a decline in social functioning may be a significant predictor of later transition to psychosis, future work will be needed to find effective treatments for this decline in functioning for CHR youth.

AIM: Individuals at clinical high risk (CHR) for psychosis have been shown to experience more trauma than the general population. However, although the effects of trauma appear to impact some symptoms it does not seem to increase the risk of transition to psychosis. The aim of this article was to examine the prevalence of trauma, and its association with longitudinal clinical and functional outcomes in a large sample of CHR individuals. METHODS: From the North American Prodrome Longitudinal Study-3 (NAPLS-3) 690 CHR individuals and 91 healthy controls from nine study sites between 2015 and 2018 were assessed. Historical trauma experiences were captured at baseline. Participants completed longitudinal assessments measuring clinical outcomes including positive and negative symptoms, depression, social and role functioning and assessing transition to psychosis. RESULTS: From the 690 CHR participants and 96 healthy controls, 343 (49.6%) and 15 (15.6%), respectively, reported a history of trauma (p

Research reveals that a dimeric ubiquitin-conjugating enzyme complex Ubc13/Uev1A takes part not only in the assembly of polyubiquitin chains but also supports IkB kinase activation by the signal transducer TRAF6. Data further show that ubiquitin plays a regulatory role in activating the kinase through polyubiquitin chains.

Background: Individuals at clinical high‐risk (CHR) for psychosis experience high rates of bullying. There is little research on the differences between CHR who did and did not experience bullying. However, there is evidence that bullying may be related to negative schemas and social impairment. Objectives: To examine differences in core schemas, asocial and defeatist beliefs, and social functioning between those who did and did not report bullying experiences in a large sample of CHR individuals. We hypothesized that bullying in CHR youth would be associated with poorer social functioning, increased maladaptive beliefs, and negative core schemas. Methods: CHR participants (N = 203) were split into those who did and did not report experiencing bullying. The two groups were compared on demographic characteristics, social functioning, and belief variables, using the Brief Core Schemas Scale, the Asocial Beliefs Scale, the Defeatist Performance Attitudes Scale, and the First Episode Social Functioning Scale. Results: 72.9% reported experiencing bullying. These participants had greater severity of negative schemas about others and asocial and defeatist performance beliefs, and lower social functioning scores. Conclusions: Prevalence of bullying among CHR participants is high. Bullying may be a risk factor for increased asocial and defeatist beliefs, negative core schemas, and poor social functioning. Targeting maladaptive schemas and beliefs during treatment may serve to improve functional outcomes in this group. [ABSTRACT FROM AUTHOR]

Immediate early genes (IEGs) typically are the first genetic responders to a variety of cellular activations. The IEG that encodes activity-regulated cytoskeleton-associated protein ( arc/arg3.1) has attracted much interest because its mRNA is transported to and translated near activated synapses. Moreover, arc has been implicated in both long-term potentiation (LTP) and long-term depression (LTD). However, little is known about the time course of altered arc expression during LTP and LTD. Here we characterized arc mRNA levels in area CA1 of the adult rat hippocampus in vivo after LTP- and LTD-inducing stimulations that were identical, except for the temporal patterning of the stimulation pulses. We observed a persistent increase in arc mRNA level during LTP. In contrast, during LTD, arc mRNA level first was decreased and then transiently increased relative to control level. These findings demonstrate that arc mRNA is regulated differently during LTP and LTD, and they provide evidence for stimulation-induced downregulation of mRNA availability during LTD. Findings of abbreviated LTD when transcription was inhibited indicate that the prolonged maintenance of the type of N-methyl- D-aspartate receptor-dependent LTD studied here requires de novo transcription. Furthermore, lack of evidence for a LTD-associated change in the mRNA level of the IEG zif268 demonstrates that the decrease in arc mRNA during LTD is not a general genetic response. Thus, the regulation of arc expression not only differs between LTP and LTD, but also diverges from that of other IEGs implicated in activity-dependent synaptic plasticity. © 2010 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]