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Although protein drugs are powerful biologic therapeutics, they cannot be delivered orally because their large size and hydrophilicity limit their absorption across the intestinal epithelium. One potential solution is the incorporation of permeation enhancers into oral protein formulations; however, few have advanced clinically due to toxicity concerns surrounding chronic use. To better understand these concerns, we conducted a 30-day longitudinal study of daily oral permeation enhancer use in mice and resultant effects on intestinal health. Specifically, we investigated three permeation enhancers: sodium caprate (C10), an industry standard, as well as 1-phenylpiperazine (PPZ) and sodium deoxycholate (SDC). Over 30 days of treatment, all mice gained weight, and none required removal from the study due to poor health. Furthermore, intestinal permeability did not increase following chronic use. We also quantified the gene expression of four tight junction proteins (claudin 2, claudin 3, ZO-1, and JAM-A). Significant differences in gene expression between untreated and permeation enhancer-treated mice were found, but these varied between treatment groups, with most differences resolving after a 1-week washout period. Immunofluorescence microscopy revealed no observable differences in protein localization or villus architecture between treated and untreated mice. Overall, PPZ and SDC performed comparably to C10, one of the most clinically advanced enhancers, and results suggest that the chronic use of some permeation enhancers may be therapeutically viable from a safety standpoint. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety are prevalent in youth populations and typically emerge during adolescence. Repetitive negative thinking (RNT) is a putative transdiagnostic mechanism with consistent associations with depression and anxiety. Targeting transdiagnostic processes like RNT for youth depression and anxiety may offer more targeted, personalised and effective treatment. Methods: A meta-analysis was conducted to examine the effect of psychological treatments on RNT, depression and anxiety symptoms in young people with depression or anxiety, and a meta-regression to examine relationships between outcomes. Results: Twenty-eight randomised controlled trials examining 17 different psychological interventions were included. Effect sizes were small to moderate across all outcomes (Hedge's g depression = −0.47, CI −0.77 to −0.17; anxiety = −0.42, CI −0.65 to −0.20; RNT = −0.45, CI −0.67 to −0.23). RNT-focused and non-RNT focused approaches had comparable effects; however, those focusing on modifying the process of RNT had significantly larger effects on RNT than those focusing on modifying negative thought content. Meta-regression revealed a significant relationship between RNT and depression outcomes only across all intervention types and with both depression and anxiety for RNT focused interventions only. Conclusion: Consistent with findings in adults, this review provides evidence that reducing RNT with psychological treatment is associated with improvements in depression and anxiety in youth. Targeting RNT specifically may not lead to better outcomes compared to general approaches; however, focusing on modifying the process of RNT may be more effective than targeting content. Further research is needed to determine causal pathways. [ABSTRACT FROM AUTHOR]

Aim: Major depressive disorder (MDD) has far reaching impacts for young people, their families and society. Cognitive behavioural therapy (CBT) is one of the first‐line treatments for young people experiencing MDD; however, there is limited research examining how young people with MDD experience CBT. The aim of this study was to explore their experience and their views of this intervention. Methods: We employed a qualitative research design, with semi‐structured interviews and thematic analysis. Eight participants aged between 17 and 24 years who received CBT for MDD in a randomized controlled trial were recruited. Results: Five themes were identified: the importance of relationship with clinician; the range of useful components within CBT; the ability for CBT to accommodate different techniques and presenting issues; the importance of checking in with clients during the process of therapy; and the impacts of MDD on therapy. Conclusions: The findings highlight the importance of clinicians having a youth friendly and collaborative approach that allows a modular delivery of a range of CBT techniques to suit the client's presenting issue and formulation. There is a need to continually check how young people are responding to interventions, and to be aware of potential cognitive deficits and adjust therapy accordingly. This is a small study that provides insight into how young people with MDD experience CBT and avenues to explore for tailoring provision of CBT to enhance the therapeutic experience for this population. [ABSTRACT FROM AUTHOR]

Objective: Caregivers of individuals with severe mental illness often experience significant negative experiences of care, which can be associated with higher levels of expressed emotion. Expressed emotion is potentially a modifiable target early in the course of illness, which might improve outcomes for caregivers and patients. However, expressed emotion and caregiver experiences in the early stages of disorders might be moderated by the type of severe mental illness. The aim was to determine whether experiences of the caregiver role and expressed emotion differ in caregivers of young people with first-episode psychosis versus young people with 'first-presentation' borderline personality disorder features. Method: Secondary analysis of baseline (pre-treatment) data from three clinical trials focused on improving caregiver outcomes for young people with first-episode psychosis and young people with borderline personality disorder features was conducted (ACTRN12616000968471, ACTRN12616000304437, ACTRN12618000616279). Caregivers completed self-report measures of experiences of the caregiver role and expressed emotion. Multivariate generalised linear models and moderation analyses were used to determine group differences. Results: Data were available for 265 caregivers. Higher levels of negative experiences and expressed emotion, and stronger correlations between negative experiences and expressed emotion domains, were found in caregivers of young people with borderline personality disorder than first-episode psychosis. Caregiver group (borderline personality disorder, first-episode psychosis) moderated the relationship between expressed emotion and caregiver experiences in the domains of need to provide backup and positive personal experiences. Conclusion: Caregivers of young people with borderline personality disorder experience higher levels of negative experiences related to their role and expressed emotion compared with caregivers of young people with first-episode psychosis. The mechanisms underpinning associations between caregiver experiences and expressed emotion differ between these two caregiver groups, indicating that different supports are needed. For borderline personality disorder caregivers, emotional over-involvement is associated with both negative and positive experiences, so a more detailed understanding of the nature of emotional over-involvement for each relationship is required to guide action. [ABSTRACT FROM AUTHOR]

Objective: Comorbid social anxiety is common in psychotic disorders and is associated with multiple negative consequences. However, the long‐term effects of persistent social anxiety versus fluctuating or no anxiety on social functioning and health‐related quality of life (HR‐QoL) have received scant attention. Therefore, we aimed to examine the prevalence of persistent social anxiety to determine its effect on social functioning and HR‐QoL in first‐episode psychosis (FEP). Methods: One hundred and eight individuals with remitted FEP were classified into three groups (persistent, fluctuating or no social anxiety) according to the Social Interaction Anxiety Scale over an 18‐month follow‐up period. The three groups were then compared at 18 months follow‐up to assess the influence of social anxiety on social functioning and HR‐QoL before and after controlling for confounders. Results: Of the 108 individuals with FEP, 25 (23.1%) had persistent social anxiety. This group presented lower social functioning and HR‐QoL levels compared to the groups with fluctuating or no anxiety symptoms. The effect on HR‐QoL remained significant after controlling for positive psychotic and depressive symptoms. Conclusions: In this study, nearly one‐quarter of young people with remitted FEP experienced persistent social anxiety symptoms, which had a negative impact on HR‐QoL. Thus, individuals with persistent social anxiety constitute a highly vulnerable group and may require targeted interventions to improve their social functioning and HR‐QoL. [ABSTRACT FROM AUTHOR]