Risky decision-making in the Context of Contingency Management for Methamphetamine Use Disorder

Background: Risky decision-making is strongly implicated in adverse real-world risk-taking behaviour, and is associated with Substance Use Disorder, including Methamphetamine Use Disorder. Laboratory neurocognitive tasks typically utilized to assess risky decision-making have been able to distinguish participants with Substance Use Disorder from controls, although considerable heterogeneity is still evident within substance-using populations, which remains largely unexplained. Preliminary evidence has also tied risky decision-making to treatment outcomes, although no research has investigated risk-decision-making within Methamphetamine Use Disorder in the context of Contingency Management treatment. Methods: This study aimed to investigate decision-making on the Iowa Gambling Task and the Balloon Analogue Risk at baseline as both a function and predictor of treatment response on an 8-week treatment of Contingency Management. Of 26 participants with Methamphetamine Use Disorder, 17 responded to Contingency Management treatment, whilst 9 were non-responders. Using various mixed-effect modelling techniques and ANCOVA, performance by nonresponders were compared to responders, as well as a group of 19 healthy, nonsubstance-using control participants. Results: Group differences between non-responders, responders and controls were exclusively obtained on the Iowa Gambling Task. A trend-level (p=.051), large effect size (g=-0.98) was observed in the effect of reward magnitude between non-responders and healthy controls. More specifically, non-responders tended to seek-out large short-term rewards in spite of long-term losses relative to controls, however, groups did not also differ in effect of short-term loss magnitude. Non-responders also appeared to demonstrate poorer learning than healthy controls, although this finding was also at trend-level (p=.081) with a medium effect size (g =-0.63). In addition, results showed that responders and non-responders were differentially influenced by the frequency of outcomes, where responders demonstrated a greater preference for frequent rewards and infrequent losses relative to non-responders. This difference was at trend-level (p=.053) and the effect was moderately sized (g =-0.74). Impulsivity did not moderate group differences in decision-making, but did positively predict a greater likelihood of relapse at least once during Contingency Management (p =.035), although this effect was small (OR=1.10). Poor overall performance on the IGT appeared to predict a greater likelihood of prolonged relapse on Contingency Management following initial relapse, although this was at trend-level (p =.071) with a small effect size (OR=1.80). Conclusion: Findings provide evidence for individual differences in risky decision-making within Methamphetamine User Disorder, suggesting that risky decision-making is unlikely to be a homogeneous characteristic of substance-using populations, as is typically treated in the literature. Risky decision-making may also act as a risk factor for poor treatment success on Contingency Management, which in turn suggests that assessing risky decision-making of individuals with Methamphetamine Use disorder prior to commencing Contingency Management treatment might assist in identifying those at high risk

Investigating pupillometry to detect emotional regulation difficulties in post-traumatic stress disorder

Objective: Individuals with posttraumatic stress disorder (PTSD) have been found to exhibit emotional regulation difficulties. However, the specific neural mechanisms that underlie these difficulties remain understudied. This study aimed to use pupillometry as an index function of parasympathetic nervous system activation, to investigate the mechanisms underlying emotional regulation difficulties in individuals with PTSD. Method: A total of 87 trauma-exposed mothers (34 with PTSD and 53 non-PTSD controls) completed an eye tracking assessment in which pupillary dilation in response to emotionally valenced stimuli was measured. The participants also completed two self-report measures of emotional regulation, namely the Difficulties in Emotional Regulation Scale and the Emotional Regulations Questionnaire. Linear mixed-effect modelling was used to assess potential group differences. Results: The PTSD group exhibited increased pupillary dilation to positively valenced stimuli compared to the non-PTSD group. However, no significant associations between the self-report measures and pupillary response to emotionally valenced stimuli were found. Conclusion: Increased pupillary dilation in PTSD may reflect impaired parasympathetic nervous system processes. The lack of association of these measures with self-reported emotion regulation may suggest reporting biases. Larger studies with more generalised populations are required to consolidate these preliminary findings.acceptedVersionPeer reviewe

Efficacy of a dialogic book-sharing intervention in a South African birth cohort: a randomized controlled trial

Evidence shows that dialogic book-sharing improves language development in young children in low-middle income countries (LMICs), particularly receptive and expressive language. It is unclear whether this intervention also boosts development of other neurocognitive and socio-emotional domains in children. Using a randomized controlled trial (RCT) nested in the Drakenstein Child Health Study (DCHS), a book-sharing intervention was implemented in caregivers of 3.5-year-old preschool children living in low-income South African communities. 122 Caregivers and their children (mean age 3.5 years) were randomly assigned to an intervention group (n = 61) or waitlist control group (n = 61). A neurocognitive battery determined baseline receptive and expressive language, executive function, theory of mind, and behavior scores. No differences were observed between intervention and control groups on receptive and expressive language, or any of the neurocognitive or socio-emotional measures from baseline (3.5 years) to 4 months post-intervention administration (4 years). The benefits noted in prior literature of book-sharing in infants did not appear to be demonstrated at 4 months post-intervention, in children from 3.5 to 4 years of age. This suggests the importance of early intervention and emphasizes the need for further research on adaptation of book-sharing for older participants in a South African context. retrospectively registered on 03/04/2022 PACTR202204697674974

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival