Phase IIb Trial of an α7 Nicotinic Receptor Partial Agonist With and Without Nicotine Patch for Withdrawal-Associated Cognitive Deficits and Tobacco Abstinence.

PURPOSE/BACKGROUND: The objective of this study was to determine whether a novel α7 nicotinic acetylcholine receptor partial agonist improves cognition during nicotine withdrawal and improves abstinence rates. To do so, the effect of the α7 nicotinic acetylcholine receptor partial agonist, encenicline, on cognition and abstinence was evaluated when given as monotherapy and when combined with transdermal nicotine patch (nicotine replacement therapy [NRT]). METHODS: Adult daily smokers, n = 160, who were motivated to quit smoking completed cognitive testing at satiated baseline and after overnight abstinence and then were randomized to receive a 12-week trial of encenicline 1 mg twice daily or identical placebo the day of the overnight abstinent cognitive testing. In the first 6 weeks of the 12-week encenicline administration, participants were also randomized to 6 weeks of NRT patch or placebo patch. Primary outcomes were cognition during abstinence and 7-day point-prevalence abstinence at week 12. RESULTS: No beneficial effects of encenicline were observed on cognition or abstinence when compared with placebo or when combined with NRT compared with placebo capsule + NRT. Of the 4 conditions, abstinence rates were lowest among those assigned to encenicline alone. CONCLUSIONS: Beneficial effects of NRT were observed on cognitive and abstinence outcomes when combined with encenicline compared with encenicline plus placebo patch. Addition of NRT to encenicline improved odds of abstinence approximately 3-fold compared with encenicline plus placebo patch. We conclude that encenicline, 1 mg/d, did not improve abstinence-associated cognitive impairment or abstinence rates as monotherapy or adjunctive therapy to NRT patch.

Negative world views after trauma: Neurophysiological evidence for negative expectancies.

OBJECTIVE: Negative views of both the self and the world are commonly seen in individuals who have suffered psychological trauma. These negative cognitions are thought to be significant as they are likely to play a critical role in furthering, if not promoting, other symptoms and exacerbating the dysfunction sometimes seen after a traumatic event. This has led to the inclusion of "persistent negative beliefs and expectations about oneself or the world" in the DSM-5 (American Psychiatric Association, 2013). Although there is considerable self-report and behavioral evidence for negative biases after trauma, there is less concurrent neurophysiological data. This study used the N400, an event-related potential sensitive to semantic expectancies, to assess negative expectations in a trauma sample. METHOD: In this study, 39 participants completed an N400 task in which they read ambiguous sentence stems that ended either with a positive final word (Things will turn out . . . fine) or a negative final word (Things will turn out . . . badly). The authors predicted that those trauma survivors with negative cognitions (as measured by the Posttraumatic Cognitions Inventory [PTCI]: Foa et al., 1999) would show N400 amplitudes indicating expectancies for negative endings. Augmenting the previous self-report data, this would provide evidence for negative expectancies that are fairly early and relatively automatic. RESULTS: N400 amplitudes to negative sentence endings were significantly related to negative views of the world as measured by the PTCI. CONCLUSIONS: This suggests that negative world views in trauma survivors have demonstrable neurophysiological correlates and impact on expectations in ambiguous situations. (PsycINFO Database Record