Plasma Endocannabinoid Levels in Patients with Borderline Personality Disorder and Healthy Controls.

Borderline personality disorder (BPD) is a highly prevalent psychiatric disorder and presents a complex therapeutic challenge due to limited treatment modalities. Recent focus has converged on the endocannabinoid system (ECS) as a prospective modulator of psychopathological processes in BPD. To address this hypothesis, we analysed plasma endocannabinoid concentrations, specifically anandamide (AEA) and 2-arachidonoylglycerol (2-AG), in a cohort of 49 female BPD patients and 32 matched healthy controls (HC). Additionally, we examined the effect of the FAAH polymorphism rs324420 and correlates with psychopathology. The results indicate heightened AEA levels and, by trend, augmented 2-AG levels within the patient group, as compared to the HC group. Significant between group differences in AEA levels were evident in the CC genotype (FAAH_rs324420) but not in A-allele carriers while the commonly observed difference in AEA levels between A-allele carriers as compared to the CC genotype was not evident in patients. An effect of genotype was found with higher ratings of depression (Beck's depression inventory, BDI-II) in the CC genotype compared to A-allele carriers (FAAH_rs32442), particularly in the patients. Significant alterations in AEA (and by trend in 2-AG) in patients with BPD may relate to compensatory ECS activity. The finding that the effect is most pronounced in CC homozygotes, might point towards a countermeasure to balance physiologically lower baseline AEA levels. The findings warrant further research to develop potentially beneficial psychopharmacological therapies.

Intranasal Oxytocin Modulates Decision-Making Depending on Outcome Predictability-A Randomized Within-Subject Controlled Trial in Healthy Males.

Oxytocin (OT) has been extensively studied with regard to its socio-cognitive and -behavioral effects. Its potential as a therapeutic agent is being discussed for a range of neuropsychiatric conditions. However, there is limited evidence of its effects on non-social cognition in general and decision-making in particular, despite the importance of these functions in neuropsychiatry. Using a crossover/within-subject, blinded, randomized design, we investigated for the first time if intranasal OT (24 IU) affects decision-making differently depending on outcome predictability/ambiguity in healthy males. The Iowa Gambling Task (IGT) and the Cambridge Risk Task (CRT) were used to assess decision-making under low outcome predictability/high ambiguity and under high outcome probability/low ambiguity, respectively. After administration of OT, subjects performed worse and exhibited riskier performance in the IGT (low outcome predictability/high ambiguity), whereas they made borderline-significant less risky decisions in the CRT (high outcome probability/low ambiguity) as compared to the control condition. Decision-making in healthy males may therefore be influenced by OT and adjusted as a function of contextual information, with implications for clinical trials investigating OT in neuropsychiatric conditions.

Divergent effects of oxytocin on "mind-reading" in healthy males.

The neuropeptide oxytocin (OT) has been associated with a broad range of human behaviors, particularly in the domain of social cognition, and is being discussed to play a role in a range of psychiatric disorders. Studies using the Reading The Mind In The Eyes Test (RMET) to investigate the role of OT in mental state recognition reported inconsistent outcomes. The present study applied a randomized, double-blind, cross-over design, and included measures of serum OT. Twenty healthy males received intranasal placebo or OT (24 IU) before performing the RMET. Frequentist and Bayesian analyses showed that contrary to previous studies (Domes et al., 2007; Radke & de Bruijn, 2015), individuals performed worse in the OT condition compared to the placebo condition (p = 0.023, Cohen's d = 0.55, 95% confidence interval [CI] [0.08, 1.02], BF10 = 6.93). OT effects did not depend on item characteristics (difficulty, valence, intensity, sex) of the RMET. Furthermore, OT serum levels did not change after intranasal OT administration. Given that similar study designs lead to heterogeneous outcomes, our results highlight the complexity of OT effects and support evidence that OT might even interfere with social cognitive abilities. However, the Bayesian analysis approach shows that there is only moderate evidence that OT influences mind-reading, highlighting the need for larger-scale studies considering the discussed aspects that might have led to divergent study results.