The Selective Dopamine D2 Blocker Sulpiride Modulates the Relationship Between Agentic Extraversion and Executive Functions.

Initial studies suggest that agentic extraversion and executive functions (EF) are associated, because they share influences of individual differences in the dopamine (DA) system. However, it is unclear whether previously reported associations are specific to certain EFs (e.g., to updating or shifting) or due to shared variance among EF tasks. We investigated the DA-related relationship between agentic extraversion and two EF tasks in a placebo-controlled between-group design with the DA D2 receptor blocker sulpiride (200 mg) in 92 female volunteers. Our goals were to investigate whether (1) there is an association between agentic extraversion and EFs measured with two different tasks (3-back and switching), (2) this association is sensitive to a pharmacological manipulation of DA, and (3) the effects can be ascribed to shared or specific task variance. We observed the expected interaction between drug condition and agentic extraversion for both tasks in a multivariate multiple linear regression model, which supports the DA theory of extraversion. Subsequent univariate analyses revealed a highly similar interaction effect between drug condition and agentic extraversion on two of three performance measures and this effect was somewhat attenuated when we controlled for shared task variance. This pattern matches the interpretation that the association between agentic extraversion and both tasks is partly due to DA-based processes shared among the tasks. Our results, although limited by the low reliability of the switching task, suggest that variance components and measurement difficulties of EF tasks should be considered when investigating personality-related individual differences in EFs.

Mitotane Monotherapy in Patients With Advanced Adrenocortical Carcinoma.

Context: Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting: Multicenter cohort study of three German referral centers. Patients: One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures: Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results: Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions: At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.