Enhanced 'Reading the Mind in the Eyes' in borderline personality disorder compared to healthy controls.

BACKGROUND: Borderline personality disorder (BPD) is partly characterized by chronic instability in interpersonal relationships, which exacerbates other symptom dimensions of the disorder and can interfere with treatment engagement. Facial emotion recognition paradigms have been used to investigate the bases of interpersonal impairments in BPD, yielding mixed results. We sought to clarify and extend past findings by using the Reading the Mind in the Eyes Test (RMET), a measure of the capacity to discriminate the mental state of others from expressions in the eye region of the face. METHOD: Thirty individuals diagnosed with BPD were compared to 25 healthy controls (HCs) on RMET performance. Participants were also assessed for depression severity, emotional state at the time of assessment, history of childhood abuse, and other Axis I and personality disorders (PDs). RESULTS: The BPD group performed significantly better than the HC group on the RMET, particularly for the Total Score and Neutral emotional valences. Effect sizes were in the large range for the Total Score and for Neutral RMET performance. The results could not be accounted for by demographics, co-occurring Axis I or II conditions, medication status, abuse history, or emotional state. However, depression severity partially mediated the relationship between RMET and BPD status. CONCLUSIONS: Mental state discrimination based on the eye region of the face is enhanced in BPD. An enhanced sensitivity to the mental states of others may be a basis for the social impairments in BPD.

Effects of nutrient enrichment on surface microbial community gene expression in the oligotrophic North Pacific Subtropical Gyre.

Marine microbial communities are critical for biogeochemical cycles and the productivity of ocean ecosystems. Primary productivity in the surface ocean is constrained by nutrients which are supplied, in part, by mixing with deeper water. Little is known about the time scales, frequency, or impact of mixing on microbial communities. We combined in situ sampling using the Environmental Sample Processor and a small-scale mixing experiment with lower euphotic zone water to determine how individual populations respond to mixing. Transcriptional responses were measured using the MicroTOOLs (Microbiological Targets for Ocean Observing Laboratories) microarray, which targets all three domains of life and viruses. The experiment showed that mixing substantially affects photosynthetic taxa as expected, but surprisingly also showed that populations respond differently to unfiltered deep water which contains particles (organisms and detritus) compared to filtered deep water that only contains nutrients and viruses, pointing to the impact of biological interactions associated with these events. Comparison between experimental and in situ population transcription patterns indicated that manipulated populations can serve as analogs for natural populations, and that natural populations may be frequently or continuously responding to nutrients from deeper waters. Finally, this study also shows that the microarray approach, which is complementary to metatranscriptomic sequencing, is useful for determining the physiological status of in situ microbial communities.

Physiological melatonin inhibition of human breast cancer cell growth in vitro: evidence for a glutathione-mediated pathway.

Melatonin, the chief hormone secreted by the pineal gland, has been previously shown to inhibit human breast cancer cell growth at the physiological concentration of 1 nM in vitro. In this study, using the estrogen receptor (ER)-positive human breast tumor cell line MCF-7, we have shown that 10 microM L-buthionine-[S,R]-sulfoximine (L-BSO), an inhibitor of gamma-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis), blocks the oncostatic action of 1 nM melatonin over a 5-day incubation, indicating that glutathione is required for melatonin action. The result was repeated with ZR75-1 cells, suggesting that the glutathione requirement is a general phenomenon among ER+ breast cancer cells. Addition of exogenous glutathione (1 microM) to L-BSO-treated groups restored the melatonin response in both cell lines. Further demonstration of the importance of glutathione was shown using the ER- breast tumor cell line HS578T, which is normally unresponsive to melatonin. Growth in this cell line was inhibited in the presence of 1 microM ethacrynic acid (an inhibitor of glutathione S-transferase) plus 1 nM melatonin, and this effect was blocked with 10 microM L-BSO. We also observed a steady decrease of intracellular glutathione in MCF-7 cells over a 5-day incubation, suggesting that these cells metabolize glutathione differently than do normal cells.

Melatonin augments the sensitivity of MCF-7 human breast cancer cells to tamoxifen in vitro.

Cultured MCF-7 human breast cancer cells were pre-exposed to either melatonin (232 ng/mL) or vehicle for 24 hrs prior to being washed and then re-exposed to either ethanol-vehicle or varying concentrations of tamoxifen (37.1 ng/mL, 3.71 micrograms/mL, 371 micrograms/mL) or melatonin (2.32 pg/mL, 232 ng/mL, 23.2 ng/mL) for 5 additional days. Only 371 ng/mL tamoxifen caused a 38% growth inhibition of cells pre-exposed to vehicle whereas all concentrations of tamoxifen inhibited the growth of melatonin pre-exposed cells by 28% to 61% in a dose-dependent manner. Melatonin pre-exposure, potentiated the inhibitory effect of only 232 ng/mL melatonin. Comparison of IC50 values indicate that tamoxifen is approximately a 100 times more potent inhibitor of breast cancer cell growth following the pretreatment of cells with a physiological concentration of melatonin. These results indicate that melatonin has the capability to augment the inhibitory actions of tamoxifen, and to a lesser extent itself, on human breast cancer cell growth.

Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: potential involvement of antiestrogenic mechanisms in vivo.

The N-methyl-N-nitrosourea (NMU) model of hormone-responsive rat mammary carcinogenesis was used to address the hypothesis that melatonin (Mel), the principle hormone of the pineal gland, inhibits tumorigenesis by acting as an anti-promoting rather than an anti-initiating agent. Daily late-afternoon injections of Mel (500 micrograms/day), restricted to the initiation phase of NMU mammary tumorigenesis, were ineffective in altering tumor growth over a 20-week period. When Mel treatment was delayed for 4 weeks after NMU and then continued through the remainder of the promotion phase, only tumor number was significantly lower than in controls. However, when Mel injections encompassed the entire promotion phase, both tumor incidence and number were significantly lower than in the controls. Although elimination of the endogenous Mel signal via pinealectomy promoted tumor growth, the effect was not statistically significant. Serum levels of estradiol and tumor estrogen receptor content were unaltered by either Mel or pinealectomy. While Mel treatment failed to affect circulating prolactin levels, pinealectomy caused a two-fold increase in serum prolactin. The estradiol-stimulated recrudescence of tumors following ovariectomy was completely blocked by either 20, 100 or 500 micrograms Mel/day or tamoxifen (20 micrograms/day). Thus, Mel appears to be an anti-promoting hormone that may antagonize the tumor-promoting actions of estradiol in this model of mammary tumorigenesis.

Effects of an alternative reinforcer on intravenous heroin self-administration by humans.

Five heroin-dependent research volunteers, maintained on divided daily oral morphine doses, participated in an inpatient study designed to evaluate intravenous (i.v.) heroin self-administration when money ($10, $20 or $40) was concurrently available. Each morning participants received a single injection of heroin (placebo, 6.25, 12.5, 25, or 50 mg/70 kg, i.v.) and each afternoon, they had the opportunity to self-administer all or part of the morning dose. Participants responded under a progressive-ratio schedule (50, 100, ..., 2800) during a 10-trial self-administration task. During each trial, participants could respond for 1/10th of the sampled heroin dose or 1/10th of a single money value. The progressive-ratio value increased independently for each option. The total amount of heroin and/or money chosen during the self-administration task was administered at the end of the task. Heroin dose-dependently increased ratings of 'good drug effect' and 'high', impaired task performance and decreased pupil diameter and blood oxygen saturation. Heroin also dose-dependently increased progressive-ratio break point values, which varied as a function of the alternative money amount. Consistent with previous studies, the present results demonstrate that alternative reinforcers, depending on magnitude, are effective in reducing heroin use in opioid-dependent individuals.