One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

Neural health relies on cortical excitation-inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear. Thus, in a randomized double-blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired resting-state electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state

The attention-emotion interaction in healthy female participants on oral contraceptives during 1-week escitalopram intake

Previous findings in healthy humans suggest that selective serotonin reuptake inhibitors (SSRIs) modulate emotional processing via earlier changes in attention. However, many previous studies have provided inconsistent findings. One possible reason for such inconsistencies is that these studies did not control for the influence of either sex or sex hormone fluctuations. To address this inconsistency, we administered 20 mg escitalopram or placebo for seven consecutive days in a randomized, double-blind, placebo-controlled design to sixty healthy female participants with a minimum of 3 months oral contraceptive (OC) intake. Participants performed a modified version of an emotional flanker task before drug administration, after a single dose, after 1 week of SSRI intake, and after a 1-month wash-out period. Supported by Bayesian analyses, our results do not suggest a modulatory effect of escitalopram on behavioral measures of early attentional-emotional interaction in female individuals with regular OC use. While the specific conditions of our task may be a contributing factor, it is also possible that a practice effect in a healthy sample may mask the effects of escitalopram on the attentional-emotional interplay. Consequently, 1 week of escitalopram administration may not modulate attention toward negative emotional distractors outside the focus of attention in healthy female participants taking OCs. While further research in naturally cycling females and patient samples is needed, our results represent a valuable contribution toward the preclinical investigation of antidepressant treatment

Decreased thalamo-cortico connectivity during an implicit sequence motor learning task and 7 days escitalopram intake

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram

Osmium isotopic constraints on sulphide formation in the epithermal environment of magmatic-hydrothermal mineral deposits

In the magmatic-hydrothermal environment, fluids with similar metal concentrations and sources may yield contrasting mineral assemblages in successive stages of sulphide mineralization. These differences are linked to the physico-chemical conditions of the mineralizing fluids (e.g., T, pH, fS2, fO2) acquired during their interaction with country rocks and/or by mixing with groundwater. Here, we integrate petrography and osmium (Os) isotope (187Os/188Os) sulphide geochemistry, and discuss novel constraints on magmatic fluid-rock interaction and magmatic fluid-groundwater mixing that are deemed to govern sulphide deposition in magmatic-hydrothermal systems. We studied pyrite (FeS2) and enargite (Cu3AsS4) from the porphyry-related polymetallic Cerro de Pasco (14.54–14.41 Ma) and Colquijirca (10.83–10.56 Ma) epithermal deposits in the Central Andes, Peru. Sulphide mineralization is genetically associated with Miocene magmatism and includes breccia and replacement bodies of carbonate country rocks, and veins cutting the magmatic and sedimentary country rocks. At both deposits, pyrite is followed by enargite in the paragenesis. Pyrite has a radiogenic initial 187Os/188Os isotopic composition (187Os/188Osi-pyrite or Osi-pyrite = 0.80 to 1.45). Enargite (I) enclosing pyrite or filling in cracks in pyrite also has a radiogenic initial 187Os/188Os isotopic composition (Osi-enargite I = 0.56 to 1.24). Conversely, enargite (II) that formed on irregular surfaces on earlier pyrite has an unradiogenic 187Os/188Os isotopic composition (Osi-enargite II = 0.13 to 0.17). Our data show that the paragenetic evolution from pyrite to enargite records a sharp change in the osmium isotope composition within these sulphides. Pyrite and enargite (I) record radiogenic initial 187Os/188Os isotopic compositions, indicating interaction of magmatic hydrothermal fluids with the sedimentary country rocks. However, the unradiogenic initial 187Os/188Os isotopic composition of enargite (II) suggests that magmatic fluids with a mantle-like 187Os/188Os signature ascended from parental magmatic chambers to the epithermal environment without incorporation of crustal Os via fluid-rock interaction or mixing with groundwater. This difference may be due to the country rocks being altered during previous stages, with the radiogenic crustal Os signature being flushed by earlier magmatic pulses. Our findings imply that ore metals (i.e., Cu, Au) are magma-derived, whereas the Os isotopic composition of pyrite and some enargite in epithermal deposits may capture the signature of the interaction of magmatic fluids with country rock lithologies (e.g., the Eifelian black shale in the study area) and/or groundwater. Thus, the isotopic composition of the siderophile and chalcophile trace element Os in sulphides may act as a tracer of metal source, and degree of wall-rock interaction

Assessment of reward-related brain function after a single-dose of oxytocin in autism: A randomized controlled trial

Background Autism spectrum disorder (ASD) is characterized by difficulties in social communication and interaction, which have been related to atypical neural processing of rewards, especially in the social domain. Since intranasal oxytocin has been shown to modulate activation of the brain’s reward circuit, oxytocin might ameliorate the processing of social rewards in ASD and thus improve social difficulties. Methods In this randomized, double-blind, placebo-controlled, crossover fMRI study, we examined effects of a 24 IU dose of intranasal oxytocin on reward-related brain function in 37 men with ASD without intellectual impairment and 37 age- and IQ-matched control participants. Participants performed an incentive delay task that allows the investigation of neural activity associated with the anticipation and receipt of monetary and social rewards. Results Non-significant tests suggested that oxytocin did not influence neural processes related to the anticipation of social or monetary rewards in either group. Complementary Bayesian analyses indicated moderate evidence for a null model, relative to an alternative model. Our results are inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. There were no significant differences in reward-related brain function between the two groups under placebo. Conclusions Our results do not support the hypothesis that intranasal oxytocin generally enhances activation of reward-related neural circuits in men with and without ASD

Putting the “We” Into Well‐being: Using Collectivism‐Themed Measures of Well‐Being Attenuates Well‐being's Association With Individualism

Studies repeatedly have documented that societal well‐being is associated with individualism. Most of these studies, however, have conceptualized/measured well‐being as individual life satisfaction—a type of well‐being that originates in Western research traditions. Drawing from the latest research on interdependent happiness and on family well‐being, we posit that people across cultures pursue different types of well‐being, and test whether more collectivism‐themed types of well‐being that originate in Confucian traditions also are associated with individualism. Based on data collected from 2,036 participants across 12 countries, we find support for the association between individual life satisfaction and individualism at the societal level, but show that well‐being's association with individualism is attenuated when some collectivism‐themed measures of well‐being are considered. Our article advances knowledge on the flourishing of societies by suggesting that individualism may not always be strongly linked with societal well‐being. Implications for public policies are signaled

Introduction to a Culturally Sensitive Measure of Well-Being: Combining Life Satisfaction and Interdependent Happiness Across 49 Different Cultures

How can one conclude that well-being is higher in country A than country B, when well-being is being measured according to the way people in country A think about well-being? We address this issue by proposing a new culturally sensitive method to comparing societal levels of well-being. We support our reasoning with data on life satisfaction and interdependent happiness focusing on individual and family, collected mostly from students, across forty-nine countries. We demonstrate that the relative idealization of the two types of well-being varies across cultural contexts and are associated with culturally different models of selfhood. Furthermore, we show that rankings of societal well-being based on life satisfaction tend to underestimate the contribution from interdependent happiness. We introduce a new culturally sensitive method for calculating societal well-being, and examine its construct validity by testing for associations with the experience of emotions and with individualism-collectivism. This new culturally sensitive approach represents a slight, yet important improvement in measuring well-being

Keratinocyte Growth Factor Induces Gene Expression Signature Associated with Suppression of Malignant Phenotype of Cutaneous Squamous Carcinoma Cells

Keratinocyte growth factor (KGF, fibroblast growth factor-7) is a fibroblast-derived mitogen, which stimulates proliferation of epithelial cells. The expression of KGF by dermal fibroblasts is induced following injury and it promotes wound repair. However, the role of KGF in cutaneous carcinogenesis and cancer progression is not known. We have examined the role of KGF in progression of squamous cell carcinoma (SCC) of the skin. The expression of KGF receptor (KGFR) mRNA was lower in cutaneous SCCs (n = 6) than in normal skin samples (n = 6). Expression of KGFR mRNA was detected in 6 out of 8 cutaneous SCC cell lines and the levels were downregulated by 24-h treatment with KGF. KGF did not stimulate SCC cell proliferation, but it reduced invasion of SCC cells through collagen. Gene expression profiling of three cutaneous SCC cell lines treated with KGF for 24 h revealed a specific gene expression signature characterized by upregulation of a set of genes specifically downregulated in SCC cells compared to normal epidermal keratinocytes, including genes with tumor suppressing properties (SPRY4, DUSP4, DUSP6, LRIG1, PHLDA1). KGF also induced downregulation of a set of genes specifically upregulated in SCC cells compared to normal keratinocytes, including genes associated with tumor progression (MMP13, MATN2, CXCL10, and IGFBP3). Downregulation of MMP-13 and KGFR expression in SCC cells and HaCaT cells was mediated via ERK1/2. Activation of ERK1/2 in HaCaT cells and tumorigenic Ha-ras-transformed HaCaT cells resulted in downregulation of MMP-13 and KGFR expression. These results provide evidence, that KGF does not promote progression of cutaneous SCC, but rather suppresses the malignant phenotype of cutaneous SCC cells by regulating the expression of several genes differentially expressed in SCC cells, as compared to normal keratinocytes