Siblings' similarity in neural responses to loss reflects mechanisms of familial transmission for depression.

Having a depressed first-degree relative is one of the most replicated risk factors for depression. Research on the familial transmission of depression, however, has largely ignored siblings, even though sibling relationships are commonplace and characterized by frequent and intense emotions. It has been suggested that frequent contacts in close relationships lead to similarities in emotions and cognitions over time, a process underpinned by biobehavioral synchrony.

The effects of family support and smartphone-derived homestay on daily mood and depression among sexual and gender minority adolescents.

Sexual and gender minority (SGM) adolescents are at elevated risk for depression. This risk is especially pronounced among adolescents whose home environment is unsupportive or nonaffirming, as these adolescents may face familial rejection due to their identity. Therefore, it is critical to better understand the mechanisms underlying this risk by probing temporally sensitive associations between negative mood and time spent in potentially hostile home environments.

Cognitive inflexibility and heightened error monitoring are related to lower sexual functioning.

Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30.

Detecting adolescent depression through passive monitoring of linguistic markers in smartphone communication.

Background: Cross sectional studies have identified linguistic correlates of major depressive disorder (MDD) in smartphone communication. However, it is unclear whether monitoring these linguistic characteristics can detect when an individual is experiencing MDD, which would facilitate timely intervention.

Methods: Approximately 1.

Capturing mood dynamics through adolescent smartphone social communication.

Most adolescents with depression remain undiagnosed and untreated-missed opportunities that are costly from both personal and public health perspectives. A promising approach to detecting adolescent depression in real-time and at a large scale is through their social communication on the smartphone (e.g.

Electrophysiological evidence of mal-adaptation to error in remitted depression.

Identifying risk markers for major depressive disorder (MDD) that persist into remission is key to address MDD's high rate of recurrence. Central to MDD recurrence are the disorder's negative information processing biases, such as heightened responses to errors, which may subsequently impair abilities to monitor performance and adjust behaviors based on environmental demands. However, little is known regarding the neurophysiological correlates of post-error adaptation in depression.

Preliminary evidence that individuals with remitted alcohol use disorder and major depressive disorder exhibit enhanced neural responses to reward: An EEG study.

Introduction: Disruptions in neural responses to reward are implicated in risk for Alcohol Use Disorder (AUD) and Major Depressive Disorder (MDD). It is not clear whether these findings extend to those in remission from AUD and MDD, a critical question as studies of remission can (a) rule out effects due to current symptoms, and (b) can reveal potential trait-like differences.

Methods: Individuals with and without remitted AUD (rAUD) and/or rMDD (rMDD) were drawn from a larger study to create four groups: rAUD (n = 54), rMDD (n = 66), rAUD + rMDD (n = 53), and a community control group (CCG; n = 81).

Childhood trauma predicts blunted error monitoring in adulthood: An event-related potential study.

Abuse and neglect have detrimental consequences on emotional and cognitive functioning during childhood and adolescence, including error monitoring, which is a critical aspect of cognition that has been implicated in certain internalizing and externalizing psychopathologies. It is unclear, however, whether (a) childhood trauma has effects on error monitoring and, furthermore whether, (b) error monitoring mediates the relation between childhood trauma and psychopathology in adulthood. To this end, in a large sample of young adults (ages 18-30) who were oversampled for psychopathology (N = 390), the present study assessed relations between childhood trauma and error-related negativity (ERN), which is a widely used neurophysiological indicator of error monitoring.

Event-related potentials to acoustic startle probes during unpredictable threat are associated with individual differences in intolerance of uncertainty.

Individual differences in sensitivity to unpredictable threat may be a critical mechanism for internalizing psychopathology phenotypes. The present study examined whether the startle probe-elicited N100 and P300 during unpredictable threat - two event-related potentials indexing early and elaborative attentional processing of unpredictable threat - may be endophenotypes for internalizing psychopathology, including fear and distress/misery disorders and intolerance of uncertainty (IU), a clinical trait that is transdiagnostically associated with internalizing disorders. A large sample of adult siblings (N = 375) completed the no, predictable, and unpredictable threat task, during which the N100 and P300 were recorded.

Exposure-response analyses of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma.

Background: Exposure-response analyses were conducted to explore the relationship between selected efficacy and safety endpoints and serum phosphate (PO4) concentrations, a potential biomarker of efficacy and safety, in locally advanced or metastatic urothelial carcinoma patients with FGFR alterations treated with erdafitinib.

Methods: Data from two dosing regimens of erdafitinib in a phase 2 study (NCT02365597), 6 and 8-mg/day with provision for pharmacodynamically guided titration per serum PO4 levels, were analyzed using Cox proportional hazard or logistic regression models. Efficacy endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Erdafitinib's effect on serum phosphate justifies its pharmacodynamically guided dosing in patients with cancer.

A population pharmacokinetic (PK)-pharmacodynamic (PD) model was developed using data from 345 patients with cancer. The population PK-PD model evaluated the effect of erdafitinib total and free plasma concentrations on serum phosphate concentrations after once-daily oral continuous (0.5-12 mg) and intermittent (10-12 mg for 7 days on/7 days off) dosing, and investigated the potential covariates affecting erdafitinib-related changes in serum phosphate levels.

An Effortful Approach to Social Affiliation in Schizophrenia: Preliminary Evidence of Increased Theta and Alpha Connectivity during a Live Social Interaction.

People with schizophrenia often experience a profound lack of motivation for social affiliation-a facet of negative symptoms that detrimentally impairs functioning. However, the mechanisms underlying social affiliative deficits remain poorly understood, particularly under realistic social contexts. Here, we investigated subjective reports and electroencephalography (EEG) functional connectivity in schizophrenia during a live social interaction.

Prediction of the drug-drug interaction potential of the α1-acid glycoprotein bound, CYP3A4/CYP2C9 metabolized oncology drug, erdafitinib.

Erdafitinib is a potent oral pan-fibroblast growth factor receptor inhibitor being developed as oncology drug for patients with alterations in the fibroblast growth factor receptor pathway. Erdafitinib binds preferentially to α1-acid glycoprotein (AGP) and is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. This article describes a physiologically based pharmacokinetic (PBPK) model for erdafitinib to assess the drug-drug interaction (DDI) potential of CYP3A4 and CYP2C9 inhibitors and CYP3A4/CYP2C9 inducers on erdafitinib pharmacokinetics (PK) in patients with cancer exhibiting higher AGP levels and in populations with different CYP2C9 genotypes.

Comparability of social anhedonia across epidemiological dimensions: A multinational study of measurement invariance of the Revised Social Anhedonia Scale.

Social anhedonia, or the loss of motivation in and pleasure from social engagement, is an important feature in understanding the etiology and outcome of various psychopathologies. While the Revised Social Anhedonia Scale (RSAS) represents one of the most commonly used self-report measures of social anhedonia, little is known regarding the construct comparability across populations. We examined measurement invariance of the full and brief RSAS in a diverse, international sample of 14,064 participants across nine epidemiological dimensions, including gender, age, ethnicity, education, community income, continent, migrant status, ethnic density, and urbanicity.

Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19.

The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CL) in a post-translational processing step that is critical for coronavirus replication. The 3CL sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage.

What you want may not be what you like: A test of the aberrant salience hypothesis in schizophrenia risk.

Motivational abnormalities represent a key area of dysfunction in individuals with, or at risk for, schizophrenia and severely limit broad domains of functioning in these populations. The aberrant salience hypothesis posits that motivational abnormalities are the result of an over-attribution of salience to nonpleasurable stimuli but an under-attribution of salience to pleasurable ones. Consequently, people "want" what they do not "like" but do not "want" what they "like.

Schizotypy dimensions are associated with altered resting state alpha connectivity.

The disconnection hypothesis of schizophrenia says that symptoms are explained by dysfunctional connections across a wide range of brain networks. Despite some support for this hypothesis, there have been mixed findings. One reason for these may be the multidimensional nature of schizophrenia symptoms.

Electrophysiological responses to images ranging in motivational salience: Attentional abnormalities associated with schizophrenia-spectrum disorder risk.

Individuals at risk for schizophrenia-spectrum disorders display abnormalities related to motivational salience, or the ability of stimuli to elicit attention due to associations with rewards or punishments. However, the nature of these abnormalities is unclear because most focus on responses to stimuli from broad "pleasant" and "unpleasant" categories and ignore the variation of motivational salience within these categories. In two groups at risk for schizophrenia-spectrum disorders-a Social Anhedonia group and a Psychotic-like Experiences group-and a control group, the current study examined event-related potential components sensitive to motivational salience-the Early Posterior Negativity (EPN), reflecting earlier selective attention, and the Late Positive Potential (LPP), reflecting sustained attention.

Differential item functioning of the Multidimensional Schizotypy Scale and Multidimensional Scale-Brief across ethnicity.

Schizotypy refers to traits or symptoms similar to schizophrenia, but in a diminished form, and schizotypy is thought to reflect a liability for the future development of schizophrenia. The Multidimensional Schizotypy Scale (MSS) is a new measure of schizotypy that improves on existing measures. The MSS contains full and brief subscales for positive, negative, and disorganized schizotypy.

Population Pharmacokinetics of Total and Free Erdafitinib in Adult Healthy Volunteers and Cancer Patients: Analysis of Phase 1 and Phase 2 Studies.

A population pharmacokinetic (PK) model was developed using data pooled from 6 clinical studies (3 in healthy volunteers and 3 in cancer patients) to characterize total and free plasma concentrations of erdafitinib following single- and multiple-dose administration, to understand clinically relevant covariates, and to quantify the inter- and intraindividual variability in erdafitinib PK. An open, linear, 3-compartment disposition model with first-order absorption and a lag time was used to describe the PK profile of total and free erdafitinib plasma concentrations. The PK of erdafitinib were linear and time independent.

Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adults: A Randomized, Open-Label, Drug-Drug Interaction Study.

Background And Objectives: Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. The aim of this phase 1 study was to assess the pharmacokinetics and safety of erdafitinib in healthy participants when coadministered with fluconazole (moderate CYP2C9 and CYP3A inhibitor), and itraconazole (a strong CYP3A4 and P-glycoprotein inhibitor). The effect of CYP2C9 genotype variants (*1/*1, *1/*2, *1/*3) on the pharmacokinetics of erdafitinib was also investigated.

Effect of Plasma Protein Binding on the Pharmacokinetics of Erdafitinib: Results of an Integrated Cross-Study Analysis.

Erdafitinib, a potent oral fibroblast growth factor receptor inhibitor, is a low extraction ratio drug highly bound to alpha-1-acid glycoprotein (AGP) with free fraction (f ) varying across populations. This analysis aimed to characterize the impact of plasma protein binding on erdafitinib pharmacokinetics (PK). Plasma protein-binding data (f , AGP, albumin) and PK parameters were pooled from 6 phase 1 studies in healthy participants and 1 first-in-human study in patients with cancer.

Assessment of the effect of erdafitinib on cardiac safety: analysis of ECGs and exposure-QTc in patients with advanced or refractory solid tumors.

Purpose: To characterize the effect of erdafitinib on electrocardiogram (ECG) parameters and the relationship between erdafitinib plasma concentrations and QTc interval changes in patients with advanced or refractory solid tumors.

Methods: Triplicate ECGs and continuous 12-lead Holter data were collected in the dose escalation part (Part 1) of the first-in-human study, with doses ranging from 0.5 to 12 mg.