Remembering the null hypothesis when searching for brain sex differences.

Human brain sex differences have fascinated scholars for centuries and become a key focus of neuroscientists since the dawn of MRI. We recently published a major review in Neuroscience and Biobehavioral Reviews showing that most male-female brain differences in humans are small and few have been reliably replicated. Although widely cited, this work was the target of a critical Commentary by DeCasien et al.

Why and How to Account for Sex and Gender in Brain and Behavioral Research.

Long overlooked in neuroscience research, sex and gender are increasingly included as key variables potentially impacting all levels of neurobehavioral analysis. Still, many neuroscientists do not understand the difference between the terms "sex" and "gender," the complexity and nuance of each, or how to best include them as variables in research designs. This TechSights article outlines rationales for considering the influence of sex and gender across taxa, and provides technical guidance for strengthening the rigor and reproducibility of such analyses.

Breaking the binary: Gender versus sex analysis in human brain imaging.

Despite decades of pursuit, human brain imaging has yet to uncover clear neural correlates of male-female behavioral differences. Given that such behavior does not always align with sex categories, we argue that neuroimaging research may find more success by partitioning subjects along nonbinary gender attributes in addition to sex. We review the handful of studies that have done this, several of which find as good or better association between brain measures and "gender" as they do with "sex.

How hype and hyperbole distort the neuroscience of sex differences.

Sex/gender differences in the human brain attract attention far beyond the neuroscience community. Given the interest of nonspecialists, it is important that researchers studying human female-male brain difference assume greater responsibility for the accurate communication of their findings.

Dump the "dimorphism": Comprehensive synthesis of human brain studies reveals few male-female differences beyond size.

With the explosion of neuroimaging, differences between male and female brains have been exhaustively analyzed. Here we synthesize three decades of human MRI and postmortem data, emphasizing meta-analyses and other large studies, which collectively reveal few reliable sex/gender differences and a history of unreplicated claims. Males' brains are larger than females' from birth, stabilizing around 11 % in adults.

Consensus Parameter: Research Methodologies to Evaluate Neurodevelopmental Effects of Pubertal Suppression in Transgender Youth.

Pubertal suppression is standard of care for early pubertal transgender youth to prevent the development of undesired and distressing secondary sex characteristics incongruent with gender identity. Preliminary evidence suggests pubertal suppression improves mental health functioning. Given the widespread changes in brain and cognition that occur during puberty, a critical question is whether this treatment impacts neurodevelopment.

Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

Introduction: Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters.

Methods: Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin).

Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume.

The amygdala plays a key role in many affective behaviors and psychiatric disorders that differ between men and women. To test whether human amygdala volume (AV) differs reliably between the sexes, we performed a systematic review and meta-analysis of AVs reported in MRI studies of age-matched healthy male and female groups. Using four search strategies, we identified 46 total studies (58 matched samples) from which we extracted effect sizes for the sex difference in AV.

Sex in Context: Limitations of Animal Studies for Addressing Human Sex/Gender Neurobehavioral Health Disparities.

Many brain and behavioral disorders differentially affect men and women. The new National Institutes of Health requirement to include both male and female animals in preclinical studies aims to address such health disparities, but we argue that the mandate is not the best solution to this problem. Sex differences are highly species-specific, tied to the mating system and social ecology of a given species or even strain of animal.

The human hippocampus is not sexually-dimorphic: Meta-analysis of structural MRI volumes.

Hippocampal atrophy is found in many psychiatric disorders that are more prevalent in women. Sex differences in memory and spatial skills further suggest that males and females differ in hippocampal structure and function. We conducted the first meta-analysis of male-female difference in hippocampal volume (HCV) based on published MRI studies of healthy participants of all ages, to test whether the structure is reliably sexually dimorphic.

The trouble with sex differences.

Sex differences in the brain are real and clinically important but often grossly distorted in popular discourse. Considering the public's deep fascination with sex difference research and its impact on issues from mental health to education and workplace equity, neuroscientists should pay greater heed to its misappropriation and to studying how gender enculturation shapes neural function.

Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart.

1. Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism.

Steady-state pharmacokinetic comparison of a new, extended-release, once-daily morphine formulation, Avinza, and a twice-daily controlled-release morphine formulation in patients with chronic moderate-to-severe pain.

Extended-release morphine formulations are widely used in the management of chronic pain. Avinza (morphine sulfate extended-release [MSER, Morphelan]) is a new, once-a-day, extended-release morphine formulation designed to reach target concentrations rapidly and maintain concentrations throughout a 24-hour period. The primary objective of this study was to compare the 24-hour steady-state pharmacokinetic (PK) profiles of morphine and its metabolites (morphine-6-glucuronide [M6G] and morphine-3-glucuronide [M3G]) following ingestion of MSER once-a-day and MS Contin (controlled-release morphine sulfate [CRM]) twice-a-day in patients with chronic moderate-to-severe pain.

Efficacy and safety of a once-daily morphine formulation in chronic, moderate-to-severe osteoarthritis pain: results from a randomized, placebo-controlled, double-blind trial and an open-label extension trial.

A randomized, 4-week, double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily, extended-release morphine formulation (Avinza (previously referred to as Morphelan)) in 295 patients with chronic, moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen. Participants received one of four treatments: Avinza 30 mg once daily (QAM or QPM), MS Contin(R) 15 mg twice daily, or placebo twice daily. Patients (n =181) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control.

Pharmacokinetic evaluation of a sprinkle-dose regimen of a once-daily, extended-release morphine formulation.

Background: Morphine sulfate extended-release (MSER) uses a drug-delivery technology that allows once-daily dosing. It is possible to open the MSER capsule and sprinkle the contents on soft food, a potentially useful alternative to the intact capsule in patients who have difficulty swallowing.

Objective: This study compared the bioavailability of MSER and its metabolites morphine-3-glucuronide and morphine-6-glucuronide after administration of MSER in a sprinkle-dose regimen relative to an intact capsule swallowed whole.