Multifaceted origins of sex differences in the brain

McCarthy, Margaret M.

doi:10.1098/rstb.2015.0106

Cited by 144 publications

(85 citation statements)

References 97 publications

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“…Sex is an increasingly recognized biological variable in understanding consequences of early life events (McCarthy, 2016). As mentioned in several of the earlier sections, male and female offspring do not always show comparable phenotypes after LBN.…”

Section: Sex Differences In Outcomesmentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

273

322

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The immediate and long term effects of exposure to early life stress (ELS) have been documented in humans and animal models. Even relatively brief periods of stress during the first 10 days of life in rodents can impact later behavioral regulation and the vulnerability to develop adult pathologies, in particular an impairment of cognitive functions and neurogenesis, but also modified social, emotional and conditioned fear responses. The development of preclinical models of ELS exposure allows the examination of mechanisms and testing of therapeutic approaches that are not possible in humans. Here we describe limited bedding and nesting (LBN) procedures, with models that produce altered maternal behavior ranging from fragmentation of care to maltreatment of infants. The purpose of this paper is to discuss important issues related to the implementation of this chronic ELS procedure and to describe some of the most prominent endpoints and consequences, focusing on areas of convergence between laboratories. Effects on the hypothalamic-pituitary adrenal (HPA) axis, gut axis and metabolism are presented in addition to changes in cognitive and emotional functions. Interestingly, recent data have suggested a strong sex difference in some of the reported consequences of the LBN paradigm, with females being more resilient in general than males. As both the chronic and intermittent variants of the LBN procedure have profound consequences on the offspring with minimal external intervention from the investigator, this model is advantageous ecologically and has a large translational potential. In addition to the direct effect of ELS on neurodevelopmental outcomes, exposure to adverse early environments can also have intergenerational impacts on mental health and function in subsequent generation offspring. Thus, advancing our understanding of the effect of ELS on brain and behavioral development is of critical concern for the health and wellbeing of both the current population, and for generations to come.

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Section: Sex Differences In Outcomesmentioning

confidence: 99%

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Walker

Bath

Joëls

et al. 2017

Stress

273

322

View full text Add to dashboard Cite

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“…This would only increase the more sharply bimodal the distribution. We have found this to be the case for a large number of sexually differentiated end points in the developing rat brain, ranging from density of dendritic spines, to morphology of astroglia and microglia to rates of cell genesis (see for review McCarthy (2016)). Moreover, we also find that when we induce masculinization in neonatal females by means of hormone injections, we never produce a 'super-male', meaning the end point never exceeds that achieved normally in males.…”

Section: Is There a Male Brain And A Female Brain? Mccarthymentioning

confidence: 99%

Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?

Joel

McCarthy

2016

Neuropsychopharmacol

132

113

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Understanding the multiplicity of ways in which sex can alter the brain is essential to crafting policies and treatments that are beneficial for all human beings. This is particularly true for the field of neuropsychopharmacology, as many neuropsychiatric disorders exhibit gender bias in the frequency, severity, or response to treatment. The goal of this circumspective is to provide two views on the current state of the art of the relations between sex and the brain, relations that are studied almost exclusively by comparing females and males on specific end points, from gene expression to behavior. We start by suggesting a framework for defining what is being measured and what it means. We suggest that 'sex differences' can be classified on four dimensions: (1) persistent vs transient across the lifespan; (2) context independent vs dependent; (3) dimorphic vs continuous; and (4) a direct vs an indirect consequence of sex. To accurately classify a sex difference along these dimensions, one may need to compare females and males under varied conditions. We next discuss current data on the mechanisms of sexual differentiation of the brain and on sex differences in the brain to conclude that the brain of each male and female is a mosaic of relative masculinization, feminization, and sameness, which theoretically could produce an infinite variety of individuals. We also raise the possibility that sex differences in the brain are canalized, which may act to both enhance and restrain variation between males and females. We end by discussing ways to consider sex when studying neuropsychiatric disorders.

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“…There are several reasons for the paradigm shift. First, there is ever‐mounting evidence for sex differences in the human brain coming from systematic reviews, meta‐analyses, and journal special issues . Differences span overall volume, regional morphology, trajectories of development, localized function, and patterns of connectivity.…”

Section: Introductionmentioning

confidence: 99%

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

Beltz

Moser

2019

Annals of the New York Academy of Sciences

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Cognitive neuroscience research has traditionally overlooked half of the population. Arguing that variability in ovarian hormones confounds empirical findings, girls and women have been excluded from research for decades. But times are changing. This review summarizes historical trends that have led to a knowledge gap in the role of ovarian hormones in neuroscience, synthesizes recent findings on ovarian hormone contributions to cognitive brain structures and function, and highlights areas ripe for future work. This is accomplished by reviewing research that has leveraged natural experiments in humans across the life span that focus on puberty, the menstrual cycle, hormonal contraceptive use, menopause, and menopausal hormone therapy. Although findings must be considered in light of study designs (e.g., sample characteristics and group comparisons versus randomized crossover trials), across natural experiments there is consistent evidence for associations of estradiol with cortical thickness, especially in frontal regions, and hippocampal volumes, as well as with frontal regions during cognitive processing. There are also emerging investigations of resting state connectivity and progesterone along with exciting opportunities for future work, particularly concerning biopsychosocial moderators of and individual differences in effects in novel natural experiments. Thus, delineating complex ovarian hormone contributions to cognitive brain structures and function will advance neuroscience.

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Multifaceted origins of sex differences in the brain

Cited by 144 publications

References 97 publications

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Chronic early life stress induced by limited bedding and nesting (LBN) material in rodents: critical considerations of methodology, outcomes and translational potential

Incorporating Sex As a Biological Variable in Neuropsychiatric Research: Where Are We Now and Where Should We Be?

Ovarian hormones: a long overlooked but critical contributor to cognitive brain structures and function

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