Sex bias in neuroscience and biomedical research

Robert Wood Johnson Health & Society Scholar at University of California, San Francisco, CA, USA.
Neuroscience & Biobehavioral Reviews (Impact Factor: 8.8). 01/2011; 35(3):565-72. DOI: 10.1016/j.neubiorev.2010.07.002
Source: PubMed


Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex.

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Available from: Annaliese K Beery, Oct 02, 2015
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    • "However, in studies that employ animal models of depression and anxiety, there exists a large male bias, again due to the hormonal fluctuations at play during the estrous cycle which cause significant changes in both physiology and behaviour (for review see [45]. Zucker and Beery [5] [69] found that even in studies of diseases that predominantly affect women such as anxiety and depression, the research is primarily carried out with male animals. The environment can also play a large role in the development of depression. "
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    ABSTRACT: While the efficacy of pharmacological interventions to treat depression has been well-studied in animal models, much less work has been done to shed light on how changes in the immediate environment can impact behaviour. Furthermore, most studies have focused on male rodents despite the prevalence of mood disorders in women. In this study, 36 Wistar Kyoto (validated animal model of depression) and 36 Wistar (control) female rats were used to examine the effects of environmental manipulation on depressive- and anxiety-like behaviours. Animals were assigned to one of three groups: standard (3 rats/cage), enriched (6 rats/cage plus physical enrichment), and isolation (1 rat/cage) housing. The elevated plus maze (EPM) and forced swim test (FST) were conducted prior to, and four weeks after environmental assignment to measure anxiety-like and depressive-like behaviours, respectively. Sucrose preference assessed anhedonia both before and after environmental assignment. Weight was measured every week to monitor weight-gain over time. Post-environment sucrose preference was significantly increased in animals in enriched housing as compared to those in isolated housing in both strains. While there were significant differences between strains in measures of open arm duration in the EPM and immobility in the FST, there appeared to be no differences between environmental groups. The results of this study highlight the importance of environmental factors in the expression of anhedonia. Enrichment appears to reduce anhedonia while isolation increases anhedonia. These effects should be studied further to assess whether longer periods of social and physical enrichment alleviate other symptoms of depression. Copyright © 2015. Published by Elsevier B.V.
    Behavioural brain research 07/2015; 293. DOI:10.1016/j.bbr.2015.07.035 · 3.03 Impact Factor
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    • "The results of this study support the need to integrate research on women and their physiology, including aspects that differ significantly from the physiology of men, into sleep-and metabolism-related research. The relative exclusion of women, especially those in their reproductive years, from health-related research has been noted previously (Correa-de-Araujo, 2006), as well as a similar exclusion of other female mammals from biological research (Beery and Zucker, 2011). Further research into the physiological changes in women following sleep loss may ultimately provide a better understanding of how reductions in hours of sleep affect risks for weight gain and hormonal disruption, as well as the development of associated chronic diseases in women, and may ultimately improve diagnosis and treatment of women's health prob- lems. "
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    ABSTRACT: There is extensive evidence that sleep restriction alters endocrine function in healthy young men, increasing afternoon cortisol levels and modifying levels of other hormones that regulate metabolism. Recent studies have confirmed these effects in young women, but have not investigated whether menstrual cycle phase influences these responses. The effects on cortisol levels of limiting sleep to 3 h for one night were assessed in two groups of women at different points in their menstrual cycles: mid-follicular and mid-luteal. Eighteen healthy, young women, not taking oral contraceptives (age: 21.8 ± 0.53; BMI: 22.5 ± 0.58 [mean ± SEM]), were studied. Baseline sleep durations, eating habits and menstrual cycles were monitored. Salivary samples were collected at six times of day (08:00, 08:30, 11:00, 14:00, 17:00, 20:00) during two consecutive days: first after a 10 h overnight sleep opportunity (Baseline) and then after a night with a 3 h sleep opportunity (Post-sleep restriction). All were awakened at the same time of day. Women in the follicular phase showed a significant decrease (p = 0.004) in their cortisol awakening responses (CAR) after sleep restriction and a sustained elevation in afternoon/evening cortisol levels (p = 0.008), as has been reported for men. Women in the luteal phase showed neither a depressed CAR, nor an increase in afternoon/evening cortisol levels. Secondary analyses examined the impact of sleep restriction on self-reported hunger and mood. Menstrual cycle phase dramatically altered the cortisol responses of healthy, young women to a single night of sleep restriction, implicating effects of spontaneous changes in endocrine status on adrenal responses to sleep loss.
    Psychoneuroendocrinology 11/2014; 49(1):34–46. DOI:10.1016/j.psyneuen.2014.06.002 · 4.94 Impact Factor
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    • "It is also well established now that BDNF is highly regulated by sex steroid hormones and alterations in BDNF expression are highly sex-dependent (Hill, 2012; Hill et al., 2012). Sex differences also exist in a variety of behavioral domains such as cognition and emotional responses, however, despite this the majority of studies are still not including female animals (Beery and Zucker, 2011; McCarthy et al., 2012). "
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    ABSTRACT: Post-mortem studies have demonstrated reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of schizophrenia and major depression patients. The "two hit" hypothesis proposes that two or more major disruptions at specific time points during development are involved in the pathophysiology of these mental illnesses. However, the role of BDNF in these "two hit" effects is unclear. Our aim was to behaviorally characterize a "two hit" rat model of developmental stress accompanied by an in-depth assessment of BDNF expression and signalling. Wistar rats were exposed to neonatal maternal separation (MS) stress and/or adolescent/young-adult corticosterone (CORT) treatment. In adulthood, models of cognitive and negative symptoms of mental illness were analyzed. The hippocampus was then dissected into dorsal (DHP) and ventral (VHP) regions and analyzed by qPCR for exon-specific BDNF gene expression or by Western blot for BDNF protein expression and downstream signaling. Male "two hit" rats showed marked disruptions in short-term spatial memory (Y-maze) which were absent in females. However, female "two hit" rats showed signs of anhedonia (sucrose preference test), which were absent in males. Novel object recognition and anxiety (elevated plus maze) were unchanged by either of the two "hits". In the DHP, MS caused a male-specific increase in BDNF Exons I, II, IV, VII, and IX mRNA but a decrease in mature BDNF and phosphorylated TrkB (pTrkB) protein expression in adulthood. In the VHP, BDNF transcript expression was unchanged; however, in female rats only, MS significantly decreased mature BDNF and pTrkB protein expression in adulthood. These data demonstrate that MS causes region-specific and sex-specific long-term effects on BDNF expression and signaling and, importantly, mRNA expression does not always infer protein expression. Alterations to BDNF signaling may mediate the sex-specific effects of developmental stress on anhedonic behaviors.
    Hippocampus 10/2014; 24(10). DOI:10.1002/hipo.22302 · 4.16 Impact Factor
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