YEXNR-11728; No. of page: 1; 4C: Experimental Neurology xxx (2014) xxx
Contents lists available at ScienceDirect
Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr
Editorial
2
Editor introduction to special issue
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1
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References
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and reviews animal models that can be used to study sex differences in the laboratory. In this issue, current knowledge of gender/sex differences in the occurrence of epilepsy (Savic) and coagulation/stroke (Roy-O'Reilly and McCullough) are reviewed. Pharmacological mechanisms related to the neural processing of pain sensation through endogenous opiate receptors (Lyod and Murphy) and the related circuits underlying drug addiction are discussed with a particular emphasis on the role of sex and hormonal modulation (Bobzean, Denobrega, and Perrotti). Neurotransmission is the focus of a review of sex differences in movement disorders by Smith and Dahodwala. Recovery from spinal cord injury can be facilitated by the administration of sex hormones and can effect treatment options in patients, as reviewed by Elkabes and Nicot. Similar questions are addressed regarding the effects of androgen on recovery following stroke in males by Quillinan, Deng, Grewal, and Herson. Finally, interactions between sex and inherited temperament upon cortical processes associated with attention are presented in a proposed theory of anxiety vulnerability (Catuzzi and Beck). Thus, this issue provides a survey of diverse neurological and psychiatric diseases and disorders that are identified to have sex-influenced etiology and/or treatment. An important consideration for the readers of this special issue is to recognize the breadth of diseases that exhibit sex differences, and that these are not limited to disorders of the central nervous system, but are pervasive throughout biology and medicine. This special issue hopefully highlights the large number of unanswered questions that remain and indeed have grown, from attaining a greater clarity of the role of sex in these conditions. With greater knowledge comes greater opportunity to establish more efficient therapeutic approaches. It is the hope of the special issue editors that the articles contained herein not just educate, but excite readers in recognizing that the most fundamental difference between half the humans in this world, sex, is now being addressed by biomedical researchers.
E
17 18
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15 16
C
13 14
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11 12
R
9 10
R
7 8
For decades, sex differences in the prevalence of various neurological and psychological disorders have been recognized, but an equal understanding of the mechanisms underlying these disparities has occurred much more slowly. A pivotal event that enhanced research efforts to address the etiology of sex differences came in 1993 when Public Law 103-43 was passed in the United States. Known as the “National Institutes of Health Revitalization Act of 1993”, the U.S. National Institute of Health was charged with increasing the inclusion of women and other minority groups in clinical trials. Now just over 20 years later, the annual number of published studies citing sex or gender differences in biological mechanisms of health and disease has substantially increased. International centers of excellence have been established focusing on sex and gender-based differences in both medicine and pre-clinical research. Much of the research presented in this special issue of Experimental Neurology comes as a result of the recent emphasis to enhance our understanding of sex-based differences in the etiology, progression, and treatment of neurological and psychiatric disorders. We live in an era of “personalized medicine”, and individual differences and genetic polymorphisms will likely determine treatment strategies in the near future. It is astonishing that one of the most fundamental differences in biology, whether you are male or female, is often not considered. This is pervasive through the most basic cellular studies (as the sex of cell lines or primary cultures is almost never reported), to animal studies (which are predominately performed in young male animals), to early phase clinical trials. This has led to significant knowledge gaps in our understanding of disease expression in women, as recently highlighted in a recent report by the Connors Center (SexSpecific Medical Research — Why Women's Health Can't Wait). Luckily, there has been growing recognition both by the lay public and the scientific community this lack of adequate studies examining sex and gender has likely hindered scientific advancement and medical care for both men and women. This recognition has led to an increase in the number of published studies that have primary, secondary, or tertiary evaluation of the effects of sex/gender on biological mechanisms and disease expression. An important framework to consider as one peruses this special issue is that sex and gender are distinct but inter-related concepts. Sex is fundamentally chromosome-linked (XX vs XY) and gender is linked to environmental/societal factors (perception of self as “male” or “female”). These terms are often used interchangeably, leading to confusion. It is also difficult to separate out the effects of chromosomal compliment (XX vs. XY) from that of organizational or activational effects of gonadal hormones (primarily estrogen vs. testosterone) adding to the complexity of this field (not to mention the newly discovered processes involved in epigenetic changes in structure and function). The first paper in this Special issue (Arnold) discusses these concepts
N C O
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4
O
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51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81
Sex-Specific Medical Research — Why Women's Health Can't Wait, t. http://www. 83 brighamandwomens.org/Departments_and_Services/womenshealth/ConnorsCenter/ 84 Policy/ConnorsReportFINAL.pdf. 85
86 87 88
Louise D. McCullough M.D. Ph.D. 89 90
Kevin Beck Ph.D. 91 92
Available online xxxx 93
94 http://dx.doi.org/10.1016/j.expneurol.2014.05.005 0014-4886/© 2014 Published by Elsevier Inc.
Please cite this article as: McCullough, L.D., Beck, K., Editor introduction to special issue, Exp. Neurol. (2014), http://dx.doi.org/10.1016/ j.expneurol.2014.05.005
Contents lists available at ScienceDirect
Experimental Neurology journal homepage: www.elsevier.com/locate/yexnr
Editorial
2
Editor introduction to special issue
F
1
19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49
50
References
82
D
P
R O
and reviews animal models that can be used to study sex differences in the laboratory. In this issue, current knowledge of gender/sex differences in the occurrence of epilepsy (Savic) and coagulation/stroke (Roy-O'Reilly and McCullough) are reviewed. Pharmacological mechanisms related to the neural processing of pain sensation through endogenous opiate receptors (Lyod and Murphy) and the related circuits underlying drug addiction are discussed with a particular emphasis on the role of sex and hormonal modulation (Bobzean, Denobrega, and Perrotti). Neurotransmission is the focus of a review of sex differences in movement disorders by Smith and Dahodwala. Recovery from spinal cord injury can be facilitated by the administration of sex hormones and can effect treatment options in patients, as reviewed by Elkabes and Nicot. Similar questions are addressed regarding the effects of androgen on recovery following stroke in males by Quillinan, Deng, Grewal, and Herson. Finally, interactions between sex and inherited temperament upon cortical processes associated with attention are presented in a proposed theory of anxiety vulnerability (Catuzzi and Beck). Thus, this issue provides a survey of diverse neurological and psychiatric diseases and disorders that are identified to have sex-influenced etiology and/or treatment. An important consideration for the readers of this special issue is to recognize the breadth of diseases that exhibit sex differences, and that these are not limited to disorders of the central nervous system, but are pervasive throughout biology and medicine. This special issue hopefully highlights the large number of unanswered questions that remain and indeed have grown, from attaining a greater clarity of the role of sex in these conditions. With greater knowledge comes greater opportunity to establish more efficient therapeutic approaches. It is the hope of the special issue editors that the articles contained herein not just educate, but excite readers in recognizing that the most fundamental difference between half the humans in this world, sex, is now being addressed by biomedical researchers.
E
17 18
T
15 16
C
13 14
E
11 12
R
9 10
R
7 8
For decades, sex differences in the prevalence of various neurological and psychological disorders have been recognized, but an equal understanding of the mechanisms underlying these disparities has occurred much more slowly. A pivotal event that enhanced research efforts to address the etiology of sex differences came in 1993 when Public Law 103-43 was passed in the United States. Known as the “National Institutes of Health Revitalization Act of 1993”, the U.S. National Institute of Health was charged with increasing the inclusion of women and other minority groups in clinical trials. Now just over 20 years later, the annual number of published studies citing sex or gender differences in biological mechanisms of health and disease has substantially increased. International centers of excellence have been established focusing on sex and gender-based differences in both medicine and pre-clinical research. Much of the research presented in this special issue of Experimental Neurology comes as a result of the recent emphasis to enhance our understanding of sex-based differences in the etiology, progression, and treatment of neurological and psychiatric disorders. We live in an era of “personalized medicine”, and individual differences and genetic polymorphisms will likely determine treatment strategies in the near future. It is astonishing that one of the most fundamental differences in biology, whether you are male or female, is often not considered. This is pervasive through the most basic cellular studies (as the sex of cell lines or primary cultures is almost never reported), to animal studies (which are predominately performed in young male animals), to early phase clinical trials. This has led to significant knowledge gaps in our understanding of disease expression in women, as recently highlighted in a recent report by the Connors Center (SexSpecific Medical Research — Why Women's Health Can't Wait). Luckily, there has been growing recognition both by the lay public and the scientific community this lack of adequate studies examining sex and gender has likely hindered scientific advancement and medical care for both men and women. This recognition has led to an increase in the number of published studies that have primary, secondary, or tertiary evaluation of the effects of sex/gender on biological mechanisms and disease expression. An important framework to consider as one peruses this special issue is that sex and gender are distinct but inter-related concepts. Sex is fundamentally chromosome-linked (XX vs XY) and gender is linked to environmental/societal factors (perception of self as “male” or “female”). These terms are often used interchangeably, leading to confusion. It is also difficult to separate out the effects of chromosomal compliment (XX vs. XY) from that of organizational or activational effects of gonadal hormones (primarily estrogen vs. testosterone) adding to the complexity of this field (not to mention the newly discovered processes involved in epigenetic changes in structure and function). The first paper in this Special issue (Arnold) discusses these concepts
N C O
5 6
U
4
O
3
51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81
Sex-Specific Medical Research — Why Women's Health Can't Wait, t. http://www. 83 brighamandwomens.org/Departments_and_Services/womenshealth/ConnorsCenter/ 84 Policy/ConnorsReportFINAL.pdf. 85
86 87 88
Louise D. McCullough M.D. Ph.D. 89 90
Kevin Beck Ph.D. 91 92
Available online xxxx 93
94 http://dx.doi.org/10.1016/j.expneurol.2014.05.005 0014-4886/© 2014 Published by Elsevier Inc.
Please cite this article as: McCullough, L.D., Beck, K., Editor introduction to special issue, Exp. Neurol. (2014), http://dx.doi.org/10.1016/ j.expneurol.2014.05.005
