Biological factors underlying sex differences in neurological disorders

Loke, Hannah; Harley, Vincent R.; Lee, Joohyung

doi:10.1016/j.biocel.2015.05.024

Cited by 122 publications

(95 citation statements)

References 196 publications

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“…Sex is sometimes a significant variable in the prevalence and incidence of neurological disorders [1,2,3,4,5,6,7]. In addition, sexual differences also exist in the age-of-onset, progression, disease severity, underlying neuropathology and treatment response of neurological diseases [1,3,4,5,7,8,9].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, sexual differences also exist in the age-of-onset, progression, disease severity, underlying neuropathology and treatment response of neurological diseases [1,3,4,5,7,8,9]. Whilst this attention to sexual dimorphism has traditionally been stronger in fields like cancer, cardiovascular and endocrine disorders [10,11], accumulating evidence demonstrates significant sex differences in brain physiology and behavior throughout development and adulthood [1,4,12]. Indeed, girls are more likely to suffer from depression than boys, and following puberty this female susceptibility for anxiety increases to around twice that for males [13].…”

Section: Introductionmentioning

confidence: 99%

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Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

et al. 2018

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Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely considered when making treatment decisions in neurological disorders. A better understanding of the molecular mechanism(s) underlying sex differences in the healthy and diseased brain will help to devise diagnostic and therapeutic strategies optimal for each sex. Thus, the aim of this review is to discuss the available evidence on sex differences in neuropsychiatric and neurodegenerative disorders regarding prevalence, progression, symptoms and response to therapy. We also discuss the sex-related factors such as gonadal sex hormones and sex chromosome genes and how these might help to explain some of the clinically observed sex differences in these disorders. In particular, we highlight the emerging role of the Y-chromosome gene, SRY, in the male brain and its potential role as a male-specific risk factor for disorders such as PD, autism, and ADHD in many individuals.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

et al. 2018

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“…Given the sex‐related difference in prevalence and incidence of brain disorders8 as well as in drug absorption, bioavailability and its response in brain,9 we have explored an aspect rarely investigated on: whether or not there is a sex difference in the permeability of the brain barriers.…”

Section: Introductionmentioning

confidence: 99%

Evidence for sex difference in the CSF/plasma albumin ratio in ~20 000 patients and 335 healthy volunteers

Parrado-Fernández

Blennow

Hansson

et al. 2018

J Cellular Molecular Medi

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Given sex‐related differences in brain disorders, it is of interest to study if there is a sex difference in the permeability of the blood‐cerebrospinal fluid barrier (BCSFB) and the blood‐brain barrier (BBB). The CSF/serum albumin ratio (QA lb) is a standardized biomarker that evaluates the function of these barriers. In previous studies, contradictory results have been reported with respect to sex difference using this quotient, possibly because of small population sizes and heterogeneity with respect to ages. QA lb measurements in more than 20 000 patients between 1 and 90 years visiting our hospitals revealed a significant sex difference in all age groups also when excluding patients with pathologically high CSF albumin > 400 mg/L. Similar pattern was found in 335 healthy volunteers in similar age intervals. Although also other factors are likely important, our observation is consistent with lower integrity of the brain barriers in males. If the difference in QA lb is caused mainly by a difference in barrier function, this may require different drug doses and strategies for efficient central nervous system (CNS) delivery in males and females, as well as it may indicate differences in brain metabolism. Moreover, our study emphasizes that different reference values should be used both for different ages and sexes.

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“…Indeed, it is expressed in the brain in mice and other mammals (Loke et al, 2015). This could place male-specific traits under selection, perhaps explaining aspects of rapid Sry evolution.…”

Section: Discussionmentioning

confidence: 99%

Of sex and determination: marking 25 years of Randy, the sex-reversed mouse

2016

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On Thursday 9 May 1991, the world awoke to front-page news of a breakthrough in biological research. From Washington to Wollongong, newspapers, radio and TV were abuzz with the story of a transgenic mouse in London called Randy. Why was this mouse so special? The mouse in question was a chromosomal female (XX) made male by the presence of a transgene containing the Y chromosome gene Sry. This sex-reversal provided clear experimental proof that Sry was the elusive mammalian sex-determining gene. Twenty-five years on, we reflect on what this discovery meant for our understanding of how males and females arise and what remains to be understood.

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Biological factors underlying sex differences in neurological disorders

Cited by 122 publications

References 196 publications

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

Evidence for sex difference in the CSF/plasma albumin ratio in ~20 000 patients and 335 healthy volunteers

Of sex and determination: marking 25 years of Randy, the sex-reversed mouse

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