Page 19 - Read Online

Yanguas-Casás. Neuroimmunol Neuroinflammation 2020;7:13-22 I http://dx.doi.org/10.20517/2347-8659.2019.31 Page 15

Table 1. Sex differences in the incidence of neurological disorders in humans
Male brain Female brain
Autism Spectrum Disorders (4:1) Alzheimer’s Disease (3:1)
Parkinson’s Disease (3:1) Depression (2:1)
Attention Deficit Hyperactivity Disorder Anxiety (2:1)
Attention Deficit Hyperactivity Disorder (3:1) Multiple Sclerosis (2-3:1)
Schizophrenia (1.4:1)
Amyotrophic Lateral Sclerosis (1.6:1) Adult-onset neurological disorders
Early-onset neurological disorders

Most frequent neurological disorders in humans. Global prevalence of each disorder is shown in parenthesis as the ratio of men vs.
women (left side) or women vs. men (right side)

differentiation, resulting in sex specific microglia subpopulations in different brain areas. This is relevant
because microglia phenotypes vary across regions of the CNS, in disease as well as in physiological
conditions at different stages in life, especially in early development and aging, which are two critical life
stages for the appearance of neurological disorders, in both humans and rodents [44-47] .

Sex differences in neurological disorders
There is an increasing concern for the real relevance of experimental results obtained in current research.
Experimental procedures are often done using only one sex, and results are often extrapolated to both
sexes without solid grounds. Several funding agencies, such as the European Commission, the Canadian
Institutes of Health Research, and the US National Institutes of Health, have tried to influence researchers
to integrate sex/gender not only in clinical research, but also in basic and preclinical research, especially
since they identified a sex bias in most clinical trials, usually done in male subjects, in which females are
under-represented, leading to mistreatment of women [48,49] . In the specific case of neurological disorders,
there is a well described sex bias in the prevalence, severity, progression, and outcome of these diseases
[29]
[Table 1] . Therefore, there is a need of development, implementation, and prioritization of treatments
and preventive interventions specific for sex, age, and population to reduce the burden from these
[50]
disorders .

[51]
Many early-onset neurodevelopmental disorders show a strong sex-bias toward males while adult-
onset neurological disorders are female biased . As microglia play an important role in both sexual
[52]
differentiation of the brain and progression of most neurological disorders [27,33,53,54] , it is critical to
understand how the dynamics and potential dysfunction of microglia at certain developmental points affect
the onset and progression of these disorders.

Women have a higher prevalence of Alzheimer’s disease (AD, 1.6-3:1 ratio compared to men) [55,56] ,
autoimmune diseases such as multiple sclerosis (MS, 2-3:1 ratio) , or mood related disorders such
[57]
as depression or anxiety disorders (2:1) [58,59] . On the other hand, men are more prone to suffer from
Parkinson’s disease (PD, 3.5:1 compared to women) [60,61] , motor neuron disorders such as amyotrophic
lateral sclerosis (ALS, 1.6:1) [62,63] , autism spectrum disorders (ASD, 4:1) [64-66] , attention deficit hyperactivity
disorder (3:1) [67-70] , or schizophrenia (1.4:1) [71,72] .

[73]
Beyond the prevalence of these disorders, women show greater cognitive decline than men with AD
and a slower rate of decline when suffering from PD [60,61] . In this line, women show increased severity of
depression or anxiety disorder symptoms, and men show earlier onset of schizophrenia and more severe
symptoms along with worse response to antipsychotic drugs than women [58,59,71,74] . On the other hand, men
suffering from MS have a faster progression of the disease than women [57,75] , and women suffering from
ALS have worse survival rates than men [62,63] .