Sex differences in the incidence of neuropsychiatric disorders have been known for
decades. Syndromes as diverse as depression and Alzheimer’s disease are roughly twice
as common in females than males, and anorexia nervosa occurs more than an order of
magnitude more frequently in females. By contrast, autism spectrum disorder (ASD)
is fourfold more common in males, with schizophrenia showing a modest (40%) higher
incidence in males. Despite these epidemiological data, it is only relatively recently
that insight into the molecular bases of such sex differences is beginning to appear.
This progress coincides with the 2016 National Institutes of Health mandate requiring
that all National Institutes of Health–funded research consider sex as a biological
variable. Prior to this mandate, most clinical investigators focused on male subjects
or did not power studies to analyze each sex separately, while most basic laboratories
studied male rodents only, reasoning that including females would require several-fold
more animals and add too much complexity due to their estrous cycle. Notably, recent
efforts suggest that female rodents are in fact not more variable than males (
1
,
2
,
3
), arguing against excluding females to limit experimental variability. In just 5
short years since the National Institutes of Health mandate, the results have been
transformational, as an increasing number of publications have validated and added
to a long-standing literature of sex differences in neuroscientific phenomena. The
advent of next-generation sequencing approaches (e.g., the quantification of all RNAs
expressed in a tissue or given cell type through RNA sequencing) has provided an important
additional level of evidence for dramatic sex differences in the biological underpinnings
of a range of neuropsychiatric syndromes. This special issue of Biological Psychiatry focuses on these recent transcriptomic datasets and the fundamentally new insights
they are providing into the influence of sex on brain function under normal and pathological
conditions. Launch of this special issue of Biological Psychiatry coincided with a Neuroscience Forum Workshop sponsored by the National Academies
highlighting sex differences in transcriptomic characterization of brain and nervous
system disorders (
4
).To read this article in full you will need to make a payment
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References
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- Female rats are not more variable than male rats: A meta-analysis of neuroscience studies.Biol Sex Differ. 2016; 7: 34
- Male and female mice show equal variability in food intake across 4-day spans that encompass estrous cycles.PLoS One. 2019; 14e0218935
- Sex Differences in Brain Disorders: Emerging Transcriptomic Evidence: Proceedings of a Workshop.The National Academies Press, Washington, DC2021
- Sex differences in learning processes of classical and operant conditioning.Physiol Behav. 2009; 97: 229-238
- Sex differences in the molecular signature of the developing mouse hippocampus.BMC Genomics. 2017; 18: 237
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- Opposite molecular signatures of depression in men and women.Biol Psychiatry. 2018; 84: 18-27
- Transcriptomic organization of the human brain in post-traumatic stress disorder.Nat Neurosci. 2021; 24: 24-33
- Sex differences in adult mood and in stress-induced transcriptional coherence across mesocorticolimbic circuitry.Transl Psychiatry. 2020; 10: 59
- Posttraumatic stress disorder brain transcriptomics: Convergent genomic signatures across biological sex.Biol Psychiatry. 2022; 91: 6-13
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- Translating the transcriptome: Sex differences in the mechanisms of depression and stress, revisited.Biol Psychiatry. 2022; 91: 25-35
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- Sex differences in the brain transcriptome related to alcohol effects and alcohol use disorder.Biol Psychiatry. 2022; 91: 43-52
- Sex-specific transcriptional changes in response to adolescent social stress in the brain’s reward circuitry.Biol Psychiatry. 2022; 91: 118-128
- Neural transcriptomic analysis of sex differences in autism spectrum disorder: Current insights and future directions.Biol Psychiatry. 2022; 91: 53-60
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- Sex differences in neurodegeneration: The role of the immune system in humans.Biol Psychiatry. 2022; 91: 72-80
- Sex differences in nociceptor translatomes contribute to divergent prostaglandin signaling in male and female mice.Biol Psychiatry. 2022; 91: 129-140
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- Sex differences in molecular rhythms in the human cortex.Biol Psychiatry. 2022; 91: 152-162
Article info
Publication history
Accepted:
September 8,
2021
Received:
September 7,
2021
Identification
Copyright
© 2021 Society of Biological Psychiatry.
