Exploring sex differences: insights into gene expression, neuroanatomy, neurochemistry, cognition, and pathology

Abstract

Increased knowledge about sex differences is important for development of individualized treatments against many diseases as well as understanding behavioral and pathological differences. This review summarizes sex chromosome effects on gene expression, epigenetics, and hormones in relation to the brain. We explore neuroanatomy, neurochemistry, cognition, and brain pathology aiming to explain the current state of the art. While some domains exhibit strong differences, others reveal subtle differences whose overall significance warrants clarification. We hope that the current review increases awareness and serves as a basis for the planning of future studies that consider both sexes equally regarding similarities and differences.

Sex Differences in Albumin Quotient and Cerebrospinal Fluid Total Protein Content Do Not Depend on Anthropometric Factors

“…Moreover, the female hormone 17β-estradiol [34] may influence the expression of enzymes involved in blood-CSF barrier breakdown [35,36], potentially leading to a protective effect [37]. Notably, despite stable QAlb sex-specific values during puberty or menopause, it is essential to consider the role of genetic predisposition associated with sex chromosomes, along with hormonal influences [2].…”

“…For each patient, body height and weight data were collected during hospitalisation, and BMI was calculated with the formula: BMI = weight(kg) ÷ height(meters) 2 . Males and females were further grouped on their BMI weight status categories as follows: (i) underweight, if BMI was less than 18.5 (0 males, 12 females); (ii) healthy weight, if BMI was in the range of 18.5 to 24.9 (28 males, 94 females); (iii) overweight, if BMI was between 25.0 and 29.9 (31 males, 34 females); (iv) obese, when BMI was greater than 30.0 (9 males, 17 females).…”

“…Brain sexual dimorphisms notably impact brain anatomy, biochemistry, and various psychological and cognitive processes [1,2].…”

“…Men and women present pronounced differences in the susceptibility, onset, progression, and severity of neurological and psychiatric diseases [2]. Men are more likely to be diagnosed with Parkinson's disease [3], attention deficit hyperactivity disorder [4], and autism spectrum disorders [5] and are prone to present an early onset of schizophrenia spectrum disorders [6].…”

“…Studies on the differences in brain structure revealed that males, on average, have almost 10% larger brain volumes compared to females, and this sexual dimorphism is not 2 of 11 diffusely distributed across the brain but rather is region-specific [10]. On the one hand, women have a higher percentage of grey matter, while on the other hand, men have a higher percentage of white matter, greater lateral ventricles, and higher sulcal and cerebrospinal fluid (CSF) volumes than women [2]. Moreover, CSF in men presents a higher density than in women [11].…”