Brain sex theories

Reframing sexual differentiation of the brain

20th century linear model for brain sex 

"For the past 50 years, the prevailing view of sexual differentiation of the brain has been a linear model in which chromosomal sex determines gonadal sex, which determines brain sex. (...) This iconic model based on the organizational/activational hypothesis14 has proved a sturdy framework for elucidating some, but not all, of the aspects of sexual differentiation of the brain."

(image source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165173/figure/F1/)

21st century model for brain sex

"Redefining sexual differentiation. In a twenty-first-century view of sexual differentiation of the brain, the importance of genetics and environment are incorporated along with the effects of hormones to provide a more nuanced portrayal of the types of variables that cause sex differences. Included in this view are the principles that hormones, sex chromosome genes and sex-specific environments have independent parallel differentiating effects that can interact with each other, often synergistically, to cause sex differences in the brain. However, there are also compensatory sex-specific variables that act to reduce sex differences rather than induce them. The result is that some aspects of male and female brain, behavior and physiology are unique from each other, whereas others are highly similar. Two important aspects of the redefined view are not illustrated here: sex differences are pervasive throughout the brain and not restricted to reproductively relevant neural circuits, and variability in the degree to which brain regions are masculinized or feminized in one individual results in a mosaic of relative maleness or femaleness and thereby greatly increases the variance between individuals of the same sex in a population."


(image source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3165173/figure/F4/)

(McCarthy, Margaret M., and Arthur P. Arnold. "Reframing sexual differentiation of the brain." Nature neuroscience 14.6 (2011): 677-683.)

Sexual differentiation of the brain not only because of (prenatal) hormones, but also neuroimmunology and epigenetics

"Recent research in rodent models has led to dramatic shifts in our views of the mechanisms underlying the sexual differentiation of the brain. These include the surprising discoveries of a role for immune cells and inflammatory mediators in brain masculinization and a role for epigenetic suppression in brain feminization. How and to what degree these findings will translate to human brain development will be questions of central importance in future research in this field."

(McCarthy, Margaret M., Bridget M. Nugent, and Kathryn M. Lenz. "Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain." Nature Reviews Neuroscience (2017).)

Immune cells co-responsible for brain sex differentiation

"These studies demonstrate that immune cells in the brain interact with the nervous and endocrine systems during development, and are crucial for sexual differentiation of brain and behavior."

(Lenz, Kathryn M., et al. "Microglia are essential to masculinization of brain and behavior." Journal of Neuroscience 33.7 (2013): 2761-2772.)

AI detects differences between male and female brain rhythms

"The electric brain signals, measured by using EEG, of males and females show differences. The difference can't be detected by visual inspection, not even by the trained eye of a neurologist. A 'deep learning' computer is able to find it. (...) The main difference is in the 'beta activity', a frequency range between 20 and 25 Hz. These rhythms have to do with cognition and with tasks that are emotionally positive or negative. It is known from previous research that females are better capable of recognizing emotion: this could indicate a difference in beta activity. Within the context of this research project, this has not been elaborated further."

(University of Twente. "Male and female brain rhythms show differences." ScienceDaily. ScienceDaily, 15 February 2018.)

MRI shows significant differences in brain development between male and female fetuses

"However, models of relative growth accounting for global measures revealed a complex temporal form, with strikingly similar cortical development in males and females at lobe scales. In contrast, local cortical growth patterns and larger scale white matter volume and surface measures differed significantly between male and female. Many proportional differences were maintained during neurogenesis and over 18 weeks of growth. These indicate sex related sculpting of neuroanatomy begins early in development, before cortical folding, potentially influencing postnatal development."

(Studholme, C., Kroenke, C. D., & Dighe, M. (2020). Motion corrected MRI differentiates male and female human brain growth trajectories from mid-gestation. Nature Communications, 11(1), 1-16.)

The (extreme) female brain

(NOTE: I personally think that the terms "feminine" brain instead of "female" brain, and "masculine" brain instead of "male" brain would be much more appropriate, given that biological males can have feminine brains and vice versa (cfr. EMPATHIZING AND SYSTEMIZING IN MALES, FEMALES, AND AUTISM, Nigel Goldenfeld, Simon Baron-Cohen, Sally Wheelwright, Clinical Neuropsychiatry (2005) 2, 6, 338-345))

Women have more active brains than men

"The study findings of increased prefrontal cortex blood flow in women compared to men may explain why women tend to exhibit greater strengths in the areas of empathy, intuition, collaboration, self-control, and appropriate concern. The study also found increased blood flow in limbic areas of the brains of women, which may also partially explain why women are more vulnerable to anxiety, depression, insomnia, and eating disorders."

(Women have more active brains than men, Sciecedaily, August 7, 2017)

The ‘extreme female brain’: increased cognitive empathy as a dimension of psychopathology

Abstract

Baron-Cohen's ‛extreme male brain’ theory postulates that autism involves exaggerated male-typical psychology, with reduced empathizing (considered here as social–emotional interest, motivation and abilities) and increased systemizing (non-social, physical-world and rule-based interest, motivation and abilities), in association with its male-biased sex ratio. The concept of an ‘extreme female brain’, involving some combination of increased empathizing and reduced systemizing, and its possible role in psychiatric conditions, has been considerably less well investigated. Female-biased sex ratios have been described in two conditions, depression and borderline personality disorder (BPD), that also show evidence of increases in aspects of empathy in some studies. We evaluated the hypothesis that BPD and depression can be conceptualized in the context of the ‘extreme female brain’ by: (1) describing previous conceptualizations of the extreme female brain model, (2) reviewing evidence of female-biased sex ratios in BPD and depression, (3) conducting meta-analyses of performance on the Reading the Mind in the Eyes test (RMET) among individuals with BPD, clinical or sub-clinical depression, and other psychiatric conditions involving altered social cognition and mood (schizophrenia, bipolar disorder, eating disorders, and autism), in relation to disorder sex ratios, and (4) evaluating previous evidence of increased empathic performance in these, and related, psychiatric conditions, and (5) synthesizing these lines of evidence into models for causes and effects of an ‘extreme female brain’. Our primary empirical results are that RMET performance is enhanced in sub-clinical depression, preserved in borderline personality disorder, and reduced in other disorders (by meta-analyses), and that across disorders, more male-biased patient sex ratios are strongly associated with worse RMET performance of patients relative to controls. Our findings, in conjunction with previous work, suggest that increased cognitive empathizing mediates risk and expression of some psychiatric conditions with evidence of female biases, especially sub-clinical depression and borderline personality disorder, in association with increased attention to social stimuli, higher levels of social and emotional sensitivity, negative emotion biases, and over-developed mentalist thought. These results link evolved human sex differences with psychiatric vulnerabilities and symptoms, and lead to specific suggestions for future work.
(Dinsdale, Natalie, Mikael Mokkonen, and Bernard Crespi. "The ‘extreme female brain’: increased cognitive empathy as a dimension of psychopathology." Evolution and Human Behavior 37.4 (2016): 323-336.)

2D:4D digit ratio positively correlated to emotional instability, neuroticism and borderline disorder

"2D:4D finger length ratios, the preferred biomarker for the evaluation of brain masculinity/femininity, is positively correlated to emotional instability (Lindová, Hrušková, Pivoňková, Kuběna, & Flegr, 2008). This means that the most feminized a brain is, the most emotionally unstable a person is. 2D:4D ratios correlate positively with neuroticism scores (Austin, Manning, McInroy, & Mathews, 2002; Fink, Manning, & Neave, 2004). Neuroticism is the trait of the Big Five on which men and women differ the most globally (Schmitt, Voracek, Realo, & Allik, 2008), and unsurprisingly, girls with borderline are acutely neurotic. 2D:4D ratios correlate with borderline characteristics: estrogen, neuroticism, and correlates negatively with autistic symptoms (which is the diametrical opposite of borderline interpersonal tendencies; extreme unresponsiveness to social stimuli; Putz, Gaulin, Sporter, & McBurney, 2004). 2D:4D ratios significantly predicted overall borderline traits, and the affective component of the borderline presentation more specifically (Evardone, Alexander, & Morey, 2008). In short, converging methods have provided evidence that borderline personality disorder is related to a pronounced femininity."

(Kilsdonk-Gervais, N. (2017). Social Motivation as The Extreme Female Brain: Borderline, Dependent, and Histrionic Personality Disorders. Unpublished manuscript.)

Neuroticism

Neuroticism is the tendency to experience negative emotions, such as anger, anxiety, or depression. It is sometimes called emotional instability, or is reversed and referred to as emotional stability. According to Eysenck's (1967) theory of personality, neuroticism is interlinked with low tolerance for stress or aversive stimuli. Those who score high in neuroticism are emotionally reactive and vulnerable to stress. They are more likely to interpret ordinary situations as threatening, and minor frustrations as hopelessly difficult. Their negative emotional reactions tend to persist for unusually long periods of time, which means they are often in a bad mood. For instance, neuroticism is connected to a pessimistic approach toward work, confidence that work impedes personal relationships, and apparent anxiety linked with work. Furthermore, those who score high on neuroticism may display more skin-conductance reactivity than those who score low on neuroticism. These problems in emotional regulation can diminish the ability of a person scoring high on neuroticism to think clearly, make decisions, and cope effectively with stress.[citation needed] Lacking contentment in one's life achievements can correlate with high neuroticism scores and increase one's likelihood of falling into clinical depression. Moreover, individuals high in neuroticism tend to experience more negative life events, but neuroticism also changes in response to positive and negative life experiences.

At the other end of the scale, individuals who score low in neuroticism are less easily upset and are less emotionally reactive. They tend to be calm, emotionally stable, and free from persistent negative feelings. Freedom from negative feelings does not mean that low-scorers experience a lot of positive feelings.

Neuroticism is similar but not identical to being neurotic in the Freudian sense (i.e., neurosis.) Some psychologists prefer to call neuroticism by the term emotional stability to differentiate it from the term neurotic in a career test.

Sample items:
I get irritated easily.
I get stressed out easily.
I get upset easily.
I have frequent mood swings.
I worry about things.
I am much more anxious than most people.
I am relaxed most of the time. (reversed)
I seldom feel blue. (reversed)

(source: Wikipedia, accessed 2017-05-23)