The gender bias of depression

Why do women experience disproportionately high rates of depression compared to men?

Writer: Lucy White
Editor: Lucy Masdin
Artist: Lydia Popplewell


Just under twice as many women are affected by depression as men, and the Global Burden of Disease report by the World Health Organisation (WHO) found it to be the leading cause of disease burden in women aged 15-44. Despite this, treatment for men and women is much the same, and many animal studies investigating depression use only males in order to avoid complications due to the fluctuation of hormones associated with the menstrual cycle. 

This gender difference in rates of depression is true globally, and no significant difference has been found in countries where women have, on average, a lower socioeconomic status than men. Social factors may play a role – for example, education, income, rates of abuse, and how ‘acceptable’ it is deemed for women to seek help for depression, perhaps leading to a higher rate of diagnosis in women compared to men. However, they are unlikely to account for the discrepancy on their own.

According to the WHO, 50% of mental health disorders begin by age 14 – the same age at which the difference between rates of depression (and other mood disorders, such as anxiety) between girls and boys becomes apparent. Sex-differential development of the brain may be a potential origin of this phenomenon. Several differences between male and female brains have been found in areas associated with emotion and memory. 

A 2019 study took Magnetic Resonance Imaging (MRI) scans of 729 people, aged 5-25, to map the growth of different areas of the brain. The amygdala (part of the limbic system, involved in emotional responses) and the hippocampus (involved in learning and memory) were both found to have sexually dimorphic qualities. Amygdala growth, by volume, slowed significantly in females at around age 13, but this did not occur until the early 20s in males. Hippocampus differences were less marked, but males showed faster hippocampus growth during their late teens than females.

The amygdala and hippocampus have been implicated in many mental illnesses, including depression.

The amygdala is particularly associated with the processing of negative emotions, and, when activated, can trigger a stress response. Over-activation of this response, or under-activation of negative feedback loops designed to control the extent of this response, can lead to depressive episodes. Studies have shown that when depressed people view images of sad faces, their amygdala is more active than in healthy people. Similarly, several studies have suggested that people suffering from recurrent depression have reduced hippocampal volumes compared to unaffected individuals. 

It is notable, therefore, that these two parts of the brain develop differently in men and women, especially around the time of puberty, when many mental health issues are thought to manifest.

However, the mechanism behind depression is complex, and the discrepancy in rates between men and women is unlikely due to one factor only. 

Hormones may also play a role. Researchers at Michigan State University found a neurological circuit involved in the stress response that is controlled by testosterone. Testosterone has previously been shown to affect mood: men who suffer from hypogonadism (low testosterone levels) have increased incidence of mood disorders, and administration of  testosterone has also been shown to improve mood. In this study, using male and female mice, the circuit, which runs between the ventral hippocampus (involved in stress and emotion) and the nucleus accumbens (involved in reward), was seen to have lower activity in males than females under stress. Upon removal of testosterone, male rats showed depression-like behaviours. The opposite was true in females: when testosterone was administered, females became “resistant” to depression-like behaviours.

Women commonly suffer from depression at points in their life associated with hormonal changes, such as during puberty, after birth, as well as during and after menopause. Interestingly, rates of depression in men and women align in older age – post-menopause – suggesting that female hormones, such as oestrogen, may have an effect on depression. Some studies have indicated that artificially giving oestrogen through Hormone Replacement Therapy (HRT) in the perimenopausal period may help to prevent post-menopausal depression. Women taking the oral contraceptive pill, which contains oestrogen, also appear to have lower rates of major depressive disorder. 

Taken together, this evidence suggests that oestrogen may be protective against depression. Why, then, is it women who experience nearly double the rate of depression that men do? 

Although oestrogen is typically considered the ‘female hormone’, men do have constant circulating levels of oestrogen. In the male brain, testosterone is converted into oestrogen by the enzyme aromatase. By contrast, women have higher levels of oestrogen, but the concentration varies depending on menstrual cycles and their stage in life. It is thought, therefore, that while oestrogen is protective against depression, fluctuating levels of oestrogen may have the opposite effect. 

All of the aforementioned factors are likely to play a role in the disparate rates of depression between men and women. However, depression is complex and not well understood, so it is likely that many more factors are at play, including societal factors and aspects of biology that are as of yet outside of our understanding. 

Sources

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4478054/

https://www.sciencedaily.com/releases/2019/10/191009132324.htm

https://www.sciencedaily.com/releases/2019/10/191002110323.htm

https://www.sciencedaily.com/releases/2015/08/150812135651.htm

https://www.who.int/news-room/fact-sheets/detail/adolescent-mental-health

https://www.psypost.org/2012/04/exploring-the-antidepressant-effects-of-testosterone-10837

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527720/

https://qbi.uq.edu.au/brain/brain-diseases/depression/depression-and-brain

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