Hormones play a vital part in keeping our bodies working properly. But they can also have a powerful – and sometimes negative – effect on our mood and mental health.
We all like to think that our feelings and emotions are under our control, but are they?
Scientists have long known that chemical messengers called neurotransmitters exert a huge influence on our brain. Yet as scientists learn more, they are finding that hormones too can mess with our heads in unexpected ways.
Now, some are trying to harness this knowledge to find new treatments for conditions like depression and anxiety.
Hormones are chemical messengers released by certain glands, organs, and tissues. They enter the bloodstream and travel around the body, before binding to receptors in a specific place. The binding acts as a kind of biological “handshake” which tells the body to do something.
For example, the hormone insulin tells liver and muscle cells to suck up excess glucose from the blood and store it as glycogen.
Hormones’ invisible control
Scientists have identified more than 50 hormones in the human body so far. Together they manage hundreds of bodily processes, including a person’s growth and development, sexual function, reproduction, sleep-wake cycle and – importantly – their mental wellbeing.
“Hormones really impact our mood and our emotions,” says Nafissa Ismail, professor of psychology at the University of Ottawa, Canada.
“They do this by interacting with the neurotransmitters that are produced and released in specific brain regions, but also by influencing processes like cell death or neurogenesis – when new neurons are created or born.”
The prevalence of mental health disorders, such as depression, anxiety, and post-traumatic stress disorder (PTSD) is higher during major hormonal transitions. This is particularly true for women. Rates of depression are essentially equal between boys and girls during childhood, but by adolescence, girls are twice as likely as boys to be depressed – a difference which persists across the whole life course.
So could hormones be to blame? It may not be a surprise to learn that, if you are a woman, sex hormones exert a striking influence on mood. In the days and weeks preceding a woman’s period, levels of oestrogen and progesterone fall, coinciding with feelings of irritability, fatigue, sadness and anxiety for some, but not all. Some women can even experience premenstrual dysphoric disorder (PMDD), a severe, hormone-related mood disorder characterised by extreme mood swings, anxiety, depression, and sometimes suicidal thoughts during the two weeks before menstruation.
“For a lot of women with PMDD it’s a very chronic issue that they deal with every month, and it can have a really profound effect on people’s lives,” says Liisa Hantsoo, assistant professor of psychiatry and behavioural sciences at The Johns Hopkins University School of Medicine, US.
Conversely, high levels of oestrogen immediately before ovulation have been linked to feelings of wellbeing and happiness. Meanwhile allopregnanolone, a product of the breakdown of progesterone, is also known for its calming effects.
“If you give someone an injection of allopregnanolone, it will relax them,” says Hantsoo.
It’s not just the “time of the month” that women have to deal with. Hormonal fluctuations in pregnancy, perimenopause and menopause can also wreak havoc with mental health. Up to 13% of women who have just given birth experience depression.
But why is this? Immediately after giving birth, women experience a precipitous drop in hormones progesterone and oestrogen. In perimenopause, women can also experience dramatic fluctuations in ovarian hormones.
“It’s probably not about the exact level of hormones that somebody has, but likely these transitions where a person is going from low to high levels, or high to low levels,” says says Liisa Galea, professor of psychiatry at the University of Toronto, Canada.
“Some people are more sensitive to these kinds of fluctuations. While others will sail through menopause and won’t have any symptoms at all.”
It’s not just women. Men also experience a decrease in testosterone levels when they get older, although the change is gradual and not as pronounced as in women. However there is some evidence to suggest that even this small change is enough to trigger mood changes in some, but not all men.
“We do see changes in the mood of some men as testosterone levels change throughout the lifespan, and that is definitely a topic that does not receive enough attention,” says Ismail.
One way that sex hormones could influence mood is through increasing levels of the neurotransmitters serotonin and dopamine in the brain. Low levels of serotonin have long been touted as a cause of depression, with most modern antidepressants boosting levels of this brain chemical. There’s evidence that certain oestrogens can make serotonin receptors more responsive and increase the number of dopamine receptors in the brain.
Another theory is that oestrogen protects neurons from damage and can even stimulate the growth of new neurons in a region of the brain known as the hippocampus – known to play a role in memory and emotions. People with depression and Alzheimer’s disease are known to suffer from a loss of neurons in the hippocampus. Meanwhile antidepressants and mood-boosting psychedelic drugs like psilocybin – found in magic mushrooms – cause new neurons to grow in this region.
“Oestrogen is neuro-protective, so it will promote neurogenesis,” says Ismail. “This is why, when women enter menopause, we see sort of this retraction of the dendrites [branches sprouting from nerve cells], the dendritic projections that we had earlier on in life.” This is why women undergoing the menopause often have to deal with brain fog and memory problems.
When our body’s stress response goes wrong
A loss of neurons in the hippocampus could have knock on consequences for another hormone systems, known as the hypothalamus-pituitary-adrenal (HPA) axis, which regulates the body’s response to stress.
When we feel anxious, the hypothalamus – a region of the brain that ultimately controls the release of most hormones in the body – sends a signal to the pituitary gland to release a hormone called adrenocorticotropic hormone (ACTH). ACTH then stimulates the adrenal glands to release cortisol, a stress hormone. Cortisol tells the body to release sugar into the bloodstream, giving the brain and body the energy it needs to act in an emergency.
“The HPA axis becomes activated when someone is stressed out, and in the short term, that is adaptive because it helps your body deal with stress,” says Hantsoo. “But in the long term, it can be detrimental.”
Usually, the cortisol flooding your body should activate a negative feedback loop, whereupon the hippocampus tells the hypothalamus to stop its communication with the pituitary gland, ending the stress response. However, if a person experiences chronic stress – such as from intimidation, abuse or violence – this doesn’t happen, and the brain gets flooded with cortisol.
This is bad, because over time cortisol raises inflammation in the brain, killing off neurons in the hippocampus, and preventing it from providing that negative feedback. What’s more, cortisol can destroy neurons in other brain regions too, such as the amygdala and prefrontal cortex – impacting memory, concentration and mood.
“The amygdala is our brain region that allows us to control our emotions, and a loss of volume in that area is associated with increased emotionality, increased irritability and a difficulty in controlling those negative emotions,” says Ismail.
“The atrophy in the prefrontal cortex is associated with difficulty in concentrating, and in making the right decisions at the right time. And the atrophy in the hippocampus is associated with a difficulty in remembering information.”
While cortisol may make us stressed out, oxytocin, often known as the “love hormone”, reportedly does the opposite. It has a reputation for helping to promote warm fuzzy feelings, and kindness. It’s released during childbirth, breastfeeding and orgasm, but also seems to play a role in animal and human bonding.
“Oxytocin has been associated with bonding and this feeling of secure attachment, and of course that helps with countering the effects of stress,” says Ismail. “When we feel safe, and we feel like there is support around us, it does decrease the levels of cortisol that could have been increased by stress.”
Studies have also shown that sniffing an oxytocin nasal spray makes people more generous, cooperative and empathetic, and more likely to trust strangers.
However, not everyone is convinced. It hasn’t been conclusively shown that oxytocin can cross the blood brain barrier, for instance.
Much more accepted is the theory that imbalances in two key hormones produced by the thyroid – a butterfly-shaped gland in the throat – can cause depression and anxiety.
The hormones are triiodothyronine (T3) and thyroxine (T4), and together they help to regulate heart rate and temperature. However, when levels are too high – for example when someone has an overactive thyroid – anxiety can result. On the flip side, when levels are too low, depression is common. Luckily, correcting hormone levels usually cures patients of their symptoms.
“When patients go in to see their doctor and complain of changes in mood, one of the first things that physicians are going to do is check for their hormonal profile, because often when we’re able to correct the hormone that is experiencing a change, we are able to adjust the mood,” says Ismail.
Again, the reason for thyroid hormone’s impact on mood isn’t known, but one theory is that T3 in particular may increase levels of serotonin and dopamine in the brain, or enhance the sensitivity of receptors for these neurotransmitters. Thyroid hormone receptors are also prevalent in brain regions heavily involved in mood regulation.
New treatments
The hope is that this new knowledge of hormones, and their mood-altering effects, will trickle down into new treatments. There are signs this is beginning to happen, with a drug called Brexanolone, which mimics the hormone allopregnanolone, proving very effective at treating post-partum depression.
There is also some evidence that if you have lower levels of testosterone, then taking testosterone supplements alongside certain antidepressants can make them more effective. Studies show that oestrogen therapy, including hormone replacement therapy (HRT), can also help improve the mood of some but not all women going through perimenopause and menopause.
Hormonal birth control, meanwhile, can work wonders for some women with PMDD, however it can make symptoms worse for others, highlighting how the search for new treatments is hampered by the fact that we still don’t understand exactly why some people are so sensitive to hormonal fluctuations, while others aren’t.
“We know that hormones impact mood and mental health, but we need to figure out how they do so before we can come up with the proper treatments,” says Ismail.
“As we know, current antidepressants that regulate serotonin levels are not effective in all cases, with some studies suggesting they are less effective in adolescents particularly, so we need to learn what it is about that age group, and the brain and its development at that stage that might make them more resistant to treatment.”
BBC
