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."
Fluctuations in hormones
can have many effects, including disruption of a normal sleep cycle (Credit:
Getty Images)
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."
Boys and girls have
similar levels of depression before adolescence, but in the teenage years,
girls are twice as likely to have it (Credit: Getty Images)
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.
Oxytocin, often known as
the "love hormone", is linked to moments of bonding and believed to
counter some of the effects of stress (Credit: Getty Images)
"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 show that
oestrogen therapy, including hormone replacement therapy (HRT) can help some
women who are experiencing menopause (Credit: Getty Images)
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.
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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."
