The Science Behind Depression

Depression is the most common mood disorder in the UK, affecting 8-12% of the population in any year (although statistics on this tend to vary), but still a lot of us know relatively little about it. While temporary negative feelings are a completely healthy part of life, they can become a serious problem when they begin to affect us on a long term basis, and interfere with our everyday lives and activities, and the symptoms can range from mild cases, to severe, when depression can be accompanied by hallucinations and delusions. While depression is often characterised by its emotional symptoms, such as low moods, lingering on negative thoughts, apathy, low self-esteem and a lack of motivation, depression also has its biological symptoms, such as loss of appetite, slowed thoughts and actions, decreased libido (sex drive) and difficulty sleeping.

Causes of Depression

Particularly for this section, it’s important to bear in mind that I’m talking about unipolar depression, characterised by low moods, not bipolar (manic) depression, which involves alternating periods of extreme lows, and extreme, and often dangerous, highs).

Depression appears to be caused by a combination of biological, genetic, psychological and environmental factors, and when we attempt to look at the underlying biochemistry, it can’t simply be attributed to neuronal activity in one single brain region, but instead seems to involve areas including the prefrontal cortex (linked to decision making, social behaviour and personality expression), the amygdala (involved in memory, decision making and emotional reactions) and the hippocampus (functions involve memory and spatial awareness).

Molecular structure of serotonin. Image from:
Molecular structure of serotonin. Image from: “Serotonin-Spartan-HF-based-on-xtal-3D-balls-web” by Ben Mills – Own work. Licensed under Public Domain via Wikimedia Commons – http://commons.wikimedia.org/wiki/File:Serotonin-Spartan-HF-based-on-xtal-3D-balls-web.png#/media/File:Serotonin-Spartan-HF-based-on-xtal-3D-balls-web.png

The main theory thought to explain depression is the “Monoamine Theory”, which was first proposed in 1965. According to the theory, depression is related to low levels of the monoamine transmitters, noradrenaline and serotonin in certain areas of the brain (though episodes of mania in bipolar disorder are associated with an excess of these neurotransmitters). These small molecules are responsible for passing chemical messages between neurones, which helps to transmit signals around both the brain and the body. The most common role of noradrenaline is as a “fight or flight” neurotransmitter, increasing heart rate in times of stress, and increasing levels of alertness and arousal, so in the absence of “normal” levels of noradrenaline, our levels of alertness drop, potentially playing a role in the apathy and slow movements associated with depression. Meanwhile, serotonin is thought to play a role in happiness and wellbeing, and can influence sleep, appetite, memory and mood. For whatever reason, people with depression seem to have lower levels of these neurotransmitters, and most antidepressants work to increase their levels, and alleviate symptoms.

How Do Antidepressants Work?

Fluoxetine (trade names Prozac or Serafem). Image from public domain.
Molecular structure of fluoxetine (trade names Prozac or Serafem). Image from public domain.

The “Monoamine Theory” is actually based on the effectiveness of antidepressants; the theory was arrived at by examining the mechanisms of drugs which appear to improve symptoms of depression. There are several different classes of antidepressants, using different methods to increase levels of noradrenaline and serotonin. Ordinarily, when either serotonin or noradrenaline is released from one neurone (think of neurones as like wires, carrying electrical messages around the brain and body, but with gaps between them – synapses – which certain chemicals, neurotransmitters, must cross to pass on the message to the next neurone, or wire). After being released from the first neurone, noradrenaline/serotonin must then cross the synapse, before reaching the next neurone (called the postsynaptic neurone). When they reach the next neurone, they bind to receptors on the outside surface of the neurone, causing the signal to be passed along the postsynaptic neurone. After binding to the receptors, the neurotransmitters must be removed, to prevent overstimulation (this would cause the message to be constantly transmitted, when we only want it to be transmitted at certain times). To remove them from the area, the neurotransmitters are taken back up into the neurone which they originally came from, preventing them from lingering around the synapse and exerting their effects for too long. They can either be broken down by enzymes, so they no longer function, or re-used later on, when needed.

Fluoxetine: also known as Prozac or Serafem. By Tom Varco (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)], via Wikimedia Commons
Fluoxetine: also known as Prozac or Serafem. By Tom Varco (Own work) [CC BY-SA 3.0 (http://creativecommons.org/licenses/by-sa/3.0)%5D, via Wikimedia Commons
Antidepressants aim to increase levels of noradrenaline and serotonin. One way in which they can do this is by inhibiting (decreasing the chances of) noradrenaline and serotonin re-uptake. This means serotonin and noradrenaline remain in the synapse for longer, and so can exert their effect for longer, counteracting the decrease in their numbers, by increasing the amount still present in the synapse. This allows more binding of serotonin and noradrenaline to receptors, and increases the strength of the signal transmitted, in an attempt to bring it up to a “healthy” level. Some antidepressants, for example fluoxetine, commonly known as Prozac, target only serotonin reuptake, while others only target noradrenaline re-uptake, and some, particularly newer antidepressants, target both. Monoamine oxidase inhibitors are a class of less commonly used antidepressant, which prevent enzymes which usually break down serotonin and noradrenaline, from functioning, therefore increasing levels of these.

Of course, antidepressants aren’t the only course of treatment for depression.

Treatments such as talking therapies, cognitive behavioural therapy and counselling are commonly used to treat mild depression, while for moderate to severe cases of depression, a combination of these therapies and antidepressants are often used. The social cognitive approach examines how our thoughts and actions influence levels of depression, and how our mindset changes how we interpret an event, as though we are looking at the world through tinted glasses – rose tinted, or not. Treatments like cognitive behavioural therapy aim to break the vicious cycle of thoughts, actions and feelings that depression-sufferers often have trouble with, by challenging negative and harmful thoughts, and taking actions which hope to change attitudes and feelings. Even exercise can help with some symptoms of depression, as doing exercise increases serotonin levels, improving mood; it’s not just a form of distraction, it helps to solve the imbalance of chemicals in the brain.

15250-a-young-woman-stretching-outdoors-before-exercising-pv

While we are still learning about where these “chemical imbalances” come from, we’re getting closer to finding out the causes of depression, and in turn, finding more effective treatments. With this knowledge also comes a reassuring, but gradual change in attitudes towards mental illnesses, including depression, as they become more widely recognised as a serious issue which need to combat, to prevent the loss of life, talent and potential that mental illness can too often bring.

Featured image by: Thomas Leuthard from Hünenberg.

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