What is Depression?

In any given year, about one in five Australians will experience symptoms of mental illness, and two in five in their lifetime. Anxiety disorders and affective disorders are the most common groups of mental illness.

Whilst sadness is a transient emotion that we all experience in our lives, depression is very different from feeling low. It’s a Catch 22 though: the universality of sadness can help us get a sense of what depression is like, but the experience of depression is very different to sadness. You can lift yourself out of sadness, so why not depression? The familiarity can breed stigma - more on this for another post.

Depression re-wires your brain and alters the brain’s soup of neurotransmitters. This changes the expression of genes, which reinforces the changes and the symptoms. Depression changes your interactions with other people, and their response affects your own behaviour and experience, in turn reinforcing those complex biological changes, which alters your cognitive processes.

You don’t simply choose to get better or stay unwell. You need a helping hand. But that hand looks different for each type of depression.

Types of depression

Broadly speaking there are two main types of depression: reactive depression and melancholic depression. There are other types of depression (such as Persistent Depressive Disorder and Psychotic Depression) but I’ll focus on these two as reactive depression is more common than other forms of depression, and melancholic depression is the most common form of “biological” depression.

Reactive depression is triggered by something external, such as a life stresses, and is tecnhically called an Adjustment Disorder with Depressed Mood. Generally, this type of depression resolves once the stressors have resolved. It is characterised by persistence of low mood after a major life event, but generally doesn’t have the “biological” features of difficulty thinking, slowed body movement and thinking, sleeplessness, or loss of appetite, among other “classic” signs of depression.

But it’s not so black and white. Symptoms of reactive depression may persist and they may also significantly impact a person’s life. And if the person has a genetic vulnerability to other forms of depression, then a reactive depression may evolve.

A melancholic depression - or Major Depressive Disorder - must have depressive symptoms for at least two weeks and includes biological features such as those listed above. The onset may be gradual with no clear trigger. It is pervasive and consuming.

The biological features are an important clue about how much the brain’s neurotransmitter soup has been disrupted.

Monoamine hypothesis of depression

It’s worth mentioning the monoamine hypothesis of depression, which is captures our understanding of the neurobiology of depression. Monoamines are a group of neurotransmitters that share a certain chemical structure. They include serotonin, dopamine, melatonin, adrenaline, and noradrenaline, which all play a part in how we treat deperssion with medication.

The monoamine hypothesis of depression is empirical. It was proposed after scientists discovered that earlier antidepressants increased levels of serotonin, dopamine, and noradrenaline. This change correlated with an improvement in depressive symptoms. As we’ve furthered our understanding of the brain, we now have a deeper understanding of the specific brain circuits and how different medication enhance connectivity.

This led to the discovery of new medications that specifically targeted these neurotransmitters - such as SSRIs (increases serotonin) and SNRIs (increases serotonin and noradrenaline) - with less side effects compared with older antidepressants.

As noted above, depression is much more than neurobiology and the neurobiology can be affected by other illnesses, both physical and mental. As the image above suggests, there is a complex interaction of biological, psychological, social, and cultural factors. But the monoamine hypothesis of depression is useful for drug discovery. It also helps to understand why medication in isolation of other treatments may not be as effective as hoped.

Diagnosis guides Treatment

It is important to distinguish between reactive and melancholic depression, as well as the other less common types of depression. Getting the diagnosis wrong will lead to the wrong type of treatment. For instance, medication may only have minimal benefit in a reactive depression because there isn’t a significant biological component to it.

With the wrong diagnosis, someone may find that they’ve tried two or more types of medication. This would fit the criteria for a treatment-resistant depression, which can lead to other forms of therapy without much benefit.

This is why medical doctors are taught to keep in mind the “differential diagnosis” - alternative conditions that can also explain the symptoms that a person presents with. Regardless of your specialty, the differential diagnosis helps to guide investigation into the question of “why this person, why these symptoms, why now?”

Evidence shows that medication combined with psychotherapy leverages synergies between the two treatments. I think about it like this: medication balances the underlying neurobiology, which in turn enhances engagement in and response to other therapies, including psychological therapies and complimentary therapies.

Rational prescribing enhances the effects of psychotherapy by leveraging the underlying neurobiology - it’s essentially hacking the brain so that “talking therapies” can get inside the thoughts.

Whilst, psychotherapy is an important component to treatment of depression, it can be difficult to access and may not be appropriate at a given time. Cognitive Behavioural Therapy (CBT) for instance is beneficial for a reactive depression, but the acute phase of a melancholic depression impacts cognition and therefore can disrupt the benefits of CBT. In its more severe forms, melancholic depression can leave a person stuck in a loop and unable to benefit from CBT - or any other form of psychotherapy for that matter.

Bespoke treatment of depression

Treatment of depression therefore needs to be tailored to the individual. Their sociocultural situation, their readiness and other illnesses, the type and the stage of depression, the person’s readiness and acceptance of different modalities.

In all its hues, depression is a dynamic and complex interplay of genes, environment and neurobiology. All of these can be changed, but it’s slow and a hard won. Working through depression takes years of effort; it’s not just a matter of waking up and choosing happiness.

#mentalhealth #depression #monoaminehypothesis #psychiatry #psychotherapy #psychopharmacology