What is… Melancholic Depression


The word melancholia comes from the Greek for black bile, part of the ancient four humours medical belief system. In the 5th century BCE, Hippocrates first identified melancholia as a disease with various mental and physical symptoms. In the 16th and 17th centuries, the idea of a melancholic temperament became fashionable in English art and literature.

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What is now called depression with melancholic features has been referred to in the past as endogenous (as opposed to reactive) depression, and before that, melancholia.

In the DSM-5, the melancholic features specifier can be used to describe a major depressive episode (in major depressive disorder or bipolar disorder) with a certain cluster of symptoms. That symptom cluster includes:
Anhedonia (near-total inability to feel pleasure).
Lack of positive reaction to normally pleasurable things.
A quality of mood that’s distinct from grief/loss, i.e. it subjectively feels different.
Early morning awakening.
Psychomotor retardation (slowed movement and thinking) or agitation.
Significant loss of appetite.
Symptoms that are worse in the morning.
Excessive/inappropriate guilt.

Either symptom #1 or 2 must be present, in addition to at least 3 symptoms from #3-8. Symptom #5 (psychomotor changes) is nearly always present. The full criteria for a major depressive episode must be met, including the presence of symptoms almost all day, almost every day, for at least 2 weeks, with clinically significant distress or impairment in social and occupational functioning.

While many people experiencing a major depressive episode experience some of these symptoms, it’s this particular symptom cluster occurring together that gets labelled as melancholic features. There are many different potential combinations of symptoms in a major depressive episode, and not everyone who’s having a major depressive episode has a features specifier of any kind.

There’s some question as to whether melancholic depression represents a distinct illness from depression with atypical features, which involves a cluster of symptoms like increased sleep and appetite, mood reactivity to pleasurable stimuli, and leaden paralysis. At this point, though, the DSM’s categorical system treats them as different features of the same illness.
The biology of melancholia
There do appear to be differences in how melancholic depression affects the brain, including changes that can be seen on electroencephalogram (EEG) and MRI across groups of patients with melancholic vs. non-melancholic depression.
Melancholic depression appears to have a strong biological component, including a genetic element. There appear to be disruptions in the hypothalamic-pituitary-adrenal (HPA) axis that connects the brain and the adrenal glands, as well as elevated inflammation.

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Despite these elements that have been observed across groups of patients, no biological feature has been identified, at least at this point, that’s a definite diagnostic marker.
Characteristics of melancholic depression
People with melancholic features tend to have relatively normal childhoods, and when well, they tend not to have significant problems with relationships and work functioning. The depression is more likely to be identified as an imposed illness rather than a logical reaction to life stressors.
Episodes can occur with no apparent situational triggers, and they tend to be more severe than one might expect given the situational circumstances. Melancholic episodes can also occur in response to minor, non-severe stressors, and researchers from Queen’s University have suggested that melancholic depression may be especially sensitive to stress. This would fit with the idea of inflammation playing some role in this particular form of depression.

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The Lundby Study, a longitudinal community-based study in Sweden, showed that people whose first depressive episode had melancholic features were at a greater risk for recurrence of their depression compared to people with a non-melancholic first depressive episode.
Melancholic features have been associated with greater cognitive dysfunction than non-melancholic depression, including poorer processing speed, problem-solving, and visual memory. Psychotic features are also more common in this form of depression.
Researchers have observed deficits in reward-based learning tasks, meaning people are less likely to develop behaviours geared towards maximizing rewards. This may be related to dysfunction in dopamine signalling in the brain’s reward areas.

Response to treatment
Melancholic depression tends to respond better to biological treatments like antidepressants and electroconvulsive therapy (ECT) than it does to psychotherapy, and it’s less responsive to placebo than other forms of depression.
Some research has shown an improved response to antidepressants that target multiple neurotransmitter systems rather than just serotonin, although there have been contradictory findings. In keeping with this, some studies have suggested that tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may be the most effective. It can sometimes be helpful to add other medications to augment antidepressants, including atypical antipsychotics or psychostimulants (e.g. Ritalin, Dexedrine).

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