The brain is made up of anatomical sections and numerous circuits (the latter like railroad tracks). If, for example, the basal ganglia (the brain centres refining motor performance) and the pre-frontal cortex (a structural region at the front of the brain) are disrupted, there are three principal effects: depressed mood, observable PMD and cognitive problems.
Disruption of these circuits can occur in response to stress or even spontaneously. We can presume that certain neurotransmitters (these modulate mood and other mental states) have been ‘turned off’. Many factors may influence neurotransmitter function.
In melancholic depression (and, less clearly in psychotic depression) there is often a family history of depression, suggesting a genetic influence. People with melancholic depression will commonly report a significant stress prior to their first, or first few, episodes. Subsequent episodes tend to appear more spontaneously and are less clearly related to stressful events. Therefore, certain genetic influences may create a vulnerability that initially requires a stress event to trigger the depressive state.
Physics provides a useful analogy with Hookes’ Law, which states that if elastic objects are stretched within their limitations, they will ‘bounce back’ to their previous state. If, however, they are stretched beyond a certain point, their elasticity is lost. In melancholic depression, for example, it seems that initial elasticity allows the vulnerable individual to be unaffected by stressful events-for a period at least. However, once a formal episode has occurred, the elasticity is lessened and future episodes may occur without the individual being ‘stretched’ or ‘stressed’. Vulnerability has been manifested and is no longer latent.
Certain drugs and some diseases can also act like environmental stressors, in that they have the capacity to disrupt some of the brain’s neural circuits linking the basal ganglia and pre-frontal cortex (presumably by using differing pathways and affecting mechanisms). In older people, the effects of the aging brain may disrupt the circuits in other ways. There are parallels between these depressive conditions and Parkinson’s disease (which causes changes in the basal ganglia and other parts of the brain), including depression and a movement disorder.
These parallels provide some understanding of biological depressive disorders such as melancholia. In psychotic melancholia, the disruptions in the brain’s circuitry are more severe and extend to other brain circuits and regions, causing delusions and hallucinations as well as severe PMD.

The Mood Disorders Unit suspects that non-melancholic disorders are primarily caused by psychological processes reflecting an interaction between stress and the individual’s personality. A central feature of ‘depression’ is loss of one’s self-esteem (that is, thinking less of oneself or being increasingly self-critical). Any event, therefore, that impacts on an individual’s sense of self-worth risks precipitating depression.
A common stress event to impact on self-esteem is the break-up of an intimate relationship. The event itself is irrelevant- it is the individual’s response to the event that is crucial.
Consider an individual who responds to a marital break-up with, ‘My wife has left me for another man as she thinks I’m a jerk, and everything recently just confirms what a hopeless human being I am.’ Contrast this with somebody who says, ‘My wife-what a jerk-has left me. Great. I can get on with life again.’ The chance of developing depression is greater for the first respondent than the second. This is because the event differed in terms of its impact on each individual’s self-esteem levels or because they ‘processed’ the event differently as a result of their differing personalities.
Stressful events can be acute (a marital break-up) or ongoing (a dysfunctional marriage), but both have an impact on an individual’s self-esteem.
Many people who develop a non-melancholic disorder have such a low ongoing self-image, or their personality type is such, that any stressful event is likely to trigger depression. In a sense, some people actually create their own triggers. For example, a woman who thinks that everyone rejects her may misinterpret a remark at a party and become immediately and distinctly depressed.