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Psychopathology and Pathophysiology of Depression

Psychopathology and Pathophysiology of Depression


What is depression? When talking about depression in this article, I refer to the kind of depression that is part of the major depressive disorders. Let us look at a Case Vignette as the guide to explain what depression is, what it is not, and how it may be treated it in the future.


Mrs J has been working as an executive assistant for the CEO (Mr X) of a major corporation for 13 years. Mrs J and Mr X have developed a good working relationship—he is generally very nice but is known for this temper. As is often the case in such long-term working relationships, they have developed certain rituals over time. One of those rituals is the Monday morning coffee that she prepares for him, to his taste. This Monday morning, she prepares the coffee in the usual way: nothing out of the ordinary there. However, his reaction is extraordinary. He begins to shout that the coffee tastes bad and that she cannot make a decent cup of coffee. She is surprised and puzzled, although she knows that Mr X has recently been having both private and professional trouble. Three days later, she is hospitalized for the third time with a severe episode of depression.

What does this Case Vignette tell us? First, it tells us that depression is closely related to life events. However, we need to be more specific. It is not the life event itself that is important but rather how the respective person perceives certain events. Although Mrs J knows that Mr X has been under a lot of stress lately and that he occasionally loses his temper, which may explain his rude behavior, she is unable to put things into perspective, just as she had been incapable of doing in the past.

Mrs J perceives everyday events subjectively, and if these events are negative, they often trigger a depressive episode. How is this possible? Recent research shows that stressful life events are encoded in the brain’s intrinsic activity (ie, neural activity that is continuously ongoing in the brain independent of whether a particular stimulus or task is processed).1 This intrinsic activity in the brain is established by measuring neural activity during a resting state in which the person closes his or her eyes and does not receive any specific stimuli or need to perform a task.

Although the intrinsic activity of the brain is continuous—no matter the stimuli—it does not mean that it is not affected by certain life events. Findings from recent research suggest that the brain’s intrinsic activity encodes information about stressful life events.2 Stressful life events and especially their environmental context seem to leave their traces in the brain’s intrinsic activity. Life events shape the way different brain regions and their neural activity relate to each other during the resting state. The relationship between regions and networks (ie, their functional connectivity) may thus reflect, to some yet unclear degree, a person’s life history.

What are the initial symptoms of depression in our patient? She has the feeling that things have changed. She later recounts that the most painful aspect is her emotional disconnect from her husband and children. She sees how much they care and are concerned about her, but she cannot feel anything. She has difficulty in getting up in the morning, her mood is dark, and she sleeps badly (she stays awake most of the night and finally falls asleep for 1 or 2 hours in the early morning).

During depressive episodes, patients withdraw into themselves. They experience themselves as detached from the environment and are no longer able to properly relate to and connect with their environment. It has been shown that depressed patients no longer neuronally process exteroceptive stimuli in the same way that healthy persons do.3,4 This shifts the balance between interoceptive and exteroceptive stimuli toward the interoceptive stimuli at the expense of the exteroceptive stimuli.5


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