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Introduction
Having suffered from a first episode of major depressive disorder (MDD) a large number of sufferers experience recurrences. Each recurrence seems to then increase the likelihood of subsequent recurrences (Kendler et al. 2001). In some patients, therefore, depression becomes a long-term, cyclical condition.
A large body of work has focused on the changes that occur in depression. Of these the most immediately obvious is in (1) mood. This is accompanied by a change in (2) cognitive performance which includes 'negative biases'. Additional abnormalities in (3) monoaminergic neurotransmission [serotonin (5-HT), dopamine (DA) and noradrenaline (NA)] are also found alongside (4) a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (de Kloet et al. 2005). These changes are associated with all episodes of depression.
The literature is sparse with specific regard to recurrent episodes, but the studies that do exist seem to suggest that these changes return but in an increasingly pronounced manner. Rumination, negative biases, memory problems and cortisol release all show relative increase with successive episodes whilst sleep efficacy and social interaction ability diminish (Thase et al. 1995; Bouhuys & Sam, 2000; Nandrino et al. 2002, 2004; Fossati et al. 2004; Sher et al. 2004). This pattern of decline may continue until at least the ninth episode (Kendler et al. 2001).
This alteration in symptom severity is accompanied by an alteration in the factors that trigger an episode. A consistently implicated trigger of depression is that of environmental stress. Stress can induce negative mood, provoke cognitive change, reduce cerebral 5-HT (Russo et al. 2003) and increase HPA axis activity and therefore provides a common link between the different symptoms. These stress-induced changes are normally temporary but it is thought that following chronic or extreme stress, they can persist and an episode of depression is experienced (de Kloet et al. 2005). A first episode of depression therefore tends to be triggered by a 'major life event' (such as bereavement). Subsequent episodes, however, tend to either be triggered by milder stressors or become totally independent of stress (Lewinsohn et al. 1999). This indicates a pattern of reducing stress threshold with each successive episode which might, in turn, explain the increasing risk of recurrence. The concept of 'kindling', in which the first episode is said to leave behind...