Exposure to one or more uncontrollable stressors over an extended period of time can be associated with the development of non-melancholic depression. These stressors include chronic psychosocial adversity, physical illness, or exposure to recurrent psychological abuse and trauma. Unremitting and adverse life events can test the mettle of the most resilient individuals and exhaust their ability to adapt and cope.

At times, chronic stress-related depression may occur within the context of a history of early developmental deprivation. People who have had the misfortune to be exposed to early adversity may develop an expectation of further hardship and a pessimistic world view. Due to their long-standing experiences with uncontrollable and overwhelming stressors, such individuals may not have learnt effective problem-solving strategies to control or minimise the effects of future stressors.

The psychotransmitter model

Chronic and multiple salient and non-salient life events stimulate the production of large amounts of psychotransmitter which bombards the postsynaptic neuron and binds to receptor sites. Ion channels (perceptual and attributional biases) are stimulated to remain open, thus allowing the unremitting passage of ions into the neuron which, in turn, sets off numerous metabolic processes within the cell. Consequently, the neuron reacts to an unrelenting source of chronic stimulation and is flooded by the effects of high concentrations of intracellular chemical mediators (coping repertoires).