Exactly what causes depression is not known, but research has revealed several possible causes and contributory factors. These include both biological/physical and social/psychological factors. There is often a combination of factors at play in an individual’s history and environment and different people become depressed for different reasons.

Sometimes a specific trigger may be identified but at other times people seem to become depressed for no reason at all. This is more likely when the person has experienced previous depressive episodes.

Biological factors

• Neurotransmitters: Studies have shown that brain chemicals (neurotransmitters) play a mediating role in the development of depression. When the functioning of brain chemicals is disturbed, depression can occur (e.g. following the use of recreational drugs such as Ecstasy). Several different neurotransmitter systems may be involved but the two that have been more frequently implicated are serotonin (5-HT) and norepinephrine (NE). Studies have also shown a third brain chemical, dopamine, to play a role in both depressed and elevated mood.  
• Hormonal factors: Increased secretion of cortisol from the adrenal gland during stress is associated with depression. Hypercortisolaemia has been shown to damage the hippocampus (an area of the brain associated with hormonal and behavioural regulation). Thyroid gland disorders are often associated with mood disorders. All patients suffering from a MDD should be tested for hypothyroidism (i.e. underactive thyroid). Studies have shown about 10 percent of patients, especially those with a Bipolar Disorder, have detectable concentrations of anti-thyroid antibodies (produced by the body in order to fight disease which in this instance turns upon the body itself). There is also an association between anti-thyroid antibodies and post-natal depression. Alterations in the pattern of growth hormone release has also been observed.  
• Neuroanatomical/Neurophysiological considerations: CT Scans and MRI studies, although inconsistent, have shown differences in the size of some of the brain structures (e.g. caudate nucleus) in depressed patients as well as alterations in blood flow to certain areas. Mood disorders involve pathology of the limbic system (emotional centre, memory function). The basal ganglia (stooped posture, motor slowness) and the hypothalamus (changes in sleep, appetite and sexual behaviour) have also been implicated.  
• Genetic factors: Inherited factors are an important component in the development of mood disorders. Having a close relative who has suffered from a depressive disorder, especially Bipolar Disorder, increases the likelihood of developing depression. People with a genetic susceptibility are more vulnerable to depression in the face of various stressors.  
• Recreational drugs/medication: Some drugs (recreational and prescription) and alcohol can cause or exacerbate depression. This is possibly because they interfere with the regulation of brain chemicals or the physical structure of the brain (excessive alcohol and sleeping tablets cause shrinkage of the brain).  
• Medical illness: Illness including strokes, Parkinson’s disease, Cushing’s disease and thyroid disease, among others, may be a contributory physiological factor.

Psychosocial factors

Stressful life events (e.g. loss of a loved one, illness, financial worries) more often precede the first episode of mood disorders than subsequent episodes. It is believed that the initial episode in a mood disorder results in long lasting changes in the biology of the brain (e.g. the functional state and interaction of neurotransmitters; also possibly a loss of neurones and a decrease in synaptic contacts). This increases the person’s vulnerability to subsequent episodes.

A family’s style of interacting with different members, the family environment (e.g. a broken home) as well as its coping patterns may increase a vulnerability to a depressive disorder. An individual’s underlying personality type (e.g. dependent, obsessive compulsive) may also be a contributory factor.