Major depressive disorders can occur in the context of neurological and somatic diseases, and also with the natural process of aging.

Damage to certain areas of the brain can produce affective symptoms ...For example, left-hemispherer damage, espeically toward the frontmost part (anterior pole), can produce a severe depression...Subcortical damage can also produce affective disorder; for example, damage to the basal ganglia can produce either depression or mania...Exactly how and why specifiable brain damage produces affective disorder is uncertain, although at least two possibilities have been raised. One possibility is that the neural mechanisms of affect are more easily activated. In other words, the brain damage has made the person more sensitive and emotionally reactive. Another possibility is that the spared parts of the brain may enable the patient to recognize the loss of a subjectively important function. For example, patients with Broca's aphasia (anterior left damage) and more likely to develop severe depression than patients with Wernicke's aphasia (posterior left damage). Perhaps this difference lies in the fact that in Brocha's aphasia, the posterior temporal and parietal cortex responsible for comprenhension is spared; this sparing enables the patient to appreciate the sudden loss of subjectively important left frontal functions such as those related to a coherent and enduring sense of self, or personal identity...in Sum, depressions associated with brain damage may express a damaged affective mechanism per se, while others may represent a normal depressive mechanism mobilized in an objectively depressing situation involving the sudden loss of subjectively important functions. (p.373-4)

Aging: Depression is frequently associated with aging ... could represent any of the following complex changes:

(a) a lowered threshold for expressing a preexisting depressive liability
(b) diminished endocrine, metabolic, and/or brain functions that interfere with the capacity for pleasure (secondary depression)
(c) the effect of prescribed medications (that is, physician-caused, or iatrogenic depression)
(d) a conscious reaction to diminished capacities with a consequent reduction in self-esteem (situational depression) (p.375)

Depression and Personality Disorders: Depression frequently accompanies those personality disorders that display what many clinicians call "neurotic" traits: anxiety, dependency, defensiveness, immaturity, sensitivity, and emotional disturbances in a depression marked by anxiety and irritability.(p.376)

The clinicial picture of any depression depends on preexisting personality patterns. For example, depressions associated with histrionic and borderline personality patterns have a flamboyant and self-destructive quality...(p.376)

What is neurotic depression? The label neurotic has traditionally been applied to relatively minor, nonpsychotic, highly reactive depressions that are associated with anxiety, sensitivity, and inner conflict and with inhibited or socially disruptive behaviors...The neurotic behavior of neurotic depression can be thought of as a cause or an effect. First, consider it as a cause. The neurotic behavior of a sensitive and emotional person increases the liability of depression. For example, reactive depressions often occur when such a person becomes acutely aware of the self-destructive and socially disruptive consequences of his maladaptive behavior. Morever, the repetition of such experiences may lead to a decline in self-esteem, an increase in negative expectations about prospects, and consequently an even further increase in liability to depression.

Neurotic behavior can also be an effect-in particular, a defense against the liability to depression. For example, compulsive, hypochondriacal, or seductive behavior can deflect attention from depressing thoughts or depressed mood, perhaps delaying the onset of even a genetically influence affective disorder. The depression that finally occurs could represent, among other things, a breakdown of defensive coping. (p.377)

Uncontrollable Events: Depressed people complain of hopelessness, or being unable to control emotionally significant facts of life... According to the revised theory, helplessness depressions as the products of three kinds of attributions, or interpretations, of stressful events. An internal attribution locates the cause of the events within the self ("It's my fault") with the effect of lowering self-esteem; in contrast, an external attribution ("This task is unfair") would protect self-esteem so that depression might be less likely. A stable attribution ("Failure has happened to me before and is likely to recur") represents the element of hopelessness that explains the persistence of a depressive reaction; in contrast, an unstable attribution ("I was in a bad mood") would tend to shorten the duration of any depression. Finally, a global attribution ("This kind of failure seems to occur in many situations") would explain why a depression might generalize to other situations that are objectively different from one another; in contrast, a specific attribution ("I do poorly in math") would tend to make any depression situation-specific. (p.381-2)