Depression can be classified into three major types:

• early-onset, with longstanding psychobiological vulnerability (i.e., positive family history and prior episodes)
• late-onset, associated with stressful life events
• late-onset, with underlying vascular pathology

Anatomical changes in the frontolimbic areas of the brain (e.g., the orbitofrontal cortex, anterior cingulate, and gyrus rectus) have recently been associated with depression, including white-matter hyperdensities and an increased volume of cerebrospinal fluid (CSF). The severity of the hyperdensities, especially those involving the amygdala and periventricular region, correlates with the degree of depression and cognitive problems and may also help to predict treatment-refractory or unstable depression. White-matter lesions are more significant in men with late-onset. Gray matter decreases in patients with early-onset depression.

Cerebrovascular lesions in the region of the stri-ato-pallido-thalamocortical pathways and other areas have been associated with depression, cognitive problems, apathy, and lack of insight. There is growing evidence that late-onset depression in the “oldest old” population is linked to cardiovascular and cerebrovascular burden.

Elevated corticosteroids activate the hypo-thalamic-pituitary-adrenal (H-P-A) axis, deregulate the serotonergic system, and are associated with hippocampal atrophy, cognitive impairment, and depression. It is well recognized that depression is included in the differential diagnosis for dementia in the elderly.

As with all other diseases, the fundamental approach to the diagnosis of depression consists of taking a systematic history, including its onset (gradual rather than sudden), its duration (longer than two weeks), its intensity, and the presence of confounding medical illness. In general, older adults do not recognize their own depression and thus might not admit to feeling depressed if asked directly about it. More commonly, they are preoccupied with bodily functions and report symptoms such as memory loss, falls, anxiety, or a variety of somatic complaints. Sleep disturbances, appetite or weight fluctuations, and changes in mentation are more common in the elderly.

Relevant items that might need to be tested include reminiscences and a life review. Stability, personality, and coherence of one’s life story are related to mood and a sense of mastery over health-related issues in the oldest old. Practitioners should actively look for psychotic symptoms related to violence and suicide risk. When a patient is asked, “How are you doing?”, the patient’s automatic, simple answer of “fine” should not be taken at face value.

Table 1 Definition of Depression*

1. Depressed mood most of the day nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful).
2. Markedly diminished interest or pleasure in all (anhedonia), or almost all activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
3. A significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.
4. Insomnia or hypersomnia nearly every day.
5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
6. Fatigue or loss of energy nearly every day.
7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
10. The symptoms do not meet the criteria for a Mixed Episode.
11. The symptoms cause a clinically significant distress or impairment in social, occupational, or other important areas of functioning. canadian antibiotics
12. The symptoms are not due to the direct physiological effects of a
substance (e.g., a drug of abuse, or a medication) or a general medical condition (e.g., hypothyroidism).
13.   The symptoms are not better accounted for by bereavement (i.e., after loss of a loved one); the symptoms persist for longer than two months or as characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.