The most common trigger of the first episode of major depression is

A Impact of Depression

Major and minor depressions are the two most prevalent forms of acute depressive illness. Major depression has an estimated lifetime prevalence of 17% and affects approximately twice as many women as men (6,7). The exact prevalence of minor depression is unclear due to differences in the diagnostic criteria used across studies; however, its prevalence is thought to approximate that of major depression (8,9). Recently, major depression was identified as a leading source of disease-related disability in developed countries, and it is predicted to be a leading cause of disability worldwide by the year 2020 (second only to heart disease) (10). Minor depressions, by definition, have fewer and less severe symptoms than major depressions (11,12). Nonetheless, they are associated with disability comparable to that of major depression (13–15). In fact, major depressions of moderate severity are not distinguished from minor depressions by family history (16,17), course (i.e., both major and minor depressions occur in subjects over their lifetime) (11,16), or biologic characteristics (18,19). In addition to the functional disability directly attributed to major and minor depressions, adverse medical sequelae of major depression have been identified, including increased risks for osteoporosis, the metabolic syndrome, and cardiovascular disease (20–24). Finally, if depression exists as a comorbid condition, it may increase both the morbidity and mortality of several medical illnesses, particularly heart disease (25–28).

Major depression is an illness that affects how individuals feel about themselves, those closest to them, and the world around them. Those with major depression often feel worthless about their future, lose interest in their daily activities, and show a profound decrease in their capacity to experience pleasure. In addition, patients with major depression show changes in fundamental biological processes that regulate sleep, appetite, sexual activity, autonomic function, and neuroendocrine activity. These behavioral and physiological changes closely resemble those that occur as adaptive responses to threatening or stressful situations. Thus, depression, like the stress response, involves relatively stereotyped behaviors as well as alterations in metabolism, growth, reproduction, and food intake. This article reviews common metabolic, endocrine, and neurobiological mechanisms underlying both stress system activity and the syndromes of major depression.

Epidemiology and Risk Factors

Major depression is a common disorder and is reported to have a lifetime prevalence of 16.2% and a prevalence of 6.6% for the past 12 months in U.S. adults, with an increased risk (odds ratio [OR], 1.7) in women.4 The reason for increased rates of major depressive episodes in women is unclear, but it might include hormonal factors as well as differences in psychosocial stressors, and it is likely that the increased rates of both insomnia and depression in women are related. In contrast to major depression, bipolar I and II disorders each affect about 1% of the population (lifetime) and show no sexual predilection.5 Most bipolar disorder patients have at least one other DSM-IV comorbidity (such as substance use or anxiety disorders) and are more likely to have a persistent course and severe impairment.5 Major depression and bipolar disorders have an onset in early adulthood; the median age for major depression is 32 years and for bipolar disorders 18 to 20 years.5 Major depression and bipolar disorder both usually have recurrent episodes with recovery between episodes. However, increased number and severity of episodes and poorer interepisode recovery can lead to an overall worse prognosis, suggesting that chronic treatment may be beneficial for patients with recurrent illness.

Major Depression

Major depression is associated with disturbances of the HPA axis and the SNS. Specifically, melancholic depression, a subtype of major clinical depression characterized by insomnia, loss of appetite, and weight loss, is associated with significantly higher cerebrospinal fluid norepinephrine levels around the clock.

Similar to the changes that are observed with aging, a higher mean 24 h plasma concentration cortisol has been observed in patients suffering from major depression, mainly due to a shortened quiescent period and an increase in the magnitude of the secretory episodes. Thus, patients suffering from major depression are exposed to higher glucocorticoid and catecholamine concentrations over time, which could theoretically accelerate the aging process.

Major Depression Disorder

MDD is a common mood disorder. Although it is related to ordinary emotions such as sadness, it persists even when there is no reasonable cause and is also disproportionate to an individual’s circumstances. It is recognized through distinct changes in mood, with persistent sadness and detachment. MDD not only changes the way a person feels, it also changes thoughts, behaviors, and physiology. Eventually it can result in serious emotional and physical health problems. The lifetime US incidence of depression in the general population is more than 12% in men and 20% in women (Belmaker and Agam, 2008). It is also the second most common mental health issue among disaster victims. MDD prevalence increases following disasters and is observed in about 36% of those directly impacted (Norris et al., 2002).

Major Depressive Disorder

Unipolar major depression is the most common mood disorder. Major depressive episodes are discrete periods of time (usually months to years) when individuals experience a variety of cognitive, affective, and physiological symptoms such as depressed mood, anhedonia, difficulty with concentration, feelings of worthlessness, sleep disturbance, appetite disturbance, psychomotor agitation/retardation, fatigue, and suicidal ideation or attempts.

Individuals often experience major depressive episodes in the months following their MVA. One empirical question is whether the depression is a consequence of the MVA or whether the presenting individuals had problems with major depression prior to their MVA. Longitudinal studies suggest that a large number of individuals who experience major depressive episodes following MVAs are experiencing depression for the first time in their life. The incidence of depression during the time periods of these studies is greater than one would expect in non-MVA representative population samples during the same period of time. In addition, the onset of episodes is quite often close in time to the occurrence of the MVA. Considering these two findings, it is tempting to attribute causal status to MVAs for inducing major depressive episodes in some individuals. In addition, individuals who have had difficulties with major depression prior to their accident quite often experience another episode of depression following their MVA.

Thus, a large portion of the cases of major depression noted are a direct consequence of the MVA itself. Not surprisingly, major depression is a common comorbid condition with PTSD. The limited amount of research on the impact of comorbid depression with PTSD indicates poorer outcomes in major role functioning in individuals with comorbidity relative to individuals with one condition or the other.

Major Depression

Major depression (MD) is one of the most common mental disorders, with a lifetime prevalence of at least 10%. Heritability based on twin studies is 40–50%, suggesting that it is a complex disorder with genetic and environmental risk factors. The potent environmental risk factors include childhood abuse and neglect and stressful life events. As in the case of other psychiatric disorders, genetic linkage and association studies have identified some susceptibility genes for MD, but replications of the results have been rare. However, one of the recent meta-analyses has shown that serotonin transporter gene polymorphism may be associated with MD. Other suggested susceptibility genes include serotonin 2A receptor, tyrosine hydroxylase, tryptophan hydroxylases 1 and 2, catechol-o-methyltransferase (COMT), and brain-derived neurotrophic factor.

A recent study investigated gene expression profiles of three brain regions, the orbital cortex, the dorsolateral prefrontal cortex, and the motor cortex in French Canadian individuals. The study included 24 people who had committed suicide, of whom 16 had a diagnosis of MD and eight did not. In addition, 12 controls were included. Twenty-six genes were differentially expressed between patients and controls, and one of these, spermine/spermidine N1-acetyltransferase (SSAT), was targeted for further studies. The expression difference has been confirmed with other methods. It is interesting that an association analysis of genetic markers in the gene coding for SSAT revealed evidence of association in an independent cohort of males who had committed suicide. Therefore, this study suggests that SSAT, the rate-limiting enzyme in the catabolism of polyamines, might have a role in the predisposition to suicide and depression. Another recent study looked at gene expression profiles of eight patients with MD, six with BPD, and seven control individuals. The brain regions studied included anterior cingulate cortex and dorsolateral prefrontal cortex. Altered expression of a specific subset of genes encoding the glial high-affinity glutamate transporters, glutamate-ammonia ligase, and various subunits of glutamate receptors and γ-aminobutyric acid receptors was found in patients with MD compared with controls. Altered expression of fibroblast growth factor system-related genes in MD patients was also observed in this data set.

Diagnosis and differential

Major depression can occur as a single episode, as recurrent episodes, or as part of bipolar or manic-depressive disorder. It is characterized by persistent depressed mood over a number of weeks. Associated symptoms can include insomnia, especially terminal insomnia, but sometimes hypersomnia, a distinct lack of energy, and a hopeless or at least grim outlook on one's future. Appetite may be decreased with associated, significant weight loss. Appetite can be increased for some patients. There may be a loss of interest or loss of pleasure in usually pleasurable activities along with significant feelings of worthlessness. Suicidal ideation or thoughts of death are often present. Signs may include either psychomotor retardation or agitation, loss of concentration and some impairment of short-term memory. In general, patients with major depression will have significant impairment in their ability to function.

A number of medical conditions can cause depression of this sort, including pancreatic cancer, hypothyroidism, sleep apnea, and a number of infectious and inflammatory diseases, to name a few. Some medications have been associated with major depression, such as reserpine (Serpalan) or propranolol (Inderal). The reader is referred to a textbook of general psychiatry for a complete listing. A general medical evaluation is recommended. A personal or family history of prior episodes or of bipolar illness may help clarify the diagnosis. Substance abuse does occur with major depression, and patients with a primary diagnosis of alcohol dependence can often appear severely depressed. Patients may also use alcohol, stimulants or marijuana concurrently with major depression, either to alleviate symptoms or because of concurrent substance abuse disorders. Certainly, evaluation should include a substance use history in some detail. Major depressive episodes can also occur with psychotic features such as delusions or hallucinations, which are usually mood congruent. The presence of psychotic features usually means that the patient will be more difficult to treat and certainly makes the situation emergent.

Epidemiology

Major depressive disorder has a point prevalence of approximately 1% to 2% in community-dwelling elderly, and 5% to 6% in older patients in a primary care setting. The prevalence is even higher in severely or chronically ill medical populations and in institutional settings, including nursing home or rehabilitations units.1,2 Moreover, the prevalence of so-called minor or subsyndromal depressive conditions—that is, clinically significant symptoms not meeting diagnostic criteria for major depression (see later)—is higher than that for major depression alone. The increased rate of depression in younger adult women (1.6 to 1.8 times that of younger adult men) decreases to some degree in older women (approaching 1.1 to 1.2 times that of men). Bipolar disorder is an infrequent cause of depression in older patients, with a point prevalence less than 1% in primary care, whereas new-onset primary (idiopathic) mania is rare in later life.