The cause of major depressive disorder is unknown. The biopsychosocial model proposes that biological, psychological, and social factors all play a role in causing depression. The diathesis–stress model specifies that depression results when a preexisting vulnerability, or diathesis, is activated by stressful life events. The preexisting vulnerability can be either genetic, implying an interaction between nature and nurture, or schematic, resulting from views of the world learned in childhood.

Childhood abuse, either physical, sexual or psychological are all risk factors for depression, among other psychiatric issues that co-occur such as anxiety and drug abuse. Childhood trauma also correlates with severity of depression, lack of response to treatment and length of illness. However, some are more susceptible to developing mental illness such as depression after trauma, and various genes have been suggested to control susceptibility.

There are no known biological causes that apply consistently to all cases of dysthymia, which suggests diverse origin of the disorder. However, there are some indications that there is a genetic predisposition to dysthymia: "The rate of depression in the families of people with dysthymia is as high as fifty percent for the early-onset form of the disorder". Other factors linked with dysthymia include stress, social isolation, and lack of social support.

In a study using identical and fraternal twins, results indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is in part caused by heredity.

While the causes of PPD are not understood, a number of factors have been suggested to increase the risk:

- Prenatal depression or anxiety

- A personal or family history of depression

- Moderate to severe premenstrual symptoms

- Maternity blues

- Birth-related psychological trauma

- Birth-related physical trauma

- Previous stillbirth or miscarriage

- Formula-feeding rather than breast-feeding

- Cigarette smoking

- Low self-esteem

- Childcare or life stress

- Low social support

- Poor marital relationship or single marital status

- Low socioeconomic status

- Infant temperament problems/colic

- Unplanned/unwanted pregnancy

- Elevated prolactin levels

- Oxytocin depletion

Of these risk factors, formula-feeding, a history of depression, and cigarette smoking have been shown to have additive effects.

These above factors are known to correlate with PPD. This correlation does not mean these factors are causal. Rather, they might both be caused by some third factor. Contrastingly, some factors almost certainly attribute to the cause of postpartum depression, such as lack of social support.

Not surprisingly, women with fewer resources indicate a higher level of postpartum depression and stress than those women with more resources, such as financial. Rates of PPD have been shown to decrease as income increases. Women with fewer resources may be more likely to have an unintended or unwanted pregnancy, increasing risk of PPD. Women with fewer resources may also include single mothers of low income. Single mothers of low income may have more limited access to resources while transitioning into motherhood.

Studies have also shown a correlation between a mother's race and postpartum depression. African American mothers have been shown to have the highest risk of PPD at 25%, while Asian mothers had the lowest at 11.5%, after controlling for social factors such as age, income, education, marital status, and baby's health. The PPD rates for First Nations, Caucasian and Hispanic women fell in between.

Sexual orientation has also been studied as a risk factor for PPD. In a 2007 study conducted by Ross and colleagues, lesbian and bisexual mothers were tested for PPD and then compared with a heterosexual sample group. It was found that lesbian and bisexual biological mothers had significantly higher Edinburgh Postnatal Depression Scale scores than did the heterosexual women in the sample. These higher rates of PPD in lesbian/bisexual mothers may reflect less social support, particularly from their families of origin and additional stress due to homophobic discrimination in society.

A correlation between postpartum thyroiditis and postpartum depression has been proposed but remains controversial. There may also be a link between postpartum depression and anti-thyroid antibodies.

The 5-HTTLPR, or serotonin transporter promoter gene's short allele has been associated with increased risk of depression. However, since the 1990s results have been inconsistent, with three recent reviews finding an effect and two finding none. Other genes that have been linked to a GxE interaction include CRHR1, FKBP5 and BDNF, the first two of which are related to the stress reaction of the HPA axis, and the latter of which is involved in neurogenesis.

Major Depression is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and loss of interest or pleasure in normally enjoyable activities.Nearly 5 million of the 31 million Americans who are 65 years or older are clinically depressed, and 1 million have major depression. Approximately 3 percent of healthy elderly persons living in the community have major depression. Recurrence may be as high as 40 percent. Suicide rates are nearly twice as high in depressed patients as in the general population. Major depression is more common in medically ill patients who are older than 70 years and hospitalized or institutionalized. Severe or chronic diseases associated with high rates of depression include stroke (30 to 60 percent), coronary heart disease (8 to 44 percent), cancer (1 to 40 percent), Parkinson's disease (40 percent), Alzheimer's disease (20 to 40 percent), and dementia (17 to 31 percent).

Minor depression is a clinically significant depressive disorder that does not fulfill the duration criterion or the number of symptoms necessary for the diagnosis of major depression. Minor depression, which is more common than major depression in elderly patients, may follow a major depressive episode. It also can be a reaction to routine stressors in older populations. Fifteen to 50 percent of patients with minor depression develop major depression within two years.

Women who experience miscarriage are at risk of PTSD. Those who experience subsequent miscarriages have an increased risk of PTSD compared to those experiencing only one. PTSD can also occur after childbirth and the risk increases if a woman has experienced trauma prior to the pregnancy. Prevalence of PTSD following normal childbirth (that is, excluding stillbirth or major complications) is estimated to be between 2.8 and 5.6% at 6 weeks postpartum, with rates dropping to 1.5% at 6 months postpartum. Symptoms of PTSD are common following childbirth, with prevalence of 24-30.1% at 6 weeks, dropping to 13.6% at 6 months. Emergency childbirth is also associated with PTSD. Some women experience PTSD from their experiences related to breast cancer and mastectomy.

Medical conditions associated with an increased risk of PTSD include cancer, heart attack, and stroke. Intensive-care unit (ICU) hospitalization is also a risk factor for PTSD. Some women experience PTSD from their experiences related to breast cancer and mastectomy.

Estimates of the numbers of people suffering from major depressive episodes and Major Depressive Disorder (MDD) vary significantly. In their lifetime, 10% to 25% of women, and 5% to 12% of men will suffer a major depressive episode. Fewer people, between 5% and 9% of women and between 2% and 3% of men, will have MDD, or full-blown depression. The greatest differences in numbers of men and women diagnosed are found in the United States and Europe. The peak period of development is between the ages of 25 and 44 years. Onset of major depressive episodes or MDD often occurs to people in their mid-20s, and less often to those over 65. Prepubescent girls and boys are affected equally. The symptoms of depression are the same in both children and adolescents though there is evidence that their expression within an individual may change as he or she ages.

In a National Institute of Mental Health study, researchers found that more than 40 percent of people with post-traumatic stress disorder suffered from depression 4 months after the traumatic event they experienced.

Cultural factors can influence the symptoms displayed by a person experiencing a major depressive episode. The values of a specific culture may also influence which symptoms are more concerning to the person or and their friends and family. It is essential that a trained professional knows not to dismiss specific symptoms as merely being the "norm" of a culture.

Women who have recently given birth may be at increased risk for having a major depressive episode. This is referred to as postpartum depression and is a different health condition than the baby blues, a low mood that resolves within 10 days after delivery.

"At least three-quarters of patients with dysthymia also have a chronic physical illness or another psychiatric disorder such as one of the anxiety disorders, cyclothymia, drug addiction, or alcoholism". Common co-occurring conditions include major depression (up to 75%), anxiety disorders (up to 50%), personality disorders (up to 40%), somatoform disorders (up to 45%) and substance abuse (up to 50%). People with dysthymia have a higher-than-average chance of developing major depression. A 10-year follow-up study found that 95% of dysthymia patients had an episode of major depression. When an intense episode of depression occurs on top of dysthymia, the state is called "double depression."

Various factors have been found to be more associated with a diagnosis of AD than other axis I disorders, including:

- younger age

- more identified psychosocial and environmental problems

- increased suicidal behaviour, more likely to be rated as improved by the time of discharge from mental healthcare

- less frequent previous psychiatric history

- shorter length of treatment

Those exposed to repeated trauma are at greater risk, even if that trauma is in the distant past. Age can be a factor due to young children having fewer coping resources; children are also less likely to assess the consequences of a potential stressor.

A stressor is generally an event of a serious, unusual nature that an individual or group of individuals experience. The stressors that cause adjustment disorders may be grossly traumatic or relatively minor, like loss of a girlfriend/boyfriend, a poor report card, or moving to a new neighborhood. It is thought that the more chronic or recurrent the stressor, the more likely it is to produce a disorder. The objective nature of the stressor is of secondary importance. Stressors' most crucial link to their pathogenic potential is their perception by the patient as stressful. The presence of a causal stressor is essential before a diagnosis of adjustment disorder can be made.

There are certain stressors that are more common in different age groups:

Adulthood:

- Marital conflict

- Financial conflict

- Health issues with Oneself/Partner or Dependent children

- Personal tragedy (Death/personal loss)

- Loss of job or unstable employment conditions (e.g. Corporate takeover/redundancy)

Adolescence and childhood:

- Family conflict/parental separation

- School problems/changing schools

- Sexuality issues

- Death/illness/trauma in the family

In a study conducted from 1990 to 1994 on 89 psychiatric outpatient adolescents, 25% had attempted suicide in which 37.5% had misused alcohol, 87.5% displayed aggressive behaviour, 12.5% had learning difficulties, and 87.5% had anxiety symptoms.

Postpartum depression is found across the globe, with rates varying from 11% to 42%. Around 3% to 6% of women will experience depression during pregnancy or shortly after giving birth. About 1 in 750 mothers will have postpartum depression with psychosis and their risk is higher if they have had postpartum episodes in the past.

Major depressive episodes may show comorbidity (association) with other physical and mental health problems. About 20-25% of individuals with a chronic general medical condition will develop major depression. Common comorbid disorders include: eating disorders, substance-related disorders, panic disorder, and obsessive-compulsive disorder. Up to 25% of people who experience a major depressive episode have a pre-existing dysthymic disorder.

Some persons who have a fatal illness or are at the end of their life may experience depression, although this is not universal.

Winter depression is a common slump in the mood of some inhabitants of most of the Nordic countries. It was first described by the 6th century Goth scholar Jordanes in his "Getica" wherein he described the inhabitants of Scandza (Scandinavia). Iceland, however, seems to be an exception. A study of more than 2000 people there found the prevalence of seasonal affective disorder and seasonal changes in anxiety and depression to be unexpectedly "low" in both sexes. The study's authors suggested that propensity for SAD may differ due to some genetic factor within the Icelandic population. A study of Canadians of wholly Icelandic descent also showed low levels of SAD. It has more recently been suggested that this may be attributed to the large amount of fish traditionally eaten by Icelandic people, in 2007 about 90 kilograms per person per year as opposed to about 24 kg in the US and Canada, rather than to genetic predisposition; a similar anomaly is noted in Japan, where annual fish consumption in recent years averages about 60 kg per capita. Fish are high in vitamin D. Fish also contain docosahexaenoic acid (DHA), which help with a variety of neurological dysfunctions.

A study on comorbidity of GAD and other depressive disorders has shown that treatment is not more or less effective when there is some sort of comorbidity of another disorder. The severity of symptoms did not affect the outcome of the treatment process in these cases.

According to a substantial amount of epidemiology studies conducted, women are twice as likely to develop certain mood disorders, such as major depression. Although there is an equal number of men and women diagnosed with bipolar II disorder, women have a slightly higher frequency of the disorder.

In 2011, mood disorders were the most common reason for hospitalization among children aged 1–17 years in the United States, with approximately 112,000 stays. Mood disorders were top principal diagnosis for Medicaid super-utilizers in the United States in 2012. Further, a study of 18 States found that mood disorders accounted for the highest number of hospital readmissions among Medicaid patients and the uninsured, with 41,600 Medicaid patients and 12,200 uninsured patients being readmitted within 30 days of their index stay—a readmission rate of 19.8 per 100 admissions and 12.7 per 100 admissions, respectively. In 2012, mood and other behavioral health disorders were the most common diagnoses for Medicaid-covered and uninsured hospital stays in the United States (6.1% of Medicaid stays and 5.2% of uninsured stays).

A study conducted in 1988 to 1994 amongst young American adults involved a selection of demographic and health characteristics. A population-based sample of 8,602 men and women ages 17–39 years participated. Lifetime prevalence were estimated based on six mood measures:

1. major depressive episode (MDE) 8.6%,

2. major depressive disorder with severity (MDE-s) 7.7%,

3. dysthymia 6.2%,

4. MDE-s with dysthymia 3.4%,

5. any bipolar disorder 1.6%, and

6. any mood disorder 11.5%.

In many species, activity is diminished during the winter months in response to the reduction in available food, the reduction of sunlight (especially for diurnal animals) and the difficulties of surviving in cold weather. Hibernation is an extreme example, but even species that do not hibernate often exhibit changes in behavior during the winter. Presumably, food was scarce during most of human prehistory, and a tendency toward low mood during the winter months would have been adaptive by reducing the need for calorie intake. The preponderance of women with SAD suggests that the response may also somehow regulate reproduction.

Various proximate causes have been proposed. One possibility is that SAD is related to a lack of serotonin, and serotonin polymorphisms could play a role in SAD, although this has been disputed. Mice incapable of turning serotonin into N-acetylserotonin (by serotonin N-acetyltransferase) appear to express "depression-like" behavior, and antidepressants such as fluoxetine increase the amount of the enzyme serotonin N-acetyltransferase, resulting in an antidepressant-like effect. Another theory is that the cause may be related to melatonin which is produced in dim light and darkness by the pineal gland, since there are direct connections, via the retinohypothalamic tract and the suprachiasmatic nucleus, between the retina and the pineal gland. Melatonin secretion is controlled by the endogenous circadian clock, but can also be suppressed by bright light.

One study looked at whether some people could be predisposed to SAD based on personality traits. Correlations between certain personality traits, higher levels of neuroticism, agreeableness, openness, and an avoidance-oriented coping style, appeared to be common in those with SAD.

Bipolar disorder can cause suicidal ideation that leads to suicidal attempts. Individuals whose bipolar disorder begins with a depressive or mixed affective episode seem to have a poorer prognosis and an increased risk of suicide. One out of two people with bipolar disorder attempt suicide at least once during their lifetime and many attempts are successfully completed. The annual average suicide rate is 0.4 percent, which is 10–20 times that of the general population. The standardized mortality ratio from suicide in bipolar disorder is between 18 and 25. The lifetime risk of suicide has been estimated to be as high as 20 percent in those with bipolar disorder.

In addition to coexisting with depression, research shows that GAD often coexists with conditions associated with stress, such as irritable bowel syndrome. Patients with GAD can sometimes present with symptoms such as insomnia or headaches as well as pain, cardiac events and interpersonal problems.

Further research suggests that about 20 to 40 percent of individuals with attention deficit hyperactivity disorder have comorbid anxiety disorders, with GAD being the most prevalent.

The World Health Organization's Global Burden of Disease project did not include generalized anxiety disorders. In lieu of global statistics, here are some prevalence rates from around the world:

- Australia: 3 percent of adults

- Canada: Between 3 and 5 percent of adults

- Taiwan: 0.4 percent

- United States: approx. 3.1 percent of people age 18 and over in a given year (9.5 million)

The usual age of onset is variable, from childhood to late adulthood, with the median age of onset being approximately 31 and mean age of onset is 32.7. Most studies find that GAD is associated with an earlier and more gradual onset than the other anxiety disorders. The prevalence of GAD in children is approximately 3%; the prevalence in adolescents is reported as high as 10.8%. When GAD appears in children and adolescents, it typically begins around 8 to 9 years of age.

Populations with a higher rate of diagnosis of GAD are individuals that are traditionally oppressed. This includes individuals with low and middle socio-economic status, separated, divorced, and widowed individuals. Women are twice as likely to develop GAD as men. This is primarily because women are more likely than men to live in poverty, be subject to discrimination, and be sexually and physically abused. African Americans have significantly higher odds of enduring GAD and the disorder often manifests itself in different patterns. Other populations that are more diagnosed with GAD are those who live alone, those with a low level of education, and the unemployed. GAD is also common in the elderly population.

Compared to the general population, patients with internalizing disorders such as depression, generalized anxiety disorder (GAD) and post-traumatic stress disorder (PTSD) have higher mortality rates, but die of the same age-related diseases as the population, such as heart disease, cerebrovascular disease and cancer.

According to the DSM IV-TR, the development of the emotional or behavioral symptoms of this diagnosis have to occur within three months of the onset of the identifiable stressor(s). Some emotional signs of adjustment disorder are:

However, the stress-related disturbance does not only exist as an exacerbation of a pre-existing axis I or axis II disorder and cannot be diagnostic as axis 1 disorder.

Suicidal behavior is prominent among people with AD of all ages, and up to one-fifth of adolescent suicide victims may have an adjustment disorder. Bronish and Hecht (1989) found that 70% of a series of patients with AD attempted suicide immediately before their index admission and they remitted faster than a comparison group with major depression. Asnis et al. (1993) found that AD patients report persistent ideation or suicide attempts less frequently than those diagnosed with major depression. According to a study on 82 AD patients at a clinic, Bolu et al. (2012) found that 22 (26.8%) of these patients were admitted due to suicide attempt, consistent with previous findings. In addition, it was found that 15 of these 22 patients chose suicide methods that involved high chances of being saved. Henriksson et al. (2005) states statistically that the stressors are of one-half related to parental issues and one-third in peer issues.

The cause (etiology) of RBD is unknown, but recent findings may suggest a link between RBD and bipolar disorders, pointing to the importance of genetic factors. A small sub-group of patients with RBD has temporal lobe epilepsy.

It is proposed that ameliorating the stress response will allow neurotransmission to return to homeostasis. Anxiolytic medications that act as 5-HT receptor agonists (in particular, 5-HT1A) together with CRH and/or cortisol antagonists (which are implicated in the stress response) are hypothesized to be an appropriate method of achieving this therapeutic response. Psychological interventions can also help to raise the threshold for stress and thereby restore the stress response to normal.

Meta-analyses show that high scores on the personality domain neuroticism is a strong predictor for the development of mood disorders. A number of authors have also suggested that mood disorders are an evolutionary adaptation. A low or depressed mood can increase an individual's ability to cope with situations in which the effort to pursue a major goal could result in danger, loss, or wasted effort. In such situations, low motivation may give an advantage by inhibiting certain actions. This theory helps to explain why negative life incidents precede depression in around 80 percent of cases, and why they so often strike people during their peak reproductive years. These characteristics would be difficult to understand if depression were a dysfunction.

A depressed mood is a predictable response to certain types of life occurrences, such as loss of status, divorce, or death of a child or spouse. These are events that signal a loss of reproductive ability or potential, or that did so in humans' ancestral environment. A depressed mood can be seen as an adaptive response, in the sense that it causes an individual to turn away from the earlier (and reproductively unsuccessful) modes of behavior.

A depressed mood is common during illnesses, such as influenza. It has been argued that this is an evolved mechanism that assists the individual in recovering by limiting his/her physical activity. The occurrence of low-level depression during the winter months, or seasonal affective disorder, may have been adaptive in the past, by limiting physical activity at times when food was scarce. It is argued that humans have retained the instinct to experience low mood during the winter months, even if the availability of food is no longer determined by the weather.

Much of what we know about the genetic influence of clinical depression is based upon research that has been done with identical twins. Identical twins both have exactly the same genetic code. It has been found that when one identical twin becomes depressed the other will also develop clinical depression approximately 76% of the time. When identical twins are raised apart from each other, they will both become depressed about 67% of the time. Because both twins become depressed at such a high rate, the implication is that there is a strong genetic influence. If it happened that when one twin becomes clinically depressed the other always develops depression, then clinical depression would likely be entirely genetic.

Bipolar disorder is also considered a mood disorder. In the case of bipolar disorder several causes have been considered as possible, please see the wikipedia page Bipolar disorder for more details on the most common attributed causes. Recently, apart of the recent knowledge, it is hypothesized and there is evidence that bipolar disorder might be caused by mitochondrial dysfunction or mitochondrial disease.

Both psychotherapy as well as different drugs (e.g. serotonin reuptake inhibitors - SSRIs or mood stabilizers, e.g. lithium, antiepileptics) have been suggested as treatments. However, no randomized controlled treatment trial of RBD has been conducted.

Brain imaging (functional/structural MRI) may help direct the search for microscopic abnormalities in brain structure and function responsible for late life depression. Ultimately, imaging technologies may serve as tools for early diagnosis and subtyping of depression.

A lifelong condition with periods of partial or full recovery in between recurrent episodes of relapse, bipolar disorder is considered to be a major health problem worldwide because of the increased rates of disability and premature mortality. It is also associated with co-occurring psychiatric and medical problems and high rates of initial under- or misdiagnosis, causing a delay in appropriate treatment interventions and contributing to poorer prognoses. After a diagnosis is made, it remains difficult to achieve complete remission of all symptoms with the currently available psychiatric medications and symptoms often become progressively more severe over time.

Compliance with medications is one of the most significant factors that can decrease the rate and severity of relapse and have a positive impact on overall prognosis. However, the types of medications used in treating BD commonly cause side effects and more than 75% of individuals with BD inconsistently take their medications for various reasons.

Of the various types of the disorder, rapid cycling (four or more episodes in one year) is associated with the worst prognosis due to higher rates of self-harm and suicide. Individuals diagnosed with bipolar who have a family history of bipolar disorder are at a greater risk for more frequent manic/hypomanic episodes. Early onset and psychotic features are also associated with worse outcomes, as well as subtypes that are nonresponsive to lithium.

Early recognition and intervention also improve prognosis as the symptoms in earlier stages are less severe and more responsive to treatment. Onset after adolescence is connected to better prognoses for both genders, and being male is a protective factor against higher levels of depression. For women, better social functioning prior to developing bipolar disorder and being a parent are protective towards suicide attempts.