Major depression significantly affects a person's family and personal relationships, work or school life, sleeping and eating habits, and general health. Its impact on functioning and well-being has been compared to that of other chronic medical conditions such as diabetes.

A person having a major depressive episode usually exhibits a very low mood, which pervades all aspects of life, and an inability to experience pleasure in activities that were formerly enjoyed. Depressed people may be preoccupied with, or ruminate over, thoughts and feelings of worthlessness, inappropriate guilt or regret, helplessness, hopelessness, and self-hatred. In severe cases, depressed people may have symptoms of psychosis. These symptoms include delusions or, less commonly, hallucinations, usually unpleasant. Other symptoms of depression include poor concentration and memory (especially in those with melancholic or psychotic features), withdrawal from social situations and activities, reduced sex drive, irritability, and thoughts of death or suicide. Insomnia is common among the depressed. In the typical pattern, a person wakes very early and cannot get back to sleep. Hypersomnia, or oversleeping, can also happen. Some antidepressants may also cause insomnia due to their stimulating effect.

A depressed person may report multiple physical symptoms such as fatigue, headaches, or digestive problems; physical complaints are the most common presenting problem in developing countries, according to the World Health Organization's criteria for depression. Appetite often decreases, with resulting weight loss, although increased appetite and weight gain occasionally occur. Family and friends may notice that the person's behavior is either agitated or lethargic. Older depressed people may have cognitive symptoms of recent onset, such as forgetfulness, and a more noticeable slowing of movements. Depression often coexists with physical disorders common among the elderly, such as stroke, other cardiovascular diseases, Parkinson's disease, and chronic obstructive pulmonary disease.

Depressed children may often display an irritable mood rather than a depressed mood, and show varying symptoms depending on age and situation. Most lose interest in school and show a decline in academic performance. They may be described as clingy, demanding, dependent, or insecure. Diagnosis may be delayed or missed when symptoms are interpreted as normal moodiness.

A person experiencing a major depressive episode may report depressed mood or may appear depressed to others. Often, interest or pleasure in everyday activities is decreased; this is referred to as anhedonia. These feelings must be present on an everyday basis for two weeks or longer to meet DSM-IV criteria for a major depressive episode.

Depressed people may have feelings of guilt that go beyond a normal level or are delusional. Depressed people may think of themselves in very negative, unrealistic ways, such as manifesting a preoccupation with past failures, personalisation of trivial events, or believing that minor mistakes prove their inadequacy. They also may have an unrealistic sense of personal responsibility and see things beyond their control as being their fault. Additionally, self-loathing is common in clinical depression, and can lead to a downward spiral when combined with other symptoms.

A person experiencing a depressive episode may have a marked loss or gain of weight (such as 5% of their body weight in one month) or a change in appetite.

Changes in appetite take on two manifestations: under- or over-eating.

In the first instance, some people never feel hungry, can go long periods without wanting to eat, or may forget to eat; if they do eat, a small amount of food may be sufficient. In children, failure to make expected weight gains may be counted towards this criteria. Under-eating is often associated with a melancholic type of depression.

In the second instance, some people tend toward an increase in appetite and may gain significant amounts of weight. They may crave certain types of food, such as sweets or carbohydrates. People with seasonal affective disorder (SAD) often crave foods high in carbohydrates. Over-eating is often associated with a type of depression called atypical depression.

Psychotic symptoms are often missed in psychotic depression, either because patients do not think their symptoms are abnormal or they attempt to conceal their symptoms from others. On the other hand, psychotic depression may be confused with schizoaffective disorder. Due to overlapping symptoms, differential diagnosis includes also dissociative disorders.

Individuals with psychotic depression experience the symptoms of a major depressive episode, along with one or more psychotic symptoms, including delusions and/or hallucinations. Delusions can be classified as mood congruent or incongruent, depending on whether or not the nature of the delusions is in keeping with the individual's mood state. Common themes of mood congruent delusions include guilt, persecution, punishment, personal inadequacy, or disease. Half of patients experience more than one kind of delusion. Delusions occur without hallucinations in about one-half to two-thirds of patients with psychotic depression. Hallucinations can be auditory, visual, olfactory (smell), or haptic (touch), and are congruent with delusional material. Affect is sad, not flat. Severe anhedonia, loss of interest, and psychomotor retardation are typically present.

Major depression frequently co-occurs with other psychiatric problems. The 1990–92 "National Comorbidity Survey" (US) reports that half of those with major depression also have lifetime anxiety and its associated disorders such as generalized anxiety disorder. Anxiety symptoms can have a major impact on the course of a depressive illness, with delayed recovery, increased risk of relapse, greater disability and increased suicide attempts. There are increased rates of alcohol and drug abuse and particularly dependence, and around a third of individuals diagnosed with ADHD develop comorbid depression. Post-traumatic stress disorder and depression often co-occur. Depression may also coexist with attention deficit hyperactivity disorder (ADHD), complicating the diagnosis and treatment of both. Depression is also frequently comorbid with alcohol abuse and personality disorders.

Depression and pain often co-occur. One or more pain symptoms are present in 65% of depressed patients, and anywhere from 5 to 85% of patients with pain will be suffering from depression, depending on the setting; there is a lower prevalence in general practice, and higher in specialty clinics. The diagnosis of depression is often delayed or missed, and the outcome can worsen if the depression is noticed but completely misunderstood.

Depression is also associated with a 1.5- to 2-fold increased risk of cardiovascular disease, independent of other known risk factors, and is itself linked directly or indirectly to risk factors such as smoking and obesity. People with major depression are less likely to follow medical recommendations for treating and preventing cardiovascular disorders, which further increases their risk of medical complications. In addition, cardiologists may not recognize underlying depression that complicates a cardiovascular problem under their care.

To meet criteria for a major depressive episode, a patient must have 5 of these 9 symptoms nearly every day for at least 2 weeks.

1. Depressed or sad mood

2. Anhedonia (loss of interest in pleasurable activities)

3. Sleep disturbance (increased or decreased sleep)

4. Appetite disturbance (increased or decreased appetite) typically with weight change

5. Energy disturbance (increased or decreased energy/activity level), usually fatigue

6. Poor memory and/or concentration

7. Feelings of guilt or worthlessness

8. Psychomotor retardation or agitation (a change in mental and physical speed perceived by other people)

9. Thoughts of wishing you were dead; suicidal ideation or suicide attempts

The forefront indication a depressive episode is manifesting is the sudden loss of energy or motivation in daily routines. When this occurs, it is not uncommon for individuals to seek medical attention with excessive worrying or anxiety that a more severe, physiological disease may be the underlying issue. However, without an actual disease present, this neurotic thinking often results in severe anxiety, sleep disturbance, and mood swings which may hinder social relationships. Individuals with endogenous depression may experience inconsistencies in symptom severity which is often the reason for delayed treatment. If left untreated, symptoms may progress to a major depressive episode.

Depressive mixed states occur when patients experience depression and non-euphoric, usually subsyndromal, hypomania at the same time. As mentioned previously, it is particularly difficult to diagnose BP-II when a patient is in this state.

In a mixed state, mood is depressed, but the following symptoms of hypomania present as well:

- Irritability

- Mental overactivity

- Behavioral overactivity

Mixed states are associated with greater levels of suicidality than non-mixed depression. Antidepressants may increase this risk.

Depression is a state of a low mood and aversion to activity that can affect a person's thoughts, behavior, feelings, and sense of well-being. A depressed mood is a normal temporary reaction to life events such as loss of a loved one. It is also a symptom of some physical diseases and a side effect of some drugs and medical treatments. Depressed mood is also a symptom of some mood disorders such as major depressive disorder or dysthymia.

People with a depressed mood may be notably sad, anxious, or empty; they may also feel notably hopeless, helpless, dejected, or worthless. Other symptoms expressed may include senses of guilt, irritability, or anger. Further feelings expressed by these individuals may include feeling ashamed or an expressed restlessness. These individuals may notably lose interest in activities that they once considered pleasurable to family and friends or otherwise experience either a loss of appetite or overeating. Experiencing problems concentrating, remembering general facts or details, otherwise making decisions or experiencing relationship difficulties may also be notable factors in these individuals' depression and may also lead to their attempting or actually dying by suicide.

Expressed insomnia, excessive sleeping, fatigue, and vocalizing general aches, pains, and digestive problems and a reduced energy may also be present in individuals experiencing depression.

"Mood disorder due to a general medical condition" is used to describe manic or depressive episodes which occur secondary to a medical condition. There are many medical conditions that can trigger mood episodes, including neurological disorders (e.g. dementias), metabolic disorders (e.g. electrolyte disturbances), gastrointestinal diseases (e.g. cirrhosis), endocrine disease (e.g. thyroid abnormalities), cardiovascular disease (e.g. heart attack), pulmonary disease (e.g. chronic obstructive pulmonary disease), cancer, and autoimmune diseases (e.g. rheumatoid arthritis).

The exact changes in brain chemistry and function that cause either late life or earlier-onset depression are unknown. It is known, however, that brain changes can be triggered by the stresses of certain life events such as illness, childbirth, death of a loved one, life transitions (such as retirement), interpersonal conflicts, or social isolation. Risk factors for depression in elderly persons include a history of depression, chronic medical illness, female sex, being single or divorced, brain disease, alcohol abuse, use of certain medications, and stressful life events.

It is during depressive episodes that BP-II patients often seek help. Symptoms may be syndromal or subsyndromal. Depressive BP-II symptoms may include five or more of the below symptoms (at least one of them must be either depressed mood or loss of interest/pleasure). In order to be diagnosed, they need to be present only during the same two-week period, as a change from previous hypomanic functioning:

- Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, or hopeless) or observation made by others (e.g., appears tearful). (Note: In children and adolescents, can be irritable mood.)

- Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).

- 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. (Note: In children, consider failure to make expected weight gain.)

- Insomnia or hypersomnia nearly every day.

- Psychomotor agitation or retardation nearly every day (observable by others; not merely subjective feelings of restlessness or being slowed down).

- Fatigue or loss of energy nearly every day.

- Feelings of worthlessness or excessive or inappropriate guilt nearly every day (not merely self-reproach or guilt about being sick).

- Diminished ability to think or concentrate, possible irritability or indecisiveness, nearly every day (either by subjective account or as observed by others).

- Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, a suicide attempt, or a specific plan for committing suicide.

Evidence also suggests that BP-II is strongly associated with atypical depression. Essentially, this means that many BP-II patients exhibit reverse vegetative symptoms. BP-II patients may have a tendency to oversleep and overeat, while typically depressed patients sleep and eat less than usual.

Melancholic depression, or depression with melancholic features, is a DSM-IV subtype of clinical depression requiring at least one of the following symptoms:

- Anhedonia (the inability to find pleasure in positive things)

- Lack of mood reactivity (i.e. mood does not improve in response to positive events)

And at least three of the following:

- Depression that is subjectively different from grief or loss

- Severe weight loss or loss of appetite

- Psychomotor agitation or retardation

- Early morning awakening

- Guilt that is excessive

- Worse mood in the morning

Melancholic features apply to an episode of depression that occurs as part of either major depressive disorder or bipolar disorder I or II.

Melancholic depression is often considered to be a biologically based and particularly severe form of depression. Treatment involves antidepressants, electroconvulsive therapy, or other empirically supported treatments such as cognitive behavioral therapy and interpersonal therapy for depression. A 2008 analysis of a large study of patients with unipolar major depression found a rate of 23.5% for melancholic features. It was the first form of depression extensively studied, and many of the early symptom checklists for depression reflect this.

The incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.

According to the DSM-IV, the "melancholic features" specifier may be applied to the following only:

1. Major depressive episode, single episode

2. Major depressive episode, recurrent episode

3. Bipolar I disorder, most recent episode depressed

4. Bipolar II disorder, most recent episode depressed

Atypical depression, or depression with atypical features as it has been known in the DSM IV, is depression that shares many of the typical symptoms of the psychiatric syndromes major depression or dysthymia but is characterized by improved mood in response to positive events. In contrast, people with melancholic depression generally do not experience an improved mood in response to normally pleasurable events. Atypical depression also features significant weight gain or an increased appetite, hypersomnia, a heavy sensation in the limbs and interpersonal rejection sensitivity that results in significant social or occupational impairment.

Despite its name, "atypical" depression does not mean it is uncommon or unusual. The reason for its name is twofold: (1) it was identified with its "unique" symptoms subsequent to the identification of melancholic depression and (2) its responses to the two different classes of antidepressants that were available at the time were different from melancholic depression (i.e., MAOIs had clinically significant benefits for atypical depression, while tricyclics did not).

Atypical depression is two to three times more common in women than in men. Individuals with atypical features tend to report an earlier age of onset (e.g. while in high school) of their depressive episodes, which also tend to be more chronic and only have partial remission between episodes. Younger individuals may be more likely to have atypical features, whereas older individuals may more often have episodes with melancholic features. Atypical depression has high comorbidity of anxiety disorders, carries more risk of suicidal behavior, and has distinct personality psychopathology and biological traits.

Atypical depression is more common in individuals with bipolar I, bipolar II, cyclothymia and seasonal affective disorder. Depressive episodes in bipolar disorder tend to have atypical features, as does depression with seasonal patterns.

The DSM-IV-TR defines Atypical Depression as a subtype of Major Depressive Disorder with Atypical Features, characterized by:

1. Mood reactivity (i.e., mood brightens in response to actual or potential positive events)

2. At least two of the following:

- Significant weight gain or increase in appetite;

- Hypersomnia (sleeping too much, as opposed to the insomnia present in melancholic depression);

- Leaden paralysis (i.e., heavy, leaden feelings in arms or legs);

- Long-standing pattern of interpersonal rejection sensitivity (not limited to episodes of mood disturbance) that results in significant social or occupational impairment.

3. Criteria are not met for With Melancholic Features or With Catatonic Features during the same episode.

Cyclothymia is characterized by short cycles of baseline, stable periods of not over two months and numerous swings between depression and hypomania that fail to meet the severity of sustained duration criterion for major affective syndromes for at least two years.

Depressive/dysthymic episodes. Symptoms of the "depressive/dysthymic phase" may include any of the following conditions:difficulty making decisions, problems concentrating, poor memory recall, guilt, self-criticism, low self-esteem, pessimism, self-destructive thinking, constant sadness, apathy, hopelessness, helplessness and irritability. Also common are quick temper, poor judgment, lack of motivation, social withdrawal, appetite change, lack of sexual desire, self-neglect, fatigue, insomnia and sleepiness.

Hypomanic episodes. Symptoms of the "hypomanic episode" may include any of the following conditions: unusually good mood or cheerfulness (euphoria), extreme optimism, inflated self-esteem, rapid speech, racing thoughts, aggressive or hostile behavior, lack of consideration for others, agitation, massively increased physical activity, risky behavior, spending sprees, increased drive to perform or achieve goals, increased sexual drive, decreased need for sleep, tendency to be easily distracted, and inability to concentrate.

Hypomania is the milder form of mania, defined as at least four days of the same criteria as mania, but does not cause a significant decrease in the individual's ability to socialize or work, lacks psychotic features such as delusions or hallucinations, and does not require psychiatric hospitalization. Overall functioning may actually increase during episodes of hypomania and is thought to serve as a defense mechanism against depression by some. Hypomanic episodes rarely progress to full blown manic episodes. Some people who experience hypomania show increased creativity while others are irritable or demonstrate poor judgment.

Hypomania may feel good to some persons who experience it, though most people who experience hypomania state that the stress of the experience is very painful. Bipolar people who experience hypomania, however, tend to forget the effects of their actions on those around them. Even when family and friends recognize mood swings, the individual will often deny that anything is wrong. What might be called a "hypomanic event", if not accompanied by depressive episodes, is often not deemed problematic, unless the mood changes are uncontrollable, volatile, or mercurial. Most commonly, symptoms continue for a few weeks to a few months.

Mania is a distinct period of at least one week of elevated or irritable mood, which can range from euphoria to delirium, and those experiencing hypo- or mania may exhibit three or more of the following behaviors: speak in a rapid, uninterruptible manner, short attention span, racing thoughts, increased goal-oriented activities, agitation, or they may exhibit behaviors characterized as impulsive or high-risk, such as hypersexuality or excessive spending. To meet the definition for a manic episode, these behaviors must impair the individual's ability to socialize or work. If untreated, a manic episode usually lasts three to six months.

People with hypomania or mania may experience a decreased need of sleep, impaired judgment, and speak excessively and very rapidly. Manic individuals often have a history of substance abuse developed over years as a form of "self-medication". At the more extreme, a person in a full blown manic state can experience psychosis; a break with reality, a state in which thinking is affected along with mood. They may feel unstoppable, or as if they have been "chosen" and are on a "special mission", or have other grandiose or delusional ideas. This may lead to violent behavior and, sometimes, hospitalization in an inpatient psychiatric hospital. The severity of manic symptoms can be measured by rating scales such as the Young Mania Rating Scale, though questions remain about the reliability of these scales.

The onset of a manic or depressive episode is often foreshadowed by sleep disturbances. Mood changes, psychomotor and appetite changes, and an increase in anxiety can also occur up to three weeks before a manic episode develops.

The DSM-5, released in May 2013, separates the mood disorder chapter from the DSM-TR-IV into two sections: Depressive and Related Disorders and Bipolar and Related Disorders. Bipolar Disorders falls in between Depressive Disorders and Schizophrenia Spectrum and Related Disorders “in recognition of their place as a bridge between the two diagnostic classes in terms of symptomatology, family history and genetics” (Ref. 1, p 123). Bipolar Disorders underwent a few changes in the DSM-5, most notably the addition of more specific symptomology related to hypomanic and mixed manic states. Depressive Disorders underwent the most changes, the addition of three new disorders: disruptive mood dysregulation disorder, persistent depressive disorder (previously dysthymia), and premenstrual dysphoric disorder (previously in Appendix B, the section for disorders needing further research). Disruptive mood dysregulation disorder is meant as a diagnosis for children and adolescents who would normally be diagnosed with bipolar disorder as a way to limit the bipolar diagnosis in this age cohort. Major depressive disorder (MDD) also underwent a notable change, in that the bereavement clause has been removed. Those previously exempt from a diagnosis of MDD due to bereavement are now candidates for the MDD diagnosis.

Endogenous depression was initially considered valuable as a means of diagnostic differentiation with reactive depression. While the latter's onset could be attributed to adverse life events and treated with talk therapy, the former would indicate treatment with antidepressants. Indeed, this view of endogenous depression is at the root of the popular view that mood disorders are a reflection of a 'chemical imbalance' in the brain. More recent research has shown that the probability of an endogenous depression patient experiencing an adverse life event prior to a depressive episode is roughly the same as for a reactive depression patient and the efficacy of antidepressant therapy bears no statistical correlation with the patient's diagnostic classification along this axis.

The essential feature of bipolar I disorder is a clinical course characterized by the occurrence of one or more manic episodes or mixed episodes (DSM-IV-TR, 2000). Often, individuals have had one or more major depressive episodes. One episode of mania is sufficient to make the diagnosis of bipolar disorder; the patient may or may not have history of major depressive disorder. Episodes of substance-induced mood disorder due to the direct effects of a medication, or other somatic treatments for depression, drug abuse, or toxin exposure, or of mood disorder due to a general medical condition need to be excluded before a diagnosis of bipolar I disorder can be made. In addition, the episodes must not be better accounted for by schizoaffective disorder or superimposed on schizophrenia, schizophreniform disorder, delusional disorder, or a psychotic disorder not otherwise specified.

Comorbid psychiatric disorders commonly go undetected in the treatment of depression. If left untreated, the symptoms of these disorders can interfere with both evaluation and treatment.

Anxiety disorders are one of the most common disorder types associated with treatment-resistant depression. The two disorders commonly co-exist, and have some similar symptoms. Some studies have shown that patients with both MDD and panic disorder are the most likely to be nonresponsive to treatment.

Substance abuse may also be a predictor of treatment-resistant depression. It may cause depressed patients to be noncompliant in their treatment, and the effects of certain substances can worsen the effects of depression.

Other psychiatric disorders that may predict treatment-resistant depression include personality disorders, obsessive compulsive disorder, and eating disorders.

Because the nature of acute schizophrenia is similar to depression, it is difficult to differentiate normal levels of depression in patients with schizophrenia from depressive levels in post-schizophrenic depression. "Prominent subjectively low mood, suggesting depression, and prominent blunting of affect, suggesting negative symptoms, are the two features which are most helpful in differentiating [schizophrenia and depression]." A number of researchers believe that depression is actually a symptom of schizophrenia that has been hidden by the psychosis. However, symptoms usually arise after the first psychotic episodes if they will arise at all. Officially, diagnosing post-schizophrenia depression in a patient requires for the patient to be experiencing a depressive episode of either short or long term following the overcoming of schizophrenia. The patient must still demonstrate some schizophrenic symptoms but those symptoms must no longer be the focus of the illness. Typically, the depressive symptoms are not severe enough to be classified as a severe depressive episode. Formally, diagnosis entails the patient having had schizophrenia within the past year, a number of schizophrenic symptoms, and depression being present for two weeks or more. Mild schizophrenic signs may be withdrawing socially, agitation or hostility, and irregular sleep such as in the case of insomnia and hypersomnia.

Postpartum depression onset usually begins between two weeks to a month after delivery. Recent studies have shown that 50% of postpartum depressive episodes begin prior to delivery. Therefore, in the DSM-5 postpartum depression is diagnosed under "depressive disorder with peripartum onset", in which "peripartum onset" is defined as anytime either during pregnancy or within the four weeks following delivery. PPD may last several months or even a year. Postpartum depression can also occur in women who have suffered a miscarriage.