The prevalence of MDD varies widely from country to country, and is impacted by the presence of co-morbidities and Psychiatric specifiers. Psychiatric specifiers provide context for diagnosis with additional descriptors such as the presence of catatonic features, whether a patient is post-partum, whether co-existing features of anxiety or psychotic features are present. Often considered in terms of 12-month or lifetime prevalence, these have been found to vary between 5-10% and 2-20% respectively.

This may be exhibited in a range of ways including mood or affect disturbance (complaints of low mood, depression, of facial expressions displaying either), anxiety, irritability or somatic complaints, such as bodily pains. Somatic complaints are often reported in place of mood disturbance to either avoid the social stigma of mental illness or through patients' own cultural interpretations of their symptoms. Depressed mood is directly linked to neurotransmitter (Norepinephrine, Dopamine and Serotonin) deficiency and the related receptor and cellular changes that occur in depression.

Loss of interest or pleasures in activities that were previously enjoyed, such as hobbies. This may also manifest as social withdrawal. Anhedonia occurs as a consequence of the neurotransmitter deficiency and related receptor and cellular changes which occur in depression.

This can present as psychomotor agitation (PMA) or psychomotor retardation (PMR). PMA presents as the inability to sit still, pacing, handwringing or pulling or rubbing of the skin, while PMR can present as slowed speech, thinking, and body movements; increased pauses before answering/speech latency; speech that is decreased in volume, inflection, amount, or variety of content, or muteness.

Neurotransmitter deficiencies and related receptor and cellular changes have been implicated in the psychomotor disturbances seen in MDD.

Patients may report difficulty thinking or maintaining concentration to complete tasks. They may also display easy distractability and an inability to maintain focus. Neurotransmitter deficiencies and related receptor and cellular changes have been implicated in the lack of focus and motivation seen in MDD.

This includes recurrent suicidal ideation and planning or actual suicide attempts. Patients may also report underlying desires to go to sleep and never wake up, or that it would be better if they were dead.

Recurrent suicidality with or without planning or attempt is a strong feature of MDD and requires hospitalization if it persists. Neurotransmitter deficiencies and related receptor and cellular changes have been directly linked to the suicidal tendencies seen in MDD.

Substance abuse is commonly comorbid with MDD, with shared predisposing factors being suggested as a common cause. Increased substance abuse has been found to be a coping mechanism for stress linked to dealing with MDD symptoms, and in the absence of substance use in one with a diagnosed substance abuse disorder, depressive symptoms can present.

MDD has been found to have a bilateral relationship with chronic medical conditions such as diabetes, cancer, stroke and heart disease, among others with each causing and/or worsening the prognosis of the other. MDD has been linked to an increase in morbidity and mortality in those medically afflicted compared to the general population.

Catatonia is a neuropsychiatric syndrome characterized by psychomotor symptoms, including mutism, rigidity, catalepsy (“waxy flexibility”), echolalia, and echopraxia. Though not exclusively caused by MDD, MDD is a common associated precursor.