July 31st, 2020

Major Depressive Disorder

Clinicals - History


Known as major depressive disorder (MDD), this is characterized by episodes of low mood and disruption in somatic and cognitive functioning. It is defined by DSM-V criteria and includes the presence of the following symptoms: depressed mood, anhedonia, weight gain/loss, hypersomnia or insomnia, psychomotor retardation or agitation, fatigue, feelings of worthless, guilt and suicidality for at least 2 weeks, resulting in a change of function from the patient's premorbid state.


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.


MDD is a multi-factorial illness. Genetic, physiological environmental factors have been linked to its development. Genes, such as the serotonin transporter, neurochemicals (serotonin, norepinephrine, dopamine) inflammatory cytokines, and psychosocial stressors have all been implicated.

Depressed mood

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.

Changes in appetite

This can present as decreased appetite or hyperphagia. Specific foods may be craved (such as sweets) and weight gain or loss can result. These changes are due to hypoactivity and hyperactivity respectively, of brain areas that control appetite during 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.

Changes in sleep pattern

This may manifest as either insomia or hypersomnia. Insomnia typically presents as initial (difficulty falling asleep), middle (waking up in the middle of the night) or terminal (waking up too early or unable to return to sleep) insomnia. Hypersomnia presents as prolonged sleep or daytime sleepiness. These sleep disturbances occur because of changes to cerebral blood flow in brain areas affected by depression, which affect overall sleep architecture and slow wave or deep sleep.

Changes in psychomotor activity

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 complain of decreased energy or increased tiredness or fatigue without sustained physical effort. Efficiency is difficult to sustain and copious amounts of energy may be needed for small tasks. Fatigue is due to the neurotransmitter deficiency and related receptor and cellular changes that occur in depression.

Poor concentration and lack of motivation

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.

Feelings of guilt and worthlessness

This may include unrealistic and self-derogatory ruminations about oneself, or guilty preoccupation over minor past failures. Patients may also excessively inflict self-blame upon themselves. Neurotransmitter deficiencies and related receptor and cellular changes have been directly linked to the feelings of guilt and worthlessness 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.

Psychotic features

MDD can occur with or without delusions and hallucinations. These can be mood-congruent (consistent with depressive theme, include low self-worth, guilt, death) or mood-incongruent (content is not consistent with depression).

Substance abuse

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.

Psychiatric comorbidities

Panic disorder (PD), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), bulimia nervosa (BN), and borderline personality disorder (BPD) are commonly comorbid with MDD.

Chronic medical illness

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.

Post-partum depression (PPD)

PPD is a common mood disturbance which can occur within 4 weeks of delivery. The severity of depressive symptoms can range from mild to severe and can persist for up to a year post-delivery with consequences for the offspring.


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.

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