major depressive disorder

Major depressive disorder (MDD) is the most common psychiatric disorder in both developed and developing countries. It is characterized by a persistently low mood and a reduced interest in previously pleasurable activities.


The 12-month prevalence of major depressive disorder in the general population is estimated at ~26%, while the lifetime prevalence is estimated at 24%.

Risk factors
  • family history of major depressive disorder
  • history of alcohol dependence
  • >65 years old
  • lower educational background
  • unmarried patients

Clinical presentation

The Diagnostic and Statistical Manual of Mental Disorders (DSM-5)recognizes the following criteria for the diagnosis of major depressive disorder (must be present for at least 2 weeks):

  • low mood
  • decreased interest in pleasurable activities (anhedonia)
  • poor sleep
  • poor appetite
  • decreased energy 
  • decreased libido
  • difficulty in concentration
  • psychomotor retardation
  • thoughts of suicide
  • thoughts around guilt or hopelessness

These symptoms must not be attributable to an organic cause or substance use.

In the elderly, major depressive disorder can mimic early dementia as it often presents with reduced memory and psychomotor retardation. This is often termed pseudodementia.

In young children, angry outbursts and poor performance in school may be the first signs of major depression .

Laboratory tests

Radiographic features

Although the diagnosis of major depressive disorder is made clinically, there are a number of imaging findings observed in brain imaging.

CT and MRI

Imaging reveals lower thalamic volumes in patients presenting with the first episode of major depressive disorder. This trend was consistent with patients presenting with multiple episodes. Younger patients tend to also have lower hippocampal volumes in conjunction with lower thalamic volumes. This is an important finding as it demonstrates the negative effect of high glucocorticoid concentrations (which are elevated in MDD) on the hippocampus.

However, it is important to note that studies have not been able to demonstrate any association between thalamic and hippocampal volumes and severity of MDD .

Some studies have shown an increase in the size of the amygdala in patients with MDD. There appears to be a correlation between the size of the amygdala and the severity of symptoms .


Several studies have shown increased activity in the anterior cingulate cortex (ACC), which is predominantly implicated in allostasis. There appears to be reduced communication between the ACC and the amygdala, the pallidostriatum and the medial thalamus, suggesting a decreased regulatory effect of the ACC over the mood-regulating limbic areas.

There is a reduction in communication between the posterior cingulate cortex (PCC) and the caudate which could suggest abnormalities in the reward pathway .

Treatment and prognosis

The treatment of depression depends on the severity of the disease, but broadly involves the use of antidepressants and psychotherapy; electroconvulsive therapy (ECT) is usually reserved for cases refractory to pharmacological agents. Recent work suggests that NSAIDs may be a useful adjunct therapy for major depressive disorder .

Currently, imaging findings are not used to guide treatment/prognosis.

Practical points

  • depression is the most common psychiatric disorder worldwide
  • with the rise of individualized medicine, functional imaging of the brain may become important in the future for evaluating the severity of the disease and potential treatment options for patients
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