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Differential Diagnosis and Specifiers of Major Depressive Disorder

Rashmi Nemade, Ph.D., edited by Kathryn Patricelli, MA

In addition to making a diagnosis of a particular disorder, a clinician can also say how it is different from other conditions that may have similar symptoms. This is known as a differential diagnosis. This information can help a clinician narrow down which treatments may work best for the patient. It may also be used to provide information about a person's anticipated course of the disorder and their prognosis (outcome).

For example, a differential diagnosis of MDD with attention-deficit/hyperactivity disorder narrows down the diagnosis to describe that a person is highly distractible and irritable during a depressive episode rather than just being sad.

depressed man on bench

Clinicians may use the following differential diagnoses to describe the current or most recent Major Depressive Disorder:

  • Manic episodes with irritable mood or mixed episodes - in this situation, the person may be very irritable or have mood symptoms that are similar to those seen in bipolar disorder.
  • Mood disorder due to another medical condition - the person has a medical condition such as multiple sclerosis, stroke, or heart disease and is also experiencing depression. It is important for a clinician to understand whether a person is depressed because they have a true mood disturbance or if their depression is due to a medical condition. In this case, treatment options might be very different.
  • Substance/medication-induced depressive or bipolar disorder - This description is used when the depressive symptoms are related to the use of a substance (medication or drug of abuse). For example, a person suffering from cocaine withdrawal would be diagnosed as cocaine-induced depressive disorder.
  • Attention-deficit/hyperactivity disorder - people with this type are distracted and easily frustrated. This can be a tricky diagnosis in children because instead of being sad or losing interest, children tend to become irritable with depression.
  • Adjustment disorder with depressed mood - this is used when not all the criteria are met for MDD and the depressive episode occurs in response to a stressful event involving other people such as a death or loss (divorce).
  • Sadness - Feeling sad is part of being human, and everyone has periods when they feel sad. These should not be diagnosed as MDD unless the DSM criteria for MDD have been met and a person is unable to function because of their sadness.

Clinicians can also label the episode as occurring with:

Anxious Distress - this is when a person feels keyed up/tense, is unusually restless, or has a feeling or fear that something awful may happen or they may lose control. A clinician will typically label the disorder as mild to severe based on the number of anxiety symptoms the person experiences along with MDD.

Mixed Features - These are behaviors that are typically observed by others and represent a change from the person's usual behavior. They include:

  • Elevated, expansive mood - someone who may express hostility, criticism and be emotionally over-involved in life events. Typically, they consider themselves very important;
  • Inflated self-esteem or grandiosity - someone who believes themselves to be larger than they are. For example, they believe that they have special powers, spiritual connections, or religious relationships;
  • More talkative than usual - someone who cannot stop themselves from talking or in a group cannot stop long enough for others to contribute to a conversation;
  • Racing thoughts - this is when someone's thoughts race or go very fast, so fast that their thoughts change very quickly;
  • Increase in energy and goal-directed activity - when a person goes from being low energy and motivation with few goals to suddenly having energy, goals, and is motivated to pursue and achieve goals;
  • Increased or excessive involvement in activities that may be dangerous or risky - this might include skydiving, risky business investments, or sexual behavior that is not usual for the person
  • Decreased need for sleep - the high energy and goal-directed activity may result in less sleep because of the new goals to be achieved.

To others, this behavior may seem exaggerated, boastful, and pompous and the person is felt to be conceited. These behaviors fall into the manic category. If these symptoms appear, but do not seem as extreme or as severe as mania (such as having all the symptoms), then that person is said to be hypomanic (having just a few or all, but in a more subdued way). If at least three of these manic/hypomanic symptoms are present nearly every day during the most of the days that the person has a major depressive episode, then the person is said to have mixed features along with MDD. NOTE: Mixed features with MDD are found to be a risk factor for a person developing bipolar I or bipolar II disorder.

Melancholic Features - A person is said to have MDD with melancholic features if at the most severe stage of the episode if he/she shows:

  • An inability to enjoy anything and does not react to anything pleasurable along with a mood that is regularly worse in the morning
  • early morning awakening (at least two hours before the usual time)
  • thinking or moving slowly or speeding up of physical activity (agitation)
  • significant loss of appetite or unplanned weight loss
  • excessive or inappropriate guilt.

Atypical Features - this is when MDD occurs with mood reactivity. For example, the person's mood brightens when good things happen, when they gain weight or have an increase in appetite, sleep more than usual, or have heavy almost paralyzing feeling in their arms and legs. These features should not occur in the same episode with melancholic or catatonic features.

Psychotic Features - this is used when delusions and/or hallucinations are experienced. When the delusions and/or hallucinations are consistent with typical depressive feelings such as personal weakness, guilt, disease, or deserved punishment, they are said to be mood-congruent. When they do not follow typical depressive feelings, but are instead the opposite or a mixture of the two, they are known as mood-incongruent.

Catatonia - In MDD with catatonia, a person displays one or many unusual movements and mannerisms, including:

  • stupor (periods during which they do not move or actively relate to the environment)
  • excessive movement
  • catalepsy (passively being put into postures and holding them for periods of time, sometimes against gravity)
  • waxy flexibility (resistance to positioning)
  • mutism (no verbal response)
  • negativism (opposition or no response to instructions)
  • posturing (spontaneous and active maintenance of a posture held against gravity)
  • mannerism (odd caricature of normal actions)
  • stereotypy (repeating behaviors over and over without a goal)
  • prominent grimacing; echolalia (mimicking someone else's speech)
  • echopraxia (mimicking another's movements).

For example, a person sitting on a park bench who seems unable to stop imitating gestures and words of passers-by might be suffering from MDD with catatonic features.

Peripartum Onset - this is used if the onset of MDD occurs during pregnancy or in the 4 weeks following childbirth. This is just when the symptoms first appear, but they may last longer than the noted four weeks. Because 50% of 'postpartum' depressive episodes begin during pregnancy, this category is now called peripartum rather than postpartum.

Common symptoms include changing moods and high preoccupation with the baby's well-being. It is very normal for parents to be concerned about their new babies and their parenting skills. However, calling the doctor multiple times each day for weeks on end is not typical parenting behavior. Excessive worry about typical newborn behaviors, such as straining during a bowel movement, and treating these behaviors as a major medical event requiring immediate attention is also not normal behavior.

Postpartum depression can also include psychotic thinking with unshakable false beliefs (delusions). Delusional thoughts that include themes of harming the infant are particularly dangerous. For example, a mother may hallucinate that the baby or other people are telling her that she is a bad mother, hear voices that tell her to kill the baby, or think that her infant is possessed. Infanticide (murder of an infant) is most common with women who experience delusions or hallucinations; but women who are severely depressed without psychotic features have also killed their children. If a woman has mood and anxiety symptoms during pregnancy, she is more likely to experience a postpartum major depressive episode. In addition, once a woman has had a postpartum depressive episode with psychotic features; her risk of having a similar episode with each subsequent delivery is between 30-50%.

Seasonal Pattern - this occurs when a person experiences depressive symptoms at a particular time of year, and then feels a lifting of symptoms at other times of the year on a regular basis for the past two years. For example, if a person's depressive symptoms typically start in the fall or winter and lift in the spring, this individual is diagnosed with MDD with a seasonal pattern.

It is important to separate this from other stressful events, such as seasonal unemployment during the winter or a school schedule. Typically, for a person to be diagnosed with a seasonal pattern, they must have more seasonal episodes than nonseasonal episodes during their lifetime. This disorder can occur as mild, moderate or severe in individuals depending on the level of problems that the person has doing their daily activities (work, school, etc.).

This pattern has been previously called Seasonal Affective Disorder. However, in the DSM-5, it is seen as a variation of Major Depressive Disorder and not something unique or separate from MDD. Seasonal Affective Disorder is not considered a disorder or condition on its own.

When the winter months start and daylight grows shorter, some people start feeling a little slow, experience a bit of weight gain, have difficulty getting out of bed, and have periods of "the blues". Symptoms begin in the fall, peak in the winter and usually resolve in the spring. The typical symptoms of this seasonal pattern include low mood, lack of energy, changes in appetite and sleep, feelings of guilt and self-blame, and hopelessness.

Most people with this pattern experience relatively mild symptoms, but others have more crippling symptoms that cause problems at school, work or in the relationships with others.


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