Catatonia

Catatonia is a neuropsychiatric syndrome most commonly seen in people with underlying mood disorders, such as major depressive disorder, or psychotic disorders, such as schizophrenia. People with catatonia exhibit abnormal movement and behaviors that vary from person to person and may fluctuate in intensity within a single episode.
People with catatonia appear withdrawn, meaning that they do not interact with the outside world and have difficulty processing information. They may be nearly motionless for days on end or perform repetitive purposeless movements. People may exhibit very different sets of behaviors and still be diagnosed with catatonia. Treatment with benzodiazepines or electroconvulsive therapy is most effective and leads to remission of symptoms in most cases.
There are different subtypes of catatonia, which represent groups of symptoms that commonly occur together. These include stuporous/akinetic catatonia, excited catatonia, malignant catatonia, and periodic catatonia.
Catatonia has historically been related to schizophrenia, but is most often seen in mood disorders. It is now known that catatonic symptoms are nonspecific and may be observed in other mental, neurological, and medical conditions.

Signs and symptoms

To properly diagnose catatonia, both the ICD-11 and DSM-5 require three or more of the symptoms defined in the table below. However, each person can have a different set of symptoms that may worsen, improve, and change in appearance throughout a single episode. Symptoms may develop in a variable amount of time, and can take hours, days, or even weeks.

Symptom	Definition
Stupor	A marked lack of psychomotor activity; the individual appears immobile and unresponsive
Catalepsy	Passive induction of a posture held against gravity
Waxy flexibility	Slight resistance to positioning by the examiner, allowing limbs to remain in imposed positions
Mutism	Lack of verbal response despite apparent alertness
Negativism	Resistance or no response to external instructions or stimulus
Posturing	Voluntary assumption of inappropriate or bizarre postures
Mannerism	Odd, exaggerated movements or behaviors
Stereotypy	Repetitive, non-goal-directed movements or gestures
Agitation	Restlessness or excessive motor activity without external stimulus
Grimacing	Facial contortions or expressions unrelated to emotional context
Echolalia	Mimicking or repeating another person's speech
Echopraxia	Mimicking or imitating another person's movements

Because most patients with catatonia have an underlying psychiatric illness, the majority will present with worsening depression, mania, or psychosis, followed by catatonia symptoms. Even when they are unable to interact, patients presenting with catatonia should not be assumed to be unaware of their surroundings, as some can recall their catatonic state and their actions in detail.

Subtypes

There are several subtypes of catatonia recognized: stuporous catatonia, excited catatonia, malignant catatonia, and periodic catatonia. Subtypes are defined by the group of symptoms and associated features that a person is experiencing or displaying. Notably, while catatonia can be divided into subtypes, its presentation is often dynamic, and the same individual may exhibit different subtypes at different times.
Stuporous catatonia is characterized by immobility, mutism, and a lack of response to the world around them. They may appear frozen in one position for long periods of time unable to eat, drink, or speak.
Excited catatonia is characterized by odd mannerisms and gestures, purposeless or inappropriate actions, excessive motor activity, restlessness, stereotypy, impulsivity, agitation, and combativeness. Patients suffering from excited catatonia may have speech and actions that are repetitive or mimic another person's. This state is often characterized by hyperactivity, and the patient may have delusions and hallucinations.
Malignant catatonia is characterized by fever, dramatic and rapid changes in blood pressure, increased heart rate and respiratory rate, and excessive sweating. This condition is life-threatening, and the patient's laboratory tests may come back abnormal.
Periodic catatonia is characterized by a person having recurrent episodes of catatonia. Individuals will experience multiple episodes over time, with no signs of catatonia between episodes. Historically, the Wernicke-Kleist-Leonhard school considered periodic catatonia a distinct form of "non-system schizophrenia", characterized by recurrent acute phases with hyperkinetic and akinetic features and often psychotic symptoms. There is also a residual state between these phases, characterized by low-level catatonic features and aboulia of varying severity.

Causes

Catatonia develops in the presence of an underlying condition, including psychiatric and neurological disorders, other medical conditions, and substance use.

Neuropsychiatric

Mood disorders like bipolar disorder and clinical depression are the most common conditions underlying catatonia. Other psychiatric conditions that can cause catatonia include schizophrenia and other primary psychotic disorders, autism spectrum disorder, ADHD, and post-traumatic stress disorder.
Psychodynamic theorists have historically interpreted catatonia as a psychological defense against the potentially destructive consequences of responsibility, with the passivity of the disorder providing relief.

Other conditions

Catatonia is also seen in many medical disorders, including encephalitis, meningitis, autoimmune disorders, focal neurological lesions, alcohol withdrawal, abrupt or overly rapid benzodiazepine withdrawal, cerebrovascular disease, neoplasms, head injury, and some metabolic conditions.

Neurological

Catatonia can occur due to several neurological conditions. For instance, certain types of encephalitis can cause catatonia. Anti-NMDA receptor encephalitis is a form of autoimmune encephalitis known to cause catatonia, albeit very rarely. Additionally, encephalitic catatonia has been reported in cases of severe HIV and herpes simplex virus infections. A small amount of evidence suggests that catatonia can develop after traumatic brain injury in the absence of a primary psychiatric disorder. Similarly, there are several case reports of catatonia after a stroke, with some having catatonia-associated symptoms that were unexplainable by stroke itself and which improved after treatment with benzodiazepines. Parkinson's disease can cause catatonia for some people by impairing their ability to produce and secrete dopamine, a neurotransmitter which is thought to contribute to motor dysfunction in people with catatonia.

Metabolic and endocrine

Abnormal thyroid function may result in the development of catatonia when the thyroid overproduces or underproduces thyroid hormones. This is thought to occur due to the impact of thyroid hormones on metabolism, including in the cells of the nervous system. Abnormal electrolyte levels have also been shown to cause catatonia in rare cases. Most notably, low blood sodium levels can cause catatonia in some people.

Infectious

Certain infections are known to cause catatonia, either by directly impairing brain function or by increasing a person's susceptibility to other diseases that can do so. HIV and AIDS can cause catatonia by predisposing one to infections in the brain, including different types of viral encephalitis. Borrelia burgdorferi causes Lyme disease, which has been shown to cause catatonia by infecting the brain and causing encephalitis.

Medications

, a drug used to treat alcoholism, can cause catatonia. It is theorized that the medication can cause alterations in dopamine metabolism, as it blocks dopamine beta-hydroxylase. Additionally, phencylidine, corticosteroid, and antipsychotics, among other drugs, are known to cause catatonia.

Pathogenesis

The mechanisms underlying brain catatonia are poorly understood. Currently, there are two main categories of explanations for what may be happening in the brain to cause catatonia. The first is a disruption of normal neurotransmitter production or release in certain brain areas, preventing normal cognitive function and leading to behavioral and motor symptoms associated with catatonia. The second claims that disruption of communication between different areas of the brain causes catatonia.

Neurotransmitters

The neurotransmitters that are most strongly associated with catatonia are GABA, dopamine, and glutamate. GABA is the primary inhibitory neurotransmitter of the brain, meaning it slows down the activity of the systems it acts on. In catatonia, people have low levels of GABA, which causes them to be overly activated, especially in areas of the brain that normally inhibit activity. This is thought to cause the behavioral symptoms associated with catatonia, including withdrawal. Dopamine can increase or decrease the activity of the area of the brain it acts on, depending on where in the brain it is. Dopamine is lower than normal in people with catatonia, which is thought to cause many of the motor symptoms, because dopamine is the main neurotransmitter that activates the parts of the brain responsible for movement. Glutamate is an excitatory neurotransmitter, meaning that it increases the activity of the areas of the brain it acts on. Notably, glutamate tells the neuron it acts on to fire by binding to the NMDA receptor. People with anti-NMDA receptor encephalitis can develop catatonia because their antibodies attack the NMDA receptor, reducing the brain's ability to activate different areas through glutamate.