Catatonia following an attack of melancholia

Catatonic depression is characterized as a spectrum of mood disorders and is distinguished by the co-occurrence of

catatonia Catatonia is a complex 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, wh ...

and

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

(MDD). Catatonic symptoms involve a variety of motor abnormalities and behavioral disturbances, such as

stupor Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin '' stupor'' ("numbness, in ...

, immobility,

mutism In human development, muteness or mutism is defined as an absence of speech, with or without an ability to hear the speech of others. Mutism is typically understood as a person's inability to speak, and commonly observed by their family members, c ...

, negativism, posturing, rigidity, and repetitive or purposeless movements. Individuals suffering from catatonic depression frequently demonstrate a significant decline in their capacity to engage in voluntary behaviors and communicate effectively. These symptoms can significantly impair daily functioning and pose challenges in their personal and professional lives. The exact cause of catatonic depression is not fully understood. However, it is believed to arise from a complex interplay of genetic,

biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...

, and environmental factors. Some research suggests that disturbances in neurotransmitters like

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. It is an amine synthesized ...

and

gamma-aminobutyric acid GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

(GABA) may contribute to the development of catatonic symptoms. Furthermore, stressful life events, trauma, and certain medical disorders can raise the risk of developing this condition. Diagnosing catatonic depression requires a comprehensive evaluation by a qualified mental health professional. The Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has specific criteria for diagnosing catatonic symptoms associated with depression. Catatonic depression is often treated using a multimodal approach.

Antidepressants Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include dry mouth, weight gain, dizziness, headaches, akathisia, sexu ...

mood stabilizers A mood stabilizer is a psychiatric medication used to treat mood disorders characterized by intense and sustained mood shifts, such as bipolar disorder and the bipolar type of schizoaffective disorder. Uses Mood stabilizers are best known for t ...

, and

antipsychotics Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizo ...

may be prescribed to manage depression symptoms and underlying neurotransmitter imbalances. Electroconvulsive therapy (ECT) has also shown effectiveness in treating catatonic depression, particularly in cases where immediate intervention is required if other therapies have been unsuccessful. Individuals can benefit from supportive psychotherapy, cognitive-behavioral therapy (CBT), and psychosocial therapies to cope with symptoms and create management strategies for their illness. Catatonic depression is a debilitating and chronic condition that requires early intervention for optimal treatment. Individuals suffering from catatonic depression can benefit from appropriate treatment and support, resulting in symptom reduction and an improved overall quality of life. Seeking expert help and support is critical to ensuring the patient's accurate diagnosis and treatment.

Signs and symptoms

Catatonic depression is a complex psychiatric condition which involves both major depressive disorder and catatonia. Catatonic depression is characterised by a mix of symptoms and indications that overlap with major depressive disorder and catatonia.

Stupor Stupor is the lack of critical mental function and a level of consciousness, in which an affected person is almost entirely unresponsive and responds only to intense stimuli such as pain. The word derives from the Latin '' stupor'' ("numbness, in ...

and 

are the two most common symptoms. Although symptoms of catatonic depression can vary by individual, common signs of catatonia include grimacing (making a facial expression of pain), negativism, posturing, rigidity, and

waxy flexibility Waxy flexibility is one of the twelve symptoms that can lead to the diagnosis of catatonia. It is a psychomotor symptom that results in a decreased response to stimuli and a tendency to remain in an immobile posture. If one were to move the arm o ...

. Major depressive symptoms are also experienced by a person suffering from catatonic depression. These symptoms can include hopelessness,

irritability Irritability is the excitatory ability that living organisms have to respond to changes in their environment. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimul ...

, a loss of interest in or enjoyment from normal activities,

sleep disturbances Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with the surrounding environme ...

(

insomnia Insomnia, also known as sleeplessness, is a sleep disorder where people have difficulty sleeping. They may have difficulty falling asleep, or staying asleep for as long as desired. Insomnia is typically followed by daytime sleepiness, low ene ...

or excessive sleeping), exhaustion, anxiety,

psychomotor retardation Psychomotor retardation involves a slowing down of thought and a reduction of physical movements in an individual. It can cause a visible slowing of physical and emotional reactions, including speech and affect. Psychomotor retardation is most ...

, feelings of worthlessness, difficulty concentrating, remembering things, and suicidal thoughts.

Physiological mechanism

The

pathophysiology Pathophysiology (or physiopathology) is a branch of study, at the intersection of pathology and physiology, concerning disordered physiological processes that cause, result from, or are otherwise associated with a disease or injury. Pathology is ...

of catatonic depression is not currently well understood and mainly shrouded in mystery, but researchers have suggested possible pathophysiology explaining the major depressive disorder coupled with catatonic features.

Reduced gamma-aminobutyric acid (GABA) activity

GABA-A (GABA type A) receptor activation in the right lateral orbitofrontal and right posterior parietal cortex is suggested to be a plausible cause of catatonia syndrome dysfunction, which helps explain the motor and affective symptoms seen in catatonic individuals. Reduced GABA-A receptor density is found on imaging in cortical regions such as the left sensorimotor cortex, which suggests malfunctioning GABA-A signalling in catatonia.

Dopamine dysfunction

There is some evidence that blockage of

dopamine D2 receptor Dopamine receptor D2, also known as D2R, is a protein that, in humans, is encoded by the ''DRD2'' gene. After work from Paul Greengard's lab had suggested that dopamine receptors were the site of action of antipsychotic drugs, several groups, ...

has led to reduced risk of exacerbating catatonia. This can be seen in

neuroleptic malignant syndrome Neuroleptic malignant syndrome (NMS) is a rare but life-threatening reaction that can occur in response to antipsychotics (neuroleptic) or other drugs that block the effects of dopamine. Symptoms include high fever, confusion, rigid muscles, va ...

, which has similar symptoms to catatonia. An alternative idea suggests that the mesostriatal and mesocorticolimbic systems, and the hypothalamus need to maintain a balance between GABA-A and

Glutamate dysfunction

Glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

anomalies have been observed in the

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

(clusters of neurones located in

subcortical The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...

region) as such excitatory glutamatergic N-methyl-D-aspartate receptors (NMDARs) within this brain region appear to be associated with catatonia. Catatonic symptoms are thought to be caused by glutamate hyperactivity. There is a high correlation between catatonia and NMDAR

encephalitis Encephalitis is inflammation of the Human brain, brain. The severity can be variable with symptoms including reduction or alteration in consciousness, aphasia, headache, fever, confusion, a stiff neck, and vomiting. Complications may include se ...

. (NMDARs are internalised into cells during this inflammatory process, resulting in a drop in the receptor's total abundance.)

Abnormalities of the brain and brainstem pathway

The disruption of the following three motor pathways is hypothesised to be associated with catatonia. The first pathway involves the primary motor cortex (M1),

putamen The putamen (; from Latin, meaning "nutshell") is a subcortical nucleus (neuroanatomy), nucleus with a rounded structure, in the basal ganglia nuclear group. It is located at the base of the forebrain and above the midbrain. The putamen and c ...

, internal and external palladium and

thalamus The thalamus (: thalami; from Greek language, Greek Wikt:θάλαμος, θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the wikt:dorsal, dorsal part of the diencephalon (a division of ...

. The second pathway runs between the M1,

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

, and

pontine nuclei The pontine nuclei (or griseum pontis) are all the neurons of the ventral pons. Corticopontine fibres project from the primary motor cortex to the ipsilateral pontine nucleus; pontocerebellar fibers then relay the information to the contralater ...

. The third pathway is composed of the M1, supplementary motor area (SMA),

posterior parietal cortex The posterior parietal cortex (the portion of parietal neocortex posterior to the primary somatosensory cortex) plays an important role in planned movements, spatial reasoning, and attention. Damage to the posterior parietal cortex can produce a ...

, and

medial prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA ...

. It has been shown that individuals with catatonia have more blood flow to the M1 and SMA than those without catatonia. This implies a relation between catatonic depression and elevated neuronal activity in the M1 and SMA.

Autoimmune disorders

Catatonia is also associated with autoimmune

encephalopathies Encephalopathy (; ) means any disorder or disease of the brain, especially chronic degenerative conditions. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of overall brain dysfunction; this syndrome ...

that involves anti-neuronal

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

(acting on neurones over pathogens). These antibodies become internalised within neurones and cause its dysfunction, leading to catatonic symptoms.

Causes

Genetic susceptibility of an individual has been extensively supported in the case of major depressive disorders. In 2023, the genome-wide association studies (GWAS) have identified 178 genetic risk loci with more than 200 candidate genes. Based on the stress diathesis theory, people with a family history of mood disorder are more prone to developing depression due to stressful life events. However, major depressive disorder is not entirely dependent on genetics and is influenced by other factors. Research has indicated that there is a 27% chance of a patient developing catatonic symptoms if a first-degree relative has the disorder. Catatonia is also highly heritable. One gene linked to the heredity of catatonia is CNP, which codes for the enzyme

cyclic nucleotide phosphodiesterase 3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate: :nucleoside 3′,5′-cyclic phosphate ...

, which is necessary for

myelination Myelination, or myelinogenesis, is the formation and development of myelin sheaths in the nervous system, typically initiated in late prenatal neurodevelopment and continuing throughout postnatal development. The term ''myelinogenesis'' is also ...

and

oligodendrocyte Oligodendrocytes (), also known as oligodendroglia, are a type of neuroglia whose main function is to provide the myelin sheath to neuronal axons in the central nervous system (CNS). Myelination gives metabolic support to, and insulates the axons ...

function. Depletion of this gene causes the affected mice to develop catatonic depression.

Environmental factors

Traumatic events and immense stress are well-documented factors of major depressive disorders. Early life trauma is strongly correlated with the onset of

mood disorder A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the ''Diagnostic ...

such as depression as well as the severity and duration of the malady. However, people with such experience may or may not develop depression while those without impactful life events may also develop major depressive disorder. This could be explained by the gene-environment interaction which influences the impact of life events on the development of a disease. A functional polymorphism of the promoter region of the

serotonin transporter The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...

gene (5-HTT) was found to moderate the influence of stressful life events on depression.

Intense terror

Catatonic depression has been possibly associated with extreme fear. Catatonia may be an end-state reaction to emotions of impending doom stemming from early experiences with predators whose attack instincts were focused on movements. A 2020 study on an older population discovered that hyperactivity and nervousness were more common in catatonic patients.

Diagnosis

In order to identify catatonic symptoms in individuals with major depressive disorder, a comprehensive physical and psychological evaluation is part of a diagnostic catatonic depression assessment. Often, people with catatonic depression cannot respond to questions in which case the person's closed ones could be inquired.

Clinical assessment

It is important for the physician to rule other medical conditions which mimic symptoms of catatonic depression. The physician may take the patient's medical history, including details about symptoms and current medications, perform a thorough

physical examination In a physical examination, medical examination, clinical examination, or medical checkup, a medical practitioner examines a patient for any possible medical signs or symptoms of a Disease, medical condition. It generally consists of a series of ...

by observing the patient's posture and movements, perform a

neurological examination A neurological examination is the assessment of sensory neuron and motor responses, especially reflexes, to determine whether the nervous system is impaired. This typically includes a physical examination and a review of the patient's medical his ...

, and order an electroencephalogram (EEG) or magnetic resonance imaging (MRI) to rule out other neurological conditions.

DCM and ICD criteria

The American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) together with the International Classification of Disease (ICD-11) are generally used to diagnose catatonic depression. Although definitive diagnostic criteria for catatonic depression is still in debate, the two classifications is in agreement for catatonic depression diagnostics.

DCM-5 and ICD-11 classification

To diagnose catatonic depression, it requires the presence of 3 of the following 12 clinical signs, which includes

(impaired responsiveness indicated by a lack of movement and speech),

catalepsy Catalepsy (from Ancient Greek , , "seizing, grasping") is a neurological condition characterized by muscular rigidity and fixity of posture regardless of external stimuli, as well as decreased sensitivity to pain. Signs and symptoms Sympt ...

(a lack of response to external stimuli due to

muscular rigidity Spasticity () is a feature of altered skeletal muscle performance with a combination of paralysis, increased tendon reflex activity, and hypertonia. It is also colloquially referred to as an unusual "tightness", stiffness, or "pull" of muscles. ...

(resistance to repositioning after being moved),

(being unable or unwilling to speak), negativism (resistance to suggestions or instructions), posturing (holding an abnormal position for an extended period), mannerisms (involve an unusual, exaggerated, or peculiar way of performing a normal action like movement or speech),

stereotypies A stereotypy (, ) is a repetitive or ritualistic movement, posture, or utterance. Stereotypies may be simple movements such as body rocking, or complex, such as self-caressing, crossing and uncrossing of legs, and marching in place. They are foun ...

(these behaviors include repetitive, non-goal-directed movements and speech, disrupting normal functioning),

psychomotor agitation Psychomotor agitation is a symptom in various disorders and health conditions. It is characterized by unintentional and purposeless motions and restlessness, often but not always accompanied by emotional distress and is always an indicative for ...

(increased movement, restlessness, and irritability coupled with enhanced responsiveness to internal and external stimuli), grimacing (making a facial expression of pain),

echolalia Echolalia is the unsolicited repetition of vocalizations made by another person; when repeated by the same person, it is called palilalia. In its profound form it is automatic and effortless. It is one of the echophenomena, closely related to ...

(mimicking another person's speech) and

echopraxia Echopraxia (also known as echokinesis) is the involuntary repetition or imitation of another person's actions. Similar to echolalia, the involuntary repetition of sounds and language, it is one of the echophenomena ("automatic imitative actions ...

(mimicking another person's movements or behaviors for no reason).

Misdiagnosis

Major depressive disorder subtype catatonia can be easily overlooked which could result in

misdiagnosis A medical error is a preventable adverse effect of care (" iatrogenesis"), whether or not it is evident or harmful to the patient. This might include an inaccurate or incomplete diagnosis or treatment of a disease, injury, syndrome, behavior, ...

and thus worsen the patient's condition. Therefore, physicians ought to be cautious when diagnosing major depressive disorder and consider the possible subtypes.

Managements

Catatonic depression is a severe but manageable subtype of depression.

Benzodiazepines Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat co ...

, such as

lorazepam Lorazepam, sold under the brand name Ativan, Tavor among others, is a benzodiazepine medication. It is used to treat anxiety (including anxiety disorders), insomnia, severe agitation, active seizures including status epilepticus, alcoh ...

, are often prescribed as the first-line treatment for catatonia. These medications contain anxiety-relieving and muscle relaxing characteristics.

Combination therapy

Antipsychotic medications can be combined with benzodiazepines to treat catatonic depression.

Combination therapy In mathematics, a combination is a selection of items from a set that has distinct members, such that the order of selection does not matter (unlike permutations). For example, given three fruits, say an apple, an orange and a pear, there are ...

can help relieve symptoms and enhance overall function. When medication alone is ineffective, the use of electroconvulsive therapy (ECT) is recommended. ECT is the use of electrical currents to produce a

seizure A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

while under

general anesthesia General anaesthesia (UK) or general anesthesia (US) is medically induced loss of consciousness that renders a patient unarousable even by painful stimuli. It is achieved through medications, which can be injected or inhaled, often with an analgesi ...

. It is thought to reset brain chemistry and may be beneficial in treating severe mental illnesses, including catatonia. Workout 7th Brigade Park Chermside P1070570

Workout 7th Brigade Park Chermside P1070570

Lifestyle

It is suggested to create a scheduled daily regimen that includes consistent sleep, meals, and activities that can provide a sense of stability and manage symptoms better. It is also recommended to engage in regular physical activity, such as walking, yoga, or swimming, as exercise has been demonstrated to elevate mood and lessen symptoms of depression.

Psychotherapies

Supportive treatment can be effective in resolving underlying depression and assisting patients in coping with symptoms. A person suffering from catatonic depression requires acute psychiatric care, which includes contacting an

inpatient A patient is any recipient of health care services that are performed by healthcare professionals. The patient is most often ill or injured and in need of treatment by a physician, nurse, optometrist, dentist, veterinarian, or other heal ...

mental facility or seeking emergency medical attention to ensure that the person receives therapy as soon as possible.

Epidemiology

Catatonic depression is underdiagnosed and may impact up to 38% of acute psychiatric patients, as it creates particular symptoms as indicated above and necessitates a specific treatment approach with an emphasis on medications to relieve symptoms. Catatonia affects over 10% of all persons hospitalized to psychiatric facilities. Catatonia may be associated with depression, although it also affects approximately 20% of persons with

autism spectrum disorder Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing di ...

, and up to 50% of catatonia instances are caused by medical difficulties. Catatonic depression is frequently associated with other mental health illnesses, including

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

mood disorders A mood disorder, also known as an affective disorder, is any of a group of conditions of mental and behavioral disorder where the main underlying characteristic is a disturbance in the person's mood. The classification is in the ''Diagnostic ...

personality disorders Personality disorders (PD) are a class of mental health conditions characterized by enduring maladaptive patterns of behavior, cognition, and inner experience, exhibited across many contexts and deviating from those accepted by the culture. T ...

, and

anxiety disorders Anxiety disorders are a group of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a person's social, occupational, and personal functions are significantly impaired. Anxiety may cause phys ...

References

{{Reflist Major depressive disorder Mood disorders

Signs and symptoms

Physiological mechanism

Reduced gamma-aminobutyric acid (GABA) activity

Dopamine dysfunction

Glutamate dysfunction

Abnormalities of the brain and brainstem pathway

Autoimmune disorders

Causes

Environmental factors

Intense terror

Diagnosis

Clinical assessment

DCM and ICD criteria

DCM-5 and ICD-11 classification

Misdiagnosis

Managements

Combination therapy

Lifestyle

Psychotherapies

Epidemiology

See also

References