From the Guidelines
The pathophysiology of catatonia involves dysregulation of several neurotransmitter systems in the brain, primarily affecting GABA, glutamate, and dopamine, leading to abnormal motor behaviors and cognitive disturbances. According to the most recent evidence [ 1 ], catatonia is characterized by a syndrome of primarily psychomotor disturbances, including stupor, catalepsy, waxy flexibility, mutism, negativism, posturing, mannerisms, stereotypies, psychomotor agitation, grimacing, echolalia, and echopraxia.
Key Features of Catatonia
- Abnormal motor behaviors, ranging from extreme immobility to excessive and purposeless movement
- Hypoactivity in the frontal lobes combined with hyperactivity in motor circuits
- GABA receptor dysfunction plays a central role
- Glutamate excess through NMDA receptors contributes to the syndrome
- Dopamine imbalance is also implicated, particularly in cases associated with psychotic disorders or neuroleptic malignant syndrome
The condition can be triggered by various psychiatric disorders (particularly mood disorders and schizophrenia), medical conditions, medications, or substance withdrawal [ 1 ]. Understanding this pathophysiology explains why GABA-enhancing medications are effective and why electroconvulsive therapy (ECT) works in treatment-resistant cases by resetting these dysregulated neural circuits [ 1 ].
Treatment Options
- Benzodiazepines like lorazepam (1-2mg every 4-6 hours) are effective first-line treatments
- NMDA antagonists like amantadine (100-400mg daily) or memantine (5-20mg daily) are useful in refractory cases
- ECT may be considered in cases of treatment-resistant catatonia, particularly when there is a high risk of mortality or significant morbidity [ 1 ].
From the Research
Pathophysiology of Catatonia
The pathophysiology of catatonia is complex and not fully understood, but several factors have been proposed as contributing to its development. These include:
- Aberrant neuronal activity in different motor pathways 2
- Defective neurotransmitter regulation, particularly involving gamma-aminobutyric acid (GABA) and glutamate signaling 2, 3, 4
- Impaired oligodendrocyte function 2, 4
- Imbalance in neurotransmission and density of GABA and dopamine receptors 4
- Genetic factors related to oligodendrocytes 4
- Cortico-cortical and cortico-subcortical pathways, including structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, involved in decision-making, emotion regulation, storage, planning, and motor processing 4
Neurotransmitter Imbalance
An imbalance in neurotransmitter activity, particularly GABA and glutamate, has been suggested as a causative factor in catatonia 3, 4. The use of benzodiazepines, which enhance GABA activity, is often effective in treating catatonia, supporting the role of GABA in its pathophysiology 2, 3, 4, 5.
Brain Regions Involved
The cortico-cortical and cortico-subcortical pathways, including structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, are thought to play a central role in the pathophysiology of catatonia 4. These regions are involved in various functions, including decision-making, emotion regulation, storage, planning, and motor processing.