What is the physiological basis of catatonia?

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Last updated: March 19, 2025View editorial policy

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From the Guidelines

Catatonia is a neuropsychiatric syndrome characterized by abnormal movements, behaviors, and withdrawal that stems from dysregulation in several neurotransmitter systems and brain circuits, primarily involving dysfunction in GABA-ergic and glutamatergic neurotransmission, as described in the most recent study 1. The primary physiological basis involves decreased GABA activity and increased glutamate activity in key brain regions, affecting the cortico-striatal-thalamic circuits, particularly in the orbitofrontal, prefrontal, and motor cortices. Some key points about catatonia include:

  • Dysregulation in neurotransmitter systems, including GABA, glutamate, dopamine, serotonin, and acetylcholine
  • Altered activity in brain regions such as the supplementary motor area, premotor cortex, and parietal regions
  • Inflammatory processes may contribute to catatonia in some cases, with elevated cytokines and autoantibodies affecting neural function
  • Treatment approaches target these physiological abnormalities, with benzodiazepines and NMDA antagonists being used to modulate neurotransmitter activity The study 1 provides the most recent and highest quality evidence for the physiological basis of catatonia, and its findings should be prioritized in clinical practice. In terms of treatment, the study 1 provides guidance on the use of electroconvulsive therapy, which can be effective in severe cases of catatonia. However, the most recent study 1 should be consulted for the most up-to-date information on the diagnosis and treatment of catatonia. Some key symptoms of catatonia include:
  • Stupor
  • Catalepsy
  • Waxy flexibility
  • Mutism
  • Negativism
  • Posturing
  • Mannerisms
  • Stereotypies
  • Psychomotor agitation
  • Grimacing
  • Echolalia
  • Echopraxia These symptoms can be used to diagnose catatonia, as described in the study 1.

From the Research

Physiological Basis of Catatonia

The physiological basis of catatonia is not fully understood, but several factors have been proposed as contributing to its pathophysiology. 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
  • Glutamatergic activity, as analyzed from the pathophysiological model of autoimmune encephalitis 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 Regulation

The regulation of neurotransmitters, particularly GABA and glutamate, is thought to play a crucial role in the pathophysiology of catatonia.

  • Prolonged use of benzodiazepines or clozapine may increase GABA activity, and discontinuation may increase excitatory neurotransmission, leading to catatonia 2
  • Abnormalities in GABA and glutamate signaling have been suggested as causative factors in catatonia 3
  • Imbalance in neurotransmission and density of GABA and dopamine receptors may contribute to the development of catatonia 4

Pathways Involved

The physiological basis of catatonia involves various pathways, including:

  • Motor pathways, which are affected by aberrant neuronal activity 2
  • Cortico-cortical and cortico-subcortical pathways, which are involved in decision-making, emotion regulation, storage, planning, and motor processing 4
  • Structures such as the orbitofrontal and temporal cortex, basal nuclei, and brainstem, which play a central role in the pathophysiology of catatonia 4

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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