Molecular and cellular mechanisms leading to catatonia: an integrative approach from clinical and preclinical evidence

Abstract

This review aims to describe the clinical spectrum of catatonia, in order to carefully assess the involvement of astrocytes, neurons, oligodendrocytes, and microglia, and articulate the available preclinical and clinical evidence to achieve a translational understanding of the cellular and molecular mechanisms behind this disorder. Catatonia is highly common in psychiatric and acutely ill patients, with prevalence ranging from 7.6% to 38%. It is usually present in different psychiatric conditions such as mood and psychotic disorders; it is also a consequence of folate deficiency, autoimmunity, paraneoplastic disorders, and even autistic spectrum disorders. Few therapeutic options are available due to its complexity and poorly understood physiopathology. We briefly revisit the traditional treatments used in catatonia, such as antipsychotics, electroconvulsive therapy, and benzodiazepines, before assessing novel therapeutics which aim to modulate molecular pathways through different mechanisms, including NMDA antagonism and its allosteric modulation, and anti-inflammatory drugs to modulate microglia reaction and mitigate oxidative stress, such as lithium, vitamin B12, and NMDAr positive allosteric modulators.

Sudden onset catatonia following tricyclic antidepressant withdrawal - A case report

“…[ 5 ] TCAs also act on dopaminergic receptors, and this neurotransmitter is also implicated in catatonia. [ 6 ] In the present case, the possibility of lorazepam withdrawal catatonia was ruled out, in view of the apparent lack of response to reinstitution of lorazepam in the index case and non-emergence of catatonia, even after stopping lorazepam. The possibility of nortriptyline withdrawal catatonia was considered because of the improvement in catatonia within 48 hours of starting of nortriptyline and lack of depressive symptoms prior to onset and after resolution of catatonia.…”

Rapid symptom control in neuroleptic malignant syndrome with electroconvulsive therapy: A case report

“…And benzodiazepines, such as lorazepam, a GABA-A agonist, are thought to improve catatonia by acting on this pathway ( 19 ). Conversely, reduced GABA-A inhibition of frontal corticostriatal tracts is associated with increased N -methyl-D-aspartate (NDMA) receptor activity, which is also thought to play a role in the pathogenesis of catatonia ( 20 ). Finally, amantadine and memantine, which antagonize such NMDA receptors, are sometimes used as adjunctive or alternative treatments for catatonia ( 21 ).…”

Delayed drug-induced catatonia in an adolescent girl – clinical implications: A case report

“…The physiopathology of catatonia is complex and not fully understood. At the molecular level, theories include hypo functioning of GABA-A receptors, dysregulated dopamine signaling and NMDA receptor activity resulting in NMDA hyperactivity in the striato-cortical or the cortico-cortical pathways [5].…”