Genetics of catatonia: a systematic review of case reports and a gene pathway analysis

• Published in: European Psychiatry
• Main Authors: Mylene Moyal, Anton Iftimovici, Wafa Ghoul, Marion Plaze, Boris Chaumette
• Format: Article
• Language: English
• Published: Cambridge University Press 2025-01-01
• Subjects: catatonic syndrome; excitation/inhibition imbalance; GABAergic interneurons; genetic; neurodevelopmental; variants
• Online Access: https://www.cambridge.org/core/product/identifier/S0924933825024587/type/journal_article
• ISSN: 0924-9338; 1778-3585

Abstract Background Neurodevelopmental conditions are crucial risk factors for catatonia in pediatric and adult populations. Recent case reports and studies have identified an increasing number of genetic abnormalities likely contributing to catatonia. Catatonia associated with genetic abnormalities is challenging in terms of identification, chronicity, and resistance to treatment. In addition, understanding these genetic abnormalities through identifying rare single nucleotide and copy number variants may offer valuable insights into the underlying pathophysiology. Methods We conducted a systematic review of all genetic abnormalities reported with catatonia and performed a gene-set enrichment analysis. Our systematic literature search for relevant articles published through July 15, 2024, using combinations of “catatonia,” “catatonic syndrome,” “genetic,” and “genes” in PubMed, yielded 317 articles. Of these, 94 were included, covering 374 cases of catatonia and 78 distinct genetic abnormalities. Results This review discusses the clinical presentation of catatonia for each genetic disorder, the treatment strategies, and the putative underlying mechanisms. Conclusions The review highlights that catatonia underpinned by genetic abnormalities presents specific clinical and treatment-response features. Therefore, we propose genetic testing guidelines for catatonia and advocate for systematically investigating catatonia in several genetic diseases. Regarding the pathophysiology of catatonia, the gene ontology of biological processes reveals significant enrichment of variants in synaptic and post-synaptic regulatory genes, particularly within GABAergic neurons, reinforcing the implication of the excitatory/inhibitory imbalance. Finally, genetic variants are enriched in microglial cells, highlighting the role of brain inflammation in triggering catatonia. This comprehensive insight could pave the way for more effective management strategies for this condition.