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ASEF BioX: Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia

June 24, 2024 | 12:26 am |

At the May BioX reading circle which took place on Tuesday, May 28th 2024, we had an opportunity to listen to Ines Žabkar, ASEF fellow generation 2023. She introduced a new method for identifying clinical biomarkers of psychiatric diseases related to decision-making and cognition processes.

Schizophrenia and anti-NMDAR encephalitis are psychiatric disorders that manifest with very similar symptoms, though their underlying mechanisms are completely different. Both conditions involve hypofunction of NMDA receptors (NMDARs), which play a crucial role in synaptic potentiation (strengthening of synapses with frequent activation) and various phases of working memory. This means they participate in different stages of synaptic potentiation, from immediate modifications to long-term structural changes, facilitating adaptation to stimuli and memory stabilization, essential for memory maintenance and learning. Schizophrenia is characterized by reduced density of prefrontal NMDARs, while anti-NMDAR encephalitis is an autoimmune process where IgG antibodies attack the MR1 subunit of the receptor in the central nervous system. Both diseases acutely present with similar neuropsychiatric symptoms, such as psychosis and working/long-term memory disorders, affecting decision-making and cognition processes.

The article investigates the phenomenon of serial dependence, defined as the tendency for previous stimuli to influence current perception. This is linked to short-term or working memory, as decisions are always based on recently presented stimuli. Individuals with anti-NMDAR encephalitis and schizophrenia exhibit reduced serial dependence due to impaired synaptic potentiation, suggesting that synaptic abnormalities may be responsible for cognitive and perceptual disturbances in these conditions.

The study demonstrated that proper synaptic function is crucial for normal cognitive function and found that treatment can improve serial dependence in anti-NMDAR encephalitis patients. Based on these findings, serial dependence, combined with other psychiatric tests and scales, could be used as a clinical marker for easier detection of these psychiatric disorders.  After the presentation, we had a brief discussion with the audience.

Source: Stein H., Barbosa J., Rosa-Justicia M. et al. 2020. Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia. Nature  Communications: 11, 4250. https://doi.org/10.1038/s41467-020-18033-3

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