Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study
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| Názov: | Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study |
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| Autori: | Camporesi, Sara, Xin, Lijing, Golay, Philippe, Eap, Chin Bin, Cleusix, Martine, Cuenod, Michel, Fournier, Margot, Hashimoto, Kenji, Jenni, Raoul, Ramain, Julie, Restellini, Romeo, Solida, Alessandra, Conus, Philippe, Do, Kim Q, Khadimallah, Ines |
| Zdroj: | Mol Psychiatry Molecular psychiatry, vol. 29, no. 11, pp. 3669-3679 Camporesi, Sara; Xin, Lijing; Golay, Philippe; Eap, Chin Bin; Cleusix, Martine; Cuenod, Michel; Fournier, Margot; Hashimoto, Kenji; Jenni, Raoul; Ramain, Julie; Restellini, Romeo; Solida, Alessandra; Conus, Philippe; Do, Kim Q; Khadimallah, Ines (2024). Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study. (In Press). Molecular psychiatry Springer Nature 10.1038/s41380-024-02631-4 <http://dx.doi.org/10.1038/s41380-024-02631-4> Camporesi, Sara; Xin, Lijing; Golay, Philippe; Eap, Chin Bin; Cleusix, Martine; Cuenod, Michel; Fournier, Margot; Hashimoto, Kenji; Jenni, Raoul; Ramain, Julie; Restellini, Romeo; Solida, Alessandra; Conus, Philippe; Do, Kim Q; Khadimallah, Ines (2024). Neurocognition and NMDAR co-agonists pathways in individuals with treatment resistant first-episode psychosis: a 3-year follow-up longitudinal study. Molecular psychiatry, 29(11), pp. 3669-3679. Springer Nature 10.1038/s41380-024-02631-4 <http://dx.doi.org/10.1038/s41380-024-02631-4> |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2024. |
| Rok vydania: | 2024 |
| Predmety: | Male, Adult, Adolescent, Psychotic Disorders / metabolism, Glutamic Acid, 610 Medicine & health, Schizophrenia, Treatment-Resistant / metabolism, Glutamic Acid / metabolism, Neuropsychological Tests, Humans, Female, Longitudinal Studies, Psychotic Disorders/drug therapy, Psychotic Disorders/metabolism, Receptors, N-Methyl-D-Aspartate/metabolism, Young Adult, Follow-Up Studies, Cognitive Dysfunction/drug therapy, Cognitive Dysfunction/metabolism, Antipsychotic Agents/therapeutic use, Antipsychotic Agents/pharmacology, Case-Control Studies, Cognition/physiology, Cognition/drug effects, Schizophrenia, Treatment-Resistant/drug therapy, Schizophrenia, Treatment-Resistant/metabolism, Glutamic Acid/metabolism, Schizophrenia/drug therapy, Schizophrenia/metabolism, Brain/metabolism, Receptors, N-Methyl-D-Aspartate, Receptors, N-Methyl-D-Aspartate / metabolism, Article, Cognition, Psychotic Disorders / drug therapy, Cognitive Dysfunction, Cognition / physiology, Cognitive Dysfunction / drug therapy, Schizophrenia / metabolism, Antipsychotic Agents / pharmacology, Schizophrenia, Treatment-Resistant / drug therapy, Schizophrenia / drug therapy, Brain, Cognitive Dysfunction / metabolism, Psychotic Disorders, Cognition / drug effects, 616.89, Schizophrenia, Brain / metabolism, Antipsychotic Agents / therapeutic use, Schizophrenia, Treatment-Resistant, Antipsychotic Agents |
| Popis: | This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 1476-5578 1359-4184 |
| DOI: | 10.1038/s41380-024-02631-4 |
| DOI: | 10.48350/197694 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38849515 https://archive-ouverte.unige.ch/unige:184121 https://doi.org/10.1038/s41380-024-02631-4 http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_23EAC9CDB4DD2 https://serval.unil.ch/notice/serval:BIB_23EAC9CDB4DD https://serval.unil.ch/resource/serval:BIB_23EAC9CDB4DD.P001/REF.pdf https://boris.unibe.ch/197694/ |
| Rights: | CC BY |
| Prístupové číslo: | edsair.doi.dedup.....2b060d9c00dca680e4c35cf5b22e073c |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | This study aims to determine whether 1) individuals with treatment-resistant schizophrenia display early cognitive impairment compared to treatment-responders and healthy controls and 2) N-methyl-D-aspartate-receptor hypofunction is an underlying mechanism of cognitive deficits in treatment-resistance. In this case‒control 3-year-follow-up longitudinal study, n = 697 patients with first-episode psychosis, aged 18 to 35, were screened for Treatment Response and Resistance in Psychosis criteria through an algorithm that assigns patients to responder, limited-response or treatment-resistant category (respectively resistant to 0, 1 or 2 antipsychotics). Assessments at baseline: MATRICS Consensus Cognitive Battery; N-methyl-D-aspartate-receptor co-agonists biomarkers in brain by MRS (prefrontal glutamate levels) and plasma (D-serine and glutamate pathways key markers). Patients were compared to age- and sex-matched healthy controls (n = 114). Results: patient mean age 23, 27% female. Treatment-resistant (n = 51) showed lower scores than responders (n = 183) in processing speed, attention/vigilance, working memory, verbal learning and visual learning. Limited responders (n = 59) displayed an intermediary phenotype. Treatment-resistant and limited responders were merged in one group for the subsequent D-serine and glutamate pathway analyses. This group showed D-serine pathway dysregulation, with lower levels of the enzymes serine racemase and serine-hydroxymethyltransferase 1, and higher levels of the glutamate-cysteine transporter 3 than in responders. Better cognition was associated with higher D-serine and lower glutamate-cysteine transporter 3 levels only in responders; this association was disrupted in the treatment resistant group. Treatment resistant patients and limited responders displayed early cognitive and persistent functioning impairment. The dysregulation of NMDAR co-agonist pathways provides underlying molecular mechanisms for cognitive deficits in treatment-resistant first-episode psychosis. If replicated, our findings would open ways to mechanistic biomarkers guiding response-based patient stratification and targeting cognitive improvement in clinical trials. |
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| ISSN: | 14765578 13594184 |
| DOI: | 10.1038/s41380-024-02631-4 |