Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia
Abstract Antipsychotic effects seem to decrease in relapsed schizophrenia patients and the underlying mechanisms remain to be elucidated. Based on the essential role of polyunsaturated fatty acids in brain function and the treatment of schizophrenia, we hypothesize that disordered fatty acid metabol...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-02-01
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| Series: | npj Schizophrenia |
| Online Access: | https://doi.org/10.1038/s41537-022-00214-2 |
| _version_ | 1797428466868551680 |
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| author | Nana Li Ping Yang Mimi Tang Yong Liu Wenbin Guo Bing Lang Jianjian Wang Haishan Wu Hui Tang Yan Yu Xiangxin Wu Cuirong Zeng Ting Cao Hualin Cai |
| author_facet | Nana Li Ping Yang Mimi Tang Yong Liu Wenbin Guo Bing Lang Jianjian Wang Haishan Wu Hui Tang Yan Yu Xiangxin Wu Cuirong Zeng Ting Cao Hualin Cai |
| author_sort | Nana Li |
| collection | DOAJ |
| description | Abstract Antipsychotic effects seem to decrease in relapsed schizophrenia patients and the underlying mechanisms remain to be elucidated. Based on the essential role of polyunsaturated fatty acids in brain function and the treatment of schizophrenia, we hypothesize that disordered fatty acid metabolism may contribute to treatment resistance in multi-episode patients. We analyzed the erythrocyte membrane fatty acids in 327 schizophrenia patients under various episodes (numbers of patients: first-episode drug naïve 89; 2–3 episodes 110; 4–6 episodes 80; over 6 episodes 48) and 159 age- and gender-matched healthy controls. Membrane fatty acid levels and PANSS scales were assessed at baseline of antipsychotic-free period and one-month of follow-up after treatment. Totally, both saturated and unsaturated fatty acids were reduced at baseline when compared to healthy controls. Subgroup analyses among different episodes indicated that in response to atypical antipsychotic treatment, the membrane fatty acids were only increased in patients within 3 episodes, and this therapeutic effects on omega-3 index were merely present in the first episode. Results of fatty acid ratios suggested that dysregulations of enzymes such as D6 desaturase, D5 desaturase, and elongases for polyunsaturated fatty acids in patients with multi-episode schizophrenia could account for the differences. Additionally, certain fatty acid level/ratio changes were positively correlated with symptom improvement. The alterations of C22:5n3 and omega-3 index, gender, and the number of episodes were significant risk factors correlated with treatment responsiveness. Using targeted metabolomic approach, we revealed the potential mechanisms underlying abnormal fatty acid metabolism responsible for reduced treatment response in patients with multi-episode schizophrenia. |
| first_indexed | 2024-03-09T08:59:19Z |
| format | Article |
| id | doaj.art-75f5a6d2a56b413c994cf8c4b517ea6d |
| institution | Directory Open Access Journal |
| issn | 2334-265X |
| language | English |
| last_indexed | 2024-03-09T08:59:19Z |
| publishDate | 2022-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Schizophrenia |
| spelling | doaj.art-75f5a6d2a56b413c994cf8c4b517ea6d2023-12-02T12:09:07ZengNature Portfolionpj Schizophrenia2334-265X2022-02-018111210.1038/s41537-022-00214-2Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophreniaNana Li0Ping Yang1Mimi Tang2Yong Liu3Wenbin Guo4Bing Lang5Jianjian Wang6Haishan Wu7Hui Tang8Yan Yu9Xiangxin Wu10Cuirong Zeng11Ting Cao12Hualin Cai13Department of Pharmacy, the Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, the Second People’s Hospital of Hunan ProvinceDepartment of Pharmacy, Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, Changsha Psychiatric HospitalDepartment of Pharmacy, the Second Xiangya Hospital of Central South UniversityDepartment of Pharmacy, the Second Xiangya Hospital of Central South UniversityDepartment of Pharmacy, the Second Xiangya Hospital of Central South UniversityDepartment of Pharmacy, the Second Xiangya Hospital of Central South UniversityAbstract Antipsychotic effects seem to decrease in relapsed schizophrenia patients and the underlying mechanisms remain to be elucidated. Based on the essential role of polyunsaturated fatty acids in brain function and the treatment of schizophrenia, we hypothesize that disordered fatty acid metabolism may contribute to treatment resistance in multi-episode patients. We analyzed the erythrocyte membrane fatty acids in 327 schizophrenia patients under various episodes (numbers of patients: first-episode drug naïve 89; 2–3 episodes 110; 4–6 episodes 80; over 6 episodes 48) and 159 age- and gender-matched healthy controls. Membrane fatty acid levels and PANSS scales were assessed at baseline of antipsychotic-free period and one-month of follow-up after treatment. Totally, both saturated and unsaturated fatty acids were reduced at baseline when compared to healthy controls. Subgroup analyses among different episodes indicated that in response to atypical antipsychotic treatment, the membrane fatty acids were only increased in patients within 3 episodes, and this therapeutic effects on omega-3 index were merely present in the first episode. Results of fatty acid ratios suggested that dysregulations of enzymes such as D6 desaturase, D5 desaturase, and elongases for polyunsaturated fatty acids in patients with multi-episode schizophrenia could account for the differences. Additionally, certain fatty acid level/ratio changes were positively correlated with symptom improvement. The alterations of C22:5n3 and omega-3 index, gender, and the number of episodes were significant risk factors correlated with treatment responsiveness. Using targeted metabolomic approach, we revealed the potential mechanisms underlying abnormal fatty acid metabolism responsible for reduced treatment response in patients with multi-episode schizophrenia.https://doi.org/10.1038/s41537-022-00214-2 |
| spellingShingle | Nana Li Ping Yang Mimi Tang Yong Liu Wenbin Guo Bing Lang Jianjian Wang Haishan Wu Hui Tang Yan Yu Xiangxin Wu Cuirong Zeng Ting Cao Hualin Cai Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia npj Schizophrenia |
| title | Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia |
| title_full | Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia |
| title_fullStr | Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia |
| title_full_unstemmed | Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia |
| title_short | Reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi- versus first-episode schizophrenia |
| title_sort | reduced erythrocyte membrane polyunsaturated fatty acid levels indicate diminished treatment response in patients with multi versus first episode schizophrenia |
| url | https://doi.org/10.1038/s41537-022-00214-2 |
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