Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex
Abstract Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance fo...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2023-10-01
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| Series: | Translational Psychiatry |
| Online Access: | https://doi.org/10.1038/s41398-023-02616-x |
| _version_ | 1827632997017321472 |
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| author | Tiannan Shao Jing Huang Yuxin Zhao Weiyan Wang Xiaohan Tian Gangrui Hei Dongyu Kang Yong Gao Fangkun Liu Jingping Zhao Bing Liu Ti-Fei Yuan Renrong Wu |
| author_facet | Tiannan Shao Jing Huang Yuxin Zhao Weiyan Wang Xiaohan Tian Gangrui Hei Dongyu Kang Yong Gao Fangkun Liu Jingping Zhao Bing Liu Ti-Fei Yuan Renrong Wu |
| author_sort | Tiannan Shao |
| collection | DOAJ |
| description | Abstract Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material. |
| first_indexed | 2024-03-09T14:53:23Z |
| format | Article |
| id | doaj.art-8b19aa12420b498e96c67fcfd31db151 |
| institution | Directory Open Access Journal |
| issn | 2158-3188 |
| language | English |
| last_indexed | 2024-03-09T14:53:23Z |
| publishDate | 2023-10-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Translational Psychiatry |
| spelling | doaj.art-8b19aa12420b498e96c67fcfd31db1512023-11-26T14:19:23ZengNature Publishing GroupTranslational Psychiatry2158-31882023-10-0113111010.1038/s41398-023-02616-xMetformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortexTiannan Shao0Jing Huang1Yuxin Zhao2Weiyan Wang3Xiaohan Tian4Gangrui Hei5Dongyu Kang6Yong Gao7Fangkun Liu8Jingping Zhao9Bing Liu10Ti-Fei Yuan11Renrong Wu12Department of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityDepartment of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityBrainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of SciencesDepartment of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal UniversityDepartment of Psychiatry, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityDepartment of Orthopedics, The First People’s Hospital of Changde, Changde Hospital Affiliated to Xiangya Medical College of Central South UniversityDepartment of Neurosurgery, Xiangya Hospital, Central South UniversityDepartment of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityState Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal UniversityShanghai Key Laboratory of Psychotic Disorders, Brain Health Institute, National Center for Mental Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of MedicineDepartment of Psychiatry, National Clinical Research Center for Mental Disorders, and National Center for Mental Disorders, The Second Xiangya Hospital of Central South UniversityAbstract Cognitive impairment is a core feature of schizophrenia, which is aggravated by antipsychotics-induced metabolic disturbance and lacks effective pharmacologic treatments in clinical practice. Our previous study demonstrated the efficiency of metformin in alleviating metabolic disturbance following antipsychotic administration. Here we report that metformin could ameliorate cognitive impairment and improve functional connectivity (FC) in prefrontal regions. This is an open-labeled, evaluator-blinded study. Clinically stable patients with schizophrenia were randomly assigned to receive antipsychotics plus metformin (N = 48) or antipsychotics alone (N = 24) for 24 weeks. The improvement in cognition was assessed by the MATRICS Consensus Cognitive Battery (MCCB). Its association with metabolic measurements, and voxel-wise whole-brain FC with dorsolateral prefrontal cortex (DLPFC) subregions as seeds were evaluated. When compared to the antipsychotics alone group, the addition of metformin resulted in significantly greater improvements in the MCCB composite score, speed of processing, working memory, verbal learning, and visual learning. A significant time × group interaction effect of increased FC between DLPFC and the anterior cingulate cortex (ACC)/middle cingulate cortex (MCC), and between DLPFC subregions were observed after metformin treatment, which was positively correlated with MCCB cognitive performance. Furthermore, the FC between left DLPFC A9/46d to right ACC/MCC significantly mediated metformin-induced speed of processing improvement; the FC between left A46 to right ACC significantly mediated metformin-induced verbal learning improvement. Collectively, these findings demonstrate that metformin can improve cognitive impairments in schizophrenia patients and is partly related to the FC changes in the DLPFC. Trial Registration: The trial was registered with ClinicalTrials.gov (NCT03271866). The full trial protocol is provided in Supplementary Material.https://doi.org/10.1038/s41398-023-02616-x |
| spellingShingle | Tiannan Shao Jing Huang Yuxin Zhao Weiyan Wang Xiaohan Tian Gangrui Hei Dongyu Kang Yong Gao Fangkun Liu Jingping Zhao Bing Liu Ti-Fei Yuan Renrong Wu Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex Translational Psychiatry |
| title | Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| title_full | Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| title_fullStr | Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| title_full_unstemmed | Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| title_short | Metformin improves cognitive impairment in patients with schizophrenia: associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| title_sort | metformin improves cognitive impairment in patients with schizophrenia associated with enhanced functional connectivity of dorsolateral prefrontal cortex |
| url | https://doi.org/10.1038/s41398-023-02616-x |
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