Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder
Abstract Persistent cognitive challenges in bipolar disorder (BD) may be tied to insulin resistance, which crucially affects both metabolism and brain health. Additionally, mitochondrial DNA (mtDNA) copy number has emerged as an indicator of cognitive performance and response to treatment in BD. How...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12914 |
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| author | Tsung Han Tsai Cheng Ying Wu Cheng Chen Chang Ta Tsung Lin Chin San Liu Po See Chen |
| author_facet | Tsung Han Tsai Cheng Ying Wu Cheng Chen Chang Ta Tsung Lin Chin San Liu Po See Chen |
| author_sort | Tsung Han Tsai |
| collection | DOAJ |
| description | Abstract Persistent cognitive challenges in bipolar disorder (BD) may be tied to insulin resistance, which crucially affects both metabolism and brain health. Additionally, mitochondrial DNA (mtDNA) copy number has emerged as an indicator of cognitive performance and response to treatment in BD. However, it remains unclear whether and how this indicator might serve as a bridge between metabolic dysfunction and cognitive capacity. In 68 study participants with euthymic BD, insulin resistance was assessed according to fasting glucose and insulin levels. mtDNA copy number was quantified from leukocytes, and executive function was measured with the Wisconsin card‐sorting test (WCST). Mediation models were applied to explore the statistical relationship between insulin resistance, mtDNA copy number, and executive function. Both linear regression and Poisson distribution approaches with robust bootstrap simulations were used for significance testing. The results indicated that insulin resistance indirectly affects executive function via mtDNA copy number. This mediation relationship was statistically significant for both preservation errors and completion of categories in the WCST, although there were no significant direct effects of insulin resistance on the executive functions. We therefore concluded that insulin resistance is associated with reduced mtDNA copy number in blood, which may negatively impact executive functions in patients with euthymic BD. Further work is warranted to determine if improving metabolic and mitochondrial health may lead to better cognitive outcomes in BD. |
| format | Article |
| id | doaj-art-a66ccf3ca110400f98075ba5416aae0d |
| institution | Kabale University |
| issn | 1607-551X 2410-8650 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj-art-a66ccf3ca110400f98075ba5416aae0d2025-01-11T05:35:55ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502025-01-01411n/an/a10.1002/kjm2.12914Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorderTsung Han Tsai0Cheng Ying Wu1Cheng Chen Chang2Ta Tsung Lin3Chin San Liu4Po See Chen5Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan TaiwanDepartment of Psychiatry, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan TaiwanSchool of Medicine Chung Shan Medical University Taichung TaiwanVascular and Genomic Center, Institute of ATP Changhua Christian Hospital Changhua TaiwanVascular and Genomic Center, Institute of ATP Changhua Christian Hospital Changhua TaiwanDepartment of Psychiatry, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan TaiwanAbstract Persistent cognitive challenges in bipolar disorder (BD) may be tied to insulin resistance, which crucially affects both metabolism and brain health. Additionally, mitochondrial DNA (mtDNA) copy number has emerged as an indicator of cognitive performance and response to treatment in BD. However, it remains unclear whether and how this indicator might serve as a bridge between metabolic dysfunction and cognitive capacity. In 68 study participants with euthymic BD, insulin resistance was assessed according to fasting glucose and insulin levels. mtDNA copy number was quantified from leukocytes, and executive function was measured with the Wisconsin card‐sorting test (WCST). Mediation models were applied to explore the statistical relationship between insulin resistance, mtDNA copy number, and executive function. Both linear regression and Poisson distribution approaches with robust bootstrap simulations were used for significance testing. The results indicated that insulin resistance indirectly affects executive function via mtDNA copy number. This mediation relationship was statistically significant for both preservation errors and completion of categories in the WCST, although there were no significant direct effects of insulin resistance on the executive functions. We therefore concluded that insulin resistance is associated with reduced mtDNA copy number in blood, which may negatively impact executive functions in patients with euthymic BD. Further work is warranted to determine if improving metabolic and mitochondrial health may lead to better cognitive outcomes in BD.https://doi.org/10.1002/kjm2.12914bipolar disordercognitionexecutive functioninsulin resistancemitochondrial DNA copy number |
| spellingShingle | Tsung Han Tsai Cheng Ying Wu Cheng Chen Chang Ta Tsung Lin Chin San Liu Po See Chen Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder Kaohsiung Journal of Medical Sciences bipolar disorder cognition executive function insulin resistance mitochondrial DNA copy number |
| title | Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| title_full | Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| title_fullStr | Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| title_full_unstemmed | Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| title_short | Mitochondrial DNA copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| title_sort | mitochondrial dna copy number as a mediator of the relationship between insulin resistance and cognitive function in patients with euthymic bipolar disorder |
| topic | bipolar disorder cognition executive function insulin resistance mitochondrial DNA copy number |
| url | https://doi.org/10.1002/kjm2.12914 |
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