Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes
Abstract
1. Introduction
2. Results
2.1. Descriptive Analysis
2.2. Bivariate Analysis
2.3. Linear Regression Models
3. Discussion
4. Materials and Methods
4.1. Design
4.2. Participants
4.3. Instruments
4.4. Clinical Variables
4.5. Inflammatory Variables
4.5.1. hs-CRP
4.5.2. IL-6
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BD | Bipolar disorder |
hs-CRP | High-sensitivity C-reactive protein |
IL-6 | Interleukin-6 |
ACER-T | Addenbrooke’s Cognitive Examination Revised—Total |
ACER-L | Addenbrooke’s Cognitive Examination Revised—Language |
ACER-VE | Addenbrooke’s Cognitive Examination Revised—Visuospatial abilities |
ACER-OA | Addenbrooke’s Cognitive Examination Revised—Orientation/attention |
ACER-M | Addenbrooke’s Cognitive Examination Revised—Memory |
ACER-VF | Addenbrooke’s Cognitive Examination Revised—Verbal fluency |
TE | Time of evolution |
NH | Number of hospitalizations |
SA | Number of suicide attempts |
GWAS | Genome-wide association study |
SMD | Standardized mean difference |
CI | Confidence interval |
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Variable | Mean | Standard Deviation |
---|---|---|
IL-6 (pg/mL) | 8.3 | ±28.4 |
hs-CRP (mg/L) | 0.2 | ±0.4 |
ACER-T | 85.7 | ±9.2 |
ACER-L | 24.1 | ±1.9 |
ACER-VE | 14.3 | ±1.9 |
ACER-OA | 16.6 | ±1.7 |
ACER-M | 20 | ±4.4 |
ACER-VF | 10.5 | ±2.7 |
Age of onset (age) | 23.4 | ±9.3 |
Time of evolution (years) | 23.9 | ±12.9 |
NH | 3.3 | ±3.9 |
SA | 1.1 | ±2 |
hs-PCR | IL-6 | ACER-T | ACER-L | ACER-VE | ACER-OA | ACER-M | ACER-VF | Age | Onset | TE | NH | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
IL-6 | 0.05 (0.5946) | |||||||||||
ACER-T | 0.076 (0.4510) | −0.326 * (0.0007) | ||||||||||
ACER-L | 0.143 (0.1543) | −0.307 * (0.0015) | 0.645 * (<0.001) | |||||||||
ACER-VE | 0.062 (0.5364) | −0.322 * (0.0008) | 0.513 * (<0.001) | 0.357 * (0.0001) | ||||||||
ACER-OA | 0.029 (0.7667) | −0.312 * (0.0011) | 0.554 * (<0.001) | 0.253 * (0.0077) | 0.260 (0.0060) | |||||||
ACER-M | 0.059 (0.5529) | −0.236 * (0.0146) | 0.852 * (<0.001) | 0.422 * (<0.001) | 0.221 * (0.0203) | 0.299 * (0.0014) | ||||||
ACER-VF | −0.005 (0.9542) | −0.058 (0.5495) | 0.755 * (<0.001) | 0.342 * (0.0003) | 0.206 * (0.0302) | 0.342 * (0.0002) | 0.546 * (<0.001) | |||||
Age | 0.116 (0.2453) | 0.117 (0.2362) | −0.277 * (0.0038) | −0.176 (0.0685) | −0.283 * (0.0029) | −0.127 (0.1856) | −0.092 (0.3407) | −0.366 * (0.0001) | ||||
Onset | 0.094 (0.3456) | 0.043 (0.6601) | −0.027 (0.7752) | 0.101 (0.2976) | −0.168 (0.0822) | −0.113 (0.2407) | 0.076 (0.4278) | −0.101 (0.2929) | 0.446 * (<0.001) | |||
TE | 0.057 (0.5667) | 0.095 (0.3368) | −0.280 * (0.0035) | −0.263 * (0.0060) | −0.186 (0.0530) | −0.057 (0.5538) | −0.155 (0.1069) | −0.325 * (0.0006) | 0.765 * (<0.001) | −0.233 * (0.0144) | ||
NH | −0.021 (0.8311) | 0.399 * (<0.001) | −0.235 * (0.0147) | −0.246 * (0.0106) | −0.072 (0.4538) | −0.016 (0.8684) | −0.169 (0.0776) | −0.269 * (0.0046) | 0.206 * (0.0309) | −0.077 (0.4255) | 0.280 * (0.0032) | |
SA | 0.03 (0.7610) | −0.046 (0.6405) | 0.066 (0.4961) | 0.041 (0.6695) | 0.152 (0.1146) | −0.152 (0.1126) | 0.138 (0.1498) | −0.048 (0.6184) | −0.113 (0.2417) | −0.259 * (0.0065) | 0.063 (0.5116) | 0.025 (0.7949) |
Low ACER-T (n = 43) | High ACER-T (n = 66) | p-Value | |
---|---|---|---|
IL-6 | 10.2 ± 40.5 | 7.3 ± 16.6 | 0.61 |
hs-CRP | 0.22 ± 0.26 | 0.25 ± 0.53 | 0.79 |
Low IL-6 (n = 96) | High IL-6 (n = 10) | p-Value | |
---|---|---|---|
ACER-T | 85.8 ± 8.6 | 83.3 ± 14.4 | 0.42 |
ACER-L | 24.12 ± 1.7 | 24.6 ± 3 | 0.46 |
ACER-VE | 14.36 ± 1.87 | 13.7 ± 2.86 | 0.31 |
ACER-OA | 16.62 ± 1.7 | 16.40 ± 2.5 | 0.7 |
ACER-M | 20.12 ± 4.42 | 18.7 ± 5.69 | 0.34 |
ACER-VF | 10.59 ± 2.79 | 9.9 ± 2.99 | 0.45 |
NH | 2.97 ± 3.36 | 7.3 ± 7 | 0.001 * |
SA | 1.25 ± 2.11 | 0.9 ± 1.59 | 0.6 |
Low hs-CRP (n = 73) | High hs-CRP (n = 29) | p-Value | |
---|---|---|---|
ACER-T | 85.3 ± 10.04 | 85.92 ± 7.75 | 0.76 |
ACER-L | 0.22 ± 0.26 | 0.25 ± 0.53 | 0.79 |
ACER-VE | 14.33 ± 1.97 | 14.65 ± 1.67 | 0.44 |
ACER-OA | 16.56 ± 1.71 | 16.62 ± 2.06 | 0.88 |
ACER-M | 19.87 ± 4.94 | 19.93 ± 3.57 | 0.95 |
ACER-VF | 10.52 ± 2.96 | 10.37 ± 2.51 | 0.82 |
NH | 3.27 ± 3.89 | 3.96 ± 4.45 | 0.44 |
SA | 1.02 ± 1.75 | 1.82 ± 2.7 | 0.08 |
ACER-T | ACER-L | ACER-VE | ACER-OA | ACER-M | ACER-VF | NH | SA | |
---|---|---|---|---|---|---|---|---|
Intercept | 85.93 (83.8–88) | 24.15 (23.7–24.5) | 14.54 (14.13–14.95) | 16.7 (16.3–17.1) | 20 (19–21) | 10.53 (9.8–11.1) | 3.08 (2.2–3.9) | 1.25 (0.76–1.73) |
IL-6 | −0.107 (−0.16–−0.04) * | −0.021 (−0.03–−0.008) * | −0.02 (−0.035–−0.011) ** | −0.019 (−0.031–−0.007) * | −0.03 (−0.06–−0.007) * | −0.005 (−0.024–0.01) | 0.05 (0.03–0.08) ** | −0.003 (−0.018–0.01) |
hs-CRP | 1.98 (−2–5.9) | 0.69 (−0.12–1.52) | 0.34 (−0.44–1.14) | 0.19 (−0.58–0.96) | 0.74 (−1.25–2.75) | −0.017 (−1.29–1.25) | −0.38 (−2.06–1.29) | 0.15 (−0.78–1.09) |
Model statistics | ||||||||
R2 | 0.11 | 0.11 | 0.13 | 0.09 | 0.06 | 0.003 | 0.16 | 0.003 |
Adjusted R2 | 0.09 | 0.1 | 0.11 | 0.08 | 0.04 | −0.01 | 0.14 | −0.016 |
F-statistic | 6.4 | 6.58 | 7.65 | 5.45 | 3.21 | 0.16 | 9.38 | 0.18 |
p-Value | 0.002 * | 0.002 * | <0.001 * | 0.005 * | 0.04 * | 0.85 | <0.001 * | 0.83 |
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Ríos, U.; Pérez, S.; Martínez, C.; Moya, P.R.; Arancibia, M. Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes. Int. J. Mol. Sci. 2025, 26, 6372. https://doi.org/10.3390/ijms26136372
Ríos U, Pérez S, Martínez C, Moya PR, Arancibia M. Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes. International Journal of Molecular Sciences. 2025; 26(13):6372. https://doi.org/10.3390/ijms26136372
Chicago/Turabian StyleRíos, Ulises, Susana Pérez, Constanza Martínez, Pablo R. Moya, and Marcelo Arancibia. 2025. "Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes" International Journal of Molecular Sciences 26, no. 13: 6372. https://doi.org/10.3390/ijms26136372
APA StyleRíos, U., Pérez, S., Martínez, C., Moya, P. R., & Arancibia, M. (2025). Inflammation and Cognition in Bipolar Disorder: Diverging Paths of Interleukin-6 and Outcomes. International Journal of Molecular Sciences, 26(13), 6372. https://doi.org/10.3390/ijms26136372