Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women
Abstract
:1. Introduction
Aims
2. Methods
2.1. Characterization of Discovery Group
2.1.1. Ethics and Patient Consent
2.1.2. Blood Sample Collection, Methylation Profiling, and Data Processing (EUPD Group)
2.1.3. Annotation and Selection of DNA Methylation Probes
2.1.4. DNA Methylation Association Study
2.2. Characterization of the Validation Dataset
2.2.1. Ethics and Patient Consent
2.2.2. Validation Cohort of Suicide Attempters
2.2.3. Descriptive Statistics (Validation Group)
2.2.4. Blood Sample Collection, Methylation Profiling, and Data Processing (Validation Group)
2.2.5. DNA Methylation Association Study (Validation)
3. Results
3.1. Promotor-Associated BDNF Is Higher-Methylated in Whole Blood of EUPD Patients (n = 129)
3.2. Cohort Description (Validation Group)
3.3. Promotor-Associated BDNF-Methylation Levels Are Higher-Methylated with Dependence on Severity of Suicide Attempt (n = 60)
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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BPD | Control | Statistics (t-Test, Chisq-Test, Fisher’s Exact Test), p-Value | |
---|---|---|---|
N | 97 | 32 | |
Age (years), mean (SD) | 29.4 (7.6) | 37.2 (6.0) | <0.0001 |
Men:women, n (%) | 0 (0.0):97 (100.0) | 0 (0.0):32 (100.0) | ns |
Biological children, n (%) | 10 (10.3) | 21 (65.6) | <0.0001 |
University Education, n (%) | 28 (28.9) | N/A | - |
BMI, mean (SD) | 24.5 (4.7) | 24.1 (3.7) | ns |
Tobacco usage, n (%) | 56 (57.7) | 13 (40.6) | 0.075 |
Active Major Depressive Disorder, n (%) | 41 (42.3) | 0 (0.0) | - |
Severe MDD, n (%) | 13 (13.4) | 0 (0.0) | - |
Bipolar Disorder II or UNS, n (%) | 8 (8.2) | 0 (0.0) | - |
Comorbid Anxiety Disorder, n (%) | 59 (60.8) | 0 (0.0) | - |
Borderline personality disorder, n (%) | 97 (100.0) | 0 (0.0) | - |
- ≥7 fulfilled BPD criteria, n (%) | 31 (32.0) | 0 (0.0) | |
History of alcohol abuse, n (%) | 32 (33.0) | 0 (0.0) | |
History of substance abuse, n (%) | 26 (26.8) | 0 (0.0) | - |
KIVS exposure to violent behavior during childhood (6–14 years of age), mean (SD) | 2.66 (1.86) | 0.36 (0.71) | <0.0001 |
KIVS exposure to violent behavior as adult (>15 years of age), mean (SD) | 2.47 (1.90) | 0.35 (0.76) | <0.0001 |
Global Assessment of Functioning (GAF), mean (SD) | 49.2 (12.4) | N/A | - |
Psychotropic Medication, n (%) | |||
SSRI | 32 (33.0) | 0 (0.0) | - |
Non-SSRI antidepressants | 20 (20.6) | 0 (0.0) | - |
Mood stabilizers | 4 (4.1) | 0 (0.0) | - |
Benzodiazepines | 35 (36.1) | 0 (0.0) | - |
Neuroleptics | 12 (12.4) | 0 (0.0) | - |
History of past suicide attempt, n (%) | 97 (100.0) | 0 (0.0) | - |
Age at first suicide attempt, mean (SD) | 20.0 (7.5) | - | - |
Later confirmed death by suicide, n (%) | 8 (8.25) | 0 (0.0) | 0.20 |
Statistic | Coef. | Std. Error | t Value | p-Value |
---|---|---|---|---|
Intercept | −4.239911 | 0.1125374 | −37.676 | <2 × 10−16 |
EUPD vs. Control | 0.0838778 | 0.0391741 | 2.141 | 0.0343 |
Age | 0.0029001 | 0.0021716 | 1.335 | ns |
BMI | 0.0002664 | 0.0035534 | 0.075 | ns |
CpG | ProbeType | CHR | Pos | Location | Island_Shore | DMR | Coef. | p-Value |
---|---|---|---|---|---|---|---|---|
cg03167496 | II | 11 | 27743619 | TSS200;TSS1500;TSS1500; TSS1500 | Island | Yes | 0.116 | ns |
cg05218375 | II | 11 | 27723218 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | Yes | −0.132 | 0.0390 |
cg06046431 | I | 11 | 27744490 | TSS1500 | Island | Yes | 0.028 | ns |
cg06816235 | II | 11 | 27742219 | Body;5’UTR;TSS1500;5’UTR;1stExon;1stExon;1stExon;5’UTR | Island | Yes | 0.001 | ns |
cg06991510 | I | 11 | 27723237 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | Yes | −0.013 | ns |
cg10022526 | II | 11 | 27744557 | TSS1500 | Island | Yes | −0.022 | ns |
cg11718030 | II | 11 | 27744363 | TSS1500 | Island | Yes | 0.328 | 0.0002 |
cg14589148 | I | 11 | 27743648 | TSS200;TSS1500;TSS1500;TSS1500 | Island | Yes | 0.073 | ns |
cg15462887 | II | 11 | 27744049 | TSS1500 | Island | Yes | 0.144 | 0.0434 |
cg16257091 | II | 11 | 27743580 | TSS1500;TSS1500;1stExon;5’UTR;TSS1500 | Island | Yes | −0.130 | 0.0857 |
cg22288103 | II | 11 | 27743654 | TSS1500;TSS1500;TSS1500;TSS200 | Island | Yes | 0.109 | 0.0791 |
cg23497217 | II | 11 | 27723214 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | Yes | 0.079 | ns |
cg24377657 | I | 11 | 27723245 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;boldTSS1500;TSS1500 | S_Shore | Yes | 0.134 | 0.0057 |
cg25156688 | II | 11 | 27744054 | TSS1500 | Island | Yes | 0.108 | ns |
cg25381667 | I | 11 | 27743651 | TSS200;TSS1500;TSS1500;TSS1500 | Island | Yes | 0.053 | ns |
cg26840770 | II | 11 | 27723290 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | Yes | 0.120 | ns |
Attempted Suicide (n = 60) | |||
---|---|---|---|
High-Risk Group | Low-Risk Group | Statistics (t-Test, Mann–Whitney U-test, Chisq. Test, Fisher’s Exact Test), p-Value | |
N | 15 | 45 | |
Age (years) | 35.67 (13.2) | 34.0 (12.4) | ns |
BMI, mean (SD) | 24.3 (4.6) | 24.9 (4.3) | ns |
Borderline personality disorder, n(%) | 3 (20.0) | 5 (11.1) | ns |
Other personality disorder, n(%) | 3 (20.0) | 8 (17.8) | ns |
Alcohol dependence, (n(%)) | 4 (26.7) | 7 (15.6) | ns |
Substance dependence, n(%) | 1 (6.7) | 6 (13.3) | ns |
Completed suicide, n(%) | 1 (6.7) | 0 (0.0) | ns |
KIVS subscale, n(%) | |||
Exposure violent behavior during | |||
Childhood | 5 (33.3) | 14 (31.1) | ns |
Adulthood | 6 (40.0) | 13 (28.0) | ns |
CpG | ProbeType | CHR | Pos | Location | Island_Shore | DMR | Coef. (W) | p-Value |
---|---|---|---|---|---|---|---|---|
cg03167496 | II | 11 | 27743619 | TSS200;TSS1500;TSS1500;TSS1500 | Island | DMR | 323 | ns |
cg05218375 | II | 11 | 27723218 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | DMR | 255 | 0.082 |
cg06046431 | I | 11 | 27744490 | TSS1500 | Island | DMR | 346 | ns |
cg06816235 | II | 11 | 27742219 | Body;5’UTR;TSS1500;5’UTR;1stExon;1stExon;1stExon;5’UTR | Island | DMR | 266 | ns |
cg06991510 | I | 11 | 27723237 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | DMR | 364 | ns |
cg10022526 | II | 11 | 27744557 | TSS1500 | Island | DMR | 362 | ns |
cg11718030 | II | 11 | 27744363 | TSS1500 | Island | DMR | 321 | ns |
cg14589148 | I | 11 | 27743648 | TSS200;TSS1500;TSS1500;TSS1500 | Island | DMR | 350 | ns |
cg15462887 | II | 11 | 27744049 | TSS1500 | Island | DMR | 187 | 0.005 |
cg16257091 | II | 11 | 27743580 | TSS1500;TSS1500;1stExon;5’UTR;TSS1500 | Island | DMR | 322 | ns |
cg22288103 | II | 11 | 27743654 | TSS1500;TSS1500;TSS1500;TSS200 | Island | DMR | 328 | ns |
cg23497217 | II | 11 | 27723214 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | DMR | 169 | 0.002 |
cg24377657 | I | 11 | 27723245 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | DMR | 329 | ns |
cg25156688 | II | 11 | 27744054 | TSS1500 | Island | DMR | 246 | 0.061 |
cg25381667 | I | 11 | 27743651 | TSS200;TSS1500;TSS1500;TSS1500 | Island | DMR | 382 | ns |
cg26840770 | II | 11 | 27723290 | TSS1500;Body;5’UTR;TSS1500;5’UTR;5’UTR;TSS200;TSS1500;TSS1500;TSS1500;TSS1500;5’UTR;TSS1500;TSS1500 | S_Shore | DMR | 395 | ns |
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Jamshidi, E.; Boström, A.E.D.; Wilczek, A.; Nilsonne, Å.; Åsberg, M.; Jokinen, J. Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women. Cells 2023, 12, 350. https://doi.org/10.3390/cells12030350
Jamshidi E, Boström AED, Wilczek A, Nilsonne Å, Åsberg M, Jokinen J. Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women. Cells. 2023; 12(3):350. https://doi.org/10.3390/cells12030350
Chicago/Turabian StyleJamshidi, Esmail, Adrian E. Desai Boström, Alexander Wilczek, Åsa Nilsonne, Marie Åsberg, and Jussi Jokinen. 2023. "Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women" Cells 12, no. 3: 350. https://doi.org/10.3390/cells12030350
APA StyleJamshidi, E., Boström, A. E. D., Wilczek, A., Nilsonne, Å., Åsberg, M., & Jokinen, J. (2023). Increased Methylation of Brain-Derived Neurotrophic Factor (BDNF) Is Related to Emotionally Unstable Personality Disorder and Severity of Suicide Attempt in Women. Cells, 12(3), 350. https://doi.org/10.3390/cells12030350