Secretory Acid Sphingomyelinase in the Serum of Medicated Patients Predicts the Prospective Course of Depression
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Description
2.2. Psychometric Scales
2.3. Blood Analysis
2.4. Determination of S-ASM Activity
2.5. Statistics
3. Results
3.1. Cohort Characteristics
3.2. Group Differences and Time Course for S-ASM Activity
3.3. S-ASM Activity, Depression Severity, and Prospective Course
3.4. S-ASM Activity and State and Trait Anxiety (STAI)
3.5. S-ASM Activity and Self-Reported Health-Related Quality of Life (SF-12)
3.6. S-ASM Activity and Serum Lipid Levels
3.7. Replication of S-ASM Correlation with Liver Enzyme Activities
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALT | Alanine aminotransferase (glutamic-pyruvic transaminase, GPT) |
ASM | Acid sphingomyelinase |
AST | Aspartate aminotransferase (glutamic-oxaloacetic transaminase, GOT) |
BDI-II | Beck Depression Inventory-II |
BMI | Body mass index |
GGT | Gamma-glutamyl transferase |
FIASMA | Functional inhibitor of acid sphingomyelinase |
HAM-D | Hamilton Depression Rating Scale |
HDL | High-density lipoprotein |
L-ASM | Lysosomal acid sphingomyelinase |
LDL | Low-density lipoprotein |
MADRS | Montgomery–Åsberg Depression Rating Scale |
MDE | Major depressive episode |
MDD | Major depressive disorder |
CRP | C-reactive protein |
S-ASM | Secretory acid sphingomyelinase |
SF-12 | Self-reported health-related quality of life |
SMPD1 | Sphingomyelin phosphodiesterase 1 gene encoding ASM |
STAI | State-Trait Anxiety Inventory |
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Parameters | PU | PM | PR | HC | p Values for Group Difference | p Values for Sex Difference | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
PU vs. PM | PU vs. HC | PM vs. HC | PR vs. HC | PU | PM | PR | HC | |||||
n (females/males) at inclusion | 36/27 | 32/34 | 28/11 | 31/30 | 0.325 | 0.480 | 0.793 | 0.038 | ||||
n (females/males) at follow-up | 341/272 | 28/32 | -/- | -/- | 0.318 | |||||||
age (years) | 47 (34–53) | 46 (33–54) | 49 (46–58) | 42 (32–54) | 0.908 | 0.455 | 0.609 | 0.019 | 0.692 | 0.603 | 0.132 | 0.168 |
total education years a | 15 (13–18) | 14 (13–16) | 14 (13–16) | 15 (13–18) | 0.062 | 0.933 | 0.080 | 0.221 | 0.172 | 0.354 | 0.225 | 0.087 |
BMI (kg/m²) | 25.3 (22.5–27.8) | 28.5 (24.4–30.4) | 25.7 (23.0–29.1) | 24.4 (23–27.7) | <0.001 | 0.760 | 0.001 | 0.281 | 0.090 | 0.182 | 0.528 | 0.279 |
BDI-II score at inclusion | 28 (22–34) | 29 (24–35) | 3 (0–4) | 1 (0–3) | 0.432 | <0.001 | <0.001 | 0.280 | 0.416 | 0.020 | 0.414 | 0.683 |
BDI-II score at follow-up c | 20 (15–25) | 20 (13–31) | 0.939 | 0.154 | 0.041 | |||||||
BDI-II score at relative change c | −0.27 (−0.42–−0.12) | −0.32 (−0.51–−0.07) | 0.508 | 0.161 | 0.134 | |||||||
HAM-D score at inclusion | 21 (19–24) | 23 (20–26) | 2 (0–3) | 1 (0–2) | 0.064 | <0.001 | <0.001 | 0.018 | 0.818 | 0.151 | 0.678 | 0.050 |
HAMD-D score at follow-up c | 18 (14–21) | 15 (10–22) | 0.189 | 0.529 | 0.150 | |||||||
HAMD-D score at relative change c | −0.15 (−0.38–−0.05) | −0.32 (−0.51–−0.16) | 0.010 | 0.788 | 0.083 | |||||||
MADRS score at inclusion | 26 (23–28) | 28 (24– 34) | 1 (0–3) | 0 (0–2) | 0.057 | <0.001 | <0.001 | 0.012 | 0.460 | 0.322 | 0.818 | 0.069 |
MADRS score at follow-up c | 21 (18–25) | 18 (13–26) | 0.143 | 0.398 | 0.170 | |||||||
MADRS score relative change c | −0.19 (−0.34–−0.07) | −0.32 (−0.46–−0.14) | 0.010 | 0.387 | 0.094 | |||||||
STAI state score at inclusion | 50 (40–57) | 54 (43–63) | 32 (26–36) | 28 (26–31) | 0.080 | <0.001 | <0.001 | 0.036 | 0.160 | 0.142 | 0.158 | 0.238 |
STAI state score at follow-up c | 46 (37–52) | 47 (42–57) | 0.261 | 0.210 | 0.157 | |||||||
STAI state score relative change c | −0.06 (−0.15–0.02) | −0.05 (−0.14–0.09) | 0.583 | 0.754 | 0.917 | |||||||
STAI trait score at inclusion | 62 (56–67) | 61 (52–67) | 33 (26–40) | 28 (25–33) | 0.261 | <0.001 | <0.001 | 0.007 | 0.486 | 0.261 | 0.116 | 0.448 |
STAI trait score at follow-up c | 59 (54–63) | 56 (51–65) | 0.530 | 0.911 | 0.121 | |||||||
STAI trait score relative change c | −0.06 (−0.12–0.01) | −0.04 (−0.14–0.03) | 0.558 | 0.703 | 0.142 | |||||||
SF-12 physical component score b | 50.9 (38.7–57.6) | 50.9 (43.8–57.1) | 55.5 (50.1–56.5) | 55.7 (54.9–56.7) | 0.432 | 0.001 | 0.003 | 0.124 | 0.524 | 0.206 | 0.390 | 0.097 |
SF-12 mental component score b | 19.9 (16.6–27.6) | 18.5 (14.3–26.6) | 53.2 (48.7–57.8) | 56.2 (52.1–58.9) | 0.165 | <0.001 | <0.001 | 0.240 | 0.486 | 0.501 | 0.140 | 0.351 |
CRP (mg/L) | 0.9 (0.5–2.1) | 1.6 (1.1–3.1) | 1.4 (0.9–2.2) | 1.3 (0.7–2.3) | 0.005 | 0.139 | 0.127 | 0.373 | 0.813 | 0.913 | 0.221 | 0.129 |
Triglycerides (mg/dL) | 90 (68–124) | 127 (97–174) | 93 (68–138) | 81 (63–142) | <0.001 | 0.944 | <0.001 | 0.445 | 0.003 | 0.003 | 0.939 | 0.665 |
Total cholesterol (mg/dL) | 217 (187–264) | 235 (198–267) | 227 (201–251) | 208 (181–248) | 0.256 | 0.313 | 0.028 | 0.198 | 0.868 | 0.719 | 0.083 | 0.226 |
HDL cholesterol (mg/dL) | 59 (52–66) | 51 (43– 64) | 58 (46–68) | 58 (50–69) | 0.007 | 0.976 | 0.018 | 0.641 | <0.001 | <0.001 | <0.001 | <0.001 |
LDL cholesterol (mg/dL) | 143 (118–179) | 159 (132–196) | 151 (139–167) | 134 (117–167) | 0.070 | 0.182 | 0.001 | 0.057 | 0.433 | 0.151 | 0.414 | 0.608 |
HDL/LDL ratio | 2.4 (1.9–3.3) | 3 (2.3–4) | 2.6 (1.9–3.3) | 2.2 (1.8–3.0) | 0.003 | 0.270 | <0.001 | 0.158 | 0.002 | <0.001 | 0.037 | 0.055 |
GGT (U/L) | 21 (15–30) | 25 (17–42) | 18 (13–32) | 19 (15–26) | 0.044 | 0.527 | 0.012 | 0.966 | 0.001 | <0.001 | 0.167 | 0.104 |
ALT (U/L) | 19 (15–29) | 26 (17–41) | 18 (15–26) | 22 (16–31) | 0.043 | 0.444 | 0.209 | 0.210 | <0.001 | <0.001 | 0.040 | 0.002 |
AST (U/L) | 23 (19–26) | 24 (21–32) | 24 (20–28) | 26 (22–30) | 0.118 | 0.005 | 0.250 | 0.072 | 0.033 | 0.001 | 0.158 | 0.002 |
S-ASM (fmol/h/µL serum) at inclusion | 151 (121–206) | 176 (125–228) | 150 (101–186) | 173 (130–214) | 0.166 | 0.237 | 0.828 | 0.068 | 0.080 | 0.191 | 0.939 | 0.863 |
S-ASM (fmol/h/µL serum) at follow-up c | 160 (114–202) | 189 (143–227) | 0.013 | 0.076 | 0.917 | |||||||
S-ASM relative change c | 0.03 (−0.19–0.22) | 0.10 (−0.08–0.28) | 0.200 | 0.994 | 0.273 |
S-ASM Activity | HAM-D | MADRS | BDI-II | ||||
---|---|---|---|---|---|---|---|
n | rho | p | rho | p | rho | p | |
All | 39 | 0.143 | 0.386 | 0.451 | 0.004 | 0.385 | 0.015 |
Female | 28 | 0.146 | 0.459 | 0.368 | 0.054 | 0.424 | 0.024 |
Male | 11 | 0.155 | 0.648 | 0.667 | 0.025 | 0.259 | 0.442 |
S-ASM Activity | Relative Change of Score from Inclusion to Follow-Up | Sum Score at Follow-Up | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
HAM-D | MADRS | BDI-II | STAI (Trait) | HAM-D | MADRS | BDI-II | STAI (Trait) | |||||||||||
n | rho | p | rho | p | rho | p | rho | p | rho | p | rho | p | rho | p | rho | p | ||
Unmedicated | all | 60 | 0.231 | 0.075 | 0.066 | 0.618 | −0.112 | 0.396 | −0.149 | 0.256 | 0.082 | 0.534 | −0.054 | 0.682 | −0.007 | 0.956 | 0.044 | 0.736 |
Patients | female | 34 | 0.136 | 0.443 | −0.024 | 0.895 | −0.148 | 0.403 | −0.127 | 0.476 | 0.021 | 0.904 | −0.100 | 0.575 | 0.059 | 0.741 | 0.265 | 0.129 |
With current MDE | male | 26 | 0.295 | 0.144 | 0.236 | 0.245 | 0.069 | 0.736 | −0.119 | 0.563 | 0.213 | 0.295 | 0.100 | 0.628 | −0.123 | 0.551 | −0.269 | 0.184 |
Medicated | all | 60 | −0.300 | 0.020 | −0.306 | 0.017 | −0.411 | 0.001 | −0.344 | 0.007 | -0.206 | 0.114 | −0.240 | 0.065 | −0.367 | 0.004 | −0.376 | 0.003 |
Patients | female | 28 | −0.400 | 0.035 | −0.401 | 0.035 | −0.585 | 0.001 | −0.406 | 0.032 | -0.182 | 0.354 | −0.202 | 0.302 | −0.389 | 0.041 | −0.395 | 0.037 |
With current MDE | male | 32 | −0.094 | 0.607 | −0.130 | 0.479 | −0.184 | 0.314 | −0.231 | 0.203 | -0.127 | 0.487 | −0.158 | 0.388 | −0.271 | 0.134 | −0.291 | 0.106 |
S-ASM Activity | Triglycerides | Total Cholesterol | LDL Cholesterol | LDL/HDL Ratio | |||||
---|---|---|---|---|---|---|---|---|---|
n | rho | p | rho | p | rho | p | rho | p | |
Unmedicated females | 36 | 0.103 | 0.549 | −0.531 | 0.0009 | −0.596 | 0.0001 | −0.571 | 0.0003 |
Medicated females | 32 | 0.533 | 0.002 | 0.481 | 0.005 | 0.487 | 0.005 | 0.302 | 0.093 |
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Mühle, C.; Wagner, C.J.; Färber, K.; Richter-Schmidinger, T.; Gulbins, E.; Lenz, B.; Kornhuber, J. Secretory Acid Sphingomyelinase in the Serum of Medicated Patients Predicts the Prospective Course of Depression. J. Clin. Med. 2019, 8, 846. https://doi.org/10.3390/jcm8060846
Mühle C, Wagner CJ, Färber K, Richter-Schmidinger T, Gulbins E, Lenz B, Kornhuber J. Secretory Acid Sphingomyelinase in the Serum of Medicated Patients Predicts the Prospective Course of Depression. Journal of Clinical Medicine. 2019; 8(6):846. https://doi.org/10.3390/jcm8060846
Chicago/Turabian StyleMühle, Christiane, Claudia Johanna Wagner, Katharina Färber, Tanja Richter-Schmidinger, Erich Gulbins, Bernd Lenz, and Johannes Kornhuber. 2019. "Secretory Acid Sphingomyelinase in the Serum of Medicated Patients Predicts the Prospective Course of Depression" Journal of Clinical Medicine 8, no. 6: 846. https://doi.org/10.3390/jcm8060846