Table 3 |
|||||
| Expression of anti- and pro-apoptotic Bcl2-related genes in lithium responders and non-responders (normalized to expression levels in untreated healthy controls subjects) at each of the time points tested (baseline, 2,4,6, and 8 weeks after treatment initiation) | |||||
| Normalized Expression Levels | Time (in weeks) since starting lithium | ||||
| Anti-Apoptotic Genes | Baseline | 2 weeks | 4 weeks | 6 weeks | 8 weeks |
| BCL2 | |||||
| Lithium Responders | 0.96 | 0.89 | 1.08 | 0.86 | 0.83 |
| Non-Responders | 0.94 | 0.90 | 0.78 | 0.88 | 0.93 |
| Ratio | 1.0 | 1.0 | *1.4 | 1.0 | 0.9 |
| BCL2L1 (tx var. 1) (aka BCL-xL) | |||||
| Lithium Responders | 2.30 | 4.69 | 2.38 | 2.49 | 5.84 |
| Non-Responders | 3.04 | 3.49 | 2.08 | 3.13 | 1.85 |
| Ratio | 0.8 | 1.3 | 1.1 | 0.8 | 3.2 |
| IRS2 | |||||
| Lithium Responders | 0.78 | 1.12 | 1.51 | 0.84 | 1.35 |
| Non-Responders | 1.22 | 0.99 | 0.68 | 1.00 | 1.13 |
| Ratio | 0.6 | 1.1 | ***2.2 | 0.8 | 1.2 |
| MCL1 (tx. Var. 1) | |||||
| Lithium Responders | 0.56 | 0.81 | 0.91 | 0.74 | 0.98 |
| Non-Responders | 1.18 | 1.00 | 0.79 | 1.02 | 1.05 |
| Ratio | **0.5 | 0.8 | 1.1 | 0.7 | 0.9 |
| Pro-Apoptotic Genes | |||||
| BAD | |||||
| Lithium Responders | 1.54 | 1.49 | 1.29 | 1.44 | 1.32 |
| Non-Responders | 1.39 | 1.39 | 1.48 | 1.33 | 1.41 |
| Ratio | 1.1 | 1.1 | 0.9 | 1.1 | 0.9 |
| BAK1 | |||||
| Lithium Responders | 1.47 | 0.92 | 0.80 | 0.89 | 0.76 |
| Non-Responders | 1.29 | 1.08 | 1.23 | 1.24 | 1.29 |
| Ratio | 1.1 | 0.9 | ***0.6 | **0.7 | 0.6 |
| BAX | |||||
| Lithium Responders | 1.69 | 1.73 | 1.55 | 1.58 | 1.18 |
| Non-Responders | 1.14 | 1.39 | 1.25 | 1.42 | 1.53 |
| Ratio | **1.5 | 1.2 | 1.2 | 1.1 | 0.8 |
| BCL2L13 (aka BCL-Rambo) | |||||
| Lithium Responders | 0.86 | 0.98 | 0.96 | 0.82 | 0.96 |
| Non-Responders | 0.96 | 1.03 | 0.86 | 0.97 | 0.85 |
| Ratio | 0.9 | 0.9 | 1.1 | 0.8 | 1.1 |
| BCL2L1 (tx var. 2)(aka BCL-xL) | |||||
| Lithium Responders | 1.58 | 2.34 | 1.54 | 1.42 | 1.54 |
| Non-Responders | 1.58 | 1.98 | 1.59 | 1.96 | 1.36 |
| Ratio | 1.0 | 1.2 | 1.0 | 0.7 | 1.1 |
| BID | |||||
| Lithium Responders | 1.03 | 1.06 | 1.09 | 0.98 | 1.01 |
| Non-Responders | 1.04 | 0.99 | 1.02 | 1.12 | 0.97 |
| Ratio | 1.0 | 1.1 | 1.1 | 0.9 | 1.0 |
| BMF | |||||
| Lithium Responders | 1.09 | 1.05 | 1.06 | 1.06 | 0.96 |
| Non-Responders | 0.91 | 0.97 | 1.10 | 0.82 | 1.06 |
| Ratio | 1.2 | 1.1 | 1.0 | *1.3 | 0.9 |
| BNIP3 | |||||
| Lithium Responders | 1.02 | 0.74 | 0.89 | 0.78 | 0.78 |
| Non-Responders | 0.81 | 0.84 | 0.77 | 0.82 | 0.91 |
| Ratio | **1.3 | 0.9 | 1.2 | 0.9 | 0.9 |
| MCL1 (tx. var. 2) | |||||
| Lithium Responders | 1.08 | 1.21 | 1.14 | 1.10 | 1.34 |
| Non-Responders | 1.11 | 1.24 | 1.10 | 1.19 | 1.02 |
| Ratio | 1.0 | 1.0 | 1.0 | 0.9 | *1.3 |
Following initiation of treatment with lithium, all of the anti-apoptotic genes examined (BCL2, BCL2L1-tx var. 1, IRS2, and MCL1- tx. var. 1), showed an increase in the relative expression in lithium responders compared to non-responders during the first month of treatment. Among the pro-apoptotic genes, BAD, BAK, BAX, and BMF showed a decrease in the relative expression in lithium responders, while BCL2L13, BCL2L1-tx. var. 2, BID, BNIP3, and MCL1, tx. var. 2, showed no change or inconsistent change over this time period.
Significant differences are marked with asterisks (* p <0.10, ** p <0.05, and *** P < .01).
Lowthert et al. Biology of Mood & Anxiety Disorders 2012 2:15 doi:10.1186/2045-5380-2-15
