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).