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.

Lowthert et al. Biology of Mood & Anxiety Disorders 2012 2:15   doi:10.1186/2045-5380-2-15

Open Data