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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)

From: Increased ratio of anti-apoptotic to pro-apoptotic Bcl2 gene-family members in lithium-responders one month 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

  1. 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.
  2. Significant differences are marked with asterisks (* p <0.10, ** p <0.05, and *** P < .01).
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Biology of Mood & Anxiety Disorders

ISSN: 2045-5380

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