Table 2

Biological pathways identified by GeneGO metacore pathway analysis as differing over time between BD subjects who responded or failed to respond to treatment with lithium
GeneGO Process Networks for genes showing significant group x time interaction
Overall p-Value
1 Apoptosis_Anti-Apoptosis mediated by external signals 0.013
2 Apoptosis_Apoptotic mitochondria 0.055
3 Cytoskeleton_Actin filaments 0.055
4 Apoptosis_Endoplasmic reticulum stress pathway 0.068
5 Cell cycle_Core 0.110
6 Protein folding_Folding in normal condition 0.117
7 Cell cycle_G1-S Interleukin regulation 0.123
8 Development_Hemopoiesis, Erythropoietin pathway 0.143
9 Immune response_BCR pathway 0.147
10 Apoptosis_Apoptosis stimulation by external signals 0.159
Week 4: down-regulated genes in Lithium responders vs. non-responders
1 Apoptosis_Apoptotic mitochondria 0.053
2 Apoptosis_Endoplasmic reticulum stress pathway 0.060
3 Signal transduction_Nitric oxide signaling 0.061
4 Apoptosis_Anti-Apoptosis mediated by external signals by Estrogen 0.068
5 Protein folding_Folding in normal condition 0.081
6 Proteolysis_Proteolysis in cell cycle and apoptosis 0.085
7 Development_Hemopoiesis, Erythropoietin pathway 0.092
8 Apoptosis_Apoptosis stimulation by external signals 0.098
9 Proliferation_Negative regulation of cell proliferation 0.123
10 Cell adhesion_Amyloid proteins 0.127
Week 4: up-regulated genes in Lithium responders vs. non-responders
1 Cell adhesion_Glycoconjugates 0.010
2 Apoptosis_Anti-Apoptosis mediated by external signals via PI3K/AKT 0.017
3 Autophagy_Autophagy 0.053
4 Signal transduction_Androgen receptor signaling cross-talk 0.069
5 Signal transduction_ERBB-family signaling 0.072
6 Cytoskeleton_Macropinocytosis and its regulation 0.081
7 Inflammation_IL-13 signaling pathway 0.087
8 Signal transduction_Leptin signaling 0.098
9 Signal Transduction_Cholecystokinin signaling 0.100
10 Inflammation_IL-4 signaling 0.108
Week 6: down-regulated genes in Lithium responders vs. non-responders
1 Cell cycle_Core 0.027
2 Development_Hemopoiesis, Erythropoietin pathway 0.036
3 Response to hypoxia and oxidative stress 0.053
4 Transport_Synaptic vesicle exocytosis 0.059
5 Cell cycle_G0-G1 0.149
6 Neurophysiological process_Long-term potentiation 0.170
7 Blood coagulation 0.193
8 Apoptosis_Anti-Apoptosis mediated by external signals by Estrogen 0.202
9 Inflammation_IL-6 signaling 0.238
10 Cell cycle_G1-S Interleukin regulation 0.245
Week 6: up-regulated genes in Lithium responders vs. non-responders
1 Development_Skeletal muscle development 0.024
2 Cell adhesion_Attractive and repulsive receptors 0.034
3 Cytoskeleton_Actin filaments 0.034
4 Development_Neurogenesis:Axonal guidance 0.056
5 Protein folding_ER and cytoplasm 0.074
6 Protein folding_Response to unfolded proteins 0.111
7 Apoptosis_Apoptotic mitochondria 0.123
8 Apoptosis_Endoplasmic reticulum stress pathway 0.138
9 Apoptosis_Anti-Apoptosis mediated by external signals by Estrogen 0.156
10 Protein folding_Folding in normal condition 0.184

Pathway analysis was conducted for the entire group of 127 genes showing a significant group x time interaction, as well as for up-regulated and down-regulated genes separately at each of the time-points where significant differences were seen (4 weeks and 6 weeks after treatment initiation).

Lowthert et al.

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

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