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Alterations in phosphorylated cAMP response element‐binding protein ( pCREB ) signaling: an endophenotype of lithium‐responsive bipolar disorder?
Author(s) -
Alda Martin,
Shao Li,
Wang JunFeng,
Lara Catalina Lopez,
JaitovichGroisman Iris,
Lebel Veronique,
Sun Xiujun,
Duffy Anne,
Grof Paul,
Rouleau Guy A,
Turecki Gustavo,
Young L Trevor
Publication year - 2013
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12131
Subject(s) - creb , medicine , bipolar disorder , endocrinology , endophenotype , signal transduction , lithium (medication) , basal (medicine) , phenotype , mania , phosphorylation , forskolin , stimulation , biology , transcription factor , gene , neuroscience , genetics , cognition , insulin
Objectives Abnormalities of signal transduction are considered among the susceptibility factors for bipolar disorder (BD). These include changes in G‐protein‐mediated signaling and subsequent modification of gene expression via transcription factors such as cAMP response element‐binding protein (CREB). Methods We investigated levels of CREB in lymphoblasts from patients with BD, all responders to lithium prophylaxis (n = 13), and healthy control subjects (n = 15). Phosphorylated CREB ( pCREB ) was measured by immunoblotting in subjects with BD (n = 15) as well as in their affected (n = 17) and unaffected (n = 18) relatives, and healthy controls (n = 16). Results Basal CREB levels were comparable in patients and control subjects and were not changed by lithium treatment. pCREB levels were increased in both patients and their relatives compared to controls (p = 0.003). Forskolin stimulation led to a 24% increase in pCREB levels in cells from healthy subjects (p = 0.002) but not in the other three groups. When using basal and stimulated pCREB levels as a biochemical phenotype in a preliminary linkage study, we found the strongest support for linkage in regions largely overlapping with those showing linkage with the clinical phenotype (3p, 6p, 16p, 17q, 19q, and 21q). Conclusions Abnormal pCREB signaling could be considered a biochemical phenotype for lithium‐responsive BD.