Alterations in phosphorylated cAMP response element-binding protein (pCREB) signaling: an endophenotype of lithium-responsive bipolar disorder?

作者：Alda Martin^*; Shao Li; Wang Jun Feng; de Lara Catalina Lopez; Jaitovich Groisman Iris; Lebel Veronique; Sun Xiujun; Duffy Anne; Grof Paul; Rouleau Guy A; Turecki Gustavo; Young L Trevor

来源：Bipolar Disorders, 2013, 15(8): 824-831.

DOI：10.1111/bdi.12131

• bipolar disorder
• cAMP response element-binding protein (CREB)
• cAMP response element-binding protein (CREB) phosphorylation
• genetic linkage
• lithium response

ObjectivesAbnormalities 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). %26lt;br%26gt;MethodsWe 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). %26lt;br%26gt;ResultsBasal 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). %26lt;br%26gt;ConclusionsAbnormal pCREB signaling could be considered a biochemical phenotype for lithium-responsive BD.

• 出版日期2013-12
• 单位McGill