Dopamine is a brain
neurotransmitter involved in the pathology of
schizophrenia. The
dopamine hypothesis states that, in
schizophrenia, dopaminergic signal transduction is hyperactive. The
cAMP-response element binding protein (CREB) is an intracellular
protein that regulates the expression of genes that are important in dopaminergic neurons.
Dopamine affects the phosphorylation of CREB via
G protein-coupled receptors.
Neurotrophins, such as
brain derived growth factor (
BDNF), are critical regulators during neurodevelopment and synaptic plasticity. The CREB is one of the major regulators of
neurotrophin responses since phosphorylated CREB binds to a specific sequence in the promoter of
BDNF and regulates its transcription. Moreover, susceptibility genes associated with
schizophrenia also target and stimulate the activity of CREB. Abnormalities of CREB expression is observed in the brain of individuals suffering from
schizophrenia, and two variants (-933T to C and -413G to A) were found only in schizophrenic patients. The CREB was also involved in the
therapy of animal models of
schizophrenia. Collectively, these findings suggest a link between CREB and the pathophysiology of
schizophrenia. This review provides an overview of CREB structure, expression, and biological functions in the brain and its interaction with
dopamine signaling,
neurotrophins, and susceptibility genes for
schizophrenia. Animal models in which CREB function is modulated, by either overexpression of the
protein or knocked down through gene deletion/mutation, implicating CREB in
schizophrenia and
antipsychotic drugs efficacy are also discussed. Targeting research and drug development on CREB could potentially accelerate the development of novel medications against
schizophrenia.