Stress, anxiety and schizophrenia and neurotrophic factors: the pioneer studies with nerve growth factor.

The aim of this review is to highlight past and ongoing studies on neurotrophin (NT) role, in particular focusing on nerve growth factor (NGF), on behavioral response to stress, agonistic and emotional behavior, anxiety, and schizophrenia. One of the first evidences of NGF involvement in behavioral response to a social challenge was published in 1986. In male mice, agonistic encounters caused a massive NGF release into the bloodstream and in the hypothalamus. Subsequent studies revealed that this NGF release was not strictly linked to agonistic behavior, but to mice hierarchical status, with subordinates having higher NGF levels than dominants. This observation led to the hypothesis and later to the demonstration that NGF release is associated to anxiety-related behaviors. Later studies provided evidence for the involvement of NTs, including NGF, in the development of neuropsychiatric disorders. Interestingly, pharmacological treatment can reduce the effects of the maldevelopment and neuropathology due to NT imbalance during early periods of life crucial for development. Further understanding of the core pathophysiological mechanism for neurodegenerative and psychiatric disorders will eventually provide tools for amelioration of symptoms of those psychiatric disorders characterized by an NT imbalance.