Developmental pathology, dopamine, stress and schizophrenia

Psychological stress is a contributing factor for a wide variety of neuropsychiatric diseases including substance use disorders, anxiety, depression and schizophrenia. However, it has not been conclusively determined how stress augments the symptoms of these diseases. Here we review evidence that the ventral hippocampus may be a site of convergence whereby a number of seemingly discrete risk factors, including stress, may interact to precipitate psychosis in schizophrenia. Specifically, aberrant hippocampal activity has been demonstrated to underlie both the elevated dopamine neuron activity and associated behavioral hyperactivity to dopamine agonists in a verified animal model of schizophrenia. In addition, stress, psychostimulant drug use, prenatal infection and select genetic polymorphisms all appear to augment ventral hippocampal function that may therefore exaggerate or precipitate psychotic symptoms. Such information is critical for our understanding into the pathology of psychiatric disease with the ultimate aim being the development of more effective therapeutics.

Research highlights▶ Ventral hippocampal (vHipp) activity sets the gain of the dopamine signal. ▶ Stress, drug abuse, genetic and environmental factors interact to alter vHipp activity. ▶ Aberrant vHipp function underlies the augmented dopamine system function in a model of schizophrenia.