Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression

The dopamine system has been implicated in a number of psychiatric disorders, including depression and schizophrenia. Here, Grace describes evidence for disrupted afferent regulation of dopamine neuron firing in these disorders and considers the role of stress in driving this pathology. The dopamine system is unique among the brain's modulatory systems in that it has discrete projections to specific brain regions involved in motor behaviour, cognition and emotion. Dopamine neurons exhibit several activity patterns — including tonic and phasic firing — that are determined by a combination of endogenous pacemaker conductances and regulation by multiple afferent systems. Emerging evidence suggests that disruptions in these regulatory systems may underlie the pathophysiology of several psychiatric disorders, including schizophrenia and depression.