Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants

Abstract

Depression is a common, devastating illness. Current pharmacotherapies help many patients, but there are high rates of partial- or non-response and the delayed onset of the effects of antidepressant leave many patients inadequately treated. However, new insights into the neurobiology of stress and human mood disorders have shed light on mechanisms underlying the vulnerability of individuals to depression and have pointed to novel antidepressants. Environmental events and other risk factors contribute to depression through converging molecular and cellular mechanisms that disrupt neuronal function and morphology, resulting in dysfunction of the circuitry essential for mood regulation and cognitive function. Although current antidepressants such as serotonin reuptake inhibitors produce subtle changes that take effect in weeks or months, new agents have recently shown improvement in mood ratings within hours of dosing in patients resistant to typical antidepressants. These new agents have also been shown to reverse the synaptic deficits caused by stress within a similar time scale.