Journal
NATURE MEDICINE
Volume 22, Issue 3, Pages 238-249Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.4050
Keywords
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Funding
- US National Institute of Mental Health [MH045481, MH093897]
- National Center for Advancing Translational Science [1UH2TR000960-01]
- National Institute on Alcohol Abuse and Alcoholism [P50AA12870, M01RR00125]
- Yale Center for Clinical Investigation [UL1 RR024139]
- state of Connecticut's Department of Mental Health and Addiction Services (DMHAS)
- Yale University School of Medicine
- Brain and Behavior Research Foundation
- Pfeiffer Research Foundation
- National Center for Posttraumatic Stress Disorder
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Depression is a common, devastating illness. Current pharmacotherapies help many patients, but high rates of a partial response or no response, and the delayed onset of the effects of antidepressant therapies, 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 that is 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, it has recently been shown that treatment with new agents results in an improvement in mood ratings within hours of dosing patients who are resistant to typical antidepressants. Within a similar time scale, these new agents have also been shown to reverse the synaptic deficits caused by stress.
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