Why ketamine produces a fast antidepressant response

ScienceDaily (June 16, 2011) — UT Southwestern Medical Center scientists are shedding new light on why the anesthetic drug ketamine produces a fast-acting antidepressant response in patients with treatment-resistant depression.

The drug's robust effect at low doses as a fast-acting antidepressant potentially has use in emergency rooms with high-risk patients.

"Ketamine produces a very sharp increase that immediately relieves depression," said Dr. Lisa Monteggia, associate professor of psychiatry at UT Southwestern and senior author of the study published June 15 in Nature.

Typical antidepressant medications -- one of the most widely prescribed classes of drugs in the U.S. each year -- often take several weeks to relieve symptoms of depression. If they are not successful within 12 weeks, physicians must prescribe a different antidepressant to produce a response.

"Ketamine produces a fast-acting antidepressant effect, and we hope our investigation provides critical information to treat depression effectively sooner," Dr. Monteggia said.

"We now have a novel pathway to explore that may provide potential for the development of faster-acting and longer-lasting antidepressants," Dr. Monteggia said.

The next step, Dr. Monteggia said, is to investigate further the short- and long-term effects of the changes that occur when the brain cells communicate with each other.

Other UT Southwestern researchers involved in the study were Anita Autry, student research assistant in psychiatry; Dr. Megumi Adachi, instructor in psychiatry; Dr. Elena Nosyreva, instructor in neuroscience; Dr. Elisa Na, postdoctoral researcher in psychiatry; Mr. Maarteen Los, visiting junior researcher in psychiatry; Mr. Peng-fei Cheng, formerly in psychiatry; and Dr. Ege Kavalali, professor of neuroscience and physiology.

The study was funded by the National Institute of Mental Health.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by UT Southwestern Medical Center.

Journal Reference:

Anita E. Autry, Megumi Adachi, Elena Nosyreva, Elisa S. Na, Maarten F. Los, Peng-fei Cheng, Ege T. Kavalali, Lisa M. Monteggia. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature, 2011; DOI: 10.1038/nature10130

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Children's personalities linked to their chemical response to stress

ScienceDaily (July 25, 2011) — Is your kid a "dove" -- cautious and submissive when confronting new environments, or perhaps you have a "hawk" -- bold and assertive in unfamiliar settings?

These basic temperamental patterns are linked to opposite hormonal responses to stress -- differences that may provide children with advantages for navigating threatening environments, researchers report in a study published online July 8, 2011, in Development and Psychopathology.

"Divergent reactions -- both behaviorally and chemically -- may be an evolutionary response to stress," says Patrick Davies, professor of psychology at the University of Rochester and the lead author of the study. "These biological reactions may have provided our human ancestors with adaptive survival advantages. For example, dovish compliance may work better under some challenging family conditions, while hawkish aggression could be an asset in others." This evolutionary perspective, says Davies, provides an important counterpoint to the prevailing idea in psychology that "there is one healthy way of being and that all behaviors are either adaptive or maladaptive."

Coauthor Melissa Sturge-Apple agrees: "When it comes to healthy psychological behavior, one size does not fit all." The assistant professor of psychology at the University of Rochester adds that the findings "give us insight into how basic behavioral patterns are also chemical patterns."

To understand the role of stress in children's reactions, Davies, Sturge-Apple, and Dante Cicchetti, a professor of child development and psychiatry at the University of Minnesota, focused on parental conflict in young families. "Research has shown that exposure to repeated aggression between parents is a significant stressor for children," explains Davies.

The study looked at 201 two-year-old toddlers, all from impoverished families with similar socio-economic profiles. Based on interviews and questionnaires with the mothers, the authors assessed children's exposure to levels of aggression between parents.

The researchers also documented the dove or hawk tendencies of the toddlers in a variety of unfamiliar situations. Children who showed dovish tendencies were vigilant and submissive in the face of novelty. The toddlers clung to their mothers, cried, or froze when encountering new surroundings. Hawks used bold, aggressive, and dominating strategies for coping with challenge. They fearlessly explored unknown objects and new environments.

When the researchers exposed the children to a mildly stressful simulated telephone argument between their parents, distinct patterns of hormonal reactions emerged. Children exposed to high levels of interparental aggression at home showed different reactions to the telephone quarrel. Doves with parents who fought violently produced elevated levels of cortisol, a hormone that is thought to increase a person's sensitivity to stress. Hawks from such stressful home environments put the breaks on cortisol production, which is regarded as a marker for diminishing experiences of danger and alarm.

This high-and-low-cortisol reactivity provides different developmental advantages and disadvantages, the authors write. Heightened cortisol levels characteristic of the doves were related to lower attention problems but also put them at risk for developing anxiety and depression over time. By contrast, the lower cortisol levels for hawks in aggressive families were associated with lower anxiety problems; however, at the same time, these children were more prone to risky behavior, including attention and hyperactivity problems.

Story Source:

The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by University of Rochester, via EurekAlert!, a service of AAAS.

Journal Reference:

Patrick T. Davies, Melissa L. Sturge-Apple, Dante Cicchetti. Interparental aggression and children's adrenocortical reactivity: Testing an evolutionary model of allostatic load. Development and Psychopathology, 2011; 23 (03): 801 DOI: 10.1017/S0954579411000319

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

View the original article here