Category: FEATURED NEWS

How ketamine defeats chronic depression

Many chronically depressed and treatment-resistant patients experience immediate relief from symptoms after taking small amounts of the drug ketamine. For a decade, scientists have been trying to explain the observation first made at Yale University.

Today, current evidence suggests that the pediatric anesthetic helps regenerate synaptic connections between brain cells damaged by stress and depression, according to a review of scientific research written by Yale School of Medicine researchers and published in the Oct. 5 issue of the journal Science.

Ketamine works on an entirely different type of neurotransmitter system than current antidepressants, which can take months to improve symptoms of depression and do not work at all for one out of every three patients. Understanding how ketamine works in the brain could lead to the development of an entirely new class of antidepressants, offering relief for tens of millions of people suffering from chronic depression.

"The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century," said Ronald Duman, the Elizabeth Mears and House Jameson Professor of Psychiatry and Professor of Neurobiology.

Duman and George K. Aghajanian, also professor of psychiatry at Yale, are co-authors of the review.

Understanding how ketamine works is crucial because of the drug's limitations. The improvement in symptoms, which are evident just hours after ketamine is administered, lasts only a week to 10 days. In large doses, ketamine can cause short-term symptoms of psychosis and is abused as the party drug "Special K."

In their research, Duman and others show that in a series of steps ketamine triggers release of neurotransmitter glutamate, which in turn stimulates growth of synapses. Research at Yale has shown that damage of these synaptic connections caused by chronic stress is rapidly reversed by a single dose of ketamine.

The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale, and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health.

Efforts to develop drugs that replicate the effects of ketamine have produced some promising results, but they do not act as quickly as ketamine. Researchers are investigating alternatives they hope can duplicate the efficacy and rapid response of ketamine.

Video: http://www.youtube.com/watch?feature=player_embedded&v=hNsIiq-5354#!

 

Journal Reference:

  1. R. S. Duman, G. K. Aghajanian. Synaptic Dysfunction in Depression: Potential Therapeutic Targets. Science, 2012; 338 (6103): 68 DOI: 10.1126/science.1222939

How fear can skew spatial perception

 That snake heading towards you may be further away than it appears. Fear can skew our perception of approaching objects, causing us to underestimate the distance of a threatening one, finds a study published in Current Biology.

"Our results show that emotion and perception are not fully dissociable in the mind," says Emory psychologist Stella Lourenco, co-author of the study. "Fear can alter even basic aspects of how we perceive the world around us. This has clear implications for understanding clinical phobias."

Lourenco conducted the research with Matthew Longo, a psychologist at Birkbeck, University of London.

People generally have a well-developed sense for when objects heading towards them will make contact, including a split-second cushion for dodging or blocking the object, if necessary. The researchers set up an experiment to test the effect of fear on the accuracy of that skill.

Study participants made time-to-collision judgments of images on a computer screen. The images expanded in size over one second before disappearing, to simulate "looming," an optical pattern used instinctively to judge collision time. The study participants were instructed to gauge when each of the visual stimuli on the computer screen would have collided with them by pressing a button.

The participants tended to underestimate the collision time for images of threatening objects, such as a snake or spider, as compared to non-threatening images, such as a rabbit or butterfly.

The results challenge the traditional view of looming, as a purely optical cue to object approach. "We're showing that what the object is affects how we perceive looming. If we're afraid of something, we perceive it as making contact sooner," Longo says.

"Even more striking," Lourenco adds, "it is possible to predict how much a participant will underestimate the collision time of an object by assessing the amount of fear they have for that object. The more fearful someone reported feeling of spiders, for example, the more they underestimated time-to-collision for a looming spider. That makes adaptive sense: If an object is dangerous, it's better to swerve a half-second too soon than a half-second too late."

The researchers note that it's unclear whether fear of an object makes the object appear to travel faster, or whether that fear makes the viewer expand their sense of personal space, which is generally about an arm's length away.

"We'd like to distinguish between these two possibilities in future research. Doing so will allow us to shed insight on the mechanics of basic aspects of spatial perception and the mechanisms underlying particular phobias," Lourenco says.

 

Journal Reference:

  1. Eleonora Vagnoni, Stella F. Lourenco, Matthew R. Longo. Threat modulates perception of looming visual stimuli. Current Biology, 2012; 22 (19): R826 DOI: 10.1016/j.cub.2012.07.053