Posts tagged panic disorders

Posts tagged panic disorders
Neuroscientists have discovered a brain pathway that underlies the emotional behaviours critical for survival.

New research by the University of Bristol, published in the Journal of Physiology, has identified a chain of neural connections which links central survival circuits to the spinal cord, causing the body to freeze when experiencing fear.
Understanding how these central neural pathways work is a fundamental step towards developing effective treatments for emotional disorders such as anxiety, panic attacks and phobias.
An important brain region responsible for how humans and animals respond to danger is known as the PAG (periaqueductal grey), and it can trigger responses such as freezing, a high heart rate, increase in blood pressure and the desire for flight or fight.
This latest research has discovered a brain pathway leading from the PAG to a highly localised part of the cerebellum, called the pyramis. The research went on to show that the pyramis is involved in generating freezing behaviour when central survival networks are activated during innate and learnt threatening situations.
The pyramis may therefore serve as an important point of convergence for different survival networks in order to react to an emotionally challenging situation.
Dr Stella Koutsikou, first author of the study and Research Associate in the School of Physiology and Pharmacology at the University of Bristol, said: “There is a growing consensus that understanding the neural circuits underlying fear behaviour is a fundamental step towards developing effective treatments for behavioural changes associated with emotional disorders.”
Professor Bridget Lumb, Professor of Systems Neuroscience, added: “Our work introduces the novel concept that the cerebellum is a promising target for therapeutic strategies to manage dysregulation of emotional states such as panic disorders and phobias.”
The researchers involved in this work are all members of Bristol Neuroscience which fosters interactions across one of the largest communities of neuroscientists in the UK.
Professor Richard Apps said: “This is a great example of how Bristol Neuroscience brings together expertise in different fields of neuroscience leading to exciting new insights into brain function.”
Portion of Hippocampus Found to Play Role in Modulating Anxiety
Columbia University Medical Center (CUMC) researchers have found the first evidence that selective activation of the dentate gyrus, a portion of the hippocampus, can reduce anxiety without affecting learning. The findings suggest that therapies that target this brain region could be used to treat certain anxiety disorders, such as panic disorder and post-traumatic stress syndrome (PTSD), with minimal cognitive side effects. The study, conducted in mice, was published in the online edition of the journal Neuron.
The dentate gyrus is known to play a key role in learning. Some evidence suggests that the structure also contributes to anxiety. “But until now no one has been able to figure out how the hippocampus could be involved in both processes,” said senior author Rene Hen, PhD, professor of neuroscience and pharmacology (in psychiatry) at CUMC.
“It turns out that different parts of the dentate gyrus have somewhat different functions, with the dorsal portion largely dedicated to learning and the ventral portion dedicated to anxiety,” said lead author Mazen A. Kheirbek, PhD, a postdoctoral fellow in neuroscience at CUMC.
To examine the role of the dentate gyrus in learning and anxiety, the investigators used a state-of-the-art technique called optogenetics, in which light-sensitive proteins, or opsins, are genetically inserted into neurons in the brains of mice. Neurons with these genes can then be selectively activated or silenced through the application of light (via a fiber-optic strand), allowing researchers to study the function of the cells in real time. Previously, the only way to study the dentate gyrus was to silence portions of it using such long-term manipulations as drugs or lesions, techniques that yielded conflicting results.
In the current study, opsins were inserted into dentate gyrus granule cells (the principal cells of the dentate gyrus). The researchers then activated or silenced the ventral or dorsal portions of the dentate gyrus for three minutes at a time, while the mice were subjected to two well-validated anxiety tests (the elevated plus maze and the open field test).
“Our main findings were that elevating cell activity in the dorsal dentate gyrus increased the animals’ desire to explore their environment. But this also disrupted their ability to learn. Elevating activity in the ventral dentate gyrus lowered their anxiety, but had no effect on learning,” said Dr. Kheirbek. The effects were completely reversible — that is, when the stimulation was turned off, the animals returned to their previous anxiety levels.
“The therapeutic implication is that it may be possible to relieve anxiety in people with anxiety disorders by targeting the ventral dentate gyrus, perhaps with medications or deep-brain stimulation, without affecting learning,” said Dr. Hen, who is also director of the Division of Integrative Neuroscience, the New York State Psychiatric Institute, and a member of The Kavli Institute for Brain Science. “Given the immediate behavioral impact of such manipulations, these strategies are likely to work faster than current treatments, such as serotonin reuptake inhibitors.”
According to Dr. Hen, such an intervention would probably work best in people with panic disorder or PTSD. “There is evidence that people with these anxiety disorders tend to have a problem with pattern separation — the ability to distinguish between similar experiences,” he said. “In other words, they overgeneralize, perceiving minor threats to be the same as major ones, leading to a heightened state of anxiety. Such patients could conceivably benefit from therapies that fine-tune hippocampal activity.”
Dr. Hen and his team are currently exploring strategies aimed at modulating the activity of the ventral dentate gyrus by stimulating neurogenesis in the ventral dentate gyrus. “Indeed the dentate gyrus is one of the few areas in the adult brain where neurons are continuously produced, a phenomenon termed adult hippocampal neurogenesis,” added Dr. Hen.
(Image: Catherine E. Myers, Memory Loss and the Brain)