Anxiety is one of the most common psychiatric disorders characterized by excessive worry and fear about a number of events or activities which an individual finds difficult to control. Often times the individual experiences extreme symptoms of fatigue, difficulty concentrating or mind going blank, irritability, muscle tension, and sleep disturbance. Anxiety disorders appear to be caused by an interaction of biopsychosocial factors, including genetic vulnerability, which interact with situations, stress, or trauma to produce clinically significant syndromes. But for most people, anxiety may be linked to one or more underlying health issues. There are situations where anxiety signs and symptoms may be the first indicators of a medical illness.
A recent study by the Neuroscientists at Cold Spring Harbor Laboratory (CSHL) investigating the neurological basis of anxiety in the brain has identified a neural circuit in the amygdala, a specialized region of the brain that is regarded as the seat of emotion processing that gives rise to anxiety. The results of the research has revealed the critical role of a molecule called dynorphin, which could serve as a target for treatment of anxiety-related disorders including post-traumatic stress disorder (PTSD). The experiment was conducted using animal models where they were able to discover the role of the molecule, somatostatin. Their experiments in mice discovered that the mechanism leading to anxiety begins with increased excitation in the central amygdala of neurons that express a molecule called somatostatin (SOM). Overstimulation of these neurons (for instance, when an animal feels afraid after perceiving a threat) causes the release of a signaling molecule called dynorphin. This aberrant signaling interferes with a mechanism in the circuit that normally tamps down the signal of SOM neurons. Because this inhibition fails, Li’s team learned, SOM neurons in the BNST now become overexcited. The net result is a display of anxious behavior.
The findings of this research corroborates previous research findings. Previous studies have shown that two regions in the amygdala — the central amygdala and the BNST (bed nucleus of the stria terminalis) — coordinate short-term and long-term responses to various kinds of threatening stimuli. But these previous research did not reveal the underlying circuit and cellular mechanisms in these regions that control the generation of anxiety.
Hence, the neuroscientists discovered that Dynorphin signaling was identified as the force behind elevated anxiety. The team not only showed this in mice with neurons lacking Erbb4, but also, importantly, in genetically normal mice that were exposed to such stress.
“That’s why we think this is an important circuit in anxiety,” says Li. “By manipulating it in mice, we are actually able to ameliorate anxiety.” “Our results suggest that dynorphin can drive anxiety and therefore could be a cellular target for treating increased anxiety induced by stress. Our next step is to understand whether the receptors for dynorphin are expressed in the SOM+ neurons in the central amygdala itself or if they’re expressed by some other inputs onto the BNST.” Li adds.