Anxiety is the common term for the presence of certain feelings—such as worry, dread or fear—that can put the brain and body into the unusually alert state known as the “fight-or-flight” response. While this state isn’t harmful in and of itself, its ongoing or recurring effects can lead to the onset of significant mental health problems called anxiety disorders. In a study published in August 2013 in the journal Neuron, researchers from the Massachusetts Institute of Technology (MIT) uncovered a circuit or pathway in the brain that helps regulate the presence of anxiety. In the future, awareness of this circuit may help provide significantly improved anxiety disorder treatment.
Anxiety and Anxiety Disorders
Anxiety is an unavoidable feature of human emotional life. In the best of circumstances, people remain anxious only for limited periods of time, then revert to a less stressful physical/emotional state that provides a better overall sense of well-being. However, in people affected by anxiety disorders, anxiousness lingers for extended periods of time and/or rises to such intensity that it seriously degrades an affected individual’s ability to function normally and lead an enjoyable life. In this sense, anxiety disorders are magnified forms of the common, everyday anxiety that has always played a role in human societies. Prior to 2013, all officially recognized anxiety-related mental conditions were listed by the American Psychiatric Association under a single heading, known simply as anxiety disorders. However, anxiety-related conditions are now split into three categories, known as anxiety disorders, trauma- and stressor-related disorders, and obsessive-compulsive and related disorders. Illnesses now in the anxiety disorders category include agoraphobia, generalized anxiety disorder, social anxiety disorder, panic disorder, specific phobia and selective mutism. Illnesses in the trauma- and stressor-related disorders category include post-traumatic stress disorder, acute stress disorder and reactive attachment disorder. Illnesses in the obsessive-compulsive and related disorders category include obsessive-compulsive disorder (OCD), hoarding disorder, excoriation (skin-picking) disorder and body dysmorphic disorder.
Current Anxiety Disorder Treatments
Current treatments for anxiety-related conditions include a form of psychotherapy called cognitive behavioral therapy (CBT) and a wide assortment of medications sometimes referred to as anxiolytic (anti-anxiety) drugs. Common examples of anxiolytics include buspirone (Vanspar, Buspar), the antidepressant medications sertraline (Zoloft) and fluoxetine (Prozac), and the sedative medications clonazepam (Klonopin) and alprazolam (Xanax, Niravam). Many people respond well to CBT or anxiolytic medications and see a substantial reduction in their anxiety disorder symptoms. However, significant numbers of people don’t get enough benefit from these treatments to gain the relief they need to function normally.
In the study published in Neuron, MIT researchers used mice to identify the areas of the brain responsible for regulating the presence of anxiety. Both the hippocampus, which is necessary for memory formation, and the amygdala, which is involved in memory and emotion processing, have previously been implicated in anxiety. However, it was unknown how the two interact. To study those interactions, the researchers turned to optogenetics, which allows them to engineer neurons to turn their electrical activity on or off in response to light. For this study, the researchers modified a set of neurons in the basolateral amygdala (BLA); these neurons send long projections to cells of the ventral hippocampus. The researchers tested the mice’s anxiety levels by measuring how much time they were willing to spend in a situation that normally makes them anxious. Mice are naturally anxious in open spaces where they are easy targets for predators, so when placed in such an area, they tend to stay near the edges. When the researchers activated the connection between cells in the amygdala and the hippocampus, the mice spent more time at the edges of an enclosure, suggesting they felt anxious. When the researchers shut off this pathway, the mice became more adventurous and willing to explore open spaces. However, when these mice had this pathway turned back on, they scampered back to the security of the edges. After observing these reactions, the researchers concluded that artificial regulation of the brain circuit in question potentially provides a way to control the level of anxiety experienced by any given individual.
According to the authors of the study published in Neuron, the medications used to treat anxiety disorders often fail to work because they don’t specifically target the mechanisms in the brain responsible for producing anxiety. In fact, in the absence of improved information on how anxiety affects the brain, these medications are more or less bound to provide inadequate treatment benefits in large numbers of affected individuals. By identifying the brain circuit that turns anxiety levels “up” and “down,” the authors believe they have provided a critical step necessary for the eventual discovery and production of better anxiety disorder treatments that have targeted effects rather than less precise, blanket effects.
Because of the invasive nature of the experiments employed in their study, the MIT researchers used mice as substitutes for human beings. This type of substitution is quite common, since human brains and mice brains have highly similar functions in many important respects. The authors of the study note that their findings are preliminary. Before any new anxiety disorder medications become available, future researchers will need to further improve the scientific understanding of the circuit that helps regulate the effects of anxiety inside the brain.