1. Panic disorder symptoms may be tied to acid-sensing receptor

    August 22, 2017 by Ashley

    From the University of Cincinnati Academic Health Center press release:

    Panic disorder is a syndrome characterized by spontaneous and recurrent episodes of incapacitating anxiety. It typically emerges during adolescence or early adulthood and can take an exhausting emotional and physical toll on the body. Physical symptoms can include heart palpitations, sweating and/or chills, trouble breathing and dizziness, nausea and even chest pain.

    While significant progress in both diagnosis and treatment has been made with panic disorder, a lot is still not known about what triggers these panic symptoms. There is evidence that a pH inbalance disruption in the body, known as acidosis, can unexpectedly cause the panic attack.

    Researchers at the University of Cincinnati (UC) have found that a particular receptor in the body — acid-sensing T cell death associated gene-8 (TDAG8) — may have significant relevance to the physiological response in panic disorder. The research, a collaboration between Jeffrey Strawn, MD, and Renu Sah, PhD, both associate professors in the Department of Psychiatry and Behavioral Neuroscience at the UC College of Medicine, appears online in advance of publication in the journal Brain, Behavior, and Immunity.

    The TDAG8 receptor, a pH sensor, was first identified in immune cells of the body where it regulates inflammatory responses. Studies of animal models in Sah’s lab identified TDAG8 in immune cells of the brain, called microglia.

    “Although we had reported the potential relevance of TDAG8 in panic physiology in the lab, we were uncertain whether the receptor would play a role in panic disorder. It was important for us to validate this in patients with this disorder,” says Sah.

    Strawn says the UC research team then embarked on a basic science-clinical collaboration, seeking to understand the receptor’s expression in adolescents and young adults.

    “We evaluated the role of this receptor in patients with panic disorder (including adolescents who were close to the onset of panic disorder). We saw a relationship between this receptor and panic disorder symptoms, in addition to differences between patients with panic disorder and healthy individuals,” says Strawn, who is also director of the Anxiety Disorders Research program at UC.

    The study evaluated blood samples of 15 individuals between the ages 15 to 44 with a diagnosis of panic disorder and 17 healthy control participants. Anxiety symptom severity was also assessed in the study.

    The study, though small, strengthened the previous pre-clinical findings.

    “This pilot study — the first to evaluate the TDAG8 expression in patients with panic disorder — reveals significantly increased levels in patients with panic disorder, relative to their healthy control subjects,” says Strawn. “We found an association with TDAG8 and symptom severity, and we observed that there was a relationship between this receptor and treatment response in patients who had been treated with antidepressants.”

    Strawn says the findings show a direct link between increased TDAG8 expression and severity of panic disorder as well as raise the possibility that patients in treatment may reflect a “remission” of TDAG8 expression. “It will be important for additional studies to further explain the functional relevance of TDAG8 and associated inflammatory processes as well as other acid sensors in patients with panic disorder to explore the role of TDAG8 with predicting treatment response,” he says.

    Sah notes that further research could demonstrate whether altered TDAG8 is a result of a genetic variation or other factors. She also says that in future studies, perhaps drugs targeting TDAG8 or associated inflammatory responses may be developed for panic disorder.


  2. New risk factors for anxiety disorders

    March 20, 2017 by Ashley

    From the University of Würzburg press release:

    Mental, social and inherited factors all play a role in anxiety disorders. In the journal Molecular Psychiatry, a research team from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, describes a hitherto unknown genetic pathway for developing such diseases: They pinpointed at least four variants of the GLRB gene (glycine receptor B) as risk factors for anxiety and panic disorders. More than 5000 voluntary participants and 500 patients afflicted by panic disorder took part in the study that delivered these results.

    In Germany, around 15 percent of adults suffer from anxiety and panic disorders. Some people may have an extreme fear of spiders or other objects while others have breathing difficulties and accelerated heart beat in small rooms or large gatherings of people. With some afflicted persons, the anxiety attacks occur for no apparent cause. Many patients suffer from the detrimental impacts on their everyday lives — they often have problems at work and withdraw from social contacts.

    How are fear and anxiety triggered? How do anxiety disorders arise and evolve?

    Scientists from Münster, Hamburg and Würzburg have looked into these questions within the scope of Collaborative Research Center (CRC) TR 58 funded by Deutsche Forschungsgemeinschaft. Their goal is to develop new therapies that are better tailored to the individual patients. Anxiety disorders can be treated with drugs and behaviour therapy for instance.

    Gene triggers hyperekplexia

    The discovery that different variants of the GLRB gene are associated with anxiety disorders might also contribute to the development of improved therapies. The gene had been known to the researchers for some time, albeit only in connection with a different disease:

    “Some mutations of the gene cause a rare neurological disorder called hyperekplexia,” explains Professor Jürgen Deckert, member of the CRC and Director of the Department of Psychiatry at the JMU University Hospital. The patients are permanently hypertonic and show pronounced startle responses, which may even cause sufferers to fall involuntarily. Similar to persons suffering from anxiety disorders, these patients develop behaviour to avoid potentially frightening situations.

    The “fear network” in the brain is activated

    But the GLRB gene variants that have recently been associated with anxiety and panic disorders for the first time are different from the ones described above. They occur more frequently and presumably entail less severe consequences. But they, too, trigger overshooting startle responses, and as a result may excessively activate the brain’s “fear network.” High-resolution images of the brain activities of study participants provided the clues for the Würzburg scientists.

    “The results point to a hitherto unknown pathway of developing an anxiety disorder,” Deckert says. He believes that further investigations are now necessary to determine whether these findings can be harnessed to develop new or individual therapies. For example, it is conceivable to bring the “fear network” that is misregulated by the GLRB gene back on track by administering drugs.