Recent advances in the neurobiology of anxiety disorders: implications for novel therapeutics.
Anxiety disorders are a highly prevalent and disabling class of psychiatric disorders. This review focuses on new directions in neurobiological research and implications for the development of novel psychopharmacological treatments. Neuroanatomical and neuroimaging research in anxiety disorders has centered on the role of the amygdala, reciprocal connections between the amygdala and the prefrontal cortex, and, most recently, alterations in interoceptive processing by the anterior insula. Anxiety disorders are characterized by alterations in a diverse range of neurochemical systems, suggesting ample novel targets for drug therapies. Corticotropin-releasing factor (CRF) concentrations are elevated in a subset of anxiety disorders, which suggests the potential utility of CRF receptor antagonists. Pharmacological blockade of the memory-enhancing effects of stress hormones such as glucocorticoids and noradrenaline holds promise as a preventative approach for trauma-related anxiety. The glutamatergic system has been largely overlooked as a potential pharmacological target, although convergent preclinical, neuroimaging, and early clinical findings suggest that glutamate receptor antagonists may have potent anxiolytic effects. Glutamatergic receptor agonists (e.g., D-cycloserine) also have an emerging role in the treatment of anxiety as facilitators of fear extinction during concurrent behavioral interventions. The neuropeptides substance P, neuropeptide Y, oxytocin, orexin, and galanin are each implicated in anxiety pathways, and neuropeptide analogs or antagonists show early promise as anxiolytics in preclinical and/or clinical research. Each of these active areas of research holds promise for expanding and improving evidence-based treatment options for individuals suffering with clinical anxiety.
Mathew
Sanjay J
SJ
Department of Psychiatry, Mount Sinai School of Medicine, One Gustave L. Levy Place Box 1217, New York, NY 10029. sanjay.mathew@mssm.edu
Price
Rebecca B
RB
Charney
Dennis S
DS
D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D003346:Corticotropin-Releasing Hormone / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use; D005239:Fear / Q000502:physiology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology; D009446:Neurobiology; D009479:Neuropeptides / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology; D017470:Receptors, Glutamate / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D009479:Neuropeptides; D018019:Receptors, Corticotropin-Releasing Hormone; D017470:Receptors, Glutamate; D003346:Corticotropin-Releasing Hormone