Neurobiology and Mechanisms of Antidepressant Treatment Response in Anxiety

The functional anatomy of anxiety focuses on a central fear response system, with the amygdala serving as a pivotal hub. Critical to understanding the different forms of human anxiety is the relationship of the amygdala with the prefrontal executive systems that mediate cognitive and other functions. Examining the time-sequenced activation of neural centers allows exploration of preconscious (implicit) and conscious processing of information and sheds light on the nature of emotions and cognitions. Mechanisms of treatment response in anxiety can be modeled based on brain function. Psychotherapy focusing on cognitive behavioral techniques uses a top-down approach. Pharmacological treatments with antidepressants are known to influence brainstem monoaminergic systems at the molecular level, with physiological consequences, the “stress” axis to enhance negative feedback, neurogenesis in the hippocampus, and neurosteroids involved in enhancing γ-aminobutyric acid transmission. An important question is: which of these effects provides a differential benefit in anxiety versus depression?