Neurocircuitry and Neuroanatomy in Panic Disorder: A Systematic Review.

Background: This review updates our understanding of the neuroanatomical and neurocircuitry factors involved in panic disorder (PD). Many aspects remain undetermined.

Methods: Clinical studies and a randomized controlled trial were identified via PubMed database and included in this review.

Results: The search, following PRISMA guidelines, identified 13 human studies and 3 animal studies. Nine human studies compared brain activity and connectivity between regions in PD patients. Neural activity in the amygdala was highlighted in six studies. The hippocampus had higher activation in PD patients compared to those with social phobia, but generally showed less activity compared to healthy controls. The parahippocampal gyrus and thalamus exhibited greater activation in PD patients than healthy controls. Activity in the prefrontal cortices was also noted, particularly the ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC). Other regions involved included the dorsal midbrain, left brainstem (showing hyperactivation), S1, and right caudate, which showed increased activity in PD patients. The left intraparietal sulcus (IPS) exhibited hypoactivation in response to predictable cues compared to unpredictable or neutral cues within the default mode network (DMN). Three animal studies suggested that electrical and chemical activation of the dorsal periaqueductal gray (dPAG) in rats elicited fight-or-flight behaviors, providing a model for panic attacks.

Conclusions: Neuroimaging studies suggest several key regions involved in PD pathophysiology, including the brainstem, amygdala, hippocampus, parahippocampal gyrus, thalamus, insula, and prefrontal and cingulate cortices. Hypersensitivity in the brainstem and amygdala plays a role in activating the fear network. Further prospective studies are needed to identify the neuroanatomical sites involved in PD and fear circuitry.