Neurobiology of panic disorder

Anantha Shekhar, Susan G. Ball, Tammy J. Sajdyk, Andrew W. Goddard

Research output: Contribution to journalReview article

6 Scopus citations


It has become apparent that PD, like most psychiatric syndrome, has a biologically overlapping, heterogeneous pathophysiology that involves multiple genetic, neurotransmitter and neuroanatomical disturbances leading to the clinical disorder. Accordingly, future theories of PD have to focus on neural circuitry models looking at functional neural networks that could explain the clinical pathophysiology. Such an approach requires that abnormal panic responses can be generated at multiple levels along the neural axis beginning rostrally at the fronto-temporal cortical networks; progressing through deep limbic structures such as the extended amygdala, hippocampus, the bed nucleus of the stria terminalis, the hypothalamus and periaqueductal gray; and caudally the brain stem monoaminergic nuclei and sites regulating cardiorespiratory functions. This complex lattice of interconnected networks stretched along the neural axis is capable of generating panic-like responses with appropriate external or intrinsic stimuli (see Figure 1). Normal functioning of this network is essential for generating appropriate fear and anxiety responses to cope with external and internal threats. Deregulation of one of the "functional nodes" along these pathways could result in a state of pathological panic-prone state, ie, PD. A lot of the functional neuroimaging data reviewed supports the model described. In addition, the neurotransmitter systems implicated in PD, particularly the monoamines, GABA, CRF, and glutamate are all abundant in the structures inluded in these pathways, and therefore also have the potential to modify the function in the panic network. This network model also helps to account for the observation that a variety of pharmacotherapies (SSRIs, TCAs, monoamine oxidase inhibitors, BZDs) can be efficacious for PD, targeting to "normalize" the network function at different levels to produce therapeutic effects. Similarly, such a network can also be modified by cognitive inputs from higher cortical centers, providing a putative mechanism to explain the efficacy of psychological interventions such as cognitive-behavioral therapy (CBT) in treating panic disorder. There is evidence from some animal77 and a variety of human studies78 that prefrontal cortex (PFC) may have a profound modulating effect on this panic circuitry, particularly via the amygdala. It could be hypothesized that CBT techniques, by enabling the subject recognize and cope with panic-eliciting cues, may activate the dorsolateral prefrontal executive (problem solving) regions, which would then activate the more medial regions of the PFC. The medial PFC is know to have a direct inhibitory influence on the amygdalar fear pathways. Thus, CBT could enhance inhibitory drive in the amygdala and enhance extinction of fear and panic responses. In conclusion, like most psychiatric syndromes, no single set of genetic, neuroanatomical or neurotransmitter abnormalities can explain the biological basis of panic disorder. Rather, complex genetic-environmental etiologies may adversely modulate a multi-transmitter, multi-layered network of panic generating pathways to cause the clinical syndrome. Thus, future neurobiological studies will need to incorporate a complex, interconnected and interdependent functional network of neurotransmitter and neuroanatomical systems in the pathophysiology of panic and other anxiety disorders.

Original languageEnglish (US)
Pages (from-to)36-41
Number of pages6
JournalTEN Trends in Evidence-Based Neuropsychiatry
Issue number4
StatePublished - Apr 1 2002

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Health Policy
  • Psychiatry and Mental health

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    Shekhar, A., Ball, S. G., Sajdyk, T. J., & Goddard, A. W. (2002). Neurobiology of panic disorder. TEN Trends in Evidence-Based Neuropsychiatry, 4(4), 36-41.