Systematic Reviews
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 22, 2017; 7(1): 12-33
Published online Mar 22, 2017. doi: 10.5498/wjp.v7.i1.12
Functional neuroanatomy in panic disorder: Status quo of the research
Thomas Sobanski, Gerd Wagner
Thomas Sobanski, Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Thueringen-Kliniken GmbH, 07318 Saalfeld, Germany
Gerd Wagner, Psychiatric Brain and Body Research Group Jena, Department of Psychiatry and Psychotherapy, Jena University Hospital, 07743 Jena, Germany
Author contributions: All authors contributed to this paper with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Conflict-of-interest statement: The authors declare no conflict of interests for this article.
Data sharing statement: As this was a systematic review of published data there were no participants to be approached for informed consent for data sharing. No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Thomas Sobanski, MD, Chief, Department of Psychiatry, Psychotherapy, and Psychosomatic Medicine, Thueringen-Klinken GmbH, Rainweg 68, 07318 Saalfeld, Germany.
Telephone: +49-3671-541750 Fax: +49-3671-541759
Received: September 5, 2016
Peer-review started: September 5, 2016
First decision: October 20, 2016
Revised: November 16, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: March 22, 2017

To provide an overview of the current research in the functional neuroanatomy of panic disorder.


Panic disorder (PD) is a frequent psychiatric disease. Gorman et al (1989; 2000) proposed a comprehensive neuroanatomical model of PD, which suggested that fear- and anxiety-related responses are mediated by a so-called “fear network” which is centered in the amygdala and includes the hippocampus, thalamus, hypothalamus, periaqueductal gray region, locus coeruleus and other brainstem sites. We performed a systematic search by the electronic database PubMed. Thereby, the main focus was laid on recent neurofunctional, neurostructural, and neurochemical studies (from the period between January 2012 and April 2016). Within this frame, special attention was given to the emerging field of imaging genetics.


We noted that many neuroimaging studies have reinforced the role of the “fear network” regions in the pathophysiology of panic disorder. However, recent functional studies suggest abnormal activation mainly in an extended fear network comprising brainstem, anterior and midcingulate cortex (ACC and MCC), insula, and lateral as well as medial parts of the prefrontal cortex. Interestingly, differences in the amygdala activation were not as consistently reported as one would predict from the hypothesis of Gorman et al (2000). Indeed, amygdala hyperactivation seems to strongly depend on stimuli and experimental paradigms, sample heterogeneity and size, as well as on limitations of neuroimaging techniques. Advanced neurochemical studies have substantiated the major role of serotonergic, noradrenergic and glutamatergic neurotransmission in the pathophysiology of PD. However, alterations of GABAergic function in PD are still a matter of debate and also their specificity remains questionable. A promising new research approach is “imaging genetics”. Imaging genetic studies are designed to evaluate the impact of genetic variations (polymorphisms) on cerebral function in regions critical for PD. Most recently, imaging genetic studies have not only confirmed the importance of serotonergic and noradrenergic transmission in the etiology of PD but also indicated the significance of neuropeptide S receptor, CRH receptor, human TransMEMbrane protein (TMEM123D), and amiloride-sensitive cation channel 2 (ACCN2) genes.


In light of these findings it is conceivable that in the near future this research will lead to the development of clinically useful tools like predictive biomarkers or novel treatment options.

Keywords: Panic disorder, Anterior cingulate cortex, Amygdala, Insula, Functional magnetic resonance imaging, Diffusion tensor imaging, Voxel-based morphometry, Imaging genetics, Serotonin, Noradrenaline

Core tip: This systematic review is focused on the most current research in the functional neuroanatomy of panic disorder. Recent neurofunctional studies suggest that the “fear network”, as proposed by Gorman et al, may need to be amended by additional regions (ACC, insula). Most recently, imaging genetic studies have not only confirmed the importance of serotonergic and noradrenergic transmission in the etiology of panic disorder (PD) but also indicated the significance of neuropeptide S receptor and corticotropin releasing hormone receptor gene variants. Imaging genetics studies are of major importance for the refining of the neuroanatomical model, because genetic risk variants may significantly influence fear network activity in PD.