Functional neuroanatomy in panic disorder: Status quo of the research

Abstract

AIMTo provide an overview of the current research in the functional neuroanatomy of panic disorder.METHODSPanic 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.RESULTSWe 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.CONCLUSIONIn 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.

Panic disorder respiratory subtype: psychopathology and challenge tests – an update

“…2,38,39,77 Alterations in the neural circuitry that involves the brainstem and fear network and impairments in the pH chemosensory system may be the main mechanisms involved in the respiratory abnormalities observed in PD patients. [78][79][80][81] Individuals diagnosed with PD generally have a high perception of danger or threat. 82 To assess a situation as threatening and mount an anxiety-like response, an individual must first detect environmental stimuli through sensory systems and then identify them as aversive or potentially dangerous.…”

Angst und Panik

“…Studien zum Serotonin-1A-Rezeptor und zur Rezeptorbindung zeigten eine veränderte Serotoninaktivität bei Patienten mit Panikstörung in verschiedenen Hirnregionen, zum Beispiel in ACC, Hypothalamus und Amygdala. Der Serotonin-und insbesondere der Noradrenalinstoffwechsel sind eng verzahnt mit der Stressachse, die durch den Corticotropin-releasing factor (CRF), der im Hypothalamus gebildet wird, die Produktion von Kortison reguliert [56].…”

“…Überblick über innovative Therapieansätze und Stand der Forschung (modifiziert nach[57]) Panikattacken in Ratten aus; ein genetischer Polymorphismus im Gen des Angiotensin II bereitstellenden Enzyms war bei Menschen mit der Panikstörung assoziiert; bisher keine klinischen Studien. Panikstörung war die Aktivierung von orexinproduzierenden Neuronen mit panikähnlichen Reaktionen assoziiert; ein Orexin-Rezeptorantagonist konnte die Reaktion auf panikauslösende Substanzen im Tiermodell abschwächen; eine erhöhte Orexinkonzentration im Liquor wurde bei Patienten mit Panikstörung gefunden; bisher keine klinischen Studien.wurde in frontalen, limbischen sowie temporalen Regionen und in der Insula nachgewiesen[56]. Benzodiazepine, die die Wirkung von GABA verstärken, helfen gut gegen Panikattacken, haben aber ein hohes Abhängigkeitspotenzial.…”

Smaller volumes in the lateral and basal nuclei of the amygdala in patients with panic disorder

“…Recent neuroimaging studies have provided evidence that patients with PD show functional and structural abnormalities in limbic regions, frontal regions, and brainstem regions (see reviews of [ 3 ] and [ 4 ]). The amygdala has been particularly heavily implicated, consistent with its established role in fear and anxiety.…”