Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic

Ruland, Tillmann; Domschke, Katharina; Schütte, Valerie; Zavorotnyy, Maxim; Kugel, Harald; Notzon, Swantje; Vennewald, Nadja; Ohrmann, Patricia; Arolt, Volker; Pfleiderer, Bettina; Zwanzger, Peter

doi:10.1016/j.euroneuro.2015.07.011

Cited by 20 publications

(15 citation statements)

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“…Polymorphisms of the NPS receptor gene might genetically drive altered fear circuit function and therefore increase the risk of PD in humans. Ruland et al[107] performed a study of CCK-4-induced panic on brain Glx levels and enrolled thirty-five healthy volunteers with functional neuropeptide S receptor gene (NPSR1) rs324981 A/T variants. MRS during the challenge revealed significantly lower increases of Glx/Cr levels in T risk allele carriers as compared to AA homozygotes in bilateral ACC.…”

Section: Resultsmentioning

confidence: 99%

“…NPS receptors are widely distributed in the central nervous system with highest expressions in the cortex, thalamus, hypothalamus and the amygdala[106]. In a recent imaging genetic study, blunted glutamatergic ACC response due to CCK-4-induced panic was reported in NPSR1 risk allele carriers[107]. The results of additional imaging genetic studies on genetic NPSR1 variations will be presented below.…”

Section: Discussionmentioning

confidence: 99%

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Functional neuroanatomy in panic disorder: Status quo of the research

Sobanski¹,

Wagner²

2017

WJP

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional neuroanatomy in panic disorder: Status quo of the research

Sobanski¹,

Wagner²

2017

WJP

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“…NPS activates Gα q and Gα s signaling pathways via NPSR inducing mobilization of Ca 2+ and activating accumulation of cAMP to exert its functions [27,29]. In the meanwhile, we learned from other studies that the NPS precursor is coexpressed with glutamate in the brainstem [27], and a corresponding NPSR1 gene variation showed that NPSR potentially modulates glutamatergic activity in the ACC to increase the risk for panic disorder [70]. In conclusion, the NPS-NPSR system seems interested in involving in GABA and glutamate neurotransmission to process negative emotion.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture Alleviates Pain‐Related Emotion by Upregulating the Expression of NPS and Its Receptor NPSR in the Anterior Cingulate Cortex and Hypothalamus

Fang

Xiang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Correspondence should be addressed to Jianqiao Fang; fangjianqiao7532@163.com and Junying Du;Objective. Electroacupuncture (EA) is reported effective in alleviating pain-related emotion; however, the underlying mechanism of its effects still needs to be elucidated. e NPS-NPSR system has been validated for the involvement in the modulation of analgesia and emotional behavior. Here, we aimed to investigate the role of the NPS-NPSR system in the anterior cingulate cortex (ACC), hypothalamus, and central amygdala (CeA) in the use of EA to relieve affective pain modeled by complete Freund's adjuvant-(CFA-) evoked conditioned place aversion (C-CPA). Materials and Methods. CFA injection combined with a CPA paradigm was introduced to establish the C-CPA model, and the elevated O-maze (EOM) was used to test the behavioral changes after model establishment. We further explored the expression of NPS and NPSR at the protein and gene levels in the brain regions of interest by immunofluorescence staining and quantitative real-time PCR. Results. We observed that EA stimulation delivered to the bilateral Zusanli (ST36) and Kunlun (BL60) acupoints remarkably inhibited sensory pain, pain-evoked place aversion, and anxiety-like behavior. e current study showed that EA significantly enhanced the protein expression of this peptide system in the ACC and hypothalamus, while the elevated expression of NPSR protein alone was just confined to the affected side in the CeA. Moreover, EA remarkably upregulated the mRNA expression of NPS in CeA, ACC, and hypothalamus and NPSR mRNA in the hypothalamus and CeA. Conclusions. ese data suggest the effectiveness of EA in alleviating affective pain, and these benefits may at least partially be attributable to the upregulation of the NPS-NPSR system in the ACC and hypothalamus.

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“…On the one hand, NPS has crucial functions in extinguishing anxiety and conditioned fear responses [3][4][5] , and administration of NPS (both intranasally and intracerebroventricularly) has anxiolytic properties [6][7][8][9][10] . On the other hand, NPS has been shown to activate hypothalamic-pituitary-adrenal axis and increases the release of ACTH [3][4][5] and mutations that make NPSR more active, for both single nucleotide polymorphisms and mutations at the promoter sequence, causes subjects to be more susceptible to have panic disorder [3][4][5][10][11][12][13][14][15][16][17] .…”

Section: Discussionmentioning

confidence: 99%

Relationship between panic disorder and plasma neuropeptide-S level

Baykan

Esen

et al. 2018

Arch. Clin. Psychiatry (São Paulo)

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Background: Panic disorder has long been associated with the changes in various neurotransmitters, such as Neuropeptide-S (NPS). Objective: In this study we aimed to determine whether there is a relationship between blood NPS levels and panic disorder. Methods: Twenty nine patients with panic disorder and thirty two healthy control subjects who were age and gender matched were enrolled to the study. Blood samples were taken from participants and plasma NPS levels were quantified by using an ELISA kit. Results: In the study group, median NPS blood level was 16.7 pg/mL and in the control group it was 32.5 pg/mL. There was a statistically significant difference (p = 0.021). Using receiver operating characteristics (ROC) curve, sensitivity and specificity of NPS blood level, for diagnosing panic disorder was calculated, and it was found 79.3% and 56.25% respectively (AUC:0.672, 95% CI: 0.540-0.787). Discussion: Malfunction at the NPS modulatory system in the cortical areas (which is causing excitations in brain areas, such as amygdala and hypothalamus) does not only increase anxiety symptoms and risk of panic disorder but also causes panic disorder patients to have lower plasma NPS levels than the control group. Therefore it can be argued that such malfunction can be treated with a systemic treatment. H et al. / Arch Clin Psychiatry. 2018;45(4):79-81 Baykan

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Neuropeptide S receptor gene variation modulates anterior cingulate cortex Glx levels during CCK-4 induced panic

Cited by 20 publications

References 26 publications

Functional neuroanatomy in panic disorder: Status quo of the research

Functional neuroanatomy in panic disorder: Status quo of the research

Electroacupuncture Alleviates Pain‐Related Emotion by Upregulating the Expression of NPS and Its Receptor NPSR in the Anterior Cingulate Cortex and Hypothalamus

Relationship between panic disorder and plasma neuropeptide-S level

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