CCK-B receptor gene and response to cholecystokinin-tetrapeptide in healthy volunteers

Koszycki, Diana; Prichard, Zoë M.; Fiocco, Alexandra J.; Shlik, Jakov; Kennedy, James L.; Bradwejn, Jacques

doi:10.1016/j.peptides.2012.02.014

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…A handful of candidate genes have been tested for association with AS. One study reported association of CCKBR with AS and cholecystokinin‐induced panic [Koszycki et al, ]. A German PD research consortium reported association of AS with NPSR1 [Domschke et al, ], CRHR1 [Weber et al, ], and the gene coding for microRNA hsa‐miR‐4717‐5p, which regulates the gene RGS2 [Hommers et al, ], in conjunction with other PD‐related phenotypes.…”

Section: Resultsmentioning

confidence: 99%

The genetics of anxiety‐related negative valence system traits

Savage

Sawyers

Roberson‐Nay

et al. 2016

American J of Med Genetics Pt B

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NIMH’s Research Domain Criteria (RDoC) domain of negative valence systems (NVS) captures constructs of negative affect such as fear and distress traditionally subsumed under the various internalizing disorders. Through its aims to capture dimensional measures that cut across diagnostic categories and are linked to underlying neurobiological systems, a large number of phenotypic constructs have been proposed as potential research targets. Since “genes” represent a central “unit of analysis” in the RDoC matrix, it is important for studies going forward to apply what is known about the genetics of these phenotypes as well as fill in the gaps of existing knowledge. This article reviews the extant genetic epidemiological data (twin studies, heritability) and molecular genetic association findings for a broad range of putative NVS phenotypic measures. We find that scant genetic epidemiological data is available for experimentally-derived measures such as attentional bias, peripheral physiology, or brain-based measures of threat response. The molecular genetic basis of NVS phenotypes is in its infancy, since most studies have focused on a small number of candidate genes selected for putative association to anxiety disorders (ADs). Thus, more research is required to provide a firm understanding of the genetic aspects of anxiety-related NVS constructs.

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Section: Resultsmentioning

confidence: 99%

The genetics of anxiety‐related negative valence system traits

Savage

Sawyers

Roberson‐Nay

et al. 2016

American J of Med Genetics Pt B

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“…One study found an association of the tryptophan hydroxylase gene isomer 2 ( TPH2 ) with subjects experiencing panic attacks after CCK infusion (Maron et al, 2008). Another study found an association to the CCKBR gene in subjects with greater pre-challenge anxiety (Koszycki et al, 2012). Additional studies have utilized CCK-peptide infusion to determine its effects on EEG and ERP measures in healthy human subjects (Knott et al, 2002; Knott et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

“…In human subjects, CCK infusion has also been demonstrated to increase eye-blink startle as well as produce a mild increase in anxiety and heart rate as well as increases in plasma concentrations of ACTH, cortisol, prolactin, and growth hormone (Shlik et al, 1999). Since, CCK peptides have been demonstrated to enhance anxiety, several studies have investigated the role of the CCK system in anxiety and panic disorders, using CCK-related peptide administration as a challenge method (Koszycki et al, 2012; Maron et al, 2008). These CCK challenge studies were able to explore genetic factors in panic disorders by performing candidate gene analyses to find alleles that may be associated with greater sensitivity to the CCK peptides.…”

Section: Discussionmentioning

confidence: 99%

Variants Near CCK Receptors are Associated With Electrophysiological Responses to Pre-pulse Startle Stimuli in a Mexican American Cohort

et al. 2015

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Neurophysiological measurements of the response to prepulse and startle stimuli have been suggested to represent an important endophenotype for both substance dependence and other select psychiatric disorders. We have previously shown, in young adult Mexican Americans (MA), that presentation of a short delay acoustic prepulse, prior to the startle stimuli can elicit a late negative component at about 400 msec (N4S), in the event-related potential (ERP), recorded from frontal cortical areas. In the present study we investigated whether genetic factors associated with this endophenotype could be identified. The study included 420 (age 18 – 30 years) MA men (n=170) and women (n=250). DNA was genotyped using an Affymetrix Axiom Exome1A chip. An association analysis revealed that the CCKAR and CCKBR (cholecystokinin A and B receptor) genes each had a nearby variant that showed suggestive significance with the amplitude of the N4S component to prepulse stimuli. The neurotransmitter cholecystokinin (CCK), along with its receptors, CCKAR and CCKBR, have been previously associated with psychiatric disorders, suggesting that variants near these genes may play a role in the prepulse/startle response in this cohort.

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“…It binds two receptor subtypes, namely CCK 1 and CCK 2 , expressed at relatively low and high levels in the brain [ 2 ]. Relevant behavioral functions attributed to CCK are memory and cognition [ 3 - 6 ], reward-related behaviors [ 7 - 9 ], and more importantly, anxiety [ 10 - 16 ]. Yet systemic administration of selective CCK 2 agonists like CCK4 and pentagastrin triggers panic in humans [ 10 , 17 , 18 ], CCK 2 antagonists have never been proven to ameliorate human anxiety [ 19 - 21 ].…”

Section: Introductionmentioning

confidence: 99%

Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A “Dimmer-Switch” Hypothesis

Ballaz

Bourin

2021

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: Cholecystokin (CCK), the most abundant brain neuropeptide, is involved in relevant behavioral functions like memory, cognition, and reward through its interactions with the opioid and dopaminergic systems in the limbic system. CCK excites neurons by binding two receptors, CCK1 and CCK2, expressed at low and high levels in the brain, respectively. Historically, CCK2 receptors have been related to the induction of panic attacks in humans. Disturbances in brain CCK expression also underlie the physiopathology of schizophrenia, which is attributed to the modulation by CCK1 receptors of the dopamine flux in the basal striatum. Despite this evidence, neither CCK2 receptor antagonists ameliorate human anxiety nor have CCK agonists consistently shown neuroleptic effects in clinical trials. A neglected aspect of the function of brain CCK is its neuromodulatory role in mental disorders. Interestingly, CCK is expressed in pivotal inhibitory interneurons that sculpt cortical dynamics and the flux of nerve impulses across corticolimbic areas and the excitatory projections to mesolimbic pathways. At the basal striatum, CCK modulates the excitability of glutamate, the release of inhibitory GABA, and the discharge of dopamine. Here we focus on how CCK may reduce rather than trigger anxiety by regulating its cognitive component. Adequate levels of CCK release in the basal striatum may control the interplay between cognition and reward circuitry, which is critical in schizophrenia. Hence, it is proposed that disturbances in the excitatory/inhibitory interplay modulated by CCK may contribute to the imbalanced interaction between corticolimbic and mesolimbic neural activity found in anxiety and schizophrenia.

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CCK-B receptor gene and response to cholecystokinin-tetrapeptide in healthy volunteers

Cited by 8 publications

References 39 publications

The genetics of anxiety‐related negative valence system traits

The genetics of anxiety‐related negative valence system traits

Variants Near CCK Receptors are Associated With Electrophysiological Responses to Pre-pulse Startle Stimuli in a Mexican American Cohort

Cholecystokinin-Mediated Neuromodulation of Anxiety and Schizophrenia: A “Dimmer-Switch” Hypothesis

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