Exploring the association between a cholecystokinin promoter polymorphism (rs1799923) and posttraumatic stress disorder in combat veterans

Badour, Christal L.; Hirsch, Rebecca; Zhang, Jingmei; Mandel, Howard; Hamner, Mark B.; Wang, Zhewu

doi:10.1016/j.janxdis.2015.09.009

Cited by 8 publications

(3 citation statements)

References 50 publications

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“…In this vein, the panic challenge with CCK4, the gold standard CCK 2 agonist, inhibits the HPA axis and produces a reduction of anxiety [ 199 ]. The association between CCK gene expression and post-traumatic stress disorder [ 133 , 200 ] supports the notion that certain levels of CCK 2 receptor activity might be necessary to restore the normal levels of anxiety [ 201 ].…”

Section: Cck-mediated Neuromodulation Of Anxiety and Schizophreniamentioning

confidence: 78%

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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Section: Cck-mediated Neuromodulation Of Anxiety and Schizophreniamentioning

confidence: 78%

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

Ballaz

Bourin

2021

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“…Cholecystokinin (CCK) is a neuropeptide that has been implicated fear acquisition and extinction in rodents (81). A study in war veterans has demonstrated that a single nucleotide polymorphism in the promoter region of the CCK gene was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms (81).…”

Section: Candidate Gene Studiesmentioning

confidence: 99%

“…A study in war veterans has demonstrated that a single nucleotide polymorphism in the promoter region of the CCK gene was associated with an increased prevalence of PTSD as well as with severity of PTSD symptoms (81). …”

Section: Candidate Gene Studiesmentioning

confidence: 99%

Genetic approaches for the study of PTSD: Advances and challenges

Banerjee

Morrison

Ressler

2017

Neuroscience Letters

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Post-traumatic stress disorder (PTSD) is a highly debilitating stress and anxiety-related disorder that occurs in response to specific trauma or abuse. Genetic risk factors may account for up to 30–40% of the heritability of PTSD. Understanding the gene pathways that are associated with PTSD, and how those genes interact with the fear and stress circuitry to mediate risk and resilience for PTSD will enable the development of targeted therapies to prevent the occurrence of or decrease the severity of this complex multi-gene disorder. This review will summarize recent research on genetic approaches to understanding PTSD risk and resilience in human populations, including candidate genes and their epigenetic modifications, genome-wide association studies and neural imaging genetics approaches. Despite challenges faced within this field of study such as inconsistent results and replications, genetic approaches still offer exciting opportunities for the identification and development of novel therapeutic targets and therapies in the future.

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Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

Asim,

Wang,

Waris

et al. 2024

BioFactors

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Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific role in the brain. As a result, the existing body of literature on the subject is complex and sometimes conflicting. The primary objective of this review article is to provide a comprehensive overview of recent advancements in understanding the central nervous system role of CCK, with a specific emphasis on elucidating CCK's mechanisms for neuroplasticity, exploring its interactions with other neurotransmitters, and discussing its significant involvement in neurological disorders. Studies demonstrate that CCK mediates both inhibitory long‐term potentiation (iLTP) and excitatory long‐term potentiation (eLTP) in the brain. Activation of the GPR173 receptor could facilitate iLTP, while the Cholecystokinin B receptor (CCKBR) facilitates eLTP. CCK receptors' expression on different neurons regulates activity, neurotransmitter release, and plasticity, emphasizing CCK's role in modulating brain function. Furthermore, CCK plays a pivotal role in modulating emotional states, Alzheimer's disease, addiction, schizophrenia, and epileptic conditions. Targeting CCK cell types and circuits holds promise as a therapeutic strategy for alleviating these brain disorders.

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Exploring the association between a cholecystokinin promoter polymorphism (rs1799923) and posttraumatic stress disorder in combat veterans

Abstract: These data offer preliminary evidence supporting an association between the rs1799923 polymorphism in the CCK gene and PTSD. Additional research is needed to better understand the nature of this relationship.

Cited by 8 publications

References 50 publications

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

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

Genetic approaches for the study of PTSD: Advances and challenges

Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

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