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Cholecystokinin B receptor gene polymorphism (rs2941026) is associated with anxious personality and suicidal thoughts in a longitudinal study

Published online by Cambridge University Press:  20 December 2021

Aneth Lvovs
Affiliation:
School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Tartu, Estonia
Denis Matrov
Affiliation:
School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia
Triin Kurrikoff
Affiliation:
Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Tartu, Estonia
Toomas Veidebaum
Affiliation:
National Institute for Health Development, Tallinn, Estonia
Jaanus Harro*
Affiliation:
School of Natural Sciences and Health, Tallinn University, Tallinn, Estonia Chair of Neuropsychopharmacology, Institute of Chemistry, University of Tartu, Tartu, Estonia
*
Author for correspondence: Jaanus Harro, Email: jaanus.harro@ut.ee

Abstract

Objectives:

Cholecystokinin is a neuropeptide with a role in the neurobiology of adaptive behaviour that is implicated in anxiety disorders, while the underlying mechanisms currently remain insufficiently explained. The rs2941026 variation in the cholecystokinin B receptor gene has previously been associated with trait anxiety. Our aim was to investigate associations between the CCKB receptor gene polymorphism rs2941026 with anxiety, personality, depressiveness and suicidality in a longitudinal study of late adolescence and early adulthood.

Methods:

We used reports on trait and state anxiety, depressiveness and suicidal thoughts, as well as Affective Neuroscience Personality Scales, from the two birth cohorts of the Estonian Children Personality, Behaviour and Health Study. We measured associations between the CCKBR gene rs2941026 and anxiety-related phenotypes both longitudinally and cross-sectionally at ages 15, 18, 25 and 33.

Results:

Homozygosity for both alleles of the CCKBR rs2941026 was associated with higher trait and state anxiety in the longitudinal analysis. Cross-sectional comparisons were statistically significant at ages 18 and 25 for trait anxiety and at ages 25 and 33 for state anxiety. Higher depressiveness and suicidal thoughts were associated with the A/A genotype at age 18. Additionally, homozygosity for the A-allele was related to higher FEAR and SADNESS in the Affective Neuroscience Personality Scales. The genotype effects were more apparent in females, who displayed higher levels of negative affect overall.

Conclusions:

CCKBR genotype is persistently associated with negative affect in adolescence and young adulthood. The association of the CCKBR rs2941026 genotype with anxiety-related phenotypes is more pronounced in females.

Type
Original Article
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of Scandinavian College of Neuropsychopharmacology

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References

Abelson, JL, Nesse, RM and Vinik, AI (1991) Stimulation of corticotropin release by pentagastrin in normal subjects and patients with panic disorder. Biological Psychiatry 29, 12201223.CrossRefGoogle ScholarPubMed
Abramov, U, Raud, S, Innos, J, Lasner, H, Kurrikoff, K, Türna, T, Puussaar, T, Okva, K, Matsui, T and Vasar, E (2008) Different housing conditions alter the behavioural phenotype of CCK(2) receptor-deficient mice. Behavioural Brain Research 193, 108116.CrossRefGoogle ScholarPubMed
Adams, JB, Pyke, RE, Costa, J, Cutler, NR, Schweizer, E, Wilcox, CS, Wisselink, PG, Greiner, M, Pierce, MW and Pande, AC (1995) A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder. Journal of Clinical Psychopharmacology 15, 428434.CrossRefGoogle ScholarPubMed
Altemus, M, Sarvaiya, N and Epperson, CN (2014) Sex differences in anxiety and depression clinical perspectives. Frontiers in Neuroendocrinology 35, 320330.CrossRefGoogle ScholarPubMed
Ballaz, SJ, Akil, H and Watson, SJ (2007) The CCK-system mediates adaptation to novelty-induced stress in the rat: a pharmacological evidence. Neuroscience Letters 428, 2732.CrossRefGoogle ScholarPubMed
Ballaz, SJ, Bourin, M, Akil, H and Watson, SJ (2020) Blockade of the cholecystokinin CCK-2 receptor prevents the normalization of anxiety levels in the rat. Progress in Neuropsychopharmacology and Biological Psychiatry 96, 109761.CrossRefGoogle ScholarPubMed
Becker, C, Thiébot, MH, Touitou, Y, Hamon, M, Cesselin, F and Benoliel, JJ (2001) Enhanced cortical extracellular levels of cholecystokinin-like material in a model of anticipation of social defeat in the rat. Journal of Neuroscience 21, 262269.CrossRefGoogle Scholar
Becker, C, Zeau, B, Rivat, C, Blugeot, A, Hamon, M and Benoliel, JJ (2008) Repeated social defeat-induced depression-like behavioral and biological alterations in rats: involvement of cholecystokinin. Molecular Psychiatry 13, 10791092.CrossRefGoogle ScholarPubMed
Belzung, C, Pineau, N, Beuzen, A and Misslin, R (1994) PD135158, a CCK-B antagonist, reduces “state,” but not “trait” anxiety in mice. Pharmacology Biochemistry and Behavior 49, 433436.CrossRefGoogle Scholar
Binkley, K, King, N, Poonai, N, Seeman, P, Ulpian, C and Kennedy, J (2001) Idiopathic environmental intolerance: Increased prevalence of panic disorder–associated cholecystokinin B receptor allele 7. Journal of Allergy and Clinical Immunology 107, 887890.CrossRefGoogle ScholarPubMed
Bowers, ME and Ressler, KJ (2015) Interaction between the cholecystokinin and endogenous cannabinoid systems in cued fear expression and extinction retention. Neuropsychopharmacology 40, 688700.CrossRefGoogle ScholarPubMed
Bradwejn, J, Koszycki, D and Bourin, M (1991a) Dose ranging study of the effects of cholecystokinin in healthy volunteers. Journal of Psychiatry and Neuroscience 16, 91.Google ScholarPubMed
Bradwejn, J, Koszycki, D and Meterissian, G (1990) Cholecystokinin-tetrapeptide induces panic attacks in patients with panic disorder. The Canadian Journal of Psychiatry 35, 8385.CrossRefGoogle ScholarPubMed
Bradwejn, J, Koszycki, D and Shriqui, C (1991b) Enhanced sensitivity to cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings. Archives of General Psychiatry 48, 603610.CrossRefGoogle ScholarPubMed
Canetto, SS and Sakinofsky, I (1998) The gender paradox in suicide. Suicide and Life-Threatening Behavior 28, 123.CrossRefGoogle ScholarPubMed
Chen, Q, Nakajima, A, Meacham, C and Tang, YP (2006) Elevated cholecystokininergic tone constitutes an important molecular/neuronal mechanism for the expression of anxiety in the mouse. Proceedings of the National Academy of Sciences USA 103, 38813886.CrossRefGoogle ScholarPubMed
Chung, L and Moore, SD (2007) Cholecystokinin enhances GABAergic inhibitory transmission in basolateral amygdala. Neuropeptides 41, 453463.CrossRefGoogle ScholarPubMed
Cooper, DN (2010) Functional intronic polymorphisms: Buried treasure awaiting discovery within our genes. Human Genomics 4, 284288.CrossRefGoogle ScholarPubMed
Davis, KL, Panksepp, J and Normansell, L (2003) The affective neuroscience personality scales: normative data and implications. Neuropsychoanalysis 5, 5769.CrossRefGoogle Scholar
de Montigny, C (1989) Cholecystokinin tetrapeptide induces panic-like attacks in healthy volunteers: preliminary findings. Archives of General Psychiatry 46(6), 511517.CrossRefGoogle ScholarPubMed
Ebihara, M, Ohba, H, Hattori, E, Yamada, K and Yoshikawa, T (2003) Transcriptional activities of cholecystokinin promoter haplotypes and their relevance to panic disorder susceptibility. American Journal of Medical Genetics B Neuropsychiatric Genetics 118B(1), 3235.CrossRefGoogle ScholarPubMed
Erlich, JC, Bush, DE and LeDoux, JE (2012) The role of the lateral amygdala in the retrieval and maintenance of fear-memories formed by repeated probabilistic reinforcement. Frontiers in Behavioral Neuroscience 6, 16.CrossRefGoogle ScholarPubMed
Ersig, AL, Schutte, DL, Standley, J, Leslie, E, Zimmerman, B, Kleiber, C, Hanrahan, K, Murray, JC and McCarthy, AM (2017) Relationship of genetic variants with procedural pain, anxiety, and distress in children. Biological Research for Nursing 19, 339349.CrossRefGoogle ScholarPubMed
Farook, JM, McLachlan, CS, Zhu, YZ, Lee, L, Moochhala, SM and Wong, PTH (2004) The CCK2 agonist BC264 reverses freezing behavior habituation in PVG hooded rats on repeated exposures to a cat. Neuroscience Letters 355, 205208.CrossRefGoogle ScholarPubMed
Flint, A, Bradwejn, J, Vaccarino, F, Gutkowska, J, Palmour, R and Koszycki, D (2002) Aging and panicogenic response to cholecystokinin tetrapeptide: an examination of the cholecystokinin system. Neuropsychopharmacology 27, 663671.Google ScholarPubMed
Fuchshuber, J, Hiebler-Ragger, M, Kresse, A, Kapfhammer, HP and Unterrainer, HF (2019) Do primary emotions predict psychopathological symptoms? A multigroup path analysis. Frontiers in Psychiatry 10, 610.CrossRefGoogle ScholarPubMed
Greisen, MH, Bolwig, TG and Wörtwein, G (2005) Cholecystokinin tetrapeptide effects on HPA axis function and elevated plus maze behaviour in maternally separated and handled rats. Behavioural Brain Research 161, 204212.CrossRefGoogle ScholarPubMed
Griebel, G and Holmes, A (2013) 50 years of hurdles and hope in anxiolytic drug discovery. Nature Reviews Drug Discovery 12, 667687.CrossRefGoogle ScholarPubMed
Gruber, D, Gilling, KE, Albrecht, A, Bartsch, JC, Çalışkan, G, Richter-Levin, G, Stork, O, Heinemann, U and Behr, J (2015) 5-HT receptor-mediated modulation of granule cell inhibition after juvenile stress recovers after a second exposure to adult stress. Neuroscience 293, 6779.CrossRefGoogle ScholarPubMed
Gupta, PR and Prabhavalkar, K (2021) Combination therapy with neuropeptides for the treatment of anxiety disorder. Neuropeptides 102127.CrossRefGoogle ScholarPubMed
Harro, J (2006) CCK and NPY as anti-anxiety treatment targets: promises, pitfalls, and strategies. Amino Acids 31(3), 215230.CrossRefGoogle Scholar
Harro, J, Kiivet, RA, Lang, A and Vasar, E (1990a). Rats with anxious or non-anxious type of exploratory behaviour differ in their brain CCK-8 and benzodiazepine receptor characteristics. Behavioural Brain Research 39, 6371.CrossRefGoogle ScholarPubMed
Harro, J, Laas, K, Eensoo, D, Kurrikoff, T, Sakala, K, Vaht, M, Parik, J, Mäestu, J and Veidebaum, T (2019) Orexin/hypocretin receptor gene (HCRTR1) variation is associated with aggressive behaviour. Neuropharmacology 156, 107527.CrossRefGoogle ScholarPubMed
Harro, J, Löfberg, C, Rehfeld, JF and Oreland, L (1996) Cholecystokinin peptides and receptors in the rat brain during stress. Naunyn-Schmiedeberg’s Archives of Pharmacology 354, 5966.CrossRefGoogle ScholarPubMed
Harro, J, Marcusson, J and Oreland, L (1992) Alterations in brain cholecystokinin receptors in suicide victims. European Neuropsychopharmacology 2, 5763.CrossRefGoogle ScholarPubMed
Harro, J and Oreland, L (1992) Age-related differences of cholecystokinin receptor binding in the rat brain. Progress in Neuropsychopharmacology and Biological Psychiatry 16, 369375.CrossRefGoogle ScholarPubMed
Harro, J, Põld, M and Vasar, E (1990b). Anxiogenic-like action of caerulein, a CCK-8 receptor agonist, in the mouse: influence of acute and subchronic diazepam treatment. Naunyn-Schmiedeberg’s Archives of Pharmacology 341, 6267.Google ScholarPubMed
Harro, J, Vasar, E and Bradwejn, J (1993) CCK in animal and human research on anxiety. Trends in Pharmacological Sciences 14, 244249.CrossRefGoogle ScholarPubMed
Harro, M, Eensoo, D, Kiive, E, Merenäkk, L, Alep, J, Oreland, L and Harro, J (2001) Platelet monoamine oxidase in healthy 9-and 15-years old children: the effect of gender, smoking and puberty. Progress in Neuropsychopharmacology and Biological Psychiatry 25, 14971511.CrossRefGoogle ScholarPubMed
Hill, WD, Weiss, A, Liewald, DC, Davies, G, Porteous, DJ, Hayward, C, Mclntosh, AM, Gale, CR and Deary, IJ (2020) Genetic contributions to two special factors of neuroticism are associated with affluence, higher intelligence, better health, and longer life. Molecular Psychiatry 25, 30343052.CrossRefGoogle ScholarPubMed
Hökfelt, T, Barde, S, Xu, ZQ, Kuteeva, E, Rüegg, J, Maitre, EL, Risling, M, Kehr, J, Ihnatko, R, Theodorsson, E, Palkovits, M, Deakin, W, Bagdy, G, Juhasz, G, Prud’homme, HJ, Mechawar, N, Diaz-Heijtz, R and Ögren, SO (2018) Neuropeptide and small transmitter coexistence: fundamental studies and relevance to mental illness. Frontiers in Neural Circuits 12, 106.CrossRefGoogle ScholarPubMed
Hösing, VG, Schirmacher, A, Kuhlenbäumer, G, Freitag, C, Sand, P, Schlesiger, C, Jacob, C, Fritze, J, Franke, P, Rietschel, M, Garritsen, H, Nöthen, MM, Fimmers, R, Stögbauer, F and Deckert, J (2004) Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder. Journal of Neural Transmission Suppl 68, 147156.CrossRefGoogle Scholar
Jorm, AF (2000) Does old age reduce the risk of anxiety and depression? A review of epidemiological studies across the adult life span. Psychological Medicine 30, 1122.CrossRefGoogle ScholarPubMed
Karisetty, BC, Khandelwal, N, Kumar, A and Chakravarty, S (2017) Sex difference in mouse hypothalamic transcriptome profile in stress-induced depression model. Biochemical and Biophysical Research Communications 486, 11221128.CrossRefGoogle ScholarPubMed
Keiser, AA, Turnbull, LM, Darian, MA, Feldman, DE, Song, I and Tronson, NC (2017) Sex differences in context fear generalization and recruitment of hippocampus and amygdala during retrieval. Neuropsychopharmacology 42, 397407.CrossRefGoogle ScholarPubMed
Kennedy, JL, Bradwejn, J, Koszycki, D, King, N, Crowe, R, Vincent, J and Fourie, O (1999) Investigation of cholecystokinin system genes in panic disorder. Molecular Psychiatry 4, 284285.CrossRefGoogle ScholarPubMed
Knowles, KA and Olatunji, BO (2020) Specificity of trait anxiety in anxiety and depression: meta-analysis of the State-Trait Anxiety inventory. Clinical Psychology Review 82, 101928.CrossRefGoogle ScholarPubMed
Kofoed, P, Woldbye, DP, Hansen, TO, Hansen, ES, Knudsen, GM, Bolwig, TG and Rehfeld, JF (2010) Gene variations in the cholecystokinin system in patients with panic disorder. Psychiatric Genetics 20, 5964.CrossRefGoogle Scholar
Kopin, AS, McBride, EW, Gordon, MC, Quinn, SM and Beinborn, M (1997) Inter-and intraspecies polymorphisms in the cholecystokinin-B/gastrin receptor alter drug efficacy. Proceedings of the National Academy of Sciences USA 94, 1104311048.CrossRefGoogle Scholar
Koszycki, D, Zacharko, RM and Bradwejn, J (1996) Influence of personality on behavioral response to cholecystokinin-tetrapeptide in patients with panic disorder. Psychiatry Research 62, 131138 CrossRefGoogle ScholarPubMed
Kramer, MS, Cutler, NR, Ballenger, JC, Patterson, WN, Mendels, J, Chenault, A, Shrivastava, R, Matzura-Wolfe, D, Lines, C and Reines, S (1995) A placebo-controlled trial of L-365,260, a CCKB antagonist, in panic disorder. Biological Psychiatry 37, 462466.CrossRefGoogle ScholarPubMed
Leicht, G, Mulert, C, Eser, D, Sämann, PG, Ertl, M, Laenger, A, Karch, S, Pogarell, O, Meindl, T, Czisch, M and Rupprecht, R (2013) Benzodiazepines counteract rostral anterior cingulate cortex activation induced by cholecystokinin-tetrapeptide in humans. Biological Psychiatry 73, 337344.CrossRefGoogle ScholarPubMed
Levey, DF, Gelernter, J, Polimanti, R, Zhou, H, Cheng, Z, Aslan, M, Quaden, R, Concato, J, Radhakrishnan, K, Bryois, J, Sullivan, PF, the Million Veteran Program and Stein MB (2020) Reproducible genetic risk loci for anxiety: results from∼ 200,000 participants in the Million Veteran Program. American Journal of Psychiatry 177, 223232.CrossRefGoogle ScholarPubMed
Li, X, Luo, Z, Gu, C, Hall, LS, Mclntosh, AM, Zeng, Y, Porteous, DJ, Hayward, C, Li, M, Yao, YG, Zhang, C, Luo, XJ, and the 23andMe Research Team7 (2018) Common variants on 6q16. 2, 12q24. 31 and 16p13. 3 are associated with major depressive disorder. Neuropsychopharmacology 43, 21462153.CrossRefGoogle ScholarPubMed
Löfberg, C, Harro, J, Gottfries, CG and Oreland, L (1996) Cholecystokinin peptides and receptor binding in Alzheimer’s disease. Journal of Neural Transmission 103, 851860.CrossRefGoogle ScholarPubMed
Lovell, PV and Mello, CV (2011) Brain expression and song regulation of the cholecystokinin gene in the zebra finch (Taeniopygia guttata). Journal of Comparative Neurology 519, 211237.CrossRefGoogle Scholar
Maron, E, Nikopensius, T, Kõks, S, Altmäe, S, Heinaste, E, Vabrit, K, Tammekivi, V, Hallast, P, Koido, K, Kurg, A, Metspalu, A, Vasar, E, Vasar, V and Shlik, J (2005) Association study of 90 candidate gene polymorphisms in panic disorder. Psychiatric Genetics 15, 1724.CrossRefGoogle ScholarPubMed
Matsuda, K, Yoshida, D, Watanabe, K, Yokobori, E, Konno, N and Nakamachi, T (2020) Effect of intracerebroventricular administration of two molecular forms of sulfated CCK octapeptide on anxiety-like behavior in the zebrafish Danio rerio. Peptides 130, 170330.CrossRefGoogle ScholarPubMed
McLean, CP and Anderson, ER (2009) Brave men and timid women? A review of the gender differences in fear and anxiety. Clinical Psychology Review 29, 496505.CrossRefGoogle ScholarPubMed
Mills, JD, Chen, BJ, Ueberham, U, Arendt, T and Janitz, M (2016) The antisense transcriptome and the human brain. Journal of Molecular Neuroscience 58, 115.CrossRefGoogle ScholarPubMed
Miranda-Mendizabal, A, Castellví, P, Parés-Badell, O, Alayo, I, Almenara, J, Alonso, I, Blasco, MJ, Cebrià, A, Gabilondo, A, Gili, M, Lagares, C, Piqueras, JA, Rodríguez-Jiménez, T, Rodríguez-Marín, J, Roca, M, Soto-Sanz, V, Vilagut, G and Alonso, J (2019) Gender differences in suicidal behavior in adolescents and young adults: systematic review and meta-analysis of longitudinal studies. International Journal of Public Health 64, 265283.CrossRefGoogle Scholar
Miyasaka, K, Ohta, M, Masuda, M, Kawanami, T, Matsumoto, M and Funakoshi, A (1995) Sex difference in gene expressions of cholecystokinin (CCK) and CCK receptor in young and old rats. Archives of Gerontology Geriatrics 21, 157165.CrossRefGoogle ScholarPubMed
Montag, C, Widenhorn-Müller, K, Panksepp, J and Kiefer, M (2017) Individual differences in Affective Neuroscience Personality Scale (ANPS) primary emotional traits and depressive tendencies. Comprehensive Psychiatry 73, 136142.CrossRefGoogle ScholarPubMed
Montgomery, SA and Åsberg, M (1979) A new depression scale designed to be sensitive to change. The British Journal of Psychiatry 134, 382389.CrossRefGoogle ScholarPubMed
Ochi, R, Fujita, N, Goto, N, Nguyen, ST, Le, DT, Matsushita, K, Ono, T, Nishijo, H and Urakawa, S (2020) Region-specific brain area reductions and increased cholecystokinin positive neurons in diabetic OLETF rats: implication for anxiety-like behavior. The Journal of Physiological Sciences 70, 14.CrossRefGoogle ScholarPubMed
Pande, AC, Greiner, M, Adams, JB, Lydiard, RB and Pierce, MW (1999) Placebo-controlled trial of the CCK-B antagonist, CI-988, in panic disorder. Biological Psychiatry 46, 860862.CrossRefGoogle ScholarPubMed
Panksepp, J (1998) Affective Neuroscience: The Foundations of Human and Animal Emotions. New York, Oxford: Oxford University Press.Google Scholar
Panksepp, J, Burgdorf, J, Beinfeld, MC, Kroes, RA and Moskal, JR (2004) Regional brain cholecystokinin changes as a function of friendly and aggressive social interactions in rats. Brain Research 1025, 7584.CrossRefGoogle ScholarPubMed
Panksepp, J and Harro, J (2004) Future of neuropeptides in biological psychiatry and emotional psychopharmacology: goals and strategies. In Panksepp, J (ed), Textbook of Biological Psychiatry. Hoboken, NJ: John Wiley & Sons, pp. 627659.Google Scholar
Panksepp, J and Watt, D (2011) Why does depression hurt? Ancestral primary-process separation-distress (PANIC/GRIEF) and diminished brain reward (SEEKING) processes in the genesis of depressive affect. Psychiatry 74, 513.CrossRefGoogle ScholarPubMed
Parker, G and Brotchie, H (2010) Gender differences in depression. International Review of Psychiatry 22, 429436.CrossRefGoogle ScholarPubMed
Pingault, JB, Falissard, B, Côté, S and Berthoz, S (2012) A new approach of personality and psychiatric disorders: a short version of the Affective Neuroscience Personality Scales. PLoS One 7, e41489.CrossRefGoogle Scholar
Radu, D, Ahlin, A, Svanborg, P and Lindefors, N (2003) Pentagastrin test for anxiety psychophysiology and personality. Psychopharmacology 166, 139145.CrossRefGoogle Scholar
Rearick, D, Prakash, A, McSweeny, A, Shepard, SS, Fedorova, L and Fedorov, A (2011) Critical association of ncRNA with introns. Nucleic Acids Research 39, 23572366.CrossRefGoogle ScholarPubMed
Regev-Tsur, S, Demiray, YE, Tripathi, K, Stork, O, Richter-Levin, G and Albrecht, A (2020) Region-specific involvement of interneuron subpopulations in trauma-related pathology and resilience. Neurobiology of Disease 143, 104974.CrossRefGoogle ScholarPubMed
Rovira-Esteban, L, Gunduz-Cinar, O, Bukalo, O, Limoges, A, Brockway, E, Müller, K, Fenno, L, Kim, YS, Ramakrishnan, C, Andrási, T, Deisseroth, K, Holmes, A and Hájos, N (2019) Excitation of diverse classes of cholecystokinin interneurons in the basal amygdala facilitates fear extinction. eNeuro 6, doi: 10.1523/ENEURO.0220-19.2019.CrossRefGoogle ScholarPubMed
Sadeghi, M, Radahmadi, M and Reisi, P (2015) Effects of repeated treatment with cholecystokinin sulfated octapeptide on passive avoidance memory under chronic restraint stress in male rats. Advanced Biomedical Research 4, 150.Google ScholarPubMed
Sears, C, Wilson, J and Fitches, A (2013) Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort. Journal of Affective Disorders 151, 611617.CrossRefGoogle Scholar
Sherrin, T, Heng, KYC, Zhu, YZ, Tang, YM, Lau, G and Tan, GH (2004) Cholecystokinin-B receptor gene expression in cerebellum, pre-frontal cortex and cingulate gyrus and its association with suicide. Neuroscience Letters 357, 107110.CrossRefGoogle ScholarPubMed
Shindo, S and Yoshioka, N (2005) Polymorphisms of the cholecystokinin gene promoter region in suicide victims in Japan. Forensic Science International 150, 8590.CrossRefGoogle ScholarPubMed
Shiozaki, K, Kawabe, M, Karasuyama, K, Kurachi, T, Hayashi, A, Ataka, K, Iwai, H, Takeno, H, Hayasaka, O, Kotani, T, Komatsu, M and Inui, A (2020) Neuropeptide Y deficiency induces anxiety-like behaviours in zebrafish (Danio rerio). Scientific Reports 10, 5913.CrossRefGoogle Scholar
Spielberger, CD, Gorsuch, RL, Lushene, R, Vagg, PR and Jacobs, GA (1983) Manual for the State-Trait Anxiety Inventory: STAI (form Y). Palo Alto, CA: Consulting Psychologists Press.Google Scholar
Tomson-Johanson, K, Kaart, T, Kiivet, RA, Veidebaum, T and Harro, J (2020) Low cholesterol levels in children predict impulsivity in young adulthood. Acta Neuropsychiatrica 32, 196205.CrossRefGoogle ScholarPubMed
Tõru, I, Aluoja, A, Võhma, U, Raag, M, Vasar, V, Maron, E and Shlik, J (2010) Associations between personality traits and CCK-4-induced panic attacks in healthy volunteers. Psychiatry Research 178, 342347.CrossRefGoogle ScholarPubMed
Vázquez-León, P, Campos-Rodríguez, C, Gonzalez-Pliego, C and Miranda-Páez, A (2018) Differential effects of cholecystokinin (CCK-8) microinjection into the ventrolateral and dorsolateral periaqueductal gray on anxiety models in Wistar rats. Hormones and Behavior 106, 105111.CrossRefGoogle ScholarPubMed
Vialou, V, Bagot, RC, Cahill, ME, Ferguson, D, Robison, AJ, Dietz, DM, Fallon, B, Mazei-Robison, M, Ku, SM, Harrigan, E, Winstanley, CA, Joshi, T, Feng, J, Berton, O and Nestler, EJ (2014) Prefrontal cortical circuit for depression-and anxiety-related behaviors mediated by cholecystokinin: role of ΔFosB. Journal of Neuroscience 34, 38783887.CrossRefGoogle ScholarPubMed
Wang, Z, Valdes, J, Noyes, R, Zoega, T and Crowe, RR (1998) Possible association of a cholecystokinin promotor polymorphism (CCK-36CT) with panic disorder. American Journal of Medical Genetics 81, 228234.3.0.CO;2-S>CrossRefGoogle ScholarPubMed
Wendt, FR, Pathak, GA, Levey, DF, Nuñez, YZ, Overstreet, C, Tyrrell, C, Adhikari, K, De Angelis, F, Tylee, DS, Goswami, A, Krystal, JH, Abdallah, CG, Stein, MB, Kranzler, HR, Gelernter, J and Polimanti, R (2021) Sex-stratified gene-by-environment genome-wide interaction study of trauma, posttraumatic-stress, and suicidality. Neurobiology of Stress 14, 100309.CrossRefGoogle ScholarPubMed
Wiertelak, EP, Maier, SF and Watkins, LR (1992) Cholecystokinin antianalgesia: safety cues abolish morphine analgesia. Science 256, 830833.CrossRefGoogle ScholarPubMed
Zwanzger, P, Domschke, K and Bradwejn, J (2012) Neuronal network of panic disorder: the role of the neuropeptide cholecystokinin. Depression and Anxiety 29, 762774.CrossRefGoogle ScholarPubMed
Zwanzger, P, Zavorotnyy, M, Gencheva, E, Diemer, J, Kugel, H, Heindel, W, Ruland, T, Ohrmann, P, Arolt, V, Domschke, K and Pfleiderer, B (2013) Acute shift in glutamate concentrations following experimentally induced panic with cholecystokinin tetrapeptide—a 3T-MRS study in healthy subjects. Neuropsychopharmacology 38, 16481654.CrossRefGoogle Scholar