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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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General Review Article

The Complex Link Between Schizophrenia and Dementia: Targeting Ca2+/cAMP Signalling

Author(s): Leandro B. Bergantin*

Volume 26, Issue 27, 2020

Page: [3326 - 3331] Pages: 6

DOI: 10.2174/1381612826666200318144521

Price: $65

Abstract

Background: Considering a consistent body of evidence has been showing that schizophrenia patients have had an increased risk of developing dementia. The hypothesis that dementia and schizophrenia share a complex link, is emerging. It is highly discussed that dysregulations related to Ca2+ signalling, e.g., an increase of the intracellular concentration of Ca2+, could link both diseases, in addition to cAMP signalling pathways.

Objective: Thus, revealing this interplay between schizophrenia and dementia may provide novel insights into the pathogenesis of these diseases.

Methods: Publications involving Ca2+ and cAMP signalling pathways, dementia and schizophrenia (alone or combined) were collected by searching PubMed and EMBASE.

Results: Both Ca2+ and cAMP signalling pathways (Ca2+/cAMP signalling) control the release of neurotransmitters/ hormones and neuronal death, and dysregulations of these cellular processes may be involved in both diseases.

Conclusion: Bearing in mind the experience of our group in this field, this article debated the involvement of Ca2+/cAMP signalling in this link between schizophrenia and dementia, including its pharmacological implications.

Keywords: Schizophrenia, dementia, Ca2+/cAMP signalling, Ca2+ channel blockers, pharmacotherapy, neurodegeneration.

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[1]
Cai L, Huang J. Schizophrenia and risk of dementia: a meta-analysis study. Neuropsychiatr Dis Treat 2018; 14: 2047-55.
[http://dx.doi.org/10.2147/NDT.S172933] [PMID: 30147318]
[2]
Harvey PD, Silverman JM, Mohs RC, et al. Cognitive decline in late-life schizophrenia: a longitudinal study of geriatric chronically hospitalized patients. Biol Psychiatry 1999; 45(1): 32-40.
[http://dx.doi.org/10.1016/S0006-3223(98)00273-X] [PMID: 9894573]
[3]
Katagiri H, Okada G, Jitsuiki H, Kozuru T, Muraoka M, Yamawaki S. The longitudinal change of cognitive function of long-stay in patients with schizophrenia by the revised version of Hasegawa’s Dementia Scale. Int J Neuropsychopharmacol 2008; 11: 165.
[4]
Nayak Savla G, Moore DJ, Roesch SC, Heaton RK, Jeste DV, Palmer BW. An evaluation of longitudinal neurocognitive performance among middle-aged and older schizophrenia patients: use of mixed-model analyses. Schizophr Res 2006; 83(2-3): 215-23.
[http://dx.doi.org/10.1016/j.schres.2005.12.851] [PMID: 16507344]
[5]
Bergantin LB, Caricati-Neto A. A Caricati-Neto (2018) The “Calcium Paradox” and its Impact on Neurological and Psychiatric Diseases.Cambridge Scholars Publishing. 2018..NLM ID: 101734546
[6]
Bergantin LB. Hypertension, Diabetes and Neurodegenerative Diseases: Is there a Clinical Link through the Ca2+/cAMP Signalling Interaction? Curr Hypertens Rev 2018.
[http://dx.doi.org/10.2174/1573402114666180817113242] [PMID: 30117399]
[7]
Bergantin LB, Caricati-Neto A. Challenges for the pharmacological treatment of neurological and psychiatric disorders: Implications of the Ca(2+)/cAMP intracellular signalling interaction. Eur J Pharmacol 2016; 788: 255-60.
[http://dx.doi.org/10.1016/j.ejphar.2016.06.034] [PMID: 27349146]
[8]
Bergantin LB. Debating the “bidirectional link” between diabetes and depression through the Ca2+/cAMP signalling: Off-label effects of Ca2+ channel blockers. Pharmacol Res 2019; 141: 298-302.
[http://dx.doi.org/10.1016/j.phrs.2019.01.008] [PMID: 30639385]
[9]
Yarlagadda A, Clayton AH. Role of cholinergic system and calcium synchronization in schizophrenia. Psychiatry (Edgmont Pa) 2009; 6(4): 37-41.
[PMID: 19724731]
[10]
Wu CL, Wen SH. A 10-year follow-up study of the association between calcium channel blocker use and the risk of dementia in elderly hypertensive patients. Medicine (Baltimore) 2016; 95(32)e4593
[http://dx.doi.org/10.1097/MD.0000000000004593] [PMID: 27512890]
[11]
Van Dyke P, Thomas KL. Concomitant calcium channel blocker and antipsychotic therapy in patients with schizophrenia: Efficacy analysis of the CATIE-Sz phase 1 data. Ann Clin Psychiatry 2018; 30(1): 6-16.
[PMID: 29069114]
[12]
Douglas WW, Rubin RP. The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol 1961; 159: 40-57.
[http://dx.doi.org/10.1113/jphysiol.1961.sp006791] [PMID: 13887557]
[13]
Baker PF, Knight DE. Calcium-dependent exocytosis in bovine adrenal medullary cells with leaky plasma membranes. Nature 1978; 276(5688): 620-2.
[http://dx.doi.org/10.1038/276620a0] [PMID: 723944]
[14]
Neher E, Zucker RS. Multiple calcium-dependent processes related to secretion in bovine chromaffin cells. Neuron 1993; 10(1): 21-30.
[http://dx.doi.org/10.1016/0896-6273(93)90238-M] [PMID: 8427700]
[15]
Chern YJ, Kim KT, Slakey LL, Westhead EW. Adenosine receptors activate adenylate cyclase and enhance secretion from bovine adrenal chromaffin cells in the presence of forskolin. J Neurochem 1988; 50(5): 1484-93.
[http://dx.doi.org/10.1111/j.1471-4159.1988.tb03034.x] [PMID: 2834514]
[16]
Bergantin LB, Souza CF, Ferreira RM, et al. Novel model for “calcium paradox” in sympathetic transmission of smooth muscles: role of cyclic AMP pathway. Cell Calcium 2013; 54(3): 202-12.
[http://dx.doi.org/10.1016/j.ceca.2013.06.004] [PMID: 23849429]
[17]
Caricati-Neto A, García AG, Bergantin LB. Pharmacological implications of the Ca(2+)/cAMP signaling interaction: from risk for antihypertensive therapy to potential beneficial for neurological and psychiatric disorders. Pharmacol Res Perspect 2015; 3(5)e00181
[http://dx.doi.org/10.1002/prp2.181] [PMID: 26516591]
[18]
Antoni FA. Interactions between intracellular free Ca2+ and cyclic AMP in neuroendocrine cells. Cell Calcium 2012; 51(3-4): 260-6.
[http://dx.doi.org/10.1016/j.ceca.2011.12.013] [PMID: 22385836]
[19]
Bruce JI, Shuttleworth TJ, Giovannucci DR, Yule DI. Phosphorylation of inositol 1,4,5-trisphosphate receptors in parotid acinar cells. A mechanism for the synergistic effects of cAMP on Ca2+ signaling. J Biol Chem 2002; 277(2): 1340-8.
[http://dx.doi.org/10.1074/jbc.M106609200] [PMID: 11694504]
[20]
Cooper DM, Mons N, Karpen JW. Adenylyl cyclases and the interaction between calcium and cAMP signalling. Nature 1995; 374(6521): 421-4.
[http://dx.doi.org/10.1038/374421a0] [PMID: 7700350]
[21]
Halls ML, Cooper DM. Regulation by Ca2+-signaling pathways of adenylyl cyclases. Cold Spring Harb Perspect Biol 2011; 3(1)a004143
[http://dx.doi.org/10.1101/cshperspect.a004143] [PMID: 21123395]
[22]
Fagan KA, Graf RA, Tolman S, Schaack J, Cooper DM. Regulation of a Ca2+-sensitive adenylyl cyclase in an excitable cell. Role of voltage-gated versus capacitative Ca2+ entry. J Biol Chem 2000; 275(51): 40187-94.
[http://dx.doi.org/10.1074/jbc.M006606200] [PMID: 11010970]
[23]
Yule DI, Betzenhauser MJ, Joseph SK. Linking structure to function: Recent lessons from inositol 1,4,5-trisphosphate receptor mutagenesis. Cell Calcium 2010; 47(6): 469-79.
[http://dx.doi.org/10.1016/j.ceca.2010.04.005] [PMID: 20510450]
[24]
Lanner JT, Georgiou DK, Joshi AD, Hamilton SL. Ryanodine receptors: structure, expression, molecular details, and function in calcium release. Cold Spring Harb Perspect Biol 2010; 2(11)a003996
[http://dx.doi.org/10.1101/cshperspect.a003996] [PMID: 20961976]
[25]
Caricati-Neto A, Bergantin LB. Pharmacological modulation of neural Ca2+/camp signaling interaction as therapeutic goal for treatment of Alzheimer’s disease. J Syst Integr Neurosci 2017; 3.
[http://dx.doi.org/10.15761/JSIN.1000185]
[26]
Caricati-Neto A, Bergantin LB. The passion of a scientific discovery: the “calcium paradox” due to Ca2+/camp interaction. J Syst Integr Neurosci 2017; 3.
[http://dx.doi.org/10.15761/JSIN.1000186]
[27]
Caricati-Neto A, Bergantin LB. From a “eureka insight” to a novel potential therapeutic target to treat Parkinson’s disease: The Ca2+/camp signalling interaction. J Syst Integr Neurosci 2017; 4.
[http://dx.doi.org/10.15761/JSIN.1000187]
[28]
Bezprozvanny I, Mattson MP. Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 2008; 31(9): 454-63.
[http://dx.doi.org/10.1016/j.tins.2008.06.005] [PMID: 18675468]
[29]
St George-Hyslop PH, Petit A. Molecular biology and genetics of Alzheimer’s disease. C R Biol 2005; 328(2): 119-30.
[http://dx.doi.org/10.1016/j.crvi.2004.10.013] [PMID: 15770998]
[30]
Walker E, Kestler L, Bollini A, Hochman KM. Schizophrenia: etiology and course. Annu Rev Psychol 2004; 55(1): 401-30.
[http://dx.doi.org/10.1146/annurev.psych.55.090902.141950] [PMID: 14744221]
[31]
Freedman R, Schizophrenia . N Engl J Med 2003; 349(18): 1738-49.
[http://dx.doi.org/10.1056/NEJMra035458] [PMID: 14585943]
[32]
Flaum M, Schultz SK. The core symptoms of schizophrenia. Ann Med 1996; 28(6): 525-31.
[http://dx.doi.org/10.3109/07853899608999116] [PMID: 9017111]
[33]
Viertiö S, Tuulio-Henriksson A, Perälä J, et al. Activities of daily living, social functioning and their determinants in persons with psychotic disorder. Eur Psychiatry 2012; 27(6): 409-15.
[http://dx.doi.org/10.1016/j.eurpsy.2010.12.005] [PMID: 21377336]
[34]
Harvey PD, Leff J, Trieman N, Anderson J, Davidson M. Cognitive impairment in geriatric chronic schizophrenic patients: a cross-national study in New York and London. Int J Geriatr Psychiatry 1997; 12(10): 1001-7.
[http://dx.doi.org/10.1002/(SICI)10991166(199710)12:10<1001:AID-GPS674>3.0.CO;2-0] [PMID: 9395932]
[35]
Harvey PD, Reichenberg A, Bowie CR. Cognition and aging in psychopathology: focus on schizophrenia and depression. Annu Rev Clin Psychol 2006; 2(1): 389-409.
[http://dx.doi.org/10.1146/annurev.clinpsy.2.022305.095206] [PMID: 17716076]
[36]
Gupta S, Bisht SS, Kukreti R, Jain S, Brahmachari SK. Boolean network analysis of a neurotransmitter signaling pathway. J Theor Biol 2007; 244(3): 463-9.
[http://dx.doi.org/10.1016/j.jtbi.2006.08.014] [PMID: 17010384]
[37]
Ku H, Lee E-K, Lee K-U, Lee M-Y, Kwon J-W. Higher prevalence of dementia in patients with schizophrenia: A nationwide population-based study. Asia-Pac Psychiatry 2016; 8(2): 145-53.
[http://dx.doi.org/10.1111/appy.12239] [PMID: 27028507]
[38]
Lyketsos CG, Peters ME. Dementia in Patients With Schizophrenia: Evidence for Heterogeneity. JAMA Psychiatry 2015; 72(11): 1075-6.
[http://dx.doi.org/10.1001/jamapsychiatry.2015.1745] [PMID: 26444878]
[39]
Husa AP, Rannikko I, Moilanen J, et al. Lifetime use of antipsychotic medication and its relation to change of verbal learning and memory in midlife schizophrenia - An observational 9-year follow-up study. Schizophr Res 2014; 158(1-3): 134-41.
[http://dx.doi.org/10.1016/j.schres.2014.06.035] [PMID: 25034761]
[40]
Buckley PF, Miller BJ, Lehrer DS, Castle DJ. Psychiatric comorbidities and schizophrenia. Schizophr Bull 2009; 35(2): 383-402.
[http://dx.doi.org/10.1093/schbul/sbn135] [PMID: 19011234]
[41]
Manzanares N, Monseny R, Ortega L, et al. Unhealthy lifestyle in early psychoses: the role of life stress and the hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology 2014; 39: 1-10.
[http://dx.doi.org/10.1016/j.psyneuen.2013.09.023] [PMID: 24274999]
[42]
Brown S, Birtwistle J, Roe L, Thompson C. The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999; 29(3): 697-701.
[http://dx.doi.org/10.1017/S0033291798008186] [PMID: 10405091]
[43]
Leucht S, Burkard T, Henderson J, Maj M, Sartorius N. Physical illness and schizophrenia: a review of the literature. Acta Psychiatr Scand 2007; 116(5): 317-33.
[http://dx.doi.org/10.1111/j.1600-0447.2007.01095.x] [PMID: 17919153]
[44]
Deckers K, van Boxtel MP, Schiepers OJ, et al. Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies. Int J Geriatr Psychiatry 2015; 30(3): 234-46.
[http://dx.doi.org/10.1002/gps.4245] [PMID: 25504093]
[45]
McCullagh CDCD, McIlroy SP, Passmore AP. Risk factors for dementia. Adv Psychiatr Treat 2001; 7: 24-31.
[http://dx.doi.org/10.1192/apt.7.1.24]
[46]
Eaton WW, Martins SS, Nestadt G, Bienvenu OJ, Clarke D, Alexandre P. The burden of mental disorders. Epidemiol Rev 2008; 30: 1-14.
[http://dx.doi.org/10.1093/epirev/mxn011] [PMID: 18806255]
[47]
Laursen TM, Munk-Olsen T, Nordentoft M, Mortensen PB. Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia. J Clin Psychiatry 2007; 68(6): 899-907.
[http://dx.doi.org/10.4088/JCP.v68n0612] [PMID: 17592915]
[48]
Bergantin LB. The Interplay Between Asthma and Other Diseases: Role of Ca2+/cAMP Signalling. Endocr Metab Immune Disord Drug Targets 2019; 28(Aug)
[http://dx.doi.org/10.2174/1871530319666190828145854] [PMID: 31456527]
[49]
Bergantin LB. Diabetes and Parkinson’s disease: Debating the link through Ca2+/cAMP signalling. Curr Diabetes Rev 2019; 11(Jul)
[http://dx.doi.org/10.2174/1573399815666190711113644] [PMID: 31291877]
[50]
Emptage NJ, Reid CA, Fine A. Calcium stores in hippocampal synaptic boutons mediate short-term plasticity, store-operated Ca2+ entry, and spontaneous transmitter release. Neuron 2001; 29(1): 197-208.
[http://dx.doi.org/10.1016/S0896-6273(01)00190-8] [PMID: 11182091]
[51]
Garver DL, Johnson C, Kanter DR. Schizophrenia and reduced cyclic AMP production: evidence for the role of receptor-linked events. Life Sci 1982; 31(18): 1987-92.
[http://dx.doi.org/10.1016/0024-3205(82)90037-6] [PMID: 6294425]
[52]
Muly C. Signal transduction abnormalities in schizophrenia: the cAMP system. Psychopharmacol Bull 2002; 36(4): 92-105.
[PMID: 12858148]
[53]
Xiao L, O’Callaghan JP, O’Donnell JM. Effects of repeated treatment with phosphodiesterase-4 inhibitors on cAMP signaling, hippocampal cell proliferation, and behavior in the forced-swim test. J Pharmacol Exp Ther 2011; 338(2): 641-7.
[http://dx.doi.org/10.1124/jpet.111.179358] [PMID: 21566211]
[54]
Yarlagadda A. Role of calcium regulation in pathophysiology model of schizophrenia and possible interventions. Med Hypotheses 2002; 58(2): 182-6.
[http://dx.doi.org/10.1054/mehy.2001.1511] [PMID: 11812200]
[55]
Ghosh A, Greenberg ME. Calcium signaling in neurons: molecular mechanisms and cellular consequences. Science 1995; 268(5208): 239-47.
[http://dx.doi.org/10.1126/science.7716515] [PMID: 7716515]
[56]
Lidow MS. Calcium signaling dysfunction in schizophrenia: a unifying approach. Brain Res Brain Res Rev 2003; 43(1): 70-84.
[http://dx.doi.org/10.1016/S0165-0173(03)00203-0] [PMID: 14499463]
[57]
Cooper DM. Regulation and organization of adenylyl cyclases and cAMP. Biochem J 2003; 375(Pt 3): 517-29.
[http://dx.doi.org/10.1042/bj20031061] [PMID: 12940771]
[58]
Kawamoto EM, Vivar C, Camandola S. Physiology and pathology of calcium signaling in the brain. Front Pharmacol 2012; 3: 61.
[http://dx.doi.org/10.3389/fphar.2012.00061] [PMID: 22518105]
[59]
Uddin MS, Stachowiak A, Mamun AA, et al. Autophagy and Alzheimer's Disease: From Molecular Mechanisms to Therapeutic Implications. Front Aging Neurosci 2018 Jan; 3010: 04.
[http://dx.doi.org/10.3389/fnagi.2018.00004]
[60]
Behrendt RP, Young C. Hallucinations in schizophrenia, sensory impairment, and brain disease: a unifying model. Behav Brain Sci 2004; 27(6): 771-87.
[http://dx.doi.org/10.1017/S0140525X04000184] [PMID: 16035402]
[61]
Balter M. Schizophrenia’s Unyielding Mysteries. Sci Am 2017; 316(5): 54-61.
[http://dx.doi.org/10.1038/scientificamerican0517-54] [PMID: 28437403]
[62]
Elert E. Aetiology: Searching for schizophrenia’s roots. Nature 2014; 508(7494): S2-3.
[http://dx.doi.org/10.1038/508S2a] [PMID: 24695332]

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