Abstract
This chapter initially criticizes the lack of a “theoretical” (neuro)psychiatry that helps to understand mental disorders and their pharmaceutical treatment. In the chapter, the complex pathophysiology of alcohol withdrawal is used as an example to demonstrate the utility of systemic modeling of the brain: pharmaceutical treatment of alcohol withdrawal syndrome is usually based on stage-dependent polypharmacy – anti-noradrenergic drugs (clonidine), GABA-ergic drugs (benzodiazepines), anti-dopaminergic drugs (haloperidol), sometimes cholinergic drugs (physostigmine), and also anti-glutamatergic drugs (ketamine) are used. They should suppress specific symptoms such as sympathetic hyperactivity, anxiety, restlessness, generalized tonic-clonic seizures, and delirious states at different stages and forms of alcohol withdrawal. Benefit-risk evaluations for treatment decisions regarding medications are still pragmatic, as appropriate RCTs are not conducted for several reasons (organizational restrictions, questionable validity of rating scales, etc.). Nevertheless, the general treatment strategy for prevention of seizures and deliria favors benzodiazepines. They prevent seizures and may reduce hyperactivity of the sympathetic nervous system.
The chapter briefly links to neurobiological data and current recommendations for treatment of alcohol withdrawal, but focuses on the pathophysiological dynamics of the interconnected imbalanced neurotransmitter systems. This leads to the construction of a qualitative dynamic system model that is composed of six relevant neurotransmitter systems. This model has already been tested in a computerized version, and therefore, it is finally proposed that it could help to understand other mental disorders in general psychiatry.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12:366–75. https://doi.org/10.1016/0166-2236(89)90074-X.
APA, American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Arlington: American Psychiatric Publishing; 2013.
APA, American Psychiatric Association. Clinical practice guidelines. APA; 2021. https://www.psychiatry.org/psychiatrists/practice/clinical-practice-guidelines
ASAM, American Society of Addiction Medicine. The Asam clinical practice guideline on alcohol. ASAM 2021. https://www.Asam.Org/Docs/Default-Source/Quality-Science/The_Asam_Clinical_Practice_Guideline_On_Alcohol-1.pdf?sfvrsn=ba255c2_2
Berns GS, Sejnowski TJ. A computational model of how the basal ganglia produce sequences. J Cogn Neurosci. 2021;10:108–21. https://doi.org/10.1162/089892998563815.
Bertalanffy L. General system theory. New York: Braziller; 1968.
Birkmayer W, Hornykiewicz O. Der L-Dioxyphenylalanin (= L-Dopa)-Effekt bei der Parkinson- Akinese. Wien Klien Wschr. 1961;73:787–78.
Birkmayer W, Riederer P, editors. Understanding the neurotransmitters: key to the workings of the brain. Vienna, New York: Springer; 1989.
Birkmayer W, Danielczyk W, Neumayer E, et al. The balance of biogenic amines as condition for normal behaviour. J Neural Transm. 1972;33:163–78. https://doi.org/10.1007/BF01260902.
Bonhoeffer K. Die akuten Geisteskrankheiten der Gewohnheitstrinker. Eine klinische Studie. Jena: Fischer Verlag; 1901.
Buzsáki G. Rhythms of the brain. Oxford: Oxford University Press; 2006.
Carlsson A. The occurrence, distribution and physiological role of catecholamines in the nervous system. Pharmacol Rev. 1959;11(2, Part 2):490–3. [PMID: 13667431]
Carlsson A. The neurochemical circuitry of schizophrenia. Pharmacopsychiatry. 2006;39(S1):10–4.
Craver C. Explaining the brain. Oxford: Oxford University Press; 2006.
Davies M. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci. 2003;28:263–74.
Dayan P, Abbott L. Theoretical neuroscience. Computational and mathematical modeling of neural systems. Cambridge: MIT Press; 2001.
DeLong MR. Primate models of movement disorders of basal ganglia origin. Trends Neurosci. 1990;13:281–5. https://doi.org/10.1016/0166-2236(90)90110-V.
Di Chiara G. Alcohol and dopamine. Alcohol Health Res World. 1997;21(2):108–14.
Fitzgerald PJ. Elevated norepinephrine may be a unifying etiological factor in the abuse of a broad range of substances: alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Substance Abuse Res Treat. 2013;7:171–83. https://doi.org/10.4137/SART.S13019.
Foley P, Riederer P. The motor circuit of the human basal ganglia reconsidered. In: Mizuno Y, Calne DB, Horowski R, Poewe W, Riederer P, Youdim MBH, editors. Advances in research on neurodegeneration. Vienna: Springer; 2000. https://doi.org/10.1007/978-3-7091-6284-2_8.
Gossop M, Keaney F, Stewart D, Marshall EJ, Strang J. A short alcohol withdrawal scale (SAWS): development and psychometric properties. Addict Biol. 2002;7(1):37–43. https://doi.org/10.1080/135562101200100571. PMID: 11900621
HBP, Human Brian Project. The human Brian project. 2021. https://www.humanbrainproject.eu/en/about/project-structure/work-packages/work-package-1/
Himmelsbach CK. The morphine abstinence syndrome, its nature and treatment. Ann Intern Med. 1941;15:829–43.
Hoffman PL, Tabakoff B. The role of the NMDA receptor in ethanol withdrawal. EXS. 1994;71:61–70. https://doi.org/10.1007/978-3-0348-7330-7_7. PMID: 8032173
Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry. 2010;167(7):748–51.
Jakovljevic M, Jakovljevic I. Theoretical psychiatry as a link between academic and clinical psychiatry. In: Kim YK, editor. Frontiers in psychiatry. Advances in experimental medicine and biology, vol. 1192. Singapore: Springer; 2019. https://doi.org/10.1007/978-981-32-9721-0_19.
Junghanns K, Wetterling T. Der komplizierte Alkoholentzug: Grand-Mal-Anfälle, Delir und Wernicke-Enzephalopathie [Alcohol withdrawal and its major complications]. Fortschr Neurol Psychiatr. 2017;85(3):163–77. https://doi.org/10.1055/s-0043-103052. Epub 2017 Mar 20. German. PMID: 28320026
Keeler JF, Pretsell DO, Robbins TW. Functional implications of dopamine D1 vs. D2 receptors: a ‘prepare and select’ model of the striatal direct vs. indirect pathways. Neuroscience. 2014;282:156–75.
Kitano H. Systems biology: a brief overview. Science. 2002;295(5560):1662–4. https://doi.org/10.1126/science.1069492. PMID: 11872829
Klein JT. Interdisciplinarity and transdisciplinarity: keyword meanings for collaboration science and translational medicine. J Transl Med Epidemiol. 2014;2(2):1024.
Koob GF, Le Moal M. Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology. 2001;24(2):97–129. https://doi.org/10.1016/S0893-133X(00)00195-0. PMID: 11120394
Koob GF, Volkow ND. Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016;3(8):760–73. https://doi.org/10.1016/S2215-0366(16)00104-8.
Kotchoubey B, Tretter F, Braun HA, Buchheim T, Draguhn A, Fuchs T, Hasler F, Hastedt H, Hinterberger T, Northoff G, Rentschler I, Schleim S, Sellmaier S, Tebartz van Elst L, Tschacher W. Methodological problems on the way to integrative human neuroscience. Front Integr Neurosci. 2016;10:41.
Kringelbach ML, Deco G. Brain states and transitions: insights from computational neuroscience. Cell Rep. 2020;32(10):108128. https://doi.org/10.1016/j.celrep.2020.108128. PMID: 32905760
Larsson A, Edström L, Svensson L, Söderpalm B, Engel JAV. Voluntary ethanol intake increases extracellular acetylcholine levels in the ventral tegmental area in the rat. Alcohol Alcohol. 2005;40(5):349–58. https://doi.org/10.1093/alcalc/agh180.
Liljenström H. Network effects of synaptic modifications. Pharmacopsychiatry. 2010;43(Suppl. 1):S67–81.
Lovinger DM, Zhou Q. Alcohols potentiate ion current mediated by recombinant 5-HT3RA receptors expressed in a mammalian cell line. Neuropharmacology. 1994;33:1567–72.
Lovinger DM, White G, Weight FF. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science. 1989;243:1721–4.
Lovinger DM, White G, Weight FF. NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat. J Neurosci. 1990;10:1372–9.
Maldonado JR, Sher Y, Ashouri JF, Hills-Evans K, Swendsen H, Lolak S, Miller AC. The “prediction of alcohol withdrawal severity scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375–90. https://doi.org/10.1016/j.alcohol.2014.01.004. Epub 2014 Feb 19. PMID: 24657098
McBride WJ, Murphy JM, Yoshimoto K, Lumeng L, Li T-K. Serotonin mechanisms in alcohol drinking behavior. Drug Dev Res. 1993;30:170–7.
Morgan JL, Lichtman JW. Why not connectomics? Nat Methods. 2013;10(6):494–500. https://doi.org/10.1038/nmeth.2480.
Morgan JL, Lichtman JW. Digital tissue and what it may reveal about the brain. BMC Biol. 2017;15:101. https://doi.org/10.1186/s12915-017-0436-9.
Nestler EJ, Lüscher C. The molecular basis of drug addiction: linking epigenetic to synaptic and circuit mechanisms. Neuron. 2019;102(1):48–59. https://doi.org/10.1016/j.neuron.2019.01.016. PMID: 30946825; PMCID: PMC6587180
Porenta G, Riederer P. Some aspects of modeling neuronal interactions in the basal ganglia. In: Trappl R, editor. Cybernetics and systems. Vienna: Austrian Research Institute for Artificial Intelligence; 1986. p. 351–8.
Qi Z, Tretter F, Voit EO. A heuristic model of alcohol dependence. PLoS One. 2014;9(3):e92221. https://doi.org/10.1371/journal.pone.0092221. Published online 2014 Mar 21
Rasimas JJ, Sachdeva KK, Donovan IW. Revival of an antidote: bedside experience with physostigmine. Toxicol Commun. 2018;2(1):85–101. https://doi.org/10.1080/24734306.2018.1535538.
Schroll H, Hamker FH. Computational models of basal-ganglia pathway functions: focus on functional neuroanatomy. Front Syst Neurosci. 2013;7:122. https://doi.org/10.3389/fnsys.2013.00122.
Sian J, Youdim MBH, Riederer P, et al. Biochemical anatomy of the basal ganglia and associated neural systems. In: Siegel GJ, Agranoff BW, Albers RW, et al., editors. Basic neurochemistry: molecular, cellular and medical aspects. 6th ed. Philadelphia: Lippincott-Raven; 1999. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27905/.
Solomon RL, Corbit JD. An opponent-process theory of motivation: I. Temporal Dynam Affect Psychol Rev. 1974;81:119–45.
Sporns O. The human connectome: origins and challenges. NeuroImage. 2013;80:53–61.
Stahl SM. Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge: Cambridge University Press; 2013.
Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989;84(11):1353–7. https://doi.org/10.1111/j.1360-0443.1989.tb00737.x. PMID: 2597811
Tabakoff B, Hoffman PL. Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells. Behav Genet. 1993;23:231–6. https://doi.org/10.1007/BF01067428.
Tretter F. Suchtmedizin. Stuttgart: Schattauer; 2000.
Tretter F. Systemisch-kybernetische Modellansätze der Psychologie der Sucht. In: Tretter F, Müller A, editors. Psychologie der Sucht. Göttingen: Hogrefe; 2001. p. 165–99.
Tretter F. “Systems medicine” in the view of von Bertalanffy’s “organismic biology” and systems theory. Res Behav Sci. 2019;36:346–62.
Tretter F, Winterer G, Gebicke-Haerter PJ, Mendoza ER, editors. Systems biology in psychiatric research: from high-throughput data to mathematical modeling. Weinheim: Wiley-Blackwell; 2010a.
Tretter F, Rujescu D, Pogarell O, Mendoza E, editors. Systems biology of the synapse. Pharmacopsychiatry. 2010b;43:S1–S98.
Tsai G, Coyle JT. The role of glutamatergic neurotransmission in the pathophysiology of alcoholism. Annu Rev Med. 1998;49:173–84.
Volkow ND, Wang G, Begleiter H, et al. High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Arch Gen Psychiatry. 2006;63(9):999–1008. https://doi.org/10.1001/archpsyc.63.9.999.
Wang X-J, Krystal JH. Computational psychiatry. Neuron. 2014;84:638–54.
Wei W, Faria LC, Mody I. Low ethanol concentrations selectively augment the tonic inhibition mediated by δ subunit- containing GABAA receptors in hippocampal neurons. J Neurosci. 2004;24:8379–82.
Weiss F, Lorang MT, Bloom FE, Koob GF. Oral alcohol self-administration stimulates dopamine release in the rat nucleus accumbens: genetic and motivational determinants. J Pharmacol Exp Ther. 1995;267:250–8.
Weiss F, Parsons LH, Schulteis G, Hyytia P, Lorang MT, et al. Ethanol self-administration restores withdrawal-associated deficiencies in accumbal dopamine and 5-hydroxytryptamine release in dependent rats. J Neurosci. 1996;16:3474–85.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Section Editor information
Rights and permissions
Copyright information
© 2022 Springer Nature Switzerland AG
About this entry
Cite this entry
Tretter, F. (2022). Neurochemical Mobile: A Heuristic Tool for Understanding Dynamic Complexity and Treatment of Alcohol Withdrawal. In: Riederer, P., Laux, G., Nagatsu, T., Le, W., Riederer, C. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-030-62059-2_448
Download citation
DOI: https://doi.org/10.1007/978-3-030-62059-2_448
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-62058-5
Online ISBN: 978-3-030-62059-2
eBook Packages: MedicineReference Module Medicine