| Peer-Reviewed

A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders

Received: 12 November 2021    Accepted: 1 December 2021    Published: 11 December 2021
Views:       Downloads:
Abstract

Medication, psychotherapy, or both are the most common approaches to the treatment of psychiatric disorders. However, due to the high incidence, early onset, and chronicity of psychiatric symptoms, both medication and psychotherapy can be resource-intensive, yet there is little consensus about which should be applied to which clinical syndromes. This is a matter of increasing concern in light of the growing mental health crisis. Much of the problem stems from the lack of a precise psychophysiological explanation for psychiatric symptomatology, as it leaves clinicians without a clear target for treatment. However, an emerging hypothesis—one that identifies the fundamental vulnerability trait in psychiatric disorders—has the potential to help solve these problems. According to the Multi-Circuit Neuronal Hyperexcitability (MCNH) Hypothesis, psychiatric symptoms are driven by an abnormal elevation in the activity of the neural circuits with which they are associated. Particularly under the influence of stress, too many neurons fire for too long, resulting in circuit-specific symptoms, such as anxiety, depression, irritability, insomnia, inattention, apathy, and obsessional thinking. What hypothetically determines which circuits will be pathologically hyperactive at any point in time are the aberrant neuronal discharges that tend to occur spontaneously or in conjunction with willful cognitions and emotions when the neurological system is hyperexcitable. Clinical application of this hypothesis has the potential to guide which form of treatment would be most effective for which patient and to streamline the use of medications and other medical interventions because it illuminates a specific target for treatment. It also has the potential, for the first time in history, to prevent the development of psychiatric symptoms because the trait of neuronal hyperexcitability is highly modifiable and can be identified objectively by simply measuring one’s resting vital signs. Moreover, because the trait of neuronal hyperexcitability also appears to be at the root of a wide range of general medical conditions, such as diabetes, high blood pressure, cardiovascular disease, and cancer, the early detection and management of the trait could usher in history’s greatest campaign in the first against sickness and disease.

Published in American Journal of Clinical and Experimental Medicine (Volume 9, Issue 6)
DOI 10.11648/j.ajcem.20210906.16
Page(s) 223-232
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Pathophysiology of Psychiatric Disorders, Neuronal Hyperexcitability, Biomarkers of Disease, Preventive Medicine, Anticonvulsants, Mood Stabilizers, Neuroregulators, Antidepressants

References
[1] Jablensky A. Psychiatric classifications: validity and utility. World Psychiatry 2016; 15 (1): 26-31.
[2] Cuijpers P, Sijbrandij M, Koole SL, et al. The efficacy of psychotherapy and pharmacotherapy in treating depressive and anxiety disorders: a meta-analysis of direct comparisons. World Psychiatry 2013; 12 (2): 137–148.
[3] Cuijpers P, Sijbrandij M, Koole SL, et al. Adding psychotherapy to antidepressant medication in depression and anxiety disorders: a meta-analysis. World Psychiatry 2014; 13 (1): 56–67.
[4] Freud S. (1924). A general introduction to psychoalaysis, trans. Joan Riviere.
[5] Freud S. (1915). The unconscious. SE, 14: 159-204.
[6] Cerf M, Thiruvengadam N, Mormann F, et al. On-line, voluntary control of human temporal lobe neurons. Nature 2010; 467: 1104-1108.
[7] Aravanis AM, Wang L-P, Zhang F, et al. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. Journal of Neural Engineering 2007; 4 (3).
[8] Binder MR. The multi-circuit neuronal hyperexcitability hypothesis of psychiatric disorders. AJCEM 2019; 7 (1): 12-30.
[9] Binder MR. Neuronal Hyperexcitability: Significance, Cause, and Diversity of Clinical Expression. AJCEM; 9 (5): 163-173.
[10] Henkel AW, Welzel O, Groemer T W, et al. Fluoxetine prevents stimulation-dependent fatigue of synaptic vesicle exocytosis in hippocampal neurons. Journal of Neurochemistry 2010; 114 (3): 697-705.
[11] Binder MR. Electrophysiology of seizure disorders may hold key to the pathophysiology of psychiatric disorders. AJCEM 2019; 7 (5): 103-110.
[12] Binder MR: The neuronal excitability spectrum: a new paradigm in the diagnosis, treatment, and prevention of mental illness and its relation to chronic disease. AJCEM 2021; 9 (6): 193-209.
[13] Akiskal HS. The bipolar spectrum: new concepts in classification and diagnosis. In: Grinspoon L, editor. Psychiatry Update; The American Psychiatric Association Annual Review. Vol. 2. Washington DC: American Psychiatric Press 1983, pp. 271–292.
[14] Ferreira, MAR, O’Donovan MC, Sklar P. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40 (9): 1056-1058.
[15] Yuan A, Yi Z, Wang Q, et al. ANK3 as a risk gene for schizophrenia: new data in Han Chinese and meta analysis. Am J Med Genet B Neuropsychiatr Genet 2012; 159B (8): 997-1005.
[16] Green EK, Grozeva D, Jones I, et al., Wellcome Trust Case Control Consortium, Holmans, PA, Owen, MJ, O'Donovan, MC, Craddock N. The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2010; 15 (10): 1016-1022.
[17] Liu Y, Blackwood DH, Caesar S, et al. Meta-analysis of genome-wide association data of bipolar disorder and major depressive disorder. Mol Psychiatry 2011; 16 (1).
[18] Iqbal Z, Vandeweyer G, van der Voet M, et al. Homozygous and heterozygous disruptions of ANK3: at the crossroads of neurodevelopmental and psychiatric disorders. Human Molecular Genetics 2013; 22: 1960-1970.
[19] Subramanian J, Dye L, Morozov, A. Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release. Journal of Neuroscience 2013; 33 (17): 7245.
[20] Santos M, D'Amico D, Spadoni O, et al. Hippocampal hyperexcitability underlies enhanced fear memories in TgNTRK3, a panic disorder mouse model. Journal of Neuroscience 2013; 33 (38): 15259-15271.
[21] Lopez AY, Wang X, Xu M, et al. Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder. Mol Psychiatry 2017; 22 (10): 1464–1472.
[22] Contractor A, Klyachko VA, Portera-Cailliau C. Altered neuronal and circuit excitability in Fragile X syndrome. Neuron 2015; 87 (4): 699-715.
[23] O’Brien NL, Way MJ, Kandaswamy R, et al. The functional GRM3 Kozak sequence variant rs148754219 affects the risk of schizophrenia and alcohol dependence as well as bipolar disorder. Psychiatric Genetics 2014; 24: 277–278.
[24] Schizophrenia Working Group of the Psychiatric Genomics Consortium: Ripke S, Neale BM, O’Donovan MC. Biological insights from 108 schizophrenia-associated genetic loci. Nature 2014; 511 (7510): 421-427.
[25] Freedman R, Coon H, Myles-Worsley M, et al. Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. PNAS 1997; 94 (2): 587–592.
[26] Binder MR. Introducing the term “Neuroregulator” in Psychiatry. AJCEM 2019; 7 (3): 66-70.
[27] Binder MR. FLASH Syndrome: tapping into the root of chronic illness. AJCEM 2020; 8 (6): 101-109.
[28] Latvala A, Kuja-Halkola R, Rick C, et al. Association of resting heart rate and blood pressure in late adolescence with subsequent mental disorders: A longitudinal population study of more than 1 million men in Sweden. JAMA Psychiatry 2016; 73 (12): 1268-1275.
[29] Blom EH, Serlachius E, Chesney MA, Olsson EMG. Adolescent girls with emotional disorders have a lower end-tidal CO2 and increased respiratory rate compared with healthy controls. Psychophysiology 2014; 51 (5): 412-418.
[30] Colangelo LA, Yano Y, Jacobs Jr DR, Lloyd-Jones DM. Association of Resting Heart Rate With Blood Pressure and Incident Hypertension Over 30 Years in Black and White Adults: The CARDIA Study. Hypertension 2020; 76 (3): 692- 698.
[31] Shi Y, Zhou W, Liu S, et al. Resting heart rate and the risk of hypertension and heart failure: a dose-response meta- analysis of prospective studies. J Hypertens 2018; 36 (5): 995-1004.
[32] Shen L, Wang Y, Jiang X, et al. Dose-response association of resting heart rate and hypertension in adults: A systematic review and meta-analysis of cohort studies. Medicine (Baltimore) 2020; 99 (10): e19401.
[33] Dalal J, Dasbiswas A, Sathyamurthy I, et al. Heart Rate in Hypertension: Review and Expert Opinion. International Journal of Hypertension 2019.
[34] Lee DH, de Rezende LFM, Hu FB, Jeon JY, Giovannucci EL. Resting heart rate and risk of type 2 diabetes: a prospective cohort study and meta-analysis. Diabetes Metab Res Rev 2019; 35 (2): e3095.
[35] Aune D, o’Hartaigh B, Vatten LJ. Resting heart rate and the risk of type 2 diabetes: A systematic review and dose-response meta-analysis of cohort studies. Nutr Metab Cardiovasc Dis 2015; 25 (6): 526-534.
[36] Nagaya T, Yoshida H, Takahashi H, Kawai M. Resting heart rate and blood pressure, independent of each other, proportionally raise the risk for type-2 diabetes mellitus. Int J Epidemiol 2010; 39 (1): 215-222.
[37] Kannel W, Kannel C, Paffenbarger R, Cupples A. Heart rate and cardiovascular mortality: The Framingham study. Am Heart J 1987; 113: 1489-1494.
[38] Gillum R, Makuc D, Feldman J. Pulse rate, coronary heart disease, and death: The NHANES I epidemiologic follow-up study. Am Heart J 1991; 121: 172-177.
[39] Cooney MT, Vartiainen E, Laatikainen T, et al. Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. Am Heart J 2010; 159 (4): 612-619.
[40] Khan H, Kunutsor S, Kalogeropoulos AP, et al. Resting heart rate and risk of incident heart failure: three prospective cohort studies and a systematic meta-analysis. J Am Heart Assoc 2015; 4 (1): e001364.
[41] Alhalabi L, Singleton MJ, Oseni AO, et al. Relation of higher resting heart rate to risk of cardiovascular versus noncardiovascular death. Am J Cardiol 2017; 119 (7): 1003- 1007.
[42] Zhang D, Shen X, Qi X. Resting heart rate and all-cause and cardiovascular mortality in the general population: a meta- analysis. CMAJ 2016; 188 (3): E53-E63.
[43] Yu J, Dai L, Zhao Q. Association of cumulative exposure to resting heart rate with risk of stroke in general population: The Kailuan Cohort Study. Journal of Stroke and Cardiovascular Diseases 2017; (26): 11: 2501-2509.
[44] Huang Y-Q, Shen G, Huang J-Y, Zhang B, Feng Y-Q. A nonlinear association between resting heart rate and ischemic stroke among community elderly hypertensive patients. Postgrad Med 2020; 132 (2): 215-219.
[45] Aune D, Sen A, o’Hartaigh B, et al. Resting heart rate and the risk of cardiovascular disease, total cancer, and all-cause mortality - A systematic review and dose-response meta- analysis of prospective studies. Nutr Metab Cardiovasc Dis 2017; 27 (6): 504-517.
[46] Eriksen BO, Småbrekke S, Jenssen TG, et al. Office and ambulatory heart rate as predictors of age-related kidney function decline: A population-based cohort study. Hypertension 2018; 72 (3): 594-601.
[47] Anker MS, Ebner N, Hildebrandt B, et al. Resting heart rate is an independent predictor of death in patients with colorectal, pancreatic, and non-small cell lung cancer: results of a prospective cardiovascular long-term study. European Journal of Heart Failure 2016; 18 (12).
[48] Park J, Kim JH, Park Y. Resting heart rate is an independent predictor of advanced colorectal adenoma recurrence. PLoS One 2018; 13 (3): e0193753.
[49] Burke SL. Resting heart rate moderates the relationship between neuropsychiatric symptoms, MCI, and Alzheimer’s disease. Innov Aging 2019; 3 (suppl 1): S641.
[50] Jouven X, Empana J-P, Schwartz PJ, et al. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med 2005; 352: 1951-1958.
[51] Baumert M, Linz D, Stone K, et al. Mean nocturnal respiratory rate predicts cardiovascular and all-cause mortality in community-dwelling older men and women. European Respiratory Journal 2019; DOI: 10.1183/13993003.02175-2018.
[52] Eick C, Groga-Bada P, Reinhardt K, et al. Nocturnal respiratory rate as a predictor of mortality in patients with acute coronary syndrome. Openheart 2018; 5 (2).
[53] Dommasch M, Sinnecker D, Barthel P, et al. Nocturnal respiratory rate predicts non-sudden cardiac death in survivors of acute myocardial infarction. J Am Coll Cardiol 2014; 63: 2432-2433.
[54] Akiskal HS, Maser JD, Zeller PJ, et al. Switching from 'unipolar' to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995; 52 (2): 114-23.
[55] Rose GM, Diamond DM, Pang K, Dunwiddie TV. Primed burst potentiation: lasting synaptic plasticity invoked by physiologically patterned stimulation. In: Haas HL, Buzsàki G. (eds) Synaptic plasticity in the hippocampus. Springer, Berlin, Heidelberg, 1988.
[56] Pacchiarotti I, Bond DJ, Baldessarini RJ, et al. The international society for bipolar disorders (isbd) task force report on antidepressant use in bipolar disorders. Am J Psychiatry 2013; 170: 1249–1262.
[57] Kahn DA, Sachs GS, Printz DJ, Carpenter D. Medication treatment of bipolar disorder 2000: A summary of the expert consensus guidelines. Journal of Psychiatric Practice 2000; 6 (4): 197-211.
[58] Young LT. What is the best treatment for bipolar depression? J Psychiatry Neurosci 2008; 33 (6): 487-488.
[59] Ghaemi SN. Bipolar spectrum: a review of the concept and a vision for the future. Psychiatry Investig 2013; 10 (3): 218-224.
[60] Aghajanian GK and Marek GJ. Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 1997; 36 (4-5): 589-599.
[61] Cardamone L, Salzberg MR, Koe AS, et al. (2014) Chronic antidepressant treatment accelerates Kindling epileptogenesis in rats. Neurobiol Dis. 63: 194-200.
[62] El-Mallakh RS, Vöhringer PA, Ostacher MM, et al. Antidepressants worsen rapid-cycling course in bipolar depression: A STEP-BD randomized clinical trial. Journal of Affective Disorders 2015; 184: 318-321.
[63] Binder MR. Gabapentin—the popular but controversial anticonvulsant drug may be zeroing in on the pathophysiology of disease. AJCEM 2021; 9 (4): 122-134.
[64] Dean K, Stevens H, Mortensen PB, Full Spectrum of Psychiatric Outcomes Among Offspring With Parental History of Mental Disorder. Arch Gen Psychiatry 2010; 67 (8): 822-829.
[65] Hawes DJ, Brennan J, Dadds MR. Cortisol, callous-unemotional traits, and pathways to antisocial behavior. Curr Opin Psychiatry 2009; 22 (4): 357-362.
[66] Skeem J, Johansson P, Andershed H, Kerr M, Louden JE. Two subtypes of psychopathic violent offenders that parallel primary and secondary variants. J Abnorm Psychol 2007; 116 (2): 395–409.
[67] Latvala A, Kuja-Halkola R, Almqvist C, Larsson H, Lichtenstein P. A Longitudinal study of resting heart rate and violent criminality in more than 700 000 men. JAMA Psychiatry 2015; 72 (10): 971-978.
[68] Brody DJ, Gu Q. Antidepressant use among adults: United States, 2015-2018. National Center for Health Statistics. NCHS Data Brief No. 377, September 2020.
[69] Sultan RS, Correll CU, Schoenbaum M, et al. National patterns of commonly prescribed psychotropic medications to young people. J Child Adolesc Psychopharmacol 2018; 28 (3): 158-165.
[70] Chong Y, Fryar CD, Q. Prescription sleep aid use among adults: United States, 2005–2010. NCHS Data Brief. 127, August, 2013.
[71] Cascade E, Kalali AH, Weisler RH. Varying uses of anticonvulsant medications. Psychiatry (Edgmont) 2008; 5 (6): 31-33.
[72] Pigott HE. The STAR*D trial: It is time to reexamine the clinical beliefs that guide the treatment of major depression. Can J Psychiatry 2015; 60 (1); 9-13.
[73] Keuroghlian AS, Frankenburg FR, Zanarini MC. The relationship of chronic medical illnesses, poor health-related lifestyle choices, and health care utilization to recovery status in borderline patients over a decade of prospective follow-up. J Psychiatr Res. 2013 Oct; 47 (10): 1499-506.
[74] Heninger GR, Delgado PL, Charney DS. The revised monoamine theory of depression: a modulatory role for monoamines, based on new findings from monoamine depletion experiments in humans. Pharmacopsychiatry 1996; 29 (1): 2-11.
[75] Bowcut, JC and Weiser, M. Inflammation and schizophrenia. Psychiatric Annals 2018; 48 (5): 237-243.
[76] Boorman, E, Romano, GF, Russell, A, Mondelli, V, Pariante, CM. Are mood and anxiety disorders inflammatory diseases? Psychiatric Annals 2015; 45 (5): 240-248.
[77] Liu B, Liu J, Wang M, Zhang Y, Li L. From serotonin to neuroplasticity: evolvement of theories for major depressive disorder. Front Cell Neurosci 2017; 11: 305.
[78] Allen J, Roman-Tallon R, Brymer KJ, Caruncho HJ, Kalynchuk LE. Mitochondria and Mood: Mitochondrial Dysfunction as a Key Player in the Manifestation of Depression. Frontiers in Neuroscience 2018; 12: 386.
Cite This Article
  • APA Style

    Michael Raymond Binder. (2021). A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders. American Journal of Clinical and Experimental Medicine, 9(6), 223-232. https://doi.org/10.11648/j.ajcem.20210906.16

    Copy | Download

    ACS Style

    Michael Raymond Binder. A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders. Am. J. Clin. Exp. Med. 2021, 9(6), 223-232. doi: 10.11648/j.ajcem.20210906.16

    Copy | Download

    AMA Style

    Michael Raymond Binder. A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders. Am J Clin Exp Med. 2021;9(6):223-232. doi: 10.11648/j.ajcem.20210906.16

    Copy | Download

  • @article{10.11648/j.ajcem.20210906.16,
      author = {Michael Raymond Binder},
      title = {A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders},
      journal = {American Journal of Clinical and Experimental Medicine},
      volume = {9},
      number = {6},
      pages = {223-232},
      doi = {10.11648/j.ajcem.20210906.16},
      url = {https://doi.org/10.11648/j.ajcem.20210906.16},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajcem.20210906.16},
      abstract = {Medication, psychotherapy, or both are the most common approaches to the treatment of psychiatric disorders. However, due to the high incidence, early onset, and chronicity of psychiatric symptoms, both medication and psychotherapy can be resource-intensive, yet there is little consensus about which should be applied to which clinical syndromes. This is a matter of increasing concern in light of the growing mental health crisis. Much of the problem stems from the lack of a precise psychophysiological explanation for psychiatric symptomatology, as it leaves clinicians without a clear target for treatment. However, an emerging hypothesis—one that identifies the fundamental vulnerability trait in psychiatric disorders—has the potential to help solve these problems. According to the Multi-Circuit Neuronal Hyperexcitability (MCNH) Hypothesis, psychiatric symptoms are driven by an abnormal elevation in the activity of the neural circuits with which they are associated. Particularly under the influence of stress, too many neurons fire for too long, resulting in circuit-specific symptoms, such as anxiety, depression, irritability, insomnia, inattention, apathy, and obsessional thinking. What hypothetically determines which circuits will be pathologically hyperactive at any point in time are the aberrant neuronal discharges that tend to occur spontaneously or in conjunction with willful cognitions and emotions when the neurological system is hyperexcitable. Clinical application of this hypothesis has the potential to guide which form of treatment would be most effective for which patient and to streamline the use of medications and other medical interventions because it illuminates a specific target for treatment. It also has the potential, for the first time in history, to prevent the development of psychiatric symptoms because the trait of neuronal hyperexcitability is highly modifiable and can be identified objectively by simply measuring one’s resting vital signs. Moreover, because the trait of neuronal hyperexcitability also appears to be at the root of a wide range of general medical conditions, such as diabetes, high blood pressure, cardiovascular disease, and cancer, the early detection and management of the trait could usher in history’s greatest campaign in the first against sickness and disease.},
     year = {2021}
    }
    

    Copy | Download

  • TY  - JOUR
    T1  - A Pathophysiologically-Based Approach to the Treatment and Prevention of Mental Illness and Its Related Disorders
    AU  - Michael Raymond Binder
    Y1  - 2021/12/11
    PY  - 2021
    N1  - https://doi.org/10.11648/j.ajcem.20210906.16
    DO  - 10.11648/j.ajcem.20210906.16
    T2  - American Journal of Clinical and Experimental Medicine
    JF  - American Journal of Clinical and Experimental Medicine
    JO  - American Journal of Clinical and Experimental Medicine
    SP  - 223
    EP  - 232
    PB  - Science Publishing Group
    SN  - 2330-8133
    UR  - https://doi.org/10.11648/j.ajcem.20210906.16
    AB  - Medication, psychotherapy, or both are the most common approaches to the treatment of psychiatric disorders. However, due to the high incidence, early onset, and chronicity of psychiatric symptoms, both medication and psychotherapy can be resource-intensive, yet there is little consensus about which should be applied to which clinical syndromes. This is a matter of increasing concern in light of the growing mental health crisis. Much of the problem stems from the lack of a precise psychophysiological explanation for psychiatric symptomatology, as it leaves clinicians without a clear target for treatment. However, an emerging hypothesis—one that identifies the fundamental vulnerability trait in psychiatric disorders—has the potential to help solve these problems. According to the Multi-Circuit Neuronal Hyperexcitability (MCNH) Hypothesis, psychiatric symptoms are driven by an abnormal elevation in the activity of the neural circuits with which they are associated. Particularly under the influence of stress, too many neurons fire for too long, resulting in circuit-specific symptoms, such as anxiety, depression, irritability, insomnia, inattention, apathy, and obsessional thinking. What hypothetically determines which circuits will be pathologically hyperactive at any point in time are the aberrant neuronal discharges that tend to occur spontaneously or in conjunction with willful cognitions and emotions when the neurological system is hyperexcitable. Clinical application of this hypothesis has the potential to guide which form of treatment would be most effective for which patient and to streamline the use of medications and other medical interventions because it illuminates a specific target for treatment. It also has the potential, for the first time in history, to prevent the development of psychiatric symptoms because the trait of neuronal hyperexcitability is highly modifiable and can be identified objectively by simply measuring one’s resting vital signs. Moreover, because the trait of neuronal hyperexcitability also appears to be at the root of a wide range of general medical conditions, such as diabetes, high blood pressure, cardiovascular disease, and cancer, the early detection and management of the trait could usher in history’s greatest campaign in the first against sickness and disease.
    VL  - 9
    IS  - 6
    ER  - 

    Copy | Download

Author Information
  • Department of Psychiatry, North Shore University Health System, Highland Park, USA

  • Sections