Electrophysiology of Self and Mood Disorder as an Energy Shift: Mitochondrial Dysfunction and Medical Comorbidity, Beyond the Metabolic Syndrome
Main Article Content
Abstract
Depressive and manic episodes of bipolar disorder are characterized by decreased and increased energy. As the duration of the disease increases, psychomotor retardation and anhedonia become dominant. Increased activity in the Default Mode Network and decreased activity in the Salience Network and Central Executive Network have been associated with Glutamate/GABA (Gamma- Aminobutyric Acid) imbalance. Medical comorbidity has an etiological partnership as well as medication burden and lifestyle. According to the entropy change we calculated on EEG (Electroencephalography), we classified mood disorders into three groups. Including family history, which is true comorbidity, was framed by physical illnesses. We showed how the entropy change in chaotic phase transitions in cases diagnosed with bipolar disorder is regulated by lithium. Cross frequency coupling delta/beta appears both as a trait to deal with depressive symptoms and as a state to reveal mixed symptoms. Delta activity is predictive of response to lithium and ECT (Electroconvulsive Therapy), and nonresponse to antidepressants. It is a gabaergic dysfunction. Self pathology has been proposed as a mental projection of bipolar disorder. There is a decrease in glutamic acide decarboxilase enzyme activity, which is responsible for GABA production at the molecular level. GABA is a metabolite of Krebs. Also in immune cells. The GABA shunt plays an important role in preventing the accumulation of reactive oxygen species and cell death. The price for this is disruption in phosphorylation processes, which is reflected in the energy balance. In this article, three planes are tried to be brought together with their projections on each other: Self pathology on the mental plane, mood disorder on the brain plane, medical comorbidity on the body plane.
Keywords:
Mood disorder, affective spectrum, medical comorbidity, metabolic syndrome, GABA shunt, self patology, EEG
Article Details
How to Cite
KESEBIR, Sermin.
Electrophysiology of Self and Mood Disorder as an Energy Shift: Mitochondrial Dysfunction and Medical Comorbidity, Beyond the Metabolic Syndrome.
Medical Research Archives, [S.l.], v. 13, n. 7, july 2025.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/6765>. Date accessed: 05 dec. 2025.
doi: https://doi.org/10.18103/mra.v13i7.6765.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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31. Goodwin, F.K, Jamison, K.R. Manic-Depressive Illness. Second Edition. Oxford University Press. 2007; Newyork.
32. Kappelmann N., Lewis G., Dantzer R., Jones P.B., Khandaker G.M. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018;23(2):335–343.
33. Binks S. Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain. 2018;141(8):2263–2271.
34. Mass E. A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease. Nature. 2017;549(7672):389–393.
35. Kesebir S. Depresyonda nörobiyolojik açıdan tanı ve tedavide yeni gelişmeler. Psikiyatride Güncel. 2022; 12(3): 244-52.
36. Tatlidil Yaylaci E., Kesebir S., Güngördü Ö. The relationship between impulsivity and lipid levels in bipolar patients: does temperament explain it? Compr Psychiatry. 2014; 55(4):883-886.
37. Turan C., Kesebir S., Süner O. Are ICAM, VCAM and E-selectin levels different in first manic episode and subsequent remission? J Affect Disord. 2014;163:76-80. doi: 10.1016/j.jad.2014.03.052.
38. Dargél A.A., Volant S., Saha S., Etain B., Grant R., Azorin J.M., Gard S., Bellivier F., Bougerol T., Roux P., Aubin V., Courtet P., Leboyer M. & FACE-BD collaborators, Scott J., Henry C. Activation Levels, Cardiovascular Risk, and Functional Impairment in Remitted Bipolar Patients: Clinical Relevance of a Dimensional Approach. Psychother Psychosom. 2019;88(1):45-47.
39. Robert H., Cornier M.A. Update on the NCEP ATP-III emerging cardiometabolic risk factors. BMC Med. 2014;12: 115.
40. Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res. 2018;10(6):453-460. doi: 10.14740/jocmr3389w.
41. Güven S., Kesebir S,, Demirer R.M., Bilici M. Electroencephalography Spectral Power Density in First-Episode Mania: A Comparative Study with Subsequent Remission Period. Noro Psikiyatr Ars. 2015;52(2):194-197. doi: 10.5152/npa.2015.7180.
42. Kesebir S., Demirer R.M., Tarhan N. CFC delta-beta is related with mixed features and response to treatment in bipolar II depression. Heliyon. 2019;13e01898. doi: 10.1016/j.heliyon.2019.e01898.
43. Kesebir S., Vahip S., Akdeniz F., Yüncü Z., Alkan M., Akiskal H. Affective temperaments as measured by TEMPS-A in patients with bipolar I disorder and their first-degree relatives: a controlled study. J Affect Disord. 2005;85(1-2):127-33. doi: 10.1016/j.jad.2003.10.013.
44. Vahip S., Kesebir S., Alkan M., Yazici O., Akiskal K.K., Akiskal H.S. Affective temperaments in clinically-well subjects in Turkey: initial psychometric data on the TEMPS-A. J Affect Disord. 2005;85(1-2):113-25. doi: 10.1016/j.jad.2003.10.011.
45. Kesebir S. Comorbid impulse control disorder in bipolar disorder: the role of antidepressants. Turk Psikiyatri Derg. 2012;23(1):71.
46. Kesebir S., Yosmaoglu A., Tarhan N. A dimensional approach to affective disorder: The relations between Scl-90 subdimensions and QEEG parameters. Front Psychiatry. 2022;15;13:651008. doi: 10.3389/fpsyt.2022.651008.
47. Demirer R.M., Kesebir S. The entropy of chaotic transitions of EEG phase growth in bipolar disorder with lithium carbonate. Sci Rep. 2021;4;11(1):11888. doi: 10.1038/s41598-021-91350-9.
48. Tsuda I., Fujii H. A complex systems approach to an interpretation of dynamic brain activity I: chaotic itinerancy can provide a mathematical basis for information processing in cortical transitory and nonstationary dynamics. In Summer School on Neural Networks (2003).
2. Holmes S.E., Scheinost D., Finnema S.J., Naganawa M., Davis M.T., DellaGioia N., Nabulsi N., Matuskey D., Angarita G.A., Pietrzak R.H., Duman R.S., Sanacora G., Krystal J.H., Carson R.E., Esterlis I. Lower synaptic density is associated with depression severity and network alterations. Nat Commun. 2019; 4;10(1):1529.
3. Sanacora G., Frye M.A., McDonald W., Mathew S.J., Turner M.S., Schatzberg A.F., Summergrad P., Nemeroff C.B., American Psychiatric Association (APA) Council of Research Task Force on Novel Biomarkers and Treatments. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;1;74(4):399-405.
4. Kesebir S. The two new biomarker in Mood Disorder: Bipolar EEG, Bipolar Self. Medical Research Archives. 2024;12(2) https://doi.org/10.18103/mra.v12i2.5071.
5. Kesebir S., Koc M.I., Yosmaoglu A. Bipolar Spectrum Disorder May Be Associated With Family History of Diseases. J Clin Med Res. 2020;12(4):251-254. doi: 10.14740/jocmr4143.
6. Krapelin E. Manic depressive Insanity and Paranoia. E&S Livingstone, 1921. Edinburgh.
7. Kesebir S., Yosmaoğlu A. QEEG in affective disorder: about to be a biomarker, endophenotype and predictor of treatment response. Heliyon. 2018;22;4(8): e00741.
8. Kesebir S., Yosmaoğlu A. QEEG - spectral power density of brain regions in predicting risk, resistance and resilience for bipolar disorder: A comparison of first degree relatives and unrelated healthy subjects. Heliyon. 2020; 6;6(6):e04100. doi: 10.1016/j.heliyon.2020.e04100.
9. Vogel F. The genetic basis of the normal human EEG. Hum. Genet. 1970;10:91–114. doi: 10.1007/BF00295509.
10. Kohut H., Wolf E.S. The disorders of the self and their treatment: An outline. The İntl J Psychoanalysis. 1978;59: 413-426.
11. Kesebir S. Metabolic syndrome and childhood trauma: Also comorbidity and complication in mood disorder. World J Clin Cases. 2014;16;2(8):332-7. doi: 10.12998/wjcc.v2.i8.332.
12. Yüncü Z., Kesebir S., Akdeniz F., Vahip S. Anticipation in bipolar disorder: A comparison between two generations. Turk Psikiyatri Derg. 2008;19(4):349-57.
13. Kesebir S, Vahip S, Akdeniz F, Yüncü Z. (2005) The relationship of affective temperament and clinical features in bipolar disorder. Türk Psikiyatr Derg, 16: 164-9.
14. Kesebir S. (2025) Self psychology and Mood Disorder. Curr Psychiatr Appr, 32: 11-27.
15. Karova Z.Y., Kesebir S. (2021) Is there a relationship between self and mood? Bipolar Disord. 23: 68.
16. Qin P., Northoff G. How is our self related to midline regions and the default-mode network? Neuroimage. 2011;1;57(3):1221-33.
17. Northoff G., Sibille E. Cortical GABA neurons and self-focus in depression: a model linking cellular, biochemical and neural network findings. Mol Psychiatry. 2014;19(9):959.
18. Wolff A., Berberian N., Golesorkhi M., Gomez-Pilar J., Zilio F., Northoff G. Intrinsic neural timescales: temporal integration and segregation. Trends Cogn Sci. 2022;26(2):159-173.
19. Morris G., Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015;1:13:68.
20. Salminen A., Jouhten P., Sarajärvi T., Haapasalo A., Hiltunen M. Hypoxia and GABA shunt activation in the pathogenesis of Alzheimer's disease. Neurochem Int. 2016;92:13-24. doi: 10.1016/j.neuint.2015.11.005.
21. Bouche N., Fait A., Bouchez D., Møller S.G., Fromm H. Mitochondrial succinic-semialdehyde dehydrogenase of the gamma-aminobutyrate shunt is required to restrict levels of reactive oxygen intermediates in plants. Proc Natl Acad Sci U S A. 2023; 27;100(11):6843-8. doi: 10.1073/pnas.1037532100.
22. Ravasz D., Kacso G., Fodor V., Horvath K., Adam-Vizi V., Chinopoulos C. Catabolism of GABA, succinic semialdehyde or gamma-hydroxybutyrate through the GABA shunt impair mitochondrial substrate-level phosphorylation. Neurochem Int. 2017;109:41-53. doi: 10.1016/j.neuint.2017.03.008.
23. Kato T. Mitochondrial dysfunction and bipolar disorder. Curr TOP Behav Neurosci. 2011;5:187-200.
24. Lamigeon C., Prod'Hon C., De Frias V., Michoudet C., Jacquemont B. Enhancement of neuronal protection from oxidative stress by glutamic acid decarboxylase delivery with a defective herpes simplex virus vector. Exp Neurol. 2003;184(1):381-92. doi: 10.1016/s0014-4886(03)00400-x.
25. Kesebir S., HaJiyeva G., Guliyev E., Yosmaoğlu A. Bipolarity Trait Index. Bipolar Disord. 2022; 24: 47-48.
26. Cavalcanti-de-Albuquerque J.P., de-Souza-Ferreira E., de Carvalho D.P., Galina A. Coupling of GABA Metabolism to Mitochondrial Glucose Phosphorylation. Neurochem Res. 2022;47(2):470-480. doi: 10.1007/s11064-021-03463-2.
27. Kesebir S., Tatlıdil Yaylacı E., Süner O., Gültekin B.K. Uric acid levels may be a biological marker for the differentiation of unipolar and bipolar disorder: the role of affective temperament. J Affect Disord. 2014;165:131-4. doi: 10.1016/j.jad.2014.04.053.
28. Kesebir S. (2022) Bipolarity Trait Index. Bipolar Disorder, 21: 72.
29. Kesebir S., Demirer R.M. Reclassification of Mood Disorders with Comorbid Medikal Diseases based on Sinai-Ruelle-Bowen/ SRB Entropy Measures. Medical Research Archives. 2023;11(12) https://doi.org/10.18103/mra.v11i12.4881.
30. Martínez-Cagigal V. Multiple Testing Toolbox. MATLAB Central File Exchange (2021) (https://www.mathworks.com/matlabcentral/fileexchange/70604-multiple-testing-toolbox).
31. Goodwin, F.K, Jamison, K.R. Manic-Depressive Illness. Second Edition. Oxford University Press. 2007; Newyork.
32. Kappelmann N., Lewis G., Dantzer R., Jones P.B., Khandaker G.M. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. 2018;23(2):335–343.
33. Binks S. Distinct HLA associations of LGI1 and CASPR2-antibody diseases. Brain. 2018;141(8):2263–2271.
34. Mass E. A somatic mutation in erythro-myeloid progenitors causes neurodegenerative disease. Nature. 2017;549(7672):389–393.
35. Kesebir S. Depresyonda nörobiyolojik açıdan tanı ve tedavide yeni gelişmeler. Psikiyatride Güncel. 2022; 12(3): 244-52.
36. Tatlidil Yaylaci E., Kesebir S., Güngördü Ö. The relationship between impulsivity and lipid levels in bipolar patients: does temperament explain it? Compr Psychiatry. 2014; 55(4):883-886.
37. Turan C., Kesebir S., Süner O. Are ICAM, VCAM and E-selectin levels different in first manic episode and subsequent remission? J Affect Disord. 2014;163:76-80. doi: 10.1016/j.jad.2014.03.052.
38. Dargél A.A., Volant S., Saha S., Etain B., Grant R., Azorin J.M., Gard S., Bellivier F., Bougerol T., Roux P., Aubin V., Courtet P., Leboyer M. & FACE-BD collaborators, Scott J., Henry C. Activation Levels, Cardiovascular Risk, and Functional Impairment in Remitted Bipolar Patients: Clinical Relevance of a Dimensional Approach. Psychother Psychosom. 2019;88(1):45-47.
39. Robert H., Cornier M.A. Update on the NCEP ATP-III emerging cardiometabolic risk factors. BMC Med. 2014;12: 115.
40. Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res. 2018;10(6):453-460. doi: 10.14740/jocmr3389w.
41. Güven S., Kesebir S,, Demirer R.M., Bilici M. Electroencephalography Spectral Power Density in First-Episode Mania: A Comparative Study with Subsequent Remission Period. Noro Psikiyatr Ars. 2015;52(2):194-197. doi: 10.5152/npa.2015.7180.
42. Kesebir S., Demirer R.M., Tarhan N. CFC delta-beta is related with mixed features and response to treatment in bipolar II depression. Heliyon. 2019;13e01898. doi: 10.1016/j.heliyon.2019.e01898.
43. Kesebir S., Vahip S., Akdeniz F., Yüncü Z., Alkan M., Akiskal H. Affective temperaments as measured by TEMPS-A in patients with bipolar I disorder and their first-degree relatives: a controlled study. J Affect Disord. 2005;85(1-2):127-33. doi: 10.1016/j.jad.2003.10.013.
44. Vahip S., Kesebir S., Alkan M., Yazici O., Akiskal K.K., Akiskal H.S. Affective temperaments in clinically-well subjects in Turkey: initial psychometric data on the TEMPS-A. J Affect Disord. 2005;85(1-2):113-25. doi: 10.1016/j.jad.2003.10.011.
45. Kesebir S. Comorbid impulse control disorder in bipolar disorder: the role of antidepressants. Turk Psikiyatri Derg. 2012;23(1):71.
46. Kesebir S., Yosmaoglu A., Tarhan N. A dimensional approach to affective disorder: The relations between Scl-90 subdimensions and QEEG parameters. Front Psychiatry. 2022;15;13:651008. doi: 10.3389/fpsyt.2022.651008.
47. Demirer R.M., Kesebir S. The entropy of chaotic transitions of EEG phase growth in bipolar disorder with lithium carbonate. Sci Rep. 2021;4;11(1):11888. doi: 10.1038/s41598-021-91350-9.
48. Tsuda I., Fujii H. A complex systems approach to an interpretation of dynamic brain activity I: chaotic itinerancy can provide a mathematical basis for information processing in cortical transitory and nonstationary dynamics. In Summer School on Neural Networks (2003).