Projection of Bipolarity to Mitochondria: GABA Shunt is related with Self pathology and Medical Comorbidity in Bipolar Disorder

Main Article Content

Sermin Kesebir


The nature of the relationship with the self-object is the source of mental energy. At this point, the self is a spatiotemporal formation. The self has been found to be associated with the GAD enzyme activity responsible for GABA production at the molecular level. GABA is a metabolite of Krebs. Bipolar disorder is a biphasic state of energy dysregulation as a circadian rithms. Phasic nature of mitochondria to produce ATP may be crucial to the switching of affective states in bipolar disorder. The GABA shunt is an alternative energy production pathway that is activated in response to stress. The GABA shunt plays an important role in preventing the accumulation of reactive oxygen intermediates and cell death. On the other hand, GABA shunt impairs phosphorylation processes. Mitochondrial dysfunction is reflected in glucose, lipid and protein metabolism. A bipolar spectrum is possible at this point, including physical illnesses. A classification of mood disorders based on entropy levels is framed by medical comorbidity.

Keywords: Bipolar Disorder, Mitochondrial disfunction, GABA Shunt, Self pathology, Medical comorbidity

Article Details

How to Cite
KESEBIR, Sermin. Projection of Bipolarity to Mitochondria: GABA Shunt is related with Self pathology and Medical Comorbidity in Bipolar Disorder. Medical Research Archives, [S.l.], v. 12, n. 6, june 2024. ISSN 2375-1924. Available at: <>. Date accessed: 22 july 2024. doi:
Research Articles


1. Kesebir S. Two new biomarkers and Mood Disorders: Bipolar Self, Bipolar EEG. Med Res Arch. 2024;12:e5071.
2. Karova ZY, Kesebir S. Is there a relationship between self and mood ? Bipolar Disord. 2021;23:68.
3. Northoff G, Sibille E. Cortical GABA neurons and self-focus in depression: a model linking cellular, biochemical and neural network findings. Mol Psychiatry. 2014;19:959.
4. Bai Y, Nakao T, Xu J, et al. Resting state glutamate predicts elevated pre-stimulus alpha during self-relatedness: A combined EEG-MRS study on "rest-self overlap". Soc Neurosci. 2016;11:249-263.
5. Kato T. Mitochondrial dysfunction and bipolar disorder. Curr TOP Behav Neurosci. 2011;5: 187-200.
6. Arnold S, Kadenbach B. Cell Respiration is Controlled by ATP, an Allosteric Inhibitor of Cytochrome-c Oxidase. Eur J Biochem. 1997;249: 350-354.
7. Lundkvist G. A, Kwak Y, Davis EK, et al. Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons. J Neurosci. 2005;25:7682-7686.
8. Novakova M, Prasko J, Latalova K, et al. The circadian system of patients with bipolar disorder differs in episodes of mania and depression. Bipolar Disord. 2014;17: 303-314.
9. Masri S, Zocchi L, Katada S, et al. The circadian clock transcriptional complex: metabolic feedback intersects with epigenetic control. Ann N Y Acad Sci. 2012;1264: 103-109.
10. Asher G, Gatfield D, Stratmann M, et al. SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation. Cell. 2008;134:317-328.
11. Abe N, Uchida S, Otsuki K, et al. Altered sirtuin deacetylase gene expression in Patients with a mood disorder. J Psychiatric Res. 2011;45:1106-1112.
12. Zhang Y, Yamamoto T, Hisatome I, et al. Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphateactivated protein kinase and 3 extra cellular signalregulated kinase signal pathways in pancreatic β cells. Mol Cell Endocrinol. 2013;375:89-96.
13. Kesebir S, Tatlidil Yaylaci E, Suner O, et al. 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;165:131-134.
14. Kesebir S. Metabolic syndrome and childhood trauma: Also comorbidity and complication in mood disorder. World J Clin Cases. 2014;16: 332-337.
15. Kesebir S. Epigenetics of Metabolic Syndrome as a Mood Disorder. J Clin Med Res. 2018;10(6):453-460. doi: 10.14740/jocmr3389w.
16. Kesebir S, Koc MI, Yosmaoglu A. Bipolar Spectrum Disorder May Be Associated With Family History of Diseases. J Clin Med Res. 2020;12(4):251-254.
17. Kesebir S, Demirer RM. Reclassification of Mood Disorders with Comorbid Medical Diseases based on Sinai-Ruelle-Bowen/ SRB Entropy Measures. Medical Research Archives. 2023;11(12).
18. Kesebir S, HaJiyeva G, Guliyev E, et al. Bipolarity Trait Index. Bipolar Disord. 2022;24:47-48.
19. Besing R, Paul J, Hablitz L, et al. Circadian Rhythmicity of Active GSK3 Isoforms Modulates Molecular Clock Gene Rhythms in the Suprachiasmatic Nucleus. J Biol Rhythms. 2015;30:155-160.
20. de Bartolomeis A, Tomasetti C. Calcium-Dependent Networks in Dopamine– Glutamate Interaction: The Role of Postsynaptic Scaffolding Proteins. Mol Neurobiol. 2012;46:275-296.
21. Lopez A, Garcia JA, Escames G, et al. Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res. 2009;46:188–198.
22. Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015;1:13:68.
23. Cavalcanti-de-Albuquerque JP, de-Souza-Ferreira E, de Carvalho DP, et al. Coupling of GABA Metabolism to Mitochondrial Glucose Phosphorylation. Neurochem Res. 2022;47(2):470-480. doi: 10.1007/s11064-021-03463-2.
24. Bouché N, Fait A, Bouchez D, et al. 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. 2003;27;100(11):6843-8. doi: 10.1073/pnas.1037532100.
25. Ravasz D, Kacso G, Fodor V, et al. 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.
26. Salminen A, Jouhten P, Sarajärvi T, et al. 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.
27. Lamigeon C, Prod'Hon C, De Frias V, et al. 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.