The Schizophrenia hypothesis: Tyrosine hydroxylase pathway

Year 2025, Volume: 34 Issue: 1, 25 - 30, 31.03.2025

Osman Ozdemir

https://doi.org/10.17827/aktd.1574857

Abstract

It has been previously reported that there was no significant difference in tyrosine hydroxylase activity between schizophrenia patients and controls. In that case, where does an excessive dopamine come from in the patients with psychosis. It should be come back here and this hypothesis must be rehandle and reconsider over and over. On the other hand, as expected, high tyrosine hydroxylase activity showed in basal ganglia, putamen, caudate nucleus and nucleus accumbens, in patient with schizophrenia compared to controls.

Keywords

Tyrosine hydroxylase pathway, dopamine, phosphorylation, schizophrenia, hypothesis

Şizofreni hipotezi: Tirozin hidroksilaz yolağı

Abstract

Daha önce şizofreni hastaları ve kontroller arasında tirozin hidroksilaz aktivitesinde önemli bir fark olmadığı bildirilmişti. O zaman psikoz hastalarında aşırı dopamin nereden geliyor? Buraya geri dönülmeli ve bu hipotez tekrar tekrar ele alınmalı ve yeniden düşünülmelidir. Öte yandan, beklendiği gibi, şizofreni hastalarında kontrollerle karşılaştırıldığında bazal ganglionlarda, putamende, kaudat çekirdekte ve çekirdek akumbenste yüksek tirozin hidroksilaz aktivitesi gösterildi.

Keywords

Tirozin hidroksilaz yolağı, dopamin, fosforilasyon, şizofreni, hipotez

References

• 1. Glantz LA, Gilmore JH, Lieberman JA, et al. Apoptotic mechanisms and the synaptic pathology of schizophrenia. Schizophr Res 2006; 81:47–63.
• 2. Zheng W, Wang H, Zeng Z, et al. The possible role of the Akt signaling pathway in schizophrenia. Brain Res 2012; 1470, 145–158.
• 3. Crow TJ, Baker HF, Cross AJ, et al. Monoamine mechanisms in chronic schizophrenia: post-mortem neurochemical findings. Br J Psychiatry 1979; 134:249–256.
• 4. Jarskog, LF. Apoptosis in schizophrenia: pathophysiologic and therapeutic considerations. Curr Opin Psychiatry 2006;19:307–312.
• 5. Ichinose H, Ohye T, Fujita K, et al. Quantification of mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in the substantia nigra in Parkinson’s disease and schizophrenia. J Neural Transm - Parkinsons Disease and Dementia Section, 1994;8:149–158.
• 6. Meiser J, Weindl D, Hiller K. Complexity of dopamine metabolism. Cell Commun Signal 2013; 11:34.
• 7. Snyder SH. Amphetamine Psychosis: A “Model” Schizophrenia Mediated by Catecholamines. Am J Psychiatry 1973; 130:61–67.
• 8. Davis KL, Kahn RS, Ko G, et al. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991; 148:1474–1486.
• 9. American Psychiatric Association (2013) Diagnostic and Statistical Manuel of Mental Disorders, Fifth Edition. Arlington, VA, American Psychiatric Publishing.
• 10. Funk AJ, McCullumsmith RE, Haroutunian V, et al. Abnormal Activity of the MAPK- and cAMP-Associated Signaling Pathways in Frontal Cortical Areas in Postmortem Brain in Schizophrenia. Neuropsychopharmacology 2011; 37:896–905.
• 11. McGuire JL, Depasquale EA, Funk AJ, et al. Abnormalities of signal transduction networks in chronic schizophrenia. Npj Schizophrenia 2017; 3(1).
• 12. Sternberg D, VanKammen D, Lerner P, Bunney W. Schizophrenia: dopamine beta-hydroxylase activity and treatment response. Science 1982; 216:1423–1425.
• 13. Tang S, Yao B, Li N, Lin S, Huang Z. Association of Dopamine Beta-Hydroxylase Polymorphisms with Alzheimer’s Disease, Parkinson’s Disease and Schizophrenia: Evidence Based on Currently Available Loci. Cell Physiol Biochem 2018; 51:411–428.
• 14. Castellani S. Plasma Norepinephrine and Dopamine-β-Hydroxylase Activity in Schizophrenia. Arch Gen Psychiatry 1982; 39:1145-1149.
• 15. Barlas İÖ, Semiz U, Erdal ME, et al. Association between dopamine beta hydroxylase gene polymorphism and age at onset in male schizophrenia. Acta Neuropsychiatr 2012; 24:176–182.
• 16. Ichinose H, Kurosawa Y, Titani K, Fujita K, Nagatsu T. Isolation and characterization of a cDNA clone encoding human aromatic L-amino acid decarboxylase. Biochem Biophys Res Commun 1989; 164;1024–1030.
• 17. Lloyd KG, Hornykiewicz O. Occurence and distribution of aromatic L-amino acid (L-DOPA) decarboxylase in the human brain. J Neurochem 1972; 19:1549–1559.
• 18. Reith J, Benkelfat C, Sherwin A, Yasuhara Y, Kuwabara H, et al. Elevated dopa decarboxylase activity in living brain of patients with psychosis. Proc Natl Acad Sci USA 1994; 91:11651–11654.
• 19. Buckland PR, Marshall R, Watkins P, McGuffin P. Does phenylethylamine have a role in schizophrenia?: LSD and PCP up-regulate aromatic l-amino acid decarboxylase mRNA levels. Brain Res Mol Brain Res 1997; 49:266–270.
• 20. Fernstrom JD, Fernstrom MH. Tyrosine, Phenylalanine, and Catecholamine Synthesis and Function in the Brain. J Nutr 2007; 137:1539S–1547S.
• 21. Chao HM, Richardson MA. Aromatic amino acid hydroxylase genes and schizophrenia. Am J Med Genet 2002; 114:626–630.
• 22. Fernstrom JD. Aromatic amino acids and monoamine synthesis in the central nervous system: influence of the diet. J Nutr Biochem 1990; 1:508–517.
• 23. Kastner A, Hirsch EC, Agid Y, Javoy-Agid F. Tyrosine hydroxylase protein and messenger RNA in the dopaminergic nigral neurons of patients with Parkinson’s disease. Brain Res 1993; 606:341–345.
• 24. Lewis DA, Melchitzky DS, Haycock JW. Four isoforms of tyrosine hydroxylase are expressed in human brain. Neuroscience 1993; 54:477–492.
• 25. Toru M, Nishikawa T, Mataga N, et al. Dopamine metabolism increases in post-mortem schizophrenic basal ganglia. J Neural Transm 1982; 54:181–191.
• 26. Kilbourne EJ, Nankova BB, Lewis EJ, McMahon A, Osaka H, Sabban DB, and Sabban EL. Regulated expression of the tyrosine hydroxylase gene by membrane depolarization. Identification of the responsive element and possible second messengers. J Biol Chem 1992; 267:7563-7569.
• 27. Xu X, Wang R, Hao Z, et al. DJ-1 regulates tyrosine hydroxylase expression through CaMKKβ/CaMKIV/CREB1 pathway in vitro and in vivo. J Cell Physiol 2019; 235:869-879.
• 28. Masserano J, Weiner N. Tyrosine hydroxylase regulation in the central nervous system. Mol Cell Biochem 1983; 53-54:129-152.
• 29. Haavik J, Toska K. Tyrosine hydroxylase and Parkinson’s disease. Mol Neurobiol 1998; 16:285–309.
• 30. Bobrovskaya L, Gilligan C, Bolste, EK., et al. Sustained phosphorylation of tyrosine hydroxylase at serine 40: a novel mechanism for maintenance of catecholamine synthesis. J Neurochem 2007; 100:479–489.
• 31. Ames MM, Lerner P, Lovernberg W. Tyrosine Hydroxylase activation by protein phosphorylation and end product inhibition. J Biol Chem 1978; 253:27-31.
• 32. Cho SG, Choi EJ. Apoptotic signaling pathways: Caspases and stress-activated protein kinases. J Biochem Mol Biol 2002; 35:24-27.
• 33. De Nadal E, Posas F. Multilayered control of gene expression by stress-activated protein kinases. The EMBO Journal 2009; 29:4–13.
• 34. Tardito D. Abnormal Levels of cAMP-dependent Protein Kinase Regulatory Subunits in Platelets from Schizophrenic Patients. Neuropsychopharmacology 2000; 23:216–219.
• 35. Jarskog LF, Selinger ES, Lieberman JA, Gilmore JH. Apoptotic Proteins in the Temporal Cortex in Schizophrenia: High Bax/Bcl-2 Ratio Without Caspase-3 Activation. Am J Psychiatry 2004; 161:109–115.
• 36. Jarskog LF, Glantz LA, Gilmore JH, Lieberman JA. Apoptotic mechanisms in the pathophysiology of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:846–858.
• 37. Gassó P, Mas S, Molina O, et al. Increased susceptibility to apoptosis in cultured fibroblasts from antipsychotic-naïve first-episode schizophrenia patients. J Psychiatr Res 2014 48:94–101.
• 38. Féron F, Perry C, Hirning MH, McGrath J, Mackay-Sim A. Altered adhesion, proliferation and death in neural cultures from adults with schizophrenia. Schizophr Res 1999; 40:211–218.
• 39. Morén C, Treder N, Martínez-Pinteño A, et al. Systematic review of the therapeutic role of apoptotic inhibitors in neurodegeneration and their potential use in schizophrenia. Antioxidants (Basel) 2022; 11:2275.
• 40. Jones MC, Koh JM, Cheong KH. Synaptic Pruning in Schizophrenia: Does Minocycline Modulate Psychosocial Brain Development? BioEssays 2020; 42:e2000046.
• 41. Boyajyan AS, Chavushyan AS, Zakharyan RV, Mkrtchyan GM. Markers of apoptotic dysfunctions in schizophrenia. Mol Biol 2013; 47:587–591.