Những tiến bộ gần đây trong nghiên cứu biomarker trong tâm thần phân liệt: lập bản đồ con đường từ nghiên cứu đến thực hành lâm sàng

Metabolic Brain Disease - Tập 37 - Trang 2197-2211 - 2022
Shivangi Patel1, Dilip Sharma2, Ankit Uniyal3, Akhilesh3, Anagha Gadepalli3, Vinod Tiwari3
1Department of Pharmacology, Bombay College of Pharmacy, Mumbai, India
2Rutgers New Jersey Medical School, Newark, United States
3Department of Pharmaceutical Engineering, Indian Institute of Technology (Banaras Hindu University), Varanasi, India

Tóm tắt

Tâm thần phân liệt (SZ) là một rối loạn hành vi nặng nề, tiến triển và thoái hóa thần kinh, ảnh hưởng đến vô số người trên toàn cầu. Việc phát hiện ra các biomarker tiềm năng trong bối cảnh lâm sàng sẽ dẫn đến việc phát triển các phương pháp chẩn đoán hiệu quả và cung cấp hiểu biết về tiên lượng của bệnh. Hơn nữa, những phát minh đột phá cho việc điều trị và phòng ngừa căn bệnh bí ẩn này có thể phát triển nhờ vào sự hiểu biết sâu sắc về các biomarker lâm sàng. Trong bài tổng quan này, chúng tôi đã thảo luận về các biomarker cụ thể của SZ với những điểm nhấn tập trung vào (1) các biomarker chẩn đoán như biomarker thần kinh miễn dịch, biomarker chuyển hóa, biomarker tế bào oligodendrocyte và biomarker của các triệu chứng âm tính và nhận thức, (2) các biomarker điều trị như các hệ thống dẫn truyền thần kinh khác nhau và (3) các biomarker tiên lượng. Tất cả các biomarker đã được đánh giá ở các bệnh nhân chưa sử dụng thuốc (ít nhất 4 tuần) để đạt được sự so sánh rõ ràng giữa các bệnh nhân tâm thần phân liệt và các đối chứng khỏe mạnh. Ngoài ra, một nỗ lực đã được thực hiện để làm sáng tỏ các gen tiềm năng đóng vai trò như những dự đoán và công cụ cho việc xác định biomarker và cuối cùng sẽ giúp trong việc phòng ngừa và điều trị căn bệnh chết người này.

Từ khóa

#tâm thần phân liệt #biomarker #chẩn đoán #điều trị #tiên lượng #rối loạn hành vi

Tài liệu tham khảo

Acar E, Schenker C, Levin-Schwartz Y et al (2019) Unraveling diagnostic biomarkers of schizophrenia through structure-revealing fusion of multi-modal neuroimaging data. Front Neurosci 13. https://doi.org/10.3389/fnins.2019.00416 Al-Hakeim HK, Almulla AF, Maes M (2020) The Neuroimmune and Neurotoxic Fingerprint of Major Neurocognitive Psychosis or Deficit Schizophrenia: a Supervised Machine Learning Study. Neurotox Res 37:753–771. https://doi.org/10.1007/s12640-019-00112-z Al-Hakeim HK, Mousa RF, Al-Dujaili AH, Maes M (2021) In schizophrenia, non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy. Metab Brain Dis 36:939–955. https://doi.org/10.1007/s11011-021-00685-9 Ayari F, Ben Chaaben A, Ben Ammar H et al (2020) Association of high-sensitivity C-reactive protein with susceptibility to Schizophrenia in Tunisian population. Encephale 46:241–247. https://doi.org/10.1016/j.encep.2019.10.001 Brodbeck C, Presacco A, Simon JZ (2018) Neural source dynamics of brain responses to continuous stimuli: Speech processing from acoustics to comprehension. NeuroImage 172:162–174. https://doi.org/10.1016/j.neuroimage.2018.01.042 Cao H, McEwen SC, Chung Y et al (2019) Altered brain activation during memory retrieval precedes and predicts conversion to psychosis in individuals at clinical high risk. Schizophr Bull 45:924–933. https://doi.org/10.1093/schbul/sby122 Cao T, Li NN, Cai HL (2020) Candidate metabolic biomarkers for schizophrenia in CNS and periphery: Do any possible associations exist? Schizophr Res 226:95–110. https://doi.org/10.1016/j.schres.2019.03.009 Chang CH, Lane HY, Liu CY et al (2019) C-reactive protein is associated with severity of thought and language dysfunction in patients with schizophrenia. Neuropsychiatr Dis Treat 15:2621–2627. https://doi.org/10.2147/NDT.S223278 Chou P-H, Huang C-J, Sun C-W (2019) The Potential Role of Functional Near-Infrared Spectroscopy as Clinical Biomarkers in Schizophrenia. Curr Pharm Des 26:201–217. https://doi.org/10.2174/1381612825666191014164511 Dal Mas C, Nani JV, Noto C et al (2019) Ndel1 oligopeptidase activity as a potential biomarker of early stages of schizophrenia. Schizophr Res 208:202–208. https://doi.org/10.1016/j.schres.2019.02.021 Daudet L, Yadav N, Perez M et al (2017) Portable mTBI Assessment Using Temporal and Frequency Analysis of Speech. IEEE J Biomed Heal Informatics 21:496–506. https://doi.org/10.1109/JBHI.2016.2633509 De Boer JN, Brederoo SG, Voppel AE, Sommer IEC (2020) Anomalies in language as a biomarker for schizophrenia. Curr Opin Psychiatry 33:212–218. https://doi.org/10.1097/YCO.0000000000000595 de Boer JN, van Hoogdalem M, Mandl RCW et al (2020) Language in schizophrenia: relation with diagnosis, symptomatology and white matter tracts. https://doi.org/10.1038/s41537-020-0099-3. npj Schizophr 6: de Jonge JC, Vinkers CH, Hulshoff Pol HE, Marsman A (2017a) GABAergic mechanisms in schizophrenia: Linking postmortem and In vivo studies. Front Psychiatry 8:118. https://doi.org/10.3389/fpsyt.2017.00118 de Jonge JC, Vinkers CH, Hulshoff Pol HE, Marsman A (2017b) GABAergic mechanisms in schizophrenia: Linking postmortem and In vivo studies. Front Psychiatry 8:118. https://doi.org/10.3389/fpsyt.2017.00118 Delaney S, Fallon B, Alaedini A et al (2019) Inflammatory biomarkers in psychosis and clinical high risk populations. Schizophr Res 206:440–443. https://doi.org/10.1016/j.schres.2018.10.017 Deng SP, Hu W, Calhoun VD, Wang YP (2018) Integrating imaging genomic data in the quest for biomarkers of schizophrenia disease. IEEE/ACM Trans Comput Biol Bioinforma 15:1480–1491. https://doi.org/10.1109/TCBB.2017.2748944 Galińska-Skok B, Małus A, Konarzewska B et al (2018) Choline compounds of the frontal lobe and temporal glutamatergic system in bipolar and schizophrenia proton magnetic resonance spectroscopy study. https://doi.org/10.1155/2018/3654894. Dis Markers 2018: Garcia-Alvarez L, Garcia-Portilla MP, Gonzalez-Blanco L et al (2016) Differential blood-based biomarkers of psychopathological dimensions of schizophrenia. Rev Psiquiatr y Salud Ment (English Ed 9:219–227. https://doi.org/10.1016/j.rpsmen.2016.04.008 Goldsmith DR, Crooks CL, Walker EF, Cotes RO (2018) An Update on Promising Biomarkers in Schizophrenia. Focus (Madison) 16:153–163. https://doi.org/10.1176/appi.focus.20170046 Guo S, Huang CC, Zhao W et al (2018) Combining multi-modality data for searching biomarkers in schizophrenia. PLoS ONE 13. https://doi.org/10.1371/journal.pone.0191202 Gupta AK, Kumar GK, Rani K et al (2019) 2D-DIGE as a strategy to identify serum protein biomarkers to monitor pharmacological efficacy in dopamine-dictated states of Parkinson’s disease and schizophrenia. Neuropsychiatr Dis Treat 15:1031–1044. https://doi.org/10.2147/NDT.S198559 Han W, Zhang T, Ni T et al (2019) Relationship of common variants in CHRNA5 with early-onset schizophrenia and executive function. Schizophr Res 206:407–412. https://doi.org/10.1016/j.schres.2018.10.011 He K, Guo C, Guo M et al (2019) Identification of serum microRNAs as diagnostic biomarkers for schizophrenia. Hereditas 156:23. https://doi.org/10.1186/s41065-019-0099-3 Henriksen MG, Nordgaard J, Jansson LB (2017) Genetics of schizophrenia: Overview of methods, findings and limitations. Front Hum Neurosci 11. https://doi.org/10.3389/fnhum.2017.00322 Herron JW, Nerurkar L, Cavanagh J (2018) Neuroimmune biomarkers in mental illness. Curr Top Behav Neurosci 40:45–78. https://doi.org/10.1007/7854_2018_45 Hung CC, Lin CH, Lane HY (2021) Cystine/glutamate antiporter in schizophrenia: From molecular mechanism to novel biomarker and treatment. Int J Mol Sci 22. https://doi.org/10.3390/ijms22189718 Jin H, Mosweu I (2017) The Societal Cost of Schizophrenia: A Systematic Review. PharmacoEconomics 35:25–42. https://doi.org/10.1007/s40273-016-0444-6 Juchnowicz D, Dzikowski M, Rog J et al (2021) Pro/antioxidant state as a potential biomarker of schizophrenia. J Clin Med 10. https://doi.org/10.3390/jcm10184156 Kageyama Y, Kasahara T, Morishita H et al (2017a) Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis. Psychiatry Clin Neurosci 71:115–123. https://doi.org/10.1111/pcn.12461 Kageyama Y, Kasahara T, Morishita H et al (2017b) Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis. Psychiatry Clin Neurosci 71:115–123. https://doi.org/10.1111/pcn.12461 Kelly S, Guimond S, Lyall A et al (2019) Neural correlates of cognitive deficits across developmental phases of schizophrenia. Neurobiol Dis 131. https://doi.org/10.1016/j.nbd.2018.12.013 Lee EE, Ancoli-Israel S, Eyler LT et al (2019a) Sleep Disturbances and Inflammatory Biomarkers in Schizophrenia: Focus on Sex Differences. Am J Geriatr Psychiatry 27:21–31. https://doi.org/10.1016/j.jagp.2018.09.017 Lee EE, Sears DD, Liu J et al (2019b) A novel biomarker of cardiometabolic pathology in schizophrenia? J Psychiatr Res 117:31–37. https://doi.org/10.1016/j.jpsychires.2019.06.011 Lee SW, Jeong B, Park J, Il et al (2019c) Alteration of semantic networks during swear words processing in schizophrenia. Clin Psychopharmacol Neurosci 17:64–73. https://doi.org/10.9758/cpn.2019.17.1.64 Li C, Tao H, Yang X et al (2018) Assessment of a combination of serum proteins as potential biomarkers to clinically predict schizophrenia. Int J Med Sci 15:900–906. https://doi.org/10.7150/ijms.24346 Lin CH, Hashimoto K, Lane HY (2019a) Editorial: Glutamate-Related Biomarkers for Neuropsychiatric Disorders. Front Psychiatry 10. https://doi.org/10.3389/fpsyt.2019.00904 Lin CH, Hashimoto K, Lane HY (2019b) Editorial: Glutamate-Related Biomarkers for Neuropsychiatric Disorders. Front Psychiatry 10. https://doi.org/10.3389/fpsyt.2019.00904 Liu S, Zhang F, Wang X et al (2017a) Diagnostic value of blood-derived microRNAs for schizophrenia: Results of a meta-analysis and validation. Sci Rep 7. https://doi.org/10.1038/s41598-017-15751-5 Lo LH, Shiea J, Huang TL (2016) Rapid detection of alteration of serum IgG in patients with schizophrenia after risperidone treatment by matrix-assisted laser desorption ionization/time-of-flight mass spectrometry. Rapid Commun Mass Spectrom 30:2645–2649. https://doi.org/10.1002/rcm.7753 Maes M, Sirivichayakul S, Kanchanatawan B, Carvalho AF (2020) In schizophrenia, psychomotor retardation is associated with executive and memory impairments, negative and psychotic symptoms, neurotoxic immune products and lower natural IgM to malondialdehyde. World J Biol Psychiatry 21:383–401. https://doi.org/10.1080/15622975.2019.1701203 Maes M, Vojdani A, Sirivichayakul S et al (2021) Inflammatory and Oxidative Pathways Are New Drug Targets in Multiple Episode Schizophrenia and Leaky Gut, Klebsiella pneumoniae, and C1q Immune Complexes Are Additional Drug Targets in First Episode Schizophrenia. Mol Neurobiol 58:3319–3334. https://doi.org/10.1007/s12035-021-02343-8 Mäki-Marttunen V, Andreassen OA, Espeseth T (2020) The role of norepinephrine in the pathophysiology of schizophrenia. Neurosci Biobehav Rev Maletic V, Eramo A, Gwin K et al (2017) The role of norepinephrine and its α-adrenergic receptors in the pathophysiology and treatment of major depressive disorder and schizophrenia: a systematic review. Front psychiatry 8:42 McCutcheon RA, Krystal JH, Howes OD (2020) Dopamine and glutamate in schizophrenia: biology, symptoms and treatment. World Psychiatry 19:15–33. https://doi.org/10.1002/wps.20693 Miller BJ, Goldsmith DR (2019) Inflammatory biomarkers in schizophrenia: Implications for heterogeneity and neurobiology. Biomarkers in Neuropsychiatry 1:100006. https://doi.org/10.1016/j.bionps.2019.100006 Mohammadi A, Rashidi E, Amooeian VG (2018a) Brain, blood, cerebrospinal fluid, and serum biomarkers in schizophrenia. Psychiatry Res 265:25–38. https://doi.org/10.1016/j.psychres.2018.04.036 Momtazmanesh S, Zare-Shahabadi A, Rezaei N (2019a) Cytokine Alterations in Schizophrenia: An Updated Review. Front Psychiatry 10 892. https://doi.org/10.3389/fpsyt.2019.00892 Momtazmanesh S, Zare-Shahabadi A, Rezaei N (2019b) Cytokine Alterations in Schizophrenia: An Updated Review. Front Psychiatry 10. https://doi.org/10.3389/fpsyt.2019.00892 Mongan D, Ramesar M, Föcking M et al (2020) Role of inflammation in the pathogenesis of schizophrenia: A review of the evidence, proposed mechanisms and implications for treatment. Early Interv Psychiatry 14:385–397. https://doi.org/10.1111/eip.12859 Morozova A, Zorkina Y, Pavlov K et al (2021) Associations of Genetic Polymorphisms and Neuroimmune Markers With Some Parameters of Frontal Lobe Dysfunction in Schizophrenia. Front Psychiatry 12. https://doi.org/10.3389/fpsyt.2021.655178 Mousa RF, Al-Hakeim HK, Alhaideri A, Maes M (2021a) Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates. Metab Brain Dis 36:169–183. https://doi.org/10.1007/s11011-020-00619-x Mousa RF, Al-Hakeim HK, Alhaideri A, Maes M (2021b) Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates. Metab Brain Dis 36:169–183. https://doi.org/10.1007/s11011-020-00619-x Müller N (2018) Inflammation in schizophrenia: Pathogenetic aspects and therapeutic considerations. Schizophr Bull 44:973–982. https://doi.org/10.1093/schbul/sby024 Nagai T, Kirihara K, Tada M et al (2017) Reduced Mismatch Negativity is Associated with Increased Plasma Level of Glutamate in First-episode Psychosis. Sci Rep 7. https://doi.org/10.1038/s41598-017-02267-1 Nani JV, Yonamine CM, Castro Musial D et al (2020) ACE activity in blood and brain axis in an animal model for schizophrenia: Effects of dopaminergic manipulation with antipsychotics and psychostimulants. World J Biol Psychiatry 21:53–63. https://doi.org/10.1080/15622975.2019.1583372 Narahari A, Hussain M, Sreeram V (2017) MicroRNAs as biomarkers for psychiatric conditions: A review of current research. Innov Clin Neurosci 14:53–55 Nguyen TT, Dev SI, Chen G et al (2018) Abnormal levels of vascular endothelial biomarkers in schizophrenia. Eur Arch Psychiatry Clin Neurosci 268:849–860. https://doi.org/10.1007/s00406-017-0842-6 Nieto RR, Carrasco A, Corral S et al (2021) BDNF as a Biomarker of Cognition in Schizophrenia/Psychosis: An Updated Review. Front Psychiatry 12. https://doi.org/10.3389/fpsyt.2021.662407 Ohnuma T, Nishimon S, Takeda M et al (2018) Carbonyl stress and microinflammation-related molecules as potential biomarkers in schizophrenia. Front Psychiatry 9. https://doi.org/10.3389/fpsyt.2018.00082 Peng S, Li W, Lv L et al (2018) BDNF as a biomarker in diagnosis and evaluation of treatment for schizophrenia and depression. Discov Med 26:127–136 Perkovic MN, Erjavec GN, Strac DS et al (2017a) Theranostic biomarkers for schizophrenia. Int J Mol Sci 18. https://doi.org/10.3390/ijms18040733 Perkovic MN, Erjavec GN, Strac DS et al (2017b) Theranostic biomarkers for schizophrenia. Int J Mol Sci 18. https://doi.org/10.3390/ijms18040733 Prajzlerová K, Grobelná K, Pavelka K et al (2016) An update on biomarkers in axial spondyloarthritis. Autoimmun Rev 15:501–509. https://doi.org/10.1016/j.autrev.2016.02.002 Prata J, Santos SG, Almeida MI et al (2017) Bridging Autism Spectrum Disorders and Schizophrenia through inflammation and biomarkers - pre-clinical and clinical investigations. J Neuroinflammation 14. https://doi.org/10.1186/s12974-017-0938-y Pratt J, Hall J (2018a) Biomarkers in neuropsychiatry: A prospect for the twenty-first century? Curr Top Behav Neurosci 40:3–10. https://doi.org/10.1007/7854_2018_58 Pratt J, Hall J (2018b) Biomarkers in neuropsychiatry: A prospect for the twenty-first century? Curr Top Behav Neurosci 40:3–10. https://doi.org/10.1007/7854_2018_58 Rasool M, Malik A, Saleem S et al (2021) Role of Oxidative Stress and the Identification of Biomarkers Associated With Thyroid Dysfunction in Schizophrenics. Front Pharmacol 12. https://doi.org/10.3389/fphar.2021.646287 Renard J, Rushlow WJ, Laviolette SR (2018a) Effects of adolescent THC exposure on the prefrontal GABAergic system: Implications for schizophrenia-related psychopathology. Front Psychiatry 9. https://doi.org/10.3389/fpsyt.2018.00281 Renard J, Rushlow WJ, Laviolette SR (2018b) Effects of adolescent THC exposure on the prefrontal GABAergic system: Implications for schizophrenia-related psychopathology. Front Psychiatry 9. https://doi.org/10.3389/fpsyt.2018.00281 Rodríguez B, Nani JV, Almeida PGC et al (2020a) Neuropeptides and oligopeptidases in schizophrenia. Neurosci Biobehav Rev 108:679–693. https://doi.org/10.1016/j.neubiorev.2019.11.024 Rodríguez B, Nani JV, Almeida PGC et al (2020b) Neuropeptides and oligopeptidases in schizophrenia. Neurosci Biobehav Rev 108:679–693. https://doi.org/10.1016/j.neubiorev.2019.11.024 Rojas Cabrera JM, Blair Price J, Rusheen AE et al (2020) Advances in neurochemical measurements: A review of biomarkers and devices for the development of closed-loop deep brain stimulation systems. Rev Anal Chem 39. https://doi.org/10.1515/revac-2020-0117 Roy B, Yoshino Y, Allen L et al (2020) Exploiting Circulating MicroRNAs as Biomarkers in Psychiatric Disorders. Mol Diagnosis Ther 24:279–298. https://doi.org/10.1007/s40291-020-00464-9 Schmitt A, Rujescu D, Gawlik M et al (2016) Consensus paper of the WFSBP Task Force on Biological Markers: Criteria for biomarkers and endophenotypes of schizophrenia part II: Cognition, neuroimaging and genetics. World J Biol Psychiatry 17:406–428. https://doi.org/10.1080/15622975.2016.1183043 Schoonover KE, Dienel SJ, Lewis DA (2020) Prefrontal cortical alterations of glutamate and GABA neurotransmission in schizophrenia: Insights for rational biomarker development. Biomarkers in Neuropsychiatry 3:100015. https://doi.org/10.1016/j.bionps.2020.100015 Seth G, Sundaresh A, Mariaselvam CM et al (2020) Immunological biomarkers in neuropsychiatric systemic lupus erythematosus: a comparative cross-sectional study from a tertiary care center in South India. Lupus 29:413–420. https://doi.org/10.1177/0961203320908940 Shen Y, Xu J, Li Z et al (2018) Analysis of gut microbiota diversity and auxiliary diagnosis as a biomarker in patients with schizophrenia: A cross-sectional study. Schizophr Res 197:470–477. https://doi.org/10.1016/j.schres.2018.01.002 Sinkeviciute I, Begemann M, Prikken M et al (2018) Efficacy of different types of cognitive enhancers for patients with schizophrenia: a meta-analysis. https://doi.org/10.1038/s41537-018-0064-6. npj Schizophr 4: Sonnenschein SF, Grace A (2021) Emerging therapeutic targets for schizophrenia: a framework for novel treatment strategies for psychosis. Expert Opin Ther Targets 25:15–26. https://doi.org/10.1080/14728222.2021.1849144 Stępnicki P, Kondej M, Kaczor AA (2018) Current concepts and treatments of schizophrenia. Molecules 23. https://doi.org/10.3390/molecules23082087 Tamminga CA, Pearlson GD, Stan AD et al (2017) Strategies for Advancing Disease Definition Using Biomarkers and Genetics: The Bipolar and Schizophrenia Network for Intermediate Phenotypes. Biol Psychiatry Cogn Neurosci Neuroimaging 2:20–27. https://doi.org/10.1016/j.bpsc.2016.07.005 Taylor SF, Grove TB, Ellingrod VL, Tso IF (2019) The fragile brain: Stress vulnerability, negative affect and gabaergic neurocircuits in psychosis. Schizophr Bull 45:1170–1183. https://doi.org/10.1093/schbul/sbz046 Thomas KT, Zakharenko SS (2021) MicroRNAs in the onset of Schizophrenia. https://doi.org/10.3390/cells10102679. Cells 10: Tomasik J, Rahmoune H, Guest PC, Bahn S (2016) Neuroimmune biomarkers in schizophrenia. Schizophr Res 176:3–13. https://doi.org/10.1016/j.schres.2014.07.025 Trotta A, Arseneault L, Danese A et al (2021) Associations between childhood victimization, inflammatory biomarkers and psychotic phenomena in adolescence: A longitudinal cohort study. Brain Behav Immun 98:74–85. https://doi.org/10.1016/j.bbi.2021.08.209 Tu CH, MacDonald I, Chen YH (2019) The effects of acupuncture on glutamatergic neurotransmission in depression, anxiety, schizophrenia, and Alzheimer’s disease: A review of the literature. Front Psychiatry 10. https://doi.org/10.3389/fpsyt.2019.00014 van den Berg MMJ, Krauskopf J, Ramaekers JG et al (2020) Circulating microRNAs as potential biomarkers for psychiatric and neurodegenerative disorders. Prog Neurobiol 185. https://doi.org/10.1016/j.pneurobio.2019.101732 Viviano JD, Buchanan RW, Calarco N et al (2018) Resting-State Connectivity Biomarkers of Cognitive Performance and Social Function in Individuals With Schizophrenia Spectrum Disorder and Healthy Control Subjects. Biol Psychiatry 84:665–674. https://doi.org/10.1016/j.biopsych.2018.03.013 Wang Z, Li P, Chi D et al (2017) Association between C-reactive protein and risk of schizophrenia: An updated meta-analysis. Oncotarget 8:75445–75456. https://doi.org/10.18632/oncotarget.17995 Watkins CC, Andrews SR (2016) Clinical studies of neuroinflammatory mechanisms in schizophrenia. Schizophr Res 176:14–22. https://doi.org/10.1016/j.schres.2015.07.018 Xu H, Chen Z, Shang Q hua, et al (2019) Asymmetric Dimethylarginine Predicts One-year Recurrent Cardiovascular Events: Potential Biomarker of “Toxin Syndrome” in Coronary Heart Disease. Chin J Integr Med 25:327–333. https://doi.org/10.1007/s11655-019-2701-y Xu MY, Wong AHC (2018) GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia. Acta Pharmacol Sin 39:733–753. https://doi.org/10.1038/aps.2017.172 Yadav M, Kumar N, Kumar A et al (2021a) Possible Biomarkers and Contributing Factors of Psychosis: a Review. Curr Pharmacol Reports 7:123–134. https://doi.org/10.1007/s40495-021-00260-x Yadav M, Kumar N, Kumar A et al (2021b) Possible Biomarkers and Contributing Factors of Psychosis: a Review. Curr Pharmacol Reports 7:123–134. https://doi.org/10.1007/s40495-021-00260-x Yan J, Kuzhiumparambil U, Bandodkar A et al (2021a) Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation. Dev Med Child Neurol 63:552–559. https://doi.org/10.1111/dmcn.14774 Yan J, Kuzhiumparambil U, Bandodkar A et al (2021b) Cerebrospinal fluid metabolites in tryptophan-kynurenine and nitric oxide pathways: biomarkers for acute neuroinflammation. Dev Med Child Neurol 63:552–559. https://doi.org/10.1111/dmcn.14774 Yang YJ, Xiong JW, Zhao Y et al (2016) Increased plasma asymmetric dimethylarginine is associated with cognitive deficits in patients with schizophrenia. Psychiatry Res 246:480–484. https://doi.org/10.1016/j.psychres.2016.10.015 You X, Zhang Y, Long Q et al (2020) Investigating aberrantly expressed microRNAs in peripheral blood mononuclear cells from patients with treatment-resistant schizophrenia using miRNA sequencing and integrated bioinformatics. Mol Med Rep 22:4340–4350. https://doi.org/10.3892/mmr.2020.11513 Yu Z, Zhao Y, Zhan J et al (2019a) Treatment Responses of Cognitive Function and Plasma Asymmetric Dimethylarginine to Atypical Antipsychotic in Patients With Schizophrenia. Front Psychiatry 9. https://doi.org/10.3389/fpsyt.2018.00733 Yu Z, Zhao Y, Zhan J et al (2019b) Treatment Responses of Cognitive Function and Plasma Asymmetric Dimethylarginine to Atypical Antipsychotic in Patients With Schizophrenia. Front Psychiatry 9. https://doi.org/10.3389/fpsyt.2018.00733 Zhang Y, Fang X, Fan W et al (2018a) Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study. Psychopharmacology 235:1191–1198. https://doi.org/10.1007/s00213-018-4835-6 Zhang Y, Fang X, Fan W et al (2018b) Brain-derived neurotrophic factor as a biomarker for cognitive recovery in acute schizophrenia: 12-week results from a prospective longitudinal study. Psychopharmacology 235:1191–1198. https://doi.org/10.1007/s00213-018-4835-6 Zhang Y, Liao J, Li Q et al (2021) Altered Resting-State Brain Activity in Schizophrenia and Obsessive-Compulsive Disorder Compared With Non-psychiatric Controls: Commonalities and Distinctions Across Disorders. Front Psychiatry 12. https://doi.org/10.3389/fpsyt.2021.681701