Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment
Abstract
:1. Introduction
2. Neurofeedback
3. Vagus Nerve Stimulation (VNS)
4. Repetitive Transcranial Magnetic Stimulation (rTMS)
5. Transcranial Direct Current Stimulation (tDCS)
6. Virtual Reality (VR) Therapy for Patients with Schizophrenia
7. Cognitive Remediation Therapy
8. Pharmacotherapy and Neuroplasticity
9. Detection and Modulation of Neuroplasticity Effects
10. Discussion
11. Conclusions
- Since randomized controlled studies of long-term schizophrenia treatment do not exceed 2–3 years, they may not fully capture the long-term effects of patient treatment, and the pharmacological treatment itself has an incompletely estimated long-term benefit-risk ratio. Thus, treatment methods based on other paradigms, including neuronal self-regulatory and neural plasticity mechanisms, should be considered.
- Neural plasticity can be a common platform for evaluating effective treatment of schizophrenia, defined as meeting the sustainable criteria of symptomatic and functional remission using both pharmacological and non-pharmacological treatment methods.
- There are increasingly more methods available for monitoring neuroplastic effects during schizophrenia therapy (e.g., fMRI, neuropeptides in serum), as well as unfavorable parameters (e.g., features of the metabolic syndrome). The use of these methods enables individualized monitoring of the effectiveness of long-term treatment of schizophrenia; however, the availability and cost of some alternative treatments (e.g., neurofeedback, rTMS, neuropeptides in serum, fMRI) may limit their use among patients and may not be available in all centers and treatment conditions.
- The effectiveness of alternative treatments may vary across individuals and may not be effective for everyone.
- The potential adverse effects of some of the alternative treatments, such as transcranial magnetic stimulation and vagus nerve stimulation, may limit their use in some patients.
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Citri, A.; Malenka, R.C. Synaptic plasticity: Multiple forms, functions, and mechanisms. Neuropsychopharmacology 2008, 33, 18–41. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Derkach, V.A.; Oh, M.C.; Guire, E.S.; Soderling, T.R. Regulatory mechanisms of AMPA receptors in synaptic plasticity. Nat. Rev. Neurosci. 2007, 8, 101–113. [Google Scholar] [CrossRef] [PubMed]
- Ho, V.M.; Lee, J.A.; Kelsey, M. The cell biology of synaptic plasticity. Science 2011, 334, 623–628. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Glausier, J.R.; Lewis, D.A. Dendritic spine pathology in schizophrenia. Neuroscience 2013, 251, 90–107. [Google Scholar] [CrossRef] [Green Version]
- Tønnesen, J.; Nägerl, U.V. Dendritic spines as tunable regulators of synaptic signals. Front. Psychiatry 2016, 7, 101. [Google Scholar] [CrossRef] [Green Version]
- Forsyth, J.; Lewis, D. Mapping the consequences of impaired synaptic plasticity in schizophrenia through development: An integrative model for diverse clinical features. Trends Cogn. Sci. 2017, 21, 760–778. [Google Scholar] [CrossRef]
- Dehorter, N.; Marichal, N.; Marin, O.; Berninger, B. Tuning neural circuits by turning the interneuron knob. Curr. Opin. Neurobiol. 2017, 42, 144–151. [Google Scholar] [CrossRef] [Green Version]
- Caroni, P.; Donato, F.; Muller, D. Structural plasticity upon learning: Regulation and functions. Nat. Rev. Neurosci. 2012, 13, 478–490. [Google Scholar] [CrossRef] [Green Version]
- Johansen, J.P.; Kain, C.h.; Ostroff, L.; LeDoux, J.E. Molecular mechanisms of fear learning and memory. Cell 2011, 147, 509–524. [Google Scholar] [CrossRef] [Green Version]
- Grueter, B.A.; Rothwell, P.; Malenka, R. Integrating synaptic plasticity and striatal circuit function in addiction. Curr. Opin. Neurobiol. 2012, 22, 545–551. [Google Scholar] [CrossRef] [Green Version]
- Yin, H.H.; Mulcare, S.P.; Hilário, M.R.F.; Clouse, E.; Holloway, T.; Davis, M.; Hansson, A.C.; Lovinger, D.M.; Costa, R.M. Dynamic reorganization of striatal circuits during the acquisition and consolidation of a skill. Nat. Neurosci. 2009, 12, 333–341. [Google Scholar] [CrossRef] [Green Version]
- Yu, X.; Zuo, Y. Spine plasticity in the motor cortex. Curr. Opin. Neurobiol. 2011, 21, 169–174. [Google Scholar] [CrossRef] [Green Version]
- Feldman, D.E. Synaptic mechanisms for plasticity in neocortex. Annu. Rev. Neurosci. 2009, 32, 33–55. [Google Scholar] [CrossRef] [Green Version]
- Kessels, H.W.; Malinow, R. Synaptic AMPA receptor plasticity and behavior. Neuron 2009, 61, 340–350. [Google Scholar] [CrossRef] [Green Version]
- Fu, M.; Yu, X.; Lu, J.; Zuo, Y. Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature 2012, 483, 92–95. [Google Scholar] [CrossRef] [Green Version]
- Tau, G.; Peterson, B. Normal development of brain circuits. Neuropsychopharmacology 2010, 35, 147–168. [Google Scholar] [CrossRef] [Green Version]
- Zhang, Z.W.; Peterson, M.; Liu, H. Essential role of postsynaptic NMDA receptors in developmental refinement of excitatory synapses. Proc. Natl. Acad. Sci. USA 2013, 110, 1095–1110. [Google Scholar] [CrossRef] [Green Version]
- Ehrlich, I.; Malinow, R. Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J. Neurosci. 2004, 24, 916–927. [Google Scholar] [CrossRef] [Green Version]
- Johnson, M.H. Functional brain development in humans. Nat. Rev. Neurosci. 2001, 2, 475–483. [Google Scholar] [CrossRef]
- Gogtay, N.; Thompson, P. Mapping gray matter development: Implications for typical development and vulnerability to psychopathology. Brain Cogn. 2010, 72, 6–15. [Google Scholar] [CrossRef] [Green Version]
- Costandi, M. Neuroplasticity; The MIT Press: Cambridge, MA, USA, 2016; ISBN 9780262529334. [Google Scholar]
- Takesian, A.E.; Hensch, T.K. Balancing plasticity/stability across brain development. Prog. Brain Res. 2013, 207, 3–34. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Knott, G.; Lu, J.; Cristo, G.; Huang, Z. GABA signaling promotes synapse elimination and axon pruning in developing cortical inhibitory interneurons. J. Neurosci. 2012, 32, 331–343. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hayama, T.; Noguchi, J.; Watanabe, S.; Takahashi, N.; Hayashi-Takagi, A.; Ellis-Davies, G.C.R.; Matsuzaki, M.; Kasai, H. GABA promotes the competitive selection of dendritic spines by controlling local Ca2+ signaling. Nat. Neurosci. 2013, 16, 1409–1416. [Google Scholar] [CrossRef] [PubMed]
- Pennington, K.; Beasley, C.L.; Dicker, P.; Fagan, A.; English, J.; Pariante, C.M.; Wait, R.; Dunn, M.J.; Cotter, D.R. Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder. Mol. Psychiatry 2008, 13, 1102–1117. [Google Scholar] [CrossRef] [Green Version]
- Funk, A.J.; McCullumsmith, R.; Horoutunian, V.; Meador-Woodruff, J. Abnormal activity of the MAPK-and cAMP-associated signaling pathways in frontal cortical areas in postmortem brain in schizophrenia. Neuropsychopharmacology 2012, 37, 896–905. [Google Scholar] [CrossRef] [Green Version]
- Li, W.; Ghose, S.; Gleason, K.; Begovic’, A.; Perez, J.; Bartko, J.; Russo, S.; Wagner, A.D.; Selemon, L.; Tamminga, C.A. Synaptic Proteins in the Hippocampus Indicative of Increased Neuronal Activity in CA3 in Schizophrenia. Am. J. Psychiatry 2015, 172, 373–382. [Google Scholar] [CrossRef] [Green Version]
- Kirov, G.; Pocklington, A.J.; Holmans, P.; Ivanov, D.; Ikeda, M.; Ruderfer, D.; Moran, J.; Chambert, K.; Toncheva, D.; Georgieva, L.; et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol. Psychiatry 2012, 17, 142–153. [Google Scholar] [CrossRef] [Green Version]
- Glantz, L.A.; Lewis, D.A. Decreased dendritic spine density on prefrontal cortical pyramidal neurons in schizophrenia. Arch. Gen. Psychiatry 2000, 57, 65–73. [Google Scholar] [CrossRef] [Green Version]
- Garey, L. When cortical development goes wrong: Schizophrenia as a neurodevelopmental disease of microcircuits. J. Anat. 2010, 217, 324–333. [Google Scholar] [CrossRef]
- Paus, T.; Keshavan, M.; Giedd, J. Why do many psychiatric disorders emerge during adolescence? Nat. Rev. Neurosci. 2008, 9, 947–957. [Google Scholar] [CrossRef] [Green Version]
- Tamnes, C.K.; Ostby, Y.; Fjell, A.M.; Westlye, L.T.; Due-Tønnessen, P.; Walhovd, K.B. Brain Maturation in Adolescence and Young Adulthood: Regional Age-Related Changes in Cortical Thickness and White Matter Volume and Microstructure. Cereb. Cortex. 2010, 20, 534–548. [Google Scholar] [CrossRef] [Green Version]
- Krystal, J.H.; Anticevic, A.; Yang, G.J.; Dragoi, G.; Driesen, N.R.; Wang, X.-J.; Murray, J.D. Impaired Tuning of Neural Ensembles and the Pathophysiology of Schizophrenia: A Translational and Computational Neuroscience Perspective. Biol. Psychiatry 2017, 81, 874–885. [Google Scholar] [CrossRef] [Green Version]
- Rubio, J.M.; Perez-Rodriguez, M. Chronic use of antipsychotics in schizophrenia: Are we asking the right question? Schizophr. Bull. Open 2022, 3, sgac059. [Google Scholar] [CrossRef]
- Remington, G.; Addington, D.; Honer, W.; Ismail, Z.; Raedler, T.; Teehan, M. Guidelines for the pharmacotherapy of schizophrenia in adults. Can. J. Psychiatry 2017, 62, 604–616. [Google Scholar] [CrossRef] [Green Version]
- Price, R.; Salavati, B.; Graff-Guerrero, A.; Blumberger, D.M.; Mulsant, B.H.; Daskalakis, Z.J.; Rajji, T.K. Effects of antipsychotic D2 antagonists on long-term potentiation in animals and implications for human studies. Prog. Neuropsychopharmacol. Biol. Psychiatry 2014, 54, 83–91. [Google Scholar] [CrossRef] [Green Version]
- Kilgard, M.P. Harnessing plasticity to understand learning and treat disease. Trends Neurosci. 2012, 35, 715–722. [Google Scholar] [CrossRef] [Green Version]
- Lozano, A.M. Harnessing plasticity to reset dysfunctional neurons. N. Engl. J. Med. 2011, 364, 1367–1368. [Google Scholar] [CrossRef]
- Hays, S.A.; Rennaker, R.L.; Kilgard, M.P. Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog. Brain Res. 2013, 207, 275–299. [Google Scholar] [CrossRef] [Green Version]
- Ghaziri, J.; Tucholka, A.; Larue, V.; Blanchette-Sylvestre, M.; Rayburn, G.; Gilbert, G.; Levesque, J.; Beauregard, M. Neurofeedback training induces changes in white and gray matter. Clin. EEG Neurosci. 2013, 44, 265–272. [Google Scholar] [CrossRef]
- Thompson, M.; Thompson, L. Neurofeedback. Introduction to the Basic Concepts of Applied Psychophysiology; Biomed Neurotechnologie: Wrocław, Poland, 2013. (In Polish) [Google Scholar]
- Sarchiapone, M.; Gramaglia, C.; Iosue, M.; Carli, V.; Mandelli, L.; Serretti, A.; Marangon, D.; Zeppegno, P. The association between electrodermal activity (EDA), depression and suicidal behavior: A systematic review and narrative synthesis. BMC Psychiatry 2018, 18, 22. [Google Scholar] [CrossRef] [Green Version]
- Thorell, L.; Wolfersdorf, M.; Straub, R.; Steyer, J.; Hodgkinson, S.; Kaschka, W. Electrodermal hyporeactivity as a trait marker for suicidal propensity in uni-and bipolar depression. J. Psychiatr. Res. 2013, 47, 1925–1931. [Google Scholar] [CrossRef] [PubMed]
- Wincewicz, K.; Nasierkowski, T. Electrodermal activity and suicide risk assessment in patients with affective disorders. Psychiatr. Pol. 2020, 54, 1137–1147. [Google Scholar] [CrossRef] [PubMed]
- Gandara, V.; Pineda, J.A.; Shu, I.-W.; Singh, F. A systematic review of the potential use of neurofeedback in patients with schizophrenia. Schizophr. Bull. Open 2020, 1, sgaa005. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lin, C.-J.; Hung, Y.Y.; Lin, C.C.; Tsai, M.C.; Huang, T.L. Does biofeedback improve symptoms of schizophrenia (emotion, psychotic symptoms, and cognitive function)? Taiwan J. Psychiatry 2016, 30, 120–127. [Google Scholar]
- Batail, J.-M.; Bioulac, S.; Cabestaing, F.; Daudet, C.; Drapier, D.; Fouillen, M.; Fovet, T.; Hakoun, A.; Jardri, R.; Jeunet, C.; et al. EEG neurofeedback research: A fertile ground for psychiatry? Encephale 2019, 45, 245–255. [Google Scholar] [CrossRef]
- Cordes, J.S.; Mathiak, K.A.; Dyck, M.; Alawi, E.M.; Gaber, T.J.; Zepf, F.D.; Klasen, M.; Zvyagintsev, M.; Gur, R.C.; Mathiak, K. Cognitive and neural strategies during control of the anterior cingulate cortex by fMRI neurofeedback in patients with schizophrenia. Front. Behav. Neurosci. 2015, 9, 169. [Google Scholar] [CrossRef]
- Penadés, R.; Pujol, N.; Catalán, R.; Massana, G.; Rametti, G.; García-Rizo, C.; Bargalló, N.; Gastó, C.; Bernardo, M.; Junqué, C. Brain Effects of Cognitive Remediation Therapy in Schizophrenia: A Structural and Functional Neuroimaging Study. Biol. Psychiatry 2013, 73, 1015–1023. [Google Scholar] [CrossRef]
- Miranda, M.; Morici, J.F.; Zanoni, M.B.; Bekinschtein, P. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front. Cell. Neurosci. 2019, 13, 363. [Google Scholar] [CrossRef]
- Di Rosa, M.C.; Zimbone, S.; Saab, M.W.; Tomasello, M.F. The pleiotropic potential of BDNF beyond neurons: Implication for a healthy mind in a healthy body. Life 2021, 11, 1256. [Google Scholar] [CrossRef]
- Hendriati, D.; Effendy, E.; Amin, M.M.; Camellia, V.; Husada, M.S. Brain-derived neurotropic factor serum level and severity symptom of Bataknese male patients with schizophrenia in North Sumatera, Indonesia. Open Access Maced. J. Med. Sci. 2019, 7, 1957–1961. [Google Scholar] [CrossRef] [Green Version]
- Markiewicz, R.; Kozioł, M.; Olajossy, M.; Masiak, J. Can brain-derived neurotrophic factor (BDNF) be an indicator of effective rehabilitation interventions in schizophrenia? Psychiatr. Pol. 2018, 52, 819–834. [Google Scholar] [CrossRef]
- Li, J.; Ye, F.; Xiao, W.; Tang, X.; Sha, W.; Zhang, X.; Wang, J. Increased serum brain-derived neurotrophic factor levels following electroconvulsive therapy or antipsychotic treatment in patients with schizophrenia. Eur. Psychiatry 2016, 36, 23–28. [Google Scholar] [CrossRef]
- Alcami, P.; Pereda, A.E. Beyond plasticity: The dynamic impact of electrical synapses on neural circuits. Nat. Rev. Neurosci. 2019, 20, 253–271. [Google Scholar] [CrossRef]
- McPhee, G.M.; Downey, L.A.; Stough, C. Neurotrophins as a reliable biomarker for brain function, structure, and cognition: A systematic review and meta-analysis. Neurobiol. Learn. Mem. 2020, 175, 107298. [Google Scholar] [CrossRef]
- Lu, Y.; Christian, K.; Lu, B. BDNF: A key regulator for protein synthesis dependent LTP and long-term memory? Neurobiol. Learn. Mem. 2008, 89, 312–323. [Google Scholar] [CrossRef] [Green Version]
- Bathina, S.; Das, U.N. Brain-derived neurotrophic factor, and its clinical implications. Arch. Med. Sci. 2015, 11, 1164–1178. [Google Scholar] [CrossRef]
- Howland, R.H. Vagus nerve stimulation. Curr. Behav. Neurosci. Rep. 2014, 1, 64–73. [Google Scholar] [CrossRef] [Green Version]
- Schlaepfer, T.E.; Frick, C.; Zobel, A.; Maier, W.; Heuser, I.; Bajbouj, M.; O’Keane, V.; Corcoran, C.; Adolfsson, R.; Trimble, M.; et al. Vagus nerve stimulation for depression: Efficacy and safety in a European study. Psychol. Med. 2008, 38, 651–661. [Google Scholar] [CrossRef] [Green Version]
- Englot, D.J.; Chang, E.F.; Auguste, K.I. Vagus nerve stimulation for epilepsy: A meta-analysis of efficacy and predictors of response. J. Neurosurg. 2011, 115, 1248–1255. [Google Scholar] [CrossRef]
- Hasan, A.; Wolff-Menzler, C.; Pfeiffer, S.; Falkai, P.; Weidinger, E.; Jobst, A.; Hoell, I.; Malchow, B.; Yeganeh-Doost, P.; Strube, W.; et al. Transcutaneous noninvasive vagus nerve stimulation (tVNS) in the treatment of schizophrenia: A bicentric randomized controlled pilot study. Eur. Arch. Psychiatry Clin. Neurosci. 2015, 265, 589–600. [Google Scholar] [CrossRef]
- George, M.S.; Sackeim, H.A.; Rush, A.; Marangell, L.B.; Nahas, Z.; Husain, M.M.; Lisanby, S.; Burt, T.; Goldman, J.; Ballenger, J.C. Vagus nerve stimulation: A new tool for brain research and therapy. Biol. Psychiatry 2000, 47, 287–295. [Google Scholar] [CrossRef] [PubMed]
- Hamer, H.M.; Bauer, S. Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Epilepsy Res. 2019, 153, 83–84. [Google Scholar] [CrossRef] [PubMed]
- Smucny, J.; Visani, A.; Tregellas, J.R. Could vagus nerve stimulation target hippocampal hyperactivity to improve cognition in schizophrenia? Front. Psychiatry 2015, 6, 43. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Clark, K.; Krahl, S.; Smith, D.; Jensen, R. Post-training unilateral vagal stimulation enhances retention performance in the rat. Neurobiol. Learn. Mem. 1994, 63, 213–216. [Google Scholar] [CrossRef] [PubMed]
- Berthoud, H.; Neuhuber, W.L. Functional and chemical anatomy of the afferent vagal system. Auton. Neurosci. 2000, 85, 1–17. [Google Scholar] [CrossRef]
- Pigato, G.; Rosson, S.; Bresolin, N.; Toffanin, T.; Sambataro, F.; Olivo, D.; Perini, G.; Causin, F.; Denaro, L.; Landi, A.; et al. Vagus nerve stimulation in treatment-resistant depression: A case series of long-term follow-up. J. ECT 2023, 39, 23–27. [Google Scholar] [CrossRef]
- Follesa, P.; Biggio, F.; Gorini, G.; Caria, S.; Talani, G.; Dazzi, L.; Puligheddu, M.; Marrosu, F.; Biggio, G. Vagus nerve stimulation increases norepinephrine concentration and the gene expression of BDNF and bFGF in the rat brain. Brain Res. 2007, 1179, 28–34. [Google Scholar] [CrossRef]
- Raedt, R.; Clinckers, R.; Mollet, L.; Vonck, K.; El Tahry, R.; Wyckhuys, T.; De Herdt, V.; Carrette, E.; Wadman, W.; Michotte, Y.; et al. Increased hippocampal noradrenaline is a biomarker for efficacy of vagus nerve stimulation in a limbic seizure model. J. Neurochem. 2011, 117, 461–469. [Google Scholar] [CrossRef]
- Nichols, J.; Nichols, A.; Smirnakis, S.; Engineer, N.; Kilgard, M.; Atzori, M. Vagus nerve stimulation modulates cortical synchrony and excitability through the activation of muscarinic receptors. Neuroscience 2011, 189, 207–214. [Google Scholar] [CrossRef] [Green Version]
- Ramanathan, D.; Tuszynski, M.H.; Conner, J.M. The basal forebrain cholinergic system is required specifically for behaviorally mediated cortical map plasticity. J. Neurosci. 2009, 29, 5992–6000. [Google Scholar] [CrossRef] [Green Version]
- Freitas, C.; Fregni, F.; Pascual-Leone, A. Meta-analysis of the effects of repetitive transcranial magnetic stimulation (rTMS) on negative and positive symptoms in schizophrenia. Schizophr. Res. 2009, 108, 11–24. [Google Scholar] [CrossRef] [Green Version]
- Harvey, P.D.; Koren, D.; Reichenberg, A.; Bowie, C.R. Negative symptoms, and cognitive deficits: What is the nature of their relationship. Schizophr. Bull. 2006, 32, 250–258. [Google Scholar] [CrossRef] [Green Version]
- Sciortino, D.; Pigoni, A.; Delevecchio, G.; Maggioni, E.; Schiena, G.; Brambilla, P. Role of rTMS in the treatment of cognitive impairments in bipolar disorder and schizophrenia: A review of randomized controlled trials. J. Affect. Disord. 2021, 280, 148–155. [Google Scholar] [CrossRef]
- Siever, L.J.; Davis, K.L. The pathophysiology of schizophrenia disorders: Perspectives from the spectrum. Am. J. Psychiatry 2004, 161, 398–413. [Google Scholar] [CrossRef]
- Mogg, A.; Purvis, R.; Eranti, S.; Contell, F.; Taylor, J.P.; Nicholson, T.; Brown, R.G.; McLoughlin, D.M. Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: A randomized controlled pilot study. Schizophr. Res. 2007, 93, 221–228. [Google Scholar] [CrossRef]
- Cohen, E.; Bernardo, M.; Masana, J.; Arrufat, F.J.; Navarro, V.; Valls-Sole, J.; Boget, T.; Barrantes, N.; Catarineu, S.; Font, M.; et al. Repetitive transcranial magnetic stimulation in the treatment of chronic negative schizophrenia: A pilot study. J. Neurol. Neurosurg. Psychiatry 1999, 67, 129–130. [Google Scholar] [CrossRef] [Green Version]
- Sachdev, P.; Loo, C.; Mitchell, P.; Malhi, G. Transcranial magnetic stimulation for the deficit syndrome of schizophrenia: A pilot investigation. Psychiatry Clin. Neurosci. 2005, 59, 354–357. [Google Scholar] [CrossRef]
- Xie, Y.; Guan, M.; Wang, Z.; Ma, Z.; Wang, H.; Fang, P.; Yin, H. rTMS induces brain functional and structural alternations in schizophrenia patient with auditory verbal hallucination. Front. Neurosci. 2021, 15, 722894. [Google Scholar] [CrossRef]
- Guan, H.Y.; Zhao, J.M.; Wang, K.Q.; Su, X.R.; Pan, Y.F.; Guo, J.M.; Jiang, L.; Wang, Y.H.; Liu, H.Y.; Sun, S.G.; et al. High-frequency neuronavigated rTMS effect on clinical symptoms and cognitive dysfunction: A pilot double-blind, randomized controlled study in Veterans with schizophrenia. Transl. Psychiatry 2020, 10, 79. [Google Scholar] [CrossRef] [Green Version]
- Brandt, S.J.; Oral, H.Y.; Arellano-Bravo, C.; Plawecki, M.H.; Hummer, T.A.; Francis, M.M. Repetitive transcranial magnetic stimulation as a therapeutic and probe in schizophrenia: Examining the role of neuroimaging and future directions. Neurotherapeutics 2021, 18, 827–844. [Google Scholar] [CrossRef]
- Lang, N.; Harms, J.; Weyh, T.; Lemon, R.N.; Paulus, W.; Rothwell, J.; Siebner, H.R. Stimulus intensity and coil characteristics influence the efficacy of rTMS to suppress cortical excitability. Clin. Neurophysiol. 2006, 117, 2292–2301. [Google Scholar] [CrossRef] [PubMed]
- Pell, G.S.; Roth, Y.; Zangen, A. Modulation of cortical excitability induced by repetitive transcranial magnetic stimulation: Influence of timing and geometrical parameters and underlying mechanisms. Prog. Neurobiol. 2011, 93, 59–98. [Google Scholar] [CrossRef] [PubMed]
- Shi, C.; Yu, X.; Cheung, E.F.C.; Shum, D.H.K.; Chan, R.C.K. Revisiting the therapeutic effect of rTMS on negative symptoms in schizophrenia: A meta-analysis. Psychiatry Res. 2014, 215, 505–513. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hovinhton, C.L.; McGirr, A.; Lepage, M.; Berlim, M.T. Repetitive transcranial magnetic stimulation (rTMS) for treating major depression and schizophrenia: A systematic review of recent meta-analyses. Ann. Med. 2013, 45, 308–321. [Google Scholar] [CrossRef] [PubMed]
- Wolwer, W.; Lowe, A.; Brinkmeyer, J.; Streit, M.; Habakuck, M.; Angelink, M.W.; Mobascher, A.; Gaebel, W.; Cordes, J. Repetitive transcranial magnetic stimulation (rTMS) improves facial affect recognition in schizophrenia. Brain Stimul. 2014, 7, 559–563. [Google Scholar] [CrossRef]
- Hajak, G.; Marienhagen, J.; Langguth, B.; Werner, S.; Binder, H.; Eichhammer, P. High-frequency repetitive transcranial magnetic stimulation in schizophrenia: A combined treatment and neuroimaging study. Psychol. Med. 2004, 34, 1157–1163. [Google Scholar] [CrossRef]
- Trippe, J.; Mix, A.; Aydin-Abidin, S.; Funke, K.; Benali, A. Theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex. Exp. Brain Res. 2009, 199, 411–421. [Google Scholar] [CrossRef]
- Woods, A.J.; Antal, A.; Bikson, M.; Boggio, P.S.; Brunoni, A.R.; Celnik, P.; Cohen, L.G.; Fregni, F.; Herrmann, C.S.; Kappenman, E.S.; et al. A technical guide to tDCS, and related non-invasive brain stimulation tools. Clin. Neurophysiol. 2016, 127, 1031–1048. [Google Scholar] [CrossRef] [Green Version]
- Podda, M.V.; Cocco, S.; Mastrodonato, A.; Fusco, S.; Leone, L.; Barbati, S.A.; Colussi, C.; Ripoli, C.; Grassi, C. Anodal transcranial direct current stimulation boosts synaptic plasticity and memory in mice via epigenetic regulation of Bdnf expression. Sci. Rep. 2016, 6, 22180. [Google Scholar] [CrossRef] [Green Version]
- Pulvermuller, F. Neural reuse of action perception circuits for language, concepts, and communication. Prog. Neurobiol. 2018, 160, 1–44. [Google Scholar] [CrossRef]
- Chindemi, G.; Abdellah, M.; Amsalem, O.; Benavides-Piccione, R.; Delattre, V.; Doron, M.; Ecker, A.; Jaquier, A.T.; King, J.; Kumbhar, P.; et al. A calcium-based plasticity model for predicting long-term potentiation and depression in the neocortex. Nat. Commun. 2022, 13, 3038. [Google Scholar] [CrossRef]
- Diering, G.H.; Huganir, R.L. The AMPA receptor code of synaptic plasticity. Neuron. 2018, 100, 314–329. [Google Scholar] [CrossRef] [Green Version]
- El-Hagrassy, M.; Jones, F.; Rosa, G.; Fregni, F. CNS non-invasive brain stimulation. In Adult and Pediatric Neuromodulation; Gilleran, J.P., Alpert, S.A., Eds.; Springer: Berlin/Heidelberg, Germany, 2018. [Google Scholar]
- Tremblay, S.; Larochelle-Brunet, F.; Louis-Philippe, L.; El Mouderrib, S.; Lepge, J.-F.; Theoret, H. Systmatic assessment of duration and intensity of anodal transcranial direct current stimulation on primary motor cortex excitability. Eur. J. Neurosci. 2016, 44, 2184–2190. [Google Scholar] [CrossRef]
- Samani, M.M.; Agboada, D.; Jamil, A.; Kuo, M.-F.; Nitsche, M.A. titrating the neuroplastic effects of cathodal transcranial direct current stimulation (tDCS) over the primary motor cortex. Cortex 2019, 119, 350–361. [Google Scholar] [CrossRef]
- Desslegn, D.; Girma, S.; Abdeta, T. Quality of life and its association with psychiatric symptoms and socio-demographic characteristics among people with schizophrenia: A hospital-based cross-sectional study. PLoS ONE 2020, 15, e0229514. [Google Scholar] [CrossRef]
- Tyrovolas, S.; El Bcheraoui, C.; A Alghnam, S.; Alhabib, K.F.; Almadi, M.A.H.; Al-Raddadi, R.M.; Bedi, N.; El Tantawi, M.; Krish, V.S.; A Memish, Z.; et al. The burden of disease in Saudi Arabia 1990–2017: Results from the Global Burden of Disease Study 2017. Lancet Planet. Health 2020, 4, e195–e208. [Google Scholar] [CrossRef]
- Kennedy, J.L.; Altar, C.A.; Taylor, D.L.; Degitar, I.; Hornberger, J.C. The social and economic burden of treatment-resistant schizophrenia: A systematic literature review. Int. Clin. Psychopharmacol. 2014, 29, 63–76. [Google Scholar] [CrossRef]
- Kubera, K.M.; Barth, A.; Hirjak, D.; Thomann, P.A.; Wolf, R.C. Noninvasive brain stimulation for the treatment of auditory verbal hallucinations in schizophrenia: Methods, effects, and challenges. Front. Syst. Neurosci. 2015, 9, 131. [Google Scholar] [CrossRef] [Green Version]
- Mondino, M.; Brunelin, J.; Palm, U.; Brunoni, A.R.; Poulet, E.; Fecteau, S. Transcranial direct current stimulation for the treatment of refractory symptoms of schizophrenia. Current evidence and future directions. Curr. Pharm. Des. 2015, 21, 3373–3383. [Google Scholar] [CrossRef]
- Xiang, Y.; Li, Y.; Shu, C.; Liu, Z.; Wang, H.; Wang, G. Prefrontal cortex activation during verbal fluency task and tower of London task in schizophrenia and major depressive disorder. Front. Psychiatry 2021, 12, 709875. [Google Scholar] [CrossRef]
- Cheng, P.W.C.; Louie, L.L.C.; Wong, Y.L.; Wong, S.M.C.; Leung, W.Y.; Nitsche, M.A.; Chan, W.C. The effects of transcranial direct current stimulation (tDCS) on clinical symptoms in schizophrenia: A systematic review and meta-analysis. Asian. J. Psychiatry 2020, 53, 102392. [Google Scholar] [CrossRef] [PubMed]
- Brunelin, J.; Mondino, M.; Gassab, L.; Haesebaert, F.; Gaha, L.; Suaud-Chagny, M.-F.; Saoud, M.; Mechri, A.; Poulet, E. Examining Transcranial Direct-Current Stimulation (tDCS) as a Treatment for Hallucinations in Schizophrenia. Am. J. Psychiatry 2012, 169, 719–724. [Google Scholar] [CrossRef] [PubMed]
- Mondino, M.; Haesebaert, F.; Poulet, E.; Saoud, M.; Brunelin, J. Efficacy of cathodal transcranial direct current stimulation over the left orbitofrontal cortex in a patient with treatment-resistant obsessive-compulsive disorder. J. ECT 2015, 31, 271–272. [Google Scholar] [CrossRef] [PubMed]
- Lindenmayer, J.P.; Kulsa, M.K.C.; Sultana, T.; Kaur, A.; Yang, R.; Ljuri, I.; Parker, B.; Khan, A. Transcranial direct-current stimulation in ultra-treatment-resistant schizophrenia. Brain Stimul. 2019, 12, 54–61. [Google Scholar] [CrossRef] [PubMed]
- Tseng, P.-T.; Zeng, B.-S.; Hung, C.-M.; Liang, C.-S.; Stubbs, B.; Carvalho, A.F.; Brunoni, A.R.; Su, K.-P.; Tu, Y.-K.; Wu, Y.-C.; et al. Assessment of Noninvasive Brain Stimulation Interventions for Negative Symptoms of Schizophrenia: A systematic review and network meta-analysis. JAMA Psychiatry 2022, 79, 770. [Google Scholar] [CrossRef]
- Moreira de Costa, R.M.; Vidal de Carvalho, L.A. The acceptance of virtual reality devices for cognitive rehabilitation: A report of positive results with schizophrenia. Comput. Methods Programs Biomed. 2004, 73, 173–182. [Google Scholar] [CrossRef]
- Rizzo, A. The Application of Virtual Environments for Mental Healthcare. In Tutorial 1 of the IEEE Virtual Reality; IEEE: New York, NY, USA, 2001. [Google Scholar]
- Tsang, M.M.Y.; Man, D.W.K. A virtual reality-based vocational training system (VRVTS) for people with schizophrenia in vocational rehabilitation. Schizophr. Res. 2013, 144, 51–62. [Google Scholar] [CrossRef]
- Hakulinen, C.; McGrath, J.J.; Timmerman, A.; Skipper, N.; Mortensen, P.B.; Pedersen, C.B.; Agerbo, E. The association between early-onset schizophrenia with employment, income, education, and cohabitation status: Nationwide study with 35 years of follow-up. Soc. Psychiatry Psychiatr. Epidemiol. 2019, 54, 1343–1351. [Google Scholar] [CrossRef] [Green Version]
- Gainsford, K.; Fitzgibbon, B.; Fitzgerald, P.B.; Hoy, K.E. Transforming treatments for schizophrenia: Virtual reality, brain stimulation and social cognition. Psychiatry Res. 2020, 288, 112974. [Google Scholar] [CrossRef]
- Novo, A.; Fonseca, J.; Barroso, B.; Guimaraes, M.; Louro, A.; Fernandes, H.; Lopes, R.P.; Leitao, P. Virtual reality rehabilitation’s impact on negative symptoms and psychosocial rehabilitation in schizophrenia spectrum disorder: A systematic review. Healthcare 2021, 9, 1429. [Google Scholar] [CrossRef]
- Mooler, H.J. The relevance of negative symptoms in schizophrenia and how to treat them with psychopharmaceuticals? Psychiatr. Danub. 2016, 28, 435–440. [Google Scholar]
- Freeman, D.; Bradley, J.; Antley, A.; Bourke, E.; DeWeever, N.; Evans, N.; Černis, E.; Sheaves, B.; Waite, F.; Dunn, G.; et al. Virtual reality in the treatment of persecutory delusions: Randomised controlled experimental study testing how to reduce delusional conviction. Br. J. Psychiatry 2016, 209, 62–67. [Google Scholar] [CrossRef] [Green Version]
- A Pot-Kolder, R.M.C.; Geraets, C.N.W.; Veling, W.; van Beilen, M.; Staring, A.B.P.; Gijsman, H.J.; Delespaul, P.A.E.G.; van der Gaag, M. Virtual-reality-based cognitive behavioural therapy versus waiting list control for paranoid ideation and social avoidance in patients with psychotic disorders: A single-blind randomised controlled trial. Lancet Psychiatry 2018, 5, 217–226. [Google Scholar] [CrossRef]
- Lopes, R.P.; Barroso, B.; Deusdado, L.; Novo, A.; Guimaraes, M.; Teixeira, J.P.; Leitao, P. Digital technologies for innovative mental health rehabilitation. Electronics 2021, 10, 2260. [Google Scholar] [CrossRef]
- Macedo, M.; Marques, A.; Queiros, C. Virtual reality in assessment and treatment of schizophrenia: A systematic review. J. Bras. Psiquiatr. 2015, 64, 70–81. [Google Scholar] [CrossRef] [Green Version]
- Solmi, M.; Croatto, G.; Piva, G.; Rosson, S.; Fusar-Poli, P.; Rubio, J.M.; Carvalho, A.F.; Vieta, E.; Arango, C.; DeTore, N.R.; et al. Efficacy and acceptability of psychosocial interventions in schizophrenia: Systematic overview and quality appraisal of the meta-analytic evidence. Mol. Psychiatry 2023, 28, 354–368. [Google Scholar] [CrossRef]
- Yeo, H.; Yoon, S.; Lee, J.; Kurtz, M.M.; Choi, K. A meta-analysis of the effects of social-cognitive training in schizophrenia: The role of treatment characteristics and study quality. Br. J. Clin. Psychol. 2022, 61, 37–57. [Google Scholar] [CrossRef]
- Lejeune, J.A.; Northrop, A.; Kurtz, M.M. A meta-analysis of cognitive remediation for schizophrenia: Efficacy and the role of participant and treatment factors. Schizophr. Bull. 2021, 47, 997–1006. [Google Scholar] [CrossRef]
- Markiewicz-Gospodarek, A.; Markiewicz, R.; Dobrowolska, B.; Rahnama, M.; Łoza, B. Relationship of neuropeptide S (NPS) with neurocognitive, clinical, and electrophysiological parameters of patients during structured rehabilitation therapy for schizophrenia. J. Clin. Med. 2022, 11, 5266. [Google Scholar] [CrossRef]
- Chen, A.T.; Nasrallah, H.A. Neuroprotective effects of the second-generation antipsychotics. Schizophr. Res. 2019, 208, 1–7. [Google Scholar] [CrossRef]
- Murray, R.M.; Quattrone, D.; Natesan, S.; van Os, J.; Nordentoft, M.; Howes, O.; Di Forti, M.; Taylor, D. Should psychiatrists be more cautious about the long-term prophylactic use of antipsychotics? Br. J. Psychiatry 2016, 209, 361–365. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fernandes, B.S.; Steiner, J.; Berk, M.; Molendijk, M.L.; Gonzalez-Pinto, A.; Turck, C.W.; Nardin, P.; Gonçalves, C.-A. Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: Meta-analysis and implications. Mol. Psychiatry 2015, 20, 1108–1119. [Google Scholar] [CrossRef] [PubMed]
- Bartolomeis, A.d.; Barone, A.; Begni, V.; Riva, M.A. Present, and future antipsychotic drugs: A systematic review of the putative mechanisms of action for efficacy and a critical appraisal under a translational perspective. Pharmacol. Res. 2022, 176, 106078. [Google Scholar] [CrossRef] [PubMed]
- Ogawa, S.; Sung, Y.W. Selected topics relating to functional MRI study of the brain. Keio J. Med. 2019, 68, 73–86. [Google Scholar] [CrossRef] [Green Version]
- Furtner, J.; Schöpf, V.; Erfurth, A.; Sachs, G. An fMRI study of cognitive remediation in drug-naïve subjects diagnosed with first episode schizophrenia. Wien. Klin. Wochenschr. 2022, 34, 249–254. [Google Scholar] [CrossRef]
- Mothersill, D.; Donohoe, G. Neural effects of cognitive training in schizophrenia: A systematic review and activation likelihood estimation meta-analysis. Biol. Psychiatry Cogn. Neurosci. Neuroimaging 2019, 4, 688–696. [Google Scholar] [CrossRef]
- Finc, K.; Bonna, K.; Lewandowska, M.; Wolak, T.; Nikadon, J.; Dreszer, J.; Duch, W.; Kühn, S. Transition of the functional brain network related to increasing cognitive demands. Hum. Brain Mapp. 2017, 38, 3659–3674. [Google Scholar] [CrossRef] [Green Version]
- Klomjai, W.; Katz, R.; Lackmy-Vallée, A. Basic principles of transcranial magnetic stimulation (TMS) and repetitive TMS (rTMS). Ann. Phys. Rehabil. Med. 2015, 58, 208–213. [Google Scholar] [CrossRef]
- di Hou, M.; Santoro, V.; Biondi, A.; Shergill, S.S.; Premoli, I. A systematic review of TMS and neurophysiological biometrics in patients with schizophrenia. J. Psychiatry Neurosci. 2021, 46, E675–E701. [Google Scholar] [CrossRef]
- Nardone, R.; Sebastianelli, L.; Versace, V.; Ferrazzoli, D.; Saltuari, L.; Trinka, E. TMS-EEG Co-Registration in patients with mild cognitive impairment, Alzheimer’s disease, and other dementias: A systematic review. Brain Sci. 2021, 11, 303. [Google Scholar] [CrossRef]
- Sonmez, A.I.; Camsari, D.D.; Nandakumar, A.L.; Voort, J.L.V.; Kung, S.; Lewis, C.P.; Croarkin, P.E. Accelerated TMS for Depression: A systematic review and meta-analysis. Psychiatry Res. 2019, 273, 770–781. [Google Scholar] [CrossRef]
- Brookes, M.J.; Leggett, J.; Rea, M.; Hill, R.M.; Holmes, N.; Boto, E.; Bowtell, R. Magnetoencephalography with optically pumped magnetometers (OPM-MEG): The next generation of functional neuroimaging. Trends Neurosci. 2022, 45, 621–634. [Google Scholar] [CrossRef]
- Kim, J.A.; Davis, K.D. Magnetoencephalography: Physics, techniques, and applications in the basic and clinical neurosciences. J. Neurophysiol. 2021, 125, 938–956. [Google Scholar] [CrossRef]
- Edgar, J.C.; Guha, A.; Miller, G.A. Magnetoencephalography for schizophrenia. Neuroimaging Clin. N. Am. 2020, 30, 205–216. [Google Scholar] [CrossRef]
- Burbulla, L.F.; Mc Donald, J.M.; Valdez, C.; Gao, F.; Bigio, E.H.; Krainc, D. Modeling brain pathology of Niemann-Pick disease type C using patient-derived neurons. Mov. Disord. 2021, 36, 1022–1027. [Google Scholar] [CrossRef]
- Habela, C.W.; Song, H.; Ming, G.L. Modeling synaptogenesis in schizophrenia and autism using human iPSC derived neurons. Mol. Cell. Neurosci. 2016, 73, 52–62. [Google Scholar] [CrossRef]
- Notaras, M.; Lodhi, A.; Fang, H.; Greening, D.; Colak, D. The proteomic architecture of schizophrenia iPSC-derived cerebral organoids reveals alterations in GWAS and neuronal development factors. Transl. Psychiatry 2021, 11, 541. [Google Scholar] [CrossRef]
- Howes, O.D.; Cummings, C.; Chapman, G.E.; Shatalina, E. Neuroimaging in schizophrenia: An overview of findings and their implications for synaptic changes. Neuropsychopharmacology 2023, 48, 151–167. [Google Scholar] [CrossRef]
- De Picker, L.J.; Morrens, M.; Chance, S.A.; Boche, D. Microglia and brain plasticity in acute psychosis and schizophrenia Illness course: A meta-review. Front. Psychiatry 2017, 8, 238. [Google Scholar] [CrossRef] [Green Version]
- Krauss, J.K.; Lipsman, N.; Aziz, T.; Boutet, A.; Brown, P.; Chang, J.W.; Davidson, B.; Grill, W.M.; Hariz, M.I.; Horn, A.; et al. Technology of deep brain stimulation: Current status and future directions. Nat. Rev. Neurol. 2021, 17, 75–87. [Google Scholar] [CrossRef]
- Gault, J.M.; Davis, R.; Cascella, N.G.; Saks, E.R.; Corripio, I.; Anderson, W.S.; Olincy, A.; A Thompson, J.; Pomarol-Clotet, E.; Sawa, A.; et al. Approaches to neuromodulation for schizophrenia. J. Neurol. Neurosurg. Psychiatry 2018, 89, 777–787. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Qi, S.; Abbott, C.C.; Narr, K.L.; Jiang, R.; Upston, J.; McClintock, S.M.; Espinoza, R.; Jones, T.; Zhi, D.; Sun, H.; et al. Electroconvulsive therapy treatment responsive multimodal brain networks. Hum. Brain Mapp. 2020, 41, 1775–1785. [Google Scholar] [CrossRef] [PubMed]
- Perugi, G.; Medda, P.; Toni, C.; Mariani, M.G.; Socci, C.; Mauri, M. The role of electroconvulsive therapy (ECT) in bipolar disorder: Effectiveness in 522 patients with bipolar depression, mixed-state, mania, and catatonic features. Curr. Neuropharmacol. 2017, 15, 359–371. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sinclair, D.J.M.; Zhao, S.; Qi, F.; Nyakyoma, K.; Kwong, J.S.W.; Adams, C.E. Electroconvulsive therapy for treatment-resistant’s schizophrenia. Schizophr. Bull. 2019, 45, 730–732. [Google Scholar] [CrossRef]
- Parker, D.A.; Trotti, R.L.; McDowell, J.E.; Keedy, S.K.; Gershon, E.S.; Ivleva, E.I.; Pearlson, G.D.; Keshavan, M.S.; Tamminga, C.A.; Sweeney, J.A.; et al. Auditory paired-stimuli responses across the psychosis and bipolar spectrum and their relationship to clinical features. Biomark. Neuropsychiatry 2020, 3, 100014. [Google Scholar] [CrossRef]
- Du, X.; Li, J.; Xiong, D.; Pan, Z.; Wu, F.; Ning, Y.; Chen, J.; Wu, K. Research on electroencephalogram specifics in patients with schizophrenia under cognitive load. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2020, 37, 45–53. [Google Scholar] [CrossRef]
- Mojtabavi, H.; Saghazadeh, A.; van den Heuvel, L.; Bucker, J.; Rezaei, N. Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis. PLoS ONE 2020, 15, e0241928. [Google Scholar] [CrossRef]
- Liu, D.Y.; Shen, X.M.; Yuan, F.F. The physiology of BDNF and its relationship with ADHD. Mol. Neurobiol. 2015, 52, 1467–1476. [Google Scholar] [CrossRef]
- Chao, D.L.; Ma, L.; Shen, K. Transient cell-cell interactions in neural circuit formation. Nat. Rev. Neurosci. 2009, 10, 262–271. [Google Scholar] [CrossRef] [Green Version]
- Panja, D.; Bramham, C.R. BDNF mechanisms in late LTP formation: A synthesis and breakdown. Neuropharmacology 2014, 76, 664–676. [Google Scholar] [CrossRef]
- Wunderink, L.; Nieboer, R.M.; Wiersma, D.; Sytema, S.; Nienhuis, F.J. Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: Long-term follow-up of a 2-year randomized clinical trial. JAMA Psychiatry 2013, 70, 913–920. [Google Scholar] [CrossRef] [PubMed]
- Correll, C.U.; Rubio, J.M.; Kane, J.M. What is the risk-benefit ratio of long-term antipsychotic treatment in people with schizophrenia? World Psychiatry 2018, 17, 149–160. [Google Scholar] [CrossRef] [Green Version]
- MacKenzie, N.E.; Kowalchuk, C.; Agarwal, S.M.; Costa-Dookhan, K.; Caravaggio, F.; Gerretsen, P.; Chintoh, A.; Remington, G.J.; Taylor, V.; Müeller, D.J.; et al. Antipsychotics, Metabolic Adverse Effects, and Cognitive Function in Schizophrenia. Front. Psychiatry 2018, 9, 622. [Google Scholar] [CrossRef] [Green Version]
- Kullmann, S.; Heni, M.; Hallschmid, M.; Fritsche, A.; Preissl, H.; Haring, H.U. Brain insulin resistance at the crossroads of metabolic and cognitive disorders in humans. Physiol. Rev. 2016, 96, 1169–1209. [Google Scholar] [CrossRef] [Green Version]
- Spinelli, M.; Fusco, S.; Mainardi, M.; Scala, F.; Natale, F.; Lapenta, R.; Mattera, A.; Rinaudo, M.; Puma, D.D.L.; Ripoli, C.; et al. Brain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a. Nat. Commun. 2017, 8, 2009. [Google Scholar] [CrossRef] [Green Version]
- Ramos-Rodriguez, J.J.; Molina-Gil, S.; Ortiz-Barajas, O.; Jimenez-Palomares, M.; Perdomo, G.; Cozar-Castellano, I.; Lechuga-Sancho, A.; Garcia-Alloza, M. Central Proliferation and Neurogenesis Is Impaired in Type 2 Diabetes and Prediabetes Animal Models. PLoS ONE 2014, 9, e89229. [Google Scholar] [CrossRef]
- Tiihonen, J.; Lönnqvist, J.; Wahlbeck, K.; Klaukka, T.; Niskanen, L.; Tanskanen, A.; Haukka, J. 11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study). Lancet 2009, 374, 620–627. [Google Scholar] [CrossRef] [PubMed]
- Yang, C.; Tang, J.; Liu, N.; Yao, L.; Xu, M.; Sun, H.; Tao, B.; Gong, Q.; Cao, H.; Zhang, W.; et al. The effects of antipsychotic treatment on the brain of patients with first-episode schizophrenia: A selective review of longitudinal MRI studies. Front. Psychiatry 2021, 12, 593703. [Google Scholar] [CrossRef] [PubMed]
Method Type | Characteristic | Ref. |
---|---|---|
Functional magnetic resonance imaging (fMRI) | Unveils changes in the blood perfusion of those brain parts that are active during simple task management, as they require increased oxygen intake. Most fMRI studies involving patients with schizophrenia have directly examined working memory (BOLD effect), e.g., after cognitive remediation or after an intensive computerized training, exploring patterns of arousal in the measurements. Finc et al. (2017) describes patients dealing with experimental tasks that were leading to the positive reorganization (adaptation) of the brain process. | [128,129,130,131] |
Transcranial magnetic stimulation (TMS) | Is a non-invasive method generating magnetic stimulation, which influences the cortex of the brain through the patient’s scalp. Among various cortical regions, TMS activates motoneurons and their tracts, which can be detected, making the model of CNS integrity. TMS can be used in the diagnosis and assessment of the severity of neurodegenerative diseases like schizophrenia. TMS is not only a diagnostic measure but can also be applied as a stimulation in drug-resistant neuropsychiatric disorders, including schizophrenia. | [132,133,134,135] |
Magnetoencephalography (MEG) | Detects magnetic fields caused by the synchronous activity of neurons and provides high-quality spatiotemporal maps of electrophysiological activity. The new version of MED offers increasingly higher resolution of the map of neuronal activity and the ability to conduct research in motion (optically pumped magnetometers; OPM-MEG). MEG studies in schizophrenia are focused on the whole-brain resting state activity, auditory encoding processes, and functional connectivity. MEG in schizophrenia, as in diseases associated with brain damage, could monitor the neuronal healing process. | [136,137,138] |
Pluripotential stem cells | By analogy with the experiment of Burbulla et al. (2021), in which the development of neurons with pluripotent stem cells was induced, which enabled the analysis of abnormalities in neuroplastic effects in patients struggling with Niemann-Pick type C syndrome, attempts are also made to use this method in patients with schizophrenia. | [139,140,141] |
Positron emission tomography (PET) | Is a functional imaging technique that uses radiotracers to visualize and measure metabolic processes. PET imaging of synaptic protein 2A (SV2A) in schizophrenic patients presented its decreased regional level and other metabolic markers in comparison to controls. PET meta-analysis suggested that psychotic exacerbations are accompanied by immunological changes in microglia different from those seen in non-acute states and that the symptoms of schizophrenia can be modified by compounds such as non-steroidal anti-inflammatory drugs. | [142,143] |
Deep brain stimulation (DBS) | Is mostly used to control Parkinson’s symptoms. This neurosurgical procedure is based on putting an electrode into the patient’s brain, and then connecting it to a pacemaker-like device. Based on this success, there is growing interest in using DBS to treat schizophrenia. DBS could target mostly the striatal dysregulation and is also considered for treating negative and cognitive symptoms. | [144,145] |
Electroconvulsive therapy (ECT) | In this procedure, physicians induce a controlled epileptic seizure, which leads to some positive functional and structural changes in the CNS. That could explain the effectiveness of ECT in drug-resistant cases of schizophrenia. | [146,147,148] |
Electrophysiological methods | There are many techniques to measure the electrical potentials of the CNS (evoked potentials, quantitative electroencephalography, mapping). In studies of patients with schizophrenia, these methods allow for the fundamental identification of inability to filter out (gating) useful from nonsensical information. However, linking electrophysiological results with cognitive disorders has so far turned out to be inconclusive. | [123,149,150] |
Neurochemistry | There are lots of potential biochemical biomarkers of neuroplasticity in cerebrospinal fluid, blood, urine, and saliva. The key problem of clinical trials is the methodology of their measurements. It seems that the neurological effects of neuropeptides, like BDNF, can be monitored by the peripheral serum level. | [151,152,153,154] |
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Markiewicz-Gospodarek, A.; Markiewicz, R.; Borowski, B.; Dobrowolska, B.; Łoza, B. Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment. Brain Sci. 2023, 13, 651. https://doi.org/10.3390/brainsci13040651
Markiewicz-Gospodarek A, Markiewicz R, Borowski B, Dobrowolska B, Łoza B. Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment. Brain Sciences. 2023; 13(4):651. https://doi.org/10.3390/brainsci13040651
Chicago/Turabian StyleMarkiewicz-Gospodarek, Agnieszka, Renata Markiewicz, Bartosz Borowski, Beata Dobrowolska, and Bartosz Łoza. 2023. "Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment" Brain Sciences 13, no. 4: 651. https://doi.org/10.3390/brainsci13040651
APA StyleMarkiewicz-Gospodarek, A., Markiewicz, R., Borowski, B., Dobrowolska, B., & Łoza, B. (2023). Self-Regulatory Neuronal Mechanisms and Long-Term Challenges in Schizophrenia Treatment. Brain Sciences, 13(4), 651. https://doi.org/10.3390/brainsci13040651