Clinical and neuroimaging aspects of formal thought disorder in schizophrenia: a brief narrative review
DOI:
https://doi.org/10.14739/mmt.2024.2.299080Keywords:
formal thought disorder, schizophrenia, morphometric neuroimagingAbstract
Aim. To analyze current sources regarding the clinical and neuroimaging aspects of formal thought disorder (FTD) in patients with schizophrenia to create an up-to-date pathogenetic model of its main forms.
Materials and methods. English-language publications in the Medline database (PubMed) were analyzed for this review. We analyzed only structural magnetic resonance imaging (MRI) studies in which a clear clinical assessment of FTD in schizophrenia is provided and the neuroimaging protocol meets generally accepted standards (as in the ENIGMA Schizophrenia Working Group). For the clinical division of FTD, positive and negative FTD were distinguished according to the positive and negative syndrome scale (PANSS).
Results. From a clinical point of view, FTD includes at least 30 phenomena. For clinical and neuroimaging studies, division into positive and negative FTD is used according to the PANSS. Positive FTD is manifested by the disorganization of thinking processes and exhibits mainly in violations of its purposeful sequence. Negative FTD is manifested by violations of the abstract-symbolic way of thinking, lack of spontaneity, and stereotyping. According to morphometric MRI data, atrophic changes in brain regions related to neuronal networks of cognition and impulse control (prefrontal and anterior cingulate cortex), emotional processing (amygdala), abstract thinking, and imagination (lateral occipital cortex) are important for the development of both forms of FTD. Negative FTD is mainly associated with damage to the prefronto-cingulate circles, which are the anatomical and functional substrates of executive functions. A unique feature of positive FTD is atrophy of the structures of the left temporal lobe, which leads to language disorders at the semantic level. Using the method of virtual histology, it was established that both forms of FTD are associated with bilateral changes in astrocytes and dendritic spines in the involved anatomical regions. A positive FTD is also associated with pathological changes in microglia in two hemispheres, while with a negative FTD, microglial damages are present only in the right hemisphere.
Conclusions. Positive FTD in schizophrenia is mainly associated with atrophic (astroglial-microglial) processes of cognitive control networks, negative – with the atrophy of networks of semantic processing of verbal information. In both forms, networks of emotional processing, abstract thinking, and imagination are involved. Treatment strategies for FTD should include effects on astroglial and microglial dysfunction.
References
Kircher T, Bröhl H, Meier F, Engelen J. Formal thought disorders: from phenomenology to neurobiology. Lancet Psychiatry. 2018;5(6):515-26. doi: https://doi.org/10.1016/S2215-0366(18)30059-2
Kircher T, Krug A, Stratmann M, Ghazi S, Schales C, Frauenheim M, et al. A rating scale for the assessment of objective and subjective formal Thought and Language Disorder (TALD). Schizophr Res. 2014;160(1-3):216-21. doi: https://doi.org/10.1016/j.schres.2014.10.024
Jerónimo J, Queirós T, Cheniaux E, Telles-Correia D. Formal Thought Disorders-Historical Roots. Front Psychiatry. 2018;9:572. doi: https://doi.org/10.3389/fpsyt.2018.00572
Roche E, Lyne J, O'Donoghue B, Segurado R, Behan C, Renwick L, et al. The prognostic value of formal thought disorder following first episode psychosis. Schizophr Res. 2016;178(1-3):29-34. doi: https://doi.org/10.1016/j.schres.2016.09.017
Marengo JT, Harrow M. Schizophrenic thought disorder at follow-up. A persistent or episodic course? Arch Gen Psychiatry. 1987;44(7):651-9. doi: https://doi.org/10.1001/archpsyc.1987.01800190071011
Oeztuerk OF, Pigoni A, Wenzel J, Haas SS, Popovic D, Ruef A, et al. The clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study. Eur Arch Psychiatry Clin Neurosci. 2022;272(3):403-13. doi: https://doi.org/10.1007/s00406-021-01327-y
Constantinides C, Han LK, Alloza C, Antonucci LA, Arango C, Ayesa-Arriola R, et al. Brain ageing in schizophrenia: evidence from 26 international cohorts via the ENIGMA Schizophrenia consortium. Mol Psychiatry. 2023;28(3):1201-9. doi: https://doi.org/10.1038/s41380-022-01897-w
Nickl-Jockschat T, Sharkey R, Bacon C, Peterson Z, Rootes-Murdy K, Salvador R, et al. Neural Correlates of Positive and Negative Formal Thought Disorder in Individuals with Schizophrenia: An ENIGMA Schizophrenia Working Group Study. Res Sq [Preprint]. 2023 Sep 28:rs.3.rs-3179362. doi: https://doi.org/10.21203/rs.3.rs-3179362/v1
Desikan RS, Ségonne F, Fischl B, Quinn BT, Dickerson BC, Blacker D, et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage. 2006;31(3):968-80. doi: https://doi.org/10.1016/j.neuroimage.2006.01.021
van Erp TG, Walton E, Hibar DP, Schmaal L, Jiang W, Glahn DC, et al. Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biol Psychiatry. 2018;84(9):644-54. doi: https://doi.org/10.1016/j.biopsych.2018.04.023
Chen J, Wensing T, Hoffstaedter F, Cieslik EC, Müller VI, Patil KR, et al. Neurobiological substrates of the positive formal thought disorder in schizophrenia revealed by seed connectome-based predictive modeling. Neuroimage Clin. 2021;30:102666. doi: https://doi.org/10.1016/j.nicl.2021.102666
Andreasen NC. Scale for the assessment of thought, language, and communication (TLC). Schizophr Bull. 1986;12(3):473-82. doi: https://doi.org/10.1093/schbul/12.3.473
Liddle PF, Ngan ET, Caissie SL, Anderson CM, Bates AT, Quested DJ, et al. Thought and Language Index: an instrument for assessing thought and language in schizophrenia. Br J Psychiatry. 2002;181:326-30. doi: https://doi.org/10.1192/bjp.181.4.326
Johnston MH, Holzman PS. Assessing schizophrenic thinking. San Francisco: Jossey-Bass, 1979.
Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-76. doi: https://doi.org/10.1093/schbul/13.2.261
Opler MG, Yavorsky C, Daniel DG. Positive and Negative Syndrome Scale (PANSS) Training: Challenges, Solutions, and Future Directions. Innov Clin Neurosci. 2017;14(11-12):77-81.
Roche E, Creed L, MacMahon D, Brennan D, Clarke M. The Epidemiology and Associated Phenomenology of Formal Thought Disorder: A Systematic Review. Schizophr Bull. 2015;41(4):951-62. doi: https://doi.org/10.1093/schbul/sbu129
Yalincetin B, Bora E, Binbay T, Ulas H, Akdede BB, Alptekin K. Formal thought disorder in schizophrenia and bipolar disorder: A systematic review and meta-analysis. Schizophr Res. 2017;185:2-8. doi: https://doi.org/10.1016/j.schres.2016.12.015
McKenna P, Oh T. Schizophrenic speech. Cambridge: Cambridge University Press; 2005.
Palaniyappan L, Mahmood J, Balain V, Mougin O, Gowland PA, Liddle PF. Structural correlates of formal thought disorder in schizophrenia: An ultra-high field multivariate morphometry study. Schizophr Res. 2015;168(1-2):305-12. doi: https://doi.org/10.1016/j.schres.2015.07.022
Jung S, Lee A, Bang M, Lee SH. Gray matter abnormalities in language processing areas and their associations with verbal ability and positive symptoms in first-episode patients with schizophrenia spectrum psychosis. Neuroimage Clin. 2019;24:102022. doi: https://doi.org/10.1016/j.nicl.2019.102022
Nickl-Jockschat T, Schneider F, Pagel AD, Laird AR, Fox PT, Eickhoff SB. Progressive pathology is functionally linked to the domains of language and emotion: meta-analysis of brain structure changes in schizophrenia patients. Eur Arch Psychiatry Clin Neurosci. 2011;261 Suppl 2(Suppl 2):S166-71. doi: https://doi.org/10.1007/s00406-011-0249-8
Horne CM, Vanes LD, Verneuil T, Mouchlianitis E, Szentgyorgyi T, Averbeck B, et al. Cognitive control network connectivity differentially disrupted in treatment resistant schizophrenia. Neuroimage Clin. 2021;30:102631. doi: https://doi.org/10.1016/j.nicl.2021.102631
Wensing T, Cieslik EC, Müller VI, Hoffstaedter F, Eickhoff SB, Nickl-Jockschat T. Neural correlates of formal thought disorder: An activation likelihood estimation meta-analysis. Hum Brain Mapp. 2017;38(10):4946-65. doi: https://doi.org/10.1002/hbm.23706
Yi HG, Leonard MK, Chang EF. The Encoding of Speech Sounds in the Superior Temporal Gyrus. Neuron. 2019;102(6):1096-110. doi: https://doi.org/10.1016/j.neuron.2019.04.023
Yan T, Zhuang K, He L, Liu C, Zeng R, Qiu J. Left temporal pole contributes to creative thinking via an individual semantic network. Psychophysiology. 2021;58(8):e13841. doi: https://doi.org/10.1111/psyp.13841
Palaniyappan L, Homan P, Alonso-Sanchez MF. Language Network Dysfunction and Formal Thought Disorder in Schizophrenia. Schizophr Bull. 2023;49(2):486-97. doi: https://doi.org/10.1093/schbul/sbac159
Goldberg TE, Aloia MS, Gourovitch ML, Missar D, Pickar D, Weinberger DR. Cognitive substrates of thought disorder, I: the semantic system. Am J Psychiatry. 1998;155(12):1671-6. doi: https://doi.org/10.1176/ajp.155.12.1671
Barrera A, McKenna PJ, Berrios GE. Formal thought disorder in schizophrenia: an executive or a semantic deficit? Psychol Med. 2005;35(1):121-32. doi: https://doi.org/10.1017/s003329170400279x
Stefaniak JD, Alyahya RS, Lambon Ralph MA. Language networks in aphasia and health: A 1000 participant activation likelihood estimation meta-analysis. Neuroimage. 2021;233:117960. doi: https://doi.org/10.1016/j.neuroimage.2021.117960
Bechara A, Tranel D, Damasio H. Characterization of the decision-making deficit of patients with ventromedial prefrontal cortex lesions. Brain. 2000;123 (Pt 11):2189-202. doi: https://doi.org/10.1093/brain/123.11.2189
de la Vega A, Chang LJ, Banich MT, Wager TD, Yarkoni T. Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization. J Neurosci. 2016;36(24):6553-62. doi: https://doi.org/10.1523/JNEUROSCI.4402-15.2016
Bradfield LA, Hart G. Rodent medial and lateral orbitofrontal cortices represent unique components of cognitive maps of task space. Neurosci Biobehav Rev. 2020;108:287-94. doi: https://doi.org/10.1016/j.neubiorev.2019.11.009
Aben B, Buc Calderon C, Van den Bussche E, Verguts T. Cognitive Effort Modulates Connectivity between Dorsal Anterior Cingulate Cortex and Task-Relevant Cortical Areas. J Neurosci. 2020;40(19):3838-48. doi: https://doi.org/10.1523/JNEUROSCI.2948-19.2020
Yee DM, Crawford JL, Lamichhane B, Braver TS. Dorsal Anterior Cingulate Cortex Encodes the Integrated Incentive Motivational Value of Cognitive Task Performance. J Neurosci. 2021;41(16):3707-20. doi: https://doi.org/10.1523/JNEUROSCI.2550-20.2021
Roozendaal B, McEwen BS, Chattarji S. Stress, memory and the amygdala. Nat Rev Neurosci. 2009;10(6):423-33. doi: https://doi.org/10.1038/nrn2651
Murray RJ, Brosch T, Sander D. The functional profile of the human amygdala in affective processing: insights from intracranial recordings. Cortex. 2014;60:10-33. doi: https://doi.org/10.1016/j.cortex.2014.06.010
Ganis G, Thompson WL, Kosslyn SM. Brain areas underlying visual mental imagery and visual perception: an fMRI study. Brain Res Cogn Brain Res. 2004;20(2):226-41. doi: https://doi.org/10.1016/j.cogbrainres.2004.02.012
Onitsuka T, McCarley RW, Kuroki N, Dickey CC, Kubicki M, Demeo SS, et al. Occipital lobe gray matter volume in male patients with chronic schizophrenia: A quantitative MRI study. Schizophr Res. 2007;92(1-3):197-206. doi: https://doi.org/10.1016/j.schres.2007.01.027
Tohid H, Faizan M, Faizan U. Alterations of the occipital lobe in schizophrenia. Neurosciences (Riyadh). 2015;20(3):213-24. doi: https://doi.org/10.17712/nsj.2015.3.20140757
Bergmann J, Genç E, Kohler A, Singer W, Pearson J. Smaller Primary Visual Cortex Is Associated with Stronger, but Less Precise Mental Imagery. Cereb Cortex. 2016;26(9):3838-50. doi: https://doi.org/10.1093/cercor/bhv186
Dijkstra N, Bosch SE, van Gerven MA. Vividness of Visual Imagery Depends on the Neural Overlap with Perception in Visual Areas. J Neurosci. 2017;37(5):1367-73. doi: https://doi.org/10.1523/JNEUROSCI.3022-16.2016
Barry DN, Love BC. A neural network account of memory replay and knowledge consolidation. Cereb Cortex. 2022;33(1):83-95. doi: https://doi.org/10.1093/cercor/bhac054
Shin J, French L, Xu T, Leonard G, Perron M, Pike GB, et al. Cell-Specific Gene-Expression Profiles and Cortical Thickness in the Human Brain. Cereb Cortex. 2018;28(9):3267-77. doi: https://doi.org/10.1093/cercor/bhx197
Hawrylycz MJ, Lein ES, Guillozet-Bongaarts AL, Shen EH, Ng L, Miller JA, et al. An anatomically comprehensive atlas of the adult human brain transcriptome. Nature. 2012;489(7416):391-9. doi: https://doi.org/10.1038/nature11405
Sellgren CM, Gracias J, Watmuff B, Biag JD, Thanos JM, Whittredge PB, et al. Increased synapse elimination by microglia in schizophrenia patient-derived models of synaptic pruning. Nat Neurosci. 2019;22(3):374-85. doi: https://doi.org/10.1038/s41593-018-0334-7
Glausier JR, Lewis DA. Dendritic spine pathology in schizophrenia. Neuroscience. 2013;251:90-107. doi: https://doi.org/10.1016/j.neuroscience.2012.04.044
Moyer CE, Shelton MA, Sweet RA. Dendritic spine alterations in schizophrenia. Neurosci Lett. 2015;601:46-53. doi: https://doi.org/10.1016/j.neulet.2014.11.042
Chung WS, Allen NJ, Eroglu C. Astrocytes Control Synapse Formation, Function, and Elimination. Cold Spring Harb Perspect Biol. 2015;7(9):a020370. doi: https://doi.org/10.1101/cshperspect.a020370
Dietz AG, Goldman SA, Nedergaard M. Glial cells in schizophrenia: a unified hypothesis. Lancet Psychiatry. 2020;7(3):272-81. doi: https://doi.org/10.1016/S2215-0366(19)30302-5
Notter T. Astrocytes in schizophrenia. Brain Neurosci Adv. 2021;5:23982128211009148. doi: https://doi.org/10.1177/23982128211009148
Abi-Saab WM, D'Souza DC, Moghaddam B, Krystal JH. The NMDA antagonist model for schizophrenia: promise and pitfalls. Pharmacopsychiatry. 1998;31 Suppl 2:104-9. doi: https://doi.org/10.1055/s-2007-979354
Kantrowitz JT, Javitt DC. N-methyl-d-aspartate (NMDA) receptor dysfunction or dysregulation: the final common pathway on the road to schizophrenia? Brain Res Bull. 2010;83(3-4):108-21. doi: https://doi.org/10.1016/j.brainresbull.2010.04.006
Wong TY, Radua J, Pomarol-Clotet E, Salvador R, Albajes-Eizagirre A, Solanes A, et al. An overlapping pattern of cerebral cortical thinning is associated with both positive symptoms and aggression in schizophrenia via the ENIGMA consortium. Psychol Med. 202050(12):2034-45. doi: https://doi.org/10.1017/S0033291719002149
