A narrative literature review of white matter microstructure in individuals at clinical high risk for psychosis

Abstract

Schizophrenia is a severe psychiatric disorder characterized by widespread white matter (WM) alterations, manifesting as neurodevelopmental deficits and dysconnectivity abnormalities. Over the past two decades, studies have focused on the clinical high-risk (CHR) stage of psychosis and have yielded fruitful information on WM abnormalities that exist prior to the full onset of psychosis, shedding light on biological mechanisms underlying psychosis development. This review presents a summary of current findings on cross-sectional and longitudinal WM alterations in individuals with CHR and their links to clinical symptoms and neurocognitive dysfunction. Next, we review the utilization of WM characterization in predicting clinical outcomes. Taken together, the literature suggests the clinical significance of WM characteristics and their great potential in predicting the conversion to psychosis, despite some methodological and conceptual challenges that remain to be addressed in future studies. Future CHR research would greatly benefit from utilizing WM to guide pharmacological and non-pharmacological targeted treatments, optimize clinical prediction models, and enable more accurate clinical care.

Keywords

diffusion tensor imaging / white matter microstructure / clinical high risk for psychosis / cross-sectional alteration / longitudinal development / prediction of transition risk

Supplementary data

Supplementary data is available at Psychoradiology online.

Author contributions

Wenjun Su (Conceptualization, Investigation, Visualization, Writing—original draft), Jijun Wang (Supervision, Writing—review & editing), and Yingying Tang (Supervision, Conceptualization, Visualization, Writing—review & editing).

Conflict of interests

There are no conflicts to declare.

Acknowledgements

This work was supported by the National Nature Science Foundation of China (82171497, 82151314). Yingying Tang is funded by the Shanghai Talented Youth Program and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20191836).

References

[1] Alba-Ferrara LM, de Erausquin GA (2013) What does anisotropy measure? Insights from increased and decreased anisotropy in selective fiber tracts in schizophrenia. Front Integr Neurosci. 7: 9. https://doi.org/10.3389/fnint.2013.00009.

[2] Arvindakshan M, Ghate M, Ranjekar PK, et al. (2003) Supplementation with a combination of omega-3 fatty acids and antioxidants (vitamins E and C) improves the outcome of schizophrenia. Schizophr Res. 62: 195-204.

[3] Bakker G, Caan MWA, Schluter RS, et al. (2016) Distinct white-matter aberrations in 22q11.2 deletion syndrome and patients at ultra-high risk for psychosis. Psychol Med. 46: 2299-311.

[4] Beaulieu C (2002) The basis of anisotropic water diffusion in the nervous system—a technical review. NMR Biomed. 15:435-55.

[5] Bernard JA, Orr JM, Mittal VA (2015) Abnormal hippocampal-thalamic white matter tract development and positive symptom course in individuals at ultra-high risk for psychosis. Npj Schizophrenia. 1:15009.

[6] Bernard JA, Orr JM, Mittal VA (2017) Cerebello-thalamo-cortical networks predict positive symptom progression in individuals at ultra-high risk for psychosis. NeuroImage: Clinical. 14:622-8.

[7] Bloemen OJN, De Koning MB, Schmitz N, et al. (2010) White-matter markers for psychosis in a prospective ultra-high-risk cohort. Psychol Med. 40:1297-304.

[8] Caminiti R, Carducci F, Piervincenzi C, et al. (2013) Diameter, length, speed, and conduction delay of callosal axons in macaque monkeys and humans: comparing data from histology and Magnetic resonance imaging diffusion tractography. The Journal of Neuroscience. 33:14501.

[9] Carletti F, Woolley JB, Bhattacharyya S, et al. (2012) Alterations in white matter evident before the onset of psychosis. Schizophr Bull. 38:1170-9.

[10] Carreira Figueiredo I, Borgan F, Pasternak O, et al. (2022) White-matter free-water diffusion MRI in schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology. 47:1413-20.

[11] Catalan A, Salazar De Pablo G, Aymerich C, et al. (2021) Neurocognitive functioning in individuals at clinical high risk for psychosis A systematic review and meta-analysis. Jama Psychiatry. 78:859-67.

[12] Cetin-Karayumak S, Di Biase MA, Chunga N, et al. (2020) White matter abnormalities across the lifespan of schizophrenia: a harmonized multi-site diffusion MRI study. Mol Psychiatry. 25:3208-19.

[13] Chen Z, Bo Q, Zhao L, et al. (2023) White matter microstructural abnormalities in individuals with attenuated positive symptom syndromes. J Psychiatr Res. 163:150-8.

[14] Chew LJ, Fusar-Poli P, Schmitz T (2013) Oligodendroglial alterations and the role of microglia in white matter injury: relevance to schizophrenia. Dev Neurosci. 35:102-29.

[15] Cho KIK, Shenton ME, Kubicki M, et al. (2016) Altered Thalamo-cortical white matter connectivity: probabilistic tractography study in clinical-high risk for psychosis and first-episode psychosis. Schizophr Bull. 42:723-31.

[16] Clemm Von Hohenberg C, Pasternak O, Kubicki M, et al. (2014) White matter microstructure in individuals at clinical high risk of psychosis: a whole-brain diffusion tensor imaging study. Schizophr Bull. 40:895-903.

[17] Cooper S, Alm KH, Olson IR, et al. (2018) White matter alterations in individuals experiencing attenuated positive psychotic symptoms. Early Intervention in Psychiatry. 12:372-9.

[18] Crow TJ, Ball J, Rloom SR, et al. (1989) Schizophrenia as an anomaly of development of cerebral asymmetry—a postmortem study and a proposal concerning the genetic-basis of the disease. Arch Gen Psychiatry. 46:1145-50.

[19] Damme KSF, Schiffman J, Ellman LM, et al. (2021) Sensorimotor and activity psychosis-risk (SMAP-R) scale: an exploration of scale structure with replication and validation. Schizophr Bull. 47:332-43.

[20] Davis KL, Stewart DG, Friedman JI, et al. (2003) White matter changes in schizophrenia—evidence for myelin-related dysfunction. Arch Gen Psychiatry. 60:443-56.

[21] Di Biase MA, Cetin-Karayumak S, Lyall AE, et al. (2021) White matter changes in psychosis risk relate to development and are not impacted by the transition to psychosis. Mol Psychiatry. 26:6833-44.

[22] Ellison-Wright I, Bullmore E (2009) Meta-analysis of diffusion tensor imaging studies in schizophrenia. Schizophr Res. 108:3-10.

[23] Fitzsimmons J, Rosa P, Sydnor VJ, et al. (2020) Cingulum bundle abnormalities and risk for schizophrenia. Schizophr Res. 215:385-91.

[24] Fusar-Poli P, Borgwardt S, Bechdolf A, et al. (2013) The psychosis high-risk State A comprehensive State-of-the-art review. Jama Psychiatry. 70:107-20.

[25] Fusar-Poli P, Salazar De Pablo G, Correll CU, et al. (2020) Prevention of psychosis advances in detection, prognosis, and intervention. Jama Psychiatry. 77:755-65.

[26] Fusar-Poli P (2017) The clinical high-risk State for psychosis (CHR-P), version II. Schizophr Bull. 43:44-7.

[27] Galletly C, Castle D, Dark F, et al. (2016) Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the management of schizophrenia and related disorders. Australian & New Zealand Journal of Psychiatry. 50:410-72.

[28] Giorgio A, Watkins KE, Chadwick M, et al. (2010) Longitudinal changes in grey and white matter during adolescence. Neuroimage. 49:94-103.

[29] González-Reimers E, Martín-González C, Romero-Acevedo L, et al. (2019) Effects of alcohol on the Corpus Callosum. In: Neuroscience of Alcohol. 143-52.

[30] Harvey PD, Strassnig MT, Silberstein J (2019) Prediction of disability in schizophrenia: symptoms, cognition, and self-assessment. Journal of Experimental Psychopathology. 10. https://doi.org/10.1177/2043808719865693.

[31] Hilal S, Liu S, Wong TY, et al. (2021) White matter network damage mediates association between cerebrovascular disease and cognition. Journal of Cerebral Blood Flow & Metabolism. 41:1858-72.

[32] Howes OD, Whitehurst T, Shatalina E, et al. (2021) The clinical significance of duration of untreated psychosis: an umbrella review and random-effects meta-analysis. World Psychiatry. 20:75-95.

[33] Hua JPY, Cummings J, Roach BJ, et al. (2023) Rich-club connectivity and structural connectome organization in youth at clinical high-risk for psychosis and individuals with early illness schizophrenia. Schizophr Res. 255:110-21.

[34] Jiang Y, Duan M, Li X, et al. (2021) Function-structure coupling: white matter functional magnetic resonance imaging hyper-activation associates with structural integrity reductions in schizophrenia. Hum Brain Mapp. 42:4022-34.

[35] Jiang Y, Wang J, Zhou E, et al. (2023) Neuroimaging biomarkers define neurophysiological subtypes with distinct trajectories in schizophrenia. Nature Mental Health. 1:186-99.

[36] Kahn RS, Sommer IE, Murray RM, et al. (2015) Schizophrenia. Nat Rev Dis Primers. 1:15067.

[37] Kane JM, Robinson DG, Schooler NR, et al. (2016) Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early Treatment Program. Am J Psychiatry. 173:362-72.

[38] Karlsgodt KH, Jacobson SC, Seal M, et al. (2012) The relationship of developmental changes in white matter to the onset of psychosis. Curr Pharm Des. 18:422-33.

[39] Karlsgodt KH, Niendam TA, Bearden CE, et al. (2009) White matter integrity and prediction of social and role functioning in subjects at ultra-high risk for psychosis. Biol Psychiatry. 66:562-9.

[40] Karlsgodt KH (2016) Diffusion imaging of white matter In schizophrenia: progress and future directions. Biol Psychiatry Cogn Neurosci Neuroimaging. 1:209-17.

[41] Katagiri N, Pantelis C, Nemoto T, et al. (2015) A longitudinal study investigating sub-threshold symptoms and white matter changes in individuals with an 'at risk mental state’ (ARMS). Schizophr Res. 162:7-13.

[42] Kelly S, Guimond S, Pasternak O, et al. (2021) White matter microstructure across brain-based biotypes for psychosis—findings from the bipolar-schizophrenia network for intermediate phenotypes., Psychiatry Research: Neuroimaging. 308:111234.

[43] Kelly S, Jahanshad N, Zalesky A, et al. (2018) Widespread white matter microstructural differences in schizophrenia across 4322 individuals: results from the ENIGMA Schizophrenia DTI Working Group. Mol Psychiatry. 23:1261-9.

[44] Kobayashi T, Shinnoh N, Kondo A, et al. (1997) Adrenoleukodystrophy protein-deficient mice represent abnormality of very long chain fatty acid metabolism. Biochem Biophys Res Commun. 232:631-6.

[45] Kochunov P, Coyle TR, Rowland LM, et al. (2017) Association of white matter with core cognitive deficits in patients with Schizophrenia. JAMA Psychiatry. 74:958-66.

[46] Kochunov P, Hong LE (2014) Neurodevelopmental and neurodegenerative models of schizophrenia: white matter at the center stage. Schizophr Bull. 40:721-8.

[47] Kochunov P, Williamson DE, Lancaster J, et al. (2012) Fractional anisotropy of water diffusion in cerebral white matter across the lifespan. Neurobiol Aging. 33:9-20.

[48] Konrad A, Winterer G (2008) Disturbed structural connectivity in schizophrenia primary factor in pathology or epiphenomenon?. Schizophr Bull. 34:72-92.

[49] Koutsouleris N, Dwyer DB, Degenhardt F, et al. (2021) Multimodal Machine Learning Workflows for Prediction of Psychosis in Patients With Clinical High-Risk Syndromes and Recent-Onset Depression, JAMA Psychiatry. 78:195-209.

[50] Kraguljac NV, Guerreri M, Strickland MJ, et al. (2023) Neurite orientation Dispersion and density Imaging in psychiatric disorders: a systematic literature review and a technical note. Biological Psychiatry Global Open Science. 3:10-21.

[51] Krakauer K, Ebdrup BH, Glenthøj BY, et al. (2017) Patterns of white matter microstructure in individuals at ultra-high-risk for psychosis: associations to level of functioning and clinical symptoms. Psychol Med. 47:2689-707.

[52] Krakauer K, Nordentoft M, Glenthøj BY, et al. (2018) White matter maturation during 12 months in individuals at ultra-high-risk for psychosis. Acta Psychiatr Scand. 137:65-78.

[53] Kristensen TD, Glenthøj LB, Ambrosen K, et al. (2021a) Global fractional anisotropy predicts transition to psychosis after 12 months in individuals at ultra-high risk for psychosis. Acta Psychiatr Scand. 144:448-63.

[54] Kristensen TD, Glenthøj LB, Raghava JM, et al. (2021b) Changes in negative symptoms are linked to white matter changes in superior longitudinal fasciculus in individuals at ultra-high risk for psychosis. Schizophr Res. 237:192-201.

[55] Kristensen TD, Mandl RCW, Raghava JM, et al. (2019) Widespread higher fractional anisotropy associates to better cognitive functions in individuals at ultra-high risk for psychosis. Hum Brain Mapp. 40:5185-201.

[56] Kubicki M, Lyall AE (2018) Antipsychotics and their impact on cerebral white matter: part of the problem or part of the solution?. Am J Psychiatry. 175:1056-7.

[57] Langhein M, Lyall AE, Steinmann S, et al. (2023) The decoupling of structural and functional connectivity of auditory networks in individuals at clinical high-risk for psychosis. The World Journal of Biological Psychiatry. 24:387-99.

[58] Lebel C, Gee M, Camicioli R, et al. (2012) Diffusion tensor imaging of white matter tract evolution over the lifespan. Neuroimage. 60:340-52.

[59] León-Ortiz P, Reyes-Madrigal F, Kochunov P, et al. (2022) White matter alterations and the conversion to psychosis: a combined diffusion tensor imaging and glutamate (1)H MRS study. Schizophr Res. 249:85-92.

[60] Mittal VA, Dean DJ, Bernard JA, et al. (2014) Neurological soft signs predict abnormal cerebellar-thalamic tract development and negative symptoms in adolescents at high risk for psychosis: a longitudinal perspective. Schizophr Bull. 40:1204-15.

[61] Moola S, Munn Z, Tufanaru C, et al. (2020) Chapter 7:systematic reviews of etiology and risk. In: Aromataris E, Munn Z(eds). JBI Manual for Evidence Synthesis. JBI, Available from https://synthesismanual.jbi.global.

[62] Murray RM, Bhavsar V, Tripoli G, et al. (2017) 30 Years on: how the neurodevelopmental hypothesis of schizophrenia morphed into the developmental risk factor model of psychosis. Schizophr Bull. 43:1190-6.

[63] Nägele FL, Pasternak O, Bitzan LV, et al. (2021) Cellular and extracellular white matter alterations indicate conversion to psychosis among individuals at clinical high-risk for psychosis. The World Journal of Biological Psychiatry. 22:214-27.

[64] Najjar S, Pearlman DM (2015) Neuroinflammation and white matter pathology in schizophrenia: systematic review. Schizophr Res. 161:102-12.

[65] Ning L, Rathi Y, Barbour T, et al. (2022) White matter markers and predictors for subject-specific rTMS response in major depressive disorder. J Affect Disord. 299:207-14.

[66] Pasternak O, Kelly S, Sydnor VJ, et al. (2018) Advances in microstructural diffusion neuroimaging for psychiatric disorders. Neuroimage. 182:259-82.

[67] Pasternak O, Sochen N, Gur Y, et al. (2009) Free water elimination and mapping from diffusion MRI. Magn Reson Med. 62:717-30.

[68] Patel PK, Leathem LD, Currin DL, et al. (2021) Adolescent neurodevelopment and vulnerability to psychosis. Biol Psychiatry. 89:184-93.

[69] Peters BD, Blaas J, de Haan L (2010) Diffusion tensor imaging in the early phase of schizophrenia: what have we learned?. J Psychiatr Res. 44:993-1004.

[70] Peters BD, De Haan L, Dekker N, et al. (2008) White matter fibertracking in first-episode schizophrenia, schizoaffective patients and subjects at ultra-high risk of psychosis. Neuropsychobiology. 58:19-28.

[71] Peters BD, Dingemans PM, Dekker N, et al. (2010) White matter connectivity and psychosis in ultra-high-risk subjects: a diffusion tensor fiber tracking study. Psychiatry Research: Neuroimaging. 181:44-50.

[72] Peters BD, Ikuta T, Derosse P, et al. (2014) Age-related differences in white matter tract microstructure are associated with cognitive performance from childhood to adulthood. Biol Psychiatry. 75:248-56.

[73] Peters BD, Machielsen MWJ, Hoen WP, et al. (2013) Polyunsaturated fatty acid concentration predicts myelin integrity in early-phase psychosis. Schizophr Bull. 39:830-8.

[74] Peters BD, Schmitz N, Dingemans PM, et al. (2009) Preliminary evidence for reduced frontal white matter integrity in subjects at ultra-high-risk for psychosis. Schizophr Res. 111:192-3.

[75] Pukrop R, Schultze-Lutter F, Ruhrmann S, et al. (2006) Neurocognitive functioning in subjects at risk for a first episode of psychosis compared with first- and multiple-episode schizophrenia. J Clin Exp Neuropsychol. 28:1388-407.

[76] Rapoport JL, Giedd JN, Gogtay N (2012) Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry. 17:1228-38.

[77] Rigucci S, Santi G, Corigliano V, et al. (2016) White matter microstructure in ultra-high risk and first episode schizophrenia: a prospective study. Psychiatry Research: Neuroimaging. 247:42-8.

[78] Roalf DR, De La Garza AG, Rosen A, et al. (2020) Alterations in white matter microstructure in individuals at persistent risk for psychosis. Mol Psychiatry. 25:2441-54.

[79] Sagarwala R, Nasrallah HA (2021) The effect of antipsychotic medications on white matter integrity in first-episode drug-naive patients with psychosis: a review of DTI studies. Asian Journal of Psychiatry. 102688, 61.

[80] Saito J, Hori M, Nemoto T, et al. (2017) Longitudinal study examining abnormal white matter integrity using a tract-specific analysis in individuals with a high risk for psychosis. Psychiatry Clin Neurosci. 71:530-41.

[81] Saito J, Nemoto T, Katagiri N, et al. (2020) Can reduced leftward asymmetry of white matter integrity be a marker of transition to psychosis in at-risk mental state?. Asian Journal of Psychiatry. 54:102450.

[82] Salazar De Pablo G, Besana F, Arienti V, et al. (2021) Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis. EClinicalMedicine. 36:100909.

[83] Salazar De Pablo G, Radua J, Pereira J, et al. (2021) Probability of transition to psychosis in individuals at clinical high risk: an updated meta-analysis. JAMA Psychiatry. 78:970-78.

[84] Sato Y, Sakuma A, Ohmuro N, et al. (2021) Relationship between white matter microstructure and hallucination severity in the early stages of psychosis: a diffusion tensor imaging study. Schizophrenia Bulletin Open. 2:1-10.

[85] Schmidt A, Lenz C, Smieskova R, et al. (2015) Brain diffusion changes in emerging psychosis and the impact of State-dependent psychopathology. Neurosignals. 23:71-83.

[86] Seitz-Holland J, Cetin-Karayumak S, Wojcik JD, et al. (2021) Elucidating the relationship between white matter structure, demographic, and clinical variables in schizophrenia-a multicenter harmonized diffusion tensor imaging study. Mol Psychiatry. 26:5357-70.

[87] Smigielski L, Stämpfli P, Wotruba D, et al. (2022) White matter microstructure and the clinical risk for psychosis: a diffusion tensor imaging study of individuals with basic symptoms and at ultra-high risk. NeuroImage: Clinical. 35:103067.

[88] Smith SM, Jenkinson M, Johansen-Berg H, et al. (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage. 31:1487-505.

[89] Solowij N, Zalesky A, Lorenzetti V, et al. (2017) Chronic cannabis use and axonal Fiber connectivity. Handbook of Cannabis and Related Pathologies. 391-400.

[90] Song S-K, Sun S-W, Ramsbottom MJ, et al. (2002) Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage. 17:1429-36.

[91] Steinmann S, Lyall AE, Langhein M, et al. (2021) Sex-related differences in white matter asymmetry and its implications for verbal working memory in psychosis high-risk State. Frontiers in Psychiatry. 12:686967. https://doi.org/10.3389/fpsyt.2021.686967.

[92] Straub KT, Hua JPY, Karcher NR, et al. (2020) Psychosis risk is associated with decreased white matter integrity in limbic network corticostriatal tracts. Psychiatry Research: Neuroimaging. 301:111089.

[93] Su W, Li Z, Xu L, et al. (2022) Different patterns of association between white matter microstructure and plasma unsaturated fatty acids in those with high risk for psychosis and healthy participants. General Psychiatry. 35:e100703.

[94] Szeszko PR, Robinson DG, Ikuta T, et al. (2014) White matter changes associated with antipsychotic treatment in first-episode psychosis. Neuropsychopharmacology. 39:1324-31.

[95] Tandon R, Keshavan MS, Nasrallah HA (2008) Schizophrenia, “just the facts” what we know in 2008. 2. Epidemiology and etiology. Schizophr Res. 102:1-18.

[96] Tang Y, Pasternak O, Kubicki M, et al. (2019) Altered cellular white matter but not extracellular free water on diffusion MRI in individuals at clinical high risk for psychosis. Am J Psychiatry. 176:820-8.

[97] Tang Y, Xu L, Zhu T, et al. (2023) Visuospatial learning selectively enhanced by personalized transcranial Magnetic stimulation over Parieto-hippocampal network among patients at clinical high-risk for psychosis. Schizophr Bull. 49:923-32.

[98] Taylor M, Perera U (2015) NICE CG178 Psychosis and Schizophrenia in adults: treatment and management—an evidence-based guideline?. Br J Psychiatry. 206:357-9.

[99] Tkachev D, Mimmack ML, Ryan MM, et al. (2003) Oligodendrocyte dysfunction in schizophrenia and bipolar disorder. The Lancet. 362:798-805.

[100] Tomyshev AS, Lebedeva IS, Akhadov TA, et al. (2017) MRI study for the features of brain conduction pathways in patients with an ultra-high risk of endogenous psychoses. Bull Exp Biol Med. 162:425-9.

[101] Tomyshev AS, Lebedeva IS, Akhadov TA, et al. (2019) Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: a multimodal tractography and surface-based morphometry study. Psychiatry Research: Neuroimaging. 289:26-36.

[102] Van Erp TGM, Walton E, Hibar DP, et al. (2018) 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. 84:644-54.

[103] Vargas T, Damme KSF, Mittal VA (2019) Bullying victimization in typically developing and clinical high risk (CHR) adolescents: a multimodal imaging study. Schizophr Res. 213:40-7.

[104] Voineskos AN, Jacobs GR, Ameis SH (2020) Neuroimaging heterogeneity in psychosis: neurobiological underpinnings and opportunities for prognostic and therapeutic innovation. Biol Psychiatry. 88:95-102.

[105] Wang B, Guo M, Pan T, et al. (2023) Altered higher-order coupling between brain structure and function with embedded vector representations of connectomes in schizophrenia. Cereb Cortex. 33:5447-56.

[106] Wang C, Ji F, Hong Z, et al. (2016) Disrupted salience network functional connectivity and white-matter microstructure in persons at risk for psychosis: findings from the LYRIKS study. Psychol Med. 46:2771-83.

[107] Waszczuk K, Tyburski E, Rek-Owodziń K, et al. (2022) Relationship between white matter alterations and pathophysiological symptoms in patients with ultra-high risk of psychosis, first-episode, and chronic schizophrenia. Brain Sciences. 12:354.

[108] Whitford TJ, Kubicki M, Schneiderman JS, et al. (2010) Corpus callosum abnormalities and their association with psychotic symptoms in patients with schizophrenia. Biol Psychiatry. 68:70-7.

[109] Whitford TJ, Oestreich LKL, Ford JM, et al. (2018) Deficits in cortical suppression during vocalization are associated with structural abnormalities in the arcuate fasciculus in early illness schizophrenia and clinical high risk for psychosis. Schizophr Bull. 44:1312-22.

[110] Worthington MA, Cannon TD (2021) Prediction and prevention in the clinical high-risk for psychosis paradigm: a review of the current status and recommendations for future directions of inquiry. Frontiers in Psychiatry. 12:770774.

[111] Xu H, Zhou Y, Wang J, et al. (2023) Effect of HD-tDCS on white matter integrity and associated cognitive function in chronic schizophrenia: a double-blind, sham-controlled randomized trial. Psychiatry Res. 324:115183.

[112] Zeng B, Ardekani BA, Tang Y, et al. (2016) Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment. Schizophr Res. 172:1-8.

[113] Zeng JH, Raballo A, Gan R, et al. (2022) Antipsychotic exposure in clinical high risk of psychosis: empirical insights from a large cohort study. J Clin Psychiatry. 83:21m14092.

[114] Zhang F, Cho KIK, Tang Y, et al. (2021) MK-curve improves sensitivity to identify white matter alterations in clinical high risk for psychosis. Neuroimage. 226:117564.

[115] Zhang H, Schneider T, Wheeler-Kingshott CA, et al. (2012) NODDI: practical in vivo neurite orientation dispersion and density imaging of the human brain. Neuroimage. 61:1000-16.

[116] Zhang H, Wang Y, Hu Y, et al. (2019) Meta-analysis of cognitive function in Chinese first-episode schizophrenia: MATRICS consensus cognitive battery (MCCB) profile of impairment. General Psychiatry. 32:e100043.

[117] Zhang T, Xu L, Tang X, et al. (2020) Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis). Australian & New Zealand Journal of Psychiatry. 54:696-706.

[118] Zhang T, Xu L, Tang Y, et al. (2018) Duration of untreated prodromal symptoms in a Chinese sample at a high risk for psychosis: demographic, clinical, and outcome. Psychol Med. 48:1274-81.

[119] Zhang TH, Li HJ, Woodberry KA, et al. (2017) Two-year follow-up of a Chinese sample at clinical high risk for psychosis: timeline of symptoms, help-seeking and conversion. Epidemiology and Psychiatric Sciences. 26:287-98.

[120] Zhao J, Huang C-C, Zhang Y, et al. (2023) Structure-function coupling in white matter uncovers the abnormal brain connectivity in Schizophrenia. Translational Psychiatry. 13:214. https://doi.org/10.1038/s41398-023-02520-4.