Salud Mental

Prodromes and biological markers in schizophrenia: Importance for the dopamine, glutamate, and neurodevelopmental hypothesis

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Juan Pablo Díaz-Sánchez
Héctor Solís-Chagoyán
Gloria A. Benítez-King

Abstract

Background. Since schizophrenia is a multifactorial mental illness, a basic understanding of its etiological components improves its understanding, diagnosis, and the selection of therapeutic targets.

Objective. To identify the prodromes and biological markers in schizophrenic or ultra-high risk (UHR) patients and elucidate their specificity.

Method. Narrative review of relevant sources in English and Spanish in the Medline-PubMed database on minor physical abnormalities, cognitive abnormalities, neuroanatomical, and synaptic and cell changes present in schizophrenic patients and/or subjects with a high risk of developing schizophrenia

Results. Patients with SZ and, to a lesser extent, UHR subjects present phenotypic and behavioral manifestations that correlate with underlying cell processes. The study of the latter makes it possible to characterize diagnostic biomarkers. At present, its clinical application is limited by factors such as poorly understood pathophysiology, lack of study models, homology with other psychiatric disorders, and the dearth of clinical trials conducted.

Discussion and conclusion. Schizophrenia is the final manifestation of damage to prenatal and post-natal neurodevelopment and is reflected during the prodromal stage in early biological markers with clinical relevance. It is necessary to establish new study models that will increase knowledge to offer specific biomarkers for use in early clinical diagnosis.
Keywords:
Schizophrenia, etiology, risk factors, biomarkers, synapsis, dopamine, NMDAR

References

Ambrosio-Gallardo, F., Cruz-Fuentes, C., Heinze-Martin, G., Caraveo-Anduaga, J., & Cortés-Sotres, J. (2015). Study of minor physical abnormalities in complete nuclear Mexican families. Evidence of neurodevelopmental problems in schizophrenia. PloS One, 10(1), e0117080. doi: 10.1371/journal.pone.0117080

Artigue, J., & Tizón, J. L. (2014). Una revisión sobre los factores de riesgo en la infancia para la esquizofrenia y los trastornos mentales graves del adulto [Review of risks factors in childhood for schizophrenia and severe mental disorders in adulthood]. Atencion Primaria, 46(7), 336-356. doi: 10.1016/j.aprim.2013.11.002

Barch, D. M. (2009). Neuropsychological abnormalities in schizophrenia and major mood disorders: similarities and differences. Current Psychiatry Reports, 11(4), 313-319. doi: 10.1007/s11920-009-0045-6

Barrón, H., Hafizi, S., Andreazza, A. C., & Mizrahi, R. (2017). Neuroinflammation and Oxidative Stress in Psychosis and Psychosis Risk. International Journal of Molecular Sciences, 18(3), 651. doi: 10.3390/ijms18030651

Bast, T., Pezze, M., & McGarrity, S. (2017). Cognitive deficits caused by prefrontal cortical and hippocampal neural disinhibition. British Journal of Pharmacology, 174(19), 3211-3225. doi: 10.1111/bph.13850

Benítez-King, G. (2006). Melatonin as a cytoskeletal modulator: implications for cell physiology and disease. Journal of Pineal Research, 40(1), 1-9. doi: 10.1111/j.1600-079X.2005.00282.x

Benítez-King, G., Ramírez-Rodríguez, G., Ortíz, L., & Meza, I. (2004). The neuronal cytoskeleton as a potential therapeutical target in neurodegenerative diseases and schizophrenia. Current Drug Targets. CNS and Neurological Disorders, 3(6), 515-533. doi: 10.2174/1568007043336761

Bitanihirwe, B. K., & Woo, T. U. (2014). Perineuronal nets and schizophrenia: the importance of neuronal coatings. Neuroscience and Biobehavioral Reviews, 45, 85-99. doi: 10.1016/j.neubiorev.2014.03.018

Brent, B. K., Thermenos, H. W., Keshavan, M. S., & Seidman, L. J. (2013). Gray matter alterations in schizophrenia high-risk youth and early-onset schizophrenia: a review of structural MRI findings. Child and Adolescent Psychiatric Clinics of North America, 22(4), 689-714. doi: 10.1016/j.chc.2013.06.003

Cardozo, P. L., de Lima, I. B. Q., Maciel, E. M. A., Silva, N. C., Dobransky, T., & Ribeiro, F. M. (2019). Synaptic Elimination in Neurological Disorders. Current Neuropharmacology, 17(11), 1071-1095. doi: 10.2174/1570159X17666190603170511

Carmeli, C., Knyazeva, M. G., Cuénod, M., & Do, K. Q. (2012). Glutathione precursor N-acetyl-cysteine modulates EEG synchronization in schizophrenia patients: a double-blind, randomized, placebo-controlled trial. PloS One, 7(2), e29341. doi: 10.1371/journal.pone.0029341

Chan, R. C. K., Di, X., McAlonan, G. M., & Gong, Q. Y. (2011). Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophrenia Bulletin, 37(1), 177-188. doi: 10.1093/schbul/sbp073

Charlson, F. J., Ferrari, A. J., Santomauro, D. F., Diminic, S., Stockings, E., Scott, J. G., … Whiteford, H. A. (2018). Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016. Schizophrenia Bulletin, 44(6), 1195-1203. doi: 10.1093/schbul/sby058

Chong, H. Y., Teoh, S. L., Wu, D. B. C., Kotirum, S., Chiou, C. F., & Chaiyakunapruk, N. (2016). Global economic burden of schizophrenia: a systematic review. Neuropsychiatric Disease and Treatment, 12, 357-373. doi: 10.2147/NDT.S96649

Compton, M. T., & Walker, E. F. (2009). Physical manifestations of neurodevelopmental disruption: are minor physical abnormalities part of the syndrome of schizophrenia?. Schizophrenia Bulletin, 35(2), 425-436. doi: 10.1093/schbul/sbn151

Coyle, J. T., Basu, A., Benneyworth, M., Balu, D., & Konopaske, G. (2012). Glutamatergic synaptic dysregulation in schizophrenia: therapeutic implications. Handbook of Experimental Pharmacology, (213), 267-295. doi: 10.1007/978-3-642-25758-2_10

Dahoun, T., Trossbach, S. V., Brandon, N. J., Korth, C., & Howes, O. D. (2017). The impact of Disrupted-in-Schizophrenia 1 (DISC1) on the dopaminergic system: a systematic review. Translational Psychiatry, 7(1), e1015. doi: 10.1038/tp.2016.282

Do, K. Q., Cuenod, M., & Hensch, T. K. (2015). Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia. Schizophrenia Bulletin, 41(4), 835-846. doi: 10.1093/schbul/sbv065

Dondé, C., D’Amato, T., & Rey, R. (2018). Dermatoglyphics patterns abnormalities as putative markers of psychometric-risk for schizophrenia. Psychiatria Danubina, 30(1), 109-111.

Donegan, J. J., & Lodge, D. J. (2017). Cell-based therapies for the treatment of schizophrenia. Brain Research, 1655, 262-269. doi: 10.1016/j.brainres.2016.08.010

Drevets, W. C., Price, J. L., & Furey, M. L. (2008). Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression. Brain Structure & Function, 213(1-2), 93-118. doi: 10.1007/s00429-008-0189-x

Driver, D. I., Gogtay, N., & Rapoport, J. L. (2013). Childhood onset schizophrenia and early onset schizophrenia spectrum disorders. Child and Adolescent Psychiatric Clinics of North America, 22(4), 539-555. doi: 10.1016/j.chc.2013.04.001

Egbujo, C. N., Sinclair, D., & Hahn, C. G. (2016). Dysregulations of Synaptic Vesicle Trafficking in Schizophrenia. Current Psychiatry Reports, 18(8), 77. doi: 10.1007/s11920-016-0710-5

Filice, F., Janickova, L., Henzi, T., Bilella, A., & Schwaller, B. (2020). The Parvalbumin Hypothesis of Autism Spectrum Disorder. Frontiers in Cellular Neuroscience, 14, 577525. doi: 10.3389/fncel.2020.577525

Forni, P. E., & Wray, S. (2012). Neural crest and olfactory system: new prospective. Molecular Neurobiology, 46(2), 349-360. doi: 10.1007/s12035-012-8286-5

Fornito, A., Yücel, M., Dean, B., Wood, S. J., & Pantelis, C. (2009). Anatomical abnormalities of the anterior cingulate cortex in schizophrenia: bridging the gap between neuroimaging and neuropathology. Schizophrenia Bulletin, 35(5), 973-993. doi: 10.1093/schbul/sbn025

Franco, J. G., Valero, J., & Labad, A. (2010). Minor physical abnormalities and schizophrenia: literature review. Actas Españolas de Psiquiatria, 38(6), 365-371. Retrieved from: https://www.academia.edu/2642902/Minor_physical_anomalies_and_schizophrenia_literature_review

Fu, C. H. Y., & Costafreda, S. G. (2013). Neuroimaging-based biomarkers in psychiatry: clinical opportunities of a paradigm shift. Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie, 58(9), 499-508. doi: 10.1177/070674371305800904

Fujiwara, H., Yassin, W., & Murai, T. (2015). Neuroimaging studies of social cognition in schizophrenia. Psychiatry and Clinical Neurosciences, 69(5), 259-267. doi: 10.1111/pcn.12258

Gao, X., Zhang, W., Yao, L., Xiao, Y., Liu, L., Liu, J., … Lui, S. (2018). Association between structural and functional brain alterations in drug-free patients with schizophrenia: a multimodal meta-analysis. Journal of Psychiatry & Neuroscience: JPN, 43(2), 131-142. doi: 10.1503/jpn.160219

Godsil, B. P., Kiss, J. P., Spedding, M., & Jay, T. M. (2013). The hippocampal-prefrontal pathway: the weak link in psychiatric disorders? European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 23(10), 1165-1181. doi: 10.1016/j.euroneuro.2012.10.018

Golembo-Smith, S., Walder, D. J., Daly, M. P., Mittal, V. A., Kline, E., Reeves, G., & Schiffman, J. (2012). The presentation of dermatoglyphic abnormalities in schizophrenia: a meta-analytic review. Schizophrenia Research, 142(1-3), 1-11. doi: 10.1016/j.schres.2012.10.002

Gonzalez-Burgos, G., & Lewis, D. A. (2008). GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophrenia Bulletin, 34(5), 944-961. doi: 10.1093/schbul/sbn070

Gonzalez-Burgos, G., & Lewis, D. A. (2012). NMDA receptor hypofunction, parvalbumin-positive neurons, and cortical gamma oscillations in schizophrenia. Schizophrenia Bulletin, 38(5), 950-957. doi: 10.1093/schbul/sbs010

Grace, A. A. (2016). Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression. Nature Reviews. Neuroscience, 17(8), 524-532. doi: 10.1038/nrn.2016.57

Grace, A. A. (2017). Dopamine System Dysregulation and the Pathophysiology of Schizophrenia: Insights from the Methylazoxymethanol Acetate Model. Biological Psychiatry, 81(1), 5-8. doi: 10.1016/j.biopsych.2015.11.007

Granger, B. (1996). Synaptogénèse et élagage synaptique: rôle dans le déclenchement des schizophrénies [Synaptogenesis and synaptic pruning: role in triggering schizophrenia]. Presse Medicale (Paris, France: 1983), 25(33), 1595-1598.

Guilarte, T. R., Opler, M., & Pletnikov, M. (2012). Is lead exposure in early life an environmental risk factor for Schizophrenia? Neurobiological connections and testable hypotheses. Neurotoxicology, 33(3), 560-574. doi: 10.1016/j.neuro.2011.11.008

Hardingham, G. E., & Do, K. Q. (2016). Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis. Nature Reviews. Neuroscience, 17(2), 125-134. doi: 10.1038/nrn.2015.19

Hasam-Henderson, L. A., Gotti, G. C., Mishto, M., Klisch, C., Gerevich, Z., Geiger, J. R. P., & Kovács, R. (2018). NMDA-receptor inhibition and oxidative stress during hippocampal maturation differentially alter parvalbumin expression and gamma-band activity. Scientific Reports, 8(1), 9545. doi: 10.1038/s41598-018-27830-2

Haukvik, U. K., Hartberg, C. B., & Agartz, I. (2013). Schizophrenia--what does structural MRI show? Tidsskrift for den Norske Laegeforening: Tidsskrift for Praktisk Medicin, ny Raekke, 133(8), 850-853. doi: 10.4045/tidsskr.12.1084

Hennessy, R. J., McLearie, S., Kinsella, A., & Waddington, J. L. (2005). Facial surface analysis by 3D laser scanning and geometric morphometrics in relation to sexual dimorphism in cerebral--craniofacial morphogenesis and cognitive function. Journal of Anatomy, 207(3), 283-295. doi: 10.1111/j.1469-7580.2005.00444

Hodgins, S., & Klein, S. (2017). New Clinically Relevant Findings about Violence by People with Schizophrenia. Canadian journal of psychiatry. Revue Canadienne de Psychiatrie, 62(2), 86-93. doi: 10.1177/0706743716648300

Howes, O. D., & Murray, R. M. (2014). Schizophrenia: an integrated sociodevelopmental-cognitive model. Lancet (London, England), 383(9929), 1677-1687. doi: 10.1016/S0140-6736(13)62036-X

Howes, O. D., McCutcheon, R., Owen, M. J., & Murray, R. M. (2017). The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biological Psychiatry, 81(1), 9-20. doi: 10.1016/j.biopsych.2016.07.014

Institute for Health Metrics and Evaluation, Human Development Network, The World Bank. (2013). The Global Burden of Disease: Generating Evidence, Guiding Policy – Latin America and Caribbean Regional Edition. Seattle, WA: IHME.

Jackowski, A. P., Araújo Filho, G. M., Almeida, A. G., Araújo, C. M., Reis, M., Nery, F., … Lacerda, A. L. T. (2012). The involvement of the orbitofrontal cortex in psychiatric disorders: an update of neuroimaging findings. Revista Brasileira de Psiquiatria (Sao Paulo, Brazil: 1999), 34(2), 207-212. doi: 10.1590/s1516-44462012000200014

Jarcho, J. M., Mayer, E. A., Jiang, Z. K., Feier, N. A., & London, E. D. (2012). Pain, affective symptoms, and cognitive deficits in patients with cerebral dopamine dysfunction. Pain, 153(4), 744-754. doi: 10.1016/j.pain.2012.01.002

Jiang, Z., Cowell, R. M., & Nakazawa, K. (2013). Convergence of genetic and environmental factors on parvalbumin-positive interneurons in schizophrenia. Frontiers in Behavioral Neuroscience, 7, 116. doi: 10.3389/fnbeh.2013.00116

Keshavan, M., Lizano, P., & Prasad, K. (2020). The synaptic pruning hypothesis of schizophrenia: promises and challenges. World Psychiatry: Official Journal of the World Psychiatric Association (WPA), 19(1), 110-111. doi: 10.1002/wps.20725

Kim, S. G., Song, J. Y., Joo, E. J., Jeong, S. H., Kim, S. H., Lee, K. Y., … Roh, M. S. (2011). No association of functional polymorphisms in methlylenetetrahydrofolate reductase and the risk and minor physical abnormalities of schizophrenia in Korean population. Journal of Korean Medical Science, 26(10), 1356-1363. doi: 10.3346/jkms.2011.26.10.1356

King, S., Laplante, D., & Joober, R. (2005). Understanding putative risk factors for schizophrenia: retrospective and prospective studies. Journal of Psychiatry & Neuroscience: JPN, 30(5), 342-348.

Kuswanto, C. N., Teh, I., Lee, T. S., & Sim, K. (2012). Diffusion tensor imaging findings of white matter changes in first episode schizophrenia: a systematic review. Clinical Psychopharmacology and Neuroscience: The Official Scientific Journal of the Korean College of Neuropsychopharmacology, 10(1), 13-24. doi: 10.9758/cpn.2012.10.1.13

Lakhan, S. E., Caro, M., & Hadzimichalis, N. (2013). NMDA Receptor Activity in Neuropsychiatric Disorders. Frontiers in Psychiatry, 4, 52. doi: 10.3389/fpsyt.2013.00052

Laurens, K. R., & Cullen, A. E. (2016). Toward earlier identification and preventative intervention in schizophrenia: evidence from the London Child Health and Development Study. Social Psychiatry and Psychiatric Epidemiology, 51(4), 475-491. doi: 10.1007/s00127-015-1151-x

Laurens, K. R., Luo, L., Matheson, S. L., Carr, V. J., Raudino, A., Harris, F., & Green, M. J. (2015). Common or distinct pathways to psychosis? A systematic review of evidence from prospective studies for developmental risk factors and antecedents of the schizophrenia spectrum disorders and affective psychoses. BMC Psychiatry, 15, 205. doi: 10.1186/s12888-015-0562-2

Lesh, T. A., Niendam, T. A., Minzenberg, M. J., & Carter, C. S. (2011). Cognitive control deficits in schizophrenia: mechanisms and meaning. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 36(1), 316-338. doi: 10.1038/npp.2010.156

Levine, S. Z., & Rabinowitz, J. (2010). Trajectories and antecedents of treatment response over time in early-episode psychosis. Schizophrenia Bulletin, 36(3), 624-632. doi: 10.1093/schbul/sbn120

Lieberman, J. A., Girgis, R. R., Brucato, G., Moore, H., Provenzano, F., Kegeles, L., … Small, S. A. (2018). Hippocampal dysfunction in the pathophysiology of schizophrenia: a selective review and hypothesis for early detection and intervention. Molecular Psychiatry, 23(8), 1764-1772. doi: 10.1038/mp.2017.249

Lim, D. A., & Alvarez-Buylla, A. (2016). The Adult Ventricular-Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis. Cold Spring Harbor Perspectives in Biology, 8(5), a018820. doi: 10.1101/cshperspect.a018820

Liu, C. H., Keshavan, M., Tronick, E., & Seidman, L. (2015). Perinatal Risks and Childhood Premorbid Indicators of Later Psychosis: Next Steps for Early Psychosocial Interventions. Schizophrenia Bulletin, 41(4), 801-816. doi: 10.1093/schbul/sbv047

Lobato, M. I., Belmonte-de-Abreu, P., Knijnik, D., Teruchkin, B., Ghisolfi, E., & Henriques, A. (2001). Neurodevelopmental risk factors in schizophrenia. Brazilian Journal of Medical and Biological Research, 34(2), 155-163. doi: 10.1590/s0100-879x2001000200002

Marchisella, F., Coffey, E. T., & Hollos, P. (2016). Microtubule and microtubule associated protein abnormalities in psychiatric disease. Cytoskeleton (Hoboken, N.J.), 73(10), 596-611. doi: 10.1002/cm.21300

McGrath, J. J., Féron, F. P., Burne, T. H., Mackay-Sim, A., & Eyles, D. W. (2003). The neurodevelopmental hypothesis of schizophrenia: a review of recent developments. Annals of Medicine, 35(2), 86-93. doi: 10.1080/07853890310010005

Miguel-Hidalgo, J. J. (2013). Brain structural and functional changes in adolescents with psychiatric disorders. International Journal of Adolescent Medicine and Health, 25(3), 245-256. doi: 10.1515/ijamh-2013-0058

Miyoshi, K., Honda, A., Baba, K., Taniguchi, M., Oono, K., Fujita, T., … Tohyama, M. (2003). Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth. Molecular Psychiatry, 8(7), 685-694. doi: 10.1038/sj.mp.4001352

Modinos, G., Costafreda, S. G., van Tol, M. J., McGuire, P. K., Aleman, A., & Allen, P. (2013). Neuroanatomy of auditory verbal hallucinations in schizophrenia: a quantitative meta-analysis of voxel-based morphometry studies. Cortex: a Journal Devoted to the Study of the Nervous System and Behavior, 49(4), 1046-1055. doi: 10.1016/j.cortex.2012.01.009

Moustafa, A. A., Hewedi, D. H., Eissa, A. M., Frydecka, D., & Misiak, B. (2014). Homocysteine levels in schizophrenia and affective disorders-focus on cognition. Frontiers in Behavioral Neuroscience, 8, 343. doi: 10.3389/fnbeh.2014.00343

Mubarik, A., & Tohid, H. (2016). Frontal lobe alterations in schizophrenia: a review. Trends in Psychiatry and Psychotherapy, 38(4), 198-206. doi: 10.1590/2237-6089-2015-0088

Murray, R. M., Bhavsar, V., Tripoli, G., & Howes, O. (2017). 30 Years on: How the Neurodevelopmental Hypothesis of Schizophrenia Morphed into the Developmental Risk Factor Model of Psychosis. Schizophrenia Bulletin, 43(6), 1190-1196. doi: 10.1093/schbul/sbx121

Nakahara, S., Matsumoto, M., & van Erp, T. G. M. (2018). Hippocampal subregion abnormalities in schizophrenia: A systematic review of structural and physiological imaging studies. Neuropsychopharmacology Reports, 38(4), 156-166. doi: 10.1002/npr2.12031

Nakazawa, K., & Sapkota, K. (2020). The origin of NMDA receptor hypofunction in schizophrenia. Pharmacology & therapeutics, 205, 107426. doi: 10.1016/j.pharmthera.2019.107426

Nakazawa, K., Zsiros, V., Jiang, Z., Nakao, K., Kolata, S., Zhang, S., & Belforte, J. E. (2012). GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology, 62(3), 1574-1583. doi: 10.1016/j.neuropharm.2011.01.022

Nickl-Jockschat, T., Schneider, F., Pagel, A. D., Laird, A. R., Fox, P. T., & Eickhoff, S. B. (2011). Progressive pathology is functionally linked to the domains of language and emotion: meta-analysis of brain structure changes in schizophrenia patients. European Archives of Psychiatry and Clinical Neuroscience, 2(Suppl 2), S166-S171. doi: 10.1007/s00406-011-0249-8

Ordóñez, A. E., Luscher, Z. I., & Gogtay, N. (2016). Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings. Schizophrenia Research, 173(3), 124-131. doi: 10.1016/j.schres.2015.03.003

Owen, M. J., Sawa, A., & Mortensen, P. B. (2016). Schizophrenia. Lancet (London, England), 388(10039), 86-97. doi: 10.1016/S0140-6736(15)01121-6

Parellada, M., Gomez-Vallejo, S., Burdeus, M., & Arango, C. (2017). Developmental Differences Between Schizophrenia and Bipolar Disorder. Schizophrenia Bulletin, 43(6), 1176-1189. doi: 10.1093/schbul/sbx126

Rapoport, J. L., & Gogtay, N. (2011). Childhood onset schizophrenia: support for a progressive neurodevelopmental disorder. International Journal of Developmental Neuroscience: the Official Journal of the International Society for Developmental Neuroscience, 29(3), 251-258. doi: 10.1016/j.ijdevneu.2010.10.003

Rapp, C., Bugra, H., Riecher-Rössler, A., Tamagni, C., & Borgwardt, S. (2012). Effects of cannabis use on human brain structure in psychosis: a systematic review combining in vivo structural neuroimaging and postmortem studies. Current Pharmaceutical Design, 18(32), 5070-5080. doi: 10.2174/138161212802884861

Renard, J., Rushlow, W. J., & Laviolette, S. R. (2018). Effects of Adolescent THC Exposure on the Prefrontal GABAergic System: Implications for Schizophrenia-Related Psychopathology. Frontiers in Psychiatry, 9, 281. doi: 10.3389/fpsyt.2018.00281

Ribolsi, M., Daskalakis, Z. J., Siracusano, A., & Koch, G. (2014). Abnormal asymmetry of brain connectivity in schizophrenia. Frontiers in Human Neuroscience, 8, 1010. doi: 10.3389/fnhum.2014.01010

Rubio, M. D., Drummond, J. B., & Meador-Woodruff, J. H. (2012). Glutamate receptor abnormalities in schizophrenia: implications for innovative treatments. Biomolecules & Therapeutics, 20(1), 1-18. doi: 10.4062/biomolther.2012.20.1.001

Sheffield, J. M., & Barch, D. M. (2016). Cognition and resting-state functional connectivity in schizophrenia. Neuroscience and Biobehavioral Reviews, 61, 108-120. doi: 10.1016/j.neubiorev.2015.12.007

Smucny, J., Wylie, K. P., & Tregellas, J. R. (2014). Functional magnetic resonance imaging of intrinsic brain networks for translational drug discovery. Trends in Pharmacological Sciences, 35(8), 397-403. doi: 10.1016/j.tips.2014.05.001

Steullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O’Donnell, P., Cuenod, M., & Do, K. Q. (2016). Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? Schizophrenia Research, 176(1), 41-51. doi: 10.1016/j.schres.2014.06.021

Tenyi, T. (2011). Neurodevelopment and schizophrenia: data on minor physical abnormalities and structural brain imaging. Neuropsychopharmacologia Hungarica: A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology, 13(4), 229-232.

Toga, A. W., Thompson, P. M., & Sowell, E. R. (2006). Mapping brain maturation. Trends in Neurosciences, 29(3), 148-159. doi: 10.1016/j.tins.2006.01.007

Turetsky, B., Hahn, C. G., Borgmann-Winter, K., & Moberg, P. J. (2009). Scents and nonsense: olfactory dysfunction in schizophrenia. Schizophrenia Bulletin, 35(6), 1117-1131. doi: 10.1093/schbul/sbp111

van Erp, T., Walton, E., Hibar, D. P., Schmaal, L., Jiang, W., Glahn, D. C., … Turner, J. A. (2018). Cortical Brain Abnormalities in 4474 Individuals with Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium. Biological Psychiatry, 84(9), 644-654. doi: 10.1016/j.biopsych.2018.04.023

Vijayakumar, N., Bartholomeusz, C., Whitford, T., Hermens, D. F., Nelson, B., Rice, S., … Amminger, G. P. (2016). White matter integrity in individuals at ultra-high risk for psychosis: a systematic review and discussion of the role of polyunsaturated fatty acids. BMC Psychiatry, 16(1), 287. doi: 10.1186/s12888-016-0932-4

Waddington, J. L., Katina, S., O’Tuathaigh, C., & Bowman, A. W. (2017). Translational Genetic Modelling of 3D Craniofacial Dysmorphology: Elaborating the Facial Phenotype of Neurodevelopmental Disorders Through the “Prism” of Schizophrenia. Current Behavioral Neuroscience Reports, 4(4), 322-330. doi: 10.1007/s40473-017-0136-3

Walton, E., Hibar, D. P., van Erp, T., Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., … Ehrlich, S. (2018). Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium. Psychological Medicine, 48(1), 82-94. doi: 10.1017/S0033291717001283

Wang, X., Pinto-Duarte, A., Sejnowski, T. J., & Behrens, M. M. (2013). How Nox2-containing NADPH oxidase affects cortical circuits in the NMDA receptor antagonist model of schizophrenia. Antioxidants & Redox Signaling, 18(12), 1444-1462. doi: 10.1089/ars.2012.4907

Weinberg, S. M., Jenkins, E. A., Marazita, M. L., & Maher, B. S. (2007). Minor physical anomalies in schizophrenia: a meta-analysis. Schizophrenia Research, 89(1-3), 72-85. doi: 10.1016/j.schres.2006.09.002

Wheeler, A. L., & Voineskos, A. N. (2014). A review of structural neuroimaging in schizophrenia: from connectivity to connectomics. Frontiers in Human Neuroscience, 8, 653. doi: 10.3389/fnhum.2014.00653

White, R. S., & Siegel, S. J. (2016). Cellular and circuit models of increased resting-state network gamma activity in schizophrenia. Neuroscience, 321, 66-76. doi: 10.1016/j.neuroscience.2015.11.011

Wise, T., Radua, J., Via, E., Cardoner, N., Abe, O., Adams, T. M., … Arnone, D. (2017). Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Molecular Psychiatry, 22(10), 1455-1463. doi: 10.1038/mp.2016.72

Wojtalik, J. A., Eack, S. M., Pollock, B. G., & Keshavan, M. S. (2012). Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia. Psychiatry Research, 204(2-3), 61-67. doi: 10.1016/j.pscychresns.2012.04.014

Wu, Q., Tang, W., Luo, Z., Li, Y., Shu, Y., Yue, Z., Xiao, B., & Feng, L. (2017). DISC1 Regulates the Proliferation and Migration of Mouse Neural Stem/Progenitor Cells through Pax5, Sox2, Dll1 and Neurog2. Frontiers in Cellular Neuroscience, 11, 261. doi: 10.3389/fncel.2017.00261

Xu, T., Chan, R. C., & Compton, M. T. (2011). Minor physical anomalies in patients with schizophrenia, unaffected first-degree relatives, and healthy controls: a meta-analysis. PloS One, 6(9), e24129. doi; 10.1371/journal.pone.0024129