Minimal evidence that untreated psychosis damages brain structures: A systematic review

Schizophrenia Research

Volumn 162, Issue 1-3, 2015, Pages 222-233

  Anderson, Kelly K ^a,c   Rodrigues, Myanca ^a   Mann, Kamalpreet ^a   Voineskos, Aristotle ^a,b   Mulsant, Benoit H ^a,b   George, Tony P ^a,b   McKenzie, Kwame J ^a,b  

^a CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c UNIVERSITY OF WESTERN ONTARIO   (Canada)

Author keywords

Brain structure; Duration of untreated psychosis; First episode psychosis; Neurotoxicity

Indexed keywords

BRAIN ATROPHY; BRAIN DAMAGE; BRAIN REGION; BRAIN SIZE; COMPUTER ASSISTED TOMOGRAPHY; DISEASE ASSOCIATION; DISEASE DURATION; EVIDENCE BASED MEDICINE; HUMAN; NEUROIMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PSYCHIATRIC TREATMENT; PSYCHOLOGIC ASSESSMENT; PSYCHOSIS; REVIEW; SCHIZOPHRENIA; SYSTEMATIC REVIEW; VOXEL BASED MORPHOMETRY; BRAIN; PATHOLOGY; PSYCHOTIC DISORDERS; TIME TO TREATMENT;

BRAIN; HUMANS; PSYCHOTIC DISORDERS; TIME-TO-TREATMENT;

EID: 84923223237     PISSN: 09209964     EISSN: 15732509     Source Type: Journal    
DOI: 10.1016/j.schres.2015.01.021     Document Type: Review

References (85)

1. Andreasen N.C., Liu D., Ziebell S., Vora A., Ho B.-C. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am. J. Psychiatry 2013, 170:609-615. 10.1176/appi.ajp.2013.12050674.
2. Bangalore S.S., Prasad K.M.R., Montrose D.M., Goradia D.D., Diwadkar V.a., Keshavan M.S. Cannabis use and brain structural alterations in first episode schizophrenia-a region of interest, voxel based morphometric study. Schizophr. Res. 2008, 99:1-6. 10.1016/j.schres.2007.11.029.
3. Bangalore S.S., Goradia D.D., Nutche J., Diwadkar V.a., Prasad K.M.R., Keshavan M.S. Untreated illness duration correlates with gray matter loss in first-episode psychoses. Neuroreport 2009, 20:729-734. 10.1097/WNR.0b013e32832ae501.
4. Behere R.V., Kalmady S.V., Venkatasubramanian G., Gangadhar B.N. Orbitofrontal lobe volume deficits in antipsychotic-naïve schizophrenia: a 3-Tesla MRI study. Indian J. Psychol. Med. 2009, 31:77-81. 10.4103/0253-7176.63577.
5. Boonstra G., Cahn W., Schnack H.G., Hulshoff Pol H.E., Minderhoud T.C., Kahn R.S., van Haren N.E.M. Duration of untreated illness in schizophrenia is not associated with 5-year brain volume change. Schizophr. Res. 2011, 132:84-90. 10.1016/j.schres.2011.07.018.
6. Cahn W. Brain morphology in antipsychotic-naive schizophrenia: a study of multiple brain structures. Br. J. Psychiatry 2002, 181:66s-72s. 10.1192/bjp.181.43.s66.
7. Carletti F., Woolley J.B., Bhattacharyya S., Perez-Iglesias R., Fusar Poli P., Valmaggia L., Broome M.R., Bramon E., Johns L., Giampietro V., Williams S.C.R., Barker G.J., McGuire P.K. Alterations in white matter evident before the onset of psychosis. Schizophr. Bull. 2012, 38:1170-1179. 10.1093/schbul/sbs053.
8. Chan R.C.K., Di X., McAlonan G.M., Gong Q. Brain anatomical abnormalities in high-risk individuals, first-episode, and chronic schizophrenia: an activation likelihood estimation meta-analysis of illness progression. Schizophr. Bull. 2011, 37:177-188. 10.1093/schbul/sbp073.
9. Cohen M., Rasser P.E., Peck G., Carr V.J., Ward P.B., Thompson P.M., Johnston P., Baker A., Schall U. Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults. Int. J. Neuropsychopharmacol. 2012, 15:297-307. 10.1017/S146114571100068X.
10. Collinson S.L., Gan S.C., Woon P.S., Kuswanto C., Sum M.Y., Yang G.L., Lui J.M., Sitoh Y.Y., Nowinski W.L., Sim K. Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese-Singaporean patients. Br. J. Psychiatry 2014, 204:55-60. 10.1192/bjp.bp.113.127886.
11. Compton M., Broussard B. Conceptualizing the multifaceted determinants of the duration of untreated psychosis. Curr. Psychiatry Rev. 2011, 7:1-11. 10.2174/157340011795945865.
12. Crespo-Facorro B., Roiz-Santiáñez R., Pelayo-Terán J.M., González-Blanch C., Pérez-Iglesias R., Gutiérrez A., de Lucas E.M., Tordesillas D., Vázquez-Barquero J.L. Caudate nucleus volume and its clinical and cognitive correlations in first episode schizophrenia. Schizophr. Res. 2007, 91:87-96. 10.1016/j.schres.2006.12.015.
13. Crespo-Facorro B., Roiz-Santiáñez R., Pelayo-Terán J.M., Rodríguez-Sánchez J.M., Pérez-Iglesias R., González-Blanch C., Tordesillas-Gutiérrez D., González-Mandly A., Díez C., Magnotta V.a., Andreasen N.C., Vázquez-Barquero J.L. Reduced thalamic volume in first-episode non-affective psychosis: correlations with clinical variables, symptomatology and cognitive functioning. Neuroimage 2007, 35:1613-1623. 10.1016/j.neuroimage.2007.01.048.
14. Crespo-Facorro B., Roiz-Santiáñez R., Pérez-Iglesias R., Tordesillas-Gutiérrez D., Mata I., Rodríguez-Sánchez J.M., de Lucas E.M., Vázquez-Barquero J.L. Specific brain structural abnormalities in first-episode schizophrenia. A comparative study with patients with schizophreniform disorder, non-schizophrenic non-affective psychoses and healthy volunteers. Schizophr. Res. 2009, 115:191-201. 10.1016/j.schres.2009.09.007.
15. Crespo-Facorro B., Roiz-Santiáñez R., Quintero C., Pérez-Iglesias R., Tordesillas-Gutiérrez D., Mata I., Rodríguez-Sánchez J.M., Gutiérrez A., Vázquez-Barquero J.L. Insular cortex morphometry in first-episode schizophrenia-spectrum patients: diagnostic specificity and clinical correlations. J. Psychiatr. Res. 2010, 44:314-320. 10.1016/j.jpsychires.2009.08.014.
16. Crespo-Facorro B., Roiz-Santiáñez R., Pérez-Iglesias R., Rodriguez-Sanchez J.M., Mata I., Tordesillas-Gutierrez D., Sanchez E., Tabarés-Seisdedos R., Andreasen N., Magnotta V., Vázquez-Barquero J.L. Global and regional cortical thinning in first-episode psychosis patients: relationships with clinical and cognitive features. Psychol. Med. 2011, 41:1449-1460. 10.1017/S003329171000200X.
17. De la Fuente-Sandoval C., León-Ortiz P., Favila R., Stephano S., Mamo D., Ramírez-Bermúdez J., Graff-Guerrero A. Higher levels of glutamate in the associative-striatum of subjects with prodromal symptoms of schizophrenia and patients with first-episode psychosis. Neuropsychopharmacology 2011, 36:1781-1791. 10.1038/npp.2011.65.
18. Duggal H.S., Muddasani S., Keshavan M.S. Insular volumes in first-episode schizophrenia: gender effect. Schizophr. Res. 2005, 73:113-120. 10.1016/j.schres.2004.08.027.
19. Ebdrup B. Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia. J. Psychiatry Neurosci. 2010, 35:95-104. 10.1503/jpn.090049.
20. Erickson D.H., Beiser M., Iacono W.G. Social support predicts 5-year outcome in first-episode schizophrenia. J. Abnorm. Psychol. 1998, 107:681-685.
21. Fannon D., Chitnis X., Doku V., Tennakoon L., O'Ceallaigh S., Soni W., Sumich a., Lowe J., Santamaria M., Sharma T. Features of structural brain abnormality detected in first-episode psychosis. Am. J. Psychiatry 2000, 157:1829-1834.
22. Fusar-Poli P., Radua J., McGuire P., Borgwardt S. Neuroanatomical maps of psychosis onset: voxel-wise meta-analysis of antipsychotic-naive VBM studies. Schizophr. Bull. 2012, 38:1297-1307. 10.1093/schbul/sbr134.
23. Fusar-Poli P., Smieskova R., Kempton M.J., Ho B.C., Andreasen N.C., Borgwardt S. Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci. Biobehav. Rev. 2013, 37:1680-1691. 10.1016/j.neubiorev.2013.06.001.
24. Gunduz H., Wu H., Ashtari M., Bogerts B., Crandall D., Robinson D.G., Alvir J., Lieberman J., Kane J., Bilder R. Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects. Biol. Psychiatry 2002, 51:801-808.
25. Guo W., Liu F., Liu Z., Gao K., Xiao C., Chen H., Zhao J. Right lateralized white matter abnormalities in first-episode, drug-naive paranoid schizophrenia. Neurosci. Lett. 2012, 531:5-9. 10.1016/j.neulet.2012.09.033.
26. Gutiérrez-Galve L., Wheeler-Kingshott C.a M., Altmann D.R., Price G., Chu E.M., Leeson V.C., Lobo A., Barker G.J., Barnes T.R.E., Joyce E.M., Ron M.a Changes in the frontotemporal cortex and cognitive correlates in first-episode psychosis. Biol. Psychiatry 2010, 68:51-60. 10.1016/j.biopsych.2010.03.019.
27. Ho B.-C., Alicata D., Ward J., Moser D.J., O'Leary D.S., Arndt S., Andreasen N.C. Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. Am. J. Psychiatry 2003, 160:142-148.
28. Ho B.-C., Alicata D., Mola C., Andreasen N.C. Hippocampus volume and treatment delays in first-episode schizophrenia. Am. J. Psychiatry 2005, 162:1527-1529. 10.1176/appi.ajp.162.8.1527.
29. Hoff A.L., Sakuma M., Razi K., Heydebrand G., Csernansky J.G., DeLisi L.E. Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia. Am. J. Psychiatry 2000, 157:1824-1828.
30. Ichimiya T., Okubo Y., Suhara T., Sudo Y. Reduced volume of the cerebellar vermis in neuroleptic-naive schizophrenia. Biol. Psychiatry 2001, 49:20-27.
31. Jayakumar P.N., Venkatasubramanian G., Gangadhar B.N., Janakiramaiah N., Keshavan M.S. Optimized voxel-based morphometry of gray matter volume in first-episode, antipsychotic-naive schizophrenia. Prog. Neuropsychopharmacol. Biol. Psychiatry 2005, 29:587-591. 10.1016/j.pnpbp.2005.01.020.
32. Jayakumar P.N., Venkatasubramanian G., Keshavan M.S., Srinivas J.S., Gangadhar B.N. MRI volumetric and 31P MRS metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia. Acta Psychiatr. Scand. 2006, 114:346-351. 10.1111/j.1600-0447.2006.00836.x.
33. John J.P., Shakeel M.K., Jain S. Corpus callosal area differences and gender dimorphism in neuroleptic-naïve, recent-onset schizophrenia and healthy control subjects. Schizophr. Res. 2008, 103:11-21. 10.1016/j.schres.2008.04.035.
34. Joyal C.C., Laakso M.P., Tiihonen J., Syvälahti E., Vilkman H., Laakso A., Alakare B., Räkköläinen V., Salokangas R.K., Hietala J. The amygdala and schizophrenia: a volumetric magnetic resonance imaging study in first-episode, neuroleptic-naive patients. Biol. Psychiatry 2003, 54:1302-1304. 10.1016/S0006-3223(03)00597-3.
35. Juola P., Miettunen J., Veijola J., Isohanni M., Jääskeläinen E. Predictors of short- and long-term clinical outcome in schizophrenic psychosis-the Northern Finland 1966 birth cohort study. Eur. Psychiatry 2013, 28:263-268. 10.1016/j.eurpsy.2011.11.001.
36. Keshavan M.S., Haas G.L., Kahn C.E., Aguilar E., Dick E.L., Schooler N.R., Sweeney J.a., Pettegrew J.W. Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible?. J. Psychiatr. Res. 1998, 32:161-167.
37. Keshavan M.S., Rosenberg D., Sweeney J.a., Pettegrew J.W. Decreased caudate volume in neuroleptic-naive psychotic patients. Am. J. Psychiatry 1998, 155:774-778.
38. Keshavan M.S., Diwadkar V.a, Harenski K., Rosenberg D.R., Sweeney J.a, Pettegrew J.W. Abnormalities of the corpus callosum in first episode, treatment naive schizophrenia. J. Neurol. Neurosurg. Psychiatry 2002, 72:757-760.
39. Lappin J.M., Morgan K., Morgan C., Hutchison G., Chitnis X., Suckling J., Fearon P., McGuire P.K., Jones P.B., Leff J., Murray R.M., Dazzan P. Gray matter abnormalities associated with duration of untreated psychosis. Schizophr. Res. 2006, 83:145-153. 10.1016/j.schres.2005.11.018.
40. Leung M., Cheung C., Yu K., Yip B., Sham P., Li Q., Chua S., McAlonan G. Gray matter in first-episode schizophrenia before and after antipsychotic drug treatment. Anatomical likelihood estimation meta-analyses with sample size weighting. Schizophr. Bull. 2011, 37:199-211. 10.1093/schbul/sbp099.
41. Lieberman J., Ma Alvir J., Koreen A., Geisler S., Chakos M., Sheitman B., Woerner M. Psychobiologic correlates of treatment response in schizophrenia. Neuropsychopharmacology 1996, 14(3 Suppl.):13S-21S.
42. Liu X., Lai Y., Wang X., Hao C., Chen L., Zhou Z., Yu X., Hong N. Reduced white matter integrity and cognitive deficit in never-medicated chronic schizophrenia: a diffusion tensor study using TBSS. Behav. Brain Res. 2013, 252:157-163. 10.1016/j.bbr.2013.05.061.
43. Luck D., Malla A.K., Joober R., Lepage M. Disrupted integrity of the fornix in first-episode schizophrenia. Schizophr. Res. 2010, 119:61-64. 10.1016/j.schres.2010.03.027.
44. Luck D., Buchy L., Czechowska Y., Bodnar M., Pike G.B., Campbell J.S.W., Achim A., Malla A., Joober R., Lepage M. Fronto-temporal disconnectivity and clinical short-term outcome in first episode psychosis: a DTI-tractography study. J. Psychiatr. Res. 2011, 45:369-377. 10.1016/j.jpsychires.2010.07.007.
45. Madsen a L., Karle a, Rubin P., Cortsen M., Andersen H.S., Hemmingsen R. Progressive atrophy of the frontal lobes in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment. Acta Psychiatr. Scand. 1999, 100:367-374.
46. Malla A.K., Mittal C., Lee M., Scholten D.J., Assis L., Norman R.M.G. Computed tomography of the brain morphology of patients with first-episode schizophrenic psychosis. J. Psychiatry Neurosci. 2002, 27:350-358.
47. Malla A.K., Norman R.M.G., Manchanda R., Ahmed M.R., Scholten D., Harricharan R., Cortese L., Takhar J. One year outcome in first episode psychosis: influence of DUP and other predictors. Schizophr. Res. 2002, 54:231-242.
48. Malla A.K., Bodnar M., Joober R., Lepage M. Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first episode psychosis. Schizophr. Res. 2011, 125:13-20. 10.1016/j.schres.2010.09.021.
49. Mandl R.C.W., Rais M., van Baal G.C.M., van Haren N.E.M., Cahn W., Kahn R.S., Hulshoff Pol H.E. Altered white matter connectivity in never-medicated patients with schizophrenia. Hum. Brain Mapp. 2013, 34:2353-2365. 10.1002/hbm.22075.
50. Marshall M., Lewis S., Lockwood A., Drake R., Jones P., Croudace T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: a systematic review. Arch. Gen. Psychiatry 2005, 62:975-983. 10.1001/archpsyc.62.9.975.
51. McGlashan T.H. Duration of untreated psychosis in first-episode schizophrenia: marker or determinant of course?. Biol. Psychiatry 1999, 46:899-907.
52. McGlashan T.H. Is active psychosis neurotoxic?. Schizophr. Bull. 2006, 32:609-613. 10.1093/schbul/sbl032.
53. Natsubori T., Inoue H., Abe O., Takano Y., Iwashiro N., Aoki Y., Koike S., Yahata N., Katsura M., Gonoi W., Sasaki H., Takao H., Kasai K., Yamasue H. Reduced frontal glutamate+glutamine and N-acetylaspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia. Schizophr. Bull. 2014, 40:1128-1139. 10.1093/schbul/sbt124.
54. Navari S., Dazzan P. Do antipsychotic drugs affect brain structure? A systematic and critical review of MRI findings. Psychol. Med. 2009, 39:1763-1777. 10.1017/S0033291709005315.
55. Norman R.M.G., Lewis S.W., Marshall M. Duration of untreated psychosis and its relationship to clinical outcome. Br. J. Psychiatry 2005, 48:s19-s23. 10.1192/bjp.187.48.s19.
56. Norman R.M.G., Malla A.K., Manchanda R., Harricharan R., Takhar J., Northcott S. Social support and three-year symptom and admission outcomes for first episode psychosis. Schizophr. Res. 2005, 80:227-234. 10.1016/j.schres.2005.05.006.
57. Norman R.M.G., Malla A.K., Manchanda R. Is untreated psychosis socially toxic?. Early Interv.Psychiatry 2007, 1:267-270. 10.1111/j.1751-7893.2007.00038.x.
58. Penttilä M., Jääskeläinen E., Haapea M., Tanskanen P., Veijola J., Ridler K., Murray G.K., Barnes A., Jones P.B., Isohanni M., Koponen H., Miettunen J. Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort. Schizophr. Res. 2010, 123:145-152. 10.1016/j.schres.2010.08.016.
59. Perkins D.O., Gu H., Boteva K., Lieberman J.A. Relationship between duration of untreated psychosis and outcome in first-episode schizophrenia: a critical review and meta-analysis. Am. J. Psychiatry 2005, 162:1785-1804. 10.1176/appi.ajp.162.10.1785.
60. Perneger T.V. What's wrong with Bonferroni adjustments. BMJ 1998, 316:1236-1238.
61. Rais M., Cahn W., Van Haren N., Schnack H., Caspers E., Hulshoff Pol H., Kahn R. Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. Am. J. Psychiatry 2008, 165:490-496. 10.1176/appi.ajp.2007.07071110.
62. Ren W., Lui S., Deng W., Li F., Li M., Huang X., Wang Y., Li T., Sweeney J.a., Gong Q. Anatomical and functional brain abnormalities in drug-naive first-episode schizophrenia. Am. J. Psychiatry 2013, 170:1308-1316. 10.1176/appi.ajp.2013.12091148.
63. Roiz-Santiáñez R., Pérez-Iglesias R., Quintero C., Tordesillas-Gutiérrez D., Mata I., Ayesa R., Sánchez J.M.R., Gutiérrez A., Sanchez E., Vázquez-Barquero J.L., Crespo-Facorro B. Insular cortex thinning in first episode schizophrenia patients. Psychiatry Res. 2010, 182:216-222. 10.1016/j.pscychresns.2010.03.001.
64. Roiz-Santiáñez R., Pérez-Iglesias R., Quintero C., Tordesillas-Gutiérrez D., Mata I., Gutiérrez A., Sánchez E., Pazos A., Tabarés-Seisdedos R., Vázquez-Barquero J.L., Crespo-Facorro B. Temporal pole morphology in first-episode schizophrenia patients: clinical correlations. Psychiatry Res. 2010, 184:189-191. 10.1016/j.pscychresns.2010.08.002.
65. Roiz-Santiáñez R., Pérez-Iglesias R., Ortiz-García de la Foz V., Tordesillas-Gutiérrez D., Mata I., Marco de Lucas E., Pazos A., Tabarés-Seisdedos R., Vázquez-Barquero J.L., Crespo-Facorro B. Straight gyrus morphology in first-episode schizophrenia-spectrum patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 2011, 35:84-90. 10.1016/j.pnpbp.2010.09.002.
66. Rothman K.J. No adjustments are needed for multiple comparisons. Epidemiology 1990, 1:43-46.
67. Rund B.R. Does active psychosis cause neurobiological pathology? A critical review of the neurotoxicity hypothesis. Psychol. Med. 2014, 44:1577-1590. 10.1017/S0033291713002341.
68. Seok Jeong B., Kwon J.S., Yoon Kim S., Lee C., Youn T., Moon C.-H., Yoon Kim C. Functional imaging evidence of the relationship between recurrent psychotic episodes and neurodegenerative course in schizophrenia. Psychiatry Res. 2005, 139:219-228. 10.1016/j.pscychresns.2004.01.008.
69. Smith G.N., Thornton A.E., Lang D.J., Macewan G.W., Ehmann T.S., Kopala L.C., Tee K., Shiau G., Voineskos A.N., Kennedy J.L., Honer W.G. Hippocampal volume and the brain-derived neurotrophic factor Val66Met polymorphism in first episode psychosis. Schizophr. Res. 2012, 134:253-259. 10.1016/j.schres.2011.11.022.
70. Steen R.G., Mull C., McClure R., Hamer R.M., Lieberman J.a. Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br. J. Psychiatry 2006, 188:510-518. 10.1192/bjp.188.6.510.
71. Stroup D.F., Berlin J.A., Morton S.C., Olkin I., Williamson G.D., Rennie D., Moher D., Becker B.J., Sipe T.A., Thacker S.B. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA 2000, 283:2008-2012.
72. Takahashi T., Suzuki M., Tanino R., Zhou S.-Y., Hagino H., Niu L., Kawasaki Y., Seto H., Kurachi M. Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: a preliminary report. Psychiatry Res. 2007, 154:209-219. 10.1016/j.pscychresns.2006.10.001.
73. Takayanagi Y., Takahashi T., Orikabe L., Masuda N., Mozue Y., Nakamura K., Kawasaki Y., Itokawa M., Sato Y., Yamasue H., Kasai K., Okazaki Y., Suzuki M. Volume reduction and altered sulco-gyral pattern of the orbitofrontal cortex in first-episode schizophrenia. Schizophr. Res. 2010, 121:55-65. 10.1016/j.schres.2010.05.006.
74. Tauscher-Wisniewski S., Tauscher J., Christensen B.K., Mikulis D.J., Zipursky R.B. Volumetric MRI measurement of caudate nuclei in antipsychotic-naive patients suffering from a first episode of psychosis. J. Psychiatr. Res. 2005, 39:365-370. 10.1016/j.jpsychires.2004.10.001.
75. Venkatasubramanian G., Gangadhar B.N., Jayakumar P.N., Janakiramaiah N., Keshavan M.S. Reduced Caudate Volume in Never-Treated Schizophrenia: Evidence for Neuro developmental Etiopathogenesis. Indian J. Psychiatry 2003, 45:20-26.
76. Venkatasubramanian G., Jayakumar P.N., Gangadhar B.N., Keshavan M.S. Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naïve schizophrenia. Acta Psychiatr. Scand. 2008, 117:420-431. 10.1111/j.1600-0447.2008.01198.x.
77. Venkatasubramanian G., Jayakumar P.N., Reddy V.V., Reddy U.S., Gangadhar B.N., Keshavan M.S. Corpus callosum deficits in antipsychotic-naïve schizophrenia: evidence for neurodevelopmental pathogenesis. Psychiatry Res. 2010, 182:141-145. 10.1016/j.pscychresns.2010.01.004.
78. Vernon A.C., Natesan S., Crum W.R., Cooper J.D., Modo M., Williams S.C.R., Kapur S. Contrasting effects of haloperidol and lithium on rodent brain structure: a magnetic resonance imaging study with postmortem confirmation. Biol. Psychiatry 2012, 71:855-863. 10.1016/j.biopsych.2011.12.004.
79. Vernon A.C., Crum W.R., Lerch J.P., Chege W., Natesan S., Modo M., Cooper J.D., Williams S.C.R., Kapur S. Reduced cortical volume and elevated astrocyte density in rats chronically treated with antipsychotic drugs-linking magnetic resonance imaging findings to cellular pathology. Biol. Psychiatry 2014, 75:982-990. 10.1016/j.biopsych.2013.09.012.
80. Welch K.a, Moorhead T.W., McIntosh a M., Owens D.G.C., Johnstone E.C., Lawrie S.M. Tensor-based morphometry of cannabis use on brain structure in individuals at elevated genetic risk of schizophrenia. Psychol. Med. 2013, 43:2087-2096. 10.1017/S0033291712002668.
81. Wells G., Shea B., O'Connell D., Peterson J., Welch V., Losos M., Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [WWW Document] URL, (accessed 4.25.13). http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp.
82. Whitworth A.B., Honeder M., Kremser C., Kemmler G., Felber S., Hausmann A., Wanko C., Wechdorn H., Aichner F., Stuppaeck C.H., Fleischhacker W.W. Hippocampal volume reduction in male schizophrenic patients. Schizophr. Res. 1998, 31:73-81.
83. Wyatt R.J. Neuroleptics and the natural course of schizophrenia. Schizophr. Bull. 1991, 17:325-351.
84. Xiao Y., Lui S., Deng W., Yao L., Zhang W., Li S., Wu M., Xie T., He Y., Huang X., Hu J., Bi F., Li T., Gong Q. Altered cortical thickness related to clinical severity but not the untreated disease duration in schizophrenia. Schizophr. Bull. 2013, 1-10. 10.1093/schbul/sbt177.
85. Zanetti M.V., Schaufelberger M.S., de Castro C.C., Menezes P.R., Scazufca M., McGuire P.K., Murray R.M., Busatto G.F. White-matter hyperintensities in first-episode psychosis. Br. J. Psychiatry 2008, 193:25-30. 10.1192/bjp.bp.107.038901.