Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

BMC Psychiatry

Philip G Tibbo¹  Sherry H Stewart¹  Aaron J Newman¹  Christopher C Hanstock⁴  Robert Bartha²  David McAllindon³  Jacob Cookey³  Denise Bernier³ 

[1] Department of Psychology and Neuroscience, Dalhousie University, Box 15000, Life Sciences Centre, B3H 4R2 Halifax, Nova Scotia, Canada;Robarts Research Institute, Western University, 100 Perth Drive, London N6A 5K8, Ontario, Canada;Department of Psychiatry, Dalhousie University, 5909 Veterans’ Memorial Lane, Abbie J. Lane Building, Room 3030, Halifax B3H 2E2, Nova Scotia, Canada;Department of Biomedical Engineering, University of Alberta, 8308-114 Street, Edmonton T6G 2V2, Alberta, Canada

关键词: Diffusion tensor imaging;    Proton magnetic resonance spectroscopy;    Transverse relaxation time constants;    Oligodendrocytes;    N-acetylaspartate;    White matter;    Cannabis;    Schizophrenia;   

Others  :  1123930
DOI  :  10.1186/1471-244X-13-264

 received in 2013-05-20, accepted in 2013-10-14,  发布年份 2013

【 摘 要 】

Background

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain.

Methods/Design

Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus.

Discussion

We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

【 授权许可】

   
2013 Bernier et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Maynard T, Sikich L, Lieberman JA, LaMantia A-S: Neural development, cell-cell signaling, and the “two-hit” hypothesis of schizophrenia. Schizophr Bull 2001, 27:457-476.
• [2]Cornblatt BA, Lencz T, Smith CW, Correl CU, Auther AM, Nakayama E: The schizophrenia prodrome revisited: a neurodevelopmental perspective. Schizophr Bull 2003, 29:633-651.
• [3]Kuepper R, van Os J, Lieb R, Wittchen HU, Höfler M, Henquet C: Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10-year follow-up cohort study. BMJ 2011, 342:d738.
• [4]Malone DT, Hill MN, Rubino T: Adolescent cannabis use and psychosis: epidemiology and neurodevelopmental models. Br J Pharmacol 2010, 160:511-522.
• [5]McGrath J, Welham J, Scott J, Varghese D, Degenhardt L, Hayatbakhsh MR, et al.: Association between cannabis use and psychosis-related outcomes using sibiling pair analysis in a cohort of young adults. Arch Gen Psychiatry 2010, 67:440-447.
• [6]Davis KL, Stewart DG, Friedman JI, Buchsbaum M, Harvey PD, Hof PR, et al.: White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry 2003, 60:443-456.
• [7]Baumann N, Pham-Dinh D: Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol Rev 2001, 81:871-927.
• [8]Karlsgodt KH, Jacobson SC, Seal SC, Fusar-Poli P: The relationship of developmental changes in white matter to the onset of psychosis. Curr Pharm Des 2012, 18:422-433.
• [9]Takahashi N, Sakurai T, Davis KL, Buxbaum JD: Linking oligodendrocyte and myelin dysfunction to neurocircuitry abnormalities in schizophrenia. Prog Neurobiol 2011, 93:13-24.
• [10]Hof PR, Haroutunian V, Friedrich VL Jr, Byne W, Buitron C, Perl DP, et al.: Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 2003, 53:1075-1085.
• [11]Uranova NA, Vostrikov VM, Orlovskaya DD, Rachmanova VI: Oligodendroglial density in the prefrontal cortex in schizophrenia and mood disorders: a study from the Stanley Neuropathology Consortium. Schizophr Res 2004, 67:269-275.
• [12]Byne W, Tatusov A, Yiannoulos G, Vong GS, Marcus S: Effects of mental illness and aging in two thalamic nuclei. Schizophr Res 2008, 106:172-181.
• [13]Stark AK, Uylings HB, Sanz-Arigita E, Pakkenberg B: Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry 2004, 161:882-888.
• [14]Uranova N, Orlovskaya D, Vikhreva O, Zimina I, Kolomeets N, Vostrikov V, et al.: Electron microscopy of oligodendroglia in severe mental illness. Brain Res Bull 2001, 55:597-610.
• [15]Uranova NA, Vostrikov VM, Vikhreva OV, Zimina IS, Kolomeets NS, Orlovskaya DD: The role of oligodendrocyte pathology in schizophrenia. Int J Neuropsychopharmacol 2007, 10:537-545.
• [16]Konopaske GT, Dorph-Petersen KA, Sweet RA, Pierri JN, Zhang W, Sampson AR, et al.: Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys. Biol Psychiatry 2008, 63:759-765.
• [17]Arnold SE, Rioux L: Challenges, status, and opportunities for studying developmental neuropathology in adult shizophrenia. Schizophr Bull 2001, 27:395-416.
• [18]Benes FM: Myelination of cortical-hippocampal relays during late adolescence. Schizophr Bull 1989, 15:585-593.
• [19]Peters BD, Szesko PR, Radua J, Ikuta T, Gruner P, DeRosse P, et al.: White matter development in adolescence: diffusion tensor imaging and meta-analytic results. Schizophr Bull 2012, 38:1308-1317.
• [20]McGorry PD, Killackey E, Yung A: Early intervention in psychosis: concepts, evidence and future directions. World Psychiatry 2008, 7:148-156.
• [21]Beaulieu C: The basis of anisotropic water diffusion in the nervous system - a technical review. NMR in Biomed 2002, 15:435-455.
• [22]Mukherjee P, Berman JI, Chung SW, Hess CP, Henry RG: Diffusion tensor MR imaging and fibre tractography: theoretic underpinnings. AJNR 2008, 29:632-641.
• [23]Nucifora PGP, Verma P, Lee S-K, Melhem ER: Diffusion-tensor MR imaging and tractography: exploring brain microstructure and connectivity. Radiology 2007, 245:367-384.
• [24]Ruest T, Holmes WM, Barrie JA, Griffiths IR, Anderson TJ, Dewar D, et al.: High-resolution diffusion tensor imaging of fized brain in a mouse model of pelizaeus-merzbacher disease: comparison with quantitative measures of white matter pathology. NMR in Biomed 2011, 24:1369-1379.
• [25]White T, Nelson M, Lim KO: Diffusion tensor imaging in psychiatric disorders. Top Magn Reson Imaging 2008, 19:97-109.
• [26]Kyriakopoulos M, Bargiotas T, Barker GJ, Frangou S: Diffusion tensor imaging in schizophrenia. Eur Psychiatry 2008, 23:255-273.
• [27]Peters BD, Blaas J, de Haan L: Diffusion tensor imaging in the early phase of schizophrenia: What have we learned? J Psychiatr Res 2010, 44:993-1004.
• [28]Peters BD, Dingemans PM, Dekker N, Blaas J, Akkerman E, van Amelsvoort TA, et al.: White matter connectivity and psychosis in ultra-high-risk subjects: a diffusion tensor fiber tracking study. Psychiatry Res 2010, 181:44-50.
• [29]White T, Magnotta VA, Bockholt J, Williams S, Wallace S, Ehrlich S, et al.: Global white matter abnormalities in schizophrenia: a multisite diffusion tensor imaging study. Schizophr Bull 2011, 37:222-232.
• [30]Bloemen OJN, de Koning MB, Schmitz N, Nieman DH, Becker HE, de Haan L, et al.: White-matter markers for psychosis in a prospective ultra-high-risk cohort. Psychol Med 2010, 40:1297-1304.
• [31]Carletti F, Woolkey JB, Bhattacharyya S, Perez-Iglesias R, Fusar Poli P, Valmaggia L, et al.: Alterations in white matter evident before the onset of psychosis. Schizophr Bull 2012, 38:1170-1179.
• [32]Chan W-Y, Yang G-L, Chia M-Y, Lau I-Y, Sitoh Y-Y, Nowinski WL, et al.: White matter abnormalities in first-episode schizophrenia: a combined structural MRI and DTI study. Schizophr Res 2010, 119:52-60.
• [33]Dekker N, Schmitz N, Peters BD, van Amelsvoort TA, Linszen DH, de Haan L: Cannabis use and callosal white matter structure and integrity in recent-onset schizophrenia. Psychiatry Res 2010, 181:51-56.
• [34]James A, Hough M, James S, Winmill L, Burge L, Nijhawan S, et al.: Greater white and grey matter changes associated with early cannabis use in adolescent-onset schizophrenia (AOS). Schizophr Res 2011, 128:91-97.
• [35]Lu LH, Zhou XJ, Keedy SK, Reilly JL, Sweeney JA: White matter microstructure in untreated first episode bipolar disorder with psychosis: comparison with schizophrenia. Bipolar Disord 2011, 13:604-613.
• [36]Moriya J, Kakeda S, Abe O, Goto N, Yoshimura R, Hori H, et al.: Gray and white matter volumetric and diffusion tensor imaging (DTI) analyses in the early stage of first-episode schizophrenia. Schizophr Res 2010, 116:196-203.
• [37]Pérez-Iglesias R, Tordesillas-Gutiérrez D, Barker GJ, McGuire PK, Roiz-Santiañez R, Mata I, et al.: White matter defects in first episode psychosis patients: a voxelwise analysis of diffusion tensor imaging. NeuroImage 2010, 49:199-204.
• [38]Tang J, Liao Y, Zhou B, Tan C, Liu T, Hao W, et al.: Abnormal anterior cingulum integrity in first episode, early-onset schizophrenia: a diffusion tensor imaging study. Brain Res 2010, 1343:199-205.
• [39]Kyriakopoulos M, Perez-Iglesias R, Woolley JB, Kanaan RAA, Vyas NS, Barker GJ, et al.: Effect of age at onset of schizophrenia on white matter abnormalities. Br J Psychiatry 2009, 195:346-353.
• [40]Kyriakopoulos M, Vyas NS, Barker GJ, Chitnis XA, Frangou S: A diffusion tensor imaging study of white matter in early-onset schizophrenia. Biol Psychiatry 2008, 63:519-523.
• [41]Szeszko PR, Robinson DG, Ashtari M, Vogel J, Betensky J, Sevy S, et al.: Clinical and neuropsychological correlates of white matter abnormalities in recent onset schizophrenia. Neuropshycho 2008, 33:976-984.
• [42]White T, Schmidt M, Karatekin C: White matter ‘potholes’ in early-onset schizophrenia: A new approach to evaluate white matter microstructure using diffusion tensor imaging. Psychiatry Res 2009, 174:110-115.
• [43]Cheung V, Cheung C, McAlonan M, Deng Y, Wong JG, Yip L, et al.: A diffusion tensor imaging study of structural dysconnectivity in never-medicated, first-episode schizophrenia. Psychol Med 2008, 38:877-885.
• [44]Gasparotti R, Valsecchi P, Carletti F, Galluzzo A, Liserre R, Cesana B, et al.: Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic drug-naive patients with schizophrenia. Schizophr Res 2009, 108:41-48.
• [45]Price G, Cercignani M, Parker GJM, Ltman DR, Rnes TRE, Barker GJ, et al.: Abnormal brain connectivity in first-episode psychosis: a diffusion MRI tractography study of the corpus callosum. NeuroImage 2007, 35:458-466.
• [46]Wang Q, Deng W, Huang C, Li M, Ma X, Ang Y, et al.: Abnormalities in connectivity of white-matter tracts in patients with familial and non-familial schizophrenia. Psychol Med 2011, 41:1691-1700.
• [47]Casadio P, Fernandes C, Murray RM, Di Forti M: Cannabis use in young people: the risk for schizophrenia. Neurosci Biobehav Rev 2011, 35:1779-1787.
• [48]Ehrenreich H, Rinn T, Kunert HJ, Moeller MR, Poser W, Schilling L, et al.: Specific attentional dysfunction in adults following early start of cannabis use. Psychopharmacology 1999, 142:295-301.
• [49]Pope HG, Gruber AJ, Hudson JI, Cohane G, Huestis MA, Yurgelun-Todd D: Early-onset cannabis use and cognitive deficits: what is the nature of the asociation? Drug Alcohol Depend 2003, 69:303-310.
• [50]Wilson W, Mathew R, Turkington T, Hawk T, Coleman RE, Provenzale J: Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study. J Addict Dis 2000, 19:22.
• [51]Ashtari M, Cervellione K, Cottone J, Ardekani BA, Kumra S: Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use. J Psychiatr Res 2009, 43:189-204.
• [52]Arnone D, Barrick TR, Chengappa S, Mackay CE, Clark CA, Abou-Saleh MT: Corpus callosum damage in heavy marijuana use: preliminary evidence from diffusion tensor tractography and tract-based spatial statistics. NeuroImage 2008, 41:1067-1074.
• [53]Bava S, Frank LR, McQueeny T, Schweinsburg BC, Schweinsburg AD, Tapert SF: Altered white matter microstructure in adolescent substance users. Psychiatry Res 2009, 173:228-237.
• [54]Clark DB, Chung T, Thatcher DL, Pajtek S, Long EC: Psychological dysregulation, white matter disorganization and substance use disorders in adolescence. Addiction 2012, 107:206-214.
• [55]Jacobus J, McQueeny T, Bava S, Schweinsburg BC, Frank LR, Yang TT, et al.: White matter integrity in adolescents with histories of marijuana use and binge drinking. Neurotoxicol Teratol 2009, 31:349-355.
• [56]Yücel M, Zalesky A, Takagi MJ, Bora E, Fornito A, Ditchfield M, et al.: White-matter abnormalities in adolescents with long-term inhalant and cannabis use: a diffusion magnetic resonance imaging study. J Psychiatry Neurosci 2010, 35:409-412.
• [57]Gruber SA, Silveri MM, Dahlgren MK, Yurgelun-Todd D: Why so impulsive? white matter alterations are associated with impulsivity in chronic marijuana smokers. Exp Clin Psychopharmacol 2011, 19:231-242.
• [58]Zalesky A, Solowij N, Yücel M, Lubman DI, Takagi MJ, Harding IH, et al.: Effect of long-term cannabis use on axonal fibre connectivity. Brain 2012, 135:2245-2255.
• [59]Foti DJ, Kotov R, Guey LT, Bromet EJ: Cannabis use and the course of schizophrenia: 10-year follow-up after first hospitalization. Am J Psychiatry 2010, 167:987-993.
• [60]Peters BD, de Haan L, Vlieger E-J, Majoie CB, den Heeten GJ, Linszen DH: Recent-onset schizophrenia and adolescent cannabis use: MRI evidence for structural hyperconnectivity? Psychopharmacol Bull 2009, 42:75-88.
• [61]Govindaraju V, Young K, Maudsley AA: Proton NMR chemicals shifts and coupling constants for brain metabolites. NMR Biomed 2000, 13:129-153.
• [62]Hetherington HP, Mason GF, Pan JW, Ponder SL, Vaughan JT, Twieg DB, et al.: Evaluation of cerebral gray and white matter metabolite differences by spectroscopic imaging at 4.1T. Magn Reson Med 1994, 32:565-571.
• [63]Moffet JR, Ross B, Arun P, Madhavarao CN, Namboodiri AMA: N-acetylaspartate in the CNS: from neurodiagnosis to neurobiology. Prog Neurobiol 2007, 81:89-131.
• [64]Madhavarao CN, Arun P, Moffet JR, Szucs S, Surendran S, Matalon R, et al.: Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan’s disease. PNAS 2005, 102:5221-5226.
• [65]Namboodiri AMA, Peethambaran A, Mathew R, Sambhu PA, Moffet JR, Madhavarao CN: Canavan disease and the role of N-acetylaspartate in myelin synthesis. Mol Cell Endocrinol 2006, 252:216-223.
• [66]Tkachev D, Mimmack ML, Huffaker SJ, Ryan M, Bahn S: Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia. Int J Neuropsychopharmacol 2007, 10:557-563.
• [67]Prescot AP, Locatelli AE, Renshaw PF, Yurgelun-Todd DA: Neurochemical alterations in adolescent chronic marijuana smokers: a proton MRS study. NeuroImage 2011, 57:69-75.
• [68]Ioannidis JPA: Microarrays and molecular research: noise discovery? Lancet 2005, 365:454-455.
• [69]Steen RG, Hamer RM, Lieberman JA: Measurement of brain metabolites by 1H magnetic resonance spectroscopy in patients with schizophrenia: a systematic review and meta-analysis. Neuropsychopharmacology 2005, 30:1949-1962.
• [70]Tibbo PG, Bernier D, Hanstock CC, Seres P, Lakusta B, Purdon SE: 3-T Proton magnetic spectroscopy in unmedicated first episode psychosis: a focus on creatine. Magn Reson Med 2012, 69:613-620.
• [71]Chang L, Friedman J, Ernst T, Zhong K, Tsopelas ND, Davis K: Brain metabolite abnormalities in the white matter of elderly schizophrenic subjects: implication for glial dysfunction. Biol Psychiatry 2007, 62:1396-1404.
• [72]Jessen F, Fingerhut N, Sprinkhart AM, Kühn K-U, Petrovsky N, Maier W, et al.: N-acetylaspartylglutamate (NAAG) and N-acetylaspartate (NAA) in patients with schizophrenia. Schizophr Bull 2011, 39:197-205.
• [73]Ohrmann P, Siegmund A, Suslow T, Spitzberg K, Kersting A, Arolt V, et al.: Evidence for glutamatergic neuronal dysfunction in the prefrontal cortex in chronic but not in first-episode patients with schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 2005, 73:153-157.
• [74]Ohrmann P, Siegmund A, Suslow T, Pedersen A, Spitzberg K, Kersting A, et al.: Cognitive impairment and in vivo metabolites in first-episode neuroleptic-naïve and chronic medicated schizophrenic patients: a proton magnetic resonance spectroscopy study. J Psychiatr Res 2007, 41:625-634.
• [75]Tunc-Skarka N, Weber-Fahr W, Hoerst M, Meyer-Lindenberg A, Zink M, Ende G: MR spectroscopic evaluation of N-acetylaspartate’s T2 relaxation time and concentration corroborates white matter abnormalities in schizophrenia. NeuroImage 2009, 48:525-531.
• [76]Théberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, et al.: Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry 2002, 159:1944-1946.
• [77]Galiñska B, Szulc A, Tarasów E, Kubas B, Dzienis W, Czernikiewick A, et al.: Duration of untreated psychosis and proton magnetic resonance spectroscopy (1H-MRS) findings in first-episode schizophrenia. Med Sci Monit 2009, 15:CR82-CR88.
• [78]Uhl I, Mavrogiorgou P, Norra C, Forstreuter F, Scheel M, Witthaus H, et al.: 1H-MR spectroscopy in ultra-high risk and first episode stages of schizophrenia. J Psychiatr Res 2011, 45:1135-1139.
• [79]Sigmundsson T, Maier M, Toone BK, Williams SCR, Simmons A, Greenwood K, et al.: Frontal lobe N-acetylaspartate correlates with psychopathology in schizophrenia: a proton magnetic resonance spectroscopy study. Schizophr Res 2003, 64:63-71.
• [80]Stanley JA, Williamson PC, Drost DJ, Rylett RJ, Carr TJ, Malla A, et al.: An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients. Schizophr Bull 1996, 22:597-609.
• [81]Szulc A, Galiñska B, Tarasów E, Kubas B, Dzienis W, Konarzewska B, et al.: N-acetylaspartate (NAA) levels in selected areas of the brain in patients with chronic schizophrenia treated with typical and atypical neuroleptics: a proton magnetic resonance spectroscopy (1H-MRS) study. Med Sci Monit 2007, 13:17-22.
• [82]Tang CY, Friedman J, Shungu D, Chang L, Ernst T, Stewart D, et al.: Correlations between diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (1H-MRS) in schizophrenic patients and normal controls. BMC Psychiatry 2007., 710.1186/1471-244X-7-25
• [83]Tayoshi S, Sumitani S, Taniguchi K, Shibuya-Tayoshi S, Numata S, Iga J, et al.: Metabolite changes and gender differences in schizophrenia using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). Schizophr Res 2009, 108:69-77.
• [84]Tebartz van Elst L, Valerius G, Büchert M, Thiel T, Rüsch N, Bubl E, et al.: Increased prefrontal and hippocampal glutamate concentration in schizophrenia: evidence from a magnetic resonance spectroscopy study. Biol Psychiatry 2005, 58:724-730.
• [85]Théberge J, Al-Semaan YM, Williamson PC, Menon RS, Neufeld WRJ, Rajakumar N, et al.: Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Am J Psychiatry 2003, 160:2231-2233.
• [86]Venkatraman TN, Hamer RM, Perkins DO, Song AW, Lieberman JA, Steen RG: Single-voxel 1H PRESS at 4.0 T: precision and variability of measurements in anterior cingulate and hippocampus. NMR Biomed 2006, 19:484-491.
• [87]MacKay A, Laule C, Vavasour I, Bjarnason T, Kolind S, Mädler B: Insights into brain microstructure from the T2 distribution. Magn Res Imaging 2006, 24:515-525.
• [88]Du F, Cooper A, Cohen BM, Renshaw PF, Öngür D: Water and metabolite transverse T2 relaxation time abnormalities in the white matter in schizophrenia. Schizophr Res 2012, 137:241-245.
• [89]Aydin K, Ucok A, Cakir S: Quantitative proton MR spectroscopy findings in the corpus callosum of patients with schizophrenia suggest callosal disconnection. AJNR 2007, 28:1968-1974.
• [90]Öngür D, Prescot AP, Jensen JE, Rouse ED, Cohen BM, Renshaw PF, et al.: T2 relaxation time abnormalities in bipolar disorder and schizophrenia. Magn Res Med 2010, 63:1-8.
• [91]First MB, Gibbon M, Spitzer RL, Williams JBW: User’s Guide for the structured clinical interview for DSM-IV-TR axis I disorders - research version - patient edition with psychotic screen (SCID-I/P W/PSY SCREEN). New York: Biometrics; 2002.
• [92]Van den Oord EJ, Rujescu D, Robles JR, Giegling I, Birrell C, Bukszár J, et al.: Factor structure and external validity of the PANSS revisited. Schizophr Res 2006, 82:213-223.
• [93]Kay SR, Fiszbein A, Opler LA: The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987, 13:261-276.
• [94]Morosini P-L, Magliano L, Brambilla L, Ugolini S, Pioli R: Development, reliability and acceptability of a new version of the DSM-IV social and occupational functioning assessment scale (SOFAS) to assess routine social functioning. Acta Psychiatr Scand 2000, 101:323-329.
• [95]Beck AT, Epstein N, Brown G, Steer RA: An inventory for measuring clinical anxiety: psychometric properties. J Consult Clin Psychol 1988, 56:893-897.
• [96]Addington D, Addington J, Schissel B: A depression rating scale for schizophrenia. Schizophr Res 1990, 3:247-251.
• [97]Bartha R, Drost DJ, Williamson PC: Factors affecting the quantification of short echo in-vivo 1H MR spectra: prior knowledge, peak elimination, and filtering. NMR Biomed 1999, 12:205-216.
• [98]Gilat A: MATLAB: an introduction with applications 2nd edition. Hoboken, NJ, USA: John Wiley & Sons; 2004.
• [99]Ke Y, Cohen BM, Lowen S, Hirashima L, Nassar L, Renshaw PF: Biexponential transverse relaxation (T2) of the proton MRS creatine resonance in human brain. Magn Res Med 2002, 47:232-238.
• [100]Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, et al.: Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 2006, 31:1487-1505.
• [101]Salimi-Khorshidi G, Smith S, Nichols TE: Adjusting the effect of nonstationarity in cluster-based and TFCE inference. NeuroImage 2011, 54:2006-2019.
• [102]Hua K, Zhang J, Wakana S, Jiang H, Li X, Reich DS, et al.: Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification. NeuroImage 2008, 39:336-347.
• [103]Wakana S, Caprihan A, Panzenboeck MM, Fallon JH, Perry M, Gollub RL, et al.: Reproducibility of quantitative tractography methods applied to cerebral white matter. NeuroImage 2007, 36:630-644.