Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-05T09:32:17.036Z Has data issue: false hasContentIssue false
  • English
  • Français

MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse

Published online by Cambridge University Press:  31 July 2012

O. E. Onwuameze ,
K. W. Nam ,
E. A. Epping ,
T. H. Wassink ,
S. Ziebell ,
N. C. Andreasen  and
B.-C. Ho
O. E. Onwuameze
Affiliation:
Department of Psychiatry, Southern Illinois University Medical School, Springfield, IL, USA
K. W. Nam
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
E. A. Epping
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
T. H. Wassink
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
S. Ziebell
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
N. C. Andreasen
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
B.-C. Ho*
Affiliation:
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA
*
*Address for correspondence: Dr B.-C. Ho, Department of Psychiatry, W278 GH, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Adolescent marijuana use is associated with increased risk for schizophrenia. We previously reported that marijuana misuse in conjunction with specific cannabinoid receptor 1 (CNR1) genetic variants (rs12720071-G-allele carriers) contributed to white-matter (WM) brain volume deficits in schizophrenia patients. In this study, we assessed the influence of another cannabinoid-related gene, mitogen-activated protein kinase 14 (MAPK14), and potential MAPK14–CNR1 gene–gene interactions in conferring brain volume abnormalities among schizophrenia patients with marijuana abuse/dependence. MAPK14 encodes a member of the MAPK family involved in diverse cellular processes, including CNR1-induced apoptosis.

Method

We genotyped 235 schizophrenia patients on nine MAPK14 tag single nucleotide polymorphisms (tSNPs). Approximately one quarter of the sample had marijuana abuse or dependence. Differential effects of MAPK14 tSNPs on brain volumes across patients with versus without marijuana abuse/dependence were examined using ANCOVA.

Results

Of the MAPK14 tSNPs, only rs12199654 had significant genotype effects and genotype × marijuana misuse interaction effects on WM volumes. rs12199654-A homozygotes with marijuana abuse/dependence had significantly smaller total cerebral and lobar WM volumes. The effects of MAPK14 rs12199654 on WM volume deficits remained significant even after controlling for the CNR1 rs12720071 genotype. There were significant main effects of the MAPK14 CNR1 diplotype and diplotype × marijuana interaction on WM brain volumes, with both genetic variants having additive contributions to WM volume deficits only in patients with marijuana misuse.

Conclusions

Given that CNR1-induced apoptosis is preceded by increased MAPK phosphorylation, our study suggests that potential MAPK14–CNR1 gene–gene interactions may mediate brain morphometric features in schizophrenia patients with heavy marijuana use.

Keywords

Cannabisepistasisgene–environment interactionMRIwhite matter
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 3 , March 2013 , pp. 619 - 631
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Andreasen, NC, Cizadlo, T, Harris, G, Swayze, V, O'Leary, DS, Cohen, G, Ehrhardt, J, Yuh, WT (1993). Voxel processing techniques for the antemortem study of neuroanatomy and neuropathology using magnetic resonance imaging. Journal of Neuropsychiatry and Clinical Neurosciences 5, 121–130.Google ScholarPubMed
Andreasen, NC, Flashman, L, Flaum, M, Arndt, S, Swayze, V 2nd, O'Leary, DS, Ehrhardt, JC, Yuh, WT (1994). Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. Journal of the American Medical Association 272, 1763–1769.CrossRefGoogle ScholarPubMed
Andreasen, NC, Flaum, M, Arndt, S (1992). The Comprehensive Assessment of Symptoms and History (CASH). An instrument for assessing diagnosis and psychopathology. Archives of General Psychiatry 49, 615–623.CrossRefGoogle ScholarPubMed
Andreasen, NC, Rajarethinam, R, Cizadlo, T, Arndt, S, Swayze, V 2nd, Flashman, LA, O'Leary, DS, Ehrhardt, JC, Yuh, WT (1996). Automatic atlas-based volume estimation of human brain regions from MR images. Journal of Computer Assisted Tomography 20, 98–106.CrossRefGoogle ScholarPubMed
Andreasson, S, Allebeck, P, Engstrom, A, Rydberg, U (1987). Cannabis and schizophrenia. A longitudinal study of Swedish conscripts. Lancet 2, 1483–1486.CrossRefGoogle ScholarPubMed
Arevalo-Martin, A, Garcia-Ovejero, D, Rubio-Araiz, A, Gomez, O, Molina-Holgado, F, Molina-Holgado, E (2007). Cannabinoids modulate Olig2 and polysialylated neural cell adhesion molecule expression in the subventricular zone of post-natal rats through cannabinoid receptor 1 and cannabinoid receptor 2. European Journal of Neuroscience 26, 1548–1559.CrossRefGoogle ScholarPubMed
Ashtari, M, Avants, B, Cyckowski, L, Cervellione, KL, Roofeh, D, Cook, P, Gee, J, Sevy, S, Kumra, S (2011). Medial temporal structures and memory functions in adolescents with heavy cannabis use. Journal of Psychiatric Research 45, 1055–1066.CrossRefGoogle ScholarPubMed
Ashtari, M, Cervellione, K, Cottone, J, Ardekani, BA, Sevy, S, Kumra, S (2009). Diffusion abnormalities in adolescents and young adults with a history of heavy cannabis use. Journal of Psychiatric Research 43, 189–204.CrossRefGoogle Scholar
Bangalore, SS, Prasad, KM, Montrose, DM, Goradia, DD, Diwadkar, VA, Keshavan, MS (2008). Cannabis use and brain structural alterations in first episode schizophrenia – a region of interest, voxel based morphometric study. Schizophrenia Research 99, 1–6.CrossRefGoogle ScholarPubMed
Barrett, JC, Fry, B, Maller, J, Daly, MJ (2005). Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21, 263–265.CrossRefGoogle ScholarPubMed
Benes, FM (2006). Strategies for improving sensitivity of gene expression profiling: regulation of apoptosis in the limbic lobe of schizophrenics and bipolars. Progress in Brain Research 158, 153–172.CrossRefGoogle ScholarPubMed
Benjamini, Y, Hochberg, Y (2000). On the adaptive control of the false discovery rate in multiple testing with independent statistics. Journal of Educational and Behavioral Statistics 25, 60–83.CrossRefGoogle Scholar
Casar, B, Sanz-Moreno, V, Yazicioglu, MN, Rodriguez, J, Berciano, MT, Lafarga, M, Cobb, MH, Crespo, P (2007). Mxi2 promotes stimulus-independent ERK nuclear translocation. EMBO Journal 26, 635–646.CrossRefGoogle ScholarPubMed
Chan, GC, Hinds, TR, Impey, S, Storm, DR (1998). Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. Journal of Neuroscience 18, 5322–5332.CrossRefGoogle ScholarPubMed
Cohen, M, Rasser, PE, Peck, G, Carr, VJ, Ward, PB, Thompson, PM, Johnston, P, Baker, A, Schall, U (2011). Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults. International Journal of Neuropsychopharmacology. Published online: 4 May 2011. doi:10.1017/S146114571100068X.Google ScholarPubMed
Cuadrado, A, Nebreda, AR (2010). Mechanisms and functions of p38 MAPK signalling. Biochemical Journal 429, 403–417.CrossRefGoogle ScholarPubMed
Cuenda, A, Rousseau, S (2007). p38 MAP-kinases pathway regulation, function and role in human diseases. Biochimica et Biophysica Acta 1773, 1358–1375.CrossRefGoogle ScholarPubMed
Degenhardt, L, Hall, W, Lynskey, M (2003). Testing hypotheses about the relationship between cannabis use and psychosis. Drug and Alcohol Dependence 71, 37–48.CrossRefGoogle ScholarPubMed
Dekker, N, Schmitz, N, Peters, BD, van Amelsvoort, TA, Linszen, DH, de Haan, L (2010). Cannabis use and callosal white matter structure and integrity in recent-onset schizophrenia. Psychiatry Research: Neuroimaging 181, 51–56.CrossRefGoogle ScholarPubMed
DeLisi, LE (2008). The effect of cannabis on the brain: can it cause brain anomalies that lead to increased risk for schizophrenia? Current Opinion in Psychiatry 21, 140–150.CrossRefGoogle ScholarPubMed
Derkinderen, P, Ledent, C, Parmentier, M, Girault, JA (2001). Cannabinoids activate p38 mitogen-activated protein kinases through CB1 receptors in hippocampus. Journal of Neurochemistry 77, 957–960.CrossRefGoogle ScholarPubMed
Downer, EJ, Fogarty, MP, Campbell, VA (2003). Tetrahydrocannabinol-induced neurotoxicity depends on CB1 receptor-mediated c-Jun N-terminal kinase activation in cultured cortical neurons. British Journal of Pharmacology 140, 547–557.CrossRefGoogle ScholarPubMed
D'Souza, DC, Sewell, RA, Ranganathan, M (2009). Cannabis and psychosis/schizophrenia: human studies. European Archives of Psychiatry and Clinical Neuroscience 259, 413–431.CrossRefGoogle ScholarPubMed
Fernández-Serrano, MJ, Pérez-García, M, Verdejo-García, A (2011). What are the specific vs. generalized effects of drugs of abuse on neuropsychological performance? Neuroscience and Biobehavioral Reviews 35, 377–406.CrossRefGoogle ScholarPubMed
Fragoso, G, Haines, JD, Roberston, J, Pedraza, L, Mushynski, WE, Almazan, G (2007). p38 mitogen-activated protein kinase is required for central nervous system myelination. Glia 55, 1531–1541.CrossRefGoogle ScholarPubMed
Fried, PA, Watkinson, B, Gray, R (2005). Neurocognitive consequences of marihuana – a comparison with pre-drug performance. Neurotoxicology and Teratology 27, 231–239.CrossRefGoogle ScholarPubMed
Gfroerer, JC, Wu, L-T, Penne, MA (2002). Initiation of Marijuana Use: Trends, Patterns, and Implications. Analytic Series: A-17, DHHS Publication No. SMA 02–3711. Substance Abuse and Mental Health Services Administration, Office of Applied Studies: Rockville, MD.Google Scholar
Haines, JD, Fragoso, G, Hossain, S, Mushynski, WE, Almazan, G (2008). p38 Mitogen-activated protein kinase regulates myelination. Journal of Molecular Neuroscience 35, 23–33.CrossRefGoogle ScholarPubMed
Harris, G, Andreasen, NC, Cizadlo, T, Bailey, JM, Bockholt, HJ, Magnotta, VA, Arndt, S (1999). Improving tissue classification in MRI: a three-dimensional multispectral discriminant analysis method with automated training class selection. Journal of Computer Assisted Tomography 23, 144–154.CrossRefGoogle ScholarPubMed
Henquet, C, Krabbendam, L, Spauwen, J, Kaplan, C, Lieb, R, Wittchen, H-U, van Os, J (2005). Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. British Medical Journal 330, 11.CrossRefGoogle ScholarPubMed
Henquet, C, van Os, J (2008). Letter to the Editor: The coherence of the evidence linking cannabis with psychosis. Psychological Medicine 38, 461–464.CrossRefGoogle Scholar
Hickman, M, Vickerman, P, Macleod, J, Lewis, G, Zammit, S, Kirkbride, J, Jones, P (2009). If cannabis caused schizophrenia – how many cannabis users may need to be prevented in order to prevent one case of schizophrenia? England and Wales calculations. Addiction 104, 1856–1861.CrossRefGoogle ScholarPubMed
Ho, BC, Andreasen, NC, Ziebell, S, Pierson, R, Magnotta, V (2011 a). Long-term antipsychotic treatment and brain volumes: a longitudinal study of first-episode schizophrenia. Archives of General Psychiatry 68, 128–137.CrossRefGoogle ScholarPubMed
Ho, BC, Flaum, M, Hubbard, W, Arndt, S, Andreasen, NC (2004). Validity of symptom assessment in psychotic disorders: information variance across different sources of history. Schizophrenia Research 68, 299–307.CrossRefGoogle ScholarPubMed
Ho, BC, Wassink, TH, Ziebell, S, Andreasen, NC (2011 b). Cannabinoid receptor 1 gene polymorphisms and marijuana misuse interactions on white matter and cognitive deficits in schizophrenia. Schizophrenia Research 128, 66–75.CrossRefGoogle ScholarPubMed
Howlett, AC, Mukhopadhyay, S (2000). Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chemistry and Physics of Lipids 108, 53–70.CrossRefGoogle ScholarPubMed
James, A, Hough, M, James, S, Winmill, L, Burge, L, Nijhawan, S, Matthews, PM, Zarei, M (2011). Greater white and grey matter changes associated with early cannabis use in adolescent-onset schizophrenia (AOS). Schizophrenia Research 128, 91–97.CrossRefGoogle ScholarPubMed
Jarskog, LF (2006). Apoptosis in schizophrenia: pathophysiologic and therapeutic considerations. Current Opinion in Psychiatry 19, 307–312.CrossRefGoogle ScholarPubMed
Jockers-Scherubl, MC, Wolf, T, Radzei, N, Schlattmann, P, Rentzsch, J, Gomez-Carrillo de Castro, A, Kuhl, KP (2007). Cannabis induces different cognitive changes in schizophrenic patients and in healthy controls. Progress in Neuro-Psychopharmacology and Biological Psychiatry 31, 1054–1063.CrossRefGoogle ScholarPubMed
Kumra, S (2007). Schizophrenia and cannabis use. Minnesota Medicine 90, 36–38.Google ScholarPubMed
Kyriakis, JM, Avruch, J (2001). Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiological Reviews 81, 807–869.CrossRefGoogle ScholarPubMed
Lahiri, DK, Nurnberger, JI Jr. (1991). A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Research 19, 5444.CrossRefGoogle ScholarPubMed
Lee, SH, Park, J, Che, Y, Han, P-L, Lee, J-K (2000). Constitutive activity and differential localization of p38α and p38β MAPKs in adult mouse brain. Journal of Neuroscience Research 60, 623–631.3.0.CO;2-4>CrossRefGoogle ScholarPubMed
Lopez-Larson, MP, Bogorodzki, P, Rogowska, J, McGlade, E, King, JB, Terry, J, Yurgelun-Todd, D (2011). Altered prefrontal and insular cortical thickness in adolescent marijuana users. Behavioural Brain Research 220, 164–172.CrossRefGoogle ScholarPubMed
Lorenzetti, V, Lubman, DI, Whittle, S, Solowij, N, Yucel, M (2010). Structural MRI findings in long-term cannabis users: what do we know? Substance Use and Misuse 45, 1787–1808.CrossRefGoogle ScholarPubMed
Magnotta, VA, Harris, G, Andreasen, NC, O'Leary, DS, Yuh, WTC, Heckel, D (2002). Structural MR image processing using the BRAINS2 toolbox. Computerized Medical Imaging and Graphics 26, 251.CrossRefGoogle ScholarPubMed
Martin-Santos, R, Fagundo, AB, Crippa, JA, Atakan, Z, Bhattacharyya, S, Allen, P, Fusar-Poli, P, Borgwardt, S, Seal, M, Busatto, GF, McGuire, P (2010). Neuroimaging in cannabis use: a systematic review of the literature. Psychological Medicine 40, 383–398.CrossRefGoogle ScholarPubMed
Mata, I, Perez-Iglesias, R, Roiz-Santianez, R, Tordesillas-Gutierrez, D, Pazos, A, Gutierrez, A, Vazquez-Barquero, JL, Crespo-Facorro, B (2010). Gyrification brain abnormalities associated with adolescence and early-adulthood cannabis use. Brain Research 1317, 297–304.CrossRefGoogle ScholarPubMed
McQueeny, T, Padula, CB, Price, J, Medina, KL, Logan, P, Tapert, SF (2011). Gender effects on amygdala morphometry in adolescent marijuana users. Behavioural Brain Research 224, 128–134.CrossRefGoogle ScholarPubMed
Medina, KL, McQueeny, T, Nagel, BJ, Hanson, KL, Yang, TT, Tapert, SF (2009). Prefrontal cortex morphometry in abstinent adolescent marijuana users: subtle gender effects. Addiction Biology 14, 457–468.CrossRefGoogle ScholarPubMed
Medina, KL, Nagel, BJ, Tapert, SF (2010). Abnormal cerebellar morphometry in abstinent adolescent marijuana users. Psychiatry Research 182, 152–159.CrossRefGoogle ScholarPubMed
Meyer, U, Feldon, J, Yee, BK (2009). A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophrenia Bulletin 35, 959–972.CrossRefGoogle ScholarPubMed
Mielke, K, Herdegen, T (2000). JNK and p38 stress kinases – degenerative effectors of signal-transduction-cascades in the nervous system. Progress in Neurobiology 61, 45–60.CrossRefGoogle ScholarPubMed
Moldrich, G, Wenger, T (2000). Localization of the CB1 cannabinoid receptor in the rat brain. An immunohistochemical study. Peptides 21, 1735–1742.CrossRefGoogle Scholar
Molina-Holgado, E, Vela, JM, Arevalo-Martin, A, Almazan, G, Molina-Holgado, F, Borrell, J, Guaza, C (2002). Cannabinoids promote oligodendrocyte progenitor survival: involvement of cannabinoid receptors and phosphatidylinositol-3 kinase/Akt signaling. Journal of Neuroscience 22, 9742–9753.CrossRefGoogle ScholarPubMed
Murray, RM, Lewis, SW (1987). Is schizophrenia a neurodevelopmental disorder? British Medical Journal (Clinical Research Edition) 295, 681–682.CrossRefGoogle ScholarPubMed
Murray, RM, Morrison, PD, Henquet, C, Di Forti, M (2007). Cannabis, the mind and society: the hash realities. Nature Reviews Neuroscience 8, 885–895.CrossRefGoogle Scholar
NSDUH (2005). Results from the 2004 National Survey on Drug Use and Health: National Findings. Substance Abuse and Mental Health Services Administration: Rockville, MD.Google Scholar
Olsen, L, Hansen, T, Jakobsen, K, Djurovic, S, Melle, I, Agartz, I, Hall, H, Ullum, H, Timm, S, Wang, A, Jonsson, E, Andreassen, O, Werge, T (2008). The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples. BMC Medical Genetics 9, 39.CrossRefGoogle ScholarPubMed
O'Shea, M, McGregor, IS, Mallet, PE (2006). Repeated cannabinoid exposure during perinatal, adolescent or early adult ages produces similar longlasting deficits in object recognition and reduced social interaction in rats. Journal of Psychopharmacology 20, 611–621.CrossRefGoogle ScholarPubMed
O'Shea, M, Singh, ME, McGregor, IS, Mallet, PE (2004). Chronic cannabinoid exposure produces lasting memory impairment and increased anxiety in adolescent but not adult rats. Journal of Psychopharmacology 18, 502–508.CrossRefGoogle Scholar
Pacula, RL, Grossman, M, Chaloupka, FJ, O'Malley, P, Johnston, LD, Farrelly, MC (2000). Marijuana and Youth. NBER Working Paper No. 7703. National Bureau of Economic Research: Cambridge, MA (www.nber.org/papers/w7703). Accessed 14 October 2011.CrossRefGoogle Scholar
Peters, BD, de Haan, L, Vlieger, EJ, Majoie, CB, den Heeten, GJ, Linszen, DH (2009). Recent-onset schizophrenia and adolescent cannabis use: MRI evidence for structural hyperconnectivity? Psychopharmacology Bulletin 42, 75–88.Google ScholarPubMed
Powles, T, te Poele, R, Shamash, J, Chaplin, T, Propper, D, Joel, S, Oliver, T, Liu, WM (2005). Cannabis-induced cytotoxicity in leukemic cell lines: the role of the cannabinoid receptors and the MAPK pathway. Blood 105, 1214–1221.CrossRefGoogle ScholarPubMed
Quickfall, J, Crockford, D (2006). Brain neuroimaging in cannabis use: a review. Journal of Neuropsychiatry and Clinical Neurosciences 18, 318–332.CrossRefGoogle ScholarPubMed
Rabin, RA, Zakzanis, KK, George, TP (2011). The effects of cannabis use on neurocognition in schizophrenia: a meta-analysis. Schizophrenia Research 128, 111–116.CrossRefGoogle ScholarPubMed
Rais, M, Cahn, W, Van Haren, N, Schnack, H, Caspers, E, Hulshoff Pol, H, Kahn, R (2008). Excessive brain volume loss over time in cannabis-using first-episode schizophrenia patients. American Journal of Psychiatry 165, 490–496.CrossRefGoogle ScholarPubMed
Rais, M, van Haren, NE, Cahn, W, Schnack, HG, Lepage, C, Collins, L, Evans, AC, Hulshoff Pol, HE, Kahn, RS (2010). Cannabis use and progressive cortical thickness loss in areas rich in CB1 receptors during the first five years of schizophrenia. European Neuropsychopharmacology 20, 855–865.CrossRefGoogle Scholar
Rodriguez-Sanchez, JM, Ayesa-Arriola, R, Mata, I, Moreno-Calle, T, Perez-Iglesias, R, Gonzalez-Blanch, C, Perianez, JA, Vazquez-Barquero, JL, Crespo-Facorro, B (2010). Cannabis use and cognitive functioning in first-episode schizophrenia patients. Schizophrenia Research 124, 142–151.CrossRefGoogle ScholarPubMed
Rodriguez, JJ, Mackie, K, Pickel, VM (2001). Ultrastructural localization of the CB1 cannabinoid receptor in mu-opioid receptor patches of the rat caudate putamen nucleus. Journal of Neuroscience 21, 823–833.CrossRefGoogle ScholarPubMed
Schneider, M, Koch, M (2003). Chronic pubertal, but not adult chronic cannabinoid treatment impairs sensorimotor gating, recognition memory, and the performance in a progressive ratio task in adult rats. Neuropsychopharmacology 28, 1760–1769.CrossRefGoogle ScholarPubMed
Schneider, M, Koch, M (2007). The effect of chronic peripubertal cannabinoid treatment on deficient object recognition memory in rats after neonatal mPFC lesion. European Neuropsychopharmacology 17, 180–186.CrossRefGoogle ScholarPubMed
Sewell, RA, Ranganathan, M, D'Souza, DC (2009). Cannabinoids and psychosis. International Review of Psychiatry 21, 152–162.CrossRefGoogle ScholarPubMed
Solowij, N, Yucel, M, Respondek, C, Whittle, S, Lindsay, E, Pantelis, C, Lubman, DI (2011). Cerebellar white-matter changes in cannabis users with and without schizophrenia. Psychological Medicine 41, 2349–2359.CrossRefGoogle ScholarPubMed
Stefanis, NC, Delespaul, P, Henquet, C, Bakoula, C, Stefanis, CN, van Os, J (2004). Early adolescent cannabis exposure and positive and negative dimensions of psychosis. Addiction 99, 1333–1341.CrossRefGoogle ScholarPubMed
Szeszko, PR, Robinson, DG, Sevy, S, Kumra, S, Rupp, CI, Betensky, JD, Lencz, T, Ashtari, M, Kane, JM, Malhotra, AK, Gunduz-Bruce, H, Napolitano, B, Bilder, RM (2007). Anterior cingulate grey-matter deficits and cannabis use in first-episode schizophrenia. British Journal of Psychiatry 190, 230–236.CrossRefGoogle ScholarPubMed
Talairach, J, Tournoux, P (1988). Co-Planar Stereotaxic Atlas of the Human Brain. Thieme Medical Publishers: New York.Google Scholar
Turu, G, Hunyady, L (2010). Signal transduction of the CB1 cannabinoid receptor. Journal of Molecular Endocrinology 44, 75–85.CrossRefGoogle ScholarPubMed
van Os, J, Bak, M, Hanssen, M, Bijl, RV, de Graaf, R, Verdoux, H (2002). Cannabis use and psychosis: a longitudinal population-based study. American Journal of Epidemiology 156, 319–327.CrossRefGoogle ScholarPubMed
Vawter, MP, Barrett, T, Cheadle, C, Sokolov, BP, Wood, WH 3rd, Donovan, DM, Webster, M, Freed, WJ, Becker, KG (2001). Application of cDNA microarrays to examine gene expression differences in schizophrenia. Brain Research Bulletin 55, 641–650.CrossRefGoogle ScholarPubMed
Vawter, MP, Ferran, E, Galke, B, Cooper, K, Bunney, WE, Byerley, W (2004). Microarray screening of lymphocyte gene expression differences in a multiplex schizophrenia pedigree. Schizophrenia Research 67, 41–52.CrossRefGoogle Scholar
Wegener, N, Koch, M (2009). Behavioural disturbances and altered Fos protein expression in adult rats after chronic pubertal cannabinoid treatment. Brain Research 1253, 81–91.CrossRefGoogle ScholarPubMed
Weinberger, DR (1987). Implications of normal brain development for the pathogenesis of schizophrenia. Archives of General Psychiatry 44, 660–669.CrossRefGoogle ScholarPubMed
WHO (1997). Cannabis: A Health Perspective and Research Agenda. World Health Organization: Geneva.Google Scholar
Wilson, RI, Nicoll, RA (2002). Endocannabinoid signaling in the brain. Science 296, 678–682.CrossRefGoogle ScholarPubMed
Wobrock, T, Sittinger, H, Behrendt, B, D'Amelio, R, Falkai, P (2009). Comorbid substance abuse and brain morphology in recent-onset psychosis. European Archives of Psychiatry and Clinical Neuroscience 259, 28–36.CrossRefGoogle ScholarPubMed
Woods, RP, Cherry, SR, Mazziotta, JC (1992). Rapid automated algorithm for aligning and reslicing PET images. Journal of Computer Assisted Tomography 16, 620–633.CrossRefGoogle ScholarPubMed
Xu, Y, Li, F, Zhang, B, Zhang, K, Zhang, F, Huang, X, Sun, N, Ren, Y, Sui, M, Liu, P (2010). MicroRNAs and target site screening reveals a pre-microRNA-30e variant associated with schizophrenia. Schizophrenia Research 119, 219–227.CrossRefGoogle ScholarPubMed
Yagasaki, Y, Sudo, T, Osada, H (2004). Exip, a splicing variant of p38alpha, participates in interleukin-1 receptor proximal complex and downregulates NF-kappaB pathway. FEBS Letters 575, 136–140.CrossRefGoogle ScholarPubMed
Yücel, M, Bora, E, Lubman, DI, Solowij, N, Brewer, WJ, Cotton, SM, Conus, P, Takagi, MJ, Fornito, A, Wood, SJ, McGorry, PD, Pantelis, C (2012). The impact of cannabis use on cognitive functioning in patients with schizophrenia: a meta-analysis of existing findings and new data in a first-episode sample. Schizophrenia Bulletin 38, 316–330.CrossRefGoogle Scholar
Zammit, S, Allebeck, P, Andreasson, S, Lundberg, I, Lewis, G (2002). Self reported cannabis use as a risk factor for schizophrenia in Swedish conscripts of 1969: historical cohort study. British Medical Journal 325, 1199.CrossRefGoogle ScholarPubMed