Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-23T08:28:34.525Z Has data issue: false hasContentIssue false

Schizophrenia: genetics, prevention and rehabilitation

Published online by Cambridge University Press:  24 June 2014

Paolo Olgiati
Affiliation:
Department of Psychiatry, Institute of Psychiatry, Bologna University, Italy
Laura Mandelli
Affiliation:
Department of Psychiatry, Institute of Psychiatry, Bologna University, Italy
Cristina Lorenzi
Affiliation:
Department of Psychiatry, Istituto Scientifico San Raffaele, Vita-Salute University, Milan, Italy
Elena Marino
Affiliation:
Department of Psychiatry, Istituto Scientifico San Raffaele, Vita-Salute University, Milan, Italy
Pirovano Adele
Affiliation:
Department of Psychiatry, Istituto Scientifico San Raffaele, Vita-Salute University, Milan, Italy
Barbara Ferrari
Affiliation:
Department of Psychiatry, Institute of Psychiatry, Bologna University, Italy
Diana De Ronchi
Affiliation:
Department of Psychiatry, Institute of Psychiatry, Bologna University, Italy
Alessandro Serretti*
Affiliation:
Department of Psychiatry, Institute of Psychiatry, Bologna University, Italy
*
Alessandro Serretti, Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Tel: +39 051 6584233; Fax: +39 051 521030; E-mail: [email protected]

Abstract

Objective:

Genetic factors are largely implicated in predisposing to schizophrenia. Environmental factors contribute to the onset of the disorder in individuals at increased genetic risk. Cognitive deficits have emerged as endophenotypes and potential therapeutic targets for schizophrenia because of their association with functional outcome. The aims of this review were to analyse the joint effect of genetic and environmental (G×E) factors on liability to schizophrenia and to investigate relationships between genes and cognitive endophenotypes focusing on practical applications for prevention and rehabilitation.

Methods:

Medline search of relevant studies published between 1990 and 2008.

Results:

In schizophrenia, examples of G×E interaction include the catechol-O-methyl transferase (COMT) (Val158Met) polymorphism, which was found to moderate the onset of psychotic manifestations in response to stress and to increase the risk for psychosis related to cannabis use, and neurodevelopmental genes such as AKT1 (serine-threonine kinase), brain-derived neurotrophic factor (BDNF), DTNBP1 (dysbindin) and GRM3 (metabotropic glutamate receptor 3), which were associated with development of schizophrenia in adulthood after exposure to perinatal obstetric complications. Neurocognitive deficits are recognised as core features of schizophrenia that facilitate the onset of the disorder and have a great impact on functional outcome. Neurocognitive deficits are also endophenotypes that have been linked to a variety of genes [COMT, neuregulin (NRG1), BDNF, Disrupted-In-Schizophrenia 1 (DISC1) and dysbindin] conferring susceptibility to schizophrenia. Recently, it has emerged that cognitive improvement during rehabilitation therapy was under control of COMT (Val158Met) polymorphism.

Conclusion:

This review could indicate a pivotal role of psychiatric genetics in prevention and rehabilitation of schizophrenic psychoses.

Type
Review article
Copyright
Copyright © 2009 John Wiley & Sons A/S

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

Tsuang, MT, Stone, WS, Faraone, SV. Genes, environment and schizophrenia. Br J Psychiatry 2001;40(Suppl):s18s24. CrossRefGoogle Scholar
Sullivan, PF, Kendler, KS, Neale, MC. Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 2003;60:11871192. CrossRefGoogle ScholarPubMed
Cardno, AG, Marshall, EJ, Coid, Bet al. Heritability estimates for psychotic disorders: the Maudsley twin psychosis series. Arch Gen Psychiatry 1999;56:162168. CrossRefGoogle ScholarPubMed
Portin, P, Alanen, YO. A critical review of genetic studies of schizophrenia. I. Epidemiological and brain studies. Acta Psychiatr Scand 1997;95:15. CrossRefGoogle ScholarPubMed
Levinson, DF, Levinson, MD, Segurado, R, Lewis, CM. Genome scan meta-analysis of schizophrenia and bipolar disorder, part I: Methods and power analysis. Am J Hum Genet 2003;73:1733. CrossRefGoogle ScholarPubMed
Lewis, CM, Levinson, DF, Wise, LHet al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: schizophrenia. Am J Hum Genet 2003; 73:1733. CrossRefGoogle ScholarPubMed
Segurado, R, Detera-Wadleigh, SD, Levinson, DFet al. Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: bipolar disorder. Am J Hum Genet 2003;73:3448. CrossRefGoogle ScholarPubMed
Botstein, D, Risch, N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet 2003;33(Suppl):228237. CrossRefGoogle ScholarPubMed
Wong, AH, Van Tol, HH. Schizophrenia: from phenomenology to neurobiology. Neurosci Biobehav Rev 2003;27:269306. CrossRefGoogle ScholarPubMed
Prasad, S, Semwal, P, Deshpande, S, Bhatia, T, Nimgaonkar, VL, Thelma, BK. Molecular genetics of schizophrenia: past, present and future. J Biosci 2002;27(Suppl 1):3552. CrossRefGoogle ScholarPubMed
Karoutzou, G, Emrich, H, Dietrich, D. The myelin-pathogenesis puzzle in schizophrenia: a literature review. Mol Psychiatry 2008;13:245260. CrossRefGoogle ScholarPubMed
Nurnberger, JI Jr., Blehar, MC, Kaufmann, CAet al. Diagnostic interview for genetic studies. Rationale, unique features, and training. NIMH Genetics Initiative. Arch Gen Psychiatry 1994;51:849859; discussion 863–864. CrossRefGoogle ScholarPubMed
Park, N, Juo, S, Cheng, Ret al. Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry 2004;9:10911099. CrossRefGoogle ScholarPubMed
Kendler, KS. “A gene for …”: the nature of gene action in psychiatric disorders. Am J Psychiatry 2005;162:12431252. CrossRefGoogle Scholar
Gottesman, II, Gould, TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003;160:636645. CrossRefGoogle ScholarPubMed
Green, MF. Cognitive impairment and functional outcome in schizophrenia and bipolar disorder. J Clin Psychiatry 2006;67(Suppl 9):38; discussion 36–42. CrossRefGoogle ScholarPubMed
Thaker, GK. Schizophrenia endophenotypes as treatment targets. Expert Opin Ther Targets 2007;11:11891206. CrossRefGoogle ScholarPubMed
Boog, G. [Obstetrical complications and further schizophrenia of the infant: a new medicolegal threat to the obstetrician?]. J Gynecol Obstet Biol Reprod (Paris) 2003;32:720727. Google Scholar
Pearce, BD. Schizophrenia and viral infection during neurodevelopment: a focus on mechanisms. Mol Psychiatry 2001;6:634646. CrossRefGoogle ScholarPubMed
Cullberg, J. Stressful life events preceding the first onset of psychosis. An explorative study. Nord J Psychiatry 2003;57:209214. CrossRefGoogle ScholarPubMed
Moore, TH, Zammit, S, Lingford-Hughes, A, Barnes, TR, Jones, PB, Burke, M, Lewis, G. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet 2007;370:319328. CrossRefGoogle ScholarPubMed
McDonald, C, Murray, RM. Early and late environmental risk factors for schizophrenia. Brain Res Brain Res Rev 2000;31:130137. CrossRefGoogle Scholar
Tienari, P, Wynne, LC, Moring, Jet al. The Finnish adoptive family study of schizophrenia. Implications for family research. Br J Psychiatry 1994;(Suppl):2026. Google ScholarPubMed
Tienari, P, Wynne, LC, Sorri, Aet al. Genotype-environment interaction in schizophrenia-spectrum disorder. Long-term follow-up study of Finnish adoptees. Br J Psychiatry 2004;184:216222. CrossRefGoogle ScholarPubMed
Fioravanti, M, Carlone, O, Vitale, B, Cinti, M, Clare, L. A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychol Rev 2005;15:7395. CrossRefGoogle ScholarPubMed
Sitskoorn, M, Aleman, A, Ebisch, S, Appels, M, Kahn, R. Cognitive deficits in relatives of patients with schizophrenia: a meta-analysis. Schizophr Res 2004;71:285295. CrossRefGoogle ScholarPubMed
Erwin, RJ, Turetsky, BI, Moberg, P, Gur, RC, Gur, RE. P50 abnormalities in schizophrenia: relationship to clinical and neuropsychological indices of attention. Schizophr Res 1998;33:157167. CrossRefGoogle Scholar
Shajahan, PM, O’Carroll, RE, Glabus, MF, Ebmeier, KP, Blackwood, DH. Correlation of auditory ‘oddball’ P300 with verbal memory deficits in schizophrenia. Psychol Med 1997;27:579586. CrossRefGoogle Scholar
Souza, VB, Muir, WJ, Walker, MTet al. Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder. Biol Psychiatry 1995;37:300310. CrossRefGoogle ScholarPubMed
Patterson, JV, Hetrick, WP, Boutros, NNet al. P50 sensory gating ratios in schizophrenics and controls: a review and data analysis. Psychiatry Res 2008;158:226247. CrossRefGoogle ScholarPubMed
Turetsky, BI, Calkins, ME, Light, GA, Olincy, A, Radant, AD, Swerdlow, NR. Neurophysiological endophenotypes of schizophrenia: the viability of selected candidate measures. Schizophr Bull 2007;33:6994. CrossRefGoogle ScholarPubMed
Light, GA, Geyer, MA, Clementz, BA, Cadenhead, KS, Braff, DL. Normal P50 suppression in schizophrenia patients treated with atypical antipsychotic medications. Am J Psychiatry 2000;157:767771. CrossRefGoogle ScholarPubMed
Umbricht, D, Javitt, D, Novak, Get al. Effects of clozapine on auditory event-related potentials in schizophrenia. Biol Psychiatry 1998;44:716725. CrossRefGoogle Scholar
Grossman, MH, Littrell, J, Weinstein, R, Punnett, HH, Emanuel, BS, Budarf, M. The gene for human catechol-O-methyltransferase (COMT) maps to 22pter-22q11.1. Cytogenet Cell Genet 1991;58:2048. Google Scholar
Lachman, HM, Papolos, DF, Saito, T, Yu, YM, Szumlanski, CL, Weinshilboum, RM. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics 1996;6:243250. CrossRefGoogle ScholarPubMed
Glatt, SJ, Faraone, SV, Tsuang, MT. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies. Am J Psychiatry 2003;160:469476. CrossRefGoogle ScholarPubMed
Gosso, MF, De Geus, EJ, Polderman, TJ, Boomsma, DI, Heutink, P, Posthuma, D. Catechol O-methyl transferase and dopamine D2 receptor gene polymorphisms: evidence of positive heterosis and gene-gene interaction on working memory functioning. Eur J Hum Genet 2008;16:10751082. CrossRefGoogle ScholarPubMed
Opgen-Rhein, C, Neuhaus, AH, Urbanek, C, Hahn, E, Sander, T, Dettling, M. Executive attention in schizophrenic males and the impact of COMT val108/158met genotype on performance on the attention network test. Schizophr Bull 2008;34:12311239. CrossRefGoogle ScholarPubMed
Alfimova, MV, Golimbet, VE, Gritsenko, IKet al. Interaction of dopamine system genes and cognitive functions in patients with schizophrenia and their relatives and in healthy subjects from the general population. Neurosci Behav Physiol 2007;37:643650. CrossRefGoogle ScholarPubMed
Woodward, ND, Jayathilake, K, Meltzer, HY. COMT val108/158met genotype, cognitive function, and cognitive improvement with clozapine in schizophrenia. Schizophr Res 2007;90:8696. CrossRefGoogle Scholar
Rybakowski, JK, Borkowska, A, Czerski, PMet al. Performance on the Wisconsin Card Sorting Test in schizophrenia and genes of dopaminergic inactivation (COMT, DAT, NET). Psychiatry Res 2006;143:1319. CrossRefGoogle Scholar
Minzenberg, MJ, Xu, K, Mitropoulou, Vet al. Catechol-O-methyltransferase Val158Met genotype variation is associated with prefrontal-dependent task performance in schizotypal personality disorder patients and comparison groups. Psychiatr Genet 2006;16:117124. CrossRefGoogle ScholarPubMed
Stefanis, NC, VanOs, J, Avramopoulos, D, Smyrnis, N, Evdokimidis, I, Stefanis, CN. Effect of COMT Val158Met polymorphism on the continuous performance test, identical Pairs version: tuning rather than improving performance. Am J Psychiatry 2005;162:17521754. CrossRefGoogle ScholarPubMed
Galderisi, S, Maj, M, Kirkpatrick, Bet al. Catechol-O-methyltransferase Val158Met polymorphism in schizophrenia: associations with cognitive and motor impairment. Neuropsychobiology 2005;52:8389. CrossRefGoogle ScholarPubMed
Nolan, KA, Bilder, RM, Lachman, HM, Volavka, J. Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: differential effects of Val and Met alleles on cognitive stability and flexibility. Am J Psychiatry 2004;161:359361. CrossRefGoogle ScholarPubMed
Goldberg, TE, Egan, MF, Gscheidle, Tet al. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry 2003;60:889896. CrossRefGoogle Scholar
Egan, MF, Goldberg, TE, Kolachana, BSet al. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 2001;98:69176922. CrossRefGoogle ScholarPubMed
Lu, BY, Martin, KE, Edgar, JCet al. Effect of catechol O-methyltransferase val(158)met polymorphism on the p50 gating endophenotype in schizophrenia. Biol Psychiatry 2007;62:822825. CrossRefGoogle Scholar
Ma, X, Sun, J, Yao, Jet al. A quantitative association study between schizotypal traits and COMT, PRODH and BDNF genes in a healthy Chinese population. Psychiatry Res 2007;153:715. CrossRefGoogle Scholar
Schurhoff, F, Szoke, A, Chevalier, Fet al. Schizotypal dimensions: an intermediate phenotype associated with the COMT high activity allele. Am J Med Genet B Neuropsychiatr Genet 2007;144:6468. CrossRefGoogle Scholar
Falls, DL. Neuregulins: functions, forms, and signaling strategies. Exp Cell Res 2003;284:1430. CrossRefGoogle ScholarPubMed
Britsch, S. The neuregulin-I/ErbB signaling system in development and disease. Adv Anat Embryol Cell Biol 2007;190:165. Google ScholarPubMed
Bjarnadottir, M, Misner, DL, Haverfield-Gross, Set al. Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation: differential synaptic function in NRG1+/- knock-outs compared with wild-type mice. J Neurosci 2007;27:45194529. CrossRefGoogle ScholarPubMed
Corfas, G, Roy, K, Buxbaum, JD. Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia. Nat Neurosci 2004;7:575580. CrossRefGoogle ScholarPubMed
O’Tuathaigh, CM, Babovic, D, O’Meara, G, Clifford, JJ, Croke, DT, Waddington, JL. Susceptibility genes for schizophrenia: characterisation of mutant mouse models at the level of phenotypic behaviour. Neurosci Biobehav Rev 2007;31:6078. CrossRefGoogle ScholarPubMed
Karl, T, Duffy, L, Scimone, A, Harvey, RP, Schofield, PR. Altered motor activity, exploration and anxiety in heterozygous neuregulin 1 mutant mice: implications for understanding schizophrenia. Genes Brain Behav 2007;6:677687. CrossRefGoogle ScholarPubMed
Badner, JA, Gershon, ES. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry 2002;7:405411. CrossRefGoogle Scholar
Li, D, Collier, D, He, L. Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet 2006;15:19922002. CrossRefGoogle ScholarPubMed
Stefanis, NC, Trikalinos, TA, Avramopoulos, Det al. Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biol Psychiatry 2007;62:784792. CrossRefGoogle ScholarPubMed
Lang, UE, Jockers-Scherubl, MC, Hellweg, R. State of the art of the neurotrophin hypothesis in psychiatric disorders: implications and limitations. J Neural Transm 2004;111:387411. CrossRefGoogle ScholarPubMed
Takahashi, M, Shirakawa, O, Toyooka, Ket al. Abnormal expression of brain-derived neurotrophic factor and its receptor in the corticolimbic system of schizophrenic patients. Mol Psychiatry 2000;5:293300. CrossRefGoogle ScholarPubMed
Weickert, CS, Hyde, TM, Lipska, BK, Herman, MM, Weinberger, DR, Kleinman, JE. Reduced brain-derived neurotrophic factor in prefrontal cortex of patients with schizophrenia. Mol Psychiatry 2003;8:592610. CrossRefGoogle ScholarPubMed
Ringstedt, T, Linnarsson, S, Wagner, Jet al. BDNF regulates reelin expression and Cajal-Retzius cell development in the cerebral cortex. Neuron 1998;21:305315. CrossRefGoogle ScholarPubMed
Alcantara, S, Pozas, E, Ibanez, CF, Soriano, E. BDNF-modulated spatial organization of Cajal-Retzius and GABAergic neurons in the marginal zone plays a role in the development of cortical organization. Cereb Cortex 2006;16:487499. CrossRefGoogle Scholar
Rice, DS, Curran, T. Role of the reelin signaling pathway in central nervous system development. Annu Rev Neurosci 2001;24:10051039. CrossRefGoogle ScholarPubMed
Angelucci, F, Mathe, AA, Aloe, L. Brain-derived neurotrophic factor and tyrosine kinase receptor TrkB in rat brain are significantly altered after haloperidol and risperidone administration. J Neurosci Res 2000;60:783794. 3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Lipska, BK, Khaing, ZZ, Weickert, CS, Weinberger, DR. BDNF mRNA expression in rat hippocampus and prefrontal cortex: effects of neonatal ventral hippocampal damage and antipsychotic drugs. Eur J Neurosci 2001;14:135144. CrossRefGoogle ScholarPubMed
Tan, YL, Zhou, DF, Cao, LY, Zou, YZ, Zhang, XY. Decreased BDNF in serum of patients with chronic schizophrenia on long-term treatment with antipsychotics. Neurosci Lett 2005;382:2732. CrossRefGoogle ScholarPubMed
Grillo, RW, Ottoni, GL, Leke, R, Souza, DO, Portela, LV, Lara, DR. Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatr Res 2007;41:3135. CrossRefGoogle ScholarPubMed
Gratacos, M, Gonzalez, JR, Mercader, JM, De Cid, R, Urretavizcaya, M, Estivill, X. Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biol Psychiatry 2007;61:911922. CrossRefGoogle Scholar
Zintzaras, E. Brain-derived neurotrophic factor gene polymorphisms and schizophrenia: a meta-analysis. Psychiatr Genet 2007;17:6975. CrossRefGoogle ScholarPubMed
Kanazawa, T, Glatt, SJ, Kia-Keating, B, Yoneda, H, Tsuang, MT. Meta-analysis reveals no association of the Val66Met polymorphism of brain-derived neurotrophic factor with either schizophrenia or bipolar disorder. Psychiatr Genet 2007;17:165170. CrossRefGoogle ScholarPubMed
Rybakowski, JK, Borkowska, A, Skibinska, Met al. Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene. Psychiatry Clin Neurosci 2006;60:7076. CrossRefGoogle ScholarPubMed
Ho, BC, Milev, P, O’Leary, DS, Librant, A, Andreasen, NC, Wassink, TH. Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers. Arch Gen Psychiatry 2006;63:731740. CrossRefGoogle ScholarPubMed
Millar, JK, Wilson-Annan, JC, Anderson, Set al. Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet 2000;9:14151423. CrossRefGoogle ScholarPubMed
Ishizuka, K, Paek, M, Kamiya, A, Sawa, A. A review of Disrupted-In-Schizophrenia-1 (DISC1): neurodevelopment, cognition, and mental conditions. Biol Psychiatry 2006;59:11891197. CrossRefGoogle ScholarPubMed
Brandon, NJ, Handford, EJ, Schurov, Iet al. Disrupted in schizophrenia 1 and nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol Cell Neurosci 2004;25:4255. CrossRefGoogle Scholar
Kamiya, A, Tomoda, T, Chang, Jet al. DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1. Hum Mol Genet 2006;15:33133323. CrossRefGoogle ScholarPubMed
Duan, X, Chang, JH, Ge, Set al. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain. Cell 2007;130:11461158. CrossRefGoogle ScholarPubMed
Roberts, RC. Schizophrenia in translation: disrupted in schizophrenia (DISC1): integrating clinical and basic findings. Schizophr Bull 2007;33:1115. CrossRefGoogle ScholarPubMed
Morris, J, Kandpal, G, Ma, L, Austin, C. DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation. Hum Mol Genet 2003;12:15911608. CrossRefGoogle ScholarPubMed
Millar, JK, Pickard, BS, Mackie, Set al. DISC1 and PDE4B are interacting genetic factors in schizophrenia that regulate cAMP signaling. Science 2005;310:11871191. CrossRefGoogle ScholarPubMed
Liu, YL, Fann, CS, Liu, CMet al. A single nucleotide polymorphism fine mapping study of chromosome 1q42.1 reveals the vulnerability genes for schizophrenia, GNPAT and DISC1: association with impairment of sustained attention. Biol Psychiatry 2006;60:554562. CrossRefGoogle ScholarPubMed
Hennah, W, Tuulio-Henriksson, A, Paunio, Tet al. A haplotype within the DISC1 gene is associated with visual memory functions in families with a high density of schizophrenia. Mol Psychiatry 2005;10:10971103. CrossRefGoogle ScholarPubMed
Benson, MA, Newey, SE, Martin-Rendon, E, Hawkes, R, Blake, DJ. Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. J Biol Chem 2001;276:2423224241. CrossRefGoogle ScholarPubMed
Numakawa, T, Yagasaki, Y, Ishimoto, Tet al. Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Hum Mol Genet 2004;13:26992708. CrossRefGoogle Scholar
Talbot, K, Eidem, WL, Tinsley, CLet al. Dysbindin-1 is reduced in intrinsic, glutamatergic terminals of the hippocampal formation in schizophrenia. J Clin Invest 2004;113:13531363. CrossRefGoogle Scholar
Weickert, CS, Straub, RE, McClintock, BWet al. Human dysbindin (DTNBP1) gene expression in normal brain and in schizophrenic prefrontal cortex and midbrain. Arch Gen Psychiatry 2004;61:544555. CrossRefGoogle ScholarPubMed
Bray, NJ, Preece, A, Williams, NMet al. Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Hum Mol Genet 2005;14:19471954. CrossRefGoogle ScholarPubMed
Guo, AY, Sun, J, Riley, BP, Thiselton, DL, Kendler, KS, Zhao, Z. The dystrobrevin-binding protein 1 gene: features and networks. Mol Psychiatry 2009;14:1829. CrossRefGoogle ScholarPubMed
Donohoe, G, Morris, DW, De Sanctis, Pet al. Early visual processing deficits in dysbindin-associated schizophrenia. Biol Psychiatry 2008;63:484489. CrossRefGoogle ScholarPubMed
Donohoe, G, Morris, DW, Clarke, Set al. Variance in neurocognitive performance is associated with dysbindin-1 in schizophrenia: a preliminary study. Neuropsychologia 2007;45:454458. CrossRefGoogle ScholarPubMed
Burdick, KE, Lencz, T, Funke, Bet al. Genetic variation in DTNBP1 influences general cognitive ability. Hum Mol Genet 2006;15:15631568. CrossRefGoogle ScholarPubMed
Coyle, JT. The glutamatergic dysfunction hypothesis for schizophrenia. Harv Rev Psychiatry 1996;3:241253. CrossRefGoogle Scholar
Clark, M, Johnson, BG, Wright, RA, Monn, JA, Schoepp, DD. Effects of the mGlu2/3 receptor agonist LY379268 on motor activity in phencyclidine-sensitized rats. Pharmacol Biochem Behav 2002;73:339346. CrossRefGoogle ScholarPubMed
Patil, ST, Zhang, L, Martenyi, Fet al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat Med 2007;13:11021107. CrossRefGoogle ScholarPubMed
Harrison, PJ, Lyon, L, Sartorius, LJ, Burnet, PW, Lane, TA. The group II metabotropic glutamate receptor 3 (mGluR3, mGlu3, GRM3): expression, function and involvement in schizophrenia. J Psychopharmacol 2008;22:308322. CrossRefGoogle Scholar
Egan, MF, Straub, RE, Goldberg, TEet al. Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci U S A 2004;101:1260412609. CrossRefGoogle ScholarPubMed
Adler, LE, Hoffer, LJ, Griffith, J, Waldo, MC, Freedman, R. Normalization by nicotine of deficient auditory sensory gating in the relatives of schizophrenics. Biol Psychiatry 1992;32:607616. CrossRefGoogle ScholarPubMed
Adler, LE, Olincy, A, Cawthra, Eet al. Reversal of diminished inhibitory sensory gating in cocaine addicts by a nicotinic cholinergic mechanism. Neuropsychopharmacology 2001;24:671679. CrossRefGoogle ScholarPubMed
Freedman, R, Olincy, A, Ross, RGet al. The genetics of sensory gating deficits in schizophrenia. Curr Psychiatry Rep 2003;5:155161. CrossRefGoogle Scholar
Houy, E, Raux, G, Thibaut, Fet al. The promoter -194 C polymorphism of the nicotinic alpha 7 receptor gene has a protective effect against the P50 sensory gating deficit. Mol Psychiatry 2004;9:320322. CrossRefGoogle Scholar
Martin, LF, Leonard, S, Hall, MH, Tregellas, JR, Freedman, R, Olincy, A. Sensory gating and alpha-7 nicotinic receptor gene allelic variants in schizoaffective disorder, bipolar type. Am J Med Genet B Neuropsychiatr Genet 2007;144:611614. CrossRefGoogle Scholar
McGuffin, P, Asherson, P, Owen, M, Farmer, A. The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia? Br J Psychiatry 1994;164:593599. CrossRefGoogle ScholarPubMed
Clarke, MC, Harley, M, Cannon, M. The role of obstetric events in schizophrenia. Schizophr Bull 2006;32:38. CrossRefGoogle Scholar
Preti, A, Cardascia, L, Zen, T, Marchetti, M, Favaretto, G, Miotto, P. Risk for obstetric complications and schizophrenia. Psychiatry Res 2000;96:127139. CrossRefGoogle Scholar
Dalman, C, Thomas, HV, David, AS, Gentz, J, Lewis, G, Allebeck, P. Signs of asphyxia at birth and risk of schizophrenia. Population-based case-control study. Br J Psychiatry 2001;179:403408. CrossRefGoogle ScholarPubMed
Byrne, M, Agerbo, E, Bennedsen, B, Eaton, WW, Mortensen, PB. Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study. Schizophr Res 2007;97:5159. CrossRefGoogle ScholarPubMed
Cannon, TD, VanErp, TG, Rosso, IMet al. Fetal hypoxia and structural brain abnormalities in schizophrenic patients, their siblings, and controls. Arch Gen Psychiatry 2002;59:3541. CrossRefGoogle ScholarPubMed
Schmidt-Kastner, R, VanOs, J, Steinbusch, HWM, Schmitz, C. Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res 2006;84:253271. CrossRefGoogle ScholarPubMed
Nadri, C, Belmaker, RH, Agam, G. Oxygen restriction of neonate rats elevates neuregulin-1alpha isoform levels: possible relationship to schizophrenia. Neurochem Int 2007;51:447450. CrossRefGoogle Scholar
Nicodemus, KK, Marenco, S, Batten, AJet al. Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 2008;13:873877. CrossRefGoogle ScholarPubMed
Castle, D, Gill, M. Maternal viral infection and schizophrenia. Br J Psychiatry 1992;161:273274. Google Scholar
Limosin, F, Rouillon, F, Payan, C, Cohen, JM, Strub, N. Prenatal exposure to influenza as a risk factor for adult schizophrenia. Acta Psychiatr Scand 2003;107:331335. CrossRefGoogle ScholarPubMed
Fatemi, SH, Cuadra, AE, El-Fakahany, EE, Sidwell, RW, Thuras, P. Prenatal viral infection causes alterations in nNOS expression in developing mouse brains. Neuroreport 2000;11:14931496. CrossRefGoogle ScholarPubMed
Fatemi, SH, Earle, J, Kanodia, Ret al. Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol 2002;22:2533. CrossRefGoogle Scholar
Fatemi, SH, Emamian, ES, Sidwell, RWet al. Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice. Mol Psychiatry 2002;7:633640. CrossRefGoogle ScholarPubMed
Torrey, EF, Leweke, MF, Schwarz, MJet al. Cytomegalovirus and schizophrenia. CNS Drugs 2006;20:879885. CrossRefGoogle Scholar
Leweke, FM, Gerth, CW, Koethe, Det al. Antibodies to infectious agents in individuals with recent onset schizophrenia. Eur Arch Psychiatry Clin Neurosci 2004;254:48. CrossRefGoogle ScholarPubMed
Dickerson, FB, Boronow, JJ, Stallings, CR, Origoni, AE, Yolken, RH. Reduction of symptoms by valacyclovir in cytomegalovirus-seropositive individuals with schizophrenia. Am J Psychiatry 2003;160:22342236. CrossRefGoogle ScholarPubMed
Beraki, S, Aronsson, F, Karlsson, H, Ogren, SO, Kristensson, K. Influenza A virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors in mice. Mol Psychiatry 2005;10:299308. CrossRefGoogle ScholarPubMed
Kim, JJ, Shirts, BH, Dayal, Met al. Are exposure to cytomegalovirus and genetic variation on chromosome 6p joint risk factors for schizophrenia? Ann Med 2007;39:145153. CrossRefGoogle Scholar
Fowler, IL, Carr, VJ, Carter, NT, Lewin, TJ. Patterns of current and lifetime substance use in schizophrenia. Schizophr Bull 1998;24:443455. CrossRefGoogle Scholar
Rabinowitz, J, Bromet, EJ, Lavelle, J, Carlson, G, Kovasznay, B, Schwartz, JE. Prevalence and severity of substance use disorders and onset of psychosis in first-admission psychotic patients. Psychol Med 1998;28:14111419. CrossRefGoogle ScholarPubMed
Swofford, CD, Scheller-Gilkey, G, Miller, AH, Woolwine, B, Mance, R. Double jeopardy: schizophrenia and substance use. Am J Drug Alcohol Abuse 2000;26:343353. CrossRefGoogle ScholarPubMed
Buhler, B, Hambrecht, M, Loffler, W, An DerHeiden, W, Hafner, H. Precipitation and determination of the onset and course of schizophrenia by substance abuse–a retrospective and prospective study of 232 population-based first illness episodes. Schizophr Res 2002;54:243251. CrossRefGoogle ScholarPubMed
Henquet, C, Krabbendam, L, Spauwen, Jet al. Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. BMJ 2005;330:11. CrossRefGoogle ScholarPubMed
McGuire, P, Jones, P, Harvey, I, Williams, M, McGuffin, P, Murray, R. Morbid risk of schizophrenia for relatives of patients with cannabis-associated psychosis. Schizophr Res 1995;15:277281. CrossRefGoogle ScholarPubMed
Caspi, A, Moffitt, TE, Cannon, Met al. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction. Biol Psychiatry 2005;57:11171127. CrossRefGoogle ScholarPubMed
Henquet, C, Rosa, A, Krabbendam, Let al. An experimental study of catechol-o-methyltransferase Val158Met moderation of delta-9-tetrahydrocannabinol-induced effects on psychosis and cognition. Neuropsychopharmacology 2006;31:27482757. CrossRefGoogle ScholarPubMed
Zammit, S, Spurlock, G, Williams, Het al. Genotype effects of CHRNA7, CNR1 and COMT in schizophrenia: interactions with tobacco and cannabis use. Br J Psychiatry 2007;191:402407. CrossRefGoogle ScholarPubMed
Boucher, AA, Arnold, JC, Duffy, L, Schofield, PR, Micheau, J, Karl, T. Heterozygous neuregulin 1 mice are more sensitive to the behavioural effects of Delta9-tetrahydrocannabinol. Psychopharmacology 2007;192:325336. CrossRefGoogle ScholarPubMed
Kishimoto, M, Ujike, H, Motohashi, Yet al. The Dysbindin Gene (DTNBP1) is associated with methamphetamine psychosis. Biol Psychiatry 2008;63:191196. CrossRefGoogle ScholarPubMed
Ventura, J, Nuechterlein, KH, Subotnik, KL, Hardesty, JP, Mintz, J. Life events can trigger depressive exacerbation in the early course of schizophrenia. J Abnorm Psychol 2000;109:139144. CrossRefGoogle ScholarPubMed
Myin-Germeys, I, Peeters, F, Havermans, Ret al. Emotional reactivity to daily life stress in psychosis and affective disorder: an experience sampling study. Acta Psychiatr Scand 2003;107:124131. CrossRefGoogle ScholarPubMed
Myin-Germeys, I, VanOs, J. Stress-reactivity in psychosis: evidence for an affective pathway to psychosis. Clin Psychol Rev 2007;27:409424. CrossRefGoogle ScholarPubMed
Stefanis, NC, Henquet, C, Avramopoulos, Det al. COMT Val158Met moderation of stress-induced psychosis. Psychol Med 2007;37:16511656. CrossRefGoogle ScholarPubMed
van Winkel, R, Henquet, C, Rosa, Aet al. Evidence that the COMT(Val158Met) polymorphism moderates sensitivity to stress in psychosis: an experience-sampling study. Am J Med Genet B Neuropsychiatr Genet 2008;147B:1017. CrossRefGoogle Scholar
Kendler, KS, Eaves, LJ. Models for the joint effect of genotype and environment on liability to psychiatric illness. Am J Psychiatry 1986;143:279289. Google ScholarPubMed
Uranova, NA, Vostrikov, VM, Vikhreva, OV, Zimina, IS, Kolomeets, NS, Orlovskaya, DD. The role of oligodendrocyte pathology in schizophrenia. Int J Neuropsychopharmacol 2007;10:537545. CrossRefGoogle Scholar
Dwork, AJ, Mancevski, B, Rosoklija, G. White matter and cognitive function in schizophrenia. Int J Neuropsychopharmacol 2007;10:513536. CrossRefGoogle Scholar
Schlaepfer, TE, Lancaster, E, Heidbreder, Ret al. Decreased frontal white-matter volume in chronic substance abuse. Int J Neuropsychopharmacol 2006;9:147153. CrossRefGoogle ScholarPubMed
Kumra, S. Schizophrenia and cannabis use. Minn Med 2007;90:3638. Google ScholarPubMed
Doane, JA. Family interaction and communication deviance in disturbed and normal families: a review of research. Fam Process 1978;17:357376. CrossRefGoogle ScholarPubMed
Miklowitz, DJ, Stackman, D. Communication deviance in families of schizophrenic and other psychiatric patients: current state of the construct. Prog Exp Pers Psychopathol Res 1992;15:146. Google ScholarPubMed
Velligan, DI, Mahurin, RK, Eckert, SL, Hazleton, BC, Miller, A. Relationship between specific types of communication deviance and attentional performance in patients with schizophrenia. Psychiatry Res 1997;70:920. CrossRefGoogle ScholarPubMed
Wahlberg, KE, Wynne, LC, Oja, Het al. Gene-environment interaction in vulnerability to schizophrenia: findings from the Finnish Adoptive Family Study of Schizophrenia. Am J Psychiatry 1997;154:355362. Google ScholarPubMed
Wahlberg, KE, Wynne, LC, Hakko, Het al. Interaction of genetic risk and adoptive parent communication deviance: longitudinal prediction of adoptee psychiatric disorders. Psychol Med 2004;34:15311541. CrossRefGoogle ScholarPubMed
Subotnik, KL, Goldstein, MJ, Nuechterlein, KH, Woo, SM, Mintz, J. Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia? Schizophr Bull 2002;28:719729. CrossRefGoogle Scholar
Phillips, LJ, Yung, AR, McGorry, PD. Identification of young people at risk of psychosis: validation of Personal Assessment and Crisis Evaluation Clinic intake criteria. Aust N Z J Psychiatry 2000;34(Suppl):S164S169. CrossRefGoogle ScholarPubMed
McGorry, PD, Yung, AR, Phillips, LJ. The “close-in” or ultra high-risk model: a safe and effective strategy for research and clinical intervention in prepsychotic mental disorder. Schizophr Bull 2003;29:771790. CrossRefGoogle ScholarPubMed
Yung, AR, Phillips, LJ, Yuen, HPet al. Psychosis prediction: 12-month follow up of a high-risk (“prodromal”) group. Schizophr Res 2003;60:2132. CrossRefGoogle ScholarPubMed
Amminger, GP, Leicester, S, Yung, ARet al. Early-onset of symptoms predicts conversion to non-affective psychosis in ultra-high risk individuals. Schizophr Res 2006;84:6776. CrossRefGoogle ScholarPubMed
Cannon, TD, Cornblatt, B, McGorry, P. The empirical status of the ultra high-risk (prodromal) research paradigm. Schizophr Bull 2007;33:661664. CrossRefGoogle ScholarPubMed
Rentzsch, J, Penzhorn, A, Kernbichler, Ket al. Differential impact of heavy cannabis use on sensory gating in schizophrenic patients and otherwise healthy controls. Exp Neurol 2007;205:241249. CrossRefGoogle ScholarPubMed
Patrick, G, Struve, FA. Reduction of auditory P50 gating response in marihuana users: further supporting data. Clin Electroencephalogr 2000;31:8893. CrossRefGoogle ScholarPubMed
Patrick, G, Straumanis, JJ, Struve, FA, Fitz-Gerald, MJ, Leavitt, J, Manno, JE. Reduced P50 auditory gating response in psychiatrically normal chronic marihuana users: a pilot study. Biol Psychiatry 1999;45:13071312. CrossRefGoogle ScholarPubMed
Oranje, B, Van Oel, CJ, Gispen-De Wied, CC, Verbaten, MN, Kahn, RS. Effects of typical and atypical antipsychotics on the prepulse inhibition of the startle reflex in patients with schizophrenia. J Clin Psychopharmacol 2002;22:359365. CrossRefGoogle ScholarPubMed
Donohoe, G, Corvin, A, Robertson, IH. Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile. Cogn Neuropsychiatry 2006;11:1332. CrossRefGoogle ScholarPubMed
Cameron, AM, Oram, J, Geffen, GM, Kavanagh, DJ, McGrath, JJ, Geffen, LB. Working memory correlates of three symptom clusters in schizophrenia. Psychiatry Res 2002;110:4961. CrossRefGoogle Scholar
Daban, C, Amado, I, Bayle, Fet al. Disorganization syndrome is correlated to working memory deficits in unmedicated schizophrenic patients with recent onset schizophrenia. Schizophr Res 2003;61:323324. CrossRefGoogle ScholarPubMed
Hofer, A, Baumgartner, S, Bodner, Tet al. Patient outcomes in schizophrenia II: the impact of cognition. Eur Psychiatry 2005;20:395402. CrossRefGoogle ScholarPubMed
Prouteau, A, Verdoux, H, Briand, Cet al. Cognitive predictors of psychosocial functioning outcome in schizophrenia: a follow-up study of subjects participating in a rehabilitation program. Schizophr Res 2005;77:343353. CrossRefGoogle Scholar
Milev, P, Ho, BC, Arndt, S, Andreasen, NC. Predictive values of neurocognition and negative symptoms on functional outcome in schizophrenia: a longitudinal first-episode study with 7-year follow-up. Am J Psychiatry 2005;162:495506. CrossRefGoogle ScholarPubMed
Stirling, J, White, C, Lewis, Set al. Neurocognitive function and outcome in first-episode schizophrenia: a 10-year follow-up of an epidemiological cohort. Schizophr Res 2003;65:7586. CrossRefGoogle ScholarPubMed
Martinez-Aran, A, Penades, R, Vieta, Eet al. Executive function in patients with remitted bipolar disorder and schizophrenia and its relationship with functional outcome. Psychother Psychosom 2002;71:3946. CrossRefGoogle ScholarPubMed
Green, MF, Kern, RS, Heaton, RK. Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS. Schizophr Res 2004;72:4151. CrossRefGoogle ScholarPubMed
Peuskens, J, Demily, C, Thibaut, F. Treatment of cognitive dysfunction in schizophrenia. Clin Ther 2005;27(Suppl A):S25S37. CrossRefGoogle Scholar
Kasper, S, Resinger, E. Cognitive effects and antipsychotic treatment. Psychoneuroendocrinology 2003;28(Suppl 1):2738. CrossRefGoogle ScholarPubMed
Weiss, EM, Bilder, RM, Fleischhacker, WW. The effects of second-generation antipsychotics on cognitive functioning and psychosocial outcome in schizophrenia. Psychopharmacology (Berl) 2002;162:1117. CrossRefGoogle Scholar
Woodward, N, Purdon, S, Meltzer, H, Zald, D. A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol 2005;8:457472. CrossRefGoogle Scholar
Green, M. Cognitive remediation in schizophrenia: is it time yet? Am J Psychiatry 1993;150:178187. Google ScholarPubMed
McGurk, SR, Twamley, EW, Sitzer, DI, McHugo, GJ, Mueser, KT. A meta-analysis of cognitive remediation in schizophrenia. Am J Psychiatry 2007;164:17911802. CrossRefGoogle Scholar
Wykes, T, Van DerGaag, M. Is it time to develop a new cognitive therapy for psychosis–cognitive remediation therapy (CRT)? Clin Psychol Rev 2001;21:12271256. CrossRefGoogle ScholarPubMed
Bosia, M, Bechi, M, Marino, Eet al. Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia. Neurosci Lett 2007;417:271274. CrossRefGoogle Scholar