Skip to main content

Advertisement

SpringerLink
Log in

Neurodegenerative Aspects in Vulnerability to Schizophrenia Spectrum Disorders

  • Review
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

The neurodegenerative and neurotoxic aspects of schizophrenia and/or psychosis involve genetic, epigenetic, and neurotoxic propensities that impinge upon both the symptom domains and the biomarkers of the disorder, involving cellular apoptosis/excitotoxicity, increased reactive oxygen species formation, viral and bacterial infections, anoxic birth injury, maternal starvation, drugs of abuse, particularly cannabis, metabolic accidents, and other chemical agents that disrupt normal brain development or the integrity of brain tissues. Evidence for premorbid and prodromal psychotic phases, aspects of neuroimaging, dopamine, and psychosis vulnerability, and perinatal aspects provide substance for neurodegenerative influences. Not least, the agencies of antipsychotic contribute to the destructive spiral that disrupts normal structure and function. The etiopathogenesis of psychosis is distinguished also by disruptions of the normal functioning of the neurotrophins, in particular brain-derived neurotrophic factor, dyskinesic aspects, immune system disturbances, and metabolic aspects. Whether detrimental to neurodevelopment or tissue-destructive, or an acceleration of neurotoxic pathways, the notion of neurodegeneration in the pathophysiology of schizophrenia spectrum and psychotic disorders continues to gather momentum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adell A, Jiménez-Sánchez L, López-Gil X, Romón T (2012) Is the acute NMDA receptor hypofunction a valid model of schizophrenia? Schizophr Bull 38:9–14

    PubMed  PubMed Central  Google Scholar 

  • Altar CA, Cai N, Bliven T, Juhasz M, Conner JM et al (1997) Anterograde transport of brain-derived neurotrophic factor and its role in the brain. Nature 389:856–860

    PubMed  CAS  Google Scholar 

  • Aoyama N, Théberge J, Drost DJ, Manchanda R, Northcott S, Neufeld RW, Menon RS, Rajakumar N, Pavlosky WF, Densmore M, Schaefer B, Williamson PC (2011) Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia. Br J Psychiatry 198(6):448–456. doi:10.1192/bjp.bp.110.079608

    PubMed  Google Scholar 

  • Aoyama Y, Mouri A, Toriumi K, Koseki T, Narusawa S, Ikawa N, Mamiya T, Nagai T, Yamada K, Nabeshima T (2013) Clozapine ameliorates epigenetic and behavioral abnormalities induced by phencyclidine through activation of dopamine D1 receptor. Int J Neuropsychopharmacol 17:1–15

    Google Scholar 

  • Arango C, Fraguas D, Parellada M (2013) Differential neurodevelopmental trajectories in patients with early-onset bipolar and schizophrenia disorders. Schizophr Bull 40(Suppl 2):S138–S146

    PubMed  Google Scholar 

  • Archer T (2010) Neurodegeneration in schizophrenia. Expert Rev Neurother 10:1131–1141

    PubMed  Google Scholar 

  • Archer T, Kostrzewa RM, Beninger RJ, Palomo T (2010a) Staging perspectives in neurodevelopmental aspects of neuropsychiatry: agents, phases and ages at expression. Neurotox Res 18:287–305

    PubMed  CAS  Google Scholar 

  • Archer T, Kostrzewa RM, Palomo T, Beninger RJ (2010b) Clinical staging in the pathophysiology of psychotic and affective disorders: facilitation of prognosis and treatment. Neurotox Res 18:211–228

    PubMed  Google Scholar 

  • Avila J, Lucas JJ, Perez M, Hernandez F (2004) Role of tau protein in both physiological and pathological conditions. Physiol Rev 84:361–384

    PubMed  CAS  Google Scholar 

  • Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K et al (2009) Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390:191–214

    PubMed  CAS  PubMed Central  Google Scholar 

  • Barbeito S, Vega P, Ruiz de Azúa S, Saenz M, Martinez-Cengotitabengoa M, González-Ortega I, Bermudez C, Hernanz M, Corres BF, González-Pinto A (2013) Cannabis use and involuntary admission may mediate long-term adherence in first-episode psychosis patients: a prospective longitudinal study. BMC Psychiatry 13(1):326. doi:10.1186/1471-244X-13-326

    PubMed  PubMed Central  Google Scholar 

  • Berger Z, Ttofi EK, Michel CH, Pasco MY, Tenant S et al (2005) Lithium rescues toxicity of aggregate-prone proteins in Drosophila by perturbing Wnt pathway. Hum Mol Genet 14:3003–3011

    PubMed  CAS  Google Scholar 

  • Bergink V, Burgerhout KM, Weigelt K, Pop VJ, de Wit H, Drexhage RC, Kushner SA, Drexhage HA (2013a) Immune system dysregulation in first-onset postpartum psychosis. Biol Psychiatry 73(10):1000–1007. doi:10.1016/j.biopsych.2012.11.006

    PubMed  CAS  Google Scholar 

  • Bergink V, Gibney SM, Drexhage HA (2013b) Autoimmunity, inflammation and psychosis: a search for peripheral markers. Biol Psychiatry. doi:10.1016/j.biopsych.2013.09.037

    Google Scholar 

  • Bergman O, Westberg L, Lichtenstein P, Eriksson E, Larsson H (2011) Study on the possible association of brain-derived neurotrophic factor polymorphism with the developmental course of symptoms of attention deficit and hyperactivity. Int J Neuropsychopharmacol 14:1367–1376

    PubMed  CAS  Google Scholar 

  • Bloemer J, Bhattacharya S, Amin R, Suppiramaniam V (2014) Impaired insulin signaling and mechanisms of memory loss. Prog Mol Biol Transl Sci 121:413–449. doi:10.1016/B978-0-12-800101-1.00013-2

    PubMed  CAS  Google Scholar 

  • Borgwardt SJ, Radue EW, Gotz K, Aston J, Drewe M, Gschwandtner U, Haller S, Pfluger M, Stieglitz RD, McGuire PK, Riecher-Rossler A (2006) Radiological findings in individuals at high risk of psychosis. J Neurol Neurosurg Psychiatry 77(2):229–233

    PubMed  CAS  PubMed Central  Google Scholar 

  • Borgwardt SJ, Riecher-Rossler A, Dazzan P, Chitnis X, Aston J, Drewe M, Gschwandtner U, Haller S, Pfluger M, Rechsteiner E, D’Souza M, Stieglitz RD, Radu EW, McGuire PK (2007) Regional gray matter volume abnormalities in the at risk mental state. Biol Psychiatry 61(10):1148–1156

    PubMed  Google Scholar 

  • Borgwardt S, Smieskova R, Bendfeldt K, Buhlmann E, Berger G, Aston J, Gschwandtner U, Pflueger M, Stieglitz RD, Riecher-Rossler A, Radue EW (2010) Hippocampal volume reduction specific for later transition to psychosis or substance-associated effects? J Psychiatry Neurosci 35(3):214–215 author reply 215

    PubMed  PubMed Central  Google Scholar 

  • Borgwardt S, McGuire P, Fusar-Poli P (2011) Gray matters!–mapping the transition to psychosis. Schizophr Res 133(1–3):63–67

    PubMed  Google Scholar 

  • Borovcanin M, Jovanovic I, Radosavljevic G, Djukic Dejanovic S, Bankovic D, Arsenijevic N, Lukic ML (2012) Elevated serum level of type-2 cytokine and low IL-17 in first episode psychosis and schizophrenia in relapse. J Psychiatr Res 46(11):1421–1426. doi:10.1016/j.jpsychires.2012.08.016

    PubMed  Google Scholar 

  • Borovcanin M, Jovanovic I, Radosavljevic G, Djukic Dejanovic S, Stefanovic V, Arsenijevic N, Lukic ML (2013) Antipsychotics can modulate the cytokine profile in schizophrenia: attenuation of the type-2 inflammatory response. Schizophr Res 147(1):103–109. doi:10.1016/j.schres.2013.03.027

    PubMed  Google Scholar 

  • Bosia M, Buonocure M, Guglielmino C, Pirovana A, Lorenzi C et al (2011) Saitohin polymorphism and executive dysfunction in schizophrenia. Neurol Sci. doi:10.1007/s10072-0893-9

    PubMed  Google Scholar 

  • Bossong MG, Jansma JM, Bhattacharyya S, Ramsey NF (2013) Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or ∆9-tetrahydrocannabinol (THC). Prog Neuropsychopharmacol Biol Psychiatry. doi:10.1016/j.pnpbp.2013.11.017

    PubMed  Google Scholar 

  • Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263–1271

    PubMed  Google Scholar 

  • Brown AM, Baltan Tekkok S, Ransom BR (2003) Glycogen regulation and functional role in mouse white matter. J Physiol 549:501–512

    PubMed  CAS  PubMed Central  Google Scholar 

  • Buehlmann E, Berger GE, Aston J, Gschwandtner U, Pflueger MO, Borgwardt SJ, Radue EW, Riecher-Rössler A (2010) Hippocampus abnormalities in at risk mental states for psychosis? A cross-sectional high resolution region of interest magnetic resonance imaging study. J Psychiatr Res 44(7):447–453. doi:10.1016/j.jpsychires.2009.10.008

    PubMed  Google Scholar 

  • Burd I, Balakrishnan B, Kannan S (2012) Models of fetal brain injury, intrauterine inflammation, and preterm birth. Am J Reprod Immunol 67:287–294. doi:10.1111/j.1600-0897.2012.01110.x

    PubMed  CAS  Google Scholar 

  • Büschlen J, Berger GE, Borgwardt SJ, Aston J, Gschwandtner U, Pflueger MO, Kuster P, Radü EW, Stieglitz RD, Riecher-Rössler A (2011) Pituitary volume increase during emerging psychosis. Schizophr Res 125(1):41–48. doi:10.1016/j.schres.2010.09.022

    PubMed  Google Scholar 

  • Bustillo JR, Rowland LM, Mullins P, Jung R, Chen H, Qualls C, Hammond R, Brooks WM, Lauriello J (2010) 1H-MRS at 4 tesla in minimally treated early schizophrenia. Mol Psychiatry 15:629–636

    PubMed  CAS  PubMed Central  Google Scholar 

  • Cannon M, Caspi A, Moffitt TE (2002a) Evidence for early, specific, pandevelopment impairment in schizophreniform disorder: results from a longitudinal birth cohort. Arch Gen Psychiatry 59:449–456

    PubMed  Google Scholar 

  • Cannon M, Murray RM, Jones P (2002b) Obstetric complications and schizophrenia: past, present and future. Am J Psychiatry 159:1080–1092

    PubMed  Google Scholar 

  • Chen S, Hillman DE (1986) Selective ablation of neurons by methylazoxymethanol during pre- and postnatal brain development. Exp Neurol 94:103–119

    PubMed  CAS  Google Scholar 

  • Chen CC, Huang TL (2011) Effects of antipsychotics on the serum BDNF levels in schizophrenia. Psychiatry Res 189:327–330

    PubMed  CAS  Google Scholar 

  • Chen S, Broqueres-You D, Yang G, Wang Z, Li Y, Wang N, Zhang X, Yang F, Tan Y (2013) Relationship between insulin resistance, dyslipidemia and positive symptom in Chinese antipsychotic-naive first-episode patients with schizophrenia. Psychiatry Res 210(3):825–829. doi:10.1016/j.psychres.2013.08.056

    PubMed  CAS  Google Scholar 

  • Chew LJ, Fusar-Poli P, Schmitz T (2013) Oligodendroglial alterations and the role of microglia in white matter injury: relevance to schizophrenia. Dev Neurosci 35(2–3):102–129. doi:10.1159/000346157

    PubMed  CAS  Google Scholar 

  • Ciani E, Frenquelli M, Contestabile A (2003) Developmental expression of the cell cycle and apoptosis controlling gene, Lotl, in the rat cerebellum and in cerebellar granule cells. Brain Res Dev Brain Res 142:193–202

    PubMed  CAS  Google Scholar 

  • Combarros O, Rodero L, Infante J, Palacio E, Llorca J, Fernández-Viadero C, Peña N, Berciano J (2003) Age-dependent association between the Q7R polymorphism in the Saitohin gene and sporadic Alzheimer’s disease. Dement Geriatr Cogn Disord 16:132–135

    PubMed  CAS  Google Scholar 

  • Correll CU, Schenk EM (2008) Tardive dyskinesias and new antipsychotics. Curr Opin Psychiatry 21:151–156

    PubMed  Google Scholar 

  • Crossley NA, Mechelli A, Fusar-Poli P, Broome MR, Matthiasson P, Johns LC, Bramon E, Valmaggia L, Williams SC, McGuire PK (2009) Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first-episode psychosis. Hum Brain Mapp 30(12):4129–4137

    PubMed  Google Scholar 

  • Dauvermann MR, Mukherjee P, Moorhead WT, Stanfield AC, Fusar-Poli P, Lawrie SM, Whalley HC (2012) Relationship between gyrification and functional connectivity of the prefrontal cortex in subjects at high genetic risk of schizophrenia. Curr Pharm Des 18(4):434–442

    PubMed  CAS  Google Scholar 

  • Dauvermann MR, Whalley HC, Romaniuk L, Valton V, Owens DG, Johnstone EC, Lawrie SM, Moorhead TW (2013) The application of nonlinear Dynamic Causal Modelling for fMRI in subjects at high genetic risk of schizophrenia. Neuroimage 73:16–29. doi:10.1016/j.neuroimage.2013.01.063

    PubMed  Google Scholar 

  • Davis GP, Compton MT, Wang S, Levin FR, Blanco C (2013) Association between cannabis use, psychosis, and schizotypal personality disorder: findings from the National Epidemiologic Survey on Alcohol and Related Conditions. Schizophr Res 151(1–3):197–202. doi:10.1016/j.schres.2013.10.018

    PubMed  Google Scholar 

  • de la Monte SM, Tong M (2013) Brain metabolic dysfunction at the core of Alzheimer’s disease. Biochem Pharmacol. doi:10.1016/j.bcp.2013.12.012

    Google Scholar 

  • Dean OM, van den Buuse M, Berk M, Copolov DL, Mavros C, Bush AI (2011) N-acetyl cysteine restores brain glutathione loss in combined 2-cyclohexene-1-one and D-amphetamine-treated rats: relevance to schizophrenia and bipolar disorder. Neurosci Lett 499:149–153

    PubMed  CAS  Google Scholar 

  • Deutsch SI, Rosse RB, Lakshman RM (2006) Dysregulation Prog Neuropsychopharmacol Biol Psychiatry. 30(8):1369–80. of tau phosphorylation is a hypothesized point of convergence in the pathogenesis of alzheimer’s disease, frontotemporal dementia and schizophrenia with therapeutic implications

  • Di Forti M, Sallis H, Allegri F, Trotta A, Ferraro L, Stilo SA, Marconi A, La Cascia C, Reis Marques T, Pariante C, Dazzan P, Mondelli V, Paparelli A, Kolliakou A, Prata D, Gaugrhan F, David AS, Morgan C, Sthal D, Khondoker M, Maccabe JH, Murray RM (2013) Daily use, especially of high-potency cannabis, drives the earlier onset of psychosis in cannabisUsers. Schizophr Bull

  • Di Nicola M, Cattaneo A, Hepgul N, Di Forti M, Aitchison KJ, Janiri L, Murray RM, Dazzan P, Pariante CM, Mondelli V (2013) Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun 31:90–95. doi:10.1016/j.bbi.2012.06.010

    PubMed  PubMed Central  Google Scholar 

  • Dimitrov DH, Lee S, Yantis J, Valdez C, Paredes RM, Braida N, Velligan D, Walss-Bass C (2013) Differential correlations between inflammatory cytokines and psychopathology in veterans with schizophrenia: potential role for IL-17 pathway. Schizophr Res 151(1–3):29–35. doi:10.1016/j.schres.2013.10.019

    PubMed  Google Scholar 

  • Do KQ, Cabungal JH, Frank A, Steullet P, Cuenod M (2009) Redox dysregulation, neurodevelopment and schizophrenia. Curr Opin Neurobiol 19:220–230

    PubMed  CAS  Google Scholar 

  • Dringen R, Hirrlinger J (2003) Glutathione pathways in the brain. Biol Chem 384:505–516

    PubMed  CAS  Google Scholar 

  • Egerton A, Chaddock CA, Winton-Brown TT, Bloomfield MA, Bhattacharyya S, Allen P, McGuire PK, Howes OD (2013) Presynaptic striatal dopamine dysfunction in people at ultra-high risk for psychosis: findings in a second cohort. Biol Psychiatry 74(2):106–112. doi:10.1016/j.biopsych.2012.11.017

    PubMed  CAS  Google Scholar 

  • Elia J, Laracy S, Allen J, Nissley-Tsiopinis J, Borgmann-Winter K (2011) Epigenetics: genetics versus life experiences. Curr Topics Behav Neurosci. doi:10.1007/7854_2011_144

    Google Scholar 

  • Ellenbroek BA, van den Kroonenberg PT, Cools AR (1998) The effects of an early stressful life event on sensorimotor gating in adult rats. Schizophr Res 30:251–260

    PubMed  CAS  Google Scholar 

  • Ellman LM, Yolken RH, Buka SL, Torrey EF, Cannon TD (2009) Cognitive functioning prior to the onset of psychosis: the role of fetal exposure to serologically determined influenza infection. Biol Psychiatry 65(12):1040–1047. doi:10.1016/j.biopsych.2008.12.015

    PubMed  PubMed Central  Google Scholar 

  • Emamian ES, Hall D, Birnbaum MJ, Karayiorgou M, Gogos JA (2004) Convergent evidence for impaired AKT1-GSK3 signaling in schizophrenia. Nat Genet 36:131–137

    PubMed  CAS  Google Scholar 

  • Faizi M, Salimi A, Rasoulzadeh M, Naserzadeh P, Pourahmad J (2014) Schizophrenia induces oxidative stress and cytochrome C release in isolated rat brain mitochondria: a possible pathway for induction of apoptosis and neurodegeneration. Iran J Pharm Res 13(Suppl):93–100

    PubMed  CAS  PubMed Central  Google Scholar 

  • Favalli G, Li J, Belmonte-de-Abreu P, Wong AH, Daskalakis ZJ (2012) The role of BDNF in the pathophysiology and treatment of schizophrenia. J Psychiatr Res 46:1–11

    PubMed  Google Scholar 

  • Featherstone RE, Rizos Z, Nobrega JN, Kapur S, Fletcher PJ (2007) Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia. Neuropsychopharmacology 32:483–492

    PubMed  CAS  Google Scholar 

  • Ferrer I, Pozas E, Marti M, Blanco R, Planas AM (1997) Methylazoxymethanol-induced apoptosis in the external granule cell layer of the developing cerebellum of the rat is associated with strong c-jun expression and formation of high molecular weight c-jun complexes. J Neuropathol Exp Neurol 56:1–9

    PubMed  CAS  Google Scholar 

  • Fiore M, Grace AA, Korf J, Stampachiacchiere B, Aloe L (2004) Impaired brain development in the rat following prenatal exposure to methylazoxymethanol acetate at gestational day 17 and neurotrophin distribution. NeuroReport 15(11):1791–1795

    PubMed  CAS  Google Scholar 

  • Flagstad P, Glenthoj BY, Didriksen M (2005) Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia. Neuropsychopharmacology 30:250–260

    PubMed  Google Scholar 

  • Foley DL, Mackinnon A, Watts GF, Shaw JE, Magliano DJ, Castle DJ, McGrath JJ, Waterreus A, Morgan VA, Galletly CA (2013) Cardiometabolic risk indicators that distinguish adults with psychosis from the general population, by age and gender. PLoS ONE 8(12):e82606. doi:10.1371/journal.pone.0082606

    PubMed  PubMed Central  Google Scholar 

  • Fontes MA, Bolla KI, Cunha PJ, Almeida PP, Jungerman F, Laranjeira RR, Bressan RA, Lacerda AL (2011) Cannabis use before age 15 and subsequent executive functioning. Br J Psychiatry 198:442–447

    PubMed  Google Scholar 

  • Furukawa T, Mizukawa R, Hirai T, Fujihara S, Kitamura T, Takahashi K (1998) Childhood parental loss and schizophrenia: evidence against pathogens but for some pathoplastic effects. Psychiatry Res 81:353–362

    PubMed  CAS  Google Scholar 

  • Fusar-Poli P, Meyer-Lindenberg A (2013a) Striatal presynaptic dopamine in schizophrenia, part I: meta-analysis of dopamine active transporter (DAT) density. Schizophr Bull 39(1):22–32. doi:10.1093/schbul/sbr111

    PubMed  PubMed Central  Google Scholar 

  • Fusar-Poli P, Meyer-Lindenberg A (2013b) Striatal presynaptic dopamine in schizophrenia, part II: meta-analysis of [18F]/[11C] DOPA PET studies. Schizophr Bull 39(1):33–42. doi:10.1093/schbul/sbr180

    PubMed  PubMed Central  Google Scholar 

  • Fusar-Poli P, Perez J, Broome M, Borgwardt S, Placentino A, Caverzasi E, Cortesi M, Veggiotti P, Politi P, Barale F, McGuire P (2007) Neurofunctional correlates of vulnerability to psychosis: a systematic review and meta-analysis. Neurosci Biobehav Rev 31(4):465–484

    PubMed  Google Scholar 

  • Fusar-Poli P, Howes OD, Allen P, Broome M, Valli I, Asselin MC, Grasby PM, McGuire PK (2010) Abnormal frontostriatal interactions in people with prodromal signs of psychosis: a multimodal imaging study. Arch Gen Psychiatry 67(7):683–691. doi:10.1001/archgenpsychiatry.2010.77

    PubMed  Google Scholar 

  • Fusar-Poli P, Borgwardt S, Crescini A, D’Este G, Kempton M, Lawrie S, Guire PM, Sacchetti E (2011a) Neuroanatomy of vulnerability to psychosis: a voxel-based meta-analysis. Neurosci Biobehav Rev 35(5):1175–1185

    PubMed  CAS  Google Scholar 

  • Fusar-Poli P, Stone JM, Broome MR, Valli I, Mechelli A, McLean MA, Lythgoe DJ, O’Gorman RL, Barker GJ, McGuire PK (2011b) Thalamic glutamate levels as a predictor of cortical response during executive functioning in subjects at high risk for psychosis. Arch Gen Psychiatry 68(9):881–890. doi:10.1001/archgenpsychiatry.2011.46

    PubMed  CAS  Google Scholar 

  • Fusar-Poli P, Howes OD, Allen P, Broome M, Valli I, Asselin MC, Montgomery AJ, Grasby PM, McGuire P (2011c) Abnormal prefrontal activation directly related to pre-synaptic striatal dopamine dysfunction in people at clinical high risk for psychosis. Mol Psychiatry 16(1):67–75

    PubMed  CAS  Google Scholar 

  • Fusar-Poli P, Bonoldi I, Yung AR, Borgwardt S, Kempton M, Barale F, Caverzasi E, McGuire P (2012a) Predicting psychosis: a meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiatry 69(3):1–10

    Google Scholar 

  • Fusar-Poli P, Deste G, Smieskova R, Barlati G, Yung AR, Howes O, Stieglitz R, McGuire P, Borgwardt S (2012b) Cognitive functioning in prodromal psychosis: a meta-analysis. Arch Gen Psychiatry 69(6):562–571. doi:10.1001/archgenpsychiatry.2011.1592

    PubMed  Google Scholar 

  • Fusar-Poli P, Borgwardt S, Bechdolf A, Addington J, Riecher-Rössler A, Schultze-Lutter F, Keshavan M, Wood S, Ruhrmann S, Seidman L, Valmaggia L, Cannon T, Velthorst E, De Haan L, Cornblatt B, Birchwood M, McGlashan T, Carpenter W, McGorry P, Klosterkötter J, McGuire P, Yung A (2013a) The psychosis high risk state: a comprehensive state of the art review. Arch Gen Psychiatry 70(1):107–120. doi:10.1001/jamapsychiatry.2013.269

    Google Scholar 

  • Fusar-Poli P, Smieskova R, Kempton MJ, Ho BC, Andreasen NC, Borgwardt S (2013b) Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies. Neurosci Biobehav Rev. doi:10.1016/j.neubiorev.2013.06.001

    PubMed  PubMed Central  Google Scholar 

  • Fusar-Poli P, Bechdolf A, Taylor M, Bonoldi I, Carpenter W, Yung A, McGuire P (2013c) At risk for schizophrenic or affective psychosis? A meta-analysis of ICD/DSM diagnostic outcomes in individuals at high clinical risk. Schizophr Bull 39(4):923–932. doi:10.1093/schbul/sbs060

    PubMed  PubMed Central  Google Scholar 

  • Galletly CA, Foley DL, Waterreus A, Watts GF, Castle DJ, McGrath JJ, Mackinnon A, Morgan VA (2012) Cardiometabolic risk factors in people with psychotic disorders: the second Australian national survey of psychosis. Aust N Z J Psychiatry 46(8):753–761. doi:10.1177/0004867412453089

    PubMed  Google Scholar 

  • Garakani A, Welch AK, Jaffe RJ, Protin CA, McDowell DM (2013) Psychosis and low cyanocobalamin in a patient abusing nitrous oxide and cannabis. Psychosomatics. doi:10.1016/j.psym.2013.11.001

    PubMed  Google Scholar 

  • Geddes JR, Verdoux H, Takei N (1999) Schizophrenia and complications of pregnancy and labour: an individual patient data meta-analysis. Schizophrenia Bull 25:413–423

    CAS  Google Scholar 

  • Ghasemi R, Dargahi L, Haeri A, Moosavi M, Mohamed Z, Ahmadiani A (2012) Brain insulin dysregulation: implication for neurological and neuropsychiatric disorders. Mol Neurobiol 47(3):1045–1065. doi:10.1007/s12035-013-8404-z

    Google Scholar 

  • Gibbs ME, Anderson DG, Hertz L (2006) Inhibition of glycogenolysis in astrocytes interrupts memory consolidation in young chickens. Glia 54:214–222

    PubMed  Google Scholar 

  • Gill KE, Poe L, Azimov N, Ben-David S, Vadhan NP, Girgis R, Moore H, Cressman V, Corcoran CM (2013) Reasons for cannabis use among youths at ultra high risk for psychosis. Early Interv Psychiatry. doi:10.1111/eip.12112

    PubMed  Google Scholar 

  • Goldman AL, Pezawas L, Mattay VS, Fischl B, Verchinski BA, Chen Q, Weinberger DR, Meyer-Lindenberg A (2009) Widespread reductions of cortical thickness in schizophrenia and spectrum disorders and evidence of heritability. Arch Gen Psychiatry 66:467–477

    PubMed  PubMed Central  Google Scholar 

  • Gomez-Sintes R, Hernandez F, Lucas JJ, Avila J (2011) GSK-3 mouse models to study neuronal apoptosis and neurodegeneration. Fron Mol Neurosci 4:1–11. doi:10.3389/fnmol.2011.00045

    Google Scholar 

  • Goto Y, Grace AA (2006) Alterations in medial prefrontal cortical activity and plasticity in rats with disruption of cortical development. Boil psychiatry 60:1259–1267

    Google Scholar 

  • Goto N, Yoshimura R, Kakeda S, Moriya J, Hayashi K, Ikenouchi-Sugita A, Umene-Nakano W, Hori H, Ueda N, Korogi Y, Nakamura J (2010) Comparison of brain N-acetylaspartate levels and serum brain-derived neurotrophic factor (BDNF) levels between patients with first-episode schizophrenia psychosis and healthy controls. Eur Psychiatry 26:57–63

    Google Scholar 

  • Gourevitch R, Rocher C, Le Pen G, Krebs MO, Jay TM (2004) Working memory deficits in adult rats after prenatal disruption of neurogenesis. Behav Pharmacol 15:287–292

    PubMed  CAS  Google Scholar 

  • Graff J, Dohoon K, Dobbin MM, Tsai LH (2011) Epigenetic regulation of gene expression in physiological and pathological brain processes. Physiol Rev 91:603–649

    PubMed  CAS  Google Scholar 

  • Graham KA, Cho H, Brownley KA, Harp JB (2008) Early treatment-related changes in diabetes and cardiovascular disease risk markers in first episode psychosis subjects. Schizophr Res 101(1–3):287–294. doi:10.1016/j.schres.2007.12.476

    PubMed  PubMed Central  Google Scholar 

  • Gratacos M, Gonzalez JR, Mercader JM, de Cid R, Urretavizcaya M, Estivill X (2007) 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 61:911–922

    PubMed  CAS  Google Scholar 

  • Grillo RW, Ottoni GL, Leke R, Souza DO, Portela LV, Lara DR (2007) Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics. J Psychiatry Res 41:31–35

    Google Scholar 

  • Haller S, Borgwardt SJ, Schindler C, Aston J, Radue EW, Riecher-Rössler A (2009) Can cortical thickness asymmetry analysis contribute to detection of at-risk mental state and first-episode psychosis? A pilot study. Radiology 250(1):212–221. doi:10.1148/radiol.2501072153

    PubMed  Google Scholar 

  • Hertz L, O’Dowd BS, Ng KT, Gibbs ME (2003) Reciprocal changes in forebrain contents of glycogen and glutamate/glutamate during early memory consolidation in the day-old chick. Brain Res 994:226–233

    PubMed  CAS  Google Scholar 

  • Hoenicka J, Garrido E, Martínez I, Ponce G, Aragüés M, Rodríguez-Jiménez R, España-Serrano L, Alvira-Botero X, Santos JL, Rubio G, Jiménez-Arriero MA, Palomo T, PARGPARG (2010) Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet 153B:79–85

    PubMed  CAS  Google Scholar 

  • Honea RA, Meyer-Lindenberg A, Hobbs KB, Pezawas L, Mattay VS, Egan MF, Verchinski B, Passingham RE, Weinberger DR, Callicott JH (2008) Is grey matter volume an intermediate phenotype for schizophrenia? A voxel-based morphometric study of patients with schizophrenia and their healthy siblings. Biol Psychiatry 63:465–474

    PubMed  PubMed Central  Google Scholar 

  • Hope S, Ueland T, Steen NE, Dieset I, Lorentzen S, Berg AO, Agartz I, Aukrust P, Andreassen OA (2013) Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder. Schizophr Res 145(1–3):36–42. doi:10.1016/j.schres.2012.12.023

    PubMed  Google Scholar 

  • Howes OD, Montgomery AJ, Asselin M, Murray R, Grasby P, McGuire P (2007) Molecular imaging studies of the striatal dopaminergic system in psychosis and predictions for the prodromal phase of psychosis. Br J Psychiatry s51:s13–s18

    Google Scholar 

  • Huang CC, Lee CC (2010) Hsu KS (2010) The role of insulin receptor signaling in synaptic plasticity and cognitive function. Chang Gung Med J 33(2):115–125

    PubMed  Google Scholar 

  • Huttunen J, Heinimaa M, Svirskis T, Nyman M, Kajander J, Forsback S, Solin O, Ilonen T, Korkeila J, Ristkari T, McGlashan T, Salokangas RK, Hietala J (2008) Striatal dopamine synthesis in first-degree relatives of patients with schizophrenia. Biol Psychiatry 63(1):114–117

    PubMed  CAS  Google Scholar 

  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232

    PubMed  CAS  Google Scholar 

  • Ikeda Y, Yahata N, Ito I, Nagano M, Toyota T et al (2008) Low serum levels of brain derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res 101:58–66

    PubMed  Google Scholar 

  • Jablonka E, Raz G (2009) Transgenerational epigenetic inheritance: prevalence, mechanisms, and implications for the study of heredity and evolution. Q Rev Biol 84:131–176

    PubMed  Google Scholar 

  • Jacob CP, Nguyen TT, Dempfle A, Heine M, Windemuth-Kieselbach C, Baumann K, Jacob F, Prechtl J, Wittlich M, Herrmann MJ, Gross-Lesch S, Lesch KP, Reif A (2010) A gene-environment investigation on personality traits in two independent clinical sets of adult patients with personality disorder and attention deficit/hyperactivity disorder. Eur Arch Psychiatr Clin Neurosci 260:317–326

    Google Scholar 

  • Jafari S, Fernandez-Enright F, Huang XF (2012) Structural contributions of antipsychotic drugs to their therapeutic profiles and metabolic side effects. J Neurochem 120:371–384

    PubMed  CAS  Google Scholar 

  • Jaworski T, Dewachter I, Lechat B, Gees M, Kremer A, Demedts D, Borghgraef P, Devijver H, Kügler S, Patel S, Woodgett JR, Van Leuven F (2011) GSK-3α/β kinases and amyloid production in vivo. Nature 480(7376):E4–E5

    PubMed  CAS  Google Scholar 

  • Jenkins TA (2013) Perinatal complications and schizophrenia: involvement of the immune system. Front Neurosci 7:110. doi:10.3389/fnins.2013.00110

    PubMed  PubMed Central  Google Scholar 

  • Kaidanovich-Beilin O, Woodgett JR (2011) GSK-3: functional insights from cell biology and animal models. Front Mol Neurosci 4:40

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kegeles LS, Abi-Dargham A, Frankle WG, Gil R, Cooper TB, Slifstein M, Hwang DR, Huang Y, Haber SN, Laruelle M (2010) Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. Arch Gen Psychiatry 67(3):231–239

    PubMed  CAS  Google Scholar 

  • Kirkbride JB, Susser E, Kundakovic M, Kresovich JK, Davey Smith G, Relton CL (2012) Prenatal nutrition, epigenetics and schizophrenia risk: can we test causal effects? Epigenomics 4:303–315

    PubMed  CAS  PubMed Central  Google Scholar 

  • Kirkpatrick B, Miller BJ (2013) Inflammation and schizophrenia. Schizophr Bull 39(6):1174–1179. doi:10.1093/schbul/sbt141

    PubMed  Google Scholar 

  • Koutsouleris N, Borgwardt S, Meisenzahl EM, Bottlender R, Moller HJ, Riecher-Rossler A (2012) Disease prediction in the At-risk mental State for psychosis using neuroanatomical biomarkers: results from the FePsy Study. Schizophr Bull 38(6):1234–1246. doi:10.1093/schbul/sbr145

    PubMed  PubMed Central  Google Scholar 

  • Lafarga M, Lerga A, Andres MA, Polanco JL, Calle E, Berciano MT (1997) Apoptosis induced by methylazoxymethanol in developing rat cerebellum: organization of the cell nucleus and its relationship to DNA and tRNA degradation. Cell Tissue Res 289:25–38

    PubMed  CAS  Google Scholar 

  • Laruelle M, Abi-Dargham A, van Dyck CH, Gil R, D’Souza CD, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi SS, Baldwin RM, Seibyl JP, Krystal JH, Charney DS, Innis RB (1996) Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proc Natl Acad Sci USA 93(17):9235–9240

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lavoie S, Allaman I, Petit JM, Do KQ, Magistretti PJ (2011) Altered glycogen metabolism in cultured astrocytes from mice with chronic glutathione deficit: relevance for neuroenergetics in schizophrenia. PLoS ONE 6:e22875

    PubMed  CAS  PubMed Central  Google Scholar 

  • Lee AH, Lange C, Ricken R, Hellweg R, Lang UE (2011) Reduced brain-derived neurotrophic factor serum concentrations in acute schizophrenic patients increase during antipsychotic treatment. J Clin Psychopharmacol 31:334–336

    PubMed  CAS  Google Scholar 

  • Leng A, Jongen-Rêlo AL, Pothuizen HH, Feldon J (2005) Effects of prenatal methylazoxymethanol acetate (MAM) treatment in rats on water maze performance. Behav Brain Res 161(2):291–298

    PubMed  CAS  Google Scholar 

  • Lieberman JA, Kinon BJ, Loebel AD (1990) Dopaminergic mechanisms in idiopathic and drug-induced psychoses. Schizophr Bull 16(1):97–110

    PubMed  CAS  Google Scholar 

  • Lieberman JA, Sheitman BB, Kinon BJ (1997) Neurochemical sensitization in the pathophysiology of schizophrenia: deficits and dysfunction in neuronal regulation and plasticity. Neuropsychopharmacology 17(4):205–229

    PubMed  CAS  Google Scholar 

  • Lillrank SM, Lipska BK, Kolachana BS, Weinberger DR (1999) Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage. J Neural Transm 106:183–196

    PubMed  CAS  Google Scholar 

  • Lin PL, Shuldiner AR (2010) Rethinking the genetic basis of comorbidity of schizophrenia and type 2 diabetes. Schizophrenia Res 123:234–243. doi:10.1016/j.schres.2010.08.022

    CAS  Google Scholar 

  • Lipska BK, Weinberger DR (1994) Subchronic treatment with haloperidol and clozapine in rats with neonatal excitotoxic hippocampal damage. Neuropsychopharmacology 10:199–205

    PubMed  CAS  Google Scholar 

  • Lipska BK, Jaskiw GE, Chrapusta S, Karoum F, Weinberger DR (1992) Ibotenic acid lesions of the ventral hippocampus differentially affects dopamine and its metabolites in the nucleus accumbens and prefrontal cortex in the rat. Brain Res 585:1–6

    PubMed  CAS  Google Scholar 

  • Lipska BK, Swerdlow NR, Geyer MA, Jaskiw GE, Braff DL, Weinberger DR (1995) Neonatal excitotoxic lesions hippocampal damage in rats causes post pubertal changes in prepulse inhibition of startle and its disruption by apomorphine. Psychopharmacology 122:35–43

    PubMed  CAS  Google Scholar 

  • Lipska BK, Kolb B, Halim N, Weinberger DR (2001) Synaptic abnormalities in prefrontal cortex and nucleus accumbens of adult rats with neonatal hippocampal damage. Schizophr Res 49:47–51

    Google Scholar 

  • Lodge DJ, Grace AA (2008) Hippocampal dysfunction and disruption of dopamine system regulation in an animal model of schizophrenia. Neurotox Res 14:97–104

    PubMed  PubMed Central  Google Scholar 

  • Lyon GJ, Abi-Dargham A, Moore H, Lieberman JA, Javitch JA, Sulzer D (2011) Presynaptic regulation of dopamine transmission in schizophrenia. Schizophr Bull 37(1):108–117

    PubMed  PubMed Central  Google Scholar 

  • Maat A, Fett AK, Derks E, GROUP Investigators (2012) Social cognition and quality of life in schizophrenia. Schizophr Res 137(1–3):212–218. doi:10.1016/j.schres.2012.02.017

    PubMed  Google Scholar 

  • McGuire P, Howes OD, Stone J, Fusar-Poli P (2008) Functional neuroimaging in schizophrenia: diagnosis and drug discovery. Trends Pharmacol Sci. 29(2):91–98

    PubMed  CAS  Google Scholar 

  • Mechelli A, Riecher-Rossler A, Meisenzahl EM, Tognin S, Wood SJ, Borgwardt SJ, Koutsouleris N, Yung AR, Stone JM, Phillips LJ, McGorry PD, Valli I, Velakoulis D, Woolley J, Pantelis C, McGuire P (2011) Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Arch Gen Psychiatry. 68(5):489–495

    PubMed  Google Scholar 

  • Meyer-Lindenberg A (2011) Neuroimaging and the question of neurodegeneration in schizophrenia. Prog Neurobiol 95:514–516

    PubMed  Google Scholar 

  • Meyer-Lindenberg A, Miletich RS, Kohn PD, Esposito G, Carson RE, Quarantelli M, Weinberger DR, Berman KF (2002) Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci 5(3):267–271

    PubMed  CAS  Google Scholar 

  • Meyer-Lindenberg A, Olsen RK, Kohn PD, Brown T, Egan MF, Weinberger DR, Berman KF (2005) Regionally specific disturbance of dorsolateral prefrontal-hippocampal functional connectivity in Schizophrenia. Arch Gen Psychiatry 62:379–386

    PubMed  Google Scholar 

  • Miller R, Chouinard G (1993) Loss of striatal cholinergic neurons as a basis for tardive and L-dopa-induced dyskinesias, neuroleptic-induced supersensitivity psychosis and refractory schizophrenia. Biol Psychiatry 34:713–738

    PubMed  CAS  Google Scholar 

  • Miller J, Williamson P, Jensen JE, Manchanda R, Menon R et al (2009) Longitudinal 4.0 Testa (31)P magnetic resonance spectroscopy changes in the anterior cingulate and left thalamus in first episode schizophrenia. Psychiatr Res Neuroimaging 173:155–157

    Google Scholar 

  • Miyake N, Thompson J, Skinbjerg M, Abi-Dargham A (2011) Presynaptic dopamine in schizophrenia. CNS Neurosci Ther 17(2):104–109. doi:10.1111/j.1755-5949.2010.00230.x

    PubMed  CAS  Google Scholar 

  • Mohammed AK, Jonsson G, Söderberg U, Archer T (1986a) Impaired selective attention in methylazoxymethanol-induced microencephalic rats. Pharmacol Biochem Behav 24:975–981

    PubMed  CAS  Google Scholar 

  • Mohammed AK, Jonsson G, Sundström E, Minor BG, Söderberg U, Archer T (1986b) Selective attention and place navigation in rats treated prenatally with methylazoxymethanol. Brain Res Dev Brain Res 30:145–155

    CAS  Google Scholar 

  • Moore H, Jentsch JD, Ghajarnia M, Geyer MA, Grace AA (2006) A neurobehavioral systems analysis of adult rats exposed to methylazoxymethanol acetate on E17: implications for the neuropathology of schizophrenia. Biol Psychiatry 60:253–264

    PubMed  CAS  PubMed Central  Google Scholar 

  • Morgan C, Kirkbride J, Leff J, Craig T, Hutchinson G, McKenzie K, Morgan K, Dazzan P, Doody GA, Jones P, Murray R, Fearon P (2007) Parental separation, loss and psychosis in different ethnic groups: a case-control study. Psychol Med 37:495–503

    PubMed  Google Scholar 

  • Morgan VA, McGrath JJ, Jablensky A, Badcock JC, Waterreus A, Bush R, Carr V, Castle D, Cohen M, Galletly C, Harvey C, Hocking B, McGorry P, Neil AL, Saw S, Shah S, Stain HJ, Mackinnon A (2013) Psychosis prevalence and physical, metabolic and cognitive co-morbidity: data from the second Australian national survey of psychosis. Psychol Med 23:1–14

    Google Scholar 

  • Niitsu T, Shirayama Y, Matsuzawa D, Hasegawa T, Kanahara N, Hashimoto T, Shiraishi T, Shiina A, Fukami G, Fujisaki M, Watanabe H, Nakazato M, Asano M, Kimura S, Hashimoto K, Iyo M (2011) Associations of serum brain-derived neurotrophic factor with cognitive impairments and negative symptoms in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 35:1836–1840

    PubMed  CAS  Google Scholar 

  • Niu C, Yip HK (2011) Neuroprotective signaling mechanisms of telomerase are regulated by brain-derived neurotrophic factor in rat spinal cord motor neurons. J Neuropathol Exp Neurol 70(7):634–652

    PubMed  CAS  Google Scholar 

  • O’Donnell P, Lewis BL, Weinberger DR, Lipska BK (2002) Neonatal hippocampal damage alters electrophysiological properties of prefrontal cortical neurons in adult rats. Cereb Cortex 12:975–982

    PubMed  Google Scholar 

  • Onishi T, Iwashita H, Uno Y, Kunitomo J, Saitoh M, Kimura E, Fujita H, Uchiyama N, Kori M, Takizawa M (2011) A novel glycogen synthase kinase-3 inhibitor 2-methyl-5-(3-{4-[(S )-methylsulfinyl]phenyl}-1-benzofuran-5-yl)-1,3,4-oxadiazole decreases tau phosphorylation and ameliorates cognitive deficits in a transgenic model of Alzheimer’s disease. J Neurochem 119:1330–1340

    PubMed  CAS  Google Scholar 

  • Pae CU, Chiesa A, Porcelli S, Han C, Patkar AA, Lee SJ, Park MH, Serretti A, De Ronchi D (2012) Influence of BDNF variants on diagnosis and response to treatment in patients with major depression, bipolar disorder and schizophrenia. Neuropsychobiology 65(1):1–11

    PubMed  CAS  Google Scholar 

  • Palomino A, Vallejo-Illarramendi A, Gonzalez-Pinto A, Aldama A, Gonzalez-Gomez C, Mosquera F, Gonzalez-Garcia G, Matute C (2006) Decreased levels of plasma BDNF in first-episode schizophrenia and bipolar disorder patients. Schizophr Res 6:321–322

    Google Scholar 

  • Park SW, Lee JG, Kong BG, Lee SJ, Lee CH, Kim JI, Kim YH (2009) Genetic association of BDNF val66met and GSK-3beta-50T/C polymorphisms with tardive dyskinesia. Psychiatry Clin Neurosci 63:433–439

    PubMed  CAS  Google Scholar 

  • Pasternak O, Westin CF, Bouix S, Seidman LJ, Goldstein JM, Woo TU, Petryshen TL, Mesholam-Gately RI, McCarley RW, Kikinis R, Shenton ME, Kubicki M (2012) Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. J Neurosci 32(48):17365–17372. doi:10.1523/JNEUROSCI.2904-12.2012

    PubMed  CAS  PubMed Central  Google Scholar 

  • Pedrini M, Chendo I, Grande I, Lobato MI, Belmonte-de-Abreu PS et al (2011) Serum brain-derived neurotrophic factor and clozapine daily dose in patients with schizophrenia, a positive correlation. Neurosci Lett 491:207–210

    PubMed  CAS  Google Scholar 

  • Pert L, Ferriter M, Saul C (2004) Parental loss before the age of 16 years: a comparative study of patients with personality disorder and patients with schizophrenia in a high secure hospital’s population. Psychol Psychother 77(Pt 3):403–407

    PubMed  CAS  Google Scholar 

  • Powell SB, Sejnowski TJ, Behrens MM (2012) Behavioral and neurochemical consequences of cortical oxidative stress on parvalbumin-interneuron maturation in rodent models of schizophrenia. Neuropharmacology 62(3):1322–1331. doi:10.1016/j.neuropharm.2011.01.049

    PubMed  CAS  PubMed Central  Google Scholar 

  • Ricci S, Businaro R, Massoni F, Ippoliti F, Troili GM, Pontecorvi V, Morelli M, Rapp Ricciardi M, Archer T (2013) Altered cytokine and BDNF levels in autism spectrum disorder. Neurotox Res. doi:10.1007/s12640-013-9393-4

    PubMed  Google Scholar 

  • Rice D, Barone S (2000) Critical periods of vulnerability for the developing nervous system: evidence from human and animal models. Environment Health Perspect 108(Suppl. 3):511–533

    Google Scholar 

  • Rizos EN, Rontos I, Laskos E, Arsenis G, Michalopoulos PG et al (2008) Investigation of serum BDNF levels in drug-naive patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 32:1308–1311

    PubMed  CAS  Google Scholar 

  • Rizos EN, Papadopoulou A, Laskos E, Michalopoulos PG, Kastania D et al (2010) Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse, who were treated with typical or atypical antipsychotics. World J Biol Psychiatry 1:251–255

    Google Scholar 

  • Rosenberg SD, Lu W, Mueser KT, Jankowski MK, Cournos F (2007) Correlates of adverse childhood events among adults with schizophrenia spectrum disorders. Psychiatr Serv 58:245–253

    PubMed  Google Scholar 

  • Rothlisberger M, Riecher-Rossler A, Aston J, Fusar-Poli P, Radu EW, Borgwardt S (2012) Cingulate volume abnormalities in emerging psychosis. Curr Pharm Des 18(4):495–504

    PubMed  CAS  Google Scholar 

  • Sawa A, Snyder SH (2002) Schizophrenia: diverse approaches to a complex disease. Science 296:692–695

    PubMed  CAS  Google Scholar 

  • Shenton ME, Dickey CC, Frumin M, McCarley RW (2001) A review of MRI findings in schizophrenia. Schizophr Res 49(1–2):1–52

    PubMed  CAS  PubMed Central  Google Scholar 

  • Shinohara M, Ybanez MD, Win S, Than TA, Jain S, Gaarde WA, Han D, Kaplowitz N (2010) Silencing glycogen synthase kinase-3beta inhibits acetaminophen hepatotoxicity and attenuates JNK activation and loss of glutamate cysteine ligase and myeloid cell leukemia sequence 1. J Biol Chem 285:8244–8255

    PubMed  CAS  PubMed Central  Google Scholar 

  • Singh KK, De Rienzo G, Drane L, Mao Y, Flood Z, Madison J, Ferreira M, Bergen S, King C, Sklar P, Sive H, Tsai LH (2011) Common DISC1 polymorphisms disrupt Wnt/GSK3B signaling and brain development. Neuron 72:545–558

  • Singh S, Goyal S, Modi S, Kumar P, Singh N, Bhatia T, Deshpanda SN, Khushu S (2014) Motor function deficits in Schizophrenia: an fMRI and VBM study. Neuroradiology. doi:10.1007/s00234-014-1325-3

  • Smieskova R, Fusar-Poli P, Allen P, Bendfeldt K, Stieglitz RD, Drewe J, Radue EW, McGuire PK, Riecher-Rössler A, Borgwardt SJ (2010a) Neuroimaging predictors of transition to psychosis–a systematic review and meta-analysis. Neurosci Biobehav Rev 34(8):1207–1222. doi:10.1016/j.neubiorev.2010.01.016

    PubMed  CAS  Google Scholar 

  • Smieskova R, Fusar-Poli P, Allen P, Bendfeldt K, Stieglitz R, Drewe J, Radue E, McGuire P, Riecher-Rössler A, Borgwardt S (2010b) Neuroimaging predictors of transition to psychosis—a systematic review and meta-analysis. Neurosci Biobehav Rev 34(8):1207–1222

    PubMed  CAS  Google Scholar 

  • Smieskova R, Fusar-Poli P, Aston J, Simon A, Bendfeldt K, Lenz C, Stieglitz RD, McGuire P, Riecher-Rossler A, Borgwardt SJ (2012a) Insular volume abnormalities associated with different transition probabilities to psychosis. Psychol Med 42(8):1613–1625. doi:10.1017/S0033291711002716

    PubMed  CAS  PubMed Central  Google Scholar 

  • Smieskova R, Fusar-Poli P, Riecher-Rossler A, Borgwardt S (2012b) Neuroimaging and resilience factors - staging of the at-risk mental state? Curr Pharm Des 18(4):416–421

    PubMed  CAS  Google Scholar 

  • Smieskova R, Allen P, Simon A, Aston J, Bendfeldt K, Drewe J, Gruber K, Gschwandtner U, Klarhoefer M, Lenz C, Scheffler K, Stieglitz RD, Radue EW, McGuire P, Riecher-Rossler A, Borgwardt SJ (2012c) Different duration of at-risk mental state associated with neurofunctional abnormalities. A multimodal imaging study. Hum Brain Mapp 33(10):2281–2294. doi:10.1002/hbm.21360

    PubMed  Google Scholar 

  • Song X, Fan X, Song X, Zhang J, Zhang W, Li X, Gao J, Harrington A, Ziedonis D, Lv L (2013) Elevated levels of adiponectin and other cytokines in drug naïve, first episode schizophrenia patients with normal weight. Schizophr Res 150(1):269–273. doi:10.1016/j.schres.2013.07.044

    PubMed  Google Scholar 

  • Stefanis NC, Dragovic M, Power BD, Jablensky A, Castle D, Morgan VA (2013) Age at initiation of cannabis use predicts age at onset of psychosis: the 7- to 8-year trend. Schizophr Bull 39(2):251–254. doi:10.1093/schbul/sbs188

    PubMed  PubMed Central  Google Scholar 

  • Stone JM, Day F, Tsagaraki H, Valli McLean MA et al (2009) Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to grey matter volume. Biol Psychiatry 66:533–539

    PubMed  CAS  Google Scholar 

  • Sullivan PF, Kendler KS, Neale MC (2003) Schizophrenia as a complex trait: evidence from a meta-analysis of twin studies. Arch Gen Psychiatry 60:1187–1192

    PubMed  Google Scholar 

  • Suzuki A, Stern SA, Bozdagi O, Huntley GW, Walker RH, Magistretti PJ, Alberini CM (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823

    PubMed  CAS  PubMed Central  Google Scholar 

  • Swanson RA (1992) Physiologic coupling of glial glycogen metabolism to neuronal activity in brain. Can J Physiol Pharmacol 70(Suppl):S138–S144

    PubMed  CAS  Google Scholar 

  • Takei Y, Suda M, Aoyama Y, Yamaguchi M, Sakurai N, Narita K, Fukuda M, Mikuni M (2013) Temporal lobe and inferior frontal gyrus dysfunction in patients with schizophrenia during face-to-face conversation: a near-infrared spectroscopy study. J Psychiatr Res 47(11):1581–1589. doi:10.1016/j.jpsychires.2013.07.029

    PubMed  Google Scholar 

  • Tan YL, Zhou DF, Zhang XY (2005) Decreased plasma brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. Schizophr Res 74:263–270

    PubMed  Google Scholar 

  • Tayoshi S, Sumitani S, Taniguchi K, Shibuya-Tayoshi S, Numata S et al (2009) Metabolite changes and gender differences in schizophrenia using 3-Testa proton magnetic resonance spectroscopy (1H-MRS). Schizophr Res 108:69–77

    PubMed  Google Scholar 

  • Théberge J, Williamson KE, Aoyama N, Drost DJ, Manchanda R, Malla AK, Northcott S, Menon RS, Neufeld RW, Rajakumar N, Pavlosky W, Densmore M, Schaefer B, Williamson PC (2007) Longitudinal grey-matter and glutamatergic losses in first-episode schizophrenia. Br J Psychiatry 191:325–334

    PubMed  Google Scholar 

  • Tibbo P, Hanstock C, Valiakalayil A, Allen P (2004) 3-T proton MRS investigation of glutamate and glutamine in adolescents at high genetic risk for schizophrenia. Am J Psychiatry 161:1116–1118

    PubMed  Google Scholar 

  • Tosic M, Ott J, Barral S, Bovet P, Deppen P et al (2006) Schizophrenia and oxidative stress: glutamate cysteine ligase modifier as a susceptibility gene. Am J Hum Genet 79:586–592

    PubMed  CAS  PubMed Central  Google Scholar 

  • Traver S, Marien M, Martin E, Hirsch EC, Michel PP (2006) The phenotypic differentiation of locus coeruleus noradrenergic neurons mediated by brain-derived neurotrophic factor is enhanced by corticotrophin releasing factor through the activation of a cAMP-dependent signaling pathway. Mol Pharmacol 70:30–40

    PubMed  CAS  Google Scholar 

  • Wender R, Brown AM, Fern R, Swanson RA, Farrell K et al (2000) Astrocytic glycogen influences axon function and survival during glucose deprivation in central white matter. J Neurosci 20:6804–6810

    PubMed  CAS  Google Scholar 

  • Wexler EM, Geschwind DH (2011) DISC1: a schizophrenia gene with multiple personalities. Neuron 72:501–503

    PubMed  CAS  Google Scholar 

  • Yang YQ, Sun S, Yu YQ, Li WJ, Zhang X, Xiu MH (2011) Decreased serum brain-derived neurotrophic factor levels in schizophrenic patients with tardive dyskinesia. Neurosci Lett 502:37–40

    PubMed  CAS  Google Scholar 

  • Yoshimura R, Hori H, Sugita N, Ueda N, Kakihara S (2007) Treatment with risperidone for 4 weeks increased plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels, but did not alter plasma brain-derived neurotrophic factor (BDNF) levels in schizophrenic patients. Prog Neuropsychopharmacol Biol Psychiatry 31:1072–1077

    PubMed  CAS  Google Scholar 

  • Yoshimura R, Ueda N, Hori H, Ikenouchi-Sugita A, Umene-Nakano W et al (2010) Different patterns of longitudinal changes in plasma levels of catecholamine metabolites and brain-derived neurotrophic factor after administration of atypical antipsychotics in first episode untreated schizophrenic patients. World J Biol Psychiatry 11:256–261

    PubMed  Google Scholar 

  • Yu Q, Plis SM, Erhardt EB, Allen EA, Sui J, Kiehl KA, Pearlson G, Calhoun VD (2011) Modular organization of functional network connectivity in healthy controls and patients with schizophrenia during the resting State. Front Syst Neurosci 5:103

    PubMed  PubMed Central  Google Scholar 

  • Zai CC, Tiwari AK, De Luca V, Muller DJ, Bulgin N et al (2009) Genetic study of BDNF, DRD3, and their interaction in tardive dyskinesia. Eur Neuropsychopharmacol 19:317–328

    PubMed  CAS  Google Scholar 

  • Zhang XY, Xiu MH, da Chen C, Zhu FY, Wu GY, Haile CN, Lu L, Kosten TA, Kosten TR (2010) Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. J Psychiatr Res 44:429–433

    PubMed  Google Scholar 

  • Zhang XY, Liang J, Chen DC, Xiu MH, De Yang F, Kosten TA, Kosten TR (2012) Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia. Psychopharmacology 222(2):277–284. doi:10.1007/s00213-012-2643-y

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The development of this manuscript was supported by the Bliwa Stiftelsen.

Conflict of interests

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Psychology, University of Gothenburg, Box 500, 40530, Göthenburg, Sweden

    Trevor Archer, Danilo Garcia & Max Rapp Ricciardi

  2. Network for Empowerment and Well-Being, Lund, Sweden

    Trevor Archer, Danilo Garcia & Max Rapp Ricciardi

  3. Department of Anatomy, Histology, Forensic Medicine and Orthopaedics, Sapienza University, Rome, Italy

    Serafino Ricci

  4. Center for Ethics, Law and Mental Health (CELAM), University of Gothenburg, Göthenburg, Sweden

    Danilo Garcia

Authors
  1. Trevor Archer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Serafino Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Danilo Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Max Rapp Ricciardi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Trevor Archer.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Archer, T., Ricci, S., Garcia, D. et al. Neurodegenerative Aspects in Vulnerability to Schizophrenia Spectrum Disorders. Neurotox Res 26, 400–413 (2014). https://doi.org/10.1007/s12640-014-9473-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-014-9473-0

Keywords

Search

Navigation