Altering the course of schizophrenia: progress and perspectives

Despite a lack of recent progress in the treatment of schizophrenia, our understanding of its genetic and environmental causes has considerably improved, and their relationship to aberrant patterns of neurodevelopment has become clearer. This raises the possibility that 'disease-modifying' strategies could alter the course to — and of — this debilitating disorder, rather than simply alleviating symptoms. A promising window for course-altering intervention is around the time of the first episode of psychosis, especially in young people at risk of transition to schizophrenia. Indeed, studies performed in both individuals at risk of developing schizophrenia and rodent models for schizophrenia suggest that pre-diagnostic pharmacotherapy and psychosocial or cognitive-behavioural interventions can delay or moderate the emergence of psychosis. Of particular interest are 'hybrid' strategies that both relieve presenting symptoms and reduce the risk of transition to schizophrenia or another psychiatric disorder. This Review aims to provide a broad-based consideration of the challenges and opportunities inherent in efforts to alter the course of schizophrenia.

[1]  E. Mayo-Wilson,et al.  Early interventions to prevent psychosis: systematic review and meta-analysis , 2013, BMJ : British Medical Journal.

[2]  A. Ravindran,et al.  Contribution of sex hormones to gender differences in schizophrenia: A review. , 2015, Asian journal of psychiatry.

[3]  Paul J. Harrison The current and potential impact of genetics and genomics on neuropsychopharmacology , 2015, European Neuropsychopharmacology.

[4]  S. Dursun,et al.  Effects of minocycline add-on treatment on brain morphometry and cerebral perfusion in recent-onset schizophrenia , 2015, Schizophrenia Research.

[5]  G. Gross,et al.  Dopamine D3 receptor antagonism—still a therapeutic option for the treatment of schizophrenia , 2012, Naunyn-Schmiedeberg's Archives of Pharmacology.

[6]  M. Cuénod,et al.  Juvenile Antioxidant Treatment Prevents Adult Deficits in a Developmental Model of Schizophrenia , 2014, Neuron.

[7]  S. Akhondzadeh,et al.  N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study , 2013, Clinical neuropharmacology.

[8]  J. Cummings Defining and labeling disease-modifying treatments for Alzheimer's disease , 2009, Alzheimer's & Dementia.

[9]  S. Haggarty,et al.  Translation: Screening for Novel Therapeutics With Disease-Relevant Cell Types Derived from Human Stem Cell Models , 2014, Biological Psychiatry.

[10]  R. Yolken,et al.  Toxoplasma gondii and other risk factors for schizophrenia: an update. , 2012, Schizophrenia bulletin.

[11]  Jens C. Pruessner,et al.  Increased Stress-Induced Dopamine Release in Psychosis , 2012, Biological Psychiatry.

[12]  S. Nakagawa,et al.  Effects of aripiprazole and haloperidol on progression to schizophrenia-like behavioural abnormalities and apoptosis in rodents , 2011, Schizophrenia Research.

[13]  M. Cannon,et al.  Language processing abnormalities in adolescents with psychotic-like experiences: An event related potential study , 2012, Schizophrenia Research.

[14]  C. Pantelis,et al.  Neuroimaging and Treatment Evidence for Clinical Staging in Psychotic Disorders: From the At-Risk Mental State to Chronic Schizophrenia , 2011, Biological Psychiatry.

[15]  N. Iwata,et al.  Efficacy and tolerability of minocycline augmentation therapy in schizophrenia: a systematic review and meta‐analysis of randomized controlled trials , 2014, Human psychopharmacology.

[16]  Q. Pittman,et al.  Microglia-Dependent Alteration of Glutamatergic Synaptic Transmission and Plasticity in the Hippocampus during Peripheral Inflammation , 2015, The Journal of Neuroscience.

[17]  V. Calhoun,et al.  Genetic underpinnings of left superior temporal gyrus thickness in patients with schizophrenia , 2015, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[18]  J. Miettunen,et al.  Duration of untreated psychosis as predictor of long-term outcome in schizophrenia: systematic review and meta-analysis , 2014, British Journal of Psychiatry.

[19]  L. Mei,et al.  Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases , 2014, Neuron.

[20]  J. Ford,et al.  Automatic Auditory Processing Deficits in Schizophrenia and Clinical High-Risk Patients: Forecasting Psychosis Risk with Mismatch Negativity , 2014, Biological Psychiatry.

[21]  Sarah E Hetrick,et al.  Preventing the second episode: a systematic review and meta-analysis of psychosocial and pharmacological trials in first-episode psychosis. , 2011, Schizophrenia bulletin.

[22]  S. Najjar,et al.  Neuroinflammation and white matter pathology in schizophrenia: systematic review , 2015, Schizophrenia Research.

[23]  E. Walker,et al.  Stress and neurodevelopmental processes in the emergence of psychosis , 2013, Neuroscience.

[24]  L. Coolen,et al.  Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions , 2006, Neuropsychopharmacology.

[25]  K. Hashimoto,et al.  Prenatal immune activation and subsequent peripubertal stress as a new model of schizophrenia , 2013, Expert review of neurotherapeutics.

[26]  R. Buchanan,et al.  Proof-of-concept randomized controlled trial of pregnenolone in schizophrenia , 2014, Psychopharmacology.

[27]  Oscar Marín,et al.  Interneuron dysfunction in psychiatric disorders , 2012, Nature Reviews Neuroscience.

[28]  S. Ohmann,et al.  Omega-3 Fatty Acid Supplementation in Adolescents with Borderline Personality Disorder and Ultra-High Risk Criteria for Psychosis: A Post Hoc Subgroup Analysis of a Double—Blind, Randomized Controlled Trial , 2013, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[29]  M. Gerstein,et al.  FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders , 2015, Cell.

[30]  R. Dolmetsch,et al.  SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients , 2013, Nature.

[31]  Y. Ben-Ari,et al.  A randomised controlled trial of bumetanide in the treatment of autism in children , 2012, Translational Psychiatry.

[32]  M. Barbato,et al.  Pilot study of cognitive remediation therapy on cognition in young people at clinical high risk of psychosis , 2015, Psychiatry Research.

[33]  Pierre Vanderhaeghen,et al.  Thinking out of the dish: what to learn about cortical development using pluripotent stem cells , 2014, Trends in Neurosciences.

[34]  George Bartzokis,et al.  Schizophrenia: Breakdown in the Well-regulated Lifelong Process of Brain Development and Maturation , 2002, Neuropsychopharmacology.

[35]  David W. Nauen,et al.  Modeling a genetic risk for schizophrenia in iPSCs and mice reveals neural stem cell deficits associated with adherens junctions and polarity. , 2014, Cell stem cell.

[36]  B. Pollock,et al.  Neuroimaging evidence for the deficit subtype of schizophrenia. , 2013, JAMA psychiatry.

[37]  C. Bundgaard,et al.  Repeated potentiation of the metabotropic glutamate receptor 5 and the alpha 7 nicotinic acetylcholine receptor modulates behavioural and GABAergic deficits induced by early postnatal phencyclidine (PCP) treatment , 2013, Neuropharmacology.

[38]  P. Horn,et al.  Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation. , 2011, Journal of psychiatric research.

[39]  D. Bugarski-Kirola,et al.  A phase II/III trial of bitopertin monotherapy compared with placebo in patients with an acute exacerbation of schizophrenia – Results from the CandleLyte study , 2014, European Neuropsychopharmacology.

[40]  G. Cagney,et al.  Omega-3 fatty acid deficiency disrupts endocytosis, neuritogenesis, and mitochondrial protein pathways in the mouse hippocampus , 2013, Front. Genet..

[41]  D. Rusakov,et al.  Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses , 2013, Proceedings of the National Academy of Sciences.

[42]  Bita Moghaddam,et al.  From Revolution to Evolution: The Glutamate Hypothesis of Schizophrenia and its Implication for Treatment , 2012, Neuropsychopharmacology.

[43]  M. Millan,et al.  Enhancement of social novelty discrimination by positive allosteric modulators at metabotropic glutamate 5 receptors: adolescent administration prevents adult-onset deficits induced by neonatal treatment with phencyclidine , 2012, Psychopharmacology.

[44]  Lu Liu,et al.  A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis , 2011, Schizophrenia Research.

[45]  Patricia Tueting,et al.  Brain-Derived Neurotrophic Factor Epigenetic Modifications Associated with Schizophrenia-like Phenotype Induced by Prenatal Stress in Mice , 2015, Biological Psychiatry.

[46]  Fan Wang,et al.  Spine Pruning Drives Antipsychotic-sensitive Locomotion via Circuit Control of Striatal Dopamine , 2015, Nature Neuroscience.

[47]  Jennifer M. Coughlin,et al.  Inflammatory molecular signature associated with infectious agents in psychosis. , 2014, Schizophrenia bulletin.

[48]  J. Lijmer,et al.  Red blood cell polyunsaturated fatty acids measured in red blood cells and schizophrenia: A meta-analysis , 2013, Psychiatry Research.

[49]  S. Wood,et al.  Outcomes of nontransitioned cases in a sample at ultra-high risk for psychosis. , 2015, The American journal of psychiatry.

[50]  M. Boks,et al.  Cannabidiol as a potential treatment for psychosis , 2014, European Neuropsychopharmacology.

[51]  C. Pantelis,et al.  Relationship between membrane fatty acids and cognitive symptoms and information processing in individuals at ultra-high risk for psychosis , 2014, Schizophrenia Research.

[52]  D. E. López,et al.  Chronic administration of risperidone in a rat model of schizophrenia: A behavioural, morphological and molecular study , 2013, Behavioural Brain Research.

[53]  Viktoriya D. Nikolova,et al.  Preweaning Sensorimotor Deficits and Adolescent Hypersociability in Grin1 Knockdown Mice , 2012, Developmental Neuroscience.

[54]  R. Murray,et al.  Stress and inflammation reduce brain-derived neurotrophic factor expression in first-episode psychosis: a pathway to smaller hippocampal volume. , 2011, The Journal of clinical psychiatry.

[55]  L. Williams,et al.  Functional dysconnectivity in schizophrenia and its relationship to neural synchrony , 2013, Expert review of neurotherapeutics.

[56]  Danielle M. Santarelli,et al.  Maturation of the human dorsolateral prefrontal cortex coincides with a dynamic shift in microRNA expression. , 2014, Schizophrenia bulletin.

[57]  S. Berretta Extracellular matrix abnormalities in schizophrenia , 2012, Neuropharmacology.

[58]  A. Guidotti,et al.  The Dynamics of DNA Methylation in Schizophrenia and Related Psychiatric Disorders , 2013, Neuropsychopharmacology.

[59]  Andrea Mechelli,et al.  Can neuroimaging be used to predict the onset of psychosis? , 2015, The lancet. Psychiatry.

[60]  S. Oliet,et al.  Glial D-serine gates NMDA receptors at excitatory synapses in prefrontal cortex. , 2012, Cerebral cortex.

[61]  A. Azbarova Personality Traits of Alcohol-dependent Women , 2015, European Psychiatry.

[62]  M. Berk,et al.  Rationale and first results of developing at-risk (prodromal) criteria for bipolar disorder. , 2012, Current pharmaceutical design.

[63]  E. Bramon,et al.  White matter alterations related to P300 abnormalities in individuals at high risk for psychosis: an MRI-EEG study. , 2011, Journal of psychiatry & neuroscience : JPN.

[64]  E. Bora,et al.  Theory of mind impairments in first-episode psychosis, individuals at ultra-high risk for psychosis and in first-degree relatives of schizophrenia: Systematic review and meta-analysis , 2013, Schizophrenia Research.

[65]  R. Buchanan,et al.  Clinical Trials of Potential Cognitive-Enhancing Drugs in Schizophrenia: What Have We Learned So Far? , 2011, Schizophrenia bulletin.

[66]  Remco Renken,et al.  Not on speaking terms: hallucinations and structural network disconnectivity in schizophrenia , 2013, Brain Structure and Function.

[67]  G. Martinotti,et al.  The role of intranasal oxytocin in the treatment of patients with schizophrenia: a systematic review. , 2013, CNS & neurological disorders drug targets.

[68]  T. Sumiyoshi,et al.  Electrophysiological and Neuropsychological Predictors of Conversion to Schizophrenia in At-Risk Subjects , 2013, Front. Behav. Neurosci..

[69]  M. Lambert,et al.  Pre-treatment, baseline, and outcome differences between early-onset and adult-onset psychosis in an epidemiological cohort of 636 first-episode patients , 2007, Schizophrenia Research.

[70]  Vaughan J. Carr,et al.  Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia , 2012, Neuroscience & Biobehavioral Reviews.

[71]  Beatriz Paniagua,et al.  Imaging Patients with Psychosis and a Mouse Model Establishes a Spreading Pattern of Hippocampal Dysfunction and Implicates Glutamate as a Driver , 2013, Neuron.

[72]  J. O. Johannessen,et al.  First‐episode psychosis patients recruited into treatment via early detection teams versus ordinary pathways: course and health service use during 5 years , 2007, Early intervention in psychiatry.

[73]  A. Meyer-Lindenberg,et al.  Learning from the past and looking to the future: Emerging perspectives for improving the treatment of psychiatric disorders , 2015, European Neuropsychopharmacology.

[74]  J. Sato,et al.  Changes in gene expression and methylation in the blood of patients with first-episode psychosis , 2014, Schizophrenia Research.

[75]  Mikail Rubinov,et al.  Schizophrenia and abnormal brain network hubs , 2013, Dialogues in clinical neuroscience.

[76]  L. Fañanás,et al.  Neurodevelopmental liability to schizophrenia: The complex mediating role of age at onset and premorbid adjustment , 2011, Schizophrenia Research.

[77]  H. Meltzer Update on typical and atypical antipsychotic drugs. , 2013, Annual review of medicine.

[78]  S. Josselyn,et al.  Caution When Diagnosing Your Mouse With Schizophrenia: The Use and Misuse of Model Animals for Understanding Psychiatric Disorders , 2016, Biological Psychiatry.

[79]  A. Egerton,et al.  Glutamate and psychosis risk. , 2012, Current pharmaceutical design.

[80]  B. Lipska,et al.  DNA methylation changes in the postmortem dorsolateral prefrontal cortex of patients with schizophrenia , 2014, Front. Genet..

[81]  B. Emery,et al.  Mechanisms regulating the development of oligodendrocytes and central nervous system myelin , 2014, Neuroscience.

[82]  L. Howard,et al.  Br J Psychiatry , 2013 .

[83]  V. Calhoun,et al.  Deficient Suppression of Default Mode Regions during Working Memory in Individuals with Early Psychosis and at Clinical High-Risk for Psychosis , 2013, Front. Psychiatry.

[84]  Terrence J. Sejnowski,et al.  Abnormal Gamma Oscillations in N-Methyl-D-Aspartate Receptor Hypofunction Models of Schizophrenia , 2016, Biological Psychiatry.

[85]  M. Bear,et al.  Effects of STX209 (Arbaclofen) on Neurobehavioral Function in Children and Adults with Fragile X Syndrome: A Randomized, Controlled, Phase 2 Trial , 2012, Science Translational Medicine.

[86]  E. Masliah,et al.  Chronic administration of the neurotrophic agent cerebrolysin ameliorates the behavioral and morphological changes induced by neonatal ventral hippocampus lesion in a rat model of schizophrenia , 2012, Journal of neuroscience research.

[87]  N. Shomron,et al.  MicroRNA-382 expression is elevated in the olfactory neuroepithelium of schizophrenia patients , 2013, Neurobiology of Disease.

[88]  Neonatal phencyclidine administration and post-weaning social isolation as a dual-hit model of ‘schizophrenia-like’ behaviour in the rat , 2014, Psychopharmacology.

[89]  P. Glue,et al.  Bayesian analysis of posttest predictive value of screening instruments for the psychosis high-risk state. , 2013, JAMA psychiatry.

[90]  Joaquim Radua,et al.  Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia , 2014, Psychiatry Research: Neuroimaging.

[91]  Y. Noda,et al.  Behavioral phenotypes in schizophrenic animal models with multiple combinations of genetic and environmental factors. , 2013, Journal of pharmacological sciences.

[92]  Bruce N Cuthbert,et al.  The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology , 2014, World psychiatry : official journal of the World Psychiatric Association.

[93]  S. Haber,et al.  Increased synaptic dopamine function in associative regions of the striatum in schizophrenia. , 2010, Archives of general psychiatry.

[94]  Dement'eva Nm,et al.  5-HT6 Receptor Antagonists: Potential Efficacy for the Treatment of Cognitive Impairment in Schizophrenia. , 2015 .

[95]  T. Bates,et al.  Designing youth mental health services for the 21st century: examples from Australia, Ireland and the UK , 2013, British Journal of Psychiatry.

[96]  C. Kellendonk,et al.  Using human brain imaging studies as a guide toward animal models of schizophrenia , 2016, Neuroscience.

[97]  A. Keller,et al.  Adolescent Cannabinoid Exposure Permanently Suppresses Cortical Oscillations in Adult Mice , 2013, Neuropsychopharmacology.

[98]  Hok Pan Yuen,et al.  Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome. , 2013, The Journal of clinical psychiatry.

[99]  M. Leboyer,et al.  Human endogenous retrovirus type W (HERV-W) in schizophrenia: A new avenue of research at the gene–environment interface , 2013, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[100]  P. Cuijpers,et al.  Cognitive behavioral therapy for subjects at ultrahigh risk for developing psychosis: a randomized controlled clinical trial. , 2012, Schizophrenia bulletin.

[101]  Robert W McCarley,et al.  Gamma oscillation deficits and the onset and early progression of schizophrenia. , 2010, Harvard review of psychiatry.

[102]  M. Nordentoft,et al.  EPA guidance on the early intervention in clinical high risk states of psychoses , 2015, European Psychiatry.

[103]  Michael F. Green,et al.  Oxytocin-Augmented Social Cognitive Skills Training in Schizophrenia , 2014, Neuropsychopharmacology.

[104]  P. McGorry,et al.  Longer-term outcome in the prevention of psychotic disorders by the Vienna omega-3 study , 2015, Nature Communications.

[105]  A. Grace,et al.  Translating the MAM model of psychosis to humans , 2015, Trends in Neurosciences.

[106]  A. Cachia,et al.  Cortex morphology in first-episode psychosis patients with neurological soft signs. , 2013, Schizophrenia bulletin.

[107]  M. Millan An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy , 2013, Neuropharmacology.

[108]  M. Keshavan,et al.  Antioxidants, redox signaling, and pathophysiology in schizophrenia: an integrative view. , 2011, Antioxidants & redox signaling.

[109]  A. McAllister Major Histocompatibility Complex I in Brain Development and Schizophrenia , 2014, Biological Psychiatry.

[110]  J. Kehne,et al.  Therapeutic utility of non-peptidic CRF1 receptor antagonists in anxiety, depression, and stress-related disorders: evidence from animal models. , 2010, Pharmacology & therapeutics.

[111]  J. Feldon,et al.  Stress in Puberty Unmasks Latent Neuropathological Consequences of Prenatal Immune Activation in Mice , 2013, Science.

[112]  P. McGuire,et al.  Blunted Cortisol Awakening Response in People at Ultra High Risk of Developing Psychosis , 2014, Schizophrenia Research.

[113]  R. Rosenheck,et al.  The RAISE early treatment program for first-episode psychosis: background, rationale, and study design. , 2015, The Journal of clinical psychiatry.

[114]  T. Whitford,et al.  Understanding aberrant white matter development in schizophrenia: an avenue for therapy? , 2011, Expert review of neurotherapeutics.

[115]  S. Tapert,et al.  Adolescent brain development, substance use, and psychotherapeutic change. , 2013, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[116]  Matcheri S Keshavan,et al.  Gray matter alterations in schizophrenia high-risk youth and early-onset schizophrenia: a review of structural MRI findings. , 2013, Child and adolescent psychiatric clinics of North America.

[117]  J. Brunelin,et al.  N-Acetyl-Aspartate Level is Decreased in the Prefrontal Cortex in Subjects At-Risk for Schizophrenia , 2013, Front. Psychiatry.

[118]  G. Bartzokis Neuroglialpharmacology: Myelination as a shared mechanism of action of psychotropic treatments , 2012, Neuropharmacology.

[119]  F. Dickerson,et al.  Effect of probiotic supplementation on schizophrenia symptoms and association with gastrointestinal functioning: a randomized, placebo-controlled trial. , 2014, The primary care companion for CNS disorders.

[120]  Jimmy Lee,et al.  Altered striatal functional connectivity in subjects with an at-risk mental state for psychosis. , 2014, Schizophrenia bulletin.

[121]  D. Linszen,et al.  Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis , 2013, European Neuropsychopharmacology.

[122]  E. Rolls,et al.  Cognitive dysfunction in psychiatric disorders: characteristics, causes and the quest for improved therapy , 2012, Nature Reviews Drug Discovery.

[123]  P. Cuijpers,et al.  Preventing a first episode of psychosis: Meta-analysis of randomized controlled prevention trials of 12month and longer-term follow-ups , 2013, Schizophrenia Research.

[124]  D. Mathalon,et al.  Oxytocin administration enhances controlled social cognition in patients with schizophrenia , 2014, Psychoneuroendocrinology.

[125]  Daniel H. Mathalon,et al.  North American Prodrome Longitudinal Study (NAPLS 2): Overview and recruitment , 2012, Schizophrenia Research.

[126]  T. Nabeshima,et al.  Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. , 2012, The international journal of neuropsychopharmacology.

[127]  Wolf Singer,et al.  Oscillations and Neuronal Dynamics in Schizophrenia: The Search for Basic Symptoms and Translational Opportunities , 2015, Biological Psychiatry.

[128]  P. Uhlhaas Dysconnectivity, large-scale networks and neuronal dynamics in schizophrenia , 2013, Current Opinion in Neurobiology.

[129]  A. Guidotti,et al.  DNA-methyltransferase1 (DNMT1) binding to CpG rich GABAergic and BDNF promoters is increased in the brain of schizophrenia and bipolar disorder patients , 2015, Schizophrenia Research.

[130]  A. Yung,et al.  Medium term follow-up of a randomized controlled trial of interventions for young people at ultra high risk of psychosis , 2007, Schizophrenia Research.

[131]  A. Lajtha,et al.  GABAB/NMDA receptor interaction in the regulation of extracellular dopamine levels in rodent prefrontal cortex and striatum , 2009, Neuropharmacology.

[132]  Kristin A. Candan,et al.  Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial. , 2014, Journal of the American Academy of Child and Adolescent Psychiatry.

[133]  B. Stevens,et al.  Phagocytic glial cells: sculpting synaptic circuits in the developing nervous system , 2013, Current Opinion in Neurobiology.

[134]  L. Ferraro,et al.  Alterations of prefrontal cortex GABAergic transmission in the complex psychotic-like phenotype induced by adolescent delta-9-tetrahydrocannabinol exposure in rats , 2014, Neurobiology of Disease.

[135]  Daniel C. Javitt,et al.  Glutamatergic abnormalities in schizophrenia: A review of proton MRS findings , 2014, Schizophrenia Research.

[136]  Adrian Preda,et al.  Randomized, double-blind trial of olanzapine versus placebo in patients prodromally symptomatic for psychosis. , 2006, The American journal of psychiatry.

[137]  D. Lewis,et al.  Cortical circuit dysfunction and cognitive deficits in schizophrenia – implications for preemptive interventions , 2012, The European journal of neuroscience.

[138]  M. Ritsner,et al.  Pregnenolone treatment reduces severity of negative symptoms in recent‐onset schizophrenia: An 8‐week, double‐blind, randomized add‐on two‐center trial , 2014, Psychiatry and clinical neurosciences.

[139]  M. Pedrini,et al.  Effects of omega-3 dietary supplement in prevention of positive, negative and cognitive symptoms: A study in adolescent rats with ketamine-induced model of schizophrenia , 2012, Schizophrenia Research.

[140]  T. Insel Rethinking schizophrenia , 2010, Nature.

[141]  Igor Zwir,et al.  Uncovering the hidden risk architecture of the schizophrenias: confirmation in three independent genome-wide association studies. , 2015, The American journal of psychiatry.

[142]  R. Bentall,et al.  Three-year follow-up of a randomized controlled trial of cognitive therapy for the prevention of psychosis in people at ultrahigh risk. , 2007, Schizophrenia bulletin.

[143]  R. Sweet,et al.  Abnormal kalirin signaling in neuropsychiatric disorders , 2014, Brain Research Bulletin.

[144]  T. McGlashan,et al.  The psychosis high-risk state: a comprehensive state-of-the-art review. , 2013, JAMA psychiatry.

[145]  Daniel Durstewitz,et al.  Hippocampal–Dorsolateral Prefrontal Coupling as a Species-Conserved Cognitive Mechanism: A Human Translational Imaging Study , 2015, Neuropsychopharmacology.

[146]  M. Millan,et al.  Selective Blockade of Dopamine D3 Receptors Enhances while D2 Receptor Antagonism Impairs Social Novelty Discrimination and Novel Object Recognition in Rats: A Key Role for the Prefrontal Cortex , 2012, Neuropsychopharmacology.

[147]  P. Horn,et al.  Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response , 2012, Physiology & Behavior.

[148]  M. Schwarz,et al.  Anti-inflammatory treatment in schizophrenia , 2013, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[149]  Shikha Snigdha,et al.  Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism. , 2010, Pharmacology & therapeutics.

[150]  Ashley M. Wilson,et al.  Genome-wide profiling of multiple histone methylations in olfactory cells: further implications for cellular susceptibility to oxidative stress in schizophrenia , 2013, Molecular Psychiatry.

[151]  D. Malaspina,et al.  HPA axis function and symptoms in adolescents at clinical high risk for schizophrenia , 2012, Schizophrenia Research.

[152]  R. Murray,et al.  Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: a PET study , 2011, Molecular Psychiatry.

[153]  André A. Fenton,et al.  Early Cognitive Experience Prevents Adult Deficits in a Neurodevelopmental Schizophrenia Model , 2012, Neuron.

[154]  Godfrey Pearlson,et al.  Bipolar and schizophrenia network for intermediate phenotypes: outcomes across the psychosis continuum. , 2014, Schizophrenia bulletin.

[155]  A. Malla,et al.  Pharmacotherapy challenges in patients with first-episode psychosis. , 2012, Journal of affective disorders.

[156]  D. Geschwind,et al.  Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture , 2015, Nature Methods.

[157]  E. Bator,et al.  Valproic acid (VPA) reduces sensorimotor gating deficits and HDAC2 overexpression in the MAM animal model of schizophrenia , 2015, Pharmacological reports : PR.

[158]  Michael F. Green,et al.  Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. , 2013, JAMA psychiatry.

[159]  F. Smit,et al.  Cost-effectiveness of preventing first-episode psychosis in ultra-high-risk subjects: multi-centre randomized controlled trial , 2014, Psychological Medicine.

[160]  I. Weiner,et al.  Clozapine Administration in Adolescence Prevents Postpubertal Emergence of Brain Structural Pathology in an Animal Model of Schizophrenia , 2009, Biological Psychiatry.

[161]  Daniel H. Mathalon,et al.  Glutamatergic Modulation of Auditory Information Processing in the Human Brain , 2012, Biological Psychiatry.

[162]  H. Meltzer,et al.  Serotonin receptors as targets for drugs useful to treat psychosis and cognitive impairment in schizophrenia. , 2012, Current pharmaceutical biotechnology.

[163]  Hok Pan Yuen,et al.  Randomized controlled trial of interventions designed to reduce the risk of progression to first-episode psychosis in a clinical sample with subthreshold symptoms. , 2002, Archives of general psychiatry.

[164]  B. Morris,et al.  Advancing schizophrenia drug discovery: optimizing rodent models to bridge the translational gap , 2012, Nature Reviews Drug Discovery.

[165]  P. McGuire,et al.  Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. , 2012, Archives of general psychiatry.

[166]  Alan S. Brown Epidemiologic studies of exposure to prenatal infection and risk of schizophrenia and autism , 2012, Developmental neurobiology.

[167]  H. Schoemaker,et al.  Development of disease-modifying treatment of schizophrenia. , 2012, Handbook of experimental pharmacology.

[168]  P. Fusar-Poli,et al.  Effects of Antipsychotics on Dentate Gyrus Stem Cell Proliferation and Survival in Animal Models: A Critical Update , 2012, Neural plasticity.

[169]  A. Mackay-Sim Concise Review: Patient‐Derived Olfactory Stem Cells: New Models for Brain Diseases , 2012, Stem cells.

[170]  L. Vanderschuren,et al.  On the interaction between drugs of abuse and adolescent social behavior , 2014, Psychopharmacology.

[171]  M. Nordentoft,et al.  EPA guidance on the early detection of clinical high risk states of psychoses , 2015, European Psychiatry.

[172]  M. Missler,et al.  Neurexins , 2013, Genome Biology.

[173]  Korey P. Wylie,et al.  Functional magnetic resonance imaging of intrinsic brain networks for translational drug discovery. , 2014, Trends in pharmacological sciences.

[174]  J. Zwiller,et al.  The HDAC Inhibitor Phenylbutyrate Reverses Effects of Neonatal Ventral Hippocampal Lesion in Rats , 2011, Front. Psychiatry.

[175]  R. Gur,et al.  GABAB-mediated rescue of altered excitatory–inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction , 2012, Translational Psychiatry.

[176]  Swaran P Singh,et al.  Early intervention in psychosis , 2010, British Journal of Psychiatry.

[177]  T. Hyde,et al.  Molecular mechanisms and timing of cortical immune activation in schizophrenia. , 2015, The American journal of psychiatry.

[178]  C. Tamminga,et al.  Kv3.1-containing K+ channels are reduced in untreated schizophrenia and normalized with antipsychotic drugs , 2014, Molecular Psychiatry.

[179]  R. Kahn,et al.  Efficacy of anti-inflammatory agents to improve symptoms in patients with schizophrenia: an update. , 2014, Schizophrenia bulletin.

[180]  James N. Samsom,et al.  Schizophrenia and Depression Co-Morbidity: What We have Learned from Animal Models , 2015, Front. Psychiatry.

[181]  Stephan Ruhrmann,et al.  Improving the clinical prediction of psychosis by combining ultra-high risk criteria and cognitive basic symptoms , 2014, Schizophrenia Research.

[182]  David W. Nauen,et al.  Synaptic dysregulation in a human iPS cell model of mental disorders , 2014, Nature.

[183]  Amene Shahrokhi,et al.  Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring , 2014, Science.

[184]  Zheng Li,et al.  Age–dependent regulation of synaptic connections by dopamine D2 receptors , 2013, Nature Neuroscience.

[185]  O. Kann The interneuron energy hypothesis: Implications for brain disease , 2016, Neurobiology of Disease.

[186]  M. Millan,et al.  5-HT6 receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia , 2012, EMBO molecular medicine.

[187]  Bradley S. Peterson,et al.  Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits , 2014, Neuron.

[188]  Anirvan Ghosh,et al.  Drug discovery for autism spectrum disorder: challenges and opportunities , 2013, Nature Reviews Drug Discovery.

[189]  A. Kakita,et al.  Transient exposure of neonatal mice to neuregulin-1 results in hyperdopaminergic states in adulthood: implication in neurodevelopmental hypothesis for schizophrenia , 2011, Molecular Psychiatry.

[190]  M. Keshavan,et al.  Multivariate prediction of emerging psychosis in adolescents at high risk for schizophrenia , 2012, Schizophrenia Research.

[191]  T. Woo,et al.  Molecular Profiles of Parvalbumin-Immunoreactive Neurons in the Superior Temporal Cortex in Schizophrenia , 2014, Journal of neurogenetics.

[192]  Jian Guo,et al.  Cerebrolysin for vascular dementia. , 2013, The Cochrane database of systematic reviews.

[193]  M. Catani,et al.  Neuroconnectivity and valproic acid: The myelin hypothesis , 2012, Neuroscience & Biobehavioral Reviews.

[194]  A. Martinez,et al.  Phencyclidine-Induced Social Withdrawal Results from Deficient Stimulation of Cannabinoid CB1 Receptors: Implications for Schizophrenia , 2013, Neuropsychopharmacology.

[195]  T. McGlashan,et al.  At risk or not at risk? A meta‐analysis of the prognostic accuracy of psychometric interviews for psychosis prediction , 2015, World psychiatry : official journal of the World Psychiatric Association.

[196]  S. Tonegawa,et al.  Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486 , 2013, Proceedings of the National Academy of Sciences.

[197]  R. Kahn,et al.  Adolescents at ultra-high risk for psychosis: Long-term outcome of individuals who recover from their at-risk state , 2014, European Neuropsychopharmacology.

[198]  C. Pantelis,et al.  Effects of NRG1 and DAOA genetic variation on transition to psychosis in individuals at ultra-high risk for psychosis , 2013, Translational Psychiatry.

[199]  J. Kauer,et al.  Kappa Opioid Receptors Regulate Stress-Induced Cocaine Seeking and Synaptic Plasticity , 2013, Neuron.

[200]  J. Gaiarsa,et al.  Emerging neurotrophic role of GABAB receptors in neuronal circuit development , 2013, Front. Cell. Neurosci..

[201]  F. Tang,et al.  Gadd45a promotes DNA demethylation through TDG , 2015, Nucleic acids research.

[202]  Norio Ozaki,et al.  Adolescent Stress–Induced Epigenetic Control of Dopaminergic Neurons via Glucocorticoids , 2013, Science.

[203]  I. Weiner,et al.  Risperidone administered during asymptomatic period of adolescence prevents the emergence of brain structural pathology and behavioral abnormalities in an animal model of schizophrenia. , 2011, Schizophrenia bulletin.

[204]  Danielle A Schlosser,et al.  Environmental Risk and Protective Factors and Their Influence on the Emergence of Psychosis. , 2012, Adolescent psychiatry.

[205]  D. Javitt,et al.  D-serine for the treatment of negative symptoms in individuals at clinical high risk of schizophrenia: a pilot, double-blind, placebo-controlled, randomised parallel group mechanistic proof-of-concept trial. , 2015, The lancet. Psychiatry.

[206]  A. Mackinnon,et al.  Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. , 2010, Archives of general psychiatry.

[207]  S. Smesny,et al.  Polyunsaturated fatty acids in emerging psychosis: a safer alternative? , 2014, Early intervention in psychiatry.

[208]  M. Berk,et al.  The promise of N-acetylcysteine in neuropsychiatry. , 2013, Trends in pharmacological sciences.

[209]  J. Ragland,et al.  Clinical and Functional Outcomes After 2 Years in the Early Detection and Intervention for the Prevention of Psychosis Multisite Effectiveness Trial , 2014, Schizophrenia bulletin.

[210]  E. Kandel,et al.  Selective Overexpression of Dopamine D3 Receptors in the Striatum Disrupts Motivation but not Cognition , 2014, Biological Psychiatry.

[211]  Nouchine Hadjikhani,et al.  Improving emotional face perception in autism with diuretic bumetanide: A proof-of-concept behavioral and functional brain imaging pilot study , 2015, Autism : the international journal of research and practice.

[212]  Francesco Papaleo,et al.  Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110δ inhibition as a potential therapeutic strategy , 2012, Proceedings of the National Academy of Sciences.

[213]  Catherine A. Sugar,et al.  Characterization of Neurophysiologic and Neurocognitive Biomarkers for Use in Genomic and Clinical Outcome Studies of Schizophrenia , 2012, PloS one.

[214]  J. Duan,et al.  MicroRNA-9 and MicroRNA-326 Regulate Human Dopamine D2 Receptor Expression, and the MicroRNA-mediated Expression Regulation Is Altered by a Genetic Variant* , 2014, The Journal of Biological Chemistry.

[215]  G. Pearlson,et al.  Glycine treatment of the risk syndrome for psychosis: Report of two pilot studies , 2013, European Neuropsychopharmacology.

[216]  A. Guidotti,et al.  Toward the Identification of Peripheral Epigenetic Biomarkers of Schizophrenia , 2014, Journal of neurogenetics.

[217]  K. Brennand,et al.  Altered WNT Signaling in Human Induced Pluripotent Stem Cell Neural Progenitor Cells Derived from Four Schizophrenia Patients , 2015, Biological Psychiatry.

[218]  Tyrone D. Cannon,et al.  The relationship of neurocognition and negative symptoms to social and role functioning over time in individuals at clinical high risk in the first phase of the North American Prodrome Longitudinal Study. , 2014, Schizophrenia bulletin.

[219]  R. Straub,et al.  Incomplete penetrance of NRXN1 deletions in families with schizophrenia , 2014, Schizophrenia Research.

[220]  Yanhong Shi,et al.  MicroRNAs: Small molecules with big roles in neurodevelopment and diseases , 2015, Experimental Neurology.

[221]  Olena M. Babenko,et al.  Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health , 2015, Neuroscience & Biobehavioral Reviews.

[222]  David A. Lewis,et al.  Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia , 2012, Trends in Neurosciences.

[223]  Fred H. Gage,et al.  Modelling schizophrenia using human induced pluripotent stem cells , 2011, Nature.

[224]  M. Owen,et al.  Attenuated psychosis syndrome in DSM-5 , 2013, Schizophrenia Research.

[225]  N. Andreasen,et al.  Progressive brain changes in schizophrenia related to antipsychotic treatment? A meta-analysis of longitudinal MRI studies , 2013, Neuroscience & Biobehavioral Reviews.

[226]  Hassan Rahmoune,et al.  Neuroimmune biomarkers in schizophrenia , 2016, Schizophrenia Research.

[227]  Rajita Sinha,et al.  Translational and reverse translational research on the role of stress in drug craving and relapse , 2011, Psychopharmacology.

[228]  Lan Xiao,et al.  Improving myelin/oligodendrocyte-related dysfunction: a new mechanism of antipsychotics in the treatment of schizophrenia? , 2013, The international journal of neuropsychopharmacology.

[229]  Sarah-Jayne Blakemore,et al.  Is adolescence a sensitive period for sociocultural processing? , 2014, Annual review of psychology.

[230]  E. Bator,et al.  Prenatal MAM administration affects histone H3 methylation in postnatal life in the rat medial prefrontal cortex , 2014, European Neuropsychopharmacology.

[231]  R. Ghomi,et al.  Schizophrenia and the gut–brain axis , 2015, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[232]  R. Straub,et al.  Characteristics of the Cation Cotransporter NKCC1 in Human Brain: Alternate Transcripts, Expression in Development, and Potential Relationships to Brain Function and Schizophrenia , 2014, The Journal of Neuroscience.

[233]  M. Pessiglione,et al.  Confidence and psychosis: a neuro-computational account of contingency learning disruption by NMDA blockade , 2015, Molecular Psychiatry.

[234]  F. Schneider,et al.  Rationale and baseline characteristics of PREVENT: a second-generation intervention trial in subjects at-risk (prodromal) of developing first-episode psychosis evaluating cognitive behavior therapy, aripiprazole, and placebo for the prevention of psychosis. , 2011, Schizophrenia bulletin.

[235]  R. Yolken,et al.  Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset , 2015, Translational Psychiatry.

[236]  Jay N. Giedd,et al.  Adolescent mental health—Opportunity and obligation , 2014, Science.

[237]  G. Koob Addiction is a Reward Deficit and Stress Surfeit Disorder , 2013, Front. Psychiatry.

[238]  H. Möller,et al.  Coping as a predictor of treatment outcome in people at clinical high risk of psychosis , 2016, Early intervention in psychiatry.

[239]  P. O’Donnell Adolescent onset of cortical disinhibition in schizophrenia: insights from animal models. , 2011, Schizophrenia bulletin.

[240]  A. Schatzberg Anna-Monika Award Lecture, DGPPN Kongress, 2013: The role of the hypothalamic–pituitary–adrenal (HPA) axis in the pathogenesis of psychotic major depression , 2015, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[241]  Gabriele Deidda,et al.  Modulation of GABAergic transmission in development and neurodevelopmental disorders: investigating physiology and pathology to gain therapeutic perspectives , 2014, Front. Cell. Neurosci..

[242]  I. Hickie,et al.  Cultures for mental health care of young people: an Australian blueprint for reform. , 2014, The lancet. Psychiatry.

[243]  D. Muller,et al.  GluN3A Promotes Dendritic Spine Pruning and Destabilization during Postnatal Development , 2014, The Journal of Neuroscience.

[244]  Scott J. Russo,et al.  HDAC2 regulates atypical antipsychotic responses through the modulation of mGlu2 promoter activity , 2012, Nature Neuroscience.

[245]  M. Papp,et al.  S32006, a novel 5-HT2C receptor antagonist displaying broad-based antidepressant and anxiolytic properties in rodent models , 2008, Psychopharmacology.

[246]  Fred H. Gage,et al.  Modeling Hippocampal Neurogenesis Using Human Pluripotent Stem Cells , 2014, Stem cell reports.

[247]  M. Owen,et al.  Genomic insights into the overlap between psychiatric disorders: implications for research and clinical practice , 2014, Genome Medicine.

[248]  J. Waddington,et al.  Phenotypic effects of repeated psychosocial stress during adolescence in mice mutant for the schizophrenia risk gene neuregulin-1: A putative model of gene×environment interaction , 2012, Brain, Behavior, and Immunity.

[249]  E. Mayo-Wilson,et al.  Early interventions to prevent psychosis: systematic review and meta-analysis , 2013, BMJ.

[250]  P. Lichtenstein,et al.  The association between schizophrenia and rheumatoid arthritis: a nationwide population-based Swedish study on intraindividual and familial risks. , 2014, Schizophrenia bulletin.

[251]  Patrick D McGorry,et al.  Update on Omega-3 Polyunsaturated Fatty Acids in Early-Stage Psychotic Disorders , 2012, Neuropsychopharmacology.

[252]  C. Mathers,et al.  Global burden of disease in young people aged 10–24 years: a systematic analysis , 2011, The Lancet.

[253]  K. Hamazaki,et al.  Possibility of polyunsaturated fatty acids for the prevention and treatment of neuropsychiatric illnesses. , 2014, Journal of pharmacological sciences.

[254]  M. Millan,et al.  Towards improved animal models for evaluating social cognition and its disruption in schizophrenia: The CNTRICS initiative , 2013, Neuroscience & Biobehavioral Reviews.

[255]  M. Harrow,et al.  Does treatment of schizophrenia with antipsychotic medications eliminate or reduce psychosis? A 20-year multi-follow-up study , 2014, Psychological Medicine.

[256]  P. Patterson Immune involvement in schizophrenia and autism: Etiology, pathology and animal models , 2009, Behavioural Brain Research.

[257]  P. Penzes,et al.  Dendritic spine pathology in neuropsychiatric disorders , 2011, Nature Neuroscience.

[258]  Dimitris Mavridis,et al.  Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis , 2013, The Lancet.

[259]  J. Boggs,et al.  G protein‐coupled receptor 30 contributes to improved remyelination after cuprizone‐induced demyelination , 2013, Glia.

[260]  P. Churchland,et al.  Modulating social behavior with oxytocin: How does it work? What does it mean? , 2012, Hormones and Behavior.

[261]  Shuki J. Cohen,et al.  Aripiprazole in the treatment of the psychosis prodrome: an open-label pilot study. , 2007, The British journal of psychiatry. Supplement.

[262]  R. Roth,et al.  Phencyclidine-induced Loss of Asymmetric Spine Synapses in Rodent Prefrontal Cortex is Reversed by Acute and Chronic Treatment with Olanzapine , 2011, Neuropsychopharmacology.

[263]  A. Mechelli,et al.  Using Structural Neuroimaging to Make Quantitative Predictions of Symptom Progression in Individuals at Ultra-High Risk for Psychosis , 2014, Front. Psychiatry.

[264]  J. Quevedo,et al.  Omega-3 prevents behavior response and brain oxidative damage in the ketamine model of schizophrenia , 2014, Neuroscience.

[265]  A. Egerton,et al.  Modelling prefrontal cortex deficits in schizophrenia: implications for treatment , 2008, British journal of pharmacology.

[266]  Thomas Steckler,et al.  Negative symptoms of schizophrenia: Clinical characteristics, pathophysiological substrates, experimental models and prospects for improved treatment , 2014, European Neuropsychopharmacology.

[267]  T. Schmitz,et al.  Oligodendroglial Alterations and the Role of Microglia in White Matter Injury: Relevance to Schizophrenia , 2013, Developmental Neuroscience.

[268]  M. Kassiou,et al.  Effect of maternal immune activation on the kynurenine pathway in preadolescent rat offspring and on MK801-induced hyperlocomotion in adulthood: Amelioration by COX-2 inhibition , 2014, Brain, Behavior, and Immunity.

[269]  E. Rabiner,et al.  Occupancy of Brain Dopamine D3 Receptors and Drug Craving: A Translational Approach , 2013, Neuropsychopharmacology.

[270]  P. McGorry Transition to adulthood: the critical period for pre-emptive, disease-modifying care for schizophrenia and related disorders. , 2011, Schizophrenia bulletin.

[271]  I. Hickie,et al.  NEURAPRO‐E study protocol: a multicentre randomized controlled trial of omega‐3 fatty acids and cognitive‐behavioural case management for patients at ultra high risk of schizophrenia and other psychotic disorders , 2017, Early intervention in psychiatry.

[272]  P. Mcguire,et al.  Outreach and support in South London (OASIS), 2001–2011: Ten years of early diagnosis and treatment for young individuals at high clinical risk for psychosis , 2013, European Psychiatry.

[273]  Tyrone D. Cannon,et al.  Towards a Psychosis Risk Blood Diagnostic for Persons Experiencing High-Risk Symptoms: Preliminary Results From the NAPLS Project , 2014, Schizophrenia bulletin.

[274]  Klaus Scheffler,et al.  Different duration of at‐risk mental state associated with neurofunctional abnormalities. A multimodal imaging study , 2012, Human brain mapping.

[275]  Sarah-Jayne Blakemore,et al.  Adolescence: a foundation for future health , 2012, The Lancet.

[276]  J. Feldon,et al.  Evaluating early preventive antipsychotic and antidepressant drug treatment in an infection-based neurodevelopmental mouse model of schizophrenia. , 2010, Schizophrenia bulletin.

[277]  Daniel R. Weinberger,et al.  Functional neuroimaging and schizophrenia: a view towards effective connectivity modeling and polygenic risk , 2013, Dialogues in clinical neuroscience.

[278]  R. Murray,et al.  Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: an MRI study in subjects at ultrahigh risk of psychosis. , 2012, Schizophrenia bulletin.

[279]  J. Roder,et al.  Prophylactic Valproic Acid Treatment Prevents Schizophrenia-Related Behaviour in Disc1-L100P Mutant Mice , 2012, PloS one.

[280]  F. Gage,et al.  A regenerative approach to the treatment of multiple sclerosis , 2013, Nature.

[281]  P. Boksa,et al.  Abnormal synaptic pruning in schizophrenia: Urban myth or reality? , 2012, Journal of psychiatry & neuroscience : JPN.

[282]  V. Caputo,et al.  The emerging role of MicroRNA in schizophrenia. , 2015, CNS & neurological disorders drug targets.

[283]  J. Petrosino,et al.  Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders , 2013, Cell.

[284]  A. Mackinnon,et al.  Long-Chain -3 Fatty Acids for Indicated Prevention of Psychotic Disorders A Randomized, Placebo-Controlled Trial , 2010 .

[285]  R. D'Hooge,et al.  Behavioural alterations relevant to developmental brain disorders in mice with neonatally induced ventral hippocampal lesions , 2013, Brain Research Bulletin.

[286]  J. Lieberman,et al.  Signaling pathways in schizophrenia: emerging targets and therapeutic strategies. , 2010, Trends in pharmacological sciences.

[287]  Yu-Qiang Ding,et al.  Neonatal intrahippocampal injection of lipopolysaccharide induces deficits in social behavior and prepulse inhibition and microglial activation in rats: Implication for a new schizophrenia animal model , 2014, Brain, Behavior, and Immunity.

[288]  J. Klosterkötter,et al.  Forecasting Psychosis by Event-Related Potentials—Systematic Review and Specific Meta-Analysis , 2015, Biological Psychiatry.

[289]  A. Hayashi‐Takagi,et al.  PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence , 2014, Proceedings of the National Academy of Sciences.

[290]  T. Vos,et al.  The economic analysis of prevention in mental health programs. , 2011, Annual review of clinical psychology.

[291]  L. Mei,et al.  Reversal of Behavioral Deficits and Synaptic Dysfunction in Mice Overexpressing Neuregulin 1 , 2013, Neuron.

[292]  J. Veijola,et al.  A systematic review and meta-analysis of recovery in schizophrenia. , 2013, Schizophrenia bulletin.

[293]  E. Bézard,et al.  Slowing of neurodegeneration in Parkinson's disease and Huntington's disease: future therapeutic perspectives , 2014, The Lancet.

[294]  G. Bartzokis,et al.  Multimodal Magnetic Resonance Imaging Assessment of White Matter Aging Trajectories Over the Lifespan of Healthy Individuals , 2012, Biological Psychiatry.

[295]  Steven C. R. Williams,et al.  Using genetic, cognitive and multi-modal neuroimaging data to identify ultra-high-risk and first-episode psychosis at the individual level , 2013, Psychological Medicine.

[296]  M. V. D. Heuvel,et al.  Brain Networks in Schizophrenia , 2014, Neuropsychology Review.

[297]  S. Silverstein,et al.  Inflammation and the two-hit hypothesis of schizophrenia , 2014, Neuroscience & Biobehavioral Reviews.

[298]  D. Srivastava,et al.  Molecular signature of rapid estrogen regulation of synaptic connectivity and cognition , 2015, Frontiers in Neuroendocrinology.

[299]  Bita Moghaddam,et al.  The neurobiology of adolescence: Changes in brain architecture, functional dynamics, and behavioral tendencies , 2011, Neuroscience & Biobehavioral Reviews.

[300]  Stephan Heckers,et al.  Definition and description of schizophrenia in the DSM-5 , 2013, Schizophrenia Research.

[301]  W. Maier,et al.  Preventing progression to first-episode psychosis in early initial prodromal states , 2012, British Journal of Psychiatry.

[302]  A. Grace,et al.  Peripubertal Diazepam Administration Prevents the Emergence of Dopamine System Hyperresponsivity in the MAM Developmental Disruption Model of Schizophrenia , 2013, Neuropsychopharmacology.

[303]  A. Mechelli,et al.  Dysconnectivity in schizophrenia: Where are we now? , 2011, Neuroscience & Biobehavioral Reviews.

[304]  M. Olfson,et al.  Treatment of Young People With Antipsychotic Medications in the United States. , 2015, JAMA psychiatry.

[305]  T. Dinan,et al.  Microbiota and neurodevelopmental windows: implications for brain disorders. , 2014, Trends in molecular medicine.

[306]  S. Mazmanian,et al.  Modeling an autism risk factor in mice leads to permanent immune dysregulation , 2012, Proceedings of the National Academy of Sciences.

[307]  E. Walker,et al.  Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders , 2010, Expert review of neurotherapeutics.

[308]  K. Nuechterlein,et al.  The RAISE Connection Program for Early Psychosis: Secondary Outcomes and Mediators and Moderators of Improvement , 2015, The Journal of nervous and mental disease.

[309]  Tyrone D. Cannon,et al.  Progressive Reduction in Cortical Thickness as Psychosis Develops: A Multisite Longitudinal Neuroimaging Study of Youth at Elevated Clinical Risk , 2015, Biological Psychiatry.

[310]  P. Fusar-Poli,et al.  The Psychosis High-Risk State , 2016 .

[311]  J. Lieberman,et al.  Implementing Coordinated Specialty Care for Early Psychosis: The RAISE Connection Program. , 2015, Psychiatric services.

[312]  Peter B. Jones,et al.  Early detection and intervention evaluation for people at risk of psychosis: multisite randomised controlled trial , 2012, BMJ : British Medical Journal.

[313]  T. Jay,et al.  Long-term consequences of adolescent cannabinoid exposure in adult psychopathology , 2014, Front. Neurosci..

[314]  A. Gumley,et al.  A meta-analysis and theoretical critique of oxytocin and psychosis: prospects for attachment and compassion in promoting recovery. , 2014, The British journal of clinical psychology.

[315]  C. Kruse,et al.  5-HT6 Receptor Antagonists: Potential Efficacy for the Treatment of Cognitive Impairment in Schizophrenia. , 2015, Current pharmaceutical design.

[316]  E. Kong,et al.  The poly(I:C)-induced maternal immune activation model in preclinical neuropsychiatric drug discovery. , 2015, Pharmacology & therapeutics.

[317]  Robin M. Murray,et al.  Neurological soft signs in first-episode psychosis: A systematic review , 2002, British Journal of Psychiatry.

[318]  S. Rapoport,et al.  Adolescent Behavior and Dopamine Availability Are Uniquely Sensitive to Dietary Omega-3 Fatty Acid Deficiency , 2014, Biological Psychiatry.

[319]  Francesco Sforazzini,et al.  Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior , 2014, Nature Neuroscience.

[320]  J N Giedd,et al.  Neurodevelopmental model of schizophrenia: update 2012 , 2012, Molecular Psychiatry.