The blood–brain barrier in psychosis

Abbott, 2014, Anatomy and physiology of the blood–brain barriers Abbott, 2010, Structure and function of the blood–brain barrier, Neurobiol Dis, 37, 13, 10.1016/j.nbd.2009.07.030 Abbott, 2006, Astrocyte-endothelial interactions at the blood–brain barrier, Nat Rev Neurosci, 7, 41, 10.1038/nrn1824 Obermeier, 2013, Development, maintenance and disruption of the blood–brain barrier, Nat Med, 19, 1584, 10.1038/nm.3407 Obermeier, 2016, The blood–brain barrier, vol 133, 39 Blanchette, 2015, Formation and maintenance of the BBB, Mech Dev, 138, 8, 10.1016/j.mod.2015.07.007 Haseloff, 2015, Transmembrane proteins of the tight junctions at the blood–brain barrier: structural and functional aspects, Semin Cell Dev Biol, 38, 16, 10.1016/j.semcdb.2014.11.004 Stamatovic, 2016, Junctional proteins of the blood–brain barrier: new insights into function and dysfunction, Tissue Barriers, 4, e1154641, 10.1080/21688370.2016.1154641 Tietz, 2015, Brain barriers: crosstalk between complex tight junctions and adherens junctions, J Cell Biol, 209, 493, 10.1083/jcb.201412147 Qosa, 2015, Regulation of ABC efflux transporters at blood–brain barrier in health and neurological disorders, Brain Res, 1628, 298, 10.1016/j.brainres.2015.07.005 Hladky, 2016, Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles, Fluids Barriers CNS, 13, 19, 10.1186/s12987-016-0040-3 Brinker, 2014, A new look at cerebrospinal fluid circulation, Fluids Barriers CNS, 11, 10, 10.1186/2045-8118-11-10 Daneman, 2015, The blood–brain barrier, Cold Spring Harb Perspect Biol, 7, a020412, 10.1101/cshperspect.a020412 Preston, 2014, Transcytosis of macromolecules at the blood–brain barrier, Adv Pharmacol, 71, 147, 10.1016/bs.apha.2014.06.001 Muller, 2016, Transendothelial migration: unifying principles from the endothelial perspective, Immunol Rev, 273, 61, 10.1111/imr.12443 Lun, 2015, Development and functions of the choroid plexus–cerebrospinal fluid system, Nat Rev Neurosci, 16, 445, 10.1038/nrn3921 Marques, 2015, The choroid plexus is modulated by various peripheral stimuli: implications to diseases of the central nervous system, Front Cell Neurosci, 9, 136, 10.3389/fncel.2015.00136 Keaney, 2015, The dynamic blood–brain barrier, FEBS J, 282, 4067, 10.1111/febs.13412 Iadecola, 2007, Glial regulation of the cerebral microvasculature, Nat Neurosci, 10, 1369, 10.1038/nn2003 McConnell, 2017, The translational significance of the neurovascular unit, J Biol Chem, 292, 762, 10.1074/jbc.R116.760215 Stanimirovic, 2012, Pathophysiology of the neurovascular unit: disease cause or consequence?, J Cereb Blood Flow Metab, 32, 1207, 10.1038/jcbfm.2012.25 Engelhardt, 2011, Fluids and barriers of the CNS establish immune privilege by confining immune surveillance to a two-walled castle moat surrounding the CNS castle, Fluids Barriers CNS, 8, 4, 10.1186/2045-8118-8-4 Gorter, 2015, Status epilepticus, blood–brain barrier disruption, inflammation, and epileptogenesis, Epilepsy Behav, 49, 13, 10.1016/j.yebeh.2015.04.047 Lopes Pinheiro, 2016, Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke, Biochim Biophys Acta, 1862, 461, 10.1016/j.bbadis.2015.10.018 Ransohoff, 2015, Neuroinflammation: ways in which the immune system affects the brain, Neurotherapeutics, 12, 896, 10.1007/s13311-015-0385-3 Tenreiro, 2016, Cellular response of the blood–brain barrier to injury: potential biomarkers and therapeutic targets for brain regeneration, Neurobiol Dis, 91, 262, 10.1016/j.nbd.2016.03.014 Burgmans, 2013, Amyloid-β interacts with blood–brain barrier function in dementia: a systematic review, J Alzheimers Dis, 35, 859, 10.3233/JAD-122155 Bodor, 2003, Brain-targeted drug delivery. Experiences to date, Am J Drug Deliv, 1, 13, 10.2165/00137696-200301010-00002 Summerfield, 2016, Examining the uptake of central nervous system drugs and candidates across the blood–brain barrier, J Pharmacol Exp Ther, 358, 294, 10.1124/jpet.116.232447 Domenici, 2010, Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections, PLoS One, 5, e9166, 10.1371/journal.pone.0009166 Yamamori, 2013, Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) in treatment-resistant schizophrenia treated with clozapine, Neurosci Lett, 556, 37, 10.1016/j.neulet.2013.09.059 de Klerk, 2010, Regional increase in P-glycoprotein function in the blood–brain barrier of patients with chronic schizophrenia: a PET study with [(11)C]verapamil as a probe for P-glycoprotein function, Psychiatry Res, 183, 151, 10.1016/j.pscychresns.2010.05.002 Bernstein, 2016, Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: circumscribed deficits in the habenula, Schizophr Res, 177, 52, 10.1016/j.schres.2016.02.036 Wolking, 2015, Impact of genetic polymorphisms of ABCB1 (MDR1, P-glycoprotein) on drug disposition and potential clinical implications: update of the literature, Clin Pharmacokinet, 54, 709, 10.1007/s40262-015-0267-1 Omidinia, 2014, Polymorphism of the CLDN5 gene and schizophrenia in an Iranian population, Iran J Public Health, 43, 79 Wu, 2010, A weak association of the CLDN5 locus with schizophrenia in Chinese case-control samples, Psychiatry Res, 178, 223, 10.1016/j.psychres.2009.11.019 Ye, 2005, Further study of a genetic association between the CLDN5 locus and schizophrenia, Schizophr Res, 75, 139, 10.1016/j.schres.2004.11.003 Sun, 2004, The CLDN5 locus may be involved in the vulnerability to schizophrenia, Eur Psychiatry, 19, 354, 10.1016/j.eurpsy.2004.06.007 Walsh, 2002, Elevated expression of integrin alpha(IIb) beta(IIIa) in drug-naive, first-episode schizophrenic patients, Biol Psychiatry, 52, 874, 10.1016/S0006-3223(02)01400-2 Masopust, 2011, Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study, BMC Psychiatry, 11, 2, 10.1186/1471-244X-11-2 Iwata, 2007, Increased levels of serum soluble L-selectin in unmedicated patients with schizophrenia, Schizophr Res, 89, 154, 10.1016/j.schres.2006.08.026 Schwarz, 2000, Decreased levels of soluble intercellular adhesion molecule-1 (sICAM-1) in unmedicated and medicated schizophrenic patients, Biol Psychiatry, 47, 29, 10.1016/S0006-3223(99)00206-1 Schwarz, 1998, Blood-cerebrospinal fluid barrier impairment as indicator for an immune process in schizophrenia, Neurosci Lett, 253, 201, 10.1016/S0304-3940(98)00655-7 Kaur, 2016, The choroid plexus in healthy and diseased brain, J Neuropathol Exp Neurol, 75, 198, 10.1093/jnen/nlv030 Wolak, 2013, Diffusion of macromolecules in the brain: implications for drug delivery, Mol Pharm, 10, 1492, 10.1021/mp300495e Wolak, 2015, Probing the extracellular diffusion of antibodies in brain using in vivo integrative optical imaging and ex vivo fluorescence imaging, J Control Release, 197, 78, 10.1016/j.jconrel.2014.10.034 Cserr, 1981, Efflux of radiolabeled polyethylene glycols and albumin from rat brain, Am J Physiol, 240, F319 Bradbury, 1981, Drainage of cerebral interstitial fluid into deep cervical lymph of the rabbit, Am J Physiol, 240, F329 Szentistványi, 1984, Drainage of interstitial fluid from different regions of rat brain, Am J Physiol, 246, F835 Abbott, 2004, Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology, Neurochem Int, 45, 545, 10.1016/j.neuint.2003.11.006 Rennels, 1985, Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space, Brain Res, 326, 47, 10.1016/0006-8993(85)91383-6 Iliff, 2012, A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β, Sci Transl Med, 4, 147ra111, 10.1126/scitranslmed.3003748 Hladky, 2014, Mechanisms of fluid movement into, through and out of the brain: evaluation of the evidence, Fluids Barriers CNS, 11, 26, 10.1186/2045-8118-11-26 Jin, 2016, Spatial model of convective solute transport in brain extracellular space does not support a “glymphatic” mechanism, J Gen Physiol, 148, 489, 10.1085/jgp.201611684 Engelhardt, 2017, The movers and shapers in immune privilege of the CNS, Nat Immunol, 18, 123, 10.1038/ni.3666 Bache, 2015, Detection and quantification of microRNA in cerebral microdialysate, J Transl Med, 13, 149, 10.1186/s12967-015-0505-1 Herukka, 2015, Amyloid-β and tau dynamics in human brain interstitial fluid in patients with suspected normal pressure hydrocephalus, J Alzheimers Dis, 46, 261, 10.3233/JAD-142862 Wright, 2012, Cerebrospinal fluid and lumbar puncture: a practical review, J Neurol, 259, 1530, 10.1007/s00415-012-6413-x de Lange, 2013, Utility of CSF in translational neuroscience, J Pharmacokinet Pharmacodyn, 40, 315, 10.1007/s10928-013-9301-9 Bechter, 2010, Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood–CSF barrier dysfunction, J Psychiatr Res, 44, 321, 10.1016/j.jpsychires.2009.08.008 Severance, 2015, IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia, Brain Behav Immun, 44, 148, 10.1016/j.bbi.2014.09.009 McCullumsmith, 2014, Postmortem brain: an underutilized substrate for studying severe mental illness, Neuropsychopharmacology, 39, 65, 10.1038/npp.2013.239 Harris, 2008, The cerebral microvasculature in schizophrenia: a laser capture microdissection study, PLoS One, 3, e3964, 10.1371/journal.pone.0003964 Najjar, 2015, Neuroinflammation and white matter pathology in schizophrenia: systematic review, Schizophr Res, 161, 102, 10.1016/j.schres.2014.04.041 Vostrikov, 2008, Deficit of pericapillary oligodendrocytes in the prefrontal cortex in schizophrenia, World J Biol Psychiatry, 9, 34, 10.1080/15622970701210247 Webster, 2001, Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression, Brain Behav Immun, 15, 388, 10.1006/brbi.2001.0646 Webster, 2005, Glial fibrillary acidic protein mRNA levels in the cingulate cortex of individuals with depression, bipolar disorder and schizophrenia, Neuroscience, 133, 453, 10.1016/j.neuroscience.2005.02.037 Busse, 2012, Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: further evidence for disease course-related immune alterations?, Brain Behav Immun, 26, 1273, 10.1016/j.bbi.2012.08.005 Hwang, 2013, Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia, Transl Psychiatry, 3, e321, 10.1038/tp.2013.94 Kim, 2016, Transcriptome sequencing of the choroid plexus in schizophrenia, Transl Psychiatry, 6, e964, 10.1038/tp.2016.229 Strathmann, 2014, Blood-based biomarkers for traumatic brain injury: evaluation of research approaches, available methods and potential utility from the clinician and clinical laboratory perspectives, Clin Biochem, 47, 876, 10.1016/j.clinbiochem.2014.01.028 Schümberg, 2016, Serum S100B is related to illness duration and clinical symptoms in schizophrenia— a meta-regression analysis, Front Cell Neurosci, 10, 46, 10.3389/fncel.2016.00046 Aleksovska, 2014, Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia, PLoS One, 9, e106342, 10.1371/journal.pone.0106342 Steiner, 2010, S100B serum levels are closely correlated with body mass index: an important caveat in neuropsychiatric research, Psychoneuroendocrinology, 35, 321, 10.1016/j.psyneuen.2009.07.012 Niitsu, 2014, A positive correlation between serum levels of mature brain-derived neurotrophic factor and negative symptoms in schizophrenia, Psychiatry Res, 215, 268, 10.1016/j.psychres.2013.12.009 Veksler, 2014, Blood–brain barrier imaging in human neuropathologies, Arch Med Res, 45, 646, 10.1016/j.arcmed.2014.11.016 Sandyk, 1993, Choroid plexus calcification as a possible marker of hallucinations in schizophrenia, Int J Neurosci, 71, 87, 10.3109/00207459309000595 Sandyk, 1990, Calcification of the choroid plexus as a marker of depression in schizophrenia, Schizophr Res, 3, 361, 10.1016/0920-9964(90)90024-2 Szymanski, 1991, Gadolinium-DTPA enhanced gradient echo magnetic resonance scans in first episode of psychosis and chronic schizophrenic patients, Psychiatry Res, 40, 203, 10.1016/0925-4927(91)90011-E Montagne, 2015, Blood–brain barrier breakdown in the aging human hippocampus, Neuron, 85, 296, 10.1016/j.neuron.2014.12.032 Hua, 2017, Abnormal grey matter arteriolar cerebral blood volume in schizophrenia measured with 3D inflow-based vascular-space-occupancy MRI at 7T, Schizophr Bull, 43, 620 Brambilla, 2007, Assessment of cerebral blood volume in schizophrenia: a magnetic resonance imaging study, J Psychiatr Res, 41, 502, 10.1016/j.jpsychires.2006.03.002 Peruzzo, 2011, The impact of schizophrenia on frontal perfusion parameters: a DSC-MRI study, J Neural Transm (Vienna), 118, 563, 10.1007/s00702-010-0548-7 Bossong MG, Allen P, Azis M, et al. Elevated hippocampal glutamate levels predict the later onset of psychosis. 15th International Congress on Schizophrenia Research; Colorado Springs, CO, USA; March 28–April 1, 2015. Modinos, 2015, Translating the MAM model of psychosis to humans, Trends Neurosci, 38, 129, 10.1016/j.tins.2014.12.005 Merritt, 2016, Nature of glutamate alterations in schizophrenia: a meta-analysis of proton magnetic resonance spectroscopy studies, JAMA Psychiatry, 73, 665, 10.1001/jamapsychiatry.2016.0442 Vazana, 2016, Glutamate-mediated blood–brain barrier opening: implications for neuroprotection and drug delivery, J Neurosci, 36, 7727, 10.1523/JNEUROSCI.0587-16.2016 O'Kane, 1999, Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood–brain barrier. A mechanism for glutamate removal, J Biol Chem, 274, 31891, 10.1074/jbc.274.45.31891 McCullumsmith, 2016, Cell-specific abnormalities of glutamate transporters in schizophrenia: sick astrocytes and compensating relay neurons?, Mol Psychiatry, 21, 823, 10.1038/mp.2015.148 Zhang, 2015, Common variants in SLC1A2 and schizophrenia: association and cognitive function in patients with schizophrenia and healthy individuals, Schizophr Res, 169, 128, 10.1016/j.schres.2015.10.012 Poletti, 2014, Effect of glutamate transporter EAAT2 gene variants and gray matter deficits on working memory in schizophrenia, Eur Psychiatry, 29, 219, 10.1016/j.eurpsy.2013.07.003 Wang, 2003, Reduced expression of glutamate transporter EAAT2 and impaired glutamate transport in human primary astrocytes exposed to HIV-1 or gp120, Virology, 312, 60, 10.1016/S0042-6822(03)00181-8 Miller, 2011, Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects, Biol Psychiatry, 70, 663, 10.1016/j.biopsych.2011.04.013 Khandaker, 2015, Inflammation and immunity in schizophrenia: implications for pathophysiology and treatment, Lancet Psychiatry, 2, 258, 10.1016/S2215-0366(14)00122-9 2014, Biological insights from 108 schizophrenia-associated genetic loci, Nature, 511, 421, 10.1038/nature13595 Benros, 2014, The epidemiologic evidence linking autoimmune diseases and psychosis, Biol Psychiatry, 75, 300, 10.1016/j.biopsych.2013.09.023 Benros, 2012, Autoimmune diseases and infections as risk factors for schizophrenia, Ann N Y Acad Sci, 1262, 56, 10.1111/j.1749-6632.2012.06638.x Khandaker, 2013, Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies, Psychol Med, 43, 239, 10.1017/S0033291712000736 Yolken, 2008, Are some cases of psychosis caused by microbial agents? A review of the evidence, Mol Psychiatry, 13, 470, 10.1038/mp.2008.5 Goldsmith, 2016, A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression, Mol Psychiatry, 21, 1696, 10.1038/mp.2016.3 Mondelli, 2015, Cortisol and inflammatory biomarkers predict poor treatment response in first episode psychosis, Schizophr Bull, 41, 1162, 10.1093/schbul/sbv028 Perkins, 2015, Towards a psychosis risk blood diagnostic for persons experiencing high-risk symptoms: preliminary results from the NAPLS project, Schizophr Bull, 41, 419, 10.1093/schbul/sbu099 Pun, 2009, Involvement of ROS in BBB dysfunction, Free Radic Res, 43, 348, 10.1080/10715760902751902 Argaw, 2006, IL-1beta regulates blood–brain barrier permeability via reactivation of the hypoxia-angiogenesis program, J Immunol, 177, 5574, 10.4049/jimmunol.177.8.5574 Bauer, 2007, Tumor necrosis factor alpha and endothelin-1 increase P-glycoprotein expression and transport activity at the blood-brain barrier, Mol Pharmacol, 71, 667, 10.1124/mol.106.029512 Steullet, 2016, Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: a “central hub” in schizophrenia pathophysiology?, Schizophr Res, 176, 41, 10.1016/j.schres.2014.06.021 Bloomfield, 2016, Microglial activity in people at ultra high risk of psychosis and in schizophrenia: an [(11)C]PBR28 PET brain imaging study, Am J Psychiatry, 173, 44, 10.1176/appi.ajp.2015.14101358 Howes, 2017, Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization, Transl Psychiatry, 7, e1024, 10.1038/tp.2016.278 Notter, 2017, Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia, Mol Psychiatry Pollak, 2016, Autoantibodies to central nervous system neuronal surface antigens: psychiatric symptoms and psychopharmacological implications, Psychopharmacology (Berl), 233, 1605, 10.1007/s00213-015-4156-y Dalmau, 2008, Anti-NMDA-receptor encephalitis: case series and analysis of the effects of antibodies, Lancet Neurol, 7, 1091, 10.1016/S1474-4422(08)70224-2 Kayser, 2013, Frequency and characteristics of isolated psychiatric episodes in anti-N-methyl-d-aspartate receptor encephalitis, JAMA Neurol, 70, 1133, 10.1001/jamaneurol.2013.3216 Pollak, 2014, Prevalence of anti-N-methyl-D-aspartate (NMDA) receptor [corrected] antibodies in patients with schizophrenia and related psychoses: a systematic review and meta-analysis, Psychol Med, 44, 1, 10.1017/S003329171300295X Coutinho, 2014, Do neuronal autoantibodies cause psychosis? A neuroimmunological perspective, Biol Psychiatry, 75, 269, 10.1016/j.biopsych.2013.07.040 Zandi, 2014, Immunotherapy for patients with acute psychosis and serum N-Methyl D-Aspartate receptor (NMDAR) antibodies: a description of a treated case series, Schizophr Res, 160, 193, 10.1016/j.schres.2014.11.001 Hammer, 2014, Neuropsychiatric disease relevance of circulating anti-NMDA receptor autoantibodies depends on blood-brain barrier integrity, Mol Psychiatry, 19, 1143, 10.1038/mp.2013.110 Hammer, 2014, Apolipoprotein E4 carrier status plus circulating anti-NMDAR1 autoantibodies: association with schizoaffective disorder, Mol Psychiatry, 19, 1054, 10.1038/mp.2014.52 Huerta, 2006, Immunity and behavior: antibodies alter emotion, Proc Natl Acad Sci USA, 103, 678, 10.1073/pnas.0510055103 Endres, 2015, Immunological findings in psychotic syndromes: a tertiary care hospital's CSF sample of 180 patients, Front Hum Neurosci, 9, 476, 10.3389/fnhum.2015.00476 Nikkilä, 2001, Increased frequency of activated lymphocytes in the cerebrospinal fluid of patients with acute schizophrenia, Schizophr Res, 49, 99, 10.1016/S0920-9964(99)00218-2 Nikkilä, 1999, Accumulation of macrophages in the CSF of schizophrenic patients during acute psychotic episodes, Am J Psychiatry, 156, 1725, 10.1176/ajp.156.11.1725 Müller, 1998, Increased frequency of CD8 positive gamma/delta T-lymphocytes (CD8+γ/δ+) in unmedicated schizophrenic patients: relation to impairment of the blood–brain barrier and HLA-DPA*02011, Schizophr Res, 32, 69, 10.1016/S0920-9964(98)00036-X Stolp, 2009, Review: role of developmental inflammation and blood–brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases, Neuropathol Appl Neurobiol, 35, 132, 10.1111/j.1365-2990.2008.01005.x Varatharaj, 2017, The blood–brain barrier in systemic inflammation, Brain Behav Immun, 60, 1, 10.1016/j.bbi.2016.03.010 Cannon, 2002, Obstetric complications and schizophrenia: historical and meta-analytic review, Am J Psychiatry, 159, 1080, 10.1176/appi.ajp.159.7.1080 Fischer, 1999, Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO, Am J Physiol, 276, C812, 10.1152/ajpcell.1999.276.4.C812 Mark, 2002, Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation, Am J Physiol Heart Circ Physiol, 282, H1485, 10.1152/ajpheart.00645.2001 Polglase, 2012, Initiation of resuscitation with high tidal volumes causes cerebral hemodynamic disturbance, brain inflammation and injury in preterm lambs, PLoS One, 7, e39535, 10.1371/journal.pone.0039535 Molloy, 2011, Is traumatic brain injury a risk factor for schizophrenia? A meta-analysis of case-controlled population-based studies, Schizophr Bull, 37, 1104, 10.1093/schbul/sbr091 Marchi, 2013, Consequences of repeated blood–brain barrier disruption in football players, PLoS One, 8, e56805, 10.1371/journal.pone.0056805 Gurillo, 2015, Does tobacco use cause psychosis? Systematic review and meta-analysis, Lancet Psychiatry, 2, 718, 10.1016/S2215-0366(15)00152-2 Mazzone, 2010, Pathophysiological impact of cigarette smoke exposure on the cerebrovascular system with a focus on the blood-brain barrier: expanding the awareness of smoking toxicity in an underappreciated area, Int J Environ Res Public Health, 7, 4111, 10.3390/ijerph7124111 Bramness, 2012, Amphetamine-induced psychosis—a separate diagnostic entity or primary psychosis triggered in the vulnerable?, BMC Psychiatry, 12, 221, 10.1186/1471-244X-12-221 Sajja, 2016, Drugs of abuse and blood–brain barrier endothelial dysfunction: a focus on the role of oxidative stress, J Cereb Blood Flow Metab, 36, 539, 10.1177/0271678X15616978 van der Feltz-Cornelis, 2008, Psychosis in epilepsy patients and other chronic medically ill patients and the role of cerebral pathology in the onset of psychosis: a clinical epidemiological study, Seizure, 17, 446, 10.1016/j.seizure.2007.12.004 Librizzi, 2012, Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage, Ann Neurol, 72, 82, 10.1002/ana.23567 Iffland, 2013, Intracellular and circulating neuronal antinuclear antibodies in human epilepsy, Neurobiol Dis, 59, 206, 10.1016/j.nbd.2013.07.006 Morgan, 2007, Environment and schizophrenia: environmental factors in schizophrenia: childhood trauma— a critical review, Schizophr Bull, 33, 3, 10.1093/schbul/sbl053 Falcone, 2015, Does systemic inflammation play a role in pediatric psychosis?, Clin Schizophr Relat Psychoses, 9, 65, 10.3371/CSRP.FACA.030813 Malmberg, 1998, Premorbid adjustment and personality in people with schizophrenia, Br J Psychiatry, 172, 308, 10.1192/bjp.172.4.308 Schiavone, 2016, Early loss of blood–brain barrier integrity precedes NOX2 elevation in the prefrontal cortex of an animal model of psychosis, Mol Neurobiol, 54, 2013 Bergemann, 2007, Estrogen, menstrual cycle phases, and psychopathology in women suffering from schizophrenia, Psychol Med, 37, 1427, 10.1017/S0033291707000578 Maggioli, 2016, Estrogen protects the blood–brain barrier from inflammation-induced disruption and increased lymphocyte trafficking, Brain Behav Immun, 51, 212, 10.1016/j.bbi.2015.08.020 Bergink, 2015, Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study, Psychol Med, 45, 3481, 10.1017/S0033291715001385 Amburgey, 2010, Plasma from preeclamptic women increases blood–brain barrier permeability: role of vascular endothelial growth factor signaling, Hypertension, 56, 1003, 10.1161/HYPERTENSIONAHA.110.158931 Murphy, 1999, High rates of schizophrenia in adults with velo-cardio-facial syndrome, Arch Gen Psychiatry, 56, 940, 10.1001/archpsyc.56.10.940 Sirotkin, 1997, Identification, characterization, and precise mapping of a human gene encoding a novel membrane-spanning protein from the 22q11 region deleted in velo-cardio-facial syndrome, Genomics, 42, 245, 10.1006/geno.1997.4734 Nitta, 2003, Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice, J Cell Biol, 161, 653, 10.1083/jcb.200302070 Egerton, 2017, Elevated striatal dopamine function in immigrants and their children: a risk mechanism for psychosis, Schizophr Bull, 43, 293 Egerton, 2016, Adversity in childhood linked to elevated striatal dopamine function in adulthood, Schizophr Res, 176, 171, 10.1016/j.schres.2016.06.005 Demjaha, 2014, Antipsychotic treatment resistance in schizophrenia associated with elevated glutamate levels but normal dopamine function, Biol Psychiatry, 75, e11, 10.1016/j.biopsych.2013.06.011 Moons, 2011, Relationship between P-glycoprotein and second-generation antipsychotics, Pharmacogenomics, 12, 1193, 10.2217/pgs.11.55 Kirschbaum, 2008, Pharmacodynamic consequences of P-glycoprotein-dependent pharmacokinetics of risperidone and haloperidol in mice, Behav Brain Res, 188, 298, 10.1016/j.bbr.2007.11.009 Doran, 2005, The impact of P-glycoprotein on the disposition of drugs targeted for indications of the central nervous system: evaluation using the MDR1A/1B knockout mouse model, Drug Metab Dispos, 33, 165, 10.1124/dmd.104.001230 Ejsing, 2005, P-glycoprotein interaction with risperidone and 9-OH-risperidone studied in vitro, in knock-out mice and in drug-drug interaction experiments, Hum Psychopharmacol, 20, 493, 10.1002/hup.720 Wang, 2004, The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein, Int J Neuropsychopharmacol, 7, 415, 10.1017/S1461145704004390 Lally, 2016, Two distinct patterns of treatment resistance: clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses, Psychol Med, 46, 3231, 10.1017/S0033291716002014 Löscher, 2005, Drug resistance in brain diseases and the Role of drug efflux transporters, Nat Rev Neurosci, 6, 591, 10.1038/nrn1728 de Klerk, 2010, Regional increase in P-glycoprotein function in the blood–brain barrier of patients with chronic schizophrenia: a PET study with [11C]verapamil as a probe for P-glycoprotein function, Psychiatry Res, 183, 151, 10.1016/j.pscychresns.2010.05.002 Ghosh, 2003, Mannose 6-phosphate receptors: new twists in the tale, Nat Rev Mol Cell Biol, 4, 202, 10.1038/nrm1050 Caccia, 2000, Biotransformation of post-clozapine antipsychotics, Clin Pharmacokinet, 38, 393, 10.2165/00003088-200038050-00002 Loryan, 2016, In-depth neuropharmacokinetic analysis of antipsychotics based on a novel approach to estimate unbound target-site concentration in CNS regions: link to spatial receptor occupancy, Mol Psychiatry, 21, 1527, 10.1038/mp.2015.229 Elmorsy, 2014, Adverse effects of antipsychotics on micro-vascular endothelial cells of the human blood–brain barrier, Brain Res, 1583, 255, 10.1016/j.brainres.2014.08.011 Cotel, 2015, Microglial activation in the rat brain following chronic antipsychotic treatment at clinically relevant doses, Eur Neuropsychopharmacol, 25, 2098, 10.1016/j.euroneuro.2015.08.004 Zipursky, 2013, The myth of schizophrenia as a progressive brain disease, Schizophr Bull, 39, 1363, 10.1093/schbul/sbs135 Andrade, 2014, Electroconvulsive therapy, hypertensive surge, blood–brain barrier breach, and amnesia: exploring the evidence for a connection, J ECT, 30, 160, 10.1097/YCT.0000000000000133 Heringa, 2015, Sex hormones and oxytocin augmentation strategies in schizophrenia: a quantitative review, Schizophr Res, 168, 603, 10.1016/j.schres.2015.04.002 Barzilay, 2011, Intracerebral adult stem cells transplantation increases brain-derived neurotrophic factor levels and protects against phencyclidine-induced social deficit in mice, Transl Psychiatry, 1, e61, 10.1038/tp.2011.64 Okada, 2015, In-vivo imaging of blood–brain barrier permeability using positron emission tomography with 2-amino-[3-11C]isobutyric acid, Nucl Med Commun, 36, 1239, 10.1097/MNM.0000000000000385