Blood-brain barrier dysfunction in patients with bipolar disorder Blood-brain barrier dysfunction in patients with bipolar disorder Master thesis in Medicine

299 words Article: 7130 words The manuscript contains 6 figures and 2 tables Abstract Background: Bipolar disorder (BPD) is a common psychiatric disorder, characterized by recurrent episodes of mania/hypomania and depression. Similar to a majority of other psychiatric disorders, complete aetiology and/or pathogenesis are unknown in BPD. Modern research has proposed an association between an impaired blood-cerebrospinal fluid (CSF) or blood-brain barrier and subgroups of patients suffering from different psychiatric conditions, such as schizophrenia, depression and other affective disorders. The purpose of this study wasBackground: Bipolar disorder (BPD) is a common psychiatric disorder, characterized by recurrent episodes of mania/hypomania and depression. Similar to a majority of other psychiatric disorders, complete aetiology and/or pathogenesis are unknown in BPD. Modern research has proposed an association between an impaired blood-cerebrospinal fluid (CSF) or blood-brain barrier and subgroups of patients suffering from different psychiatric conditions, such as schizophrenia, depression and other affective disorders. The purpose of this study was to evaluate whether dysfunction of the blood-brain barrier is over represented in a cohort of bipolar patients, compared to an ageand gender-matched healthy control group, i.e. quantify and further validate past research findings and aim the study against a specific disorder where documentation is limited. Methods: Subjects included 134 BPD patients and 86 healthy controls. Serum and CSF were collected from all subjects and analyzed for albumin concentration by immunonephelometry, where after CSF/serum albumin ratio was determined by dividing CSF with serum albumin concentration. CSF/serum albumin ratio was then compared between patients and controls using Mann-Whitney U-test. Results: CSF/serum albumin ratio was significantly elevated in BPD patients as compared to controls, suggesting impairment of the blood-brain barrier in BPD. When excluding 35 patients and controls, on magnetic resonance imaging (MRI) of the brain displaying signs of somatic or neurological diseases known to impinge the blood-brain barrier, the significant difference in CSF/serum albumin ratio between BPD patients and controls remained. Moreover, after stratifying patients according to type of BPD, the group consisting of BPD I patients significantly excelled. Conclusions: The findings statistically establish that a subgroup of individuals with BPD has elevated CSF/serum albumin ratio, indicating that an impaired blood-brain barrier may play a role in or reflect the disease process in BPD, although the complete mechanisms causing the impairment are still unknown and further studies are required.

[1]  R. Kotov,et al.  Diagnostic shifts during the decade following first admission for psychosis. , 2011, The American journal of psychiatry.

[2]  M. Gill,et al.  Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility , 2011, Molecular Psychiatry.

[3]  D. Fuchs,et al.  Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. , 2010, Journal of psychiatric research.

[4]  K. Blennow,et al.  Cerebrospinal Fluid Analysis Should Be Considered in Patients with Cognitive Problems , 2010, International journal of Alzheimer's disease.

[5]  M. Thase,et al.  A history of childhood attention‐deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD , 2009, Acta psychiatrica Scandinavica.

[6]  P. Visscher,et al.  Common polygenic variation contributes to risk of schizophrenia and bipolar disorder , 2009, Nature.

[7]  E. Wright,et al.  Plasma CRP Levels in Premenopausal Women with Major Depression: A 12-Month Controlled Study , 2009, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[8]  Sabine Landau,et al.  Cognitive functioning in patients with affective disorders and schizophrenia: A meta-analysis , 2009, International review of psychiatry.

[9]  H. Lôo.  [On bipolar disorder]. , 2008, L'Encephale.

[10]  R. Yolken,et al.  Are some cases of psychosis caused by microbial agents? A review of the evidence , 2008, Molecular Psychiatry.

[11]  Tyrone D. Cannon,et al.  Maternal Exposure to Herpes Simplex Virus and Risk of Psychosis Among Adult Offspring , 2008, Biological Psychiatry.

[12]  L. Sher.  Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression, Second Edition. , 2008, The American journal of psychiatry.

[13]  W. Drevets,et al.  Sustained Low-Grade Pro-inflammatory State in Unmedicated, Remitted Women with Major Depressive Disorder as Evidenced by Elevated Serum Levels of the Acute Phase Proteins C-reactive Protein and Serum Amyloid A , 2007, Biological Psychiatry.

[14]  M. Irwin,et al.  Depressive disorders and immunity: 20 years of progress and discovery , 2007, Brain, Behavior, and Immunity.

[15]  H. Akiskal,et al.  [Widening the borders of the bipolar disorder: validation of the concept of bipolar spectrum]. , 2006, Vertex.

[16]  M. Schwarz,et al.  Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission , 2006, Neurotoxicity Research.

[17]  I. Gottesman,et al.  Theories of schizophrenia: a genetic-inflammatory-vascular synthesis , 2005, BMC Medical Genetics.

[18]  W. Gattaz,et al.  Childhood meningitis increases the risk for adult schizophrenia , 2005, The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry.

[19]  A. H. Berman,et al.  Evaluation of the Drug Use Disorders Identification Test (DUDIT) in Criminal Justice and Detoxification Settings and in a Swedish Population Sample , 2004, European Addiction Research.

[20]  T. Erlinger,et al.  Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. , 2004, Archives of internal medicine.

[21]  Peter B. Jones,et al.  Childhood central nervous system infections and risk for schizophrenia , 2004, European Archives of Psychiatry and Clinical Neuroscience.

[22]  W. Gattaz,et al.  Childhood meningitis, brain maturation and the risk of psychosis* , 2004, European Archives of Psychiatry and Clinical Neuroscience.

[23]  D. Kupfer,et al.  Rationale, design, and methods of the systematic treatment enhancement program for bipolar disorder (STEP-BD) , 2003, Biological Psychiatry.

[24]  Philip D. Harvey,et al.  White matter changes in schizophrenia: evidence for myelin-related dysfunction. , 2003, Archives of general psychiatry.

[25]  Viola Vaccarino,et al.  Association Between Depression and Elevated C-Reactive Protein , 2003, Psychosomatic medicine.

[26]  E. Susser,et al.  Serologic evidence for prenatal influenza in the etiology of schizophrenia , 2003, Schizophrenia Research.

[27]  E. Zorrilla,et al.  The Relationship of Depression and Stressors to Immunological Assays: A Meta-Analytic Review , 2001, Brain, Behavior, and Immunity.

[28]  C. Sindic,et al.  The Intrathecal Humoral Immune Response: Laboratory Analysis and Clinical Relevance , 2001, Clinical chemistry and laboratory medicine.

[29]  Hansotto Reiber,et al.  Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs , 2001, Journal of the Neurological Sciences.

[30]  H. Vedder,et al.  Cytokine Production and Treatment Response in Major Depressive Disorder , 2000, Neuropsychopharmacology.

[31]  K. Blennow,et al.  Impairment of the blood-CSF barrier in suicide attempters , 1996, European Neuropsychopharmacology.

[32]  H. Hampel,et al.  Fibrin degradation products in post mortem brain tissue of schizophrenics: a possible marker for underlying inflammatory processes , 1996, Schizophrenia Research.

[33]  O. Aasland,et al.  Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption--II. , 1993, Addiction.

[34]  A. Saija,et al.  Ageing influences haloperidol‐induced changes in the permeability of the blood‐brain barrier in the rat , 1992, The Journal of pharmacy and pharmacology.

[35]  K. Blennow,et al.  Blood brain barrier function in vascular dementia , 1990, Acta neurologica Scandinavica.

[36]  I Karlsson,et al.  Blood‐brain barrier disturbance in patients with Alzheimer's disease is related to vascular factors , 1990, Acta neurologica Scandinavica.

[37]  J. Kornhuber,et al.  Alcohol consumption and blood-cerebrospinal fluid barrier dysfunction in man , 1987, Neuroscience Letters.

[38]  D. Weinberger,et al.  Abnormal cerebrospinal fluid protein indices in schizophrenia , 1985, Biological Psychiatry.

[39]  T. Erkinjuntti,et al.  CSF in Alzheimer's disease: Studies on blood-brain barrier function and intrathecal protein synthesis , 1985, Journal of the Neurological Sciences.

[40]  C. Alling,et al.  Impairment of the Blood-Brain Barrier as an Aetiological Factor in Paranoid Psychosis , 1982, British Journal of Psychiatry.

[41]  G. Tibbling,et al.  Principles of albumin and IgG analyses in neurological disorders. III. Evaluation of IgG synthesis within the central nervous system in multiple sclerosis. , 1977, Scandinavian journal of clinical and laboratory investigation.

[42]  S. Ohman,et al.  Principles of albumin and IgG analyses in neurological disorders. I. Establishment of reference values. , 1977, Scandinavian journal of clinical and laboratory investigation.

[43]  C. Laurell,et al.  Measurement of IgG and albumin content of cerebrospinal fluid, and its interpretation. , 1974, Clinical chemistry.

[44]  J. Stockman,et al.  Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study , 2010 .

[45]  J. Feldon,et al.  Relative Prenatal and Postnatal Maternal Contributions to Schizophrenia-Related Neurochemical Dysfunction after In Utero Immune Challenge , 2008, Neuropsychopharmacology.

[46]  P. Allebeck,et al.  Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study of more than one million Swedish subjects. , 2008, The American journal of psychiatry.

[47]  B. Sperner-Unterweger.  Immunological aetiology of major psychiatric disorders: evidence and therapeutic implications. , 2005, Drugs.

[48]  J. Kornhuber,et al.  Blood-cerebrospinal fluid barrier in schizophrenic patients , 2004, European archives of psychiatry and neurological sciences.

[49]  D. Isenman,et al.  Philosophical assumptions in Freud, Jung and Bion: questions of causality. , 2000, The Journal of analytical psychology.

[50]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[51]  K. Blennow,et al.  Protein analysis in cerebrospinal fluid. III. Relation to blood-cerebrospinal fluid barrier function for formulas for quantitative determination of intrathecal IgG production. , 1993, European neurology.

[52]  K. Blennow,et al.  Protein analysis in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age. , 1993, European neurology.

[53]  H. Baruk.  [Discovery of the "deep personality" and revision of the Kraepelin concept of autonomic mental disease]. , 1989, Annales Medico-Psychologiques.