Genetic and Environmental Influences on Pro-Inflammatory Monocytes in Bipolar Disorder: A Twin Study | Bipolar and Related Disorders | JAMA Psychiatry | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address Please contact the publisher to request reinstatement.
Farmer  AElkin  A McGuffin  P The genetics of bipolar affective disorder.  Curr Opin Psychiatry 2007;20 (1) 8- 12PubMedGoogle ScholarCrossref
Smoller  JWFinn  CT Family, twin, and adoption studies of bipolar disorder.  Am J Med Genet C Semin Med Genet 2003;123C (1) 48- 58PubMedGoogle ScholarCrossref
Taylor  LFaraone  SVTsuang  MT Family, twin, and adoption studies of bipolar disease.  Curr Psychiatry Rep 2002;4 (2) 130- 133PubMedGoogle ScholarCrossref
Padmos  RCHillegers  MHKnijff  EMVonk  RBouvy  AStaal  FJde Ridder  DKupka  RWNolen  WADrexhage  HA A discriminating messenger RNA signature for bipolar disorder formed by an aberrant expression of inflammatory genes in monocytes.  Arch Gen Psychiatry 2008;65 (4) 395- 407PubMedGoogle ScholarCrossref
Smith  RS The macrophage theory of depression.  Med Hypotheses 1991;35 (4) 298- 306PubMedGoogle ScholarCrossref
Leonard  BE The immune system, depression and the action of antidepressants.  Prog Neuropsychopharmacol Biol Psychiatry 2001;25 (4) 767- 780PubMedGoogle ScholarCrossref
Maes  M Evidence for an immune response in major depression: a review and hypothesis.  Prog Neuropsychopharmacol Biol Psychiatry 1995;19 (1) 11- 38PubMedGoogle ScholarCrossref
Brans  RGvan Haren  NEvan Baal  GCSchnack  HGKahn  RSHulshoff Pol  HE Heritability of changes in brain volume over time in twin pairs discordant for schizophrenia.  Arch Gen Psychiatry 2008;65 (11) 1259- 1268PubMedGoogle ScholarCrossref
Hall  MHRijsdijk  FPicchioni  MSchulze  KEttinger  UToulopoulou  TBramon  EMurray  RMSham  P Substantial shared genetic influences on schizophrenia and event-related potentials.  Am J Psychiatry 2007;164 (5) 804- 812PubMedGoogle ScholarCrossref
Toulopoulou  TPicchioni  MRijsdijk  FHua-Hall  MEttinger  USham  PMurray  R Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples.  Arch Gen Psychiatry 2007;64 (12) 1348- 1355PubMedGoogle ScholarCrossref
Rijsdijk  FVvan Haren  NEPicchioni  MM McDonald  CToulopoulou  THulshoff Pol  HEKahn  RSMurray  RSham  PC Brain MRI abnormalities in schizophrenia: same genes or same environment?  Psychol Med 2005;35 (10) 1399- 1409PubMedGoogle ScholarCrossref
Vonk  Rvan der Schot  ACKahn  RSNolen  WADrexhage  HA Is autoimmune thyroiditis part of the genetic vulnerability (or an endophenotype) for bipolar disorder?  Biol Psychiatry 2007;62 (2) 135- 140PubMedGoogle ScholarCrossref
Knijff  EMBreunis  MNvan Geest  MCKupka  RWRuwhof  Cde Wit  HJNolen  WADrexhage  HA A relative resistance of T cells to dexamethasone in bipolar disorder.  Bipolar Disord 2006;8 (6) 740- 750PubMedGoogle ScholarCrossref
Gabert  JBeillard  Evan der Velden  VHBi  WGrimwade  DPallisgaard  NBarbany  GCazzaniga  GCayuela  JMCave  HPane  FAerts  JLDe Micheli  DThirion  XPradel  VGonzalez  MViehmann  SMalec  MSaglio  Gvan Dongen  JJ Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia: a Europe Against Cancer program.  Leukemia 2003;17 (12) 2318- 2357PubMedGoogle ScholarCrossref
Beillard  EPallisgaard  Nvan der Velden  VHBi  WDee  Rvan der Schoot  EDelabesse  EMacintyre  EGottardi  ESaglio  GWatzinger  FLion  Tvan Dongen  JJHokland  PGabert  J Evaluation of candidate control genes for diagnosis and residual disease detection in leukemic patients using ‘real-time’ quantitative reverse-transcriptase polymerase chain reaction (RQ-PCR): a Europe against cancer program.  Leukemia 2003;17 (12) 2474- 2486PubMedGoogle ScholarCrossref
Neale  MCBSXie  GMaes  HH Mx: statistical modeling. 7th ed. Richmond, VA Dept of Psychiatry, Virginia Commonwealth University2006;
Neale  MCMiller  MB The use of likelihood-based confidence intervals in genetic models.  Behav Genet 1997;27 (2) 113- 120PubMedGoogle ScholarCrossref
Regeer  EJten Have  MRosso  MLHakkaart-van Roijen  LVollebergh  WNolen  WA Prevalence of bipolar disorder in the general population: a reappraisal study of the Netherlands Mental Health Survey and Incidence Study.  Acta Psychiatr Scand 2004;110 (5) 374- 382PubMedGoogle ScholarCrossref
ten Have  MVollebergh  WBijl  RNolen  WA Bipolar disorder in the general population in the Netherlands (prevalence, consequences and care utilisation): results from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).  J Affect Disord 2002;68 (2-3) 203- 213PubMedGoogle ScholarCrossref
Rybakowski  JK Antiviral and immunomodulatory effect of lithium.  Pharmacopsychiatry 2000;33 (5) 159- 164PubMedGoogle Scholar
Gillespie  NAM Direction of causation models. Everitt  BSHowell  DC The Encyclopedia of Statistics in Behavioral Science. Hoboken, NJ Wiley2005;496- 499Google Scholar
Padmos  RCSchloot  NCBeyan  HRuwhof  CStaal  FJde Ridder  DAanstoot  HJTse  WKde Wit  HHerder  CDrexhage  RCMenart  BLeslie  RDDrexhage  HA Distinct monocyte gene-expression profiles in autoimmune diabetes.  Diabetes 2008;57 (10) 2768- 2773PubMedGoogle ScholarCrossref
Torrey  EFBartko  JJLun  ZRYolken  RH Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis.  Schizophr Bull 2007;33 (3) 729- 736PubMedGoogle ScholarCrossref
Hinze-Selch  D Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls.  Bipolar Disord 2002;4 ((suppl 1)) 81- 83PubMedGoogle ScholarCrossref
Taieb  OBaleyte  JMMazet  PFillet  AM Borna disease virus and psychiatry.  Eur Psychiatry 2001;16 (1) 3- 10PubMedGoogle ScholarCrossref
Yolken  RHTorrey  EF Viruses, schizophrenia, and bipolar disorder.  Clin Microbiol Rev 1995;8 (1) 131- 145PubMedGoogle Scholar
Machón  RAMednick  SAHuttunen  MO Adult major affective disorder after prenatal exposure to an influenza epidemic.  Arch Gen Psychiatry 1997;54 (4) 322- 328PubMedGoogle ScholarCrossref
Brown  AS Prenatal infection as a risk factor for schizophrenia.  Schizophr Bull 2006;32 (2) 200- 202PubMedGoogle ScholarCrossref
Torrey  EFYolken  RH At issue: is household crowding a risk factor for schizophrenia and bipolar disorder?  Schizophr Bull 1998;24 (3) 321- 324PubMedGoogle ScholarCrossref
Abe  HHidaka  NKawagoe  COdagiri  KWatanabe  YIkeda  TIshizuka  YHashiguchi  HTakeda  RNishimori  TIshida  Y Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis.  Neurosci Res 2007;59 (2) 145- 151PubMedGoogle ScholarCrossref
Costello  EJWorthman  CErkanli  AAngold  A Prediction from low birth weight to female adolescent depression: a test of competing hypotheses.  Arch Gen Psychiatry 2007;64 (3) 338- 344PubMedGoogle ScholarCrossref
Wals  MReichart  CGHillegers  MHVan Os  JVerhulst  FCNolen  WAOrmel  J Impact of birth weight and genetic liability on psychopathology in children of bipolar parents.  J Am Acad Child Adolesc Psychiatry 2003;42 (9) 1116- 1121PubMedGoogle ScholarCrossref
Van den Bergh  BRMulder  EJMennes  MGlover  V Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms—a review.  Neurosci Biobehav Rev 2005;29 (2) 237- 258PubMedGoogle ScholarCrossref
Maccari  SMorley-Fletcher  S Effects of prenatal restraint stress on the hypothalamus-pituitary-adrenal axis and related behavioural and neurobiological alterations.  Psychoneuroendocrinology 2007;32 ((suppl 1)) S10- S15PubMedGoogle ScholarCrossref
Austin  MPLeader  LRReilly  N Prenatal stress, the hypothalamic-pituitary-adrenal axis, and fetal and infant neurobehaviour.  Early Hum Dev 2005;81 (11) 917- 926PubMedGoogle ScholarCrossref
Leonard  BE HPA and immune axes in stress: involvement of the serotonergic system.  Neuroimmunomodulation 2006;13 (5-6) 268- 276PubMedGoogle ScholarCrossref
Padgett  DAGlaser  R How stress influences the immune response.  Trends Immunol 2003;24 (8) 444- 448PubMedGoogle ScholarCrossref
Willner  P Chronic mild stress (CMS) revisited: consistency and behavioural-neurobiological concordance in the effects of CMS.  Neuropsychobiology 2005;52 (2) 90- 110PubMedGoogle ScholarCrossref
Hillegers  MHBurger  HWals  MReichart  CGVerhulst  FCNolen  WAOrmel  J Impact of stressful life events, familial loading and their interaction on the onset of mood disorders: study in a high-risk cohort of adolescent offspring of parents with bipolar disorder.  Br J Psychiatry 2004;18597- 101PubMedGoogle ScholarCrossref
Parker  GGibson  NABrotchie  HHeruc  GRees  AMHadzi-Pavlovic  D Omega-3 fatty acids and mood disorders.  Am J Psychiatry 2006;163 (6) 969- 978PubMedGoogle ScholarCrossref
Original Article
September 2009

Genetic and Environmental Influences on Pro-Inflammatory Monocytes in Bipolar Disorder: A Twin Study

Author Affiliations

Author Affiliations: Department of Immunology, Erasmus Medical Center, Rotterdam (Drs Padmos and Drexhage and Ms Wijkhuijs); Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht (Drs Van Baal and Kahn); Reinier van Arkel Group, ’s-Hertogenbosch (Dr Vonk); and Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen (Dr Nolen), the Netherlands.

Arch Gen Psychiatry. 2009;66(9):957-965. doi:10.1001/archgenpsychiatry.2009.116

Context  A monocyte pro-inflammatory state has previously been reported in bipolar disorder (BD).

Objective  To determine the contribution of genetic and environmental influences on the association between monocyte pro-inflammatory state and BD.

Design  A quantitative polymerase chain reaction case-control study of monocytes in bipolar twins. Determination of the influence of additive genetic, common, and unique environmental factors by structural equation modeling (ACE).

Setting  Dutch academic research center.

Participants  Eighteen monozygotic BD twin pairs, 23 dizygotic BD twin pairs, and 18 monozygotic and 16 dizygotic healthy twin pairs.

Main Outcome Measures  Expression levels of monocytes in the previously reported coherent set of 19 genes (signature) reflecting the pro-inflammatory state.

Results  The familial occurrence of the association between the monocyte pro-inflammatory gene-expression signature and BD found in the within-trait/cross-twin correlations (twin correlations) was due to shared environmental factors (ie, both monozygotic and dizygotic ratios in twin correlations approximated 1; ACE modeling data: 94% [95% confidence interval, 53%-99%] explained by common [shared] environmental factors). Although most individual signature genes followed this pattern, there was a small subcluster of genes in which genetic influences could dominate.

Conclusion  The association of the monocyte pro-inflammatory state with BD is primarily the result of a common shared environmental factor.