title: Identification of a common neurobiological substrate for mental illness.
abstract: OBJECTIVE
  Psychiatric diagnoses are currently distinguished based on sets of specific symptoms. However, genetic and clinical analyses find similarities across a wide variety of diagnoses, suggesting that a common neurobiological substrate may exist across mental illness.
  
  
  OBJECTIVE
  To conduct a meta-analysis of structural neuroimaging studies across multiple psychiatric diagnoses, followed by parallel analyses of 3 large-scale healthy participant data sets to help interpret structural findings in the meta-analysis.
  
  
  METHODS
  PubMed was searched to identify voxel-based morphometry studies through July 2012 comparing psychiatric patients to healthy control individuals for the meta-analysis. The 3 parallel healthy participant data sets included resting-state functional magnetic resonance imaging, a database of activation foci across thousands of neuroimaging experiments, and a data set with structural imaging and cognitive task performance data.
  
  
  METHODS
  Studies were included in the meta-analysis if they reported voxel-based morphometry differences between patients with an Axis I diagnosis and control individuals in stereotactic coordinates across the whole brain, did not present predominantly in childhood, and had at least 10 studies contributing to that diagnosis (or across closely related diagnoses). The meta-analysis was conducted on peak voxel coordinates using an activation likelihood estimation approach.
  
  
  METHODS
  We tested for areas of common gray matter volume increase or decrease across Axis I diagnoses, as well as areas differing between diagnoses. Follow-up analyses on other healthy participant data sets tested connectivity related to regions arising from the meta-analysis and the relationship of gray matter volume to cognition.
  
  
  RESULTS
  Based on the voxel-based morphometry meta-analysis of 193 studies comprising 15 892 individuals across 6 diverse diagnostic groups (schizophrenia, bipolar disorder, depression, addiction, obsessive-compulsive disorder, and anxiety), we found that gray matter loss converged across diagnoses in 3 regions: the dorsal anterior cingulate, right insula, and left insula. By contrast, there were few diagnosis-specific effects, distinguishing only schizophrenia and depression from other diagnoses. In the parallel follow-up analyses of the 3 independent healthy participant data sets, we found that the common gray matter loss regions formed a tightly interconnected network during tasks and at resting and that lower gray matter in this network was associated with poor executive functioning.
  
  
  CONCLUSIONS
  We identified a concordance across psychiatric diagnoses in terms of integrity of an anterior insula/dorsal anterior cingulate-based network, which may relate to executive function deficits observed across diagnoses. This concordance provides an organizing model that emphasizes the importance of shared neural substrates across psychopathology, despite likely diverse etiologies, which is currently not an explicit component of psychiatric nosology.
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Madeleine
authors: M
authors: Goodkind
authors: Institute for Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, Germany4Institute for Clinical Neuroscience and Medical Psychology, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
authors: Simon B
authors: SB
authors: Eickhoff
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Desmond J
authors: DJ
authors: Oathes
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Ying
authors: Y
authors: Jiang
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Andrew
authors: A
authors: Chang
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Laura B
authors: LB
authors: Jones-Hagata
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Brissa N
authors: BN
authors: Ortega
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Yevgeniya V
authors: YV
authors: Zaiko
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Erika L
authors: EL
authors: Roach
authors: Brain Dynamics Centre, Westmead Millennium Institute and Sydney Medical School-Westmead, Sydney, Australia6Sydney Translational Imaging Laboratory, Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Mayuresh S
authors: MS
authors: Korgaonkar
authors: Brain Dynamics Centre, Westmead Millennium Institute and Sydney Medical School-Westmead, Sydney, Australia6Sydney Translational Imaging Laboratory, Sydney Medical School, University of Sydney, Sydney, Australia.
authors: Stuart M
authors: SM
authors: Grieve
authors: Department of Psychiatry, New York University, New York.
authors: Isaac
authors: I
authors: Galatzer-Levy
authors: Research Imaging Institute, University of Texas Health Science Center at San Antonio9South Texas Veterans Health Care System, San Antonio10School of Humanities, University of Hong Kong, Hong Kong, China11State Key Laboratory for Brain and Cognitive Scienc.
authors: Peter T
authors: PT
authors: Fox
authors: Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, California2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford.
authors: Amit
authors: A
authors: Etkin
mesh_terms: D001284:Atrophy / Q000473:pathology; D001921:Brain / Q000473:pathology*; D056344:Executive Function; D066128:Gray Matter / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D001523:Mental Disorders / Q000473:pathology* / Q000523:psychology; D059906:Neuroimaging; D049268:Positron-Emission Tomography
references: Arch Gen Psychiatry. 1978 Jun;35(6):773-82
references: 655775
references: Psychol Med. 2012 Feb;42(2):295-307
references: 21835091
references: BMC Res Notes. 2011 Sep 09;4:349
references: 21906305
references: Hum Brain Mapp. 2012 Jan;33(1):1-13
references: 21305667
references: Cogn Psychol. 2000 Aug;41(1):49-100
references: 10945922
references: Schizophr Bull. 2012 Nov;38(6):1297-307
references: 22080494
references: Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):11-6
references: 22001316
references: J Abnorm Psychol. 2013 Feb;122(1):281-94
references: 23067258
references: Neuroimage. 2011 Apr 1;55(3):868-79
references: 21224000
references: Neuroimage. 2010 Jan 15;49(2):1760-8
references: 19786103
references: PLoS One. 2012;7(11):e48298
references: 23155380
references: JAMA Psychiatry. 2014 Feb;71(2):109-18
references: 24306091
references: Asian J Psychiatr. 2012 Dec;5(4):290-6
references: 23174435
references: J Nerv Ment Dis. 2012 Dec;200(12):1022-30
references: 23197117
references: Hum Brain Mapp. 2009 Sep;30(9):2907-26
references: 19172646
references: J Neural Transm (Vienna). 2014 Sep;121(9):1157-70
references: 24752753
references: Brain Cogn. 2012 Apr;78(3):284-99
references: 22296984
references: Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12569-74
references: 18723676
references: Biol Psychiatry. 2012 Feb 15;71(4):286-93
references: 22112927
references: Biol Psychiatry. 2014 Jun 15;75(12):982-90
references: 24143881
references: J Psychiatr Res. 2012 Oct;46(10):1249-56
references: 22790253
references: Biol Psychiatry. 2005 Jul 15;58(2):119-24
references: 16038682
references: J Anxiety Disord. 2010 Jan;24(1):30-3
references: 19713071
references: Schizophr Res. 2008 Jan;98(1-3):29-39
references: 17976957
references: Am J Psychiatry. 2007 Oct;164(10):1476-88
references: 17898336
references: Neuroimage. 2013 Oct 15;80:505-14
references: 23631994
references: Trends Cogn Sci. 2011 Oct;15(10):483-506
references: 21908230
references: Neuroimage. 2012 May 1;60(4):2389-98
references: 22387170
references: Dialogues Clin Neurosci. 2013 Dec;15(4):419-29
references: 24459409
references: J Neurosci. 2010 May 5;30(18):6409-21
references: 20445067
references: Trends Cogn Sci. 2011 Feb;15(2):85-93
references: 21167765
references: Arch Gen Psychiatry. 2011 Jul;68(7):675-90
references: 21727252
references: Biol Psychiatry. 2013 Jan 1;73(1):70-4
references: 22840760
references: Psychopathology. 2012;45(6):361-5
references: 22854189
references: Psychol Med. 2009 May;39(5):793-800
references: 18713487
references: Bipolar Disord. 2012 Mar;14(2):135-45
references: 22420589
references: Neuron. 2011 Nov 17;72(4):665-78
references: 22099467
references: Arch Gen Psychiatry. 2003 Sep;60(9):929-37
references: 12963675
references: Biol Psychiatry. 1999 Jul 15;46(2):161-72
references: 10418690
references: Lancet. 2013 Apr 20;381(9875):1371-9
references: 23453885
references: Br J Psychiatry. 2009 Nov;195(5):393-402
references: 19880927
references: World Psychiatry. 2012 Jun;11(2):73-9
references: 22654932
references: Psychiatry Res. 2013 Jan 30;211(1):37-46
references: 23146253
references: Am J Psychiatry. 2012 Jul;169(7):693-703
references: 22535198
references: J Clin Psychopharmacol. 2011 Jun;31(3):287-93
references: 21508848
references: J Affect Disord. 2011 Aug;132(3):344-55
references: 21470688
references: Neuroimage. 2013 Dec;83:472-84
references: 23668971
references: Hum Brain Mapp. 2007 Nov;28(11):1194-205
references: 17266101
references: Wiley Interdiscip Rev Cogn Sci. 2010;1(2):293-300
references: 24052810
references: Hum Brain Mapp. 2010 Feb;31(2):173-84
references: 19603407
references: Brain. 2014 Jun;137(Pt 6):1799-812
references: 24755274
references: Psychol Med. 2006 Nov;36(11):1593-600
references: 16882356
references: Annu Rev Psychol. 1995;46:121-53
references: 7872729
references: Eur Neuropsychopharmacol. 2009 Dec;19(12):835-40
references: 19717283
references: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13040-5
references: 19620724
references: BMC Psychiatry. 2013;13:342
references: 24359128
references: Neuroimage. 2011 Aug 1;57(3):938-49
references: 21609770
references: Annu Rev Clin Psychol. 2012;8:49-76
references: 22224834
references: Bipolar Disord. 2012 May;14(3):217-26
references: 22548895
references: Front Neuroinform. 2009 Jul 09;3:23
references: 19636392
references: Nat Rev Neurosci. 2002 Aug;3(8):655-66
references: 12154366
references: Schizophr Res. 2010 Mar;117(1):1-12
references: 20071149
references: Biol Psychiatry. 1998 Oct 15;44(8):675-84
references: 9798070
references: Nat Rev Neurosci. 2002 Apr;3(4):319-21
references: 11967563
references: Biol Psychiatry. 2014 Apr 1;75(7):574-81
references: 24315411
references: Arch Gen Psychiatry. 2011 Feb;68(2):128-37
references: 21300943
references: Neurol Sci. 2013 Jun;34(6):813-7
references: 23207549
references: Biol Psychiatry. 2010 Jun 1;67(11):1097-105
references: 20303066
references: Neuron. 2009 Apr 16;62(1):42-52
references: 19376066
references: Neuroimage. 2012 Feb 1;59(3):2349-61
references: 21963913
references: J Affect Disord. 2012 Apr;138(1-2):9-18
references: 21511342
references: Biol Psychiatry. 2008 Mar 15;63(6):550-6
references: 17825801
references: Am J Psychiatry. 2010 Jul;167(7):748-51
references: 20595427
references: Neuropsychopharmacology. 2010 Feb;35(3):686-91
references: 19890260
references: Brain Struct Funct. 2013 Jul;218(4):929-42
references: 22777602
references: Arch Gen Psychiatry. 2010 Jul;67(7):701-11
references: 20603451
references: Curr Opin Neurobiol. 2013 Aug;23(4):615-24
references: 23523373
references: Schizophr Res. 2011 Apr;127(1-3):46-57
references: 21300524
references: Schizophr Res. 2005 Dec 1;80(1):73-84
references: 16169191
references: Neuron. 2006 Jun 1;50(5):799-812
references: 16731517
references: Neuroimage. 2009 Aug;47 Suppl 2:T66-71
references: 19285558
references: Nat Rev Neurosci. 2013 May;14(5):322-36
references: 23531697
references: Neuroimage. 2005 Apr 15;25(3):653-60
references: 15808966
references: Brain Struct Funct. 2010 Jun;214(5-6):655-67
references: 20512370
references: Int J Neurosci. 2005 Nov;115(11):1549-67
references: 16223701