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Articles   |    
Paralimbic Cortical Thickness in First-Episode Depression: Evidence for Trait-Related Differences in Mood Regulation
Philip van Eijndhoven, M.D., Ph.D.; Guido van Wingen, Ph.D.; Maartje Katzenbauer, M.D.; Wouter Groen, M.D., Ph.D.; Ralf Tepest, Ph.D.; Guillen Fernández, M.D., Ph.D.; Jan Buitelaar, M.D., Ph.D.; Indira Tendolkar, M.D., Ph.D.
Am J Psychiatry 2013;170:1477-1486. doi:10.1176/appi.ajp.2013.12121504
View Author and Article Information

In the past 3 years Dr. Buitelaar has been a consultant to, member of an advisory board of, and/or speaker for Janssen Cilag, Eli Lilly and Sons, Shire, Novartis, Roche, and Servier; he is not an employee of any of these companies and not a stock shareholder of any of these companies; he has no other financial or material support, including expert testimony, patents, or royalties. The other authors report no financial relationships with commercial interests.

From the Department of Psychiatry, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition, and Behavior, Nijmegen, the Netherlands; GGz Centraal, Amersfoort, the Netherlands; the Department of Psychiatry, University of Cologne, Cologne, Germany; the Karakter Child and Adolescent Psychiatry University Centre, Nijmegen, the Netherlands; and the Department of Psychiatry, University of Duisburg-Essen, Essen, Germany.

Address correspondence to Dr. van Eijndhoven (p.vaneijndhoven@psy.umcn.nl).

Copyright © 2013 by the American Psychiatric Association

Received December 03, 2012; Revised April 01, 2013; Accepted May 09, 2013.

Abstract

Objective  Impaired mood regulation is a key deficit of major depressive disorder that is primarily mediated by an interaction between the paralimbic cortex (i.e., orbitofrontal, cingulate, insular, parahippocampal, and temporopolar cortices) and limbic regions. The authors investigated whether depressed patients and healthy comparison subjects have differences in cortical thickness in the paralimbic cortex and whether potential differences are evident only during a depressive state or are trait related.

Method  Forty patients with a first episode of major depressive disorder participated: 20 medication-naive currently depressed patients and 20 medication-free recovered patients. The patients and 31 matched healthy comparison subjects underwent structural magnetic resonance imaging. Group differences in mean cortical thickness of the paralimbic cortex were measured by using FreeSurfer software, with adjustment for age, sex, and intracranial volume, and subgroup analyses were performed to assess state and trait effects.

Results  The medial orbitofrontal cortex was thinner in the depressed patients than in the comparison subjects. Greater thickness was present in the temporal pole and the caudal anterior and posterior cingulate cortex. All changes were trait related.

Conclusions  The data provide evidence that even early in the course of depression brain regions involved in mood regulation show trait-related differences in cortical thickness.

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FIGURE 1. Areas of the Cerebral Cortex Showing Less or More Thickness in Patients With First-Episode Major Depressive Disorder (N=40) Than in Healthy Comparison Subjects (N=31)a

a The patients with major depression had less thickness than the comparison subjects in the left medial orbitofrontal cortex and greater thickness of the bilateral temporal poles, left posterior cingulate cortex, and left rostral anterior cingulate cortex. On the color scale, negative p values indicate less thickness in the patients and positive values indicate greater thickness.

FIGURE 2. Cortical Thickness in Regions of Interest in Acutely Ill (N=20) and Recovered (N=20) Patients With First-Episode Major Depressive Disorder and in Healthy Comparison Subjects (N=31)a

a Horizontal lines indicate mean values.

FIGURE 3. Correlation Between Thickness of the Left Medial Orbitofrontal Cortex and Trait Anxiety in Healthy Comparison Subjects
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TABLE 1.Demographic, Clinical, and Neuropsychological Characteristics of Medication-Free Acutely Ill and Recovered Patients With First-Episode Major Depressive Disorder and Healthy Comparison Subjects
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a p value of likelihood ratio.

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b Treatment of the recovered patients: citalopram only, N=4; paroxetine only, N=3; fluoxetine only, N=3; CBT only, N=2; venlafaxine only, N=1; paroxetine plus fluoxetine, N=2; citalopram plus venlafaxine, N=1; paroxetine plus venlafaxine, N=1; paroxetine plus amitriptyline, N=1; citalopram, paroxetine, and venlafaxine, N=1; paroxetine, fluoxetine, and venlafaxine, N=1.

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c One-way ANOVA.

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d Ratings used by the Dutch education system (40); 5=postgraduate.

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e One-way ANOVA with two groups only (two-sample t test).

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TABLE 2.Brain Regions With Significant Differences in Cortical Thickness Between Patients With First-Episode Major Depressive Disorder and Healthy Comparison Subjects
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a Based on the Talairach and Tournoux system (41).

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b With the covariates gender, age, and intracranial volume.

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TABLE 3.Comparison of Cortical Thickness in Regions of Interest in Acutely Ill and Recovered Patients With Major Depressive Disorder and in Healthy Comparison Subjects
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a ANCOVA of the three groups with the covariates gender, age, and intracranial volume.

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b With Bonferroni adjustment for multiple comparisons.

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References

Phillips  ML;  Drevets  WC;  Rauch  SL;  Lane  R:  Neurobiology of emotion perception II: implications for major psychiatric disorders.  Biol Psychiatry 2003; 54:515–528
[CrossRef] | [PubMed]
 
Mayberg  HS:  Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment.  Br Med Bull 2003; 65:193–207
[CrossRef] | [PubMed]
 
Holtzheimer  PE;  Mayberg  HS:  Stuck in a rut: rethinking depression and its treatment.  Trends Neurosci 2011; 34:1–9
[CrossRef] | [PubMed]
 
Mesulam  MM:  From sensation to cognition.  Brain 1998; 121:1013–1052
[CrossRef] | [PubMed]
 
Drevets  WC;  Price  JL;  Furey  ML:  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression.  Brain Struct Funct 2008; 213:93–118
[CrossRef] | [PubMed]
 
Phillips  ML;  Ladouceur  CD;  Drevets  WC:  A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder.  Mol Psychiatry 2008; 13:829, 833–857
[CrossRef] | [PubMed]
 
Rajkowska  G;  Miguel-Hidalgo  JJ;  Wei  J;  Dilley  G;  Pittman  SD;  Meltzer  HY;  Overholser  JC;  Roth  BL;  Stockmeier  CA:  Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression.  Biol Psychiatry 1999; 45:1085–1098
[CrossRef] | [PubMed]
 
Rajkowska  G;  Miguel-Hidalgo  JJ;  Dubey  P;  Stockmeier  CA;  Krishnan  KR:  Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients.  Biol Psychiatry 2005; 58:297–306
[CrossRef] | [PubMed]
 
Cotter  D;  Mackay  D;  Landau  S;  Kerwin  R;  Everall  I:  Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder.  Arch Gen Psychiatry 2001; 58:545–553
[CrossRef] | [PubMed]
 
Ongür  D;  Drevets  WC;  Price  JL:  Glial reduction in the subgenual prefrontal cortex in mood disorders.  Proc Natl Acad Sci USA 1998; 95:13290–13295
[CrossRef] | [PubMed]
 
Rajkowska  G;  Miguel-Hidalgo  JJ:  Gliogenesis and glial pathology in depression.  CNS Neurol Disord Drug Targets 2007; 6:219–233
[CrossRef] | [PubMed]
 
Järnum  H;  Eskildsen  SF;  Steffensen  EG;  Lundbye-Christensen  S;  Simonsen  CW;  Thomsen  IS;  Fründ  ET;  Théberge  J;  Larsson  EM:  Longitudinal MRI study of cortical thickness, perfusion, and metabolite levels in major depressive disorder.  Acta Psychiatr Scand 2011; 124:435–446
[CrossRef] | [PubMed]
 
Peterson  BS;  Warner  V;  Bansal  R;  Zhu  H;  Hao  X;  Liu  J;  Durkin  K;  Adams  PB;  Wickramaratne  P;  Weissman  MM:  Cortical thinning in persons at increased familial risk for major depression.  Proc Natl Acad Sci USA 2009; 106:6273–6278
[CrossRef] | [PubMed]
 
Fallucca  E;  MacMaster  FP;  Haddad  J;  Easter  P;  Dick  R;  May  G;  Stanley  JA;  Rix  C;  Rosenberg  DR:  Distinguishing between major depressive disorder and obsessive-compulsive disorder in children by measuring regional cortical thickness.  Arch Gen Psychiatry 2011; 68:527–533
[CrossRef] | [PubMed]
 
Koolschijn  PC;  van Haren  NE;  Schnack  HG;  Janssen  J;  Hulshoff Pol  HE;  Kahn  RS:  Cortical thickness and voxel-based morphometry in depressed elderly.  Eur Neuropsychopharmacol 2010; 20:398–404
[CrossRef] | [PubMed]
 
Ahn  KJ;  Won  WY;  Hahn  C;  Lee  SY;  Kim  I;  Lee  CU:  Regional cortical thickness and subcortical volume changes are associated with cognitive impairments in the drug-naive patients with late-onset depression.  Neuropsychopharmacology 2012; 37:838–849
[CrossRef] | [PubMed]
 
Colloby  SJ;  Firbank  MJ;  Vasudev  A;  Parry  SW;  Thomas  AJ;  O’Brien  JT:  Cortical thickness and VBM-DARTEL in late-life depression.  J Affect Disord 2011; 133:158–164
[CrossRef] | [PubMed]
 
van Eijndhoven  P;  van Wingen  G;  van Oijen  K;  Rijpkema  M;  Goraj  B;  Jan Verkes  R;  Oude Voshaar  R;  Fernández  G;  Buitelaar  J;  Tendolkar  I:  Amygdala volume marks the acute state in the early course of depression.  Biol Psychiatry 2009; 65:812–818
[CrossRef] | [PubMed]
 
First  MB;  Spitzer  RL;  Gibbon  M;  Williams  JBW:  Structured Clinical Interview for DSM-IV Axis I Disorders (SCID), Clinician Version .  Washington, DC,  American Psychiatric Press, 1996
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Frank  E;  Prien  RF;  Jarrett  RB;  Keller  MB;  Kupfer  DJ;  Lavori  PW;  Rush  AJ;  Weissman  MM:  Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence.  Arch Gen Psychiatry 1991; 48:851–855
[CrossRef] | [PubMed]
 
Sheehan  DV;  Lecrubier  Y;  Sheehan  KH;  Amorim  P;  Janavs  J;  Weiller  E;  Hergueta  T;  Baker  R;  Dunbar  GC:  The Mini-International Neuropsychiatric Interview (MINI): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10.  J Clin Psychiatry 1998; 59(suppl 20):22–33
[PubMed]
 
Beck  AT;  Ward  CH;  Mendelson  M;  Mock  J;  Erbaugh  J:  An inventory for measuring depression.  Arch Gen Psychiatry 1961; 4:561–571
[CrossRef] | [PubMed]
 
Spielberger  CD;  Gorschuch  RL;  Lushene  RE:  STAI Manual for the State Trait Anxiety Inventory .  Palo Alto, Calif,  Consulting Psychologists Press, 1970
 
Oldfield  RC:  The assessment and analysis of handedness: the Edinburgh inventory.  Neuropsychologia 1971; 9:97–113
[CrossRef] | [PubMed]
 
Schmand  B;  Lindeboom  J;  van Harskamp  F:  Nederlandse leestest voor volwassenen: handleiding .  Lisse, the Netherlands,  Swets & Zeitlinger, 1992
 
Bouma  A;  Mulder  J;  Lindeboom  J (eds):  Nederlandse leestest voor volwassenen (NLV) .  Lisse, the Netherlands,  Swets & Zeitlinger, 1996
 
Osterrieth  PA:  Le test de copie d'une figure complexe: contribution a l'etude de la perception et de la memoire.  Arch Psychol 1944; 30:286–356
 
Saan  RJ;  De Deelman  BG:  15-woorden tests A en B: een voorlopige handleiding .  Groningen, the Netherlands,  University Medical Center Groningen, Department of Neuropsychology, 1986
 
Wechsler  D:  Wechsler Adult Intelligence Scale, 3rd ed: Administration and Scoring Manual TPC .  New York,  Oxford University Press, 1997
 
Reitan  RM:  Validity of the Trail Making Test as an indicator of organic brain damage.  Percept Mot Skills 1958; 8:271–276
 
Heaton  RK;  Chelune  RK;  Talley  JL;  Kay  GG;  Curtiss  G:  Wisconsin Card Sorting Test Manual: Revised and Expanded .  Odessa, Tex,  Psychological Assessment Resources, 1993
 
Rosas  HD;  Liu  AK;  Hersch  S;  Glessner  M;  Ferrante  RJ;  Salat  DH;  van der Kouwe  A;  Jenkins  BG;  Dale  AM;  Fischl  B:  Regional and progressive thinning of the cortical ribbon in Huntington’s disease.  Neurology 2002; 58:695–701
[CrossRef] | [PubMed]
 
Han  X;  Jovicich  J;  Salat  D;  van der Kouwe  A;  Quinn  B;  Czanner  S;  Busa  E;  Pacheco  J;  Albert  M;  Killiany  R;  Maguire  P;  Rosas  D;  Makris  N;  Dale  A;  Dickerson  B;  Fischl  B:  Reliability of MRI-derived measurements of human cerebral cortical thickness: the effects of field strength, scanner upgrade and manufacturer.  Neuroimage 2006; 32:180–194
[CrossRef] | [PubMed]
 
Fischl  B;  Sereno  MI;  Tootell  RB;  Dale  AM:  High-resolution intersubject averaging and a coordinate system for the cortical surface.  Hum Brain Mapp 1999; 8:272–284
[CrossRef] | [PubMed]
 
Dale  AM;  Fischl  B;  Sereno  MI:  Cortical surface-based analysis, I: segmentation and surface reconstruction.  Neuroimage 1999; 9:179–194
[CrossRef] | [PubMed]
 
Lyoo  IK;  Sung  YH;  Dager  SR;  Friedman  SD;  Lee  JY;  Kim  SJ;  Kim  N;  Dunner  DL;  Renshaw  PF:  Regional cerebral cortical thinning in bipolar disorder.  Bipolar Disord 2006; 8:65–74
[CrossRef] | [PubMed]
 
Ashburner  J;  Csernansky  JG;  Davatzikos  C;  Fox  NC;  Frisoni  GB;  Thompson  PM:  Computer-assisted imaging to assess brain structure in healthy and diseased brains.  Lancet Neurol 2003; 2:79–88
[CrossRef] | [PubMed]
 
Rauch  SL;  Wright  CI;  Martis  B;  Busa  E;  McMullin  KG;  Shin  LM;  Dale  AM;  Fischl  B:  A magnetic resonance imaging study of cortical thickness in animal phobia.  Biol Psychiatry 2004; 55:946–952
[CrossRef] | [PubMed]
 
Loozen  SWHC;  Post  GJ:  Het onderwijsniveau van de Nederlands bevolking: Uitkomsten van de Enquete Beroepsbevolking. Sociaal-economische maandstatistiek 1991; 4:4–13
 
Talairach  J;  Tournoux  P:  Co-Planar Stereotaxic Atlas of the Human Brain: Three-Dimensional Proportional System .  New York,  Thieme Medical, 1988
 
Murray  EA;  Wise  SP;  Drevets  WC:  Localization of dysfunction in major depressive disorder: prefrontal cortex and amygdala.  Biol Psychiatry 2011; 69:e43–e54
[CrossRef] | [PubMed]
 
Konarski  JZ;  McIntyre  RS;  Kennedy  SH;  Rafi-Tari  S;  Soczynska  JK;  Ketter  TA:  Volumetric neuroimaging investigations in mood disorders: bipolar disorder versus major depressive disorder.  Bipolar Disord 2008; 10:1–37
[CrossRef] | [PubMed]
 
Kempton  MJ;  Salvador  Z;  Munafò  MR;  Geddes  JR;  Simmons  A;  Frangou  S;  Williams  SC:  Structural neuroimaging studies in major depressive disorder: meta-analysis and comparison with bipolar disorder.  Arch Gen Psychiatry 2011; 68:675–690
[CrossRef] | [PubMed]
 
Drevets  WC:  Orbitofrontal cortex function and structure in depression.  Ann NY Acad Sci 2007; 1121:499–527
[CrossRef] | [PubMed]
 
Kühn  S;  Schubert  F;  Gallinat  J:  Structural correlates of trait anxiety: reduced thickness in medial orbitofrontal cortex accompanied by volume increase in nucleus accumbens.  J Affect Disord 2011; 134:315–319
[CrossRef] | [PubMed]
 
Parker  G;  Wilhelm  K;  Mitchell  P;  Austin  MP;  Roussos  J;  Gladstone  G:  The influence of anxiety as a risk to early onset major depression.  J Affect Disord 1999; 52:11–17
[CrossRef] | [PubMed]
 
Sandi  C;  Richter-Levin  G:  From high anxiety trait to depression: a neurocognitive hypothesis.  Trends Neurosci 2009; 32:312–320
[CrossRef] | [PubMed]
 
Rauch  SL;  Milad  MR;  Orr  SP;  Quinn  BT;  Fischl  B;  Pitman  RK:  Orbitofrontal thickness, retention of fear extinction, and extraversion.  Neuroreport 2005; 16:1909–1912
[CrossRef] | [PubMed]
 
Milad  MR;  Quinn  BT;  Pitman  RK;  Orr  SP;  Fischl  B;  Rauch  SL:  Thickness of ventromedial prefrontal cortex in humans is correlated with extinction memory.  Proc Natl Acad Sci USA 2005; 102:10706–10711
[CrossRef] | [PubMed]
 
Terasawa  Y;  Fukushima  H;  Umeda  S:  How does interoceptive awareness interact with the subjective experience of emotion? an fMRI study.  Hum Brain Mapp 2013; 34:598–612
[PubMed]
 
Olson  IR;  Plotzker  A;  Ezzyat  Y:  The enigmatic temporal pole: a review of findings on social and emotional processing.  Brain 2007; 130:1718–1731
[CrossRef] | [PubMed]
 
Murai  T;  Fujimoto  S:  Rapid cycling bipolar disorder after left temporal polar damage.  Brain Inj 2003; 17:355–358
[CrossRef] | [PubMed]
 
Mikhailova  ES;  Vladimirova  TV;  Iznak  AF;  Tsusulkovskaya  EJ;  Sushko  NV:  Abnormal recognition of facial expression of emotions in depressed patients with major depression disorder and schizotypal personality disorder.  Biol Psychiatry 1996; 40:697–705
[CrossRef] | [PubMed]
 
Peng  J;  Liu  J;  Nie  B;  Li  Y;  Shan  B;  Wang  G;  Li  K:  Cerebral and cerebellar gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study.  Eur J Radiol 2011; 80:395–399
[CrossRef] | [PubMed]
 
Beauregard  M;  Paquette  V;  Lévesque  J:  Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder.  Neuroreport 2006; 17:843–846
[CrossRef] | [PubMed]
 
Tzourio-Mazoyer  N;  Landeau  B;  Papathanassiou  D;  Crivello  F;  Etard  O;  Delcroix  N;  Mazoyer  B;  Joliot  M:  Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain.  Neuroimage 2002; 15:273–289
[CrossRef] | [PubMed]
 
Phan  KL;  Fitzgerald  DA;  Nathan  PJ;  Moore  GJ;  Uhde  TW;  Tancer  ME:  Neural substrates for voluntary suppression of negative affect: a functional magnetic resonance imaging study.  Biol Psychiatry 2005; 57:210–219
[CrossRef] | [PubMed]
 
Drevets  WC;  Savitz  J;  Trimble  M:  The subgenual anterior cingulate cortex in mood disorders.  CNS Spectr 2008; 13:663–681
[PubMed]
 
Bora  E;  Fornito  A;  Pantelis  C;  Yücel  M:  Gray matter abnormalities in major depressive disorder: a meta-analysis of voxel based morphometry studies.  J Affect Disord 2012; 138:9–18
[CrossRef] | [PubMed]
 
Hasler  G;  Northoff  G:  Discovering imaging endophenotypes for major depression.  Mol Psychiatry 2011; 16:604–619
[CrossRef] | [PubMed]
 
Gould  E;  Reeves  AJ;  Graziano  MS;  Gross  CG:  Neurogenesis in the neocortex of adult primates.  Science 1999; 286:548–552
[CrossRef] | [PubMed]
 
Ohira  K:  Injury-induced neurogenesis in the mammalian forebrain.  Cell Mol Life Sci 2011; 68:1645–1656
[CrossRef] | [PubMed]
 
Ohira  K;  Takeuchi  R;  Shoji  H;  Miyakawa  T:  Fluoxetine-induced cortical adult neurogenesis.  Neuropsychopharmacology 2013; 38:909–920
[CrossRef] | [PubMed]
 
Sheline  YI;  Barch  DM;  Price  JL;  Rundle  MM;  Vaishnavi  SN;  Snyder  AZ;  Mintun  MA;  Wang  S;  Coalson  RS;  Raichle  ME:  The default mode network and self-referential processes in depression.  Proc Natl Acad Sci USA 2009; 106:1942–1947
[CrossRef] | [PubMed]
 
Li  B;  Liu  L;  Friston  KJ;  Shen  H;  Wang  L;  Zeng  LL;  Hu  D:  A treatment-resistant default mode subnetwork in major depression.  Biol Psychiatry  (Epub ahead of print, Jan 2, 2013)
 
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