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Original Article |

Distinguishing Between Major Depressive Disorder and Obsessive-Compulsive Disorder in Children by Measuring Regional Cortical Thickness FREE

Erin Fallucca, MD; Frank P. MacMaster, PhD; Joseph Haddad, BS; Phillip Easter, BA; Rachel Dick, BA; Geoffrey May, BS; Jeffrey A. Stanley, PhD; Carrie Rix, BS; David R. Rosenberg, MD
[+] Author Affiliations

Author Affiliations: Department of Psychiatry and Behavioral Neurosciences, Wayne State University, and Children's Hospital of Michigan, Detroit, Michigan (Drs Fallucca, MacMaster, Stanley, and Rosenberg, Messrs Haddad, Easter, and May, and Mss Dick and Rix); Department of Psychiatry and Behavioral Neurosciences, George Washington University, Washington, DC (Dr Fallucca); and Departments of Psychiatry and Pediatrics, University of Calgary, Alberta, Canada (Dr MacMaster).


Arch Gen Psychiatry. 2011;68(5):527-533. doi:10.1001/archgenpsychiatry.2011.36.
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Context  Cortical abnormalities have been noted in previous studies of major depressive disorder (MDD).

Objective  To hypothesize differences in regional cortical thickness among children with MDD, children with obsessive-compulsive disorder (OCD), and healthy controls.

Design  Cross-sectional study of groups.

Setting  Children's Hospital of Michigan in Detroit.

Participants  A total of 24 psychotropic drug–naive pediatric patients with MDD (9 boys and 15 girls), 24 psychotropic drug–naive pediatric outpatients with OCD (8 boys and 16 girls), and 30 healthy controls (10 boys and 20 girls).

Intervention  Magnetic resonance imaging.

Main Outcome Measure  Cortical thickness.

Results  In the right hemisphere of the brain, the pericalcarine gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .04), the postcentral gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .02), and the superior parietal gyrus was thinner in patients with MDD than in outpatients with OCD (P = .008) or healthy controls (P = .03). The outpatients with OCD and the healthy controls did not differ in these regions of the brain. The temporal pole was thicker in patients with MDD than in outpatients with OCD (P < .001) or healthy controls (P = .01), both of which groups did not differ in temporal pole thickness. The cuneus was thinner in patients with MDD than in outpatients with OCD (P = .008), but it did not differ from that in healthy controls. In the left hemisphere, the supramarginal gyrus was thinner in both patients with MDD (P = .04) and outpatients with OCD (P = .01) than in healthy controls, and the temporal pole was thicker in patients with MDD than in both healthy controls and outpatients with OCD (P < .001).

Conclusions  To our knowledge, this is the first study to explore cortical thickness in pediatric patients with MDD. Although differences in some regions of the brain would be expected given neurobiological models of MDD, our study highlights some unexpected regions (ie, supramarginal and superior parietal gyri) that merit further investigation. These results underscore the need to expand exploration beyond the frontal-limbic circuit.

Figures in this Article

Major depressive disorder (MDD) is a common, debilitating illness with frequent onset in childhood and adolescence. It has a lifetime prevalence of approximately 5% in adolescence and is believed to be continuous with adult MDD.1,2 Studies of pediatric patients with MDD may minimize potential confounding variables, such as treatment intervention and illness duration.

Abnormalities in frontal,3,4 limbic,512 and hypothalamic-pituitary-adrenal axis1315 structures have been implicated in MDD. In a study of the cytoarchitecture of the left rostral and caudal orbitofrontal and dorsolateral prefrontal cortical regions in subjects with major depression compared with psychiatrically normal controls, Rajkowska et al16 found decreases in cortical thickness, neuronal size, and neuronal and glial densities in the upper (II-IV) cortical layers of the rostral orbitofrontal region in patients with MDD. In the caudal orbitofrontal cortex in subjects with MDD, prominent reductions in glial densities in the lower (V-VI) cortical layers were accompanied by small but significant decreases in neuronal size. In the dorsolateral prefrontal cortex of subjects with MDD, reductions in the density and size of neurons and glial cells were found in both supra- and infragranular layers. Family history may influence the underlying neurobiology of MDD.3,4,6,17,18 Recently, Peterson et al19 suggested that cortical thinning in the right hemisphere produces disturbances in arousal, attention, and memory for social stimuli, which in turn may increase the risk of developing depressive illness in those at high risk (via family history) for MDD.

The identification of relevant biomarkers in MDD is a major aim of research into the neurobiology of the illness. Previous work found compelling differences between thalamic neurochemistry in patients with obsessive-compulsive disorder (OCD) and patients with MDD20,21 and areas of similarity, like anterior cingulate neurochemistry.22 A sensitive and specific biomarker would enhance our understanding of the pathophysiology of MDD and may help us to define the phenotype and reduce heterogeneity in genetic studies and facilitate early detection and intervention. An ideal biomarker for MDD would have high sensitivity and specificity for the disorder in affected patients. The diagnostic specificity of abnormalities in cortical thickness, however, has not been widely studied.

Two-thirds of patients with OCD will develop depression during their lifetime. Prior functional imaging studies in adult and pediatric patients with OCD and MDD have demonstrated comparable findings in some regions and distinct findings in others.2023 One important area of research is to determine whether neurobiological findings are specific to a particular psychiatric diagnosis or whether they generalize across diagnoses, so we have also included a group of patients with OCD to serve as a psychiatric control group. In our study, we chose to measure cortical thickness in psychotropic drug−naive children with MDD, psychotropic drug−naive children with OCD, and healthy controls. This method employs a surface-based measurement approach that, unlike voxel-based morphometry, is able to interpret folding across the entire cortex.24 FreeSurfer's cortical thickness measurement technique has been previously validated using postmortem studies and is able to accurately detect submillimeter variations in gray matter.24 Based on previous studies of pediatric patients with MDD and pediatric patients with OCD, we hypothesized that significant differences in cortical thickness would exist in the anterior cingulate, orbital frontal cortex, and dorsolateral prefrontal cortex regions. We examined for laterality effects because several of our previously published neuroimaging studies found striking laterality effects for both volumetric and neurochemical measures in pediatric patients with MDD.3,4 Given prior investigation suggesting distinct alterations in familial vs nonfamilial MDD,3,4,6,17,18 we also conducted an exploratory analysis of the effect of familial vs nonfamilial MDD on cortical thickness.

SUBJECTS

A total of 24 psychotropic drug–naive pediatric patients with MDD (9 boys and 15 girls with a mean [SD] age, unless otherwise stated, of 13.96 [2.41] years) and 24 psychotropic drug–naive pediatric outpatients with OCD (8 boys and 16 girls [as a psychiatric control group] with a mean [SD] age of 13.02 [2.92] years) were included in our study (Table 1). In the MDD group, 15 subjects had at least 1 first-degree relative with MDD. A total of 30 healthy controls (10 boys and 20 girls with a mean [SD] age of 13.44 [2.78] years) were used as a comparison group. All patients were recruited through the Wayne State University child psychiatry outpatient clinic. Diagnoses were made using the Schedule for Affective Disorders and Schizophrenia for School-Age Children−Present and Lifetime Versions.25 A board-certified child and adolescent psychiatrist (D.R.R.) interviewed each subject and their parents to confirm the presence of DSM-IV criteria for OCD or MDD.

Table Graphic Jump LocationTable 1. Demographic and Clinical Characteristics of 78 Children

Fifteen of 24 patients with MDD exhibited comorbid disorders, including attention-deficit disorder without hyperactivity, oppositional defiant disorder, and anxiety disorders (including generalized anxiety disorder and separation anxiety disorder). Three of the patients with MDD who had comorbid attention-deficit disorder without hyperactivity had not been previously treated with stimulant medication or other pharmacotherapy for attention-deficit/hyperactivity disorder. Of the 24 patients with MDD, 9 had MDD as their sole diagnosis. Eleven of the 15 patients with MDD who had at least 1 first-degree relative with MDD and 4 of the 9 patients with MDD who had no obvious family history of MDD had comorbid disorders. Of the 24 outpatients with OCD, 9 exhibited comorbid disorders, including dysthymia, anxiety disorders, enuresis, oppositional defiant disorder, and seasonal affective disorder, and 15 had OCD as their sole diagnosis. Exclusion criteria for both patients and healthy controls included a lifetime history of bipolar disorder, psychosis, eating disorders, Sydenham chorea, conduct disorder, substance abuse or dependence, Tourette syndrome, pervasive developmental disorders, mental retardation, learning disorders, or significantly debilitating medical and neurological conditions. Outpatients with OCD did not have a lifetime history of MDD, and patients with MDD did not have a lifetime history of OCD or subthreshold obsessive-compulsive symptoms and behaviors. There was no history of psychiatric illness in the healthy controls or in any of their first-degree relatives. The parents, as well as the children, served as informants for these diagnostic assessments. After a complete description of our study to the subjects, written informed consent was obtained from the legal guardian, and the participants provided written assent. The Wayne State University Human Investigation Committee provided approval to conduct our study.

CLINICAL ASSESSMENTS

Measures of depression and anxiety were obtained using the 17-item Hamilton Depression Rating Scale26 (mean [SD] score of 17.00 [7.65] for patients with MDD and 7.13 [6.33] for outpatients with OCD) and the 17-item Hamilton Anxiety Rating Scale27 (mean [SD] score of 12.24 [5.07] for patients with MDD patients and 7.04 [5.76] for outpatients with OCD), respectively. These scales were used to ascertain depression and anxiety for consistency of measurement across diagnoses. The Children's Yale-Brown Obsessive Compulsive Scale28 was used to assess the OCD symptom severity in outpatients with OCD (mean [SD] score, 24.21 [7.00]). Mean (SD) duration of illness was 24.90 (31.32) months for the patients with MDD and 41.17 (39.75) months for the outpatients with OCD.

MAGNETIC RESONANCE IMAGING

Magnetic resonance imaging examinations were conducted at the Children's Hospital of Michigan Imaging Center in Detroit. The imaging acquisition methods have been described previously in detail.29,30 All images were acquired in the coronal plane after performing a sagittal scout series to verify patient position, patient cooperation, and image quality. The sequence was produced using a 3-dimensional spoiled gradient echo pulse sequence with a 40° flip angle, 25-millisecond repetition time, and a 5-millisecond echo time on a 1.5-T whole-body superconducting imaging system (General Electric, Milwaukee, Wisconsin). A total of 124 contiguous coronal slices (slice thickness, 1.5 mm, no gap) were produced through the whole brain using this sequence. The in-plane resolution produced was 0.94 × 0.94 mm in a 256 × 256 matrix. Axial proton density and T2-weighted images were obtained to exclude structural abnormalities. A pediatric neuroradiologist reviewed all scans to rule out clinically significant abnormalities.

IMAGE ANALYSIS

Cortical reconstruction and volumetric segmentation were performed with the automated FreeSurfer image analysis suite, which is documented and freely available for download (http://surfer.nmr.mgh.harvard.edu/). The technical details of these procedures have been described in detail previously.24 FreeSurfer uses a cortical surface model based on probabilistic information estimated from a manually labeled training set to create cortical sulci and gyri parcellations. This procedure (which incorporates geometric information derived from the cortical model) and neuroanatomical convention (as defined by the training set) have been described previously.31,32 Briefly, after the application of intensity variations to correct magnetic field inhomogeneities, nonbrain voxels from each subject's T1-weighted magnetic resonance imaging scan were removed, and then these images were segmented using an estimation of the gray-white interface.33 Each scan was inflated to create a smooth spherical surface, in order to reduce interference created by folds in the cortical mantel,33,34 and was registered to a spherical surface representation reference template that was created from an averaged pattern of a group of representative subjects and is the default template provided by FreeSurfer. Alignment of the spherical surface of the reconstructed brains to the reference template was achieved through a 2-dimensional warp of the subject's sphere surface that aligned the sulcal and gyral features of each subject to the curvature data pattern of the template, ensuring optimal alignment across subjects.33,34 Next, a circularly symmetric Gaussian kernel was used to smooth the maps, and averaging across subjects was performed to align cortical folding patterns.34 Average measures of cortical thickness were produced at each point on the reconstructed surface. The spherical transform was used to map the thickness measurements at each vertex on each subject's cortical surface into a common spherical coordinate system.33,34 The data were smoothed on the surface tessellation using an iterative nearest-neighbor averaging procedure (50 iterations were applied, equivalent to applying a 2-dimensional Gaussian smoothing kernel along the cortical surface with a full-width half-maximum of 13 mm), and a deformable surface algorithm was used to define the pial surface with submillimeter accuracy.24 Data were then resampled for participants into a common spherical coordinate system.34 Manual corrections to the segmentation were then made to each cortex. These procedures were performed by an investigator who was blinded to subject group assignment. Thickness across the cortex was measured by averaging each point between the gray-white boundary surface and the estimated pial surface.24 Validation of this technique has been confirmed by direct comparisons with manual measures on postmortem brains as well as by direct comparisons with manual measures on magnetic resonance imaging data.24

STATISTICAL ANALYSIS

All statistical analyses were conducted using the Statistical Package for Social Sciences, version 18.0.35 An analysis of covariance was used to compare the 3 groups using age as a covariate. Post hoc analysis used least significant differences tests. There were 31 comparisons (.05/31 = .002), and α was set at P < .002. Age was selected as a covariate given the wide age range and likelihood of regions of interest correlating with age. Sex was also used as a covariate to accommodate possible sex effects. Pearson correlations were used to examine the relationship between significant differences in cortical thickness and clinical variables. In an exploratory manner, a subanalysis comparing patients with familial MDD, patients with nonfamilial MDD, outpatients with OCD, and healthy controls was also performed, and because this is an exploratory subanalysis, α was set at .05.

RIGHT HEMISPHERE

In the right hemisphere of the brain, the pericalcarine gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .04), the postcentral gyrus was thinner in patients with MDD than in outpatients with OCD (P = .002) or healthy controls (P = .02), and the superior parietal gyrus was thinner in patients with MDD than in outpatients with OCD (P = .008) or healthy controls (P = .03). The outpatients with OCD and the healthy controls did not differ in these regions of the brain (Figure). The temporal pole was thicker in patients with MDD than in outpatients with OCD (P < .001) or healthy controls (P = .01), both of which groups did not differ in temporal pole thickness. The cuneus was thinner in patients with MDD than in outpatients with OCD (P = .008), but it did not differ from that in healthy controls (Table 2).

Place holder to copy figure label and caption
Figure.

Cortical thickness results for the right superior parietal gyrus (A) and the left supramarginal gyrus (B). Horizontal lines indicate mean values. MDD indicates major depressive disorder; OCD, obsessive-compulsive disorder.

Table 2

Cortical Thickness Results of 3-Group Comparison

P Value Determined From Post Hoc AnalysesCortical Thickness, Mean (SD), mmRegion of InterestHCs (n = 30)Patients With MDD (n = 24)Outpatients With OCD (n = 24)F ValueP ValueHCs vs Patients With MDDHCs vs Outpatients With OCDPatients With MDD vs Outpatients With OCDRight pericalcarine gyrus1.847 (0.205)1.722 (0.132)1.926 (0.329)8.09<.001.04.18.002Right postcentral gyrus2.408 (0.391)2.184 (0.171)2.495 (0.417)6.94.002.02.33.002Right superior parietal gyrus2.560 (0.318)2.387 (0.224)2.676 (0.380)7.33.001.03.14.008Right temporal pole3.655 (0.773)4.092 (0.316)3.446 (0.676)8.06<.001.01.22<.001Right cuneus2.306 (0.448)2.083 (0.187)2.511 (0.585)8.35<.001.06.06<.001Left supramarginal gyrus3.009 (0.457)2.843 (0.201)2.800 (0.281)6.41.003.04.01.61Left temporal pole3.586 (0.657)4.012 (0.319)3.322 (0.663)7.73<.001.005.08<.001

 Abbreviations: HCs, healthy controls; MDD, major depressive disorder; OCD, obsessive-compulsive disorder.

Graphic Jump Location
LEFT HEMISPHERE

In the left hemisphere of the brain, the supramarginal gyrus was thinner in both patients with MDD (P = .04) and outpatients with OCD (P = .01) than in healthy controls (Figure), and the temporal pole was thicker in patients with MDD than in both healthy controls and outpatients with OCD (P < .001) (Table 2).

DEMOGRAPHIC AND CLINICAL CORRELATIONS

In patients with MDD, an association with age at onset of illness was seen (r = −0.516; P = .01) with the left supramarginal gyrus. The right temporal pole correlated negatively with the Hamilton Depression Rating Scale26 in patients with MDD (r = −0.450; P = .03). No other correlations with clinical variables were significant.

EXPLORATORY ANALYSIS

The effect of variations of cortical thickness observed in patients with MDD was driven by patients with a familial history of MDD. The right postcentral gyrus was thinner in patients with familial MDD than in healthy controls (P = .01) or outpatients with OCD (P = .002), and the right superior parietal gyrus was thinner in patients with familial MDD than in healthy controls (P = .03) or outpatients with OCD (P = .001). The outpatients with OCD and the healthy controls did not differ in these regions of the brain. Similarly, the left supramarginal gyrus was also thinner in patients with familial MDD than in healthy controls (P = .04); it was also thinner in outpatients with OCD than in healthy controls (P = .01). The right temporal pole was also thicker in patients with familial MDD than in health controls (P = .02) or outpatients with OCD subjects (P = .002), and the left temporal pole was also thicker in patients with familial MDD than in health controls (P = .009) or outpatients with OCD subjects (P < .001). The outpatients with OCD and the healthy controls did not differ in these regions of the brain (eTable).

To our knowledge, ours is the first study to use the automated FreeSurfer technique to explore cortical thickness in pediatric patients with MDD and pediatric outpatients with OCD. In patients with MDD, decreased cortical thickness was observed in the left supramarginal gyrus, the right pericalcarine gyrus, the postcentral gyrus, the superior parietal lobule, and the cuneus. Greater thickness in the bilateral temporal pole was noted. In outpatients with OCD, the only significantly different region from healthy controls was a thinner left supramarginal gyrus. Our findings of cortical thickness were unexpected because no significant differences were found in the anterior cingulate, the dorsolateral prefrontal cortex, or the orbital frontal cortex in patients with MDD or outpatients with OCD. This lack of patient group differences in hypothesized regions (anterior cingulate, orbital frontal cortex, and dorsal prefrontal cortex) could possibly be due to type II error. However, it should be noted that the types of errors introduced are not limited only to type II based on significance level choices but also to limitations in specific cortical regions, proximity to subcortical gray matter structures, and cortical folding patterns.3638 Additionally, the process of subdividing our sample into 4 comparison groups (ie, healthy controls, patients with familial MDD, patients with nonfamilial MDD, and outpatients with OCD) will have weakened the statistical power and the ability to detect differences. It is also possible that this may be due to the relatively small sample size or to limitations in method, such as our use of the standard template provided by FreeSurfer rather than a pediatric template that would have been more closely representative of our sample. Although use of an adult template was not expected to have had much of an effect for the age range examined in our study, the choice of template for segmentation could have resulted in possible bias related to adult vs an age-appropriate atlas.39,40 The sample was, however, unique in that all patients with MDD and all outpatients with OCD were naive to psychotropic drugs. These findings also underscore the need to look beyond standard frontal-limbic (MDD) and frontal striatal (OCD) models in these disorders.

The neuroanatomical findings in the right postcentral gyrus, the superior parietal lobule, the left supramarginal gyrus, and the bilateral temporal pole appear to be driven by patients with familial MDD. The neuroanatomical findings in the right hemisphere are consistent with Peterson et al,19 who found cortical thinning in the right hemisphere in subjects with no personal history of MDD who were at increased risk for developing MDD. Our investigation extends these results by finding differences in affected pediatric patients with MDD compared with a psychiatric comparison group of pediatric outpatients with OCD. Although speculative, cortical thinning effects may be stronger for familial than nonfamilial depression owing to environmental and genetic factors. There may be a protective factor in pediatric patients with nonfamilial MDD who may be in an environment in which they can better cope with their illness.

Possibly consistent with our finding of a thinner postcentral gyrus in patients with MDD, lower regional cerebral blood flow has also been noted in the postcentral gyrus in these patients.41 In a group at high risk for depression, abnormal activation of the superior parietal lobule was noted compared with low-risk controls.42 Cognitive changes with MDD, like impaired sustained attention, may be associated with parietal dysfunction.43 Abnormal glucose metabolism was also noted in the cunei of patients with MDD compared with controls.44 Although we found the temporal pole to be thicker in patients with MDD than in healthy controls, no volumetric differences have been noted previously.45 Greater activation in the temporal pole has been noted in patients with MDD trying to voluntarily downregulate sad feelings.46 In 12 severely depressed subjects, Keedwell et al47 found that depression severity correlated positively with responses to sad stimuli in the temporal pole. Lower gray matter density has also been noted with voxel-based morphometry studies of the temporal pole in first-episode MDD,48 although negative findings do exist.45 The temporal pole has connections to orbital and medial prefrontal regions,49 areas commonly implicated in MDD. The supramarginal gyri have not been previously implicated in the pathogenesis of MDD. The effects noted in the right superior parietal lobule, the postcentral gyrus, the supramarginal gyrus, and the bilateral temporal poles were also driven by familial MDD primarily, akin to previous findings in the hippocampus in pediatric MDD.6

The cortical thinning found in the left supramarginal gyrus was the only significant difference noted between outpatients with OCD and healthy controls. It has been hypothesized that the repetitive behaviors of OCD reflect problems in set shifting50 and that the supramarginal gyrus plays a role in set shifting.51 Interestingly, the supramarginal gyrus and the parietal lobe, in general, have been implicated in OCD previously, but their role in the disorder remains little explored.5258

More critically, cortical thickness distinguished psychotropic drug–naive pediatric patients with MDD from both psychotropic drug–naive pediatric outpatients with OCD and healthy controls in several regions. This builds on prior work in pediatric OCD and MDD, which has demonstrated distinct functional and neurochemical alterations in some, but not all, regions of interest.2326 These results also suggest that alterations in cortical thickness may be more prominent in patients with familial MDD than in patients with nonfamilial MDD. Some of the identified regions have also been identified as being thinner in children who were born prematurely. According to history reports obtained during our assessments, all subjects were of normal gestational age and had no in utero exposure. However, more sophisticated interviews and personal histories are likely necessary for the best assessment of this. Comorbidity also differed between patients with MDD and outpatients with OCD. The cortical thinning found in patients with MDD but not in outpatients with OCD or healthy controls could be confounded by comorbid disorders (eg, attention-deficit/hyperactivity disorder in patients with MDD but not in outpatients with OCD). We also performed ancillary analyses in which we excluded patients with MDD who had comorbid anxiety disorders and nondepressed outpatients with OCD patients who had dysthymia and high levels of depressive symptoms on the Hamilton Depression Rating Scale26 because it is possible that overlap in depression-anxiety diagnoses might preclude our ability to see MDD vs OCD group differences in the frontal region and in other regions. However, comparable results were observed with these ancillary analyses, underscoring the need for further study in larger samples.

Our study did not produce the expected results in this sample of pediatric patients with MDD and pediatric outpatients with OCD. No significant abnormalities were found in the frontal lobe structures. However, changes in the parietal cortex and the temporal cortex were observed. This highlights the need to expand our exploration of brain regions from the typical standard regions of interest. Further exploration to determine whether these findings are reproducible in larger, independent samples of patients with MDD and patients with OCD is needed.

Correspondence: David R. Rosenberg, MD, Department of Psychiatry and Behavioral Neurosciences, Wayne State University, Psychiatry 9B, 4201 St Antoine Blvd, Detroit, MI 48201 (drosen@med.wayne.edu).

Submitted for Publication: May 26, 2010; final revision received December 7, 2010; accepted December 10, 2010.

Financial Disclosure: None reported.

Funding/Support: This research was supported in part by the State of Michigan Joe F. Young Sr Psychiatric Research and Training Program; the Miriam L. Hamburger Endowed Chair of Child Psychiatry at Children's Hospital of Michigan and Wayne State University, Detroit, Michigan; the Paul Strauss endowment for the integration of computer science and psychiatry; the National Institute of Mental Health (grants R01MH59299, R01MH65122, and K24MH02037); the World Heritage Foundation; the Schutt Foundation; the United Way; the National Alliance for Research on Schizophrenia and Depression; and the Mental Illness Research Association.

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Mirza  YO’Neill  JSmith  EARussell  ASmith  JMBanerjee  SPBhandari  RBoyd  CRose  MIvey  JRenshaw  PFRosenberg  DR Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol 2006;21 (2) 106- 111
PubMed
Rosenberg  DRMirza  YRussell  ATang  JSmith  JMBanerjee  SPBhandari  RRose  MIvey  JBoyd  CMoore  GJ Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 2004;43 (9) 1146- 1153
PubMed
Baxter  LR  JrSchwartz  JMGuze  BHBergman  KSzuba  MP PET imaging in obsessive compulsive disorder with and without depression. J Clin Psychiatry 1990;51(suppl)61- 69, discussion 70
PubMed
Fischl  BDale  AM Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A 2000;97 (20) 11050- 11055
PubMed
Kaufman  JBirmaher  BBrent  DRao  UFlynn  CMoreci  PWilliamson  DRyan  N Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36 (7) 980- 988
PubMed
Hamilton  M Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6 (4) 278- 296
PubMed
Hamilton  M The assessment of anxiety states by rating. Br J Med Psychol 1959;32 (1) 50- 55
PubMed
Scahill  LRiddle  MAMcSwiggin-Hardin  MOrt  SIKing  RAGoodman  WKCicchetti  DLeckman  JF Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36 (6) 844- 852
PubMed
Gilbert  ARKeshavan  MSDiwadkar  VNutche  JMacmaster  FEaster  PCBuhagiar  CJRosenberg  DR Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett 2008;435 (1) 45- 50
PubMed
Szeszko  PRChristian  CMacmaster  FLencz  TMirza  YTaormina  SPEaster  PRose  MMichalopoulou  GARosenberg  DR Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study. Am J Psychiatry 2008;165 (10) 1299- 1307
PubMed
Fischl  Bvan der Kouwe  ADestrieux  CHalgren  ESégonne  FSalat  DHBusa  ESeidman  LJGoldstein  JKennedy  DCaviness  VMakris  NRosen  BDale  AM Automatically parcellating the human cerebral cortex. Cereb Cortex 2004;14 (1) 11- 22
PubMed
Desikan  RSSégonne  FFischl  BQuinn  BTDickerson  BCBlacker  DBuckner  RLDale  AMMaguire  RPHyman  BTAlbert  MSKilliany  RJ An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006;31 (3) 968- 980
PubMed
Dale  AMFischl  BSereno  MI Cortical surface-based analysis: I, segmentation and surface reconstruction. Neuroimage 1999;9 (2) 179- 194
PubMed
Fischl  BSereno  MIDale  AM Cortical surface-based analysis: II, Inflation, flattening, and a surface-based coordinate system. Neuroimage 1999;9 (2) 195- 207
PubMed
 Statistical Package for the Social Sciences [computer program]. Version 18.0.  Chicago, IL SPSS Inc2010;
Klauschen  FGoldman  ABarra  VMeyer-Lindenberg  ALundervold  A Evaluation of automated brain MR image segmentation and volumetry methods. Hum Brain Mapp 2009;30 (4) 1310- 1327
PubMed
Pantazis  DJoshi  AJiang  JShattuck  DWBernstein  LEDamasio  HLeahy  RM Comparison of landmark-based and automatic methods for cortical surface registration. Neuroimage 2010;49 (3) 2479- 2493
PubMed
Zhong  JPhua  DYQiu  A Quantitative evaluation of LDDMM, FreeSurfer, and CARET for cortical surface mapping. Neuroimage 2010;52 (1) 131- 141
PubMed
Fonov  VEvans  ACBotteron  KAlmli  CRMcKinstry  RCCollins  DLBrain Development Cooperative Group, Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 2011;54 (1) 313- 327
PubMed
Yoon  UFonov  VSPerusse  DEvans  ACBrain Development Cooperative Group, The effect of template choice on morphometric analysis of pediatric brain data. Neuroimage 2009;45 (3) 769- 777
PubMed
Krausz  YFreedman  NLester  HBarkai  GLevin  TBocher  MChisin  RLerer  BBonne  O Brain SPECT study of common ground between hypothyroidism and depression. Int J Neuropsychopharmacol 2007;10 (1) 99- 106
PubMed
Chan  SWHarmer  CJGoodwin  GMNorbury  R Risk for depression is associated with neural biases in emotional categorisation. Neuropsychologia 2008;46 (12) 2896- 2903
PubMed
Brody  ALBarsom  MWBota  RGSaxena  S Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Semin Clin Neuropsychiatry 2001;6 (2) 102- 112
PubMed
Kimbrell  TAKetter  TAGeorge  MSLittle  JTBenson  BEWillis  MWHerscovitch  PPost  RM Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biol Psychiatry 2002;51 (3) 237- 252
PubMed
Takahashi  TYücel  MLorenzetti  VWalterfang  MKawasaki  YWhittle  SSuzuki  MPantelis  CAllen  NB An MRI study of the superior temporal subregions in patients with current and past major depression. Prog Neuropsychopharmacol Biol Psychiatry 2010;34 (1) 98- 103
PubMed
Beauregard  MPaquette  VLévesque  J Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder. Neuroreport 2006;17 (8) 843- 846
PubMed
Keedwell  PDrapier  DSurguladze  SGiampietro  VBrammer  MPhillips  M Neural markers of symptomatic improvement during antidepressant therapy in severe depression: subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score. J Psychopharmacol 2009;23 (7) 775- 788
PubMed
Peng  JLiu  JNie  BLi  YShan  BWang  GLi  K Cerebral and cerebella gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study [published ahead of print May 11, 2010]. Eur J Radiol
PubMed10.1016/j.ejrad.2010.04.006
Kondo  HSaleem  KSPrice  JL Differential connections of the temporal pole with the orbital and medial prefrontal networks in macaque monkeys. J Comp Neurol 2003;465 (4) 499- 523
PubMed
Okasha  ARafaat  MMahallawy  NEl Nahas  GEl Dawla  ASSayed  MEl Kholi  S Cognitive dysfunction in obsessive-compulsive disorder. Acta Psychiatr Scand 2000;101 (4) 281- 285
PubMed
Periáñez  JAMaestú  FBarceló  FFernández  AAmo  COrtiz Alonso  T Spatiotemporal brain dynamics during preparatory set shifting: MEG evidence. Neuroimage 2004;21 (2) 687- 695
PubMed
Schienle  ASchäfer  AStark  RWalter  BVaitl  D Neural responses of OCD patients towards disorder-relevant, generally disgust-inducing and fear-inducing pictures. Int J Psychophysiol 2005;57 (1) 69- 77
PubMed
Szeszko  PRArdekani  BAAshtari  MMalhotra  AKRobinson  DGBilder  RMLim  KO White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. Arch Gen Psychiatry 2005;62 (7) 782- 790
PubMed
Menzies  LWilliams  GBChamberlain  SROoi  CFineberg  NSuckling  JSahakian  BJRobbins  TWBullmore  ET White matter abnormalities in patients with obsessive-compulsive disorder and their first-degree relatives. Am J Psychiatry 2008;165 (10) 1308- 1315
PubMed
Amo  CQuesney  LFOrtiz  TMaestú  FFernández  ALópez-Ibor  MILópez-Ibor  JJ Limbic paroxysmal magnetoencephalographic activity in 12 obsessive-compulsive disorder patients: a new diagnostic finding. J Clin Psychiatry 2004;65 (2) 156- 162
PubMed
Rubin  RTAnanth  JVillanueva-Meyer  JTrajmar  PGMena  I Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment. Biol Psychiatry 1995;38 (7) 429- 437
PubMed
Kwon  JSKim  JJLee  DWLee  JSLee  DSKim  MSLyoo  IKCho  MJLee  MC Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder. Psychiatry Res 2003;122 (1) 37- 47
PubMed
den Braber  AEnt  DBlokland  GAvan Grootheest  DSCath  DCVeltman  DJde Ruiter  MBBoomsma  DI An fMRI study in monozygotic twins discordant for obsessive-compulsive symptoms. Biol Psychol 2008;79 (1) 91- 102
PubMed

Figures

Place holder to copy figure label and caption
Figure.

Cortical thickness results for the right superior parietal gyrus (A) and the left supramarginal gyrus (B). Horizontal lines indicate mean values. MDD indicates major depressive disorder; OCD, obsessive-compulsive disorder.

Table 2

Cortical Thickness Results of 3-Group Comparison

P Value Determined From Post Hoc AnalysesCortical Thickness, Mean (SD), mmRegion of InterestHCs (n = 30)Patients With MDD (n = 24)Outpatients With OCD (n = 24)F ValueP ValueHCs vs Patients With MDDHCs vs Outpatients With OCDPatients With MDD vs Outpatients With OCDRight pericalcarine gyrus1.847 (0.205)1.722 (0.132)1.926 (0.329)8.09<.001.04.18.002Right postcentral gyrus2.408 (0.391)2.184 (0.171)2.495 (0.417)6.94.002.02.33.002Right superior parietal gyrus2.560 (0.318)2.387 (0.224)2.676 (0.380)7.33.001.03.14.008Right temporal pole3.655 (0.773)4.092 (0.316)3.446 (0.676)8.06<.001.01.22<.001Right cuneus2.306 (0.448)2.083 (0.187)2.511 (0.585)8.35<.001.06.06<.001Left supramarginal gyrus3.009 (0.457)2.843 (0.201)2.800 (0.281)6.41.003.04.01.61Left temporal pole3.586 (0.657)4.012 (0.319)3.322 (0.663)7.73<.001.005.08<.001

 Abbreviations: HCs, healthy controls; MDD, major depressive disorder; OCD, obsessive-compulsive disorder.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Demographic and Clinical Characteristics of 78 Children

References

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Mirza  YO’Neill  JSmith  EARussell  ASmith  JMBanerjee  SPBhandari  RBoyd  CRose  MIvey  JRenshaw  PFRosenberg  DR Increased medial thalamic creatine-phosphocreatine found by proton magnetic resonance spectroscopy in children with obsessive-compulsive disorder versus major depression and healthy controls. J Child Neurol 2006;21 (2) 106- 111
PubMed
Rosenberg  DRMirza  YRussell  ATang  JSmith  JMBanerjee  SPBhandari  RRose  MIvey  JBoyd  CMoore  GJ Reduced anterior cingulate glutamatergic concentrations in childhood OCD and major depression versus healthy controls. J Am Acad Child Adolesc Psychiatry 2004;43 (9) 1146- 1153
PubMed
Baxter  LR  JrSchwartz  JMGuze  BHBergman  KSzuba  MP PET imaging in obsessive compulsive disorder with and without depression. J Clin Psychiatry 1990;51(suppl)61- 69, discussion 70
PubMed
Fischl  BDale  AM Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci U S A 2000;97 (20) 11050- 11055
PubMed
Kaufman  JBirmaher  BBrent  DRao  UFlynn  CMoreci  PWilliamson  DRyan  N Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 1997;36 (7) 980- 988
PubMed
Hamilton  M Development of a rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6 (4) 278- 296
PubMed
Hamilton  M The assessment of anxiety states by rating. Br J Med Psychol 1959;32 (1) 50- 55
PubMed
Scahill  LRiddle  MAMcSwiggin-Hardin  MOrt  SIKing  RAGoodman  WKCicchetti  DLeckman  JF Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry 1997;36 (6) 844- 852
PubMed
Gilbert  ARKeshavan  MSDiwadkar  VNutche  JMacmaster  FEaster  PCBuhagiar  CJRosenberg  DR Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: a preliminary voxel-based morphometry study. Neurosci Lett 2008;435 (1) 45- 50
PubMed
Szeszko  PRChristian  CMacmaster  FLencz  TMirza  YTaormina  SPEaster  PRose  MMichalopoulou  GARosenberg  DR Gray matter structural alterations in psychotropic drug-naive pediatric obsessive-compulsive disorder: an optimized voxel-based morphometry study. Am J Psychiatry 2008;165 (10) 1299- 1307
PubMed
Fischl  Bvan der Kouwe  ADestrieux  CHalgren  ESégonne  FSalat  DHBusa  ESeidman  LJGoldstein  JKennedy  DCaviness  VMakris  NRosen  BDale  AM Automatically parcellating the human cerebral cortex. Cereb Cortex 2004;14 (1) 11- 22
PubMed
Desikan  RSSégonne  FFischl  BQuinn  BTDickerson  BCBlacker  DBuckner  RLDale  AMMaguire  RPHyman  BTAlbert  MSKilliany  RJ An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 2006;31 (3) 968- 980
PubMed
Dale  AMFischl  BSereno  MI Cortical surface-based analysis: I, segmentation and surface reconstruction. Neuroimage 1999;9 (2) 179- 194
PubMed
Fischl  BSereno  MIDale  AM Cortical surface-based analysis: II, Inflation, flattening, and a surface-based coordinate system. Neuroimage 1999;9 (2) 195- 207
PubMed
 Statistical Package for the Social Sciences [computer program]. Version 18.0.  Chicago, IL SPSS Inc2010;
Klauschen  FGoldman  ABarra  VMeyer-Lindenberg  ALundervold  A Evaluation of automated brain MR image segmentation and volumetry methods. Hum Brain Mapp 2009;30 (4) 1310- 1327
PubMed
Pantazis  DJoshi  AJiang  JShattuck  DWBernstein  LEDamasio  HLeahy  RM Comparison of landmark-based and automatic methods for cortical surface registration. Neuroimage 2010;49 (3) 2479- 2493
PubMed
Zhong  JPhua  DYQiu  A Quantitative evaluation of LDDMM, FreeSurfer, and CARET for cortical surface mapping. Neuroimage 2010;52 (1) 131- 141
PubMed
Fonov  VEvans  ACBotteron  KAlmli  CRMcKinstry  RCCollins  DLBrain Development Cooperative Group, Unbiased average age-appropriate atlases for pediatric studies. Neuroimage 2011;54 (1) 313- 327
PubMed
Yoon  UFonov  VSPerusse  DEvans  ACBrain Development Cooperative Group, The effect of template choice on morphometric analysis of pediatric brain data. Neuroimage 2009;45 (3) 769- 777
PubMed
Krausz  YFreedman  NLester  HBarkai  GLevin  TBocher  MChisin  RLerer  BBonne  O Brain SPECT study of common ground between hypothyroidism and depression. Int J Neuropsychopharmacol 2007;10 (1) 99- 106
PubMed
Chan  SWHarmer  CJGoodwin  GMNorbury  R Risk for depression is associated with neural biases in emotional categorisation. Neuropsychologia 2008;46 (12) 2896- 2903
PubMed
Brody  ALBarsom  MWBota  RGSaxena  S Prefrontal-subcortical and limbic circuit mediation of major depressive disorder. Semin Clin Neuropsychiatry 2001;6 (2) 102- 112
PubMed
Kimbrell  TAKetter  TAGeorge  MSLittle  JTBenson  BEWillis  MWHerscovitch  PPost  RM Regional cerebral glucose utilization in patients with a range of severities of unipolar depression. Biol Psychiatry 2002;51 (3) 237- 252
PubMed
Takahashi  TYücel  MLorenzetti  VWalterfang  MKawasaki  YWhittle  SSuzuki  MPantelis  CAllen  NB An MRI study of the superior temporal subregions in patients with current and past major depression. Prog Neuropsychopharmacol Biol Psychiatry 2010;34 (1) 98- 103
PubMed
Beauregard  MPaquette  VLévesque  J Dysfunction in the neural circuitry of emotional self-regulation in major depressive disorder. Neuroreport 2006;17 (8) 843- 846
PubMed
Keedwell  PDrapier  DSurguladze  SGiampietro  VBrammer  MPhillips  M Neural markers of symptomatic improvement during antidepressant therapy in severe depression: subgenual cingulate and visual cortical responses to sad, but not happy, facial stimuli are correlated with changes in symptom score. J Psychopharmacol 2009;23 (7) 775- 788
PubMed
Peng  JLiu  JNie  BLi  YShan  BWang  GLi  K Cerebral and cerebella gray matter reduction in first-episode patients with major depressive disorder: a voxel-based morphometry study [published ahead of print May 11, 2010]. Eur J Radiol
PubMed10.1016/j.ejrad.2010.04.006
Kondo  HSaleem  KSPrice  JL Differential connections of the temporal pole with the orbital and medial prefrontal networks in macaque monkeys. J Comp Neurol 2003;465 (4) 499- 523
PubMed
Okasha  ARafaat  MMahallawy  NEl Nahas  GEl Dawla  ASSayed  MEl Kholi  S Cognitive dysfunction in obsessive-compulsive disorder. Acta Psychiatr Scand 2000;101 (4) 281- 285
PubMed
Periáñez  JAMaestú  FBarceló  FFernández  AAmo  COrtiz Alonso  T Spatiotemporal brain dynamics during preparatory set shifting: MEG evidence. Neuroimage 2004;21 (2) 687- 695
PubMed
Schienle  ASchäfer  AStark  RWalter  BVaitl  D Neural responses of OCD patients towards disorder-relevant, generally disgust-inducing and fear-inducing pictures. Int J Psychophysiol 2005;57 (1) 69- 77
PubMed
Szeszko  PRArdekani  BAAshtari  MMalhotra  AKRobinson  DGBilder  RMLim  KO White matter abnormalities in obsessive-compulsive disorder: a diffusion tensor imaging study. Arch Gen Psychiatry 2005;62 (7) 782- 790
PubMed
Menzies  LWilliams  GBChamberlain  SROoi  CFineberg  NSuckling  JSahakian  BJRobbins  TWBullmore  ET White matter abnormalities in patients with obsessive-compulsive disorder and their first-degree relatives. Am J Psychiatry 2008;165 (10) 1308- 1315
PubMed
Amo  CQuesney  LFOrtiz  TMaestú  FFernández  ALópez-Ibor  MILópez-Ibor  JJ Limbic paroxysmal magnetoencephalographic activity in 12 obsessive-compulsive disorder patients: a new diagnostic finding. J Clin Psychiatry 2004;65 (2) 156- 162
PubMed
Rubin  RTAnanth  JVillanueva-Meyer  JTrajmar  PGMena  I Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment. Biol Psychiatry 1995;38 (7) 429- 437
PubMed
Kwon  JSKim  JJLee  DWLee  JSLee  DSKim  MSLyoo  IKCho  MJLee  MC Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder. Psychiatry Res 2003;122 (1) 37- 47
PubMed
den Braber  AEnt  DBlokland  GAvan Grootheest  DSCath  DCVeltman  DJde Ruiter  MBBoomsma  DI An fMRI study in monozygotic twins discordant for obsessive-compulsive symptoms. Biol Psychol 2008;79 (1) 91- 102
PubMed

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Distinguishing Between Major Depressive Disorder and Obsessive-Compulsive Disorder in Children by Measuring Regional Cortical Thickness
Arch Gen Psychiatry.2011;68(5):527-533.eTable

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eTable. Cortical thickness results of four group comparison exploratory analysis
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