Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis
Abstract
Objective:
Method:
Results:
Conclusions:
Method
Samples
Study Principal Investigator | Site | Field Strength (teslas) | Age (years) | Control Subjects (N) | OCD Patients (N) | Total (N) | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
Control Subjects | OCD Patients | Male (%) | |||||||||
Mean | SD | Mean | SD | Control Subjects | OCD | ||||||
Adult samples | |||||||||||
Benedetti | Milan | 3.0 | 34.0 | 12.3 | 35.0 | 10.4 | 73 | 71 | 62 | 66 | 128 |
Beucke | Berlin | 1.5 | 31.9 | 9.5 | 32.4 | 9.7 | 49 | 50 | 104 | 92 | 196 |
Cheng | Kunming I | 1.5 | 31.4 | 8.0 | 30.6 | 10.2 | 33 | 38 | 40 | 24 | 64 |
Kunming II | 3.0 | 26.2 | 4.2 | 32.9 | 10.6 | 28 | 55 | 95 | 56 | 151 | |
Denys | Amsterdam | 3.0 | 39.6 | 10.3 | 33.8 | 9.6 | 44 | 21 | 25 | 24 | 49 |
van den Heuvel | Amsterdam I | 1.5 | 31.6 | 7.7 | 33.5 | 9.2 | 39 | 30 | 49 | 54 | 103 |
Amsterdam II | 3.0 | 39.6 | 11.4 | 38.3 | 10.1 | 47 | 48 | 38 | 42 | 80 | |
Hoexter | São Paulo I | 1.5 | 27.6 | 7.8 | 31.5 | 10.1 | 35 | 44 | 37 | 50 | 87 |
Koch | Munich | 3.0 | 30.2 | 9.0 | 31.1 | 9.7 | 40 | 33 | 75 | 72 | 147 |
Kwon | Seoul I | 1.5 | 24.0 | 3.6 | 24.8 | 5.4 | 56 | 76 | 104 | 45 | 149 |
Seoul II | 1.5 | 24.9 | 5.3 | 28.8 | 6.8 | 64 | 56 | 45 | 34 | 79 | |
Seoul III | 3.0 | 26.3 | 6.9 | 26.3 | 6.8 | 61 | 61 | 89 | 90 | 179 | |
Mataix-Cols | Stockholm | 1.5 | 36.1 | 11.3 | 38.7 | 10.9 | 36 | 43 | 33 | 44 | 77 |
Menchon | Barcelona | 1.5 | 33.1 | 10.2 | 34.8 | 9.2 | 45 | 50 | 66 | 117 | 183 |
Nakamae | Kyoto I | 1.5 | 30.3 | 7.8 | 31.7 | 9.3 | 52 | 49 | 48 | 82 | 130 |
Kyoto II | 3.0 | 30.0 | 7.4 | 33.3 | 9.7 | 48 | 35 | 42 | 34 | 76 | |
Nakao | Fukuoka | 3.0 | 39.3 | 13.0 | 36.6 | 10.0 | 39 | 42 | 41 | 81 | 122 |
Reddy | Bangalore I | 1.5 | 27.2 | 6.4 | 27.5 | 6.3 | 74 | 59 | 46 | 44 | 90 |
Bangalore II | 3.0 | 26.3 | 5.0 | 29.6 | 8.0 | 62 | 52 | 156 | 208 | 364 | |
Simpson | New York | 3.0 | 28.3 | 8.0 | 29.6 | 8.0 | 52 | 52 | 33 | 33 | 66 |
Spalletta | Rome | 3.0 | 36.5 | 10.5 | 36.7 | 11.6 | 59 | 67 | 128 | 84 | 212 |
Stein | Cape Town | 3.0 | 30.6 | 10.8 | 30.7 | 10.8 | 38 | 50 | 29 | 22 | 51 |
Tolin | Connecticut | 3.0 | 48.0 | 11.9 | 32.1 | 12.0 | 22 | 67 | 32 | 27 | 59 |
Walitza | Zurich I | 3.0 | 32.9 | 9.2 | 31.2 | 7.7 | 28 | 47 | 18 | 17 | 35 |
Wang | Shanghai | 3.0 | 26.2 | 7.5 | 29.6 | 9.3 | 54 | 57 | 37 | 53 | 90 |
Total, adult samples | 1,472 | 1,495 | 2,967 | ||||||||
Pediatric samples | |||||||||||
Arnold | Ontario | 3.0 | 12.3 | 2.2 | 12.9 | 2.4 | 54 | 58 | 13 | 40 | 53 |
Fitzgerald | Michigan | 3.0 | 12.9 | 2.9 | 13.9 | 2.6 | 52 | 49 | 67 | 74 | 141 |
Gruner | Connecticut | 3.0 | 14.2 | 2.2 | 14.3 | 2.1 | 52 | 57 | 23 | 23 | 46 |
Hoexter | São Paulo II | 3.0 | 12.0 | 2.4 | 12.6 | 2.5 | 57 | 61 | 28 | 28 | 56 |
Huyser | Amsterdam | 3.0 | 13.3 | 2.5 | 13.6 | 2.5 | 36 | 37 | 25 | 27 | 52 |
Lazaro | Barcelona I | 1.5 | 14.6 | 2.3 | 14.6 | 2.0 | 47 | 58 | 32 | 31 | 63 |
Barcelona II | 3.0 | 14.6 | 2.1 | 14.6 | 2.0 | 55 | 60 | 44 | 58 | 102 | |
Reddy | Bangalore III | 3.0 | 13.1 | 2.1 | 14.6 | 2.0 | 50 | 56 | 14 | 18 | 32 |
Soreni | Ontario | 3.0 | 11.2 | 3.1 | 13.4 | 2.5 | 52 | 40 | 21 | 20 | 41 |
Walitza | Zurich II | 3.0 | 14.6 | 1.3 | 15.7 | 1.4 | 50 | 81 | 20 | 16 | 36 |
Total, pediatric samples | 287 | 335 | 622 | ||||||||
Total, adult and pediatric samples | 1,759 | 1,830 | 3,589 |
Study Principal Investigator | Site | Medicated (%) | YBOCSa Score | Age at Onset (years) | Lifetime Comorbid Disorders | |||
---|---|---|---|---|---|---|---|---|
Mean | SD | Mean | SD | Anxiety (%) | Depression (%) | |||
Adult samples | ||||||||
Benedetti | Milan | 64 | 30.9 | 5.6 | 16.0 | 6.1 | 1.5 | 10.6 |
Beucke | Berlin | 40 | 20.1 | 7.1 | 17.2 | 7.8 | 12.0 | 18.5 |
Cheng | Kunming I | 71 | 31.0 | 6.1 | 26.8 | 10.4 | 50.0 | 16.7 |
Kunming II | 68 | 28.2 | 6.3 | 27.2 | 10.7 | 89.3 | 28.6 | |
Denys | Amsterdam | 63 | 26.6 | 6.2 | 18.1 | 6.9 | 4.2 | 41.7 |
van den Heuvel | Amsterdam I | 0 | 22.7 | 6.1 | 14.4 | 7.7 | 22.2 | 33.3 |
Amsterdam II | 0 | 21.5 | 6.1 | 15.5 | 6.9 | 40.5 | 52.4 | |
Hoexter | São Paulo I | 20 | 27.2 | 6.1 | 13.1 | 7.0 | 62.0 | 54.0 |
Koch | Munich | 60 | 20.9 | 6.2 | 17.0 | 6.7 | — | — |
Kwon | Seoul I | 24 | 20.2 | 6.0 | 17.4 | 5.2 | 0.0 | 0.0 |
Seoul II | 0 | 23.9 | 6.5 | 18.9 | 6.6 | 0.0 | 2.9 | |
Seoul III | 2 | 26.5 | 6.5 | 19.0 | 6.4 | 1.1 | 2.2 | |
Mataix-Cols | Stockholm | 41 | 25.9 | 7.7 | 18.4 | 9.2 | 27.3 | 34.1 |
Menchon | Barcelona | 97 | 25.5 | 5.8 | 21.4 | 8.5 | 20.5 | 18.8 |
Nakamae | Kyoto I | 49 | 25.2 | 6.4 | 25.1 | 9.4 | 9.8 | 22.0 |
Kyoto II | 0 | 22.4 | 6.9 | 25.2 | 9.1 | 8.8 | 20.6 | |
Nakao | Fukuoka | 88 | 22.5 | 5.6 | 24.6 | 9.5 | — | 35.8 |
Reddy | Bangalore I | 0 | 25.8 | 7.3 | 21.7 | 7.5 | 15.9 | 18.2 |
Bangalore II | 40 | 25.8 | 6.3 | 22.0 | 7.6 | 7.7 | 15.4 | |
Simpson | New York | 0 | 25.5 | 3.7 | 15.0 | 7.0 | 21.2 | 30.3 |
Spalletta | Rome | 88 | 23.4 | 8.9 | 18.9 | 10.9 | 9.5 | 9.5 |
Stein | Cape Town | 41 | 22.9 | 4.2 | 13.6 | 6.6 | 0.0 | 0.0 |
Tolin | Connecticut | 78 | 22.7 | 4.8 | — | — | 44.4 | 40.7 |
Walitza | Zurich I | 59 | 17.1 | 9.9 | 16.7 | 7.8 | 47.1 | 47.1 |
Wang | Shanghai | 0 | 25.5 | 5.1 | 23.3 | 10.3 | 0.0 | 0.0 |
Pediatric samples | ||||||||
Arnold | Ontario | 53 | 20.9 | 7.8 | 8.7 | 2.6 | 25.0 | 17.5 |
Fitzgerald | Michigan | 50 | 18.7 | 7.8 | 9.9 | 3.0 | 50.0 | 6.8 |
Gruner | Connecticut | 52 | 26.9 | 4.5 | — | — | 43.5 | 39.1 |
Hoexter | São Paulo II | 46 | 26.9 | 5.4 | 7.2 | 3.0 | 21.4 | 0.0 |
Huyser | Amsterdam | 0 | 25.1 | 5.0 | 10.9 | 2.8 | 48.2 | 25.9 |
Lazaro | Barcelona I | 55 | 22.2 | 6.0 | 12.4 | 2.2 | 16.1 | 3.2 |
Barcelona II | 79 | 18.6 | 7.4 | 12.0 | 2.4 | 25.9 | 5.2 | |
Reddy | Bangalore III | 83 | 22.6 | 7.3 | 13.1 | 2.1 | 22.2 | 5.6 |
Soreni | Ontario | 0 | 22.8 | 4.3 | — | — | — | — |
Walitza | Zurich II | 56 | 14.7 | 1.0 | 11.1 | 2.2 | 50.0 | 6.3 |
Image Acquisition and Processing
Meta-Analysis of Subcortical Brain Volumes
Moderator Analyses
Power Analysis
Mega-Analysis of Subcortical Brain Volumes
Results
Meta-Analysis
OCD patients versus healthy controls.
Adult comparison:
Structure | Adjusted Cohen’s da | SE | 95% CI | % Difference | p | I2 | Control Subjects (N) | OCD Patients (N) |
---|---|---|---|---|---|---|---|---|
Lateral ventricles | 0.108 | 0.063 | –0.016, 0.231 | 1.712 | 0.087 | 61.327 | 1,466 | 1,491 |
Thalamus | –0.079 | 0.042 | –0.162, 0.005 | –1.851 | 0.064 | 12.542 | 1,387 | 1,375 |
Caudate | 0.032 | 0.038 | –0.043, 0.107 | 0.844 | 0.399 | 0.003 | 1,424 | 1,441 |
Putamen | 0.017 | 0.044 | –0.070, 0.103 | 0.380 | 0.704 | 16.141 | 1,335 | 1,365 |
Pallidum | 0.160 | 0.051 | 0.061, 0.259 | 3.156 | 1.60×10–3 | 32.877 | 1,312 | 1,336 |
Hippocampus | –0.135 | 0.048 | –0.229, –0.040 | –2.802 | 5.08×10–3 | 32.692 | 1,440 | 1,444 |
Amygdala | –0.108 | 0.050 | –0.206, –0.010 | –2.163 | 0.031 | 37.194 | 1,418 | 1,452 |
Accumbens | –0.041 | 0.040 | –0.120, 0.037 | –1.025 | 0.305 | 8.384 | 1,446 | 1,465 |
Intracranial volume | 0.014b | 0.048 | –0.081, 0.109 | 0.286 | 0.775 | 35.547 | 1,470 | 1,493 |
Pediatric comparison:
Influence of medication on subcortical volume.
Adult comparisons:
Pediatric comparisons:
Structure | Adjusted Cohen’s da | SE | 95% CI | % Difference | p | I2 | Control Subjects (N) | OCD Patients (N) |
---|---|---|---|---|---|---|---|---|
Lateral ventricles | –0.022 | 0.118 | –0.253, 0.209 | –0.189 | 0.850 | 0.000 | 216 | 115 |
Thalamus | 0.384 | 0.125 | 0.139, 0.628 | 3.078 | 2.09×10–3 | 0.000 | 201 | 103 |
Caudate | –0.024 | 0.134 | –0.288, 0.239 | –0.182 | 0.855 | 14.641 | 198 | 109 |
Putamen | –0.177 | 0.202 | –0.572, 0.219 | –0.875 | 0.382 | 59.152 | 204 | 104 |
Pallidum | –0.042 | 0.237 | –0.506, 0.423 | –0.176 | 0.860 | 66.561 | 174 | 87 |
Hippocampus | 0.239 | 0.141 | –0.038, 0.516 | 1.688 | 0.091 | 22.715 | 210 | 107 |
Amygdala | –0.029 | 0.256 | –0.530, 0.473 | –0.112 | 0.911 | 72.254 | 188 | 89 |
Accumbens | –0.183 | 0.122 | –0.422, 0.056 | –1.500 | 0.134 | 0.004 | 203 | 111 |
Intracranial volume | –0.033b | 0.144 | –0.314, 0.249 | –0.226 | 0.821 | 29.531 | 219 | 116 |
Influence of comorbid major depression on subcortical volume in adult OCD.
Adult comparisons:
Pediatric comparisons:
Influence of a comorbid anxiety disorder on subcortical volume.
Adult comparisons:
Pediatric comparisons:
Influence of symptom dimensions on subcortical volume.
Adult comparisons:
Pediatric comparisons:
Influence of age at onset and illness duration on subcortical volume.
Association of illness severity with subcortical volumes.
Moderator analyses.
Mega-Analysis
Adult OCD.
Pediatric OCD.
Discussion
Acknowledgments
Footnotes
Supplementary Material
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