Introduction
Methods
Study Selection
Meta-analysis: Activation Likelihood Estimation
Results
Structural Neuroimaging Findings
Study | Total sample size (% male/ female) | Number of subjects (specified per group) | Age (years, range or M (SD)) | Analysis method | Results of comparisons between ODD/CD-only and control group, between ODD/CD+ADHD and control group, and between ODD/CD-mixed and control group. (brain regions reported show reduced volumes in the patient group, unless otherwise reported) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
ODD/CD -only | ODD/CD+ADHD | ODD/CD-mixed | ADHD- only | Controls | Amygdala | Insula | Prefrontal cortex | Other | ||||
1. Fahim et al. 2011
a,d
| 47c
(100 % male) | 22 | N/A | N/A | N/A | 25 | Patients: 8.4 (0.10) Controls: 8.4 (0.07) | Whole brain (VBM, cortical thickness) Correlational analyses |
ns
| Bilateral | Left dorsomedial | ODD/CD-only versus controls: VBM: Left medial frontal cortex /claustrum, right inferior frontal cortex/inferior parietal cortex Cortical thickness: left insula, left cingulate, left anterior cingulate, left medial frontal, left rectal/orbitofrontal, left uncus, left precuneus, right middle frontal, right superior temporal, right posterior cingulate ODD/CD-only versus controls: VBM: Negative correlation between right superior temporal cortex, left superior frontal gyrus, right occipital cortex and left precuneus volume and ODD/CD symptom severity |
2. Fairchild et al. 2011
a,d
| 90 (100 % male) | 63 | N/A | N/A | N/A | 27 | 16–21 | ROI; amygdala, insula, anterior cingulate cortex, orbitofrontal cortex (VBM) Whole brain (VBM) Correlational analyses | Bilateral (ROI) | Left (ROI) | Left dorsomedial | ODD/CD-only versus controls: Bilateral caudate, left fusiform gyrus, left inferior and superior occipital cortex ODD/CD-only versus controls: Negative correlation between right insula and CD symptoms |
3. Stevens and Haney-Caron 2012
a,d
| 72 (71 % male) | 24 | N/A | N/A | 24 | 24 | 12–18 | Whole brain (VBM) Correlational analyses | Left |
ns
|
ns
| ODD/CD-only versus controls: Left inferior frontal, right inferior/middle frontal, right parahippocampal/ fusiform, paracentral cingulate ODD/CD-only versus controls: Positive correlation between bilateral amygdala, bilateral temporal cortex and right lateral orbitofrontal volume and ODD/CD symptom severity |
4. Bussing et al. 2002
| 31 (74 % male) | N/A | 12 | N/A | N/A | 19 | 8–12 | Whole brain (VBM) |
ns
|
ns
|
ns
| ODD/CD+ADHD versus controls: Left and total posterior superior vermis, left and total posterior inferior vermis |
5. Kruesi et al. 2004
| 20b,c
(90 % male) | N/A | 10 | N/A | N/A | 10 | Patients: 16.1 (3.6) Controls: 15.9 (3.2) | Whole brain (VBM) |
ns
|
ns
|
ns
| ODD/CD+ADHD versus controls: Right temporal lobe |
6. Sterzer et al. 2007
a,d
| 24 (100 % male) | N/A | N/A | 12 (5 ODD/ CD-only) | N/A | 12 | Patients: 12.8 (0.49) Controls: 12.5 (0.45) | ROI: amygdala, anterior insula, anterior cingulate cortex, orbitofrontal cortex (VBM) Whole brain (VBM) Correlational analyses | Left (ROI) | Bilateral (ROI) |
ns
|
ns
ODD/CD-mixed versus controls: Negative correlation between left amygdala and bilateral insula volume and ODD/CD symptom severity (ROI) |
7. McAlonan et al. 2007
a,d
| 59a,c
(100 % male) | N/A | 28 | N/A | N/A | 31 | 6–13 | Whole brain (VBM) |
ns
|
ns
|
ns
| ODD/CD+ADHD versus controls: Midline cerebellum, right globus pallidus, right middle frontal gyrus, right superior frontal gyrus, right precuneus, left inferior parietal gyrus, left superior occipital gyrus |
8. Huebner et al. 2008
a,d
| 46c
(100 % male) | N/A | N/A | 23 (6 ODD/ CD-only) | N/A | 23 | 12–17 | Whole brain (VBM) Correlational analyses | Left |
ns
|
ns
| ODD/CD-mixed versus controls: Grey matter, bilateral inferior temporal lobes, left hippocampus, left orbitofrontal gyrus
Increased bilateral cerebellar volume in ODD/CD-mixed group ODD/CD-mixed versus controls: Negative correlation between bilateral amygdala volume and ODD/CD symptom severity |
9. Sasayama et al. 2010
a,d
| 35 (71 % male) | N/A | 10 | N/A | 8 | 17 | 6–16 | Whole brain (VBM) | Left |
ns
|
ns
| ODD/CD+ADHD versus controls: Bilateral temporal lobes, bilateral occipital lobes |
10. Fairchild et al. 2013a
,d
| 42b,e (100 % female) | N/A | N/A | 22 (20 3ODD/ CD-only) | N/A | 20 | 14–20 | ROI; amygdala, anterior insula, striatum, anterior cingulate cortex, orbitofrontal cortex (VBM) Whole brain (VBM) Correlational analyses |
ns
| Bilateral (ROI) | Right dorsolateral | ODD/CD-mixed versus controls: Right (ventral) striatum (ROI), right orbitofrontal cortex (ROI), left precentral gyrus, right mid-occipital cortex, right inferior frontal gyrus, left precuneus, middle temporal gyrus ODD/CD-mixed versus controls: Negative correlation between bilateral insula volume and psychopathic traits (ROI), negative correlation between both bilateral insula and left striatum volume and callous-unemotional traits (ROI), positive correlation between bilateral middle/superior orbitofrontal cortex and callous-unemotional traits (ROI). |
11. Hummer et al. 2015
| 66c
(73 % male) | 14 | 19 | 33 (14 ODD/ CD-only) | N/A | 33 | 13–17 | Whole brain (VBM) |
ns
|
ns
|
ns
|
ns
|
12. Michalska et al. 2015
| 111b
(48 % male) | N/A | 43 | N/A | N/A | 68 | 9–11 | Whole brain (VBM) Correlational analyses |
ns
|
ns
|
ns
|
ns
ODD/CD+ADHD versus controls: Negative correlation between left superior temporal sulcus volume and CD symptoms |
Functional Neuroimaging Findings
Study | Total sample (% male/ female) | Number of subjects (specified per group) | Age (years, range or M (SD)) | Analysis method | Task and conditions | Results of comparisons between ODD/CD-only and control group, between ODD/CD+ADHD and control group, and between ODD/CD-mixed and control group. (brain regions reported show reduced volumes in the patient group, unless otherwise reported) | ||||
---|---|---|---|---|---|---|---|---|---|---|
ODD/CD- only | ODD/CD+ADHD | ODD/CD -mixed | ADHD- only | Controls | ||||||
13. Rubia et al. 2009b
a,b
| 48c,d (100 % male) | 14 | N/A | N/A | 18 | 16 | 9–16 | Whole brain | Continuous Performance Task - Reward - Non-reward | ODD/CD-only versus controls: Behavioural: No significant group differences, all groups showed equally enhanced performance as a result of reward (versus non-reward trials)
Reward > non-reward: reduced activity in right lateral and medial orbitofrontal cortex |
14. Kalnin et al. 2011
| 44c,d,e (59 % male) | 22 | N/A | N/A | N/A | 22 | 13–17 | Whole brain | Emotional Stroop task - Violent words - Non-violent words | ODD/CD-only versus controls: Behavioural: No significant group differences No significant group differences |
15. Marsh et al. 2013
a
| 35c,d,f (66 % male) | 14 | N/A | N/A | N/A | 21 | 10–17 | Whole brain Correlational analyses | Viewing of pictures with three pain intensities (severe/mo-derate/none) during two conditions: pain applied to subject him/herself or to someone else | ODD/CD-only versus controls: Behavioural: No significant group differences
Group differences for the main effect of pain viewing: reduced activity in left medial frontal gyrus, rostral anterior cingulate cortex, right putamen
Other’s pain < own pain: reduced activity in left amygdala/uncus, left superior frontal gyrus, right insula ODD/CD-only versus controls: Negative correlation between left amygdala activation and aggressive behaviour, negative correlation between left anterior cingulate cortex activation and aggressive behaviour |
16. Sterzer et al. 2005
| 27d,f (100 % male) | N/A | N/A | 13 (5 ODD/ CD-only) | N/A | 14 | 9–15 | ROI: amygdala, hippocampus, orbitofrontal cortex, anterior cingulate cortex Correlational analyses | Passive viewing task of neutral and negative pictures. | ODD/CD-mixed versus controls: Behavioural: lowered arousal ratings for negative pictures and lowered valence and arousal ratings for neutral pictures in the CD-mixed group compared to controls
Negative > neutral pictures: reduced activity in left amygdala (ROI), right dorsal anterior cingulate (ROI) ODD/CD-mixed versus controls: Negative correlation between both left amygdala and right anterior cingulate cortex activation and aggressive behaviour (negative versus neutral contrast) |
17. Herpertz et al. 2008
a
| 57e
(100 % male) | N/A | N/A | 22 (6 ODD/ CD-only) | 13 | 22 | 12–17 | ROI: amygdala, anterior cingulate cortex, orbitofrontal/ medial frontal cortex, insula Whole brain | Passive viewing task Including positive, negative, neutral pictures | ODD/CD-mixed versus controls: Behavioural: CD-mixed evaluated negative and positive pictures as less arousing, and positive pictures as less pleasant compared to controls
Negative > neutral pictures
:
increased activity in left amygdala (ROI) |
18. Finger et al. 2008
a
| 42c,d,e (67 % male) | N/A | N/A | 14 (4 ODD/ CD-only) | 14 | 14 | 10–17 | Whole brain | Rewarded reversal learning Task - Punished reversal errors - Correct rewarded responses | ODD/CD-mixed versus controls: Behavioural: No significant group differences
Group differences for overall response type (reward and punishment)
:
increased activity in left precuneus, right superior frontal gyrus
Punished reversal errors > correct rewarded responses
:
increased activity in ventromedial prefrontal cortex, right caudate |
19. Marsh et al. 2008
| 36e
(58 % male) | N/A | N/A | 12 (5 ODD/ CD-only) | 12 | 12 | 10–17 | ROI: amygdala Correlational analyses | Implicit processing task: categorise gender of fearful, angry, and neutral faces | ODD/CD-mixed versus controls: Behavioural: No significant group differences
Fearful > neutral pictures: reduced activity in bilateral amygdala (ROI) ODD/CD-mixed versus controls: Negative correlation between connectivity between amygdala and right ventromedial prefrontal cortex, and ODD/CD symptom severity |
20. Gatzke-Kopp et al. 2009
| 30d,e
(100 % male) | N/A | N/A | 19 (3 ODD/ CD-only) | N/A | 11 | 12–16 | ROI: anterior cingulate cortex, caudate, putamen | Monetary incentive task - Reward - Non-reward | ODD/CD-mixed versus controls: Behavioural: No significant group differences
Non-reward > reward: reduced activity in bilateral anterior cingulate (ROI)
increased activity in bilateral striatum (caudate) (ROI) |
21. Passamonti et al. 2010
a
| 75 (100 % male) | N/A | N/A | 52 (43 ODD/ CD-only) | N/A | 23 | 16–21 | ROI: ventromedial prefrontal cortex, amygdala, insula, orbitofrontal cortex Whole brain Correlational analyses | Implicit processing task: categorise gender of angry, sad and neutral faces | ODD/CD-mixed versus controls: Behavioural: No significant group differences
Angry > neutral pictures: reduced activity in bilateral amygdala (ROI), left insula (ROI),right ventromedial prefrontal cortex (ROI), bilateral dorsolateral prefrontal cortex, bilateral dorsomedial prefrontal cortex, bilateral orbitofrontal cortex (ROI), right inferior parietal cortex, bilateral inferior temporal gyrus, left fusiform gyrus, right middle temporal gyrus, right superior temporal sulcus/gyrus, bilateral thalamus, left putamen, left cerebellum
Sad > neutral pictures: reduced activity in bilateral amygdala (ROI), ventromedial prefrontal cortex (ROI), left dorsolateral prefrontal cortex, putamen, right cerebellum, bilateral superior temporal sulcus/gyrus ODD/CD-mixed versus controls: Negative correlation between right amygdala and CD symptoms (ROI), negative correlation between ventromedial prefrontal cortex and CD symptoms (ROI), negative correlation between left insula and CD symptoms (ROI) |
22. Finger et al. 2011
a
| 30f
(60 % male) | N/A | N/A | 15 (5 ODD/ CD-only) | N/A | 15 | Patients: 14,1 (1,8) Controls: 13,2 (1,1) | ROI: amygdala, orbitofrontal cortex, striatum Whole brain | Passive avoiding learning task - Rewarded correct hits - Punished commission errors | ODD/CD-mixed versus controls: Behavioural: ODD/CD-mixed made more commission errors than controls during the late learning phase (all seven blocks after the first block).
Overall response type (reward and punishment): reduced activity in right amygdala (ROI), bilateral superior frontal gyrus, left insula, right medial frontal gyrus, left middle frontal gyrus, left superior parietal lobule, left superior temporal gyrus, left lingual gyrus, right fusiform gyrus, left caudate (ROI), right thalamus
Rewarded correct hits > punished commission errors: reduced activity in right orbitofrontal cortex (ROI), left middle frontal gyrus, parahippocampal gyrus |
23. White et al. 2013
a
| 38c,d,f,g (Patients: 82 % male Controls: 56 % male) | N/A | N/A | 20 (16 ODD/ CD-only) | N/A | 18 | Patients: 15,2 (2,0) Controls: 14,9 (2,2) | ROI: amygdala, ventromedial prefrontal cortex, caudate Whole brain | Passive avoiding learning task - Reward - Punishment | ODD/CD-mixed versus controls: Behavioural: a smaller proportion of the ODD/CD-mixed group than of the controls showed an association between expected value and choice behaviour
Receiving rewarding feedback modulated by prediction error: reduced activity in left caudate (ROI)
Receiving punishing feedback modulated by prediction error: increased activity in left caudate (ROI) |
24. White et al. 2014
a
| 30d,f (Patients: 73 % male Controls: 66 % male) | N/A | N/A | 15 (8 ODD/ CD-only) | N/A | 15 | 10–17 | Whole brain | Reinforcement learning task - Reward (appetitive image) - Punishment (aversive image) | ODD/CD-mixed versus controls: Behavioural: ODD/CD-mixed were less likely to avoid physical threat, but not contamination threat, stimuli than controls
Receiving rewarding feedback modulated by prediction error: reduced activity in right inferior parietal cortex
Receiving punishing feedback modulated by prediction error: increased activity in right inferior parietal cortex |
25. Cohn et al. 2014
a
| 68 (79 % male) | N/A | N/A | 45 (18 ODD/ CD-only) | N/A | 23 | 17,7 (1,6) | ROI: amygdala, ventral striatum, medial prefrontal cortex Whole brain Correlational analyses | Monetary incentive delay task - Reward - Neutral - Loss | ODD/CD-mixed versus controls: Behavioural: No significant group differences
Reward hit > reward miss (reward-feedback): reduced activity in right ventral striatum (ROI)
Loss miss > hit (loss-feedback):
increased activity in right amygdala (ROI) ODD/CD-mixed versus controls: Negative correlation between left amygdala and CU traits (ROI) No correlation between psychopathic traits and neural responses |
Study | Total sample (% male/ female) | Number of subjects (specified per group) | Age (years, range or M (SD)) | Analysis method | Task and conditions | Results of comparisons between ODD/CD-only and control group, between ODD/CD+ADHD and control group, and between ODD/CD-mixed and control group. (brain regions reported show reduced volumes in the patient group, unless otherwise reported) | ||||
---|---|---|---|---|---|---|---|---|---|---|
ODD/CD- only | ODD/CD+ADHD | ODD/CD -mixed | ADHD-only | Controls | ||||||
26. Rubia et al. 2008
| 48–53 (100 % male) | 13–14 | N/A | N/A | 14–20 | 16–20 | 9–17 | Whole brain | Stop Task - Failed stop - Successful stop - Go | ODD/CD-only versus controls: Behavioural: No significant group differences
Failed stops > go trials: reduced activity in right posterior cingulate gyrus, right precuneus, left parietal cortex
Go > successful stop trials: reduced activity in anterior cingulate gyrus, insula, caudate, putamen, thalamus, left superior temporal cortex, premotor cortex |
27. Rubia et al. 2009a
| Simon Task - Successful congruent - Successful incongruent - Successful oddball | Behavioural:, ODD/CD made more errors compared to controls, no differences between the ADHD-only group and controls
Successful incongruent > successful oddball trials (interference inhibition): reduced activity in right middle and superior temporal lobe, right precuneus | ||||||||
13. Rubia et al. 2009b
a
| Continuous Performance - Non-reward - Non-target | Behavioural: No significant group differences
Non-reward > non-target trials (sustained attention): reduced activity in right insula, right hippocampus, right anterior cingulate cortex, cerebellum, right thalamus, left occipital gyrus, left posterior cingulate, left precuneus | ||||||||
28. Rubia et al. 2010
| Correlational analyses (2 out of 4 studies) | Switching Task - Switch - Repeat | Behavioural: No significant group differences, but overall performance was poorer during the switch trials than repeat trials
Group differences for overall task performance: reduced activity in right inferior parietal lobe, right precentral gyrus, left-superior temporal/inferior parietal cortex, left precuneus, cuneus ODD/CD-only versus controls: Negative correlation between dorsolateral prefrontal cortex and conduct problems (1 study) | |||||||
29. Zhu et al. 2014
| 21b
(100 % male) | 11 | N/A | N/A | N/A | 10 | 10–12 | Whole brain | GoStop Task - Complete task | ODD/CD-only versus controls: Behavioural: ODD/CD-only showed higher error rate during response inhibition and a longer stop latency
Group differences for overall task performance: reduced activity in right inferior frontal gyrus, increased activity in dorsolateral parts of bilateral inferior frontal frontal gyrus, left middle frontal gyrus, right superior frontal gyrus |
Integration of Quantitative and Qualitative Review Findings
ALE Meta-Analysis | Abnormalities reported for the studies including samples of ODD/CD-only versus Controls | Abnormalities reported for the studies including samples of ODD/CD-mixed and ODD/CD+ADHD versus Controls | Conclusion ODD/CD versus controls | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Structural | Functional | Structural | Functional | Structural + unctional | Significant associations b
| Structural | Functional | Structural + functional | Significant associations e
| ||||
Hot | Cool a
| Hot | Cool a
| ||||||||||
(n = 8) | (n = 9) | (n = 3, all WBA) | (n = 3, all WBA) | (n = 5, all WBA) | (n = 11, all WBA) | (n = 5) | (n = 9, all WBA) c,d
| (n varies 7 WBA; 3 ROI) d
| (n = 0, all WBA) | (n varies) d
| (n varies) d
| ||
Total grey matter | NA | NA | 13
| NA | NA | 1 | NA | 3 / 43,5,8
| NA | NA | 3 / 4 | NA | Some evidence f
|
Amygdala | Left | Bilateral | 22,3
| 115
|
ns
| 3 | 23,15
| 36,8,9
| 6 / 916,17,19,21,22,25
| NA | 9 / 18 | 5 / 86,7,8,19,25
| Strong evidence |
Striatumg
|
ns
| Bilateral | 12
| 115
| 213,26
| 4 |
ns
| 31,7,10
| 6 / 818,20,21,22,23,25
| NA | 9 / 17 | 1 / 510
| Strong evidence |
Insula | Bilateral |
ns
| 21,2
| 115
| 213,26
| 5 | 12
| 26,10
| 2 / 621,22
| NA | 4 / 15 | 3 / 66,10,21
| Some evidence |
Frontal gyrus | Left |
ns
| 21,3
| 115
| 129
| 4 | 11
| 27,10
| 2 / 718,22
| NA | 4 / 16 |
ns / 5
| Some evidence |
Fusiform gyrus |
ns
| Left | 22,3
|
ns
|
ns
| 2 |
ns
|
ns
| 2 / 721,22
| NA | 2 / 16 |
ns / 5
| Weak evidence |
Temporal cortex |
ns
|
ns
| 11
|
ns
| 226,27
| 3 | 21,3
| 45,8,9,10
| 2 / 721,22
| NA | 6 / 16 | 1 / 512
| Weak evidence |
(Pre)cuneus |
ns
|
ns
| 11
|
ns
| 413,26,27,28
| 5 | 11
| 27,10
| 1 / 718
| NA | 3 / 16 |
ns / 5
| Weak evidence |
Parietal cortex |
ns
|
ns
| 11
|
ns
| 226,28
| 3 |
ns
| 1 7
| 3 / 721,22,24
| NA | 4 / 16 |
ns / 5
| Weak evidence |
Anterior cingulate |
ns
|
ns
|
ns
|
ns
| 213,26
| 2 | 115
| 21,3
| 3 / 615,16,20
| NA | 5 / 16 | 1 / 716
| Weak evidence |
Orbitofrontal cortex |
ns
|
ns
| 11
| 113
|
ns
| 2 |
ns
| 28,10
| 2 / 821,22
| NA | 4 / 17 |
ns / 7
| No evidence |
Prefrontal cortex |
ns
|
ns
| 21,2
|
ns
|
ns
| 2 | 128
| 110
| 2 / 718,21
| NA | 3 / 16 | 2 / 619,21
| No evidence |
Cerebellum |
ns
|
ns
|
ns
|
ns
| 113
| 1 |
ns
| 34,7,8
| 1 / 721
| NA | 4 / 16 |
ns / 5
| No evidence |
Occipital cortex |
ns
|
ns
| 12
|
ns
| 113
| 2 |
ns
| 37,8,10
|
ns / 7
| NA | 3 / 16 |
ns / 5
| No evidence |
Cingulate |
ns
|
ns
| 21,3
|
ns
| 213,26
| 4 |
ns
| 115
|
ns / 7
| NA | 1 / 16 |
ns / 5
| No evidence |
Hippocampus |
ns
|
ns
|
ns
|
ns
| 113
| 1 |
ns
| 18
| 1 / 822
| NA | 2 / 17 |
ns / 5
| No evidence |
Pre-central gyrus |
ns
|
ns
|
ns
|
ns
| 128
| 1 |
ns
| 110
|
ns / 7
| NA | 1 / 16 |
ns / 5
| No evidence |
Thalamus |
ns
|
ns
|
ns
|
ns
| 213,26
| 2 |
ns
|
ns
| 1 / 721
| NA | 1 / 16 |
ns / 5
| No evidence |
Lingual gyrus |
ns
|
ns
|
ns
|
ns
|
ns
|
ns
|
ns
|
ns
| 1 / 722
| NA | 1 / 16 |
ns / 5
| No evidence |
Uncus |
ns
|
ns
| 11
|
ns
|
ns
| 1 |
ns
|
ns
|
ns / 7
| NA | 1 / 16 |
ns / 5
| No evidence |
Premotor cortex |
ns
|
ns
|
ns
|
ns
| 113
| 1 |
ns
|
ns
|
ns / 7
| NA | 1 / 16 |
ns / 5
| No evidence |