Table 1.
Imaging-genetics studies using the intermediate phenotype approach to examine the neural effects of ASD-related risk genes.
| Study | Participants (F:M): mean ± SD | Gene | Imaging method | Gene variant studied: genotype group (n) | Key results |
|---|---|---|---|---|---|
| NEUREXIN SUPERFAMILY GENES | |||||
| Voineskos et al. (2011) | 53HCs (15F:38M): 39 ± 13.1 | Neurexin 1 | MRI: cortical/subcortical volume | rs1045881: C/C (33); C/T,T/T (20) | ↓Frontal WM volume associated with rs1045881C,rs858932G |
| rs858932: GG (6); G/C (33); C/C (14) | ↓Finger-tapping speed in rs1045881C | ||||
| Tan et al. (2010) | 314HCs | CNTNAP2 | MRI (VBM): GM/WM volume | rs779475: T/T; T/A, A/A | rs779475T/T: ↓ volume in cerebellum, fusiform gyrus, posterior occipital, frontal pole, cingulum, thalamic radiations, IFOF |
| DTI: voxel-wise FA analysis | Sex-specific associations with rs779475T/T: ↓FA in right IFOF in males, ↓FA in right thalamic radiation in females | ||||
| Scott-Van Zeeland et al. (2010) | Sample I – 16ASD; 16TD: 12 ± 2 | CNTNAP2 | fMRI: reward-processing task | rs2710102: | Sample I (fMRI)-rs2710102C: ↑mPFC activity on reward-processing, reduced left-lateralized mPFC network |
| Sample II – 39HC children: (16F:23M) | fcMRI | Sample I: C/C,T/C (9); T/T(23) Sample II: C/C,T/C (29); T/T (10) |
Sample II (fcMRI)- rs2710102C: ↓long-range (mPFC to occipital/temporal cortex) ↑short-range (mPFC to frontal cortex) connectivity | ||
| Whalley et al. (2011) | 66HCs (35F:31M):∼20 ± 2 | CNTNAP2 | fMRI: verbal fluency task | rs2710102:C/C(n = 16); C/T, T/T (n = 50) | On verbal fluency: |
| rs779745:T/T(n = 8); T/A, A/A (n = 57) | ↑Right IFG activity in rs2710102C/C ↑Right MTG activity in rs779475T/T |
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| OXYTOCIN AND ARGININE VASOPRESSIN RECEPTOR GENES | |||||
| Tost et al. (2010) | MRI: 212HCs: 29.9 ± 9 | OXTR | sMRI (VBM) | sMRI: rs53576: G/G (95); G/A (96); A/A (21) | ↓Hypothalamus volume in rs53576A |
| fMRI: 228HCs: 31.9 ± 9.9 | fMRI: face processing task (TPQ) | fMRI: rs53576: G/G (102); G/A (100); A/A (26) | ↑Amygdala volume in rs53576A males | ||
| ↓Reward dependence on TPQ in rs53576A (correlated with hypothalamus/amygdala volume) | |||||
| Face processing: ↓amygdala activity ↑amygdala–hypothalamus coupling in rs53576A | |||||
| Inoue et al. (2010) | 208 HCs (143M:65F): 33.9 ± 11.6 | OXTR | MRI: ROI volume: amygdala, hippocampus | rs2254298: A/A(77); A/G(85); G/G(44) | ↑Amygdala volume in rs2254298A |
| Furman et al. (2011) | 51 female HCs: 13 ± 1.5 | OXTR | MRI (VBM): GM/WM volume + ROI volume: amygdala | rs2254298: A/G (16); G/G (35) | ↑GM volume in rs2254298G/G |
| ↓Amygdala volume in rs2254298G/G | |||||
| Meyer-Lindenberg et al. (2011) | 258 HCs (149F:109M): 31.5 ± 9.6 | AVPR1A | fMRI: face processing task | (Select RS1, RS3 ASD-risk alleles): RS3 334bp (57); RS1 312 bp (39); RS1 320bp (54) | ↑Left amygdala activity in RS3 334bp ↑Left amygdala activity in RS1 312 bp versus 320bp ↓Left amygdala activity in RS1 320bp |
SD, standard deviation; HCs, healthy controls; F, females; M, males; CNTNAP2: contactin-associated-protein like 2; OXTR, oxytocin receptor gene; AVPR1A, arginine vasopressor receptor 1A gene; MRI, magnetic resonance imaging; sMRI, structural MRI; VBM, voxel-based morphometry; DTI, diffusion tensor imaging; FA, fractional anisotropy; fMRI, functional MRI; fcMRI, functional connectivity MRI; GM, grey matter; WM, white matter; TPQ, tridimensional personality questionnaire; ROI, region of interest; IFOF, inferior-fronto-occipital fasciculus; mPFC, medial prefrontal cortex; IFG, inferior frontal gyrus; MTG, medial temporal gyrus.