Epigenetic Mediation of AKT1 rs1130233’s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing
Abstract
:1. Introduction
2. Methods
2.1. Participants
2.2. Experimental Design
2.3. Image Acquisition
2.4. fMRI Task
2.5. Genotyping and Methylation Assay
2.6. Image Analysis
3. Results
3.1. Participants
3.2. Symptomatic and Behavioural Response to THC
3.3. Regional Brain Response to THC during Fear Processing
3.4. Relationship between AKT1 Genotype (rs1130233) and the Effect of THC on Regional Brain Activation during Fear Processing
3.5. Relationship between Methylation at CpG11–12 Site around AKT1 SNP (rs1130233) and the Effect of THC on Regional Brain Activation during Fear Processing
3.6. Relationship between Methylation at CpG11–12 Site around AKT1 SNP (rs1130233) and the Number of A Alleles at AKT1 SNP (rs1130233)
3.7. Relationship between AKT1 Genotype (rs1130233) and the Effect of THC on Regional Brain Activation during Fear Processing after Covarying for Methylation at CpG11–12 Site
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Ethical Standards
References
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Lifetime Psychoactive Substance Use | |
---|---|
Caffeine | 33 subjects; Mean number of cups of coffee, tea or caffeinated drinks/day-2.42 (SD–1.86) (range 0–11) |
Nicotine | 9 subjects; Mean number of cigarettes smoked/day-1.19 (SD–3.18) (range 0–15/day); 2 subjects smoked >10 cigarettes/day lifetime; only 1 subject smoked at that level at the time of the study. |
Cannabis | <5 times used = 12 subjects; 5–25 times used = 24 subjects |
Cocaine | A few times of reported use = 3 subjects |
Amphetamines | A few times of reported use = 5 subjects Used small quantities from time to time = 1 subject |
LSD/Psilocybin | A few times of reported use = 10 subjects |
Opiates | A few times of reported use = 2 subjects |
MDMA | A few times of reported use = 11 subjects |
Genotype | Age (Mean ± SD) | p | NART IQ (Mean ± SD) | p | Number of Years of Education (Mean ± SD) | p |
---|---|---|---|---|---|---|
AKT1(G/G) (n = 19) | 26.5 ± 5.8 | NS | 98.8 ± 6.9 | NS | 17.5 ± 3.2 | NS |
AKT1(G/A) (n = 9) | 26.3 ± 4.7 | 97.9 ± 5.3 | 16.6 ± 3.3 | |||
AKT1(A/A) (n = 7) | 23.8 ± 6.6 | 95.5 ± 8.0 | 17.0 ± 7.4 |
Cerebral Region | x | y | z | Size (No. of Voxels) | Side | p-Value |
---|---|---|---|---|---|---|
Inferior Frontal Gyrus | −43 | 26 | 4 | 14 | L | 0.006583 |
−40 | 26 | −2 | 22 | L | ||
−32 | 22 | −13 | 15 | L | ||
−36 | 19 | −7 | 17 | L | ||
Anterior Cingulate Gyrus | −4 | 22 | 37 | 10 | L | 0.002992 |
−11 | 30 | 20 | 15 | L | ||
Fusiform Gyrus | −22 | −67 | −7 | 8 | L | 0.002992 |
Cuneus | −11 | −74 | 15 | 10 | L | 0.002992 |
Middle Occipital Gyrus | −29 | −63 | 4 | 5 | L | 0.002992 |
−25 | −81 | 9 | 25 | L | ||
−18 | −85 | 15 | 8 | L | ||
Culmen | −18 | −44 | −7 | 5 | L | 0.001496 |
−22 | −44 | −18 | 7 | L | 0.008378 | |
Middle Temporal Gyrus | −51 | −33 | −13 | 63 | L | 0.001496 |
−51 | −11 | −13 | 7 | L | ||
Brainstem, Midbrain | 0 | −15 | −18 | 5 | R | 0.001496 |
Parahippocampal gyrus | −40 | −30 | −7 | 30 | L | 0.001496 |
−25 | −26 | −18 | 12 | L | ||
Cingulate Gyrus | −7 | 19 | 42 | 5 | L | 0.002992 |
−11 | 26 | 26 | 14 | L | ||
−11 | 26 | 31 | 10 | L | ||
Anterior Cingulate | 0 | 30 | 15 | 20 | R | 0.002992 |
−7 | 33 | 9 | 13 | L | ||
0 | 37 | 4 | 7 | R |
Cerebral Region | x | y | z | Size (No. of Voxels) | Side | p-Value |
---|---|---|---|---|---|---|
Superior Frontal Gyrus | 36 | 52 | 15 | 27 | R | 0.003249 |
Medial Frontal Gyrus | 40 | 48 | 9 | 11 | R | 0.003249 |
43 | 37 | 20 | 9 | R | ||
43 | 7 | 42 | 20 | R | 0.002067 | |
40 | 11 | 37 | 26 | R | ||
40 | 7 | 48 | 15 | R | ||
0 | −4 | 53 | 9 | R | 0.005907 | |
Inferior Frontal Gyrus | 51 | 26 | 20 | 12 | R | 0.003249 |
43 | 4 | 31 | 17 | R | 0.002067 | |
Sub-Gyral | 40 | 15 | 15 | 12 | R | 0.003249 |
11 | 30 | −2 | 8 | R | 0.002658 | |
−43 | −33 | −7 | 18 | L | ||
−47 | −15 | −13 | 5 | L | ||
−25 | 7 | 42 | 26 | L | 0.005907 | |
−29 | 7 | 37 | 10 | L | ||
−32 | −4 | 37 | 6 | L | ||
25 | −4 | 53 | 23 | R | 0.007383 | |
−29 | −70 | 26 | 5 | L | 0.009155 | |
Middle Occipital Gyrus | −25 | −78 | 15 | 9 | L | 0.009155 |
−25 | −74 | 9 | 8 | L | ||
Middle Temporal Gyrus | −29 | −70 | 20 | 11 | L | 0.009155 |
Precentral Gyrus | 29 | −15 | 48 | 21 | R | 0.007383 |
Precuneus. | −36 | −70 | 37 | 5 | L | 0.009155 |
Angular Gyrus | −36 | −74 | 31 | 6 | L | 0.009155 |
Fusiform Gyrus. | −32 | −37 | −18 | 18 | L | 0.002658 |
Midbrain | −4 | −26 | −13 | 47 | L | 0.002658 |
Left Brainstem, Midbrain | −4 | −22 | −18 | 6 | L | 0.002658 |
Insula | 40 | 15 | 9 | 13 | R | 0.003249 |
Extra-Nuclear Corpus Callosum | 4 | 15 | 20 | 12 | R | 0.002658 |
−4 | 26 | −2 | 8 | L | ||
Amygdala/Parahippocampal gyrus | 22 | −7 | −18 | 36 | R | 0.003249 |
Parahippocampal Gyrus | 29 | −22 | −13 | 23 | R | 0.003249 |
Anterior Cingulate | 0 | 37 | 4 | 9 | R | 0.002658 |
4 | 33 | 9 | 6 | R | ||
0 | 30 | 15 | 19 | R |
Cerebral Region | x | y | z | Size (No. of Voxels) | Side | p-Value |
---|---|---|---|---|---|---|
Middle Frontal Gyrus | 40 | 52 | 4 | 3 | R | 0.005075 |
36 | 48 | 9 | 7 | R | ||
36 | 48 | 15 | 21 | R | ||
−36 | 44 | 9 | 17 | L | ||
−40 | 41 | 15 | 13 | L | ||
40 | 37 | 20 | 8 | R | ||
Medial Frontal Gyrus | 0 | 33 | 42 | 9 | R | 0.005075 |
0 | 30 | 37 | 15 | R | ||
Inferior Frontal Gyrus | 40 | 26 | 4 | 7 | R | 0.005075 |
40 | 26 | −7 | 5 | R | ||
−47 | 19 | 4 | 13 | L | ||
Middle Temporal Gyrus | −51 | −11 | −13 | 7 | L | 0.007761 |
−51 | −33 | −13 | 63 | L | ||
Sub-Gyral | −32 | 44 | 4 | 12 | L | 0.005075 |
−40 | −30 | −7 | 28 | L | 0.007761 | |
−36 | −37 | −2 | 4 | L | ||
Middle Occipital Gyrus | −22 | −85 | 15 | 9 | L | 0.007761 |
−29 | −63 | 4 | 5 | L | ||
Culmen. | −18 | −44 | −7 | 4 | L | 0.007761 |
Cuneus | −11 | −74 | 15 | 10 | L | 0.007761 |
−18 | −85 | 20 | 3 | L | ||
Extra-Nuclear | −32 | 22 | −2 | 25 | L | 0.005075 |
32 | 22 | −2 | 7 | R | ||
−32 | 15 | −7 | 25 | L | ||
Left Brainstem, Midbrain | 0 | −15 | −18 | 4 | R | 0.007761 |
Parahippocampal Gyrus | −25 | −26 | −18 | 18 | L | 0.007761 |
Posterior Cingulate | −22 | −67 | 9 | 27 | L | 0.007761 |
Cingulate Gyrus | −7 | 19 | 42 | 7 | L | 0.005075 |
−11 | 26 | 26 | 15 | L | ||
−11 | 26 | 31 | 14 | L | ||
Anterior Cingulate | −11 | 26 | 20 | 17 | L | 0.005075 |
0 | 30 | 15 | 22 | R | ||
−4 | 33 | 9 | 12 | L | ||
0 | 37 | 4 | 7 | R |
Tal(x) | Tal(y) | Tal(z) | Cerebral Region |
---|---|---|---|
−22 | −50 | 0 | Parahippocampal Gyrus/Lingual Gyrus |
−33 | −45 | −10 | Fusiform |
−11 | −27 | −10 | Midbrain −> parahippocampal gyrus |
−34 | −26 | −7 | Hippocampus −> Insula |
−48 | −1 | −7 | Superior Temporal gyrus |
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Blest-Hopley, G.; Colizzi, M.; Prata, D.; Giampietro, V.; Brammer, M.; McGuire, P.; Bhattacharyya, S. Epigenetic Mediation of AKT1 rs1130233’s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing. Brain Sci. 2021, 11, 1240. https://doi.org/10.3390/brainsci11091240
Blest-Hopley G, Colizzi M, Prata D, Giampietro V, Brammer M, McGuire P, Bhattacharyya S. Epigenetic Mediation of AKT1 rs1130233’s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing. Brain Sciences. 2021; 11(9):1240. https://doi.org/10.3390/brainsci11091240
Chicago/Turabian StyleBlest-Hopley, Grace, Marco Colizzi, Diana Prata, Vincent Giampietro, Michael Brammer, Philip McGuire, and Sagnik Bhattacharyya. 2021. "Epigenetic Mediation of AKT1 rs1130233’s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing" Brain Sciences 11, no. 9: 1240. https://doi.org/10.3390/brainsci11091240
APA StyleBlest-Hopley, G., Colizzi, M., Prata, D., Giampietro, V., Brammer, M., McGuire, P., & Bhattacharyya, S. (2021). Epigenetic Mediation of AKT1 rs1130233’s Effect on Delta-9-Tetrahydrocannabinol-Induced Medial Temporal Function during Fear Processing. Brain Sciences, 11(9), 1240. https://doi.org/10.3390/brainsci11091240