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. 2017 Oct;27(5):178-186.
doi: 10.1097/YPG.0000000000000178.

Genetic moderation of cocaine subjective effects by variation in the TPH1, TPH2, and SLC6A4 serotonin genes

Michelle A Patriquin  1 , Sara C Hamon, Mark J Harding, Ellen M Nielsen, Thomas F Newton, Richard De La Garza 2nd, David A Nielsen
Affiliations

Genetic moderation of cocaine subjective effects by variation in the TPH1, TPH2, and SLC6A4 serotonin genes

Michelle A Patriquin et al. Psychiatr Genet. 2017 Oct.

Abstract

Objective: This study investigated variants of tryptophan hydroxylase (TPH)1, TPH2, and SLC6A4 in the moderation of the subjective effects of cocaine.

Methods: Non-treatment-seeking cocaine-dependent individuals (N=66) were intravenously administered saline and cocaine (40 mg) in a randomized order. Participants self-reported subjective effects of cocaine using a visual analog scale starting before administration of saline or cocaine (-15 min) to up to 20 min after infusion. Self-report ratings on the visual analog scale ranged from 0 (no effect) to 100 (greatest effect). Participants were genotyped for the TPH1 rs1799913, TPH2 rs4290270, and SLC6A4 5-HTTLPR variants. Repeated-measures analysis of covariance was used to examine changes in subjective effect scores over time while controlling for population structure.

Results: Participants carrying the TPH1 rs1799913 A allele reported greater subjective response to cocaine for 'stimulated' and 'access' relative to the CC genotype group. Those carrying the TPH2 rs4290270 A allele reported higher 'good effect' and lower 'depressed' effect relative to the TT genotype group. Those carrying the SLC6A4 5-HTTLPR S' allele reported greater 'desire' and 'access' compared with the L'L' genotype group.

Conclusion: These findings indicate that TPH1, TPH2, and SLC6A4 variants moderate the subjective effects of cocaine in non-treatment-seeking cocaine-dependent participants.

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Figures

Figure 1
Figure 1
Flow chart of challenge applied (squares) and timing of subjective effect ratings (circles).
Figure 2
Figure 2
Subjective effect scores by TPH1 genotype. (A) Change over time (in minutes) of participant-reported subjective effect of “stimulated” by AA/AC genotypes (n = 21) vs. CC genotype (n = 45) groups. (B) Change over time (in minutes) of participant-reported subjective effect of “access” by AA/AC genotypes vs. CC genotype groups (TPH1 rs1799913 minor T allele). Data reflect mean +/− S.E.M.
Figure 3
Figure 3
Subjective effect scores by TPH2 genotype. (A) Change over time (in minutes) of participant-reported subjective effect of “good effect” by TT genotype (n = 15) versus AA/AT genotype (n = 51) groups. (B) Change over time (in minutes) of participant-reported subjective effect of “depressed” by TT genotype versus AA plus AT genotype groups (TPH2 rs4290270 minor A allele). Data reflect mean +/− S.E.M.
Figure 4
Figure 4
Subjective effect scores by SLC6A4 genotype. (A) Change over time (in minutes) of participant-reported subjective effect of “desire” by the L′S′/S′S′ (n = 43) and the L′L′ genotype (n = 23) groups. (B) Change over time (in minutes) of participant-reported subjective effect of “access” by the L′S′/S′S′ and the L′L′ genotype groups (5-HTTLPR minor S′ allele). Data reflect mean +/− S.E.M.
Figure 5
Figure 5
Subjective effect scores by genotype pattern. (A) Change over time (in minutes) of participant-reported subjective effect of “access” by the AA/AC (TPH1 rs1799913 minor T allele), AA/AT, and L′S′/S′S′ group (n = 14) and other participants (n = 52). (B) Change over time (in minutes) of participant-reported subjective effect of “heart rate” by the AA/AC, AA/AT, and L′S′/S′S′ group and “other” participants. Data reflect mean +/− S.E.M.
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