Polymorphisms of the HTR1a allele are linked to frontal brain electrical asymmetry

Abstract

Polymorphic variations in genes related to serotonin synthesis, transport, recognition, or degradation may convey subtle changes in serotonin system architecture that may place an individual at risk for psychopathology when faced with life stressors. The relationship between three key serotonin alleles and frontal brain electrical asymmetry, a putative endophenotype of depression, was examined. Risk alleles were hypothesized to predict relatively greater right frontal brain activity regardless of current clinical state. A sample of 313 college-age individuals, spanning a range of depressive severity from no symptomotology to clinically meaningful levels, participated. Resting encephalographic (EEG) activity was recorded from 64 scalp sites on four occasions separated by at least 24h (two 8-min recording sessions occurring at each occasion). Alpha power asymmetry scores between homologous sites were calculated for each session and then averaged to form a trait metric of asymmetry for each pair. PCR based genotyping was conducted for the HTR1a, HTR2a, and HTTLPR genes. Variations in the HTR1a gene were related to trait EEG asymmetry, regardless of any history of depression. Compared to subjects with at least one non-risk allele, subjects with homozygous HTR1A risk alleles had significantly greater relative right frontal activity at sites F7/F8, F5/F6, and F1/F2. In conclusion, variation in HTR1a can influence trait level brain activity, which may ultimately be indicative of risk for psychopathology.

Figure 1

Asymmetry scores by site by HTR1a risk genotype for the full sample of 305 individuals with complete genetic data.. Individuals with genotype (G/G) show significantly more relative right activity than individuals with genotype (C/C) or C/G) across regions F7/8, F5/6 and F1/2. Symbols indicate significantly greater relative right frontal activity for G/G compared to the C/C and C/G genotypes at a given region. (*=p<.05 comparing risk to low-risk genotypes for a give scalp region).

Figure 2

Asymmetry scores by site by MDD history (+/−) for all the full sample of 305 individuals with complete 5HTR1A data. Individuals with lifetime depressive history (+) show significantly more relative right activity than individuals without a history of depressive illness at regions F5/6, F3/4 and F1/2. Symbols indicate significantly greater relative right frontal activity for MDD (+) compared to MDD (−) at a given region. (*=p<.05, comparing MDD Hx (+) to MDD Hx (−) for a given scalp region).