Jackson, Jenna

Mother-­Infant Rhesus Macaques, Serotonin and the Serotonin Transporter Gene

Faculty Mentor: Dr. James Dee Higley, Psychology

Introduction

The primary purpose of this project is to assess how a mother’s genotype sets the
environment for the infants’ genotype to react in a gene by environment interaction,
which affects the infants’ serotonin functioning. In order to effectively study a gene by
environment interaction, extensive control over the environment is needed, and rhesus
macaque monkeys were used as subjects.

The serotonin transporter genotype (5-­ HTTLPR) has two variations: the long (L) and
short (s) allele. This particular genotype is associated with serotonin metabolite (5-­
HIAA) levels (Bennett et al., 2002). The serotonin metabolite 5-­HIAA is a by-­product of
serotonin functioning, and measuring 5-­HIAA is a way of measuring serotonin use in the
brain. Subjects with the s allele are known to have lower levels of 5-­HIAA, which in turn
can impact their behavior (Spinelli et al., 2007). However, this is dependent on a gene
by environment interaction. In detrimental environments, this genotype is expressed as
a phenotype, whereas in better environments the genotype has limited effect (Bennett
et al., 2002).

Moreover, this genotype is known to affect how the mother responds to the infant. The
mothers’ genotype affects her behavior, and in turn this creates an environment for the
infant. This environment then impacts how the infants’ gene is exhibited (Zhang, Chen,
Deng, & Lu, 2014). No studies have yet examined how this interaction impacts levels of
5-­HIAA in the infant (Zhang, Chen, Deng, & Lu, 2014). By comparing the infants’ 5-­
HIAA levels by infants’ and mothers’ genotype, we may assess how the gene is
expressed. This will give us greater understanding of the GXE between 5-­ HTTLPR and
mothers’ behavior.

In our study, we looked at infants’ environment in two ways: first, as mother’s genotype
which impacts her behavior and sets and environment for the infant, and second, early
rearing condition of the infant. Infants reared by peers instead of mothers is a stressful
experience, and can impact the infant’s serotonin functioning (Bennett et al, 2002).

Methods

Infants at 6 months of age were separated from their mothers for 4 days, with 3 day
reunions, 4 different times. CSF samples were collected during this separation from the
infants, from which 5-­HIAA metabolite levels were obtained. DNA was isolated from
blood samples using gel electrophoresis, and the alleles were identified through
ethidium bromide staining. This data was gathered in a database through the National
Institute of Health. I analysed the data in Dr. Higley’s research lab at BYU.

There were 221 mother-­infant pairs studied. Some of the infants (n=143) were reared by
their mothers, and 78 were reared by other peers. The dependent variable was infant
serotonin metabolite (5-­HIAA) levels. The independent variables were the mother and
infant serotonin transporter genotype, early rearing of the infant, and sex of the infant.

Results

Results indicated that there was a significant difference in 5-­HIAA levels by mother and
infant genotype (p= 0.005). Infants with the lowest levels of 5-­HIAA had the Ls
genotype, and their mothers had the LL genotype. As predicted, the group with infants
and mothers both with the LL genotype had infants with the highest level of 5-­HIAA.

Rearing was significant across time in a repeated measures ANOVA (p=0.004). Mother-­
reared monkeys had a greater increase post-­separation in 5-­HIAA, indicating a type of
recovery from the stress of separation, whereas peer-­reared monkeys 5-­HIAA remained
low across time. Furthermore, females had higher levels of CSF 5-­HIAA (p=0.057), but
only among the mother-­reared monkeys.

Discussion

Even though we hypothesized that the lowest functioning group would be when both the
infant and the mother had heterozygous alleles, the mismatch group when the infant
had a deleterious allele and the mother had homozygous LL alleles was the group with
the lowest 5-­HIAA metabolite levels. Thomas and Chess (1978) suggest that when
mothers and infants have mismatching temperaments it has a negative impact on the
infant, which is congruent with our findings. Mother and infant genotype does impact the
infants’ serotonin metabolite levels.

Rearing also impacted infant 5-­HIAA metabolite levels. Mother-­reared infants showed a
higher degree of recovery in comparison to the peer-­reared monkeys. This suggests
that the stress of early rearing condition does impact serotonin functioning in infant
rhesus macaques.

Conclusion

In conclusion, mothers genotype does set an environment for her infant. The infant’s
genotype then interacts with this environment to modulate the infants’ 5-­HIAA
metabolite levels. This this project was presented at the American Society of
Primatology Conference in August and is currently being written up for publication.

In addition to this study, this ORCA grant enabled me to mentor other students in
statistics. Since the monkeys used in this study, we need to control for this kinship using
a pedigree analysis. This gave me an opportunity to learn and run a new software,
SOLAR, that was designed to compute these analyses. I was able to train another
student how to use the program, and we are finalizing these analyses for other projects
in the lab.

References

Bennett, A. J., Lesch, K. P., Heils, A., Long, J. C., Lorenz, J.G., Shoaf, S. E., & …Higley, J.D. (2002).
Early experience and serotonin transporter gene variation interact to influence primate CNS
function. Molecular Psychiatry, 7,118–122.
Chess, S., & Thomas, A. (1978). Temperamental individuality from childhood to adolescence. Annual
Progress in Child Psychiatry & Child Development, 223-­224.
Spinelli, S., Schwandt, M.L., Newman, T.K., Heilig, M., Suomi, S.J., &… Bar, C.S. (2007). Association
between the recombinant human serotonin transporter linked promoter region polymorphism and
behavior in rhesus macaques during a separation paradigm. Development and Psychopathology,
19(4), 977-­987
Zhang, M., Chen, X., Deng, H., & Lu, Z. (2014). Identifying the interaction of maternal sensitivity and two
serotonin-­related gene polymorphisms on infant self-­regulation. Infant Behavior and
Development, (37), 606-­614