important monoamine that influences, among other functions, the
prefrontal brain and behavior). If the infant animals with the short
gene structure are separated from their mothers when they are young
(thereby lacking touch and other stimuli), they can develop poorly
with abnormal LHPA pathways and poor serotonin function in re-
spect to the prefrontal cortex and are at risk of abnormal brain func-
tion (depression and alcohol addiction). The animals homozygous
for the long gene structure for the serotonin transporter gene are re-
sistant to adverse experience in early infant development (these are
resilient animals).
Recent studies of the 1970 Dunedin birth cohort have shown that
children who were raised in an adverse abusive environment with
one or two copies of the short allele of the serotonin gene promoter
polymorphism were at risk for depression in adult life. Those with
the short gene structure brought up in a good early child develop-
ment environment were not at risk. The children in adverse environ-
ments who were most at risk were those with the two short alleles.
Children who were homozygous for the long allele serotonin trans-
porter gene structure were resistant to the adverse effects of poor
early child development (these were resilient children).
Normally, gene abnormalities are thought to be caused by genes
producing a defective protein. However, since the DNA of both the
short and long genes is normal in terms of mRNA coding for the
transporter protein, some other mechanism related to gene activa-
tion or inhibition (epigenetics) is involved. This is an example of how
the social environment can “get under the skin” through the sensing
pathways and influence biological pathways that can influence gene
expression leading to behavior and mental health problems.
Another gene–environment interaction which is relevant for com-
plex psychiatric and behavior disorders is the gene for monoamine
oxidase A (MAOA). This enzyme oxidases the monoamine neuro-
transmitters serotonin, dopamine, and norepinephrine. Humans with
low MAOA activity tend to be associated with impulsive behavior and
conduct disorders. The MAOA gene, like the serotonin transporter
gene, has a functional length polymorphism in the transcriptional
control region for the gene.
56 J. Fraser Mustard