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A fundamental tenet of psychoanalytic theory and technique is that experiences in early life (internal and external) strongly affect all aspects of mental life, but supporting this hypothesis with other than clinical data has proved elusive. However, recent technological advancements in molecular
genetics have allowed investigators to undertake innovative studies of how genes interact with environmental characteristics to produce an observed phenotype (i.e., gene-environment [g x e] interactions).
Perhaps the most influential study demonstrating a gene-environment interaction was by . This study found that genetic variations in the promoter region of the serotonin transporter gene (5-HTTLPR) play a role in predisposition to major depression. The authors postulated that the short allele (s) of this gene confers deficient serotonergic response to stressful life events, whereas the long allele (1) is associated with an effective serotonergic response. Women were classified as s/s, s/l, l/s, or l/l and were asked to report on childhood abuse. Women with the s/s genotype had high rates of depression if they had suffered significant childhood trauma. Those without such childhood stressors did not show a high rate of depression, even if they had the s/s genotype. Conversely, patients with the l/l genotype (good serotonin response) did not become depressed at a higher rate, irrespective of the presence or absence of childhood trauma. Thus, the genotype interacts with the environment to either predispose individuals to depression in adult life or to protect them from it. This study was considered groundbreaking, and the expectation was that more g x e interactions would be demonstrated for schizophrenia, bipolar disorder, and even personality disorders.
However, a critical test of the validity of any resarch finding is whether it is replicated. In the case of the Caspi et al. study, only four of thirteen subsequent studies replicated the authors' findings. While a metaanalys