Central to the field of psychiatric genetics is the search for ‘vulnerability genes'.1
Particularly important in this search is uncovering the mechanisms whereby such genes influence disease risk, and determining whether they are directly associated with more general psychological and behavioral disturbance (that is, act through ‘main effects') or whether they are principally related to dysfunction only under specific environmental conditions or in response to particular developmental experiences (that is, act through ‘gene- × -environment (G × E) interaction'). Findings of studies linking candidate vulnerability genes (or ‘risk alleles') directly to specific psychopathological conditions have proven notoriously difficult to replicate.1
Failure to replicate direct effects of candidate vulnerability genes on specific psychopathological conditions suggests that genes may not influence behavior directly, leading many investigators to examine how genes may moderate effects of the environment on human G × E interaction. One well-studied G × E interaction involves monoamine oxidase-A (MAOA), contextual adversity and antisocial behavior. The interaction of a functional MAOA
gene polymorphism (MAOA-uVNTR) and childhood adversity, first detected by Caspi et al.2
in their research on child maltreatment, has now been replicated enough times that meta-analysis reveals it to be reliable3
—despite claims by some to the contrary.4
Thus, there is growing evidence that individuals possessing the low-MAOA-activity allele are predisposed to become antisocial when they experience a variety of adverse experiences, most notably maltreatment in childhood.
It is not just in the case of the MAOA gene that the notion of genetic vulnerability takes center stage in research on G × E interactions. Consider the evidence showing that the ‘s' allele of the 5-hydroxytryptamine-linked polymorphic region polymorphism (5-HTTLPR) is associated with increased depression in a high-stress context, with the ‘l' allele functioning protectively.5
Several studies have replicated this finding, providing further support for the conclusion that 5-HTTLPR increases vulnerability to depression in the context of environmental stress.6
The fundamental premise of this essay, however, is that viewing relations among genes, behavior and the environment from the perspective of the classic diathesis–stress model of psychopathology, as so much psychiatric genetic research on G × E interaction does, may distort these relations and thereby undermine, rather than advance, the understanding of how genes and environment collectively operate to shape behavior and development, including risk of mental illness. Central to the diathesis–stress model is the postulate that some individuals are at heightened risk—because of their genetic make up—of succumbing to psychological disturbance when they encounter adversity, whereas others, lacking the genetic vulnerability, are not so affected even when exposed to the very same adversity. Thus, whereas an individual with a particular genetic vulnerability will be prone to develop a genetically specific disorder if he or she experiences what could be some particular or any of a variety of environmental stressors (for example, child abuse, negative life events, death of parent), the same environmental exposure will not engender psychopathology in an individual possessing a different version of the candidate gene in question.7
An alternative to the diathesis–stress framework at the heart of genetic vulnerability thinking is the one which presupposes that it is not so much that individuals vary only in their susceptibility to adversity vis-à-vis psychopathology, but rather that these putatively ‘vulnerable' individuals are actually more susceptible and, thus, responsive to both positive and negative environmental conditions, that is, in a ‘for better and for worse' manner. This differential-susceptibility perspective does not just contend, as many have, that genes are neither inherently good or bad, or even that their developmental and behavioral effects depend on person–environment fit,8, 9
but rather—and distinctively—that individuals vary in their plasticity or susceptibility to environmental influences. Thus, the very genes that seem—in so much psychiatric genetic research—to make individuals disproportionately vulnerable to adversity vis-à-vis psychopathology may, simultaneously
, confer on them an advantage when it comes to benefiting from exposure to environmental support or enrichment (for example, nurturance), including just the absence of adversity. Were this the case, it would seem more appropriate to speak of ‘plasticity genes' rather than ‘vulnerability genes' and of highly plastic or malleable individuals rather than the so-called vulnerable ones. Boyce and Ellis,10
although not directly concerned with G × E effects, which is the focus of this paper, also have argued that individuals vary in their susceptibility to environmental influences, what they refer to as ‘biological sensitivity to context.' However, there is no presumption in their work that such malleability is a function of genotype, as they intriguingly entertain the prospect that experience can shape plasticity.
Ultimately, the purpose of this paper is not so much to challenge the view that diathesis–stress phenomena exist or that processes related to them operate. That seems indisputable. However, it is to contend—and illustrate empirically—that in many cases, wherein this may seem to be so, something different may be occurring, yet go virtually unnoticed as a result of expectations derived from the prevailing conceptual perspective, which guides both inquiry and interpretation of findings. Indeed, a central claim of this paper is that the disproportionate attention paid to the negative effects of contextual adversity, broadly defined and varied in its operationalization, on the problematic functioning and on disturbances in development and mental health, may actually lead scholars to mischaracterize environmental influences, as well as human development processes and phenomena. And this is because, as stipulated by the differential-susceptibility hypothesis,11, 12, 13, 14
‘the very same individuals who may be most adversely affected by many kinds of stressors, may simultaneously reap the most benefit from environmental support and enrichment (including the absence of adversity)'.
In the primary body of this paper, we provide extensive but still illustrative G × E evidence to this effect, most of it very recent and much of which has gone unnoticed, even at times by the investigators generating it. What follows should not be regarded as an exhaustive review of the literature; however, nor should it be seen to imply, much less demonstrate, that evidence of differential susceptibility outweighs evidence of diathesis–stress, either in the literature as a whole or even in each and every study cited for illustrative purposes. To make the case, as we exclusively seek to, that differential susceptibility seems operative in human development and functioning, but that individual differences in plasticity have been largely overlooked—in favor of prevailing views that some individuals are simply more vulnerable to adversity than others—it is our contention that an admittedly selective compilation of illustrative G × E findings is exactly what is appropriate at the present time. This would seem especially so in light of the fact that almost all the available human G × E research focuses on both a restricted range of environments, typically emphasizing the negative end of the spectrum and failing to measure at all the positive (except for the absence of adversity), and a restricted range of psychological and behavioral outcomes, also typically emphasizing the negative, thereby failing to assess competent functioning (except for the absence of dysfunction). As a result of these design characteristics of so many G × E investigations, it remains unknown whether extensive evidence consistent with a diathesis–stress model and seemingly inconsistent with a differential-susceptibility framework is an accurate reflection of G × E processes or an artefact of study designs. Quite conceivably, simply treating the absence of adversity as the ‘good' end of the environmental-exposure continuum and/or absence of a disorder as the ‘good' end of the psychological functioning continuum may lead to the under-detection of differential-susceptibility findings and an over representation of vulnerability ones. It is for these reasons that it is considered appropriate at the present time to provide illustrative evidence of apparent differential-susceptibility effects rather than undertake a formal meta-analysis of G × E findings in hopes of determining which model fits the data better.