40429_2015_79_Article XXXXXXXXXX
TRANSGENERATIONAL CONSIDERATIONS IN ADDICTIONS (LC MAYES AND E MCCRORY, SECTION EDITORS)
Understanding Addiction as a Developmental Disorder:
An Argument for a Developmentally Informed Multilevel
Approach
E. J. McCrory1 & L. Mayes2
Published online: 10 October 2015
# The Author(s XXXXXXXXXXThis article is published with open access at Springerlink.com
Abstract Substance abuse and drug addiction are two of the
most common psychopathologies among the general popula-
tion. While a host of risk factors are associated with the onset
of drug abuse and drug addiction, there is a growing body of
evidence pointing to the powerful influence of early adverse
experiences, both child neglect and maltreatment, as well as
drug use and abuse in parents and/or primary caretakers. We
consider the case for drug addiction as a developmental dis-
order, outlining the need to consider the role of genetic, epi-
genetic, and neurobiological factors alongside experiences of
adversity at key stages of development. Such a multilevel
approach within a developmental framework has the potential
to reframe our understanding of how addiction emerges and is
maintained, and is essential if we are to identify the mecha-
nisms underlying this disorder to better inform effective treat-
ment and prevention across the generations.
Keywords Childhoodmaltreatment . Addiction . Substance
use disorders (SUDs) . Epigenetics . Intervention
Substance abuse and drug addiction are two of the most com-
mon psychopathologies among the general population.
Across potential drugs of abuse, prevalence estimates in adult
populations for drug abuse and dependence range from 1.4 %
for 12-month to 7.7 % for lifetime drug abuse [1]. When the
ehavioral addictions are also considered (e.g., gambling,
overeating), there is significant overlap in natural history, co-
mo
idity, response to treatment, and etiologic mechanisms
with drug use and abuse [2]. Many addictions begin in ado-
lescence, which appears to be an especially vulnerable time
for the onset of drug use and abuse and the transition to ad-
diction [3]. There are also robust associations between the age
of onset of drug use and abuse and the severity and chronicity
of addiction [4]. While there are a host of risk factors associ-
ated with the onset of drug abuse and drug addiction, there is a
growing body of evidence pointing to the influence of early
adverse experiences, both child neglect and maltreatment, as
well as drug use and abuse in parents and/or primary care-
takers. Taken together, each of these lines of evidence suggest
that drug addiction (and perhaps addictions more generally)
may be construed as developmental disorders, that is, as dis-
orders with experiential and gene by experience antecedents
elating to early caregiving and exposure to adverse and/o
contexts characterized by deprivation.
In delineating any developmental pathway to addiction, it
is important to recognize the potential mechanisms by which
such a pathwaymay begin as early as conception.While many
women abstain from substance use during pregnancy, a sig-
nificant number continue to use substances during this time
and into the postpartum period. For those who do abstain,
elapse rates are high in the initial months following delivery
[5]. Further, substance abuse and addiction during pregnancy
are commonly associated with chronic prenatal stress in
mothers resulting in changes to maternal stress and immune
systems that may have direct effects on similar systems in the
This article is part of the Topical Collection on Transgenerational
Considerations in Addiction
* L. Mayes
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E. J. McCrory
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1 Developmental Risk and Resilience Unit, Division of Psychology
and Languages Sciences, University College London,
26 Bedford Way, London, UK
2 Yale Child Study Center, 280 S. Frontage Road,
New Haven, CT 06519, USA
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Addict Rep XXXXXXXXXX:326–330
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fetus [6]. A growing body of human research indicates the
deleterious effects of prenatal stress on birth outcomes and
postnatal development [7] especially in the domains of emo-
tion regulation that may predispose to greater risk for drug
abuse and addiction. Thus, parental substance use appears to
exert an influence on the following: (i) fetal development,
which may be reflected in increased rates of preterm delivery,
low birth weight, and multiple congenital abnormalities [8];
(ii) the prenatal environment construed more
oadly as ma-
ternal health and stress management; (iii) the postpartum en-
vironment in which the infant is often in the continued care of
a substance-abusing parent; and (iv) the adversity associated
with high rates of neglect and abuse which has been reported
in substance using parents [9]. High rates of abuse and neglect
in turn expose children to chronic stress and adversity that has
een linked to increased risk for later psychopathology includ-
ing drug use.
Especially in reference to the postnatal caregiving environ-
ment, recent advances in neurobiological models of parenting
eport the re-wiring of key neural circuits of stress and reward
y addiction that appear critical to supporting parenting [10•,
11•]. Indeed, for addicted parents, caring for a child is less
ewarding and more stressful owing to the dysregulation be-
tween stress and reward neural circuits. This approach pro-
vides neurobiological data to accompany observational stud-
ies that have indicated decreased engagement and increased
passivity between substance-using mothers and their newborn
infants [12]. Thus, prenatal and postnatal parental substance
use may have a detrimental effect on the developing child
early on during infancy through several pathways but espe-
cially including those relating to how parental care impacts
child stress regulatory capacities at the neural, psychobiolog-
ical, immunologic, genetic, and endocrine levels and how
those early pertu
ations in parental care are transmitted for-
ward to the caring behaviors of those offspring when they late
ecome parents themselves.
Recent data also suggest a prominent role for genetic as
well as psychosocial factors in the transmission of substance
abuse from parent to child [13, 14]. Moreover, there has been
significant progress in identifying specific genes that influ-
ence substance abuse disorders. The search for specific genes
has been aided by knowledge of developmental pathways
leading to drug abuse. For example, the central importance
of externalizing disorders in adolescence as a developmental
pathway associated with higher rates of substance use and
abuse has led to noting the importance of genes regulating
the dopamine systems for both externalizing and alcohol dis-
orders [15]. The newer techniques of genome-wide associa-
tion studies have also underscored the importance of devel-
opmental process. Of special interest has been the identifica-
tion of genes important in the earliest strategies of
ain
development which are associated with substance abuse
much later on [16]. Moreover, genetic studies have been
among the best documentation of the role of social factors in
protecting or accelerating drug use. For example, the effect of
genetic factors and delinquent behavior and alcohol use in boys
are blunted in rural communities [17]. Recent comprehensive
epidemiological studies also focus on the importance of the
child’s experience of parental ma
iage: divorce serves as a
major risk factor for subsequent alcohol abuse and dependence
controlling for family history of substance abuse disorders [18].
The identification of endophenotypes such as impulsivity,
which are risk factors for both externalizing and substance
abuse disorders, has aided in gene identification [19]. For in-
stance, a novel adoption design suggests that the first expres-
sion of a genetic risk for addictions and related impulsive be-
havior in infants and childrenmay be problems in attention and
ehavioral self-control that can be ameliorated by parents with
good emotional self-regulation who can provide appropriate
structure [20, 21]. This is consistent with data suggesting that
genetic vulnerability to substance use has been considered
through the lens of self-control and emotion regulation [22].
In particular, impulsivity has been considered a key construct
in the emergence of substance dependence during adolescence
[23], with increasing levels of impulsivity and risky behavio
more generally being higher during this developmental period.
Notably, adolescence is marked by higher rates of experimen-
tal drug use, and substance use disorders begin to emerge [3,
24], an observation underscoring the importance of this period
in the pathway to addiction before individuals even enter adult-
hood. Parents play a critical role in the socialization and regu-
lation of emotions and behaviors in children, and children also
shape and contribute to their parent’s own behavior regulatory
functioning (e.g., [25, 26]). Indeed, families have their own
capacities for self-regulation that may provide a protective ef-
fect against the transmission of substance abuse across gener-
ations [27]. Further, programs that focus on early parent-child
elationships and closely related social processes have shown
efficacy in preventing substance abuse (e.g. [28, 29]).
In sum, a growing body of research suggests a continuous
set of circumstances from the intrauterine periods though in-
fancy, childhood, and early adolescence through which indi-
viduals follow increasingly clear developmental pathways to-
wards serious addictive disorders. The papers in this special
issue each contribute distinct lines of evidence addressing the
eframing of addictions as developmental disorders, focussing
specifically on the following: (a) the role of gene-environment
interactions in the emergence of specific addictive disorders;
(b) the role of epigenetic mechanisms; (c) the role of early
adversity in changing
ain systems relevant to an addictive
process; (d) the role of emotion regulation difficulties in key
developmental periods such as adolescence in addiction and
other psychopathologies; and (e) the use of developmentally
and mechanism-informed intervention/prevention programs
to reduce the risk for drug use and abuse across the develop-
mental life span.
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Addict Rep XXXXXXXXXX:326–330 327
Milaniak,Watson, and Jaffee examine candidate gene studies
that test gene × environment interactions with a focus on vari-
ants consistently associated with substance use and abuse. They
specifically review the genes associated with nicotine, cannabis,
and alcohol use and abuse with special attention to the genes
linked to neural systems involved in addiction. What emerges is
a mixed though provocative set of findings from quantitative
ehavioral genetic studies regarding gene × environment inter-
actions in candidate gene studies. Importantly, while small, un-
derpowered studies are surely problematic, the authors point to
the challenge of obtaining adequately fine-grained measures of
environmental factors in larger samples. Further, they under-
score the need to guide genetic studies by biologically plausible
mechanisms for drug use and abuse and for a more mechanisti-
cally informed understanding of environmental variables (e.g.,
more proximal measures of parental care behavior, the caring
environment, or the impact of peer to peer interactions). Getting
closer to developmental mechanisms also requires more transla-
tional research
inging together human and animal studies.
Cecil, Walton, and Viding address the role of epigenetic
mechanisms in the onset of substance use disorders with a
particular focus on DNA methylation. Across both human
and animal studies, evidence generally supports an association
with DNA methylation and substance use/addiction with the
suggestion that developmental timing is key. The authors
point to the limited knowledge today on the normal patterns
in the methylome especially in humans and the variation by
tissue, cell-type, gender, and age as well as the relative contri-
ution of genetic and environmental influences on observed
methylation patterns and a paucity of longitudinal studies be-
ginning early with repeated