CHAMBERS

NEUROBIOLOGY OF ATTACHMENT

The Neurobiology of Attachment: From Infancy to

Clinical Outcomes

Joanna Chambers

Abstract: Attachment theory was developed by John Bowlby in the 1950s. He

defined attachment as a specific neurobiological system that resulted in the in-
fant connecting to the primary caretaker in such a way to create an inner work-
ing model of relationships that continues throughout life and affects the future
mental health and physical health of the infant. Given the significance of this
inner working model, there has been a tremendous amount of research done
in animals as well as humans to better understand the neurobiology. In this ar-
ticle the neurobiology of early development will be outlined with respect to the
formation of attachment. This article will review what we have begun to under-
stand as the neurobiology of attachment and will describe how the relationship
with the primary caretaker affects the infant in a way leading to neurobiological
changes that later in life affect emotional responses, reward, and perception dif-
ficulties that we recognize as psychiatric illness and medical morbidity.

Keywords: attachment theory, neurodevelopment, oxytocin,

hypothalamic-pituitary-adrenal axis

ATTACHMENT THEORY: A BRIEF HISTORY

The parent–infant bond has arguably been the most important pro-
cess for human survival. While the importance of the mother–infant
attachment has been understood for centuries, it was not studied until
John Bowlby developed attachment theory in the 1950s. In order to put
attachment theory in proper context, one must begin with a reminder
of Sigmund Freud’s drive theory. According to drive theory, we at-
tached to our mothers because they fed us and gratified our oral yearn-

Joanna Chambers, M.D., Associate Professor of Clinical Psychiatry, Indiana University

School of Medicine; Chair of Scientific Programs, American Academy of Psychoanalysis
and Dynamic Psychiatry.

Psychodynamic Psychiatry, 45(4) 542–563, 2017

© 2017 The American Academy of Psychoanalysis and Dynamic Psychiatry
 NEUROBIOLOGY OF ATTACHMENT 543

ings (Freud, 1923). In other words, our attachments were derived from
our libidinal drives and did not exist independently. Drive theory was
largely a one-person psychology focusing on the drives and conflicts of
the individual; our mother was simply an instigator who either grati-
fied or displeased our internal drives and wishes.
Melanie Klein led us to a two-person psychology where the other
person was more than an instigator of drives and wishes. The mother,
in particular, shaped the psychology of the infant through representa-
tions of the good and the bad breast, the merger of the two, and the
hope for reparation that allows us to stay attached to our mothers.
Klein introduced the idea that we need to feel hope for reparation to
stay connected to our loved ones in spite of our own aggressive drives
(Kristeva, 2001). For the first time, the object had relevance in our psy-
chology, though Klein believed that the emotional problems of children
still came largely from the fantasies generated by internal conflict re-
lated to the object.
John Bowlby was a supervisee of Melanie Klein and was influenced
by her, however he argued that children’s emotional problems do not
stem from their own internal conflicts based on a fantasy of the care-
taker, but rather their emotional problems stem from actual experiences
with their caretakers (Bretherton, 1992). Furthermore, Bowlby sug-
gested that the need for social bonds is independent of feeding and
sexual needs but equal in significance (Bowlby, 1977). Attachment
theory suggests that through the earliest relationship with one’s par-
ents, one develops an internal working model of relationships, which
affects the capacity for relationships later in life. These difficulties in
the earliest relationships can lead to marital difficulties, difficulties re-
lating to one’s children, neuroses, and personality disorders (Bowlby,
1977). Since then, insecure attachment has also been shown to lead to
difficulties with other psychiatric illnesses, including depression, anxi-
ety disorders, substance abuse disorders, and several medical illnesses
(Davies, Macfarlane, McBeth, Morriss, & Dickens, 2009; McWilliams &
Bailey, 2010; Puig, Englund, Simpson, & Collins, 2013).

THE IMPORTANCE OF ATTACHMENT

Since Bowlby developed attachment theory in the 1950s, significant

work has been done to investigate the importance of maternal attach-
ment in mammals, including humans. Harry Harlow, a psychologist
at the University of Wisconsin, was intrigued by John Bowlby’s work
on attachment theory and carried out the first scientific study of at-
544 CHAMBERS

tachment theory. In an effort to better understand the implications of

mother–infant attachment, Harlow isolated neonatal monkeys from
their mothers shortly after birth (Suomi, Harlow, & McKinney, 1972).
These monkeys developed severe psychopathology with locomotive,
exploratory, and social problems later on, demonstrating the neuro-
vegetative and social effects that occur when infants are removed from
their mothers. As adults, these “motherless monkeys” were unable to
appropriately mother their young, demonstrating neglectful and abu-
sive behaviors toward their young (Rupenthal, Arling, Harlow, Sackett,
& Suomi, 1976). While this seems intuitive to us in the 21st century, in
the 1970s when these experiments were carried out, this was revolu-
tionary and validating of Bowlby’s attachment theory.
The origins of attachment were still in question: was attachment de-
pendent on libidinal drives or was it a separate process? To evaluate
this question, Harlow’s isolated monkeys were given two surrogate
“mothers” to choose from: one surrogate mother was covered in terry
cloth with large eyes and the other surrogate mother was made of wire
with no soft covering, with small eyes, and held a bottle of food for the
monkeys. If attachment was indeed derived from libidinal drives, the
monkeys would show attachment behaviors toward the wire mother
with food. The monkeys showed a significant preference for the soft
mother while they would only go to the wire mother to eat. This dem-
onstrated that attachment was indeed its own process, independent of
libidinal drives (Suomi, Harlow, & McKinney, 1972).
Attachment to early childhood caretakers provided an inner working
model for all relationships later in life. In an effort to better understand
these inner working models, Mary Ainsworth, John Bowlby’s collabo-
rator, went on to define three distinct and measurable levels of attach-
ment: secure attachment, anxious attachment, and avoidant attachment
(Ainsworth & Bell, 1970). Mary Main added a fourth level, namely dis-
organized attachment (Main & Solomon, 1990). Anxious, avoidant, and
disorganized attachment were all classified as insecure attachments.
These attachment patterns could be evaluated at 12 months of age and
remain consistent over the time. Secure attachment was defined as the
ability to carry a representational model of attachment figures as being
available, responsive, and helpful. Insecure attachment was defined as
not seeking out the attachment figure when distressed or having dif-
ficulty moving away from the attachment figure, likely due to having
an unresponsive, rejecting, inconsistent, or insensitive caretaker (Ain-
sworth & Bell, 1970).
 NEUROBIOLOGY OF ATTACHMENT 545

THE DEVELOPMENT OF ATTACHMENT

In humans, similar to Harlow’s “motherless monkeys,” attachment

security is mostly intergenerational. In fact, the mother’s attachment
security can predict the security of attachment of the infant with up
to 75% certainty (Fonagy, Steele, & Steele, 1991). We understand this
intergenerational process to be at least in part a psychological phenom-
enon through the interaction between the mother and her infant (Fon-
agy, Steele, & Steele, 1991). Watching a mother interact with her infant
can be compared to a very sensitive and nuanced dance where each
partner responds to the other in a complex and sometimes subtle way.
This dance involves touch, eye contact, facial expression, and verbal
expression in both partners. When these interactions happen synchro-
nously, all goes well and the infant becomes securely attached. When
these interactions are disjointed and cues are misunderstood, the in-
fant’s attachment to his mother becomes conflicted and he later devel-
ops insecure attachment as a result. The attunement of the mother to
her infant’s cues is often an unconscious process and is a significant
predictor of her ability to exist in synchrony with her infant. Through
this process, the infant internalizes the experiences with his mother.
During the early process of attachment, as the mother responds to
her infant’s needs in a sensitive way, she is teaching the infant about
empathy. Through her empathy, she can essentially predict what needs
the infant is conveying, be it the need for soothing, feeding, diaper
changing, etc. As the mother meets the needs of the infant, he feels un-
derstood by her in a unique way. As the mother soothes her infant, he
learns that his emotions can be regulated. As the mother takes pleasure
in her infant, he is instilled with a sense of power as he realizes his ca-
pability to create pleasure in another person. These experiences by the
infant involve significant neurobiological events that have implications
for mental and medical health later in life. These experiences by the
infant are also integral in forming the psychological internal working
model (his mother) that is projected on to all future relationships.
There are several risk factors that can lead to interference in the
mother–infant relationship and the attachment process. These include
mental illness including prenatal depression and postpartum depres-
sion, insecure attachment in the mother, parental insensitivity, disrupt-
ed affective communication between parent and infant, child abuse,
and child neglect (Hayes, Goodman, & Carlson, 2013). Fortunately,
there is evidence to suggest that the attachment process is malleable
through preschool-aged children, especially if the mother undergoes
attachment-focused treatment (Hoffman, Marvin, Cooper, & Powell,
546 CHAMBERS

2006). Hence, there seems to be a window of opportunity for interven-

tion and treatment for insecurely attached infants.
As we better understand the neurodevelopmental process involved
in attachment, there has been a shift in increased importance of the
prenatal period to be included in the sensitive period of development.
This is particularly interesting as the psychological interaction between
mother and infant has not yet developed at this time, yet it is clear that
the infant is born with a preference for his mother’s smell, his moth-
er’s milk, and his mother’s voice (Vaglio, 2009). Furthermore, there is
a significant correlation between mothers with antenatal depression
and infants with disorganized attachment styles at 12 months (Hayes,
Goodman, & Carlson, 2013). Fortunately, it has been shown that higher
quality parenting in the first three months can ameliorate the risk of
disorganized attachment due to antenatal depression (Hayes, Good-
man, & Carlson, 2013). This leads to the conclusion that there is an in-
terplay between the fetal period and the first three months of life that
is critical for the attachment process. Understanding the neurobiology
of attachment can help us uncover this interaction and possible ways
to intervene.
In addition to the interpersonal and relationship problems that Bowl-
by identified as resulting from insecure attachment, there has been a
significant link of insecure attachment to psychiatric illnesses such as
depression, anxiety, and substance abuse (Heim & Nemeroff, 2001).
The developing knowledge of the neurobiology of attachment allows
for a greater understanding of how attachment insecurity may lead to
these afflictions. The hypothalamic-pitutiary-adrenal (HPA) axis and
the reward neurocircuitry are likely to have very significant roles in
the attachment process as well as in psychiatric illnesses and medical
morbidity later in life. In order to understand these connections better,
we must first explore the neurobiology of attachment.

THE NEUROBIOLOGICAL DEVELOPMENT OF THE INFANT

The Hypothalamus at Birth

The hypothalamus is developing in the fetus and is affected by the

maternal HPA axis (Giesbrecht et al., 2017), and at birth, the hypothala-
mus is already fully developed. The hypothalamus functions through
the HPA axis to produce cortisol by the adrenal glands. Cortisol has a
bipartite effect on the rest of the developing brain, where in high doses,
cortisol is largely neurotoxic and inhibits neuronal connections, while
lower levels of cortisol induces neuronal development and growth
 NEUROBIOLOGY OF ATTACHMENT 547

through neuroplasticity (Vela, 2014). Therefore, modulation of corti-

sol during this sensitive period of neural development is imperative
for future function. Oxytocin and social interaction have been shown
to decrease cortisol levels, demonstrating that even at this early stage,
physical connection between a mother and her infant has an important
effect on brain development and neuroplasticity (Heinrichs, Baumgart-
ner, Kirschbaum, & Ehlert, 2003). Furthermore, adults with insecure
attachment show a hyper-reactive HPA axis and cortisol response to
acute stress, demonstrating that these effects are long lasting (Quirin,
Pruessner, & Kuhl, 2008).
In very young rat pups, it has been shown that the HPA axis is non-
functional during postnatal days 4–14 (Rincon-Cortes et al., 2015). This
lack of cortisol inhibits any fear response, allowing the rat pups to at-
tach to their mothers during this developmental phase. In a study to
better understand how child abuse affects the attachment process, rat
pups at days 4–14 were repeatedly exposed to an odor paired with a
foot shock in the presence of the mother. Later, when the abused rats
became adults, the odor actually had a positive and antidepressant ef-
fect on the rats during stress. While the study was done in rats, it has
significant clinical implications in humans. This study demonstrates
the very powerful and non-discriminatory attachment process. This re-
markable repetitive response in the rat explains, from a neurobiological
perspective, how other mammals, including humans, who are abused
in their youth still attach to their abusive parents with the same vigor
as the non-abused child. If a child is exposed to a sensory experience,
even a traumatic one, during this sensitive time period when the neu-
robiology is primed for attachment, they will seek out those traumatic
experiences time and again. Hence, they repeatedly seek out abusive
relationships because abuse was part of the attachment process in early
childhood and the abuse became rewarding. This also explains, in part,
why humans with histories of abuse in childhood will seek out and
attach to abusive partners as adults. In this way, we begin to see that
the early attachment process is interconnected with the reward system.

The Hippocampus Develops

It is clear from the previous section that the first three months of life
are important with respect to the attachment process through modu-
lation of the HPA axis. This is also the time when the hippocampus
fully matures. The hippocampus is a part of the limbic system and is
involved in spatial and emotional memory. It is instrumental in consoli-
548 CHAMBERS

dating declarative or explicit memories, which are facts or events, and

it provides the ability to consciously recall events or facts from long-
term memory (Campbell & MacQueen, 2004). As the hippocampus de-
velops, the infant is able to recognize and remember his mother, smile
at her, begin to feel a sense of pleasure with her, and begin to actively
engage with her. This is an extremely crucial time with respect to the
development of the mother–infant bond and by four months of age,
the relationship patterns between a mother and her infant can predict
the attachment security of the infant at 12 months (Beebe et al., 2012;
Koulomzin et al., 2002).
The hippocampus has a large number of glucocorticoid receptors,
causing significant sensitivity to stress and cortisol production through
the HPA axis. When the infant is stressed, high doses of cortisol are
produced, causing neurotoxicity to the hippocampus. Furthermore,
the hippocampus is known to provide negative feedback to the HPA
axis, decreasing cortisol production (Sapolsky, Krey, & McEwen, 1986).
Hence, when the hippocampus suffers from neurotoxicity, cortisol pro-
duction is further enhanced. Therefore, neglect or abuse at this stage
can significantly impair the development of the hippocampus. Rat pups
who were separated from their mothers during early development (a
model of neglect) have been shown to have smaller hippocampi (Huot,
Plotsky, Lenox, & McNamara, 2002). In humans, hippocampal gluco-
corticoid receptors have been shown to be affected by child abuse as
well (McGowan et al., 2009). These first few months of life are vital in
terms of the future relationship between attachment, stress, and object
relations of the infant.

The Reward System

The young infant clearly experiences pleasure in her interactions

with her mother. The social smile, which usually begins between six to
eight weeks of age, is evidence for this. It is also evidence for the pres-
ence of the reward neurocircuitry. The reward system is a complex neu-
rocircuitry which has been described as a dichotomy of two systems:
the novelty seeking system and the familiarity system (Tops, Koole,
IJzerman, & Buisman-Pijlman, 2014). The ventral striatal pathway is
involved in novelty seeking as a reward. The dorsal striatal pathway
is involved in reward related to familiarity, comfort, and satiety. Early
in development, the novelty-seeking ventral striatal system is thought
to be more active. During the first three months, the mother’s face is
novel and the infant is driven in part by the reward circuitry to look at
 NEUROBIOLOGY OF ATTACHMENT 549

her. As the infant is able to respond to her by smiling, body language,

and eye contact, and if the mother is responsive, there is a shift to dor-
sal striatal activity where the familiarity of mother and the connection
with her becomes rewarding. If there is neglect or abuse during this
developmental phase, the development of the ventral novelty seeking
system relative to the dorsal familiarity system is affected. This process
has significant potential for the interaction of poor attachment with
later substance abuse problems, as the reward of familiarity and com-
fort in relationships may not protect against the reward of substances
and impulsivity (novelty). Indeed, there is evidence that both animal
models and humans with poor attachments are more likely to develop
substance abuse problems (Moffett et al., 2007). Furthermore, attach-
ment style has been found to directly impact the recovery of patients
hospitalized for the treatment of addictions, where insecure (avoidant)
attachment leads to poor treatment outcomes (Caspers, Yucuis, Trout-
man, & Spinks, 2006; Fowler, Groat, & Ulanday, 2013). If the dorsal
striatal reward network is not fully developed during the sensitive at-
tachment period, one cannot develop a preference for familiarity, com-
fort, and satiety over the rewarding sensation of novelty brought on by
substances of abuse. Strathearn (2011) found that there is an increase in
activation in the ventral striatum when securely attached mothers see
their infant’s happy face, while there is a decrease in activation in the
ventral striatum when insecurely attached mothers see their infants.
Interestingly, the ventral striatum has been shown to mount a dimin-
ished response to reward in neuroimaging of individuals with a history
of early childhood abuse (Teicher, Samson, Anderson, & Ohashi, 2016).
This is a particularly interesting finding as it demonstrates an altered
reward system in insecurely attached mothers, while also helping us
better understand how insecure attachment or a history of child abuse
in the mother can lead to psychiatric illnesses such as postpartum de-
pression, where interactions with the infant is not inherently reward-
ing.

The Amygdala

Even before birth, the fetal amygdala is affected by his mother’s affect
(Qiu et al., 2015). Specifically, both depression and cortisol spikes in the
mother during pregnancy have been shown to decrease the size of the
amygdala later in the infant (Qiu et al., 2015). The amygdala matures at
six to seven months of age (Vela, 2014). With this development, we also
see the beginnings of fear and salience, two important functions of the
550 CHAMBERS

amygdala. The infant at this age will show stranger anxiety and protest
separation from his mother. Youths who have been institutionalized
and suffer emotional deprivation, who are later adopted by families in
the U.S., show a difference in amygdala response when compared to
youths who had been raised by their biological parents without emo-
tional deprivation. The youths, who were 4–17 years of age at the time
of the imaging study, were shown pictures of their mothers (biological
or adopted mothers in the case of the adopted youths; Olavsky et al.,
2013). The youths who were raised by their mothers from birth showed
significant amygdala responses to their mothers but not to strangers.
The youths who had been institutionalized prior to adoption demon-
strated a significant amygdala response to both their mothers and the
strangers. The lack of differentiation became more significant with in-
creased age of the youth at the time of adoption. In other words, the
older the child’s age at adoption, the less likely their amygdala was to
discriminate between the mother and the stranger. This study demon-
strates that while the amygdala is important for a fear response, it is
also important for the determination of salience. The study also vali-
dates the notion that there is a sensitive period of attachment develop-
ment that has life-long consequences.
This leads to the question: “What happens if we remove the amygda-
la?” Bauman, Lavener, Mason, Capitanio, and Amaral (2004) answered
that exact question in a study with macaque monkeys. The macaques’
amygdalae were lesioned at two weeks of age and some interesting
results were found. The monkeys without their amygdala spent more
time with their mothers in the first six months. They were separated
from their mothers at six months of age and placed in a holding box
with equal proximity to their mothers and to a familiar female who
was not their mother. In this box, the control (non-lesioned) monkeys
spent all their time in proximity to their mother. The lesioned monkeys
spent an equal amount of time in proximity to the familiar female as
to their mother. Furthermore, the control monkeys screamed in pro-
test at not being able to be held by their mother, while the amygdala-
lesioned monkeys showed no distress at having limited proximity to
their mother. So while the lesioned monkeys were content with their
mothers in the first six months of life, they had no ability to understand
the salience of their mother when compared to a familiar female with-
out their amygdala.
In humans, amygdala lesions have been described in Urbach–Wiethe
syndrome, an autosomal recessively inherited syndrome that causes
bilateral calcifications of the amygdala in 50% of patients. In an inter-
esting report, the psychoanalytic findings in a 38-year-old male patient
 NEUROBIOLOGY OF ATTACHMENT 551

with bilateral amygdala calcifications due to Urbach–Wiethe syndrome

was described (Wiest & Brainin, 2010). This patient had sought treat-
ment due to new onset panic attacks and depressive symptoms. While
the patient was easily able to remember facts, he had more trouble
with emotionally salient memory as he could not remember what he
did while together with his friends. While he could remember if he
liked a certain book or movie, he had trouble remembering what hap-
pened in the stories of the books or movies. He could only remember
if a place was familiar or not, but could not recall how to get there. He
was notably unable to free associate in the analytic sessions. The ana-
lyst described each session as feeling like a repetition without any con-
nection to the previous session. He had a wide range of emotions and
was able to recognize negative emotions such as anger and sadness.
He was seemingly able to attach as he had a fulfilling relationship for
nine years with the same woman and was able to develop a transfer-
ence to his analyst. While this study is interesting, the implications for
the neurobiological function of the amygdala in attachment are unclear
since we do not know at what age the amygdala calcifications occurred.
Given the sensitive period of development, there is likely a difference
between having a functional amygdala in the first year of life which
is impaired later on and being born without an amygdala. The report
does validate the function of the amygdala in the appreciation for emo-
tional salience however. The report also suggests that the amygdala
may serve as an emotional compass, without which we feel lost, caus-
ing anxiety and depression over time.
More studies have been done in the amygdala of parents in an effort
to understand the role of the amygdala in parental attachment. First-
time mothers, imaged with fMRI in the first postpartum month while
listening to recordings of babies crying, including their own baby, dem-
onstrate an activated neurocircuitry when hearing their own baby cry
already in the first two weeks postpartum (Swain, 2008). When com-
pared to brain responses to the control babies cries, the mothers’ ac-
tivated neurocircuitry included the anterior cingulate gyrus and the
amygdala. The fathers, who were also imaged, did not show activation
in the amygdala, but instead showed other areas of activation includ-
ing the anterior cingulate, the visual cortex, and the parahippocampal
gyrus. This might be the result of mothers’ attachment neurocircuitry
being “primed” earlier than that of fathers. This could be partially due
to the effects of oxytocin elevations during the process of parturition
and nursing.
552 CHAMBERS

Oxytocin: Attachment and Synchronicity

In pregnant mothers, there is evidence that an increase in maternal

oxytocin levels during the first and second trimester of pregnancy pre-
dict mothering behavior in the postpartum (Levine, Zagoory-Sharon,
Feldman, & Weller, 2007). In securely attached individuals, oxytocin
levels are generally higher and increase during periods of stress, in-
crease with play, and oxytocin and reward activation synchronize dur-
ing interaction with one’s infant (Pierrehumbert, Torrisi, Ansermet,
Borghini, & Halfon, 2012). Women with a history of child abuse have
lower oxytocin levels in general as well as during pregnancy and the
postpartum period (Heim et al., 2009). This is significant for the infant
because in the postpartum period, there appears to be a synchronous
relationship between oxytocin in the parents and oxytocin in the infant
(Levine, Zagoory-Sharon, Feldman, & Weller, 2007). When the parent
and child interact with each other, the oxytocin levels increase in both
the parent and the infant.
Oxytocin plays an important role in the attachment process of par-
ents. An imaging study looking at mothers interacting with their
4–6-month-old infants showed a clear distinction in neurocircuitry be-
tween mothers described as either synchronous or intrusive with their
infants (Atzil, Hendler, & Feldman, 2011). In the synchronous mothers,
the right nucleus accumbens (ventral striatum) was active and showed
an organized response with the prefrontal cortex (PFC). In addition,
the oxytocin levels seem to increase and correlate with the neurocir-
cuitry response. In the intrusive mothers, the left amygdala was active
and showed a disorganized response with the PFC while the oxytocin
levels did not correlate with the neurocircuitry response. In a separate
study by Gordon, Zagoory-Sharon, Leckman, and Feldman (2010),
plasma oxytocin levels in mothers correlated with the amount of time
the mother spent in affectionate behavior with her infant. Furthermore,
salivary oxytocin levels in both mothers and fathers increase when
playing with their infants and correlate directly to infant oxytocin lev-
els (Feldman, 2010). When fathers were given intranasal oxytocin and
then interacted with their infants, the infants showed a similar increase
in oxytocin during the interaction (Naber, van IJzendoorn, Deschamps,
van Engeland, & Bakermans-Kranenburg, 2010; Weisman, Zagoory-
Sharon, & Feldman, 2012). Securely attached mothers have an increase
in oxytocin when playing with their infants while insecurely attached
mothers’ oxytocin levels actually decrease with play (Strathearn, Fon-
agy, Amico, & Montague, 2009). Furthermore, secure attachment was
correlated with higher oxytocin levels and decreased subjective stress
 NEUROBIOLOGY OF ATTACHMENT 553

during an acutely stressful situation (Pierrehumbert, Torrisi, Ansermet,

Borghini, & Halfon, 2012). Hence, it appears that oxytocin and secure
attachment may regulate the stress system.

The Maturing PreFrontal Cortex (PFC)

The prefrontal cortex (PFC) begins development in the early neonatal

stage and continues to evolve through pruning until the middle of the
third decade of life (Kolb et al., 2012). While the role of the immature
PFC in infants and children is unclear, the mature PFC has been shown
to be important in the process of attachment in adults. In a rat model
of social interaction, two adult rats who are introduced under stress-
ful conditions lessen each other’s anxiety levels during a stressful chal-
lenge. If the rats are first introduced in a non-stressful situation, they
will not have the same ability to modulate each others’ anxiety levels:
they must be introduced during a stressful event to have an anxiolytic
effect on each other. This effect is directly modulated by the medial
PFC (Lungwitz et al., 2014). Of course, we see this on a regular basis in
human situations. For example, military veterans will tell us that their
closest attachments are the other veterans who served with them. There
may be a similar effect in psychotherapy, where therapists engage their
patients in some of their most stressful memories, cognitions, and af-
fects, which may, in part, contribute to the patient’s attachment to the
therapist. It is clear that the PFC plays an important role in the attach-
ment process, especially later in development. In rat pups exposed to
an abusive caretaker early in development, brain-derived neurotrophic
factor (BDNF) gene expression has been shown to be decreased in the
PFC as adults (Roth, Lubin, Funk, & Sweatt, 2009). This may have impli-
cations for later developments of depression as BDNF has been shown
to be decreased in depression and increases with treatment (Duman,
2004) It is also likely that the proper development of the PFC depends
on the functionality of earlier neurobiological developments. However,
while the exact role of the PFC in the attachment process early in devel-
opment remains unclear, it is clear that the PFC has an important role
in modulating anxiety and depression, which may rely on a healthy
neurobiological environment during early development.

Summary of the Neurobiology

The attachment neurobiology develops early, beginning in utero

and continues through preschool age. It appears to be partially set by
554 CHAMBERS

pruning around 24 months (Vela, 2014). This is a complex process that

involves the development of HPA axis and reward system early on, fol-
lowed by the development of the amygdala, followed by PFC develop-
ment into adulthood. As we have a better understanding of the attach-
ment neurocircuitry, we can see how this sensitive period of develop-
ment leads to neurobiological changes later in life affecting emotional
response, reward, and perception difficulties. Our understanding of
neurobiology is finally catching up and validating what psychoanalytic
theory has always assumed: the importance of early development and
the necessary process of each stage of development, building on earlier
stages and experiences.

Clinical Implications of Insecure Attachment

In a 30-year prospective study by Fan et al. (2014), infants who expe-

rienced poor attachment behaviors from their mothers at eight months
of age were at higher risk for mental illness 30 years later. Depression,
anxiety, and substance use disorders have all been linked to insecure
attachment (Heim & Nemeroff, 2001). Medical morbidities, such as
chronic pain, cardiovascular disease, and inflammation-based illnesses
have also been linked to poor attachment (Davies, Macfarlane, McBeth,
Morriss, & Dickens, 2009; McWilliams & Bailey, 2010; Puig, Englung,
Simpson, & Collins, 2013). Adverse childhood events (ACE) have also
been shown to correlate to physical illness in adulthood (Felitti et al.,
1998). Epidemiological studies have shown that a lack of social relation-
ships has similar consequences on physical health as smoking, obesity,
and inactivity (Puig, Englung, Simpson, & Collins, 2013). The quality
of close relationships, especially marriage partners, had a significant ef-
fect on the immune system, the neuroendocrine system, and resiliency
to stress (Puig, Englung, Simpson, & Collins, 2013). Perhaps, this could
be in part mediated through early attachment developments.
Avoidant attachment has been correlated to chronic back pain and
neck problems, frequent and severe headaches, chronic pain, and ulcers
(McWilliams & Bailey, 2010). Anxious attachment has been correlated
to chronic back and neck problems, frequent and severe headaches,
chronic pain, as well as strokes, myocardial infarction, hypertension,
and ulcers (McWilliams & Bailey, 2010). Insecurely attached individu-
als perceived pain as more threatening, had a negative perception of
social support, demonstrated decreased support seeking, experienced
increased depression, anxiety, stress, were more inclined to catastroph-
ize, and showed decreased adaptive coping (Meredith, Ownsworth, &
 NEUROBIOLOGY OF ATTACHMENT 555

Strong, 2008). Insecure attachment correlated to increased number of

pain sites in people with chronic widespread pain (CWP), had twice
the prevalence of CWP, and demonstrated an increase in pain-related
disability (Davies, Macfarlane, McBeth, Morriss, & Dickens, 2009).
Insecurely attached individuals also had four times greater chance
of physical illness, four times greater chance of inflammatory related
illness, and were three times more likely to have nonspecific physical
symptoms (Puig, Englund, Simpson, & Collins, 2013).
It is clear from these studies that attachment security affects medi-
cal and psychological wellbeing later in life. Understanding the neuro-
biological underpinnings of the attachment process allows us to better
identify how these morbidities may be linked to insecure attachment.
Attachment insecurity may lead to these psychiatric and medical chang-
es later in life through several neurobiological mechanisms, including
stress response, inflammatory responses, neurocircuitry changes, and
epigenetics. These mechanisms are also likely to interact causing a cu-
mulative effect.

THE STRESS RESPONSE

The role of the HPA axis and cortisol is complicated and likely of
great importance in the relationship between attachment security and
medical and psychiatric comorbidity. Individuals with insecure attach-
ment show a greater perception of stress when compared to securely
attached individuals (Kidd, Hamer, & Steptoe, 2011). In general, corti-
sol levels are known to be altered in patients with depression, anxiety,
posttraumatic stress disorder, as well as in insecure attachment (Kidd,
Hamer, & Steptoe, 2010; Quirin, Pruessner, & Kuhl, 2008). It is therefore
reasonable to assume that modulation of the hypothalamus early in de-
velopment has significant effects on the individual later in life.
Interpersonal stress is increased in insecurely attached individuals
and this has several neurobiological causes. In interpersonal stress,
the prefrontal cortex is downregulated and its inhibitory control of the
amygdala decreases (Gold, 2015). In addition, the HPA axis is activated
during interpersonal stress through increased activation of the amyg-
dala, as well as through the lack of inhibition by the PFC, leading to
increased cortisol production. Cortisol further increases amygdala acti-
vation. In addition, corticotropin releasing hormone (CRH) is increased
by interpersonal stress, further increasing fear and anxiety through its
effect on the sympathetic nervous system and the amygdala (Gold,
2015). While the hippocampus generally has an inhibitory effect the
HPA stress response (Radley & Sawchenko, 2011), if the hippocampus
556 CHAMBERS

has been negatively affected by elevated cortisol in infancy, the inhibi-

tory effect of the hippocampus on the HPA axis is also likely to be com-
promised. One quickly begins to see that there is little inhibition in this
process once it gets started and the system behaves largely in a feed
forward manner, where stress increases amygdala activity, HPA activ-
ity, cortisol, CRH, and the sympathetic nervous system with minimal
inhibition.
Oxytocin has many functions, including lowering HPA activity and
cortisol. Cortisol increases plasma oxytocin levels, hence this serves
as a negative feedback system where stress increases cortisol, which
then increases oxytocin, which then decreases cortisol. In individuals
who are securely attached, oxytocin levels increase in response to stress
(Pierrehumbert, Torrisi, Ansermet, Borghini, & Halfon, 2012). Given
that women with a history of child abuse have lower oxytocin levels in
general (Heim et al., 2009), it is possible that insecurely attached indi-
viduals do not have this inhibitory process in place, allowing the stress
response to escalate to higher levels. Furthermore, insecurely attached
individuals are less likely to reach out to their loved ones in times of
stress, may have a lower oxytocin response to interaction with loved
ones, both which contribute to lower oxytocin levels (Pierrehumbert,
Torrisi, Ansermet, Borghini, & Halfon, 2012; Strathearn, Fonagy, Ami-
co, & Montague, 2009).

THE INFLAMMATORY RESPONSE

Inflammatory responses may also be a culprit in the connection be-

tween insecure attachment and psychiatric and medical morbidity.
During stress, an increase in CRH causes acute stage inflammatory
responses, including interleukin-6 and cytokines (Gold, 2015). While
acute increases in cortisol deactivate the inflammatory system, both
chronic elevations and chronic hypoactivity in cortisol levels lead to
a hyperactive inflammatory system. Insulin, which also increases in
response to acute stress, increases the inflammatory response and con-
tributes to activating the sympathetic nervous system (Gold, 2015).
These inflammatory responses are noteworthy as they contribute to a
variety of medical complications, including: auto immune disorders;
cardiovascular disease, such as hypertension, myocardial infarctions,
and stroke; pain; gastric and duodenal ulcers; and cancer (Puig, En-
glund, Simpson, & Collins, 2013). An increase in cytokines has been
shown to lead to depression, as cytokines in the brain have an effect on
the production, release, and metabolism of neurotransmitters. There-
fore, it may be that insecure attachment leads to early changes in CRH/
 NEUROBIOLOGY OF ATTACHMENT 557

HPA axis, which then leads to increases in cytokines, which contrib-

ute to the development of depression later in life. Insecure attachment
may also lead to cardiovascular events through inflammatory changes
(Gold, 2015).

NEUROCIRCUITRY

The effects that abuse and neglect have on the developing brain as
described in this article are significant. Understanding how poor attach-
ment leads to changes in neurocircuitry later in life is still in progress.
For instance, in individuals with a history of child abuse, the amyg-
dala is hyper-responsive to angry faces (Teicher, Samson, Anderson, &
Ohashi, 2016). This hyper-responsivity may be due partly to a failure to
develop appropriate inhibitory mechanisms during the first year of life.
If the amygdala is faced with an aggressive, abusive, or unpredictable
attachment figure in the first year of life, without appropriate modula-
tion through oxytocin and other neural connections, hyperactivity may
be the result. The reward neurocircuitry also appears to be affected by
attachment, which may have implications for psychopathology later
in life. For example, in depression the nucleus accumbens is less active
which is largely responsible for the sense of anhedonia in depression
(Satterthwaite et al., 2015). It is possible that the altered function of the
nucleus accumbens developed in the early stages of life as a response
to poor attachment increases the risk for anhedonia and depression. An
altered reward neurocircuitry may also lead to a vulnerability to addic-
tions. Decreased function in the PFC, which may be caused by attach-
ment insecurity, also has a negative effect on the reward process by de-
creasing activity in the nucleus accumbens (Gold 2015). Given that the
striatum and PFC are both involved in the development of attachment,
it seems possible that insecure attachment may lead to a dysfunction in
these neurocircuits, leading to later development of psychopathology.

EPIGENETICS

Gene expression is the underlying mechanism for all neuroscience

and behavior. It has become increasingly clear that early environment
affects gene expression. This is done through a process of methylation
to various sections of the DNA, causing a difference in the expression
pattern of the DNA. These methylation changes can be reversible or
permanent and can be heritable by offspring (Monk, Spicer, & Cham-
558 CHAMBERS

pagne, 2012). More recently, in utero and postpartum environments

are thought to have a significant effect on the genetic expression of the
offspring, which are evident early in the infant’s life and are sustained
throughout their lives (Fish et al., 2004). These alterations in genetic
expression seem to be affected significantly by the mother’s affective
state in pregnancy (Monk, Spicer, & Champagne, 2012), as well as the
mother’s behaviors toward the offspring in the postpartum (Fish et al.,
2004). These genetic changes are implicated in many important neu-
ropsychiatric processes, including but not limited to BDNF synthesis,
neurotransmitter receptor levels and responsivity, and synaptogenesis
in the offspring (Fish et al., 2004).
Epigenetics have been studied in humans as well as in other mam-
mals. For example, rat pups exposed to various levels of licking and
grooming and nursing postures showed different levels of glucocorti-
coid receptor gene promotors in the hippocampus, which has implica-
tions for cortisol effects on the hippocampus. These genetic alterations
were found as early as the first week of life and the changes were revers-
ible when cross-fostered (Weaver et al. 2004). In humans, McGowan et
al. (2009) found that adult suicide victims with a history of child abuse
had altered hippocampal glucocorticoid receptor genes, demonstrating
that an abusive environment in childhood had a sustained epigenetic
effect on cortisol receptors in the hippocampus. Rat pups exposed to
a stressed and hence neglectful or abusive caretaker in the first week
of life demonstrated altered BDNF gene expression, which lasted into
adulthood (Roth et al., 2009). While these epigenetic changes appear to
be relatively stable throughout life, there is some evidence that they are
potentially reversible in adulthood (Weaver, Meaney, & Szyf, 2006). The
suggestion that these epigenetic changes are both heritable and revers-
ible may have significant implications for treatment in mothers who are
pregnant and postpartum. If a mother has already passed epigenetic
changes to her child, it may be that secure attachment behaviors may
reverse these changes in the infant early on, giving the infant the op-
portunity to change the intergenerational pattern.

SUMMARY

While much work has been done to increase the understanding of the
neurobiology of attachment, we are left with many unanswered ques-
tions that require more research. For instance, can we affect attachment
style later in life? Can insecure attachment be treated? If so, how? In
addition, can psychotherapy be enhanced with direct neurobiological
modification, such as oxytocin or cortisol modulation? It might be in-
 NEUROBIOLOGY OF ATTACHMENT 559

teresting to check both cortisol and oxytocin levels in patients who are
undergoing psychoanalysis or psychodynamic psychotherapy. Would
attachment treatment be a part of the overall treatment to improve oth-
er psychiatric and medical morbidities? Given that we already have
evidence that attachment treatment to postpartum mothers improves
postpartum depression (Hoffman, Marvin, Cooper, & Powell, 2006), it
may be worth considering for other illnesses as well.
Given what we know about the role of oxytocin and cortisol spe-
cifically, are pregnancy and the postpartum periods a natural time to
intervene in mothers with poor attachment? Knowing the importance
of mother’s attachment process for the success of secure attachment
in the infant, it may be that nature has provided us with an additional
sensitive period in the attachment neurocircuitry. This would neces-
sarily lead to significant changes in how we approach women in the
obstetricians’ offices as we would want to check all pregnant mothers
for insecure attachments, oxytocin levels, early childhood trauma, in
addition to the current monitoring of fetal heart rates, etc. Furthermore,
our understanding of insecure attachment in psychiatric and medical
diagnoses may change how we understand and treat these illnesses.

REFERENCES
Ainsworth, M. D. S., & Bell, S. M. (1970). Attachment, exploration, and separation:
Illustrated by the behavior of one-year-olds in a strange situation. Child De-
velopment, 41, 49-67.
Alim, T. N., Lawson, W. B., Feder, A., Iacoviello, B. M., Saxena, S., Bailey, C. R.,
Greene, A. M., & Neumeister, A. (2012). Resilience to meet the challenge of
addiction: Psychobiology and clinical considerations. Alcohol Research: Cur-
rent Reviews, 34(4), 506-515.
Atzil, S., Hendler, T., & Feldman, R. (2011). Specifying the neurobiological basis of
human attachment: Brain, hormones, and behavior in synchronous and intru-
sive mothers. Neuropsychopharmacology, 36, 2603-2615.
Bauman, M. D., Lavener, P., Mason, W. A., Capitanio, J. P., & Amaral, D. G. (2004).
The development of mother-infant interactions after neonatal amygdala le-
sions in rhesus monkeys. Journal of Neuroscience, 24(3), 711-721.
Beebe, B., Lachmann, F., Markese, S., Buck, K. A., Bahrick, L. E., Chen, H., Cohen, P.,
Andrews, H., Feldstein, S., & Jaffe, J. (2012). On the origins of disorganized at-
tachment and internal working models: Paper II. An empirical microanalysis
of 4-month mother-infant interaction. Psychoanalytic Dialogues, 22(3), 352-374.
Bowlby, J. (1977). The making and breaking of affectional bonds. I. Aetiology and
psychopathology in the light of attachment theory. An expanded version of
the fiftieth Maudsley lecture, delivered before the Royal College of Psychia-
trists, 19 November 1976. British Journal of Psychiatry, 130, 201-209.
560 CHAMBERS

Bretherton, I. (1992). The origins of attachment theory: John Bowlby and Mary Ain-
sworth. Developmental Psychology, 28, 759-775.
Campbell, S., & MacQueen, G. (2004). The role of the hippocampus in the patho-
physiology of depression. Journal of Psychiatry and Neuroscience, 29(6), 417-426.
Caspers, K. M., Yucuis, R., Troutman, B., & Spinks, R. (2006). Attachment as an orga-
nizier of behavior: Implications for substance abuse problems and willingness
to seek treatment. Substance Abuse Treatment, Prevention, and Policy, 1, 32-41.
Davies, K. A., Macfarlane, G. J., McBeth, J., Morriss, R., & Dickens, C. (2009). In-
secure attachment style is associated with chronic widespread pain. Pain,
143(3), 200-205.
Debiec, J., & Sullivan, R. M. (2014). Intergenerational transmission of emotional
trauma through amygdala-dependent mother-to-infant transfer of specific
fear. Proceedings of National Academy of Sciences, 111(33), 12222-12227.
DeWall, C. N., Masten, C. L., Powell, C., Combs, D., Schurtz, D. R., & Eisenberger,
N. I. (2012). Do neural responses to rejection depend on attachment style? An
fMRI study. Social Cognitive and Affective Neuroscience, 7(2), 184-192.
Duman, R. (2004). Role of neurotrophic factors in the etiology and treatment of
mood disorders. Neuromolecular Medicine, 5(1), 11-25.
Fan, A. P., Buka, S. L., Kosik, R. O., Chen, Y., Wang, S., Su, T., & Eaton, W. W. (2014).
Association between maternal behavior in infancy and adult mental health: A
30-year prospective study. Comprehensive Psychiatry, 55, 283-289.
Feldman, R. (2010). The relational basis of adolescent adjustment: Trajectories of
mother-child interactive behaviors from infancy to adolescence shape adoles-
cents’ adaptation. Attachment and Human Development, 12(1-2), 173-192.
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards,
V., Koss, M. P., & Marks, J. S. (1998). Relationship of childhood abuse and
household dysfunction to many of the leading causes of death in adults. The
Adverse Childhood Experiences (ACE) study. American Journal of Preventive
Medicine, 14(4), 245-258.
Fish, E. W., Shahrokh, D., Bagot, R., Caldji, C., Bredy, T., Szyf, M., & Meaney, M.
J. (2004). Epigenetic programming of stress responses through variations in
maternal care. Annals of the New York Academy of Science, 1036, 167-180.
Fonagy, P., Steele, H., & Steele, M. (1991). Maternal representations of attachment
during pregnancy predict the organization of infant-mother attachment at
one year of age. Child Development, 62, 891-905.
Fowler, J. C., Groat, M., & Ulanday, M. (2013). Attachment style and treatment com-
pletion among psychiatric inpatients with substance use disorders. American
Journal on Addictions, 22, 14-17.
Freud, S. (1923). The ego and the id. New York; London: Norton.
Giesbricht, G. F., Letourneau, H., Campbell, T. S., & the Alberta Pregnancy Out-
comes and Nutrition Study Team. (2017). Sexually dimorphic and interactive
effects of prenatal maternal cortisol and psychological distress on infant cor-
tisol reactivity. Development and Psychopathology, 29(3), 805-818.
Gold, P. W. (2015). The organization of the stress system and its dysregulation in
depressive illness. Molecular Psychiatry, 20, 32-47.
Gordon, I., Zagoory-Sharon, O., Leckman, J. F., & Feldman, R. (2010). Oxytocin and
the development of parenting in humans. Biological Psychiatry, 68, 377-382.
 NEUROBIOLOGY OF ATTACHMENT 561

Hayes, L. J., Goodman, S. H., & Carlson, E. (2013). Maternal antenatal depression
and infant disorganized attachment at 12 months. Attachment and Human De-
velopment, 15(2), 133-153.
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiol-
ogy of mood and anxiety disorders: Preclinical and clinical studies. Biological
Psychiatry, 49(12), 1023-1039.
Heim, C., Young, L. J., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B.
(2009). Lower CSF oxytocin concentrations in women with a history of child-
hood abuse. Molecular Biology, 14, 954-958.
Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003). Social support
and oxytocin interact to suppress cortisol and subjective responses to psycho-
social stress. Biological Psychiatry, 54(12), 1389-1398.
Hoffman, K. T., Marvin, R. S., Cooper, G., & Powell, B. (2006). Changing toddlers’
and preschoolers’ attachment classifications: The Circle of Security interven-
tion. Journal of Consulting and Clinical Psychology, 74(6), 1017-1026.
Huot, R. L., Plotsky, P. M., Lenox, R. H., & McNamara, R. K. (2002). Neonatal mater-
nal separation reduces hippocampal mossy fiber density in adult Long Evans
rats. Brain Research, 950, 52-63.
Kidd, T., Hamer, M., & Steptoe, A. (2011). Examining the association between adult
attachment style and cortisol responses to acute stress. Psychoneuroendocrino-
logy, 36, 771-779.
Kolb, B., Mychasiuk, R., Muhammad, A., Li, Y., Frost, D. O., & Gibb, R. (2012). Expe-
rience and the developing prefrontal cortex. Proceedings of the National Acade-
my of Sciences, 109(Suppl 2), 17186-17193.
Koulomzin, M., Beebe, B., Anderson, S., Jaffe, J., Feldstein, S., & Crown, C. (2002).
Infant gaze, head, face, and self-touch at 4 months differentiate secure vs.
avoidant attachment at 1 year: A microanalytic approach. Attachment and Hu-
man Development, 4(1), 3-24.
Kristeva, J. (2001). Melanie Klein. New York: Columbia University Press.
Levine A., Zagoory-Sharon, O., Feldman, R., & Weller, A. (2007). Oxytocin during
pregnancy and early postpartum: Individual patterns and maternal-fetal at-
tachment. Peptides, 28, 1162-1169.
Lungwitz, E. A., Stuber, G. D., Johnson, P. L., Dietrich, A. D., Schartz, N., Hanrahan,
B., Shekhar, A., & Truitt, W. A. (2014). The role of the medial prefrontal cortex
in regulating social familiarity-induced anxiolysis. Neuropsychopharmacology,
39, 1009-1019.
Main, M., & Solomon, J. (1990). Procedures for identifying infants as disorganzied/
disoriented during the Ainsworth Strange Situation. In M. T. Greenberg, D.
Cicchetti, & E. M. Cummings (Eds.), Attachment in the preschool years: Theory,
research and intervention (pp. 121-160). Chicago: University of Chicago Press.
McGowan, P. O., Sasaki, A., D’Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., Tu-
recki, G., & Meaney, M. J. (2009). Epigenetic regulation of the glucocorticoid
receptor in human brain associates with childhood abuse. Nature Neurosci-
ence, 1(3), 342-348.
McWilliams, L. A., & Bailey S. J. (2010). Associations between adult attachment rat-
ings and health conditions: Evidence from the National Comorbidity Survey
Replication. Health Psychology, 29(4), 446-453.
562 CHAMBERS

Meredith, P., Ownsworth, T., & Strong, J. (2008). A review of the evidence linking
adult attachment theory and chronic pain: Presenting a conceptual model.
Clinical Psychology Review, 28, 407-429.
Moffett, M. C., Vicentic, A., Kozel, M., Plotsky, P., Francis, D. D., & Kuhar, M. J.
(2007). Maternal separation alters drug intake patterns in adulthood in rats.
Biochemical Pharmacology, 73, 321-330.
Monk, C., Spicer, J., & Champagne, F. A. (2012). Linking prenatal maternal adversity
to developmental outcomes in infants: The role of epigenetic pathways. Deve-
lopmental Psychopathology, 24(2), 1361-1376.
Morgan, J. K., Shaw, D. S., & Forbes, E. E. (2014). Maternal depression and warmth
during childhood predict age 20 neural response to reward. Journal of the Ame-
rican Academy of Child ans Adolescent Psychiatry, 53(1), 108-117.
Murgatroyd, C. A., Pena, C. J., Podda, G., Nestler, E. J., & Nephew, B. C. (2016). Early
life social stress induced changes in depression and anxiety associated neural
pathways which are correlated with impaired maternal care. Neuropeptides,
52, 103-111.
Naber, F., van IJzendoorn, M. H., Deschamps, P., van Engeland H., & Bakermans-
Kranenburg, M. J. (2010). Intranasal oxytocin increases fathers’ observed re-
sponsiveness during play with their children: A double-blind within-subject
experiment. Psychoneuroendocrinology, 35, 1583-1586.
Olavsky, A. K., Telzer, E. H., Shapiro, M., Humphreys, K. L., Flannery, J., Goff, B.,
& Tottenham, N. (2013). Indiscriminate amygdala response to mothers and
strangers after early maternal deprivation. Biological Psychiatry, 74, 853-860.
Pierrehumbert, B., Torrisi, R., Ansermet, F., Borghini, A., & Halfon, O. (2012). Adult
attachment representations predict cortisol and oxytocin responses to stress.
Attachment and Human Development, 14(5), 453-476.
Plant, D. T., Pawlby, S., Sharp, D., Zunszain, P. A., & Pariante, C. M. (2016). Prenatal
maternal depression is associated with offspring inflammation at 25 years: A
prospective longitudinal cohort study. Translational Psychiatry, 6(11), e936, 1-8.
Puig, J., Englund, M. M., Simpson, J. A., & Collins, W. A. (2013). Predicting adult
physical illness from infant attachment: A prospective longitudinal study.
Health Psychology, 32(4), 400-417.
Qiu, A., Anh, T. T., Li, Y., Chen, H., Rifkin-Grabol, A., Broekman, B. F. P., Kwek,
K., Saw, S.-M., Chong, Y.-S., Gluckman, P. D., Fortier, M. V., & Meaney, M. J.
(2015). Prenatal maternal depression alters amygdala functional connectivity
in 6-month old infants. Translational Psychiatry, 5, e508, 1-7.
Quirin, M., Pruessner, J., & Kuhl, J. (2008). HPA system regulation and adult at-
tachment anxiety: Individual differences in reactive and awakening cortisol.
Psychoneuroendocrinology, 33, 581-590.
Radley, J. J., & Sawchenko, P. E. (2011). A common substrate for prefrontal and hip-
pocampal inhibition of the neuroendocrine stress response. Journal of Neu-
roscience, 31(26), 9683-9695.
Rincon-Cortes, M., Barr, G. A., Mouly, A. M., Shionoya, K., Nunez, B. S., & Sullivan,
R. M. (2015). Enduring good memories of infant trauma: Rescue of adult neu-
robehavioral deficits via amygdala serotonin and corticosterone interaction.
Proceedings of the National Academy of Sciences, 112(3), 881-886.
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009). Lasting epigenetic influ-
ence of early-life adversity on the BDNF gene. Biological Psychiatry, 65, 760-
769.
 NEUROBIOLOGY OF ATTACHMENT 563

Ruppenthal, G. C., Arling, G. L., Harlow, H. F., Sackett, G. P., & Suomi, S. J. (1976). A
10-year perspective of motherless monkey behavior. Journal of Abnormal Psy-
chology, 85(4), 341-349.
Sapolsky, R. Krey, L. C., & McEwen, B. S. (1986). The neuroendocrinology of stress
and aging: The glucocorticoid cascade hypothesis. Endocrine Reviews, 7(3),
284-301.
Satterthwaite, T. D., Kable, J. W., Vandekar, L, Katchmar, N., Bassett, D. S., Baldas-
sano, C. F., . . .Wolf, D. H. (2015). Common and dissciable dysfunction of the
reward system in bipolar and unipolar depression. Neuropsychopharmacology,
40, 2258-2268.
Strathearn, L. (2011). Maternal neglect: Oxytocin, dopamine and the neurobiology of
attachment. Journal of Neuroendocrinology, 23(11), 1054-1065.
Strathearn, L., Fonagy, P., Amico, J., & Montague, P. R. (2009). Adult attachment
predicts maternal brain and oxytocin response to infant cues. Neuropsycho-
pharmacology, 34, 2655-2666.
Suomi, S. J., Harlow, H. F., & McKinney, W. T. (1972). Monkey psychiatrists. Ameri-
can Journal of Psychiatry, 128(8), 927-932.
Swain, J. (2008). Baby stimuli and the parent brain: Functional neuroimaging of the
neural substrates of parent-infant attachment. Psychiatry, 5(8), 28-36.
Teicher, M. H., Samson, J. A., Anderson, C. M., & Ohashi, K. (2016). The effects of
childhood maltreatment on brain structure, function, and connectivity. Nature
Reviews, Neuroscience, 17, 652-666.
Tops, M., Koole, S., IJzerman, H. I., & Buisman-Pijlman, F. T. A. (2014). Why social at-
tachment and oxytocin protect against addiction and stress: Insights from the
dynamics between ventral and dorsal corticostriatal systems. Pharmacology,
Biochemistry and Behavior, 119, 39-48.
Vaglio, S. (2009). Chemical communication and mother-infant recognition. Commu-
nicative and Integrative Biology, 2(3), 279-281.
Vela, R. (2014). The effect of severe stress on early brain development, attachment,
and emotions: A psychoanatomical formulation. Psychiatric Clinics of North
America, 37, 519-534.
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma, S., Seckl,
J. R., Dymov, S., Szyf, M., . . . Meaney, M. J. (2004). Epigenitic programming
by maternal behavior. Nature Neuroscience, 7(8), 847-854.
Weaver, I. C. G., Meaney, M. J., & Szyf, M. (2006). Maternal care effects on the hippo-
campal transcriptome and anxiety-mediated behaviors in the offspring that
are reversible in adulthood. Proccedings of the National Academy of Sciences of
the United States of America, 103(9), 3480-3485.
Weisman, O., Zagoory-Sharon, O., & Feldman, R. (2012). Oxytocin administration
to parent enhances infant physiological and behavioral readiness for social
engagement. Biological Psychiatry, 72, 982-989.
Wiest, G., & Brainin, E. (2010). Neuropsychoanalytic findings in a patient with bilat-
eral lesions of the amygdala. Neuropsychoanalysis, 12(2), 193-200.

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