Kai M. McCormack

Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta)

This study investigated the effects of early exposure to variable parenting style and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine metabolites and examined the role of monoaminergic function in the intergenerational transmission of infant abuse in rhesus monkeys (Macaca mulatta). Forty-three infants reared by their biological mothers and 15 infants that were cross-fostered at birth and reared by unrelated mothers were followed longitudinally through their first 3 years of life or longer. Approximately half of the infants were reared by abusive mothers and half by nonabusive controls. Abused infants did not differ from controls in CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA than low-rejection infants. The abused females who became abusive mothers in adulthood had lower CSF 5-HIAA than the abused females who did not. A similar trend was also observed among the cross-fostered females, suggesting that low serotonergic function resulting from early exposure to high rates of maternal rejection plays a role in the intergenerational transmission of infant abuse.

Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants

A functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene has been associated with variation in anxiety and hypothalamus-pituitary-adrenal (HPA) axis function in humans and rhesus macaques. Individuals carrying the short allele are at a higher risk for developmental psychopathology, and this risk is magnified in short allele carriers who have experienced early life stress. This study investigated the relationship between 5-HTTLPR allelic variation, infant abuse, and behavioral and hormonal responses to stress in rhesus macaques. Subjects were 10 abusive mothers and their infants, and 10 nonabusive mother-infant pairs. Mothers and infants were genotyped for the rh5-HTTLPR, and studied in the first 6 months of infant life. For mothers and infants, we measured social group behavior, behavioral responses to handling procedures, and plasma concentrations of ACTH and cortisol under basal conditions and in response to stress tests. The proportion of individuals carrying the short rh5-HTTLPR allele was significantly higher among abusive mothers than controls. Among mothers and infants, the short allele was associated with higher basal cortisol levels and greater hormonal stress responses in the infants. In addition, infants who carried the short rh5-HTTLPR allele had higher anxiety scores than infants homozygous for the long allele. The rh5-HTTLPR genotype also interacted with early adverse experience to impact HPA axis function in the infants. These results are consistent with those of previous studies which demonstrate associations between serotonergic activity and anxiety and stress reactivity, and add additional evidence suggesting that genetic variation in serotonergic function may contribute to the occurrence of abusive parenting in rhesus macaques and modulate emotional behavior and HPA axis function.

Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques

We investigated the association between variation in parenting style and the offsprings behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels in rhesus monkeys. Study subjects were 25 two-year-old females reared by their biological mothers and 15 same-aged females that were crossfostered at birth and reared by unrelated mothers. Subjects that were rejected more by their mothers in the first 6 months of life engaged in more solitary play and had lower CSF concentrations of 5-HIAA than subjects that were rejected less. The relation between these variables was generally similar in crossfostered and noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with rates of scratching, a behavioural indicator of anxiety. These results suggest that that early exposure to high rates of maternal rejection can result in higher anxiety later in life, and that this effect may be mediated by serotonergic mechanisms. Variation in maternal protectiveness did not affect offspring behaviour and neither protectiveness nor rejection affected CSF levels of HVA and MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play behaviour and avoidance of other individuals, suggesting that individuals with lower CSF MHPG were more fearful and socially phobic than those with higher CSF MHPG. Taken together, these findings suggest that individual differences in anxiety and fearfulness in young rhesus monkeys are accounted for, at least in part, by variation in CSF levels of monoamine metabolites, and that the development of brain monoamine systems, particularly serotonin, can be affected by early exposure to variable maternal behaviour.

Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy

BackgroundEarly adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones.MethodsDiffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity.ResultsWe found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression.ConclusionsThese findings highlight the long-term impact of infant maltreatment on brain white matter structural integrity, particularly in tracts involved in visual processing, emotional regulation, and somatosensory and motor integration. They also suggest a relationship between elevations in stress hormones detected in maltreated animals during infancy and long-term brain white matter structural effects.

Social buffering of stress responses in nonhuman primates: Maternal regulation of the development of emotional regulatory brain circuits

Social buffering, the phenomenon by which the presence of a familiar individual reduces or even eliminates stress- and fear-induced responses, exists in different animal species and has been examined in the context of the mother–infant relationship, in addition to adults. Although it is a well-known effect, the biological mechanisms that underlie it as well as its developmental impact are not well understood. Here, we provide a review of evidence of social and maternal buffering of stress reactivity in nonhuman primates, and some data from our group suggesting that when the mother–infant relationship is disrupted, maternal buffering is impaired. This evidence underscores the critical role that maternal care plays for proper regulation and development of emotional and stress responses of primate infants. Disruptions of the parent–infant bond constitute early adverse experiences associated with increased risk for psychopathology. We will focus on infant maltreatment, a devastating experience not only for humans, but for nonhuman primates as well. Taking advantage of this naturalistic animal model of adverse maternal caregiving, we have shown that competent maternal care is critical for the development of healthy attachment, social behavior, and emotional and stress regulation, as well as of the neural circuits underlying these functions.

The Development of the Hypothalamic–Pituitary–Adrenal Axis in Rhesus Monkeys: Effects of Age, Sex, and Early Experience

We investigated the development of the HPA axis in group-living rhesus monkeys. Forty-three infants were studied from birth through their third year of life; 22 infants were physically abused by their mothers, while 21 infants were not abused. Plasma cortisol levels in basal conditions and in response to a novel environment test were assessed at 6-month intervals. Both basal and stress cortisol increased steadily from 6 to 24 months of age and then dropped. Across all ages, stress cortisol levels were significantly higher than the basal levels. The cortisol responses to stress at 30 and 36 months of age were significantly lower than the responses at all other ages. At most ages there was an inverse relationship between basal and stress cortisol levels. Individual differences in basal cortisol levels were generally stable in the first 2 years and more variable in the third year while the opposite for true for cortisol responses to stress. At the end of the first year, but not later in life, abused infants had higher cortisol levels than controls across the basal and stress conditions. Rates of social interactions with the mother and other group members were positively correlated with basal cortisol levels early in life, and with cortisol responses to stress later in life. Altogether, these results indicate that there are strong individual differences in HPA function, that there is a relationship between basal activity and stress reactivity, and that early abuse has the short-term effect of increasing both basal activity and stress reactivity.

Maternal buffering beyond glucocorticoids: impact of early life stress on corticolimbic circuits that control infant responses to novelty

ABSTRACT Maternal presence has a potent buffering effect on infant fear and stress responses in primates. We previously reported that maternal presence is not effective in buffering the endocrine stress response in infant rhesus monkeys reared by maltreating mothers. We have also reported that maltreating mothers show low maternal responsiveness and permissiveness/secure-base behavior. Although still not understood, it is possible that this maternal buffering effect is mediated, at least partially, through deactivation of amygdala response circuits when mothers are present. Here, we studied rhesus monkey infants that differed in the quality of early maternal care to investigate how this early experience modulated maternal buffering effects on behavioral responses to novelty during the weaning period. We also examined the relationship between these behavioral responses and structural connectivity in one of the underlying regulatory neural circuits: amygdala-prefrontal pathways. Our findings suggest that infant exploration in a novel situation is predicted by maternal responsiveness and structural integrity of amygdala-prefrontal white matter depending on maternal presence (positive relationships when mother is absent). These results provide evidence that maternal buffering of infant behavioral inhibition is dependent on the quality of maternal care and structural connectivity of neural pathways that are sensitive to early life stress.

The development of an instrument to measure global dimensions of maternal care in rhesus macaques (Macaca mulatta)

One of the strongest predictors of healthy child development is the quality of maternal care. Although many measures of observation and self‐report exist in humans to assess global aspects of maternal care, such qualitative measures are lacking in nonhuman primates. In this study, we developed an instrument to measure global aspects of maternal care in rhesus monkeys, with the goal of complementing the individual behavioral data collected using a well‐established rhesus macaque ethogram during the first months postpartum. The 22 items of the instrument were adapted from human maternal sensitivity assessments and a maternal Q‐sort instrument already published for macaques. The 22 items formed four dimensions with high levels of internal reliability that represented major constructs of maternal care: (1) Sensitivity/Responsivity, (2) Protectiveness, (3) Permissiveness, and (4) Irritability. These dimensions yielded high construct validity when correlated with mother–infant frequency and duration behavior that was collected from focal observations across the first 3 postnatal months. In addition, comparisons of two groups of mothers (Maltreating vs. Competent mothers) showed significant differences across the dimensions suggesting that this instrument has strong concurrent validity, even after controlling for focal observation variables that have been previously shown to significantly differentiate these groups. Our findings suggest that this Instrument of Macaque Maternal Care has the potential to capture global aspects of the mother–infant relationship that complement individual behaviors collected through focal observations. Am. J. Primatol. 77:20–33, 2015.

Formative Experiences: Ethological Case Study: Infant Abuse in Rhesus Macaques

INTRODUCTION The use of animal models figures prominently in mental health research and can play an especially important role in our efforts to understand developmental psychopathologies. The vast majority of animal research is conducted with rodents, and a typical approach involves experimentally re-creating behavioral, psychological, or neurobiological conditions that share some similarities with human psychopathologies or their biological substrates. For example, human depression can be experimentally modeled as learned helplessness in rodents, and tested in a forced swimming paradigm. In this task, a rat is placed in a water tank for a given period of time. After the rats efforts at escaping from the tank through swimming have failed, some animals stop struggling, exhibiting behavioral passivity and neuroendocrine changes that share some similarities with those observed in people who suffer from clinical depression. A different approach to modeling human psychopathologies involves identifying similar pathologies that occur naturally in animals. This approach is particularly powerful if conditions similar to human mental disorders are identified in animals that are closest and most similar to us, such as the anthropomorphic primates (i.e., the Old World monkeys and apes). In this chapter, we illustrate this approach by reviewing research on the natural occurrence of infant abuse in nonhuman primate populations, and by discussing how this research can help us understand the causes and developmental consequences of child maltreatment in humans (see also Maestripieri, 1999; Maestripieri & Carroll, 1998a; Sanchez, 2006).

Enhancing Global Research and Education (G-STEM) at Spelman College

Across the USA, there is a disproportionally lower number of African-American women who choose to pursue degrees and careers in the STEM (science, technology, engineering, and mathematics) disciplines. Spelman College, a historically Black college and a global leader in the education of women of African descent, has made strategic and focused efforts to increase the international experiences of all students; however, there are specific challenges related to STEM students. To meet these challenges, the “Enhancing Global Research and Education in STEM” program (G-STEM) was created to provide African-American STEM students with formally mentored international research experiences so that they complete their undergraduate STEM major with transformative worldviews. The G-STEM program has created 15 international partnerships, and offers STEM research placements across the globe. A total of 104 students have participated in this program; and 98% of these students have graduated, or are set to graduate. Of those that have graduated, 42% are currently enrolled in STEM graduate programs (MS or PhD) or health-career graduate programs (medicine, nursing, dentistry). These numbers indicate that the exposure to structured international research experiences may significantly influence a student’s likelihood of graduation and further pursuit of a career in the STEM disciplines. This chapter reviews the development of the G-STEM program, highlighting successful international research partnership typologies, recruitment and retention practices of underrepresented students, and the development of an integrated mentoring program. Student experiences and outcomes are presented, followed by a discussion of the barriers to STEM student participation in international research experiences.