Influence of age and sex on presymptomatic phases of neurodegenerative diseases: Focus on multiple sclerosis and Alzheimer's disease.

Accumulating evidence indicates that effects associated with maltreatment in the mother’s childhood may be transmitted to her own child, including effects on the child’s social adaptation and mental health (). One proposed mechanism through which maternal childhood maltreatment may influence offspring mental health is through its effects on infant stress-response systems, including the infant HPA-axis and brain development (; ). Therefore, tracing the potential pathways of intergenerational transmission entails, in part, increasing our understanding of the links between the mother’s childhood maltreatment and the early development of infant stress response systems. To address this need, the central objective of the Mother-Infant Neurobiological Development (MIND) study has been to identify neurobiological mechanisms contributing to the intergenerational transmission of the effects of maltreatment from mother to child. Of particular interest is how maternal childhood abuse and neglect experiences are linked to alterations in the infant hypothalamic-pituitary-adrenal (HPA) axis and stress-sensitive brain regions, including the amygdala and hippocampus. This paper reviews the findings emerging from the MIND study and proposes a Developmental Salience Model of Threat to account for the pattern of findings and to guide further work in the field. As part of her ground-breaking contributions to attachment research, Mary Main set an important example for the field by integrating observations of behavior in other species into her understanding of attachment behaviors among human infants. In the work presented here on the intergenerational transmission of the effects of maltreatment, findings from other species regarding stress, attachment, and neurobiological development have also been very relevant for understanding unanticipated aspects of our current findings. In the body of this paper, we describe the findings emerging from the study regarding intergenerational transmission of adversity and consider the new questions they pose regarding how threat may be experienced over the first two years of life. We consider these emerging questions in the context of two contrasting literatures, first, studies of the effects associated with threat versus derivation among older human children and adults and, second, randomized studies of the effects of maternal low nurturance/unpredictability and maternal aversive behavior among neonatal rodent pups. We then offer a Developmental Salience Model of Threat, in which threat of lack of care is more salient to infant stress response systems, preceding developmentally the salience of threat of attack or injury. This model is discussed in the last section of the paper. From an attachment point of view, questions about the early development of infant stress-response systems are embedded in a larger question that has yet to be addressed in depth by attachment research, namely, what are the qualities of early affective communication and stress-regulation that characterize disorganized attachment relationships as they emerge over the first year of life? Only three studies to date have assessed mother- infant interaction in the first six months of life in relation to infant attachment disorganization (; ; ) and none have assessed aspects of the infant stress-response system. In addition, presented short-term longitudinal data on mother-infant interaction assessed two months before the assessment of attachment disorganization. Thus, while a few pioneering studies have been done, much more work is needed, particularly among high-risk families. We do not address this question directly in the work presented here, but we raise it to place the work reviewed here in the context of gaps in the current body of attachment theory and research. We expect that future analyses of the 15-month attachment data from the MIND study will more directly inform this question.