Fragmentation and unpredictability of early-life experience in mental disorders

Abstract

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety.

Conflict of interest statement

The authors report no financial relationships with commercial interests.

Figures

FIGURE 1. Analyses of the Fragmentation and Unpredictability of Maternal Behavior in a Naturalistic Setting in Humansa

a The bar graph in panel A depicts the behavioral profile of a mother with fragmented care behavior compared with the behavioral profile of a mother with a more complex behavioral pattern. Fragmented care is defined as a large number of simple, two-component behaviors (e.g., smiling and then holding up a toy), compared with complex behavioral patterns of three or more components. A mother with nonfragmented behavior exhibits a large number of complex (four or more components) behavioral sequences. Panel B depicts single temporal patterns from a mother interacting with her 12-month-old child while exhibiting nonfragmented care. The left top subpanels show that the temporal pattern is initiated by the behavior “no toy in hand,” has four behavioral elements (e.g., look at infant, coo at infant, touch infant, pick up toy), and is repeated 13 times. This pattern consists of two hierarchical levels (smaller patterns connected to form larger patterns). The smaller pattern, “new toy speech,” is repeated 15 times without being part of the larger pattern. Both the length and level are considered measures of complexity. The frequency and temporal ordering of the events evolving into patterns are depicted in the upper right subpanel, and the sequence of events is depicted in the bottom subpanel. (Unpublished data, available upon request from the authors.)

FIGURE 2. Fragmentation of Rodent Maternal Behavior Provoked by Adversitya

a The fragmentation resulted in little change in total care, and the provoked adversity was the limiting of the bedding and nesting materials in the cage. Panel A depicts a typical cage and a cage with limited bedding, which leads to maternal stress and fragmented nurturing behaviors. The grid charts in Panel B represent the activity of a dam in a typical cage (control condition) and in the limited bedding cage during two matched observation periods. Each grid depicts one dam’s activity during 15 1-minute epochs (starting at the top left corner); individual blocks are color-coded to represent the dam’s activity during each epoch (blue=nursing; red=licking/grooming; yellow=more than one behavior). The grid demonstrates the consecutive epochs of the same behavior (consistent) in the control condition and the short epochs of each behavior type (fragmentation) in the limited nesting cage. Also apparent is the rapid alteration among nurturing behavior types (inconsistency, unpredictability) in the limited bedding cage. Panel C depicts fragmented behavior not associated with reduced time of individual caring behaviors; the total licking/grooming duration among dams in the limited bedding cages was comparable to that of dams in the control condition. The bar graph in Panel D depicts the augmented number of epochs when the dam was away from the nest, an additional measure of fragmentation. Differences between the two conditions reached statistical significance (p<0.05). Adapted from Brunson et al. (52). Copyright © 2005. Society for Neuroscience. Used with permission. Adapted from Rice et al. (57). Copyright © 2008 Endocrinology. Used with permission.

FIGURE 3. Effect of Consistency and Fragmentation of Pre- and Postnatal Maternal Emotional States on Neuropsychiatric Outcomea

a Mean scores on the Mental Development Index of the Bayley Scales of Infant Development for 186 1-year-old children were divided into four groups according to maternal emotional states. Presence of depressive symptoms (71) was assessed both before and after delivery in the mothers. Significant difference between groups, p<0.001 (two-way analysis of covariance). Adapted from Sandman et al. (71). Copyright © 2012 Psychological Science. Used with permission.

FIGURE 4. Fragmented Maternal Care During Early Post-natal Life Leading to Impoverished Dendritic Trees in Hippocampal Area CA1 Neuronsa

a A biocytin-filled cell from a middle-aged rat with fragmented maternal care (Frag) during postnatal days 2–9 (right) is depicted. Fragmentation of maternal care was elicited as described in Figure 2. The comparison with a neuron from a matched control section (left) illustrates the reduction in total dendritic length and in dendritic arborization following fragmented care. Scale bar=80 microns. Adapted from Brunson et al. (52). Copyright © 2005. Society for Neuroscience. Used with permission.