The influence of unpredictable, fragmented parental signals on the developing brain

doi:10.1016/j.yfrne.2019.01.002

Frontiers in Neuroendocrinology

Volume 53, April 2019, 100736

https://doi.org/10.1016/j.yfrne.2019.01.002 Get rights and content

Highlights

•
Mothers provide signals to the developing brain pre-and postnatally.
•
Parental signals profoundly influence a child’s mental and cognitive outcomes.
•
Patterns-specifically predictability-of these signals influence neurodevelopment.
•
Aberrant maternal signal patterns disrupt brain circuit maturation in rodents.
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In humans, unpredictable maternal signals are linked to child mental illness risk.

Abstract

Mental illnesses originate early in life, governed by environmental and genetic factors. Because parents are a dominant source of signals to the developing child, parental signals - beginning with maternal signals in utero - are primary contributors to children’s mental health. Existing literature on maternal signals has focused almost exclusively on their quality and valence (e.g. maternal depression, sensitivity). Here we identify a novel dimension of maternal signals: their patterns and especially their predictability/unpredictability, as an important determinant of children’s neurodevelopment. We find that unpredictable maternal mood and behavior presage risk for child and adolescent psychopathology. In experimental models, fragmented/unpredictable maternal care patterns directly induce aberrant synaptic connectivity and disturbed maturation of cognitive and emotional brain circuits, with commensurate memory problems and anhedonia-like behaviors. Together, our findings across species demonstrate that patterns of maternal signals influence brain circuit maturation, promoting resilience or vulnerability to mental illness.

Section snippets

Introduction: Why parental (especially maternal) signals?

Parental care (particularly that from the mother) is a primary determinant of child survival in humans (Pavard et al., 2005, Sear et al., 2002, Willführ and Gagnon, 2013); so central is this care for the survival of the species, some have argued that the development of parental behavior may be one of the primary forces shaping the evolution of the mammalian brain (c.f. Hrdy, 2000, MacLean, 1990). Sensitive periods in early life largely overlap with developmental stages in which the child is

What maternal signals are salient to brain maturation? Current knowledge and novel principles

A robust empirical literature indicates that pre and postnatal maternal behaviors and emotional states are important determinants of risk for psychiatric disease. For example, building on the foundational work of Bowlby (1950), the importance of a secure attachment relationship, which is scaffolded by sensitive maternal behavior, has widespread implications for cognitive and emotional development (Belsky and Fearon, 2002, Masur et al., 2005, NICHD Early Child Care Research Network, 1999a, NICHD

How do maternal signals influence the developing brain?: insight from experimental models

Brain maturation spans prenatal and early postnatal (infancy) periods, and the sculpting of a number of important brain circuits continues to adulthood. Processes involved in brain circuit-maturation include axonal and dendritic growth, synaptic formation, stabilization and pruning (Garey, 1984, Speh and Moore, 1993, Hoeijmakers et al., 2014, Woo et al., 1997, Maras and Baram, 2012, Neniskyte and Gross, 2017). The perinatal period therefore represents a critical stage of development, rendering

Conclusions and therapeutic opportunities

Cognitive and emotional health, as well as vulnerability to cognitive and emotional disorders, derive from interactions between genes and environment, especially during sensitive developmental periods. We have limited control over genetic susceptibility. Thus, an emphasis on understanding and mitigating early-life environmental factors is warranted.

There is compelling evidence for broad and persisting consequences on mental health outcomes of exposure to early life adversity. Many of the

Competing interests

The authors have no competing interests to declare.

Funding

The authors’ work is supported by the National Institutes of Health (MH-096889; MH73136; NS28912).

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Patterns of sensory inputs early in life play an integral role in shaping the maturation of neural circuits, including those implicated in emotion and cognition. In both experimental animal models and observational human research, unpredictable sensory signals have been linked to aberrant developmental outcomes, including poor memory and effortful control. These findings suggest that sensitivity to unpredictable sensory signals is conserved across species and sculpts the developing brain. The current study provides a novel investigation of unpredictable maternal sensory signals in early life and child internalizing behaviors. We tested these associations in three independent cohorts to probe the generalizability of associations across continents and cultures.
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Early life exposure to unpredictable maternal sensory signals was associated with greater child fearfulness/anxiety in all three cohorts, above and beyond maternal sensitivity and sociodemographic factors. The association between unpredictable maternal sensory signals and child sadness/depression was relatively weaker and did not reach traditional thresholds for statistical significance.
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Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing.
A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings.
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These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.
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There is compelling evidence that the quality of caregiver-child interactions during toddlerhood and the preschool years supports the development of executive function (EF) (Bernier et al., 2010; 2015; 2016; Fay-Stammbach et al., 2014; Geeraerts et al., 2021). Based on such findings, we make the case herein that sensitivity may be one of the most important dimensions of parenting contributing to early EF. In the present article, we will review empirical evidence, integrating findings from a wide range of scientific disciplines – cognitive psychology, neuroscience, and developmental psychopathology – and present theoretical ideas about how two contexts of sensitive caregiving – i.e. sensitivity to distress and non-distress cues - may be contributing differently to hot and cool EF development. Implications for future investigations on the environmental contributors of early EF, and its mechanisms, are discussed.
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Citation Excerpt :
Previous work demonstrated that inconsistent or irregular maternal care, which may be a result of increased maternal anxiety, could have a negative impact on offspring development by providing irregular sensory signals during critical developmental periods (Glynn and Baram, 2019). This may interfere with the amygdala's ability to learn emotional significance of certain stimuli, potentially resulting in altered memory, self-control, and risk of internalizing disorders (Glynn and Baram, 2019). While we did not directly assess the putative molecular mechanisms that may underlie the reported links between maternal anxiety and amygdala alterations in young adulthood, we speculate that the maternal hypothalamic-pituitary-adrenal (HPA) axis may be more active in women with higher anxiety, which may in turn affect the development of the fetal HPA axis (Stephens and Wand, 2012).
The pre- and perinatal environment is thought to play a critical role in shaping brain development. Specifically, maternal mental health and maternal care have been shown to influence offspring brain development in regions implicated in emotional regulation such as the amygdala. In this study, we used data from a neuroimaging follow-up of a prenatal birth-cohort, the European Longitudinal Study of Pregnancy and Childhood, to investigate the impact of early postnatal maternal anxiety/co-dependence, and prenatal and early-postnatal depression and dysregulated mood on amygdala volume and morphology in young adulthood (n = 103). We observed that in typically developing young adults, greater maternal anxiety/co-dependence after birth was significantly associated with lower volume (right: t = −2.913, p = 0.0045, β = −0.523; left: t = −1.471, p = 0.144, β = −0.248) and non-significantly associated with surface area (right: t = −3.502, q = 0.069, <10%FDR, β = −0.090, left: t = −3.137, q = 0.117, <10%FDR, = −0.088) of the amygdala in young adulthood. Conversely, prenatal maternal depression and mood dysregulation in the early postnatal period was not associated with any volumetric or morphological changes in the amygdala in young adulthood. Our findings provide evidence for subtle but long-lasting alterations to amygdala morphology associated with differences in maternal anxiety/co-dependence in early development.
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View full text

The influence of unpredictable, fragmented parental signals on the developing brain

Highlights

Abstract

Section snippets

Introduction: Why parental (especially maternal) signals?

What maternal signals are salient to brain maturation? Current knowledge and novel principles

How do maternal signals influence the developing brain?: insight from experimental models

Conclusions and therapeutic opportunities

Competing interests

Funding

Clin. Psychol. Rev.

Biol. Psychiatry

Arch. Psychiatr. Nurs.

Biol. Psychiatry

Neurobiol. Stress

Physiol. Behav.

Horm. Behav.

Neuron

J. Am. Acad. Child Adolesc. Psychiatry

J. Affect. Disord.

Biol. Psychiatry

Exp. Neurol.

Neurosciann

J. Res. Pers.

Biol. Psychiatry

Trends Neurosci.

J. Acad. Child. Adoles. Psychiatry

Biol. Psychiatry

Neuron

Neurobiol. Stress

Brain Res. Dev. Brain Res.

Cell. Rep.

J. Affect. Disord.

J. Affect. Disord.

Neuroscience

Neuroscience

Fragmentation and unpredictability of early-life experience in mental disorders

Am. J. Psychiatry

Early attachment security, subsequent maternal sensitivity, and later child development: does continuity in development depend upon continuity of caregiving?

Attach. Hum. Dev.

Predictability modulates human brain response to reward

J. Neurosci.

Nonlinear time-series approaches in characterizing mood stability and mood instability in bipolar disorder

Proc. Biol. Sci.

Research into the origins of delinquent behavior

BMJ

Toward understanding how early-life stress reprograms cognitive and emotional brain networks

Neuropsychopharmacology

Abnormal dendritic spines in fragile X knockout mice: maturation and pruning deficits

Proc. Natl. Acad. Sci. USA

Elements of Information Theory

Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels

Transl. Psychiatry

Exposure to unpredictable maternal sensory signals influences cognitive development across species

Proc. Natl. Acad. Sci. USA

Preschool outcomes of children of depressed mothers: role of maternal behavior, contextual risk, and children's brain activity

Child. Dev.

A behavioral paradigm for identifying persons at risk for bipolar depressive disorder: a conceptual framework and five validation studies

J. Abnorm. Psychol.

The role of chaos in poverty and children's socioemotional adjustment

Psychol. Sci.

Altered ventral striatal-medial prefrontal cortex resting-state connectivity mediates adolescent social problems after early institutional care

Dev. Psychopathol.

Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions

J. Child Psychol. Psychiatry

Mutual influences between child emotion regulation and parent-child reciprocity support development across the first 10 years of life: Implications for developmental psychopathology

Dev. Psychopathol.

Emotion regulation: a transdiagnostic perspective on a new RDoC domain

Cognit. Ther. Res.

Intra-individual response variability

Psychol. Bull.

Structural development of the visual system of man

Hum. Neurobiol.

Measuring novel antecedents of mental illness: the Questionnaire of Unpredictability in Childhood

Neuropsychopharmacology

Depression in mothers

Annu. Rev. Clin. Psychol.