SAN DIEGO, CA — Using cutting edge molecular techniques in rodent models, researchers are dissecting the neurobiological mechanisms impacted by early life adversity. The findings were presented at Neuroscience 2022, the annual meeting of the Society for Neuroscience and the world’s largest source of emerging news about brain science and health.
Childhood adversity, such as abuse, neglect, poverty, lack of housing, or parental loss, can have a lifetime impact on the brain and behavior. Evidence suggests that early life adversity plays an important role in shaping brain development and is associated with abnormalities of several neurobiological systems. Adults with more adverse experiences in early childhood are more likely to have health problems including depression and anxiety; in fact, childhood adversity has been estimated to account for 28% of the risk for later-onset psychiatric disorders. With advances in molecular techniques, neuroscientists are using rodent studies to understand the brain cells and circuits underlying the links between early life adversity, brain development, and later-onset psychiatric disorders.
Today’s new findings show that:
- Sex differences in anxiety disorders may be mediated by changes in the neuropeptide corticotrophin-releasing factor, which is released in response to stress. (Camila Demaestri, New York State Psychiatric Institute)
- A novel connection between a brain area associated with reward and another brain area associated with stress responses may mediate the effects of early life adversity on motivated behavior. (Tallie Z. Baram, University of California, Irvine)
- Stress during puberty results in increased sensitivity to limited resources during pregnancy, and the combination of stresses has a negative impact on maternal behavior and offspring health outcomes (Kathleen E. Morrison, West Virginia University)
- Ketamine has sex-specific effects on behavioral responses to emotional vocalizations in rats that have experienced early life adversity (Jennifer A. Honeycutt, Bowdoin College)
“It is known from epidemiological and clinical work that early life adversity is a major risk factor for psychiatric disorders, and neuroscientists are now figuring out why this is at the level of specific neural circuits,” says Mar Sanchez, a professor at Emory University School of Medicine who studies the effects of early environment on the development of neural circuits controlling stress physiology and emotion regulation. “Importantly for the relevance to humans, the research presented today also focuses on the neurobiological mechanisms that lead to sex-specific effects of early life adversity.”
This research was supported by national funding agencies including the National Institutes of Health and private funding organizations. Find out more about early life adversity and the brain on BrainFacts.org.
Press Conference Summary
- Experiencing early life adversity, such as poverty, abuse, neglect, or violence, can have profound influences on brain development and both physical and mental health later in life.
- Using rodent models, researchers are able to leverage molecular techniques to investigate specific neural pathways impacted by early life adversity, and how early stress is associated with long-lasting changes in the brain and behavior.
Early Life Adversity in Mice Leads to Sex-Differences in Threat Reactivity and Activity of Corticotropin-Releasing Hormone Neurons in the Central Amygdala
Camila Demaestri, cd3206@cumc.columbia.edu, Abstract 221.20
- Activity of corticotrophin-releasing hormone in the central amygdala—an area of the brain associated with responding to threats—may be a sex-specific mechanism for differences in emotional regulation.
- Researchers used a model of early life adversity in which pregnant female mice were not given access to enough resources (i.e., bedding and nesting material). Female mice raised in this environment show increased reactivity to potential threats, a measure of emotional regulation that is relevant to anxiety in humans.
- Cellular techniques revealed increases in the activity of corticotrophin-releasing hormone, a stress-related peptide, in an area of the central amygdala. These changes were associated with enhanced threat responding as a result of early life adversity in females.
A Novel Cell-Specific Pathway Mediates Reward Deficits Following Early-Life Stress
Tallie Z. Baram, tallie@uci.edu, Abstract 398.10
- Disrupted brain reward circuitry is thought to underlie disorders including depression and drug abuse, which are commonly associated with early life adversity.
- In mice, researchers identified a novel GABAergic connection that also expresses the stress peptide corticotrophin-releasing factor. The connection links the basolateral amygdala and nucleus accumbens, two components of the reward circuit. Early life stress increased activity of this connection, resulting in suppressed reward-related behaviors in adult male mice that had experienced early life adversity.
- Exciting this brain projection using chemo- and optogenetic techniques reduced reward-related behaviors in unstressed mice. Inhibiting this connection in adult mice that had experienced early life adversity resulted in normalized reward-related behaviors.
- The findings point to new potential targets for preventing or treating stress-related disorders in humans, such as depression and alcohol and drug use.
Pubertal Stress Increases Sensitivity to the Negative Impact of Subthreshold Limited Resources During Pregnancy on Maternal Behavior and Brain
Kathleen E. Morrison, kathleen.morrison@mail.wvu.edu, Abstract 394.11
- Female mice who experienced both stress during puberty and limited resources during pregnancy interacted differently with their offspring. Mothers who experienced these stresses and their adult female offspring also demonstrated altered stress responses.
- Researchers investigated the molecular mechanisms underlying these behavior changes by looking at gene expression in the paraventricular nucleus of the hypothalamus, a brain region that is involved in maternal behavior and stress responses.
- Results support previous work in mice and humans showing that stress during puberty leads to increased sensitivity to stress during and after pregnancy. The findings provide insight into the complex risk factors that interact throughout the lifespan of females and how they may interact to influence maternal brain and behavior and offspring health.
Early Adversity Alters Affective Processing in Response to 22 kHz Ultrasonic Vocalization Playback Probe With Sex-Specific Responses to Therapeutic Ketamine
Jennifer A. Honeycutt, jhoneycu@bowdoin.edu, Abstract 221.15
- Rats emit ultrasonic vocalizations to communicate emotionally positive and negative social information to other rats in a manner analogous to human facial expressions. Specifically, 22 kHz vocalizations are characterized as aversive, while 55 kHz calls are characterized as positive.
- Male and female rats were exposed to early life adversity and later tested with playback of ultrasonic vocalizations. Females with a history of early life adversity were most influenced by vocalization playback.
- Brain regions associated with emotional processing, including the amygdala and prefrontal cortex, were differentially activated during ultrasonic vocalization playback in ways that were specific to playback type and may be sex-dependent.
- Treatment with ketamine had an anti-anxiety effect in males exposed to aversive vocalizations. In females with a history of early life adversity, ketamine treatment had a deleterious effect.