Summary: New research links childhood adversity with later attention deficits, sleep disruptions, and specific dopamine imbalances in the brain. Focusing on critical developmental windows, scientists found that disrupted care early in life affected males more than females.
In experiments, male mice exhibited poor attention and sleep patterns in adulthood, similar to attention-deficit effects seen in humans. Remarkably, these deficits were reversible with drugs targeting dopamine receptors.
Findings suggest that early-life stress, paired with sleep loss, impacts the anterior cingulate cortex, influencing long-term focus and emotional regulation.
Key Facts:
- Early-life adversity in mice led to lasting attention deficits in males, not females.
- Attention issues were linked to imbalanced dopamine receptors in the anterior cingulate cortex.
- Treatments adjusting dopamine receptors restored attention, even after early critical periods.
Source: Children’s Hospital Boston
New research on the effects of adversity in childhood ties together stress, sleep loss, and attention deficits later in life. It also uncovers some of the underlying brain biology and potential treatment approaches—while revealing a puzzling sex-specific effect.
The lab of Takao Hensch, Ph.D., has long studied time windows during development—commonly termed critical periods—when the brain actively revises its circuits in response to experience.
In a cover story published in Science Translational Medicine, the Hensch Lab now shows that there is an early critical period for the development of attention that is disrupted by adversity—in this case parental neglect.
“We pinpointed the timing and mechanisms underlying attention problems in mice and connected it to human children,” says Hensch, a scientist with the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and Harvard University’s Center for Brain Science.
Hensch and his colleagues modeled early adversity by studying mice whose mothers were distracted and gave erratic care during the critical newborn period. The male offspring, but not the females, showed attention deficits in adulthood, performing poorly on attention-related visual tasks that required making choices.
Aside from being sex-specific, the attention deficits appeared to be driven by disrupted sleep patterns. In fact, sleep loss alone produced the same attention deficits in adult mice that hadn’t experienced neglect.
Hensch sees a parallel in people. “We know that even just a few nights of bad sleep can cause our attention to drop,” he says.
Adversity, stress, sleep loss, and attention
Intriguingly, Hensch’s team identified a brain mechanism underlying the attention deficits: a difference in the balance of dopamine receptors in the anterior cingulate cortex (ACC), which regulates emotions and control of thoughts and actions.
One receptor, D2, was elevated, while another, D4, was reduced—whether the attention deficits resulted from parental neglect or directly from sleep loss in adulthood.
Even more strikingly, the imbalance was reversible with drugs that either suppressed the D2 receptor or stimulated D4. In either case, treatment improved attention well after the critical period was over.
“We think dopamine signaling in the ACC is closely related to attention,” says Hensch.
Finally, the team found that in male mice, early adversity was associated with oxidative stress in the brain and increased levels of a peptide called orexin in the brain’s sleep centers.
“Orexin is an arousal molecule and was associated with sleep loss in males,” says Hensch.
Teasing out sex-specific effects
Why are the effects of early adversity and sleep loss specific to males? Parallel human studies conducted by paper co-authors at the University of Pittsburgh and the University of Calgary confirmed that children (primarily boys) show attention deficits by age 3 to 5.
These findings are consistent with the known higher prevalence of ADHD in boys and further indicate that sex differences emerge soon after early life stress.
Hensch’s lab plans further work to explore what makes females more resilient to adversity, both in mice and in humans.
“We think the female brain may protect itself during unpredictable caregiving conditions by consolidating its circuits faster,” Hensch says. “The down side is that they may then be losing out on later critical periods by maturing too quickly.”
The researchers also want to better understand what causes the dopamine receptor imbalance and what specific cell types in the ACC are affected. Ultimately, the work may lead to ways of helping people with attention deficits.
The study was inspired by earlier human research on the cognitive effects of early adversity.
Over decades in Romania, Charles Nelson, Ph.D., chair in Pediatric Developmental Medicine Research at Boston Children’s, found that neglected babies in orphanages tended to develop lasting cognitive and behavioral dysfunction, including attention deficits. However, transfer to quality foster homes before age two reduced these effects.
“This study offers hope that brain circuitry might be rescuable even after passing through the crucial period,” says Hensch. “We could have an informed chance to intervene.”
About this neurodevelopment and neuroscience research news
Author: Nancy Fliesler
Source: Children’s Hospital Boston
Contact: Nancy Fliesler – Children’s Hospital Boston
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Sleep-sensitive dopamine receptor expression in male mice underlies attention deficits after a critical period of early adversity” by Yuichi Makino et al. Science Translational Medicine
Abstract
Sleep-sensitive dopamine receptor expression in male mice underlies attention deficits after a critical period of early adversity
Early life stress (ELS) yields cognitive impairments of unknown molecular and physiological origin.
We found that fragmented maternal care of mice during a neonatal critical period from postnatal days P2–9 elevated dopamine receptor D2R and suppressed D4R expression, specifically within the anterior cingulate cortex (ACC) in only the male offspring.
This was associated with poor performance on a two-choice visual attention task, which was acutely rescued in adulthood by local or systemic pharmacological rebalancing of D2R/D4R activity.
Furthermore, ELS male mice demonstrated heightened hypothalamic orexin and persistently disrupted sleep. Given that acute sleep deprivation in normally reared male mice mimicked the ACC dopamine receptor subtype modulation and disrupted attention of ELS mice, sleep loss likely underlies cognitive deficits in ELS mice.
Likewise, sleep impairment mediated the attention deficits associated with early adversity in human children, as demonstrated by path analysis on data collected with multiple questionnaires for a large child cohort.
A deeper understanding of the sex-specific cognitive consequences of ELS thus has the potential to reveal therapeutic strategies for overcoming them.
