Childhood Maltreatment and the Brain:
Key Insights

Megan Brooks

June 28, 2019

Depending on the timing of abuse, children who suffer maltreatment may be at risk for disorders related to hyperactive and hypoactive amygdala response to emotional stimuli as young adults, new research suggests

Investigators found that exposure to maltreatment during early childhood was significantly associated with blunted amygdala response via functional magnetic resonance imaging (fMRI), whereas early teen exposure was significantly associated with heightened amygdala response.

Prepubertal and postpubertal exposure to maltreatment in childhood may have "an opposite association with the amygdala response," the investigators, led by Martin Teicher, MD, PhD, Developmental Biopsychiatry Research Program, McLean Hospital, Belmont, Massachusetts, write.

"This consideration is critically important because heightened amygdala response has been associated with symptoms of anxiety and inhibition, as in [posttraumatic stress disorder] PTSD and phobias, whereas blunted response may be associated with problems with disinhibition and impaired social judgment, such as in substance use and conduct disorders," the authors note.

The study was published online June 26 in JAMA Psychiatry.

Windows of Opportunity

The researchers used the Maltreatment and Abuse Chronology of Exposure (MACE) scale to retrospectively assess type and age of exposure to childhood maltreatment.

They used activation and pattern-information functional magnetic resonance imaging (fMRI) to evaluate bilateral amygdala response to angry and fearful faces (vs neutral faces or shapes). They also used cross-validated artificial intelligence predictive analytics to pinpoint sensitive exposure (age) periods.

Participants included 202 young adults (mean age 23.2 years, 58% women). Overall, 52 (28%) reported no maltreatment in childhood (MACE score, 0); 47 (23%) reported exposure to one type of maltreatment, 38 (19%) to two types of maltreatment, and 65 (32%) to three or more types of maltreatment.

Eight participants (15%) with a MACE score of 0 (no exposure to maltreatment) and 51 (34%) with a MACE score of 1 or higher had a history of major depression (odds ratio [OR], 2.40; 95% confidence interval [CI], 1.05 - 6.06; P = .03). Eight (15%) unexposed participants and 46 (31%) with MACE score 1 or higher had a history of anxiety disorder (OR, 2.45; 95% CI, 1.03 - 6.50; P = .03).

Physical maltreatment suffered before puberty (between ages 3 and 6), and peer emotional abuse suffered after puberty (between ages 13 and 15) were associated with amygdala activation to emotional faces vs shapes.

Prepubertal exposure was associated with blunted response (β = −0.17, P < .001) and postpubertal exposure was associated with augmented response (β = 0.16, P < .001), the researchers report.

"Understanding the role of adversity in different sensitive exposure periods and the potential adaptive significance of attenuated vs enhanced amygdala response may help explain why maltreatment may be a risk factor for many different disorders and foster creation of targeted interventions to preempt the emergence of psychopathology in at-risk youths," the researchers write.

"A key question is whether the presence of multiple sensitive periods provides windows of opportunity when treatments can most effectively correct the consequences of exposure during earlier sensitive periods," they point out.

Biological Impact of Early Stressors

Commenting on the findings in a linked editorial, Gregory Fonzo, PhD, Department of Psychiatry, University of Texas at Austin, notes that "human beings are irrevocably shaped by the developmental environment via biological imprinting of early experience."

This study, writes Fonzo, provides the "first convincing evidence in humans that imprints of early stressful experiences in the adult functional patterns of a key affective brain structure widely implicated in psychopathologic development may be associated with the developmental stage in which the experience(s) occurred."

The findings have implications for maltreatment and psychiatric research, Fonzo notes. 

For example, "careful assessment of not only type and severity but also maltreatment age(s) of experience should be routinely assessed and tracked (including more common but equally stressful and developmentally potent experiences, such as peer bullying or teasing)," he writes.

In addition, "mechanism-focused psychopathologic research should now routinely investigate how maltreatment experiences at different ages uniformly or divergently contribute to variance in key biological and functional outcomes," Fonzo suggests.

He also advocates for the design, funding, and execution of "rigorous and densely sampled" longitudinal studies that would help identify biobehavioral mechanisms that link particular stressful experiences to later adverse health outcomes.

This line of research may yield a "nuanced understanding of how early-life experiences across epochs of brain development and of numerous types, qualities, and frequencies shape neurocircuitry function in ways that ensnare individuals down paths with known undesirable end points," writes Fonzo.

"Of most importance, it may offer key insights into sensitive windows of brain development during which practitioners might intervene in biologically informed ways to course correct the journey toward more favorable destinations," he concludes.

The study had no specific funding. The authors and Fonzo have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online June 26, 2019. Abstract, Editorial

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