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Childhood maltreatment tied to hyperactive amygdala response

Childhood maltreatment may be a risk factor for disorders related to and characterized by hyperactive amygdala response, according to findings published in JAMA Psychiatry.

The findings also showed differences in the link between maltreatment and amygdala response to threatening or salient stimuli depending on whether children were exposed to maltreatment in early childhood or in early adolescence.

“Earlier and later childhood exposure may have an opposite association with the amygdala response,” Martin H. Teicher, MD, PhD, of the Developmental Biopsychiatry Research Program, McLean Hospital, and colleagues wrote. “This consideration is critically important because heightened amygdala response has been associated with symptoms of anxiety and inhibition, as in 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.”

Researchers conducted a retrospective cohort study to determine the type and age of childhood maltreatment exposure (measured via the Maltreatment and Abuse Chronology of Exposure [MACE] scale) that was tied to hyperactive and hypoactive amygdala responses in young adulthood.

Using activation and pattern information functional MRI, Teicher and colleagues evaluated bilateral amygdala response to angry and fearful faces compared with neutral faces or shapes. They also used cross-validated artificial intelligence predictive analytics to detect sensitive exposure periods.

Of 202 participants, 150 reported exposure to one or more maltreatment types and 52 reported no exposure to maltreatment. Overall, eight participants with a MACE score of 0 and 51 with a score of one or higher had a history of major depressive disorder (OR = 2.4; 95% CI, 1.05-6.06), whereas eight unexposed participants and 46 with scores of one or higher had a history of anxiety disorder (OR = 2.45; 95% CI, 1.03-6.5).

The investigators reported that the most important risk factors linked to bilateral amygdala response to emotional faces vs. shapes were:

• peer emotional abuse at age 15 (P = .006) and age 13 years (P = .03);
• parental physical abuse at age 3 (P = .046) to 4 years (P = .02); and
• peer physical abuse at age 6 years (P = .01).

“Our finding suggests that maltreatment during the amygdala growth phase is associated with enhanced amygdala volume and emotional ellipse area but with a diminished degree of activation to emotional faces vs. shapes,” Teicher and colleagues wrote. “In contrast, exposure during the pruning phase may be associated with reduced volume, smaller emotional ellipse areas, and increased activation.”

While early childhood exposure to maltreatment was linked to blunted response (beta = –0.17; P < .001), later exposure was linked to augmented response (beta = 0.16; P < .001), according to the study.

“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,” the researchers wrote.

These findings reveal several important areas for future research, Gregory A. Fonzo, PhD, from the department of psychiatry, University of Texas at Austin, wrote in a related comment.

“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,” Fonzo wrote. – by Savannah Demko

Disclosure: Teicher reports grants from the NIMH, the National Institute on Drug Abuse, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the ANS Research Foundation. Please see the study for all other authors’ relevant financial disclosures. Fonzo reports no relevant financial disclosures.