For better or worse, human beings are irrevocably shaped by the developmental environment via biological imprinting of early experience. The brain mechanisms by which stressful early experiences, such as childhood maltreatment, lead to later mental and physical health challenges have been extensively sought yet remain elusive. This work has largely used structural and functional magnetic resonance imaging to retrospectively characterize alterations present in exposed individuals. A prominent finding has been exaggerated reactivity of the amygdala to threatening stimuli.1 The amygdala is crucial for the detection of salient environmental stimuli and the engagement of autonomic and behavioral responses (eg, mounting a fear response and adaptively responding to a potential threat).2 Because amygdala functional abnormalities are frequently detected across psychiatric disorders,3,4 investigators have honed in on this medial temporal lobe structure and its threat detection processes as being a potential mechanism of this maltreatment-induced maladaptive developmental trajectory toward later psychiatric difficulties.5 However, not all maltreated individuals develop a mental disorder, and individuals with the same mental disorder may manifest psychopathologic symptoms via different biologic mechanisms as a function of maltreatment history. Teicher and colleagues6 have proposed that maltreatment produces distinct neurobiological phenotypes via a cascade of experience-dependent plasticity inductions that drive developmental neurocircuitry modifications of processes serving an evolutionarily adaptive function. For example, sensitization of amygdala responses to threat cues may be near-term adaptive to the child by facilitating detection and response to potential threats in a hostile and chaotic environment, but this may come at the cost of longer-term maladaptation (eg, chronic hypervigilance) when the environment shifts and the sensitization is no longer functional. Such plasticity inductions may then promote psychopathologic development nonspecifically via selective enhancement or diminishment of environmental context–dependent brain processes. This plastic brain adaptation interaction with other disease-determining factors broadly explains how diverse mental health outcomes, from resilient to disordered,6 can result from maltreatment, including diagnoses with ostensibly divergent phenotypes and symptoms (eg, increased emotional reactivity and hyperactivity of the amygdala to threat cues, as in anxiety and posttraumatic stress disorders,3 and behavioral disinhibition and blunted amygdala reactivity to threat, as in externalizing disorders).7
Fonzo GA. Childhood Maltreatment and Amygdala Threat Reactivity in Young Adults—Timing Is Everything. JAMA Psychiatry. 2019;76(8):781–782. doi:10.1001/jamapsychiatry.2019.0432
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