Childhood trauma history differentiates amygdala response to sad faces within MDD

Abstract

Objective-Heightened amygdala reactivity to aversive stimuli in major depression is regarded as a core feature of the underlying physiology but individual differences in amygdala response may also arise secondary to persistent changes in limbic function during early neurodevelopment relative to stressors such as childhood trauma. We sought to determine whether heightened amygdala response is a core feature of depression or a general risk factor for psychopathology secondary to early life stress.Method-Twenty unipolar depressed patients with and without a history of significant early life trauma and 16 healthy comparison subjects underwent functional MRI in a cross-sectional study comparing neural response to sad and neutral faces.Results-We observed a robust positive correlation between physical abuse and right amygdala response. A much weaker relationship with other forms of abuse and neglect was also found, suggesting differences between abuse subtypes and amygdala response. Group differences in amygdala response suggest heightened reactivity was not characteristic of persons with depression in general but was true primarily in those with a significant history of abuse.Conclusion-These findings suggest the relationship between childhood trauma and risk for depression is mediated by heightened amygdala response but varies by abuse type. Preliminary evidence for two distinct depression phenotypes based on trauma history was also supported, consistent with differential etiology.Keywords childhood trauma; amygdala; stress sensitization; depression Major depressive disorder is a serious illness estimated to affect 13 to 14 million adults annually and approximately 16% of the U.S. population across the lifespan (Kessler et al., 2003). Furthermore, the considerable social, occupational and workplace related costs associated with impaired function are estimated in the tens of billions of dollars each year (Wang et al., 2006). Childhood maltreatment has emerged as a significant risk factor for the onset of adult depression with over 500,000 documented cases of physical and sexual abuse © 2010 Elsevier Ltd. All rights reserved. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. (Sedlak et al., 2010). Despite the widely appreciated magnitude of the problem, the precise mechanism by which childhood trauma may increase the risk for depression remains unclear. NIH Public AccessExaggerated amygdala response is regarded as a core feature of the underlying physiology of unipolar depression (Price and Drevets, 2010). Imaging studies utilizing both positron emission tomography (PET)...

Interpersonal early‐life trauma alters amygdala connectivity and sustained attention performance

“…Human brain imaging studies subsequently showed that I‐ELT was associated with altered structural integrity in the limbic system (Aas et al., 2012; Andersen et al., 2008; Bremner et al., 1997; Carrion, Weems, & Reiss, 2007; Corbo et al., 2014; Dannlowski et al., 2012; Driessen et al., 2004; Lupien et al., 2011; Tottenham et al., 2010; Veer et al., 2015). Functional imaging studies have further shown that, when processing emotional stimuli (e.g., angry faces), I‐ELT was associated with increased activity in the amygdala (Bremner et al., 2005; Grant, Cannistraci, Hollon, Gore, & Shelton, 2011; Maheu et al., 2010), and with decreased activity of the hippocampus (Bremner et al., 1999; Bremner et al., 2003; Carrion, Haas, Garrett, Song, & Reiss, 2010) and anterior cingulate cortex (Bremner, Vythilingam, Vermetten, Southwick, McGlashan, Nazeer, et al., 2003; Bremner, et al., 2003; Bremner et al., 2004; Mueller et al., 2010). However, these studies have been limited by the consistent use of emotional stimuli, preventing assessments of whether I‐ELT‐related limbic dysfunction potentially impacts more general aspects of cognition.…”

Traumatic Experiences Disrupt Amygdala – Prefrontal Connectivity

“…The scanned fMRI obtained in the previously institutionalized group of children showed enhanced activity in the amygdala in comparison to the control (Tottenham et al, 2011). Similarly, the results of another fMRI study comparing unipolar depressed patients with and without a history of significant early life trauma (n=20) and healthy subjects (n=16) provided a robust positive correlation between physical abuse and right amygdalar responses (Grant et al, 2011). Since childhood trauma is a predisposing factor for PTSD and adult depression, the results of these studies suggest that heightened amygdalar response is a mediator between childhood trauma and the development of trauma-related psychiatric disorders such as PTSD and MDD.…”

Different Types of Childhood Adverse Experiences and Mood Disorders

“…A fMRI study has shown a strong positive correlation between physical abuse and right amygdala response to sad faces in a sample including 20 patients with depression and 16 healthy controls. The heightened amygdala response to sad faces was not a characteristic of individuals with depression, but rather of the subjects with a significant history of maltreatment (Grant et al, 2011).…”