Stress Reduction Correlates with Structural changes in the Amygdala

Britta K. Hölzel; James Carmody; Karleyton C. Evans; Elizabeth A. Hoge; Jeffery A. Duse; Lucas Morgan; Roger K. Pitman; Sara W. Lazar

Disclosures

Soc Cogn Affect Neurosci. 2010;5(1):11-17. 

In This Article

Abstract and Introduction

Abstract

Stress has significant adverse effects on health and is a risk factor for many illnesses. Neurobiological studies have implicated the amygdala as a brain structure crucial in stress responses. Whereas hyperactive amygdala function is often observed during stress conditions, cross-sectional reports of differences in gray matter structure have been less consistent. We conducted a longitudinal MRI study to investigate the relationship between changes in perceived stress with changes in amygdala gray matter density following a stress-reduction intervention. Stressed but otherwise healthy individuals (N = 26) participated in an 8-week mindfulness-based stress reduction intervention. Perceived stress was rated on the perceived stress scale (PSS) and anatomical MR images were acquired pre- and post-intervention. PSS change was used as the predictive regressor for changes in gray matter density within the bilateral amygdalae. Following the intervention, participants reported significantly reduced perceived stress. Reductions in perceived stress correlated positively with decreases in right basolateral amygdala gray matter density. Whereas prior studies found gray matter modifications resulting from acquisition of abstract information, motor and language skills, this study demonstrates that neuroplastic changes are associated with improvements in a psychological state variable.

Introduction

Acute stress initiates hormonal and behavioral responses that enable an organism to make adaptations to environmental demands (Chrousos, 2000). The amygdala has been implicated in both human and animal studies as playing a crucial role during stress responses, including the detection of stressful and threatening stimuli and the initiation of adaptive coping responses (LeDoux, 2000; Hasler et al., 2007). Amygdala-dependent cognition is facilitated during stressful conditions—a useful function for fear-related learning (Shors and Mathew, 1998; Sapolsky, 2003). However, prolonged exposure to stress increases the risk of being affected by a number of mental and physical illnesses (Johnson et al., 1992; Chrousos, 2000; Sapolsky, Romero, & Munck, 2000).

Aberrant amygdala function has been consistently demonstrated across several stress-related psychopathologies. For example, exaggerated amygdala activation has been found in trait anxiety (Stein et al., 2007), post-traumatic stress disorder (PTSD; Rauch et al., 2000; Shin et al., 2004, 2005), social phobia (Birbaumer et al., 1998; Evans et al., 2008; Phan et al., 2006), depression (Drevets et al., 1992; Abercrombie et al., 1998; Sheline et al., 2001; Siegle et al., 2002; Dougherty et al., 2004) and impulsive aggression (Coccaro et al., 2007).

Reports of differences in gray matter structure of the amygdala in pathologic stress conditions have been less consistent (Drevets et al., 2008). While some studies found enlarged amygdala volumes in subjects with affective disorders (Altshuler et al., 1998; Strakowski et al., 1999; Frodl et al., 2002; Lange and Irle, 2004; Weniger et al., 2006), others did not find altered volumes or reported volume reductions (Sheline et al., 1998; Mervaala et al., 2000; Frodl et al., 2003; Frodl et al., 2008). Amygdala findings for patients suffering from PTSD and other anxiety disorders have also been mixed (Gurvits et al., 1996; De Bellis et al., 2000; Gilbertson et al., 2002; Massana et al., 2003; Siegle et al., 2003; Wignall et al., 2004; Milham et al., 2005; Karl et al., 2006; Atmaca et al., 2008; Woon and Hedges, 2008; Hayano et al., 2009). One study with healthy individuals failed to find a correlation between chronic life stress and gray matter volume in the amygdala (Gianaros et al., 2007). These inconsistencies in the literature might result from a number of factors that can impact gray matter measures, such as gender (Wilke et al., 2007), genetics (Meyer-Lindenberg et al., 2006) and volumetry method (Doty et al., 2008).

In contrast to studies of humans, the stress literature with animals is more consistent. Several studies have shown that prolonged stress exposure leads to increases in measures of amygdala structure in rodents (Vyas et al., 2002, 2003; Mitra et al., 2005). Increased dendritic length and increased arborization were reported within the basolateral complex of the amygdala and in the extended amygdala as a result of exposure to chronic immobilization stress (Vyas et al., 2002, 2003). Differences between the results from the human and animal studies might be due to methodological differences. First, the human studies have often investigated amygdaloid volume using MRI, while animal studies have used invasive techniques to look at specific cellular changes within this structure. Second, while most human studies have been cross-sectional investigations of pathologic conditions, the animal studies have been longitudinal, with presumably healthy animals undergoing a controlled chronic stress manipulation. While individual differences are difficult to control and can confound findings in cross-sectional studies, in longitudinal studies these variables remain constant, allowing researchers to selectively vary the factor of interest. However, to our knowledge, no longitudinal neuroimaging studies have examined the influence of stress on amygdala morphology in healthy human beings.

Here, we report a longitudinal MRI study in humans that investigated the correlation between changes in perceived stress and changes in amygdaloid gray matter density following a stress-reduction intervention. Mindfulness-based stress reduction (MBSR; Kabat-Zinn, 1990) is a popular 8-week program developed to help individuals reduce their stress levels and increase psychological well-being. Mindfulness is defined as the non-judgmental awareness of present moment experiences (Kabat-Zinn, 1990). Participants practise meditation techniques designed to increase awareness of present moment experiences such as thoughts, emotions and physical sensations. They also learn to use this awareness in responding more skillfully to stress in their everyday lives. Numerous studies have demonstrated the efficacy of this program in reducing subjective reports of stress and increasing well-being (e.g. Chang et al., 2004; Carmody and Baer, 2008). However, the underlying neural mechanisms of these changes are largely unknown. Since the amygdala has been repeatedly shown to be involved in, and responsive to, an individual's experience of stress, we hypothesized that changes in perceived stress would be associated with changes in amygdala gray matter density. Correlations within the whole brain were also explored on an exploratory basis.

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