Introduction

Spirituality’s constituent dimensions may be examined as having biological correlates that may impact on behavior and health. The human experience of spirituality involves experiences of self-transcendence and connection with something larger than oneself, which may or may not be religious in nature [1,2,3,4]. Stress involves disruptions to individuals’ psychological homeostatic processes and may take multiple forms ranging from major traumatic events to daily hassles [5, 6]. While acute stress responses may have adaptive features that promote protection against outside threats [7,8,9], chronic and repeated stress as well as maladaptive responses to stress may place individuals at elevated risk for multiple mental disorders [8, 10,11,12].

In this article, literature is reviewed on adaptive and maladaptive functions of stress responses, relationships to psychopathology, and underlying neurobiological features. With a focus on constructs related to intrinsic spirituality, as characterized by personal importance and overarching motivation of spirituality in one’s life, this manuscript reviews existing research on the relationship between spirituality and stress. Despite the growth of brain research on spirituality, the neural mechanisms by which spirituality may confer resilience to stress have not been investigated systematically to date. Preliminary functional magnetic resonance imaging (fMRI) data are presented that show a potential neural substrate for how spirituality may influence stress processing. These proof-of-concept findings suggest a role for spirituality in attenuating stress responsivity and regulating emotion during exposures to acute stress.

Spirituality and Religion

Spiritual and religious experiences contribute importantly to many people’s lives [13, 14]. While both spirituality and religion share features that may include experiences of self-transcendence and connection with a higher power and sacred dimension of existence [1,2,3, 15], religion typically refers more to institutionally held sets of beliefs, sacred texts, traditions, and practices contextualized by culture, which may support and cultivate human capacity for spirituality [16,17,18]. While individuals may describe religiosity in terms of personal beliefs about God or a higher power, organizational practices like church attendance, and an adherence to a collective belief system, spirituality is typically associated with more personal, experiential, and relational descriptions of one’s connection to something larger that oneself that may include God or a higher power or may be non-religious (e.g., a spiritual experience involving a connection with nature) [19].

Despite distinctions, many people who consider themselves religious view themselves as spiritual, although not all who consider themselves as spiritual consider themselves as religious [18]. A moderate to high degree of correlation has been observed between religiosity and spirituality (r = 0.4 to 0.9), depending on the populations examined and measures used [20,21,22]. Furthermore, both spirituality and religion may share multiple features that include personal salience of spirituality/religiosity, private contemplative and prayer practices, and related altered states of consciousness, compassionate and altruistic engagement, and virtues and character traits [23,24,25,26].

Stress and Responses

Stressors may have multiple different forms ranging from loss of loved ones to interpersonal abuse, from physical dangers to social isolation, from major traumatic events to daily hassles [27]. Stressors may be experienced as ranging from mild to severe, predictable to unpredictable, and controllable to uncontrollable, and also may occur in differing contexts, while also being acute, repeated, or chronic [28]. While stress may take multiple forms, a central element involves disruption to an organism’s necessary psychological homeostatic processes [29].

Stress responses represent ways in which organisms mobilize to respond to stimuli perceived as harmful and threatening. Typically, these responses may have evolved to protect organisms from outside threats and adapt to environments. However, stress may also trigger insufficient or poorly organized responses, which may lead to allostatic changes and deleterious consequences, mentally and physically [30].

Neurobiology of Stress

The nervous system contributes importantly to coping with stress [6]. The dynamic and widely distributed neural circuitry of the nervous system coordinates and regulates behavioral and allodynamic response systems. Biological pathways of the stress response, particularly within the sympathetic adreno-medullary system (SAM) and hypothalamic-pituitary-adrenal axis (HPA), have been well-documented [31]. Immediately following a stress induction, dynamic interactions between the SAM and HPA systems may initiate “fight-or-flight” responses and induce hypervigilant states, which can optimize detection of outside threats [32, 33].

Certain regions and circuits in the central nervous system contribute vitally to responses to environmental stressors and subsequent experience of distress. Specifically, the amygdala, hippocampus, insula, and cingulate, orbitofrontal, and medial prefrontal cortices are involved in perceiving and appraising stressful stimuli, while the brain stem, hypothalamus, striatum, thalamus, and other limbic regions are implicated in physiological and emotional responses [34,35,36,37]. Thus, a large-scale corticostriatal-limbic circuitry is involved in processing threats, anxiety, and fear and in preparing individuals for fight, flight, or freeze responses. Continuous stimulation of corticostriatal-limbic circuitry by chronic or overwhelming stress may lead to neuroplasticity that underlies maladaptive patterns in the brain and dysregulation of neural circuitry [37, 38•].

Functional and structural MRI studies demonstrate associations between corticostriatal-limbic circuitry and stress, suggestive of its deleterious effects in the brain. Individuals who reported experiencing overwhelming and uncontrollable stressors showed reduced neural responses in the medial prefrontal cortex (mPFC) [39]. In another study, those with long-term occupational stress demonstrated reductions in gray matter volume in the dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) [40]. Among individuals with major depression, those with a history of childhood trauma, compared with those without, showed reduced functional connectivity within a prefrontal-limbic-thalamic-cerebellar circuit [41]. An animal study found that chronic, unpredictable stress was associated with structural atrophy in multiple regions including prelimbic, cingulate, insular, retrosplenial, motor, somatosensory, auditory, and perirhinal/entorhinal cortices, hippocampus, thalamus, dorsomedial striatum, nucleus accumbens, septum, the bed nucleus of the stria terminalis, and several brain stem nuclei [42]. During script-driven imagery experiments, activity in regions that include the mPFC, ACC, superior/middle temporal gyrus, posterior cingulate cortex (PCC), precuneus, thalamus, striatum, midbrain, and cerebellum significantly increased during stress, in comparison with a neutral-relaxing condition [34, 35, 38, 43]. Overall, evidence indicates that corticostriatal-limbic activation increases in response to stress, which may lead to structural atrophy and reduced functional connectivity within this neural circuit as well as impaired behavioral functioning [42, 44].

Large-scale Brain Networks Involved with Stress Responses

During stress responses, regions of the brain do not function in isolation but, rather, are organized into dynamically interacting functional networks, underscoring the need to adopt a systems-level view of brain functioning during stress [45••]. Two such large-scale networks involved in stress responses include the salience network (SN) and the default-mode network (DMN). The SN—composed of the anterior insula, dorsal ACC, and amygdala and temporal poles primarily, but also inclusive of the ventral striatum, hypothalamus, thalamus, substantia nigra, midbrain, precentral gyrus, and temporoparietal junction—is involved in responses to salient environmental stimuli and emotional processing [33, 46]. During acute stress, the SN may underpin a hypervigilant state [47], which may be adaptive by promoting threat detection to immediate dangers and by decreasing sensitivity to other factors like pain, rewards, and non-relevant stimuli [33, 48].

Another primary large-scale network implicated in stress responses is the DMN, whose core regions include the mPFC, PCC, precuneus, and inferior parietal lobule [49, 50]. Although the DMN is associated with self-generated thought and self-referential processing, activity within the DMN also increases during stress exposures [36, 51, 52]. Parallel to increased activation in this network, within-DMN functional connectivity also increases following stress induction [53]. Although the precise role of the DMN during acute stress may be less apparent than that of the SN, the DMN may become activated when self-referential processing is relevant to the acute stressor.

Implications of Stress Responses for Psychopathology

Though many people exposed to acute or chronic stressors do not develop mental disorders [54], a strong link exists between stressors and psychopathology [10, 12]. Diminished tendencies to adapt to stress exposure may lead to specific mental disorders [6]. Acute and chronic stress, therefore, represents a major etiological factor in the development of multiple disorders including post-traumatic stress disorder, depression, substance-use disorders, and behavioral addictions.

Increasing levels of stress are associated with diminished behavioral control, increased impulsivity, and multiple maladaptive behaviors [35, 55]. There may be specific overlaps between brain mechanisms of acute stress in healthy states and mechanisms of psychopathology. For example, exposure to acute stress is associated with poorer integration of the DMN [56], disruptions in reward processing [48], and amygdalar hyperactivity in response to emotional stimuli [47], and similar brain mechanisms have been found in depression [57], addictive disorders [58], and post-traumatic stress disorder [59], respectively.

These disorders exert a great toll on the individual and public health [60]. Thus, the development of improved clinical treatments and preventive interventions that may mitigate the sequelae of psychological stress, and demonstrated efficacy of such interventions within randomized clinical trials, would provide important data that could affect many individuals. Concomitantly, revealing neural mechanisms that underlie the development of vulnerability and resilience to stress and are critical components for developing earlier and more effective interventions for stress-related disorders [61].

Relationships Between Spirituality and Stress

Spirituality has repeatedly been shown to link to resilience [62]. In a community sample, both greater levels of religious commitment and daily spiritual experiences predicted lower levels perceived stress [63]. Spirituality also predicted lower perceived stress among engineering students [64]. Spirituality has been associated with biological markers of resilience to stress. In one study, adults with a higher religious and spiritual commitment had a longer leukocyte telomere length, with shorter telomere length associated with chronic stress and more rapid aging [65•]. Among caregivers, telomere length correlated with level of religiosity [66]. Among family dementia caregivers who were randomly assigned to an eight-week meditation group or relaxing music group, those in the meditation group showed 43% improvement in telomerase activity (necessary for maintaining telomere length) compared with 4% improvement in the relaxing music group [67]. Furthermore, telomerase activity was greater in meditation retreat participants than in wait list controls [68]. Spirituality also appears to moderate the relationship between stress and both waist circumference and insulin resistance, as a study found that psychosocial stress predicted waist and insulin resistance only among individuals with a low level of spirituality [69].

Intervention studies have also found that spirituality was a key factor in reduced clinical symptoms. Researchers found reduced stress and improved emotion regulation and self-control after a mindfulness-based intervention, changes which correlated with increased activity in the ACC and mPFC [70]. Another study found that daily spiritual experiences were a key mechanism by which a mindfulness-based stress reduction (MBSR) intervention reduced levels of chronic stress among healthy adults [71]. In another MBSR study, daily spiritual experience and mindfulness uniquely explained improvements in depressive symptoms [72]. In a meta-analysis comparing effects of meditation-based interventions to active controls on various physiological markers of stress, meditation demonstrated reductions in cortisol, blood pressure, heart rate, C-reactive protein, triglycerides, and tumor necrosis factor-alpha, providing evidence that the practice of meditation may lead to a mitigation of physiological markers of stress across a range of populations [73].

While evidence supports a link between higher levels of spirituality and reduced stress, no research exists on the influence of spirituality during a stress exposure, nor how spirituality may be associated with underlying neural mechanisms during a stress response. Further understanding of neurobiological underpinnings of spirituality’s impact on stress responses could influence intervention development for multiple mental disorders [12, 74].

Preliminary Data on Neural Mechanisms by Which Spirituality May Reduce Stress Responsivity

Previously, we reported on the neural correlates of personalized spiritual and stressful experiences using a script-guided imagery fMRI task [75•]. During brief exposure to spiritual relative to a neutral-relaxing conditions, reduced activity in the inferior parietal lobule was observed, suggesting that this region may contribute importantly to perceptual processing of spatial and self-other representations during self-transcendent states. Compared with stress cues, responses to spiritual cues also showed reduced activity in the thalamus and striatum, regions that have been implicated in sensory and emotional processing and which were activated during the stressful condition, relative to the neutral condition.

While this investigation yielded data about neural responses to spiritual states in comparison with stressful states, the neural mechanisms by which spirituality may confer resilience to stress were not investigated. To address this question, we explored how intrinsic spirituality, a feature characterized by the personal importance and motivation spirituality provides in one’s life [20], related to neural correlates of acute stress. Specifically, we explored correlations between self-reported intrinsic spirituality and neural responses to acute stress using a personalized guided-imagery fMRI protocol. Details of the methodology employed can be found in supplemental materials.

Whole-brain correlation analyses during the stress condition indicated a correlation between intrinsic spirituality scores and reduced activity in corticostriatal-limbic regions including the hippocampus, brain stem, thalamus, ventral striatum, and orbitofrontal and ventromedial prefrontal cortex (Table 1 and Fig. 1; whole-brain-corrected at p < 0.05). Intrinsic spirituality scores correlated with reduced activity in another cluster that included the posterior cingulate and right inferior parietal lobule (Table 1 and Fig. 1; whole-brain-corrected at p < 0.05). The scatter plots in Fig. 1 illustrate negatively correlated patterns in these two clusters. As previous studies have linked increased activation of corticostriatal-limbic regions to higher childhood trauma [76], the findings suggest a neurobiological mechanism by which spirituality may operate to protect against dysregulated stress responses and stress-related mental disorders.

Table 1 Relationship between Intrinsic Spirituality Scale scores and brain activity during the stress condition in N = 24 participants
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Fig. 1
figure 1

a demonstrates a negative correlation between activity in the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), and ventral striatum during the stress condition and decreasing scores on the intrinsic spirituality scale. b demonstrates a negative correlation between activity in a posterior cingulate cluster during the stress condition and decreasing scores on the intrinsic spirituality scale. Scatterplots on the right of a and b depict percent blood-oxygen-level-dependent (BOLD) signal change in this cluster correlated with scores on the Intrinsic Spirituality Scale (ISS). In c, regions are those identified in whole-brain correlations (see Table 1). Blue color indicates negative association between the higher ISS scores and areas where participants show relatively reduced activation. The right side of the brain is on the left

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Conclusion and Future Directions

These proof-of-concept findings show that during a stressful experience, intrinsic spirituality is inversely related to activity in the hippocampus, brain stem, ventral striatum, and thalamus, extending to the orbitofrontal cortex and ventromedial prefrontal cortex, as well as in another cluster comprising the PCC and right inferior parietal lobule. These areas overlap with brain regions that are activated during a stress exposure and have been previously implicated in stress responsiveness, emotional and cognitive processing, and self-referential processing [45, 77, 78]. These novel findings demonstrate that spirituality may neurobiologically buffer stress responses. Given previous research showing a relationship between spiritual tendencies, spritual states, spiritual practices, and perceived stress [63, 72], the results complement other data suggesting how spirituality may influence stress processing.

Implications and Future Directions

The DMN has a role in both stress and spirituality. The present findings indicate that individuals high in intrinsic spirituality may exhibit less stress-related activity in the PCC, inferior parietal lobule, and the mPFC, regions with the DMN. The DMN is deactivated during tasks that are directed externally or involve present-centered attention and activated when attention is internally directed in a self-referential way [49, 50]. Stress exposure increases activity within the DMN [34,35,36, 38•], perhaps because self-referential processing may occur with personally stressful experiences [45••]. Thus, the present results suggest that individuals high in intrinsic spirituality may experience less self-focus during stressful events, although this possibility warrants future direct examination.

The current findings are also consistent with research broadly on contemplative and spiritual traits and practices. A review of studies on spiritual beliefs and practices found that a relative reduction in parietal cortex activation, particularly in the inferior parietal cortex, is reflective of spiritual belief both within and without a context of meditative practice [79]. Among individuals at high and low familial risk for depression, greater personal importance of religion or spirituality in high-risk individuals was associated with decreased DMN connectivity [80]. Deactivation in the middle and posterior cingulate and parietal cortices was part of a functional network involved in personally meaningful spiritual experiences, suggestive of a reduction in self-focus and a less bounded, more expanded sense of self during such experiences [81]. The practice of mindfulness meditation may have a similar decentering effect [82, 83], and reduction in default-mode processing may represent a central neural process in long-term practitioners of meditation [84, 85]. Another study found that long-term meditators relative to novice meditators demonstrated less activity in the PCC during both meditation and while at rest [86]. Similar to findings of DMN functional connectivity in individuals who place high personal importance in religion or spirituality [80], experienced meditators compared with beginners have also exhibited weaker functional connectivity between DMN regions [87, 88]. Considered conceptually, a spiritual orientation to life and the cultivation of one’s spirituality through contemplative practice may go hand in hand, as individuals who are intrinsically motivated by spirituality may be more likely to engage in regular spiritual practice, and vice-versa [89]. Supporting this notion, a high degree of correlation between an intrinsic commitment to spirituality and contemplative practice has been reported [26].

Research suggests, therefore, that decreased activation and functional connectivity in the DMN may represent a neural substrate shared by both experienced meditators and intrinsically spiritual individuals, and the current results suggest that such individuals may experience less self-involvement and identification with mental and emotional stimuli during stress exposures. A more subjectively spacious and diffuse sense of self, which is typically reported during contemplative and spiritual experiences [90, 91], may be important in tolerating emotional distress. Research indicates that PCC-related activation corresponds with a greater propensity to personalize distressing events, suggesting that individuals higher in trait mindfulness or spirituality may have a greater ability to gain greater experiential distance from, and therefore have higher tolerance of, aversive stimuli [92,93,94].

A potentially alternative emotion regulatory pathway warrants consideration. Emotion regulation refers to altering the nature, intensity, and duration of emotional responses through regulatory processes [95]. Substantial research has been conducted on emotion-regulation strategies that involve the control of emotion primarily through cognitive means, utilizing voluntary methods like suppression of emotional expression and cognitive reappraisal [96]. These explicit strategies involve increased activation in prefrontal cortical regions and ACC, which may lead to greater response inhibition and downregulation of subcortical regions like the amygdala [95]. Despite receiving less neuroscientific attention, other emotion-regulation strategies have demonstrated efficacy including those that are more implicit, automatic, and bottom-up [97, 98]. While future studies are warranted, the present results suggest an emotion-regulation pathway that relies less prefrontal cortical activation may be important.

Less prefrontal involvement may suggest a reduction in top-down cognitive control, which is consistent with research on experienced Buddhist meditators during physical and emotionally aversive experiences. Among individuals who received an electric shock, long-term mindfulness practitioners compared with non-practitioners experienced less unpleasantness and exhibited relatively decreased prefrontal cortical activation [99]. Similarly, Zen practitioners who experienced thermal pain exhibited reduced activation relative to non-practitioners in the PFC, amygdala, and hippocampus [100]. Years of experience with Zen, furthermore, correlated with less activation.

Differences between deliberate cognitive regulatory strategies and a more bottom-up, implicit process that may occur in intrinsically spiritual individuals parallel contrasting methods of modifying emotion within the cognitive-behavioral therapy literature, specifically the different approaches that underlie cognitive restructuring and cognitive defusion [101]. While interventions that utilize cognitive restructuring may alter the content of mental and emotional experiences and are largely antecedent-focused, interventions that involve cognitive defusion, including Acceptance and Commitment Therapy and Dialectical Behavior Therapy, alter one’s relationship to stress-provoking events and are thus response-focused. The key difference with cognitive defusion lies in learning to accept one’s inner experience, rather than reflexively focusing on and modifying cognitions [98].

Intrinsically spiritual individuals tend to trust in a higher purpose and intelligence even during ostensibly adverse circumstances [18, 102], which may also lead to greater acceptance of such situations and to less rumination, chronic worry, and other maladaptive forms of coping. Beyond the similarities in neural activation, both intrinsic spirituality and dispositional mindfulness may involve decentering one’s awareness beyond an individual sense of self and accepting rather than resisting one’s experience regardless of perceived valence or utility.

Understanding factors and mechanisms that promote rapid recovery during acutely stressful and adverse situations could inform clinical interventions for patients with stress-related mental disorders. The neural mechanisms involved in adaptive stress responses may include targets of stress exposure in the development of maladaptive states, particularly when neural activation becomes excessive and prolonged [57, 58, 61]. According to a stress-vulnerability view of mental disorders, psychopathology develops from the interaction of stressors and specific vulnerabilities in an individual [11]. For example, neurotransmitters released in the context of stressors may promote alertness necessary for survival during potentially dangerous situations, yet neuroplastic changes in circuitry over time may also lead to overgeneralization. This process has been implicated in disorders like substance-use disorders and post-traumatic stress disorder [44, 58]. Other disorders, including depression and anxiety disorders, also in healthy individuals share neural mechanisms with responses to acute stress, including hyperactivation of and hyperconnectivity in the DMN [103, 104]. Thus, studying neural mechanisms that underlie stress responsiveness may provide valuable insight into how to promote human resilience and to improve treatment of stress-related disorders.

Dysregulation resulting from multiple stressors may lead to changes in allostatic load, providing insight into how cumulative adversity may link to poor mental health [29, 35]. Cumulative adversity is related to greater activation in stress-related circuits during stress induction and structural atrophy in brain regions such as the hippocampus, brain stem, striatum, ACC, and PFC [35, 42, 105]. Factors that attenuate underlying neural mechanisms of the stress response, therefore, may reduce the cumulative effects of chronic stress. Likewise, developing interventions that can reduce behavioral and biological sequelae of psychological stress could have critical importance for prevention and treatment. Identifying imaging markers that detect susceptibility and resilience to adverse effects of stress could also facilitate clinical practice and allow earlier and more targeted interventions [106]. The current findings suggest that spirituality may be related to better mental health outcomes, in part, because of buffering brain activations involved in acute stress responses.

Conclusions

Spirituality has been linked to resilience against stress, and recent experiments are providing insights into neurobiological mechanisms underlying the relationships. The current review and preliminary proof-of-concept findings suggest a possible neural mechanism by which spirituality may buffer deleterious effects of stress. Future research may further delineate neural mechanisms that underlie the largely beneficial relationships between spirituality, mental health, and well-being. The widespread practice of spirituality in a multiplicity of forms across the globe lends real-life relevance to this line of research. Neuroscientific findings also have the potential to be translated into novel preventative and clinical interventions for individuals. Given the global prevalence of stress and related mental disorders, both need and opportunity exist to explore further the ways in which spirituality may promote greater resilience and well-being, and brain mechanisms that underlie these processes.