Advertisement
Research Article

Religious Factors and Hippocampal Atrophy in Late Life

  • Amy D. Owen,

    Affiliation: Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • R. David Hayward mail,

    david.hayward@duke.edu

    Affiliations: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America, Neuropsychiatric Imaging Research Laboratory, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Harold G. Koenig,

    Affiliations: Center for the Study of Aging and Human Development, Duke University Medical Center, Durham, North Carolina, United States of America, Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • David C. Steffens,

    Affiliations: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America, Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Martha E. Payne

    Affiliations: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, United States of America, Neuropsychiatric Imaging Research Laboratory, Duke University Medical Center, Durham, North Carolina, United States of America

    X
  • Published: March 30, 2011
  • DOI: 10.1371/journal.pone.0017006

Abstract

Despite a growing interest in the ways spiritual beliefs and practices are reflected in brain activity, there have been relatively few studies using neuroimaging data to assess potential relationships between religious factors and structural neuroanatomy. This study examined prospective relationships between religious factors and hippocampal volume change using high-resolution MRI data of a sample of 268 older adults. Religious factors assessed included life-changing religious experiences, spiritual practices, and religious group membership. Hippocampal volumes were analyzed using the GRID program, which is based on a manual point-counting method and allows for semi-automated determination of region of interest volumes. Significantly greater hippocampal atrophy was observed for participants reporting a life-changing religious experience. Significantly greater hippocampal atrophy was also observed from baseline to final assessment among born-again Protestants, Catholics, and those with no religious affiliation, compared with Protestants not identifying as born-again. These associations were not explained by psychosocial or demographic factors, or baseline cerebral volume. Hippocampal volume has been linked to clinical outcomes, such as depression, dementia, and Alzheimer's Disease. The findings of this study indicate that hippocampal atrophy in late life may be uniquely influenced by certain types of religious factors.

Introduction

Religion is considered an important part of life for many Americans, with 92% reporting a belief in God or a universal spirit, 83% belonging to a religious group, and 59% reporting that they pray at least daily [1]. Research on the neurological processes involved in spiritual beliefs and practices has been growing, but studies examining possible religious or spiritual correlates of structural neuroanatomy have been rare. Specific changes in brain function have been associated with practices including meditation [2], [3], [4], [5], [6], prayer [6], [7], and a variety of religious and spiritual experiences [8], [9], [10], [11]. Several brain regions, including the hippocampus [4], have also been implicated in religious experiences and practice [4], [5], [9], [12], [13], [14], [15], [16]. A small number of studies have found that religious beliefs, practices, and experiences are correlated with the volume of specific brain regions, but the focus has been limited to hyper-religiosity in temporal lobe epilepsy patients [17], [18] and beliefs about the nature of God [19]. The current study extends this research by examining relationships between a broad range of religious factors and hippocampal volumes, including religious group membership, religious practices, and life-changing religious experiences in a sample of older adults.

The hippocampus has several important functions, including spatial, contextual, and episodic learning and memory [20], [21], [22], [23], [24], [25], [26], [27]. The hippocampus may also influence the generation of attention and emotion through connections with the amygdala [28], and moderate cortical arousal and responsiveness through interconnections with the amygdala, hypothalamus, prefrontal cortex, and other areas [28]. Global cerebral atrophy occurs as a result of aging [29], but atrophy rates differ between brain regions [30], [31]. Rates of atrophy for the hippocampus have been found to accelerate during late life [29]. Research indicates that hippocampal volumes may be affected by exposure to elevated glucocorticoids, particularly cortisol, a hormone released in response to stress [32], [33], [34], [35], [36], [37], and that cumulative cortisol exposure may lead to hippocampal atrophy through various pathways [33], [34], [35], [36]. This atrophy has been associated with mental health outcomes, including depression [38], [39], [40], [41], [42], [43] and dementia [44], [45], [46], [47], [48], [49] in later life. Studies have also identified the hippocampus as a brain region potentially involved in religious beliefs and spiritual practices. Initial findings indicate that the hippocampus is activated during meditation [4], and that larger hippocampal volumes are associated with long-term meditation practice [28], [50]. Among certain epilepsy patients, smaller hippocampal volumes have also been associated with hyper-religiosity [18].

Building on evidence from research with meditation and temporal lobe epilepsy, within the context of hypothesized mechanisms of stress and glucocorticoids, this study focused on the potential role of religious factors in hippocampal atrophy. The objective of the present study was to delineate the pattern of prospective relationships between religious factors and hippocampal volume change in a large sample of older adults.

Methods

Ethics statement

The Psychiatry Institutional Review Board of Duke University Medical Center has approved this research. After complete description of the study to the subjects, informed written consent was obtained. All clinical investigation has been conducted according to the principles expressed in the Declaration of Helsinki.

Participants

Participants were 268 men and women aged 58 and over, recruited for the NeuroCognitive Outcomes of Depression in the Elderly (NCODE) study. Details of recruitment for this ongoing longitudinal study are described elsewhere [38]. Participants included two groups, those meeting DSM-IV [51] criteria for major depressive disorder and never-depressed comparison participants. Exclusion criteria included concurrent diagnosis of other psychiatric or neurological illness, significant cognitive impairment, and substance abuse. Requirements for inclusion in the non-depressed group were no evidence of a diagnosis of depression or self-report of neurological or depressive illness. Participants included in these analyses were enrolled between November 1994 and January 2005, and provided two or more sets of MRI measurements.

MRI scans were acquired every two years, and religious, psychosocial, and demographic data were collected at baseline and annually, using a structured psychiatric interview. Length of time between baseline and final available MRI measurement ranged from 2–8 years (mean 4.19).

Religion measures

Religious factors assessed at baseline included (1) frequency of public worship, (2) frequency of private religious activity (prayer, meditation, or Bible study), (3) religious group membership. Religious factors assessed at baseline and annually included (4) born-again status and (5) life-changing religious experiences. Born-again status was assessed with the question, “Are you a born-again Christian?” This was defined as: “A conversion experience, i.e., a specific occasion when you dedicated your life to Jesus.” Participants responding no were assessed for life-changing religious experiences with the question, “Have you ever had any other religious experience that changed your life?” Participants' responses changed over time; thus were categorized as: 1) no born again status or life-changing religious experience, 2) baseline born-again status, 3) new born-again status (i.e., responded no to born-again question at baseline, but yes at a later interview), 4) baseline life-changing religious experience, and 5) new life-changing religious experience. Religious group membership was classified as Catholic, Protestant, Other, or None. Because of the high degree of overlap between Protestant group membership and born-again status, the Protestant group was further divided into born-again and non born-again subcategories.

Image acquisition and analysis

All subjects were imaged with a 1.5-T, whole body MRI system (Signa; GE Medical Systems, Milwaukee, WI) using the standard head (volumetric) radiofrequency coil. Two sets of dual-echo, fast spin-echo acquisitions were obtained: one in the axial plane for morphometry of cerebrum and another in a coronal oblique plane for measurement of the hippocampus. Imaging acquisition parameters [52], volumetry of hippocampus and cerebrum [53], and the GRID software program used in analysis [54] have been described previously. Image analysis was performed at the Duke Neuropsychiatric Imaging Research Laboratory. Total cerebral volume was defined as white matter, gray matter, and cerebrospinal fluid in both cerebral hemispheres.

Covariates

Psychosocial and demographic covariates were included in these analyses, as well as baseline total cerebral volumes as a proxy for head size. Psychosocial factors assessed included stress (global self-reported stress experienced over the past 6 months), social support (a composite variable, primarily level of satisfaction with personal relationships [55], [56]), and depression status (membership in depressed or non-depressed group). Demographic factors assessed included age, sex, self-reported race (dichotomized as white and non-white), years of education, and duration in the study.

Data analysis

Multiple linear regression analyses were conducted to assess relationships between religious variables and hippocampal volume change between baseline and final MRI measurement, controlling for psychosocial and demographic covariates, and baseline total cerebral volume. Left and right hippocampal volumes were calculated separately; volume change measures were computed by subtracting baseline region volume from final region volume.

Results

Descriptive statistics for the study sample are presented in Table 1 (N = 268), including demographics, religious factors, covariates, and brain volumes. Table 2 presents longitudinal regression models of religious factors and covariates on change in left and right hippocampal volumes. Positive model coefficients indicate less atrophy over time. Reported life-changing religious experience at baseline was associated with greater atrophy between baseline and follow-up in the left and right hippocampus (left: b = −0.45, P<.001; right: b = −0.32, P = .012). Born-again Protestant group membership at baseline was associated with greater atrophy in the left and right hippocampus compared with non born-again Protestant group membership (left: b = −0.15, P = .046; right: b = −0.15, P = .050). Catholic group membership (n = 22) (b = −0.22, P = .046) and no religious group membership at baseline (n = 19) (b = −0.28, P = .046) were also associated with greater atrophy in the left hippocampus over time compared with non born-again Protestant group membership.

thumbnail

Table 1. Descriptive statistics (N = 268).

doi:10.1371/journal.pone.0017006.t001
thumbnail

Table 2. Regression Analyses of Religious Factors and Changes in Hippocampal Volume (N = 268).

doi:10.1371/journal.pone.0017006.t002

Discussion

The findings of this study indicate that certain religious factors may influence longitudinal change in hippocampal volume during late life. Greater hippocampal atrophy over time was predicted by baseline identification as born-again Protestants, Catholics, or no religious affiliation, compared with Protestants who were not born-again. Greater hippocampal atrophy was also predicted by reports at baseline of having had life-changing religious experiences. These longitudinal associations were not explained by baseline psychosocial or psychiatric factors (social support, stress, and depression status), demographic factors, duration in the study, or total baseline cerebral volume. Frequency of public and private religious activity did not predict changes in hippocampal volume.

One way of interpreting these findings is within the context of the hypothesized impact of cumulative stress on the hippocampus. While some religious variables have been found to be associated with positive mental health [57], [58], [59], other religious factors may be a source of stress [19], [60], [61], [62], [63], [64]. Research on biological pathways by which stress may influence hippocampal volumes has primarily explored neuronal death [32], [65], [66], [67], [68], [69], decreased neurogenesis [70], [71], [72], [73] and dendritic retraction [74], [75]. The glucocorticoid vulnerability hypothesis proposes that chronic stress alters the hippocampus by elevating levels of glucocorticoids, which in turn extends the time period during which the hippocampus is susceptible to damage from various sources [37]. The measure of stress used in this study was not correlated with changes in hippocampal volume, possibly due to the fact that it captured acute rather than cumulative stressors. Research indicates that relationships between stress and hippocampal volume likely operate at the level of cumulative rather than acute stress, leaving the cumulative stress framework a plausible interpretation of these results.

Greater hippocampal atrophy was observed longitudinally in this study among born-again Protestants, Catholics, and those reporting no religious affiliation, compared with non born-again Protestants. These findings may reflect potential cumulative stress associated with being a member of a religious minority. Though religious factors have been associated with positive mental health [59], [76], [77], studies have shown members of religious minority groups may also experience stressors related to these group affiliations [78], [79], [80]. Greater hippocampal atrophy was also found to be longitudinally associated with reported life-changing religious experiences. Spiritual experiences not easily interpreted within an existing cognitive framework or set of religious beliefs have been shown in previous research to be detrimental to subjective well-being [81]. Such experiences have the capacity to produce doubts regarding previously unquestioned convictions, potentially inducing cumulative stress even if the experience was subjectively positive. If the experience prompts a change in religious groups, existing social networks may also be disrupted. Thus, as possible sources of cumulative stress, both minority religious group membership and life-changing religious experiences may contribute to conditions that are deleterious for hippocampal volume.

These findings can be interpreted within the framework of previous studies identifying the hippocampus as a brain region potentially involved in religious or spiritual beliefs and practices. Using PET and MRI data, studies of meditation indicate that the hippocampus has been found to be activated during meditative states, compared to control states [4], [16]. Structurally, among meditation practitioners (compared to non-practitioner controls), significantly larger volumes [28], [50] and higher gray matter concentrations [28] have been found in regions activated during meditation, including the right hippocampus. The current study did not find an association between change in hippocampal volume and frequency of spiritual activities, possibly reflecting the potential of varying spiritual practices to affect neuroanatomy differently. Research on temporal lobe epilepsy indicates that features of hyper-religiosity may be positively associated with hippocampal atrophy, but findings are mixed [17], [18]. Associations found in the current study between life-changing religious experiences (but not frequency of religious practices) and hippocampal atrophy are consistent with a previous finding that the content and intensity of religious experiences (but not frequency of religious activities), differed between regular churchgoers and temporal-lobe epilepsy patients with hyper-religious features [82], symptoms linked to hippocampal atrophy in some studies [18].

The relatively large sample size, longitudinal design, and the assessment of a range of religious and psychosocial factors are strengths of this study. Limitations include the geographically and religiously constrained nature of the sample (largely Southeastern Protestant Christians), as well as the small sample size of participants reporting a life-changing religious experience. The image acquisition used in this study is also limited to the technology available when it began in 1994, which was retained throughout the study in order to have comparable scans for longitudinal analyses. Future research on qualitative aspects of life-changing religious experiences could provide critical insight into the particular features of religion underlying the observed relationships with hippocampal volume. In addition, comprehensive cognitive testing in future studies could help determine the role of cognitive performance in both late life religious experiences and hippocampal volume.

This study is among the first to examine religious and spiritual correlates of structural neuroanatomy, identifying several understudied factors associated with hippocampal atrophy. Religious factors, including religious group membership and life-changing religious experiences, but not frequency of public and private religious practices, were longitudinally associated with hippocampal atrophy. Atrophy in this region has important clinical implications, having been identified as a marker of late life mental health problems such as depression [38], [39], [40], [41], [42], [43] and dementia [44], [45], [46], [47], [48], [49]. These results may reflect an impact of cumulative stress on hippocampal volume. Mechanisms for these results, such as the elucidation of potential glucocorticoid stress pathways leading to atrophy, need to be more clearly identified, making the interpretation of these findings necessarily speculative. Future research exploring neuroanatomical changes in late life should not overlook the potential impact of religious factors, which remain relevant for a substantial proportion of the US population.

Acknowledgments

The authors acknowledge Ms. Cynthia Key of the Duke Neuropsychiatric Imaging Research Laboratory for hippocampal measures.

Author Contributions

Conceived and designed the experiments: ADO RDH MEP DCS. Performed the experiments: ADO RDH. Analyzed the data: RDH. Contributed reagents/materials/analysis tools: DCS MEP. Wrote the manuscript: ADO RDH MEP HGK DCS.

References

  1. 1. Pew Forum on Religion and Public Life (2008) U. S. Religious Landscape Survey.
  2. 2. Herzog H, Lele VR, Kuwert T, Langen K-J, Kops ER, et al. (1990) Changed pattern of regional glucose metabolism during yoga meditative relaxation. Neuropsychobiology 23: 182–187.
  3. 3. Jevning R, Anand R, Biedebach M, Fernando G (1996) Effects on regional cerebral blood flow of transcendental meditation. Physiology & Behavior 59: 399–402.
  4. 4. Lazar SW, Bush G, Gollub RL, Fricchione GL, Khalsa G, et al. (2000) Functional brain mapping of the relaxation response and meditation. NeuroReport 11: 1581–1585.
  5. 5. Newberg A, Alavi A, Baime M, Pourdehnad M, Santanna J, et al. (2001) The measurement of regional cerebral blood flow during the complex cognitive task of meditation: a preliminary SPECT study. Psychiatry Research: Neuroimaging 106: 113–122.
  6. 6. Newberg A, Pourdehnad M, Alavi A, D'Aquili EG (2003) Cerebral blood flow during meditative prayer: preliminary findings and methodological issues. Perceptual and Motor Skills 97: 625–630.
  7. 7. Schjødt U, Stødkilde-Jørgensen H, Geertz AW, Roepstorff A (2008) Rewarding prayers. Neuroscience Letters 443: 165–168.
  8. 8. Azari NP, Missimer J, Seitz RJ (2005) Religious experience and emotion: Evidence for distinctive cognitive neural patterns. International Journal for the Psychology of Religion 15: 263–281.
  9. 9. Beauregard M, Paquette V (2006) Neural correlates of a mystical experience in Carmelite nuns. Neuroscience Letters 405: 186–190.
  10. 10. Borg J, Andree B, Soderstrom H, Farde L (2003) The serotonin system and spiritual experiences. American Journal of Psychiatry 160: 1965–1969.
  11. 11. Newberg AB, Wintering NA, Morgan D, Waldman MR (2006) The measurement of regional cerebral blood flow during glossolalia: A preliminary SPECT study. Psychiatry Research: Neuroimaging 148: 67–71.
  12. 12. Britton WB, Bootzin RR (2004) Near-death experiences and the temporal lobe. Psychological Science 15: 254–258.
  13. 13. Dewhurst K, Beard AW (1970) Sudden religious conversions in temporal lobe epilepsy. British Journal of Psychiatry 117: 497–507.
  14. 14. Han S, Mao L, Gu X, Zhu Y, Ge J, et al. (2008) Neural consequences of religious belief on self-referential processing. Social Neuroscience 3: 1–15.
  15. 15. Harris S, Kaplan JT, Curiel A, Bookheimer SY, Iacoboni M, et al. (2009) The neural correlates of religious and nonreligious belief. Public Library of Science ONE 4: 1–9.
  16. 16. Lou HC, Kjaer TW, Friberg L, Wildschiodtz G, Holm S, et al. (1999) A 15O-H2O PET study of meditation and the resting state of normal consciousness. Hum Brain Mapp 7: 98–105.
  17. 17. van Elst LT, Krishnamoorthy ES, Baumer D, Selai C, von Gunten A, et al. (2003) Psychopathological profile in patients with severe bilateral hippocampal atrophy and temporal lobe epilepsy: evidence in support of the Geschwind syndrome? Epilepsy Behav 4: 291–297.
  18. 18. Wuerfel J, Krishnamoorthy ES, Brown RJ, Lemieux L, Koepp M, et al. (2004) Religiosity is associated with hippocampal but not amygdala volumes in patients with refractory epilepsy. J Neurol Neurosurg Psychiatry 75: 640–642.
  19. 19. Kapogiannis D, Barbey AK, Su M, Krueger F, Grafman J (2009) Neuroanatomical variability of religiosity. Public Library of Science ONE 4: 1–7.
  20. 20. Jarrard LE (1995) What does the hippocampus really do? Behav Brain Res 71: 1–10.
  21. 21. Bast T (2007) Toward an integrative perspective on hippocampal function: from the rapid encoding of experience to adaptive behavior. Rev Neurosci 18: 253–281.
  22. 22. Tulving E, Markowitsch HJ (1998) Episodic and declarative memory: role of the hippocampus. Hippocampus 8: 198–204.
  23. 23. Squire LR (1992) Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99: 195–231.
  24. 24. Morris RG (2006) Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas. Eur J Neurosci 23: 2829–2846.
  25. 25. Burgess N, Maguire EA, O'Keefe J (2002) The human hippocampus and spatial and episodic memory. Neuron 35: 625–641.
  26. 26. McEwen BS (2001) Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann N Y Acad Sci 933: 265–277.
  27. 27. McEwen BS (1999) Stress and hippocampal plasticity. Annu Rev Neurosci 22: 105–122.
  28. 28. Holzel BK, Ott U, Gard T, Hempel H, Weygandt M, et al. (2008) Investigation of mindfulness meditation practitioners with voxel-based morphometry. Soc Cogn Affect Neurosci 3: 55–61.
  29. 29. Raz N, Lindenberger U, Rodrigue KM, Kennedy KM, Head D, et al. (2005) Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. Cereb Cortex 15: 1676–1689.
  30. 30. Resnick SM, Pham DL, Kraut MA, Zonderman AB, Davatzikos C (2003) Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain. J Neurosci 23: 3295–3301.
  31. 31. Scahill RI, Frost C, Jenkins R, Whitwell JL, Rossor MN, et al. (2003) A longitudinal study of brain volume changes in normal aging using serial registered magnetic resonance imaging. Arch Neurol 60: 989–994.
  32. 32. Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7: 284–301.
  33. 33. McEwen BS (1998) Protective and damaging effects of stress mediators. N Engl J Med 338: 171–179.
  34. 34. Davidson RJ, Jackson DC, Kalin NH (2000) Emotion, plasticity, context, and regulation: perspectives from affective neuroscience. Psychol Bull 126: 890–909.
  35. 35. Lupien SJ, de Leon M, de Santi S, Convit A, Tarshish C, et al. (1998) Cortisol levels during human aging predict hippocampal atrophy and memory deficits. Nat Neurosci 1: 69–73.
  36. 36. Lupien SJ, Schwartz G, Ng YK, Fiocco A, Wan N, et al. (2005) The Douglas Hospital Longitudinal Study of Normal and Pathological Aging: summary of findings. J Psychiatry Neurosci 30: 328–334.
  37. 37. Conrad CD (2008) Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis. Rev Neurosci 19: 395–411.
  38. 38. Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, et al. (2000) Hippocampal volume in geriatric depression. Biol Psychiatry 48: 301–309.
  39. 39. Caetano SC, Hatch JP, Brambilla P, Sassi RB, Nicoletti M, et al. (2004) Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression. Psychiatry Research: Neuroimaging 132: 141–147.
  40. 40. Hickie I, Naismith S, Ward PB, Turner K, Scott E, et al. (2005) Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression. British Journal of Psychiatry 186: 197–202.
  41. 41. O'Brien JT, Lloyd A, McKeith I, Gholkar A, Ferrier N (2004) A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. Am J Psychiatry 161: 2081–2090.
  42. 42. Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: A meta-analysis. American Journal of Psychiatry 161: 598–607.
  43. 43. Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: A meta-analysis of MRI studies. American Journal of Psychiatry 161: 1957–1966.
  44. 44. Gosche KM, Mortimer JA, Smith CD, Markesbery WR, Snowdon DA (2002) Hippocampal volume as an index of Alzheimer neuropathology: findings from the Nun Study. Neurology 58: 1476–1482.
  45. 45. Mortimer JA, Gosche KM, Riley KP, Markesbery WR, Snowdon DA (2004) Delayed recall, hippocampal volume and Alzheimer neuropathology: findings from the Nun Study. Neurology 62: 428–432.
  46. 46. Steffens DC, Payne ME, Greenberg DL, Byrum CE, Welsh-Bohmer KA, et al. (2002) Hippocampal volume and incident dementia in geriatric depression. Am J Geriatr Psychiatry 10: 62–71.
  47. 47. Collins ML, Nelson CA, editors. (2008) Handbook of developmental cognitive neuroscience. Cambridge, MA: MIT Press.
  48. 48. Jack CR Jr, Petersen RC, Xu Y, O'Brien PC, Smith GE, et al. (2000) Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology 55: 484–490.
  49. 49. Hampel H, Bürger K, Teipel SJ, Bokde ALW, Zetterberg H, et al. (2008) Core candidate neurochemical and imaging biomarkers of Alzheimer's disease. Alzheimer's and Dementia 4: 38–48.
  50. 50. Luders E, Toga AW, Lepore N, Gaser C (2009) The underlying anatomical correlates of long-term meditation: larger hippocampal and frontal volumes of gray matter. NeuroImage 45: 672–678.
  51. 51. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders. Washington, DC: Author.
  52. 52. Steffens DC, Byrum CE, McQuoid DR, Greenberg DL, Payne ME, et al. (2000) Hippocampal volume in geriatric depression. Biological Psychiatry 48: 301–309.
  53. 53. Payne ME, Fetzer DL, MacFall JR, Provenzale JM, Byrum CE, et al. (2002) Development of a semi-automated method for quantification of MRI gray and white matter lesions in geriatric subjects. Psychiatry Research: Neuroimaging 115: 63–77.
  54. 54. MacFall JR, Byrum CE, Parashos I, Early B, Charles HC, et al. (1994) Relative accuracy and reproducibility of regional MRI brain volumes for point-counting methods. Psychiatry Res 55: 167–177.
  55. 55. Hays JC, Steffens DC, Flint EP, Bosworth HB, George LK (2001) Does social support buffer functional decline in elderly patients with unipolar depression? American Journal of Psychiatry 158: 1850–1855.
  56. 56. George L, Blazer D, Hughes D, Fowler N (1989) Social support and the outcome of major depression. The British Journal of Psychiatry 154: 478–485.
  57. 57. Miller WR, Thoresen CE (2003) Spirituality, religion, and health: an emerging research field. American Psychologist 58: 24–35.
  58. 58. Ai AL, Peterson C, Tice TN, Bolling SF, Koenig HG (2004) Faith-based and secular pathways to hope and optimism subconstructs in middle-aged and older cardiac patients. Journal of Health Psychology 9: 435–450.
  59. 59. Koenig HG, Larson DB (2001) Religion and mental health: evidence for an association. International Review of Psychiatry 13: 67–78.
  60. 60. Krause N, Chatters LM, Meltzer T (2000) Negative interaction in the church: insights from focus groups with older adults. Review of Religious Research 41: 510–533.
  61. 61. Krause N, Ellison CG, Wulff KM (1998) Church-based emotional support, negative interaction, and psychological well-being: findings from a national sample of Presbyterians. Journal for the Scientific Study of Religion 37: 725–741.
  62. 62. Pargament KI, Koenig HG, Tarakeshwar N, Hahn J (2001) Religious struggle as a predictor of mortality among medically ill elderly patients: a 2-year longitudinal study. Arch Intern Med 161: 1881–1885.
  63. 63. Ai AL, Pargament K, Kronfol Z, Tice TN, Appel H (2010) Pathways to postoperative hostility in cardiac patients: mediation of coping, spiritual struggle and interleukin-6. Journal of Health Psychology 15: 186–195.
  64. 64. Pargament KI (2002) The bitter and the sweet: An evaluation of the costs and benefits of religiousness. Psychological Inquiry 13: 168–181.
  65. 65. Muller MB, Lucassen PJ, Yassouridis A, Hoogendijk WJ, Holsboer F, et al. (2001) Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus. Eur J Neurosci 14: 1603–1612.
  66. 66. Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4: 141–194.
  67. 67. Landfield PW, Waymire JC, Lynch G (1978) Hippocampal aging and adrenocorticoids: quantitative correlations. Science 202: 1098–1102.
  68. 68. Sapolsky RM (2005) The influence of social hierarchy on primate health. Science 308: 648–652.
  69. 69. Uno H, Tarara R, Else JG, Suleman MA, Sapolsky RM (1989) Hippocampal damage associated with prolonged and fatal stress in primates. J Neurosci 9: 1705–1711.
  70. 70. Gold PW, Goodwin FK, Chrousos GP (1988) Clinical and biochemical manifestations of depression. Relation to the neurobiology of stress (1). N Engl J Med 319: 348–353.
  71. 71. Joels M, Karst H, Alfarez D, Heine VM, Qin Y, et al. (2004) Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus. Stress 7: 221–231.
  72. 72. Pham K, Nacher J, Hof PR, McEwen BS (2003) Repeated restraint stress suppresses neurogenesis and induces biphasic PSA-NCAM expression in the adult rat dentate gyrus. Eur J Neurosci 17: 879–886.
  73. 73. Rosenbrock H, Koros E, Bloching A, Podhorna J, Borsini F (2005) Effect of chronic intermittent restraint stress on hippocampal expression of marker proteins for synaptic plasticity and progenitor cell proliferation in rats. Brain Res 1040: 55–63.
  74. 74. Magarinos AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: comparison of stressors. Neuroscience 69: 83–88.
  75. 75. Watanabe Y, Gould E, McEwen BS (1992) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588: 341–345.
  76. 76. Idler EL, McLaughlin J, Kasl S (2009) Religion and the quality of life in the last year of life. Journal of Gerontology B: Psychological Sciences and Social Sciences 64B: 528–537.
  77. 77. Koenig HG, George LK, Titus P (2004) Religion, spirituality, and health in medically ill hospitalized older patients. Journal of the American Geriatrics Society 52: 554–562.
  78. 78. Abbotts J, Williams R, Ford G, Hunt K, West P (1997) Morbidity and Irish Catholic descent in Britain: An ethnic and religious minority 150 years on. Social Science & Medicine 45: 3–14.
  79. 79. Model S, Lin L (2002) The cost of not being Christian: Hindus, Sikhs and Muslims in Britain and Canada. International Migration Review 36: 1061–1092.
  80. 80. O'Reilly D, Rosato M (2008) Religious affiliation and mortality in Northern Ireland: Beyond Catholic and Protestant. Social Science & Medicine 66: 1637–1645.
  81. 81. Byrd KR, Lear D, Schwenka S (2000) Mysticism as a predictor of subjective well-being. International Journal for the Psychology of Religion 10: 259–269.
  82. 82. Trimble M, Freeman A (2006) An investigation of religiosity and the Gastaut-Geschwind syndrome in patients with temporal lobe epilepsy. Epilepsy Behav 9: 407–414.