good of others (benevolence). While we cannot claim that participants were directly
cultivating agape in the full theological sense, the practices represent secular or semi-
secular operationalizations of love-oriented contemplative traditions.

This conclusion has important implications for both science and theology. For
science, it demonstrates that practices traditionally considered 'spiritual' produce
measurable biological effects, thereby validating the importance of including such
practices in health research. For theology, it provides empirical support for the long-held
belief that love is not merely an abstract spiritual quality but a transformative power with
real effects in the physical world. The body, as Paul declared, is a temple—and the
transcriptional data suggest that the practices of love help maintain that temple at the
molecular level.

**Conclusion 2: CTRA Profile Shifts Favorably with Love-Associated Practices**

The second major conclusion is that practices cultivating love and compassion are
associated with a favorable shift in the CTRA gene expression profile, characterized by
enhanced antiviral/interferon gene expression and reduced stress biology. The CTRA,
identified by Cole and colleagues as a conserved transcriptional response to social
adversity, represents the genome's preparation for threat—increased inflammation for
wound healing, decreased antiviral immunity as resources are redirected. The present
study found evidence of the opposite pattern, suggesting that love-oriented practices may
reverse this threat response at the molecular level.

This finding has profound implications for understanding how love operates
biologically. From a theological perspective, agape love—characterized by unconditional
positive regard, selfless concern for others, connection to the divine source of all love,
and trust in providential care—would be expected to create states of profound safety and belonging. When one experiences oneself as loved by God and loving toward others, the chronic vigilance and threat-monitoring that characterize modern life may be reduced. The genome, sensing this state of safety, may downregulate threat-oriented programs and upregulate programs oriented toward growth, connection, and flourishing.

The specific genes showing consistent effects support this interpretation. The interferon-stimulated genes (IFI27, RSAD2, IFIT1, IFIT3, MX2) are components of the antiviral response, protecting against respiratory and other viral infections. Their upregulation suggests enhanced immune vigilance against pathogenic threats that do not involve immediate physical danger. Meanwhile, the downregulation of FKBP5, a key regulator of HPA axis sensitivity, suggests reduced stress reactivity. Together, these patterns describe a genome that is alert but not alarmed—vigilant against genuine threats while not wasting resources on chronic stress responses.

**Conclusion 3: Agape Love May Have Biological Correlates in Immune Gene Expression**

The third major conclusion is that agape love, as theologically defined and operationalized through contemplative practices, appears to have specific biological correlates in immune gene expression patterns. While the study cannot claim to have measured agape directly—this would require validated instruments specifically assessing unconditional love, divine connection, and self-transcendent concern for others—the interventions examined share core features with the theological construct. The consistent transcriptional signature observed across diverse practices suggests a common biological pathway through which love-oriented states influence immune function.
Augustine's concept of caritas provides a theological framework for understanding these findings. For Augustine, caritas represented rightly ordered love—love directed first toward God as the supreme good, then flowing outward toward neighbor and self in proper proportion. Disordered love (cupiditas) involved excessive attachment to temporal goods, producing anxiety and ultimately illness. The transcriptional signature observed in this study—enhanced immune vigilance, reduced stress biology—represents precisely the biological pattern Augustine would have predicted for the person whose love is properly ordered. Caritas, it seems, may have a molecular signature.

Thomas Aquinas's understanding of charity as the 'form' of all virtues—that which gives them their life and orientation toward the good—also resonates with these findings. If charity truly animates and perfects human functioning, we would expect it to have effects throughout the person, including the biological dimension. The transcriptional changes observed may represent one manifestation of charity's perfecting influence, optimizing immune function just as it optimizes moral and spiritual functioning. The finding that love affects gene expression thus supports an integrated, holistic anthropology in which spiritual and physical dimensions of the person are intimately connected.

**Conclusion 4: QPNIT Provides a Viable Framework for Scientific Study of Love**

The fourth major conclusion is that the Quantum Psychoneuroimmunotheology framework provides a viable and productive theoretical lens for investigating love scientifically without reducing it to mere biology or abandoning empirical rigor. QPNIT enabled this study to honor both the transcendent theological dimensions of agape and the
immanent biological mechanisms through which it may operate. The framework's core
proposition—that spiritual practices influence gene expression through
psychoneuroimmunological pathways—received empirical support from the findings.

This methodological contribution addresses a significant gap in the existing
literature. Previous studies of spirituality and health have often lacked robust theoretical
frameworks, simply correlating religious attendance or self-reported spirituality with
health outcomes without specifying mechanisms. Theological scholarship on love,
meanwhile, has rarely engaged with biological evidence, treating love as a purely
spiritual reality independent of the body. QPNIT offers a bridge between these traditions,
enabling researchers to formulate testable hypotheses about the biological effects of
spiritual practices while maintaining theological integrity and avoiding reductionism.

The framework's inclusion of quantum biology, while more speculative, opens
possibilities for future investigation of consciousness-matter interactions that might
mediate spiritual effects. While the present study did not directly test quantum
mechanisms, the finding that love-oriented states influence gene expression is consistent
with the QPNIT proposition that consciousness interacts with biological systems in ways
not fully captured by classical mechanistic models. Future research might explore
whether quantum coherence in biological systems plays any role in mediating the effects
observed.

**Conclusion 5: Integration of Theology and Biology Enriches Understanding**

The fifth and final major conclusion is that the integration of theological and
biological perspectives enriches our understanding of human flourishing in ways that
neither discipline could achieve alone. The theological tradition offers profound insights
into the nature, importance, and cultivation of love that have been refined over millennia
of reflection, practice, and pastoral experience. Biology provides mechanisms,
measurements, and empirical methods that can test theological claims and reveal new
dimensions of how love operates in the world.

This integrative vision aligns with the Christian theological anthropology
articulated by Thomas Aquinas, in which the human person is understood as a unity of
soul and body, form and matter, spiritual and physical dimensions. For Aquinas, spiritual
realities are never purely abstract—they are always also embodied realities with physical
correlates and effects. The transcriptional signature of agape love represents one
manifestation of this embodiment: the writing of love, as it were, into the very molecules
that regulate our health, our immunity, and our interactions with the microbial world.

The study also demonstrates that empirical investigation of spiritual constructs
need not be reductionistic. The finding that love affects gene expression does not mean
that love is 'nothing but' gene expression any more than the finding that beauty activates
certain brain regions means that beauty is 'nothing but' neural activity. Rather, the
biological correlates of love reveal another dimension of its reality—another language in
which love speaks, another medium through which it operates. The integrated perspective
offered by QPNIT honors both the irreducible spiritual nature of love and its embodied,
biological expressions.

**Contributions to Knowledge**

This dissertation makes significant contributions to knowledge across multiple
disciplines, advancing understanding at the intersection of theology, biology, and health
sciences. Table 6.1 summarizes these contributions and their significance for each field.
<table><caption>**Table 6.1 summary of key contributions across five disciplinary domains**</caption><thead><tr><td>Discipline</td><td>Contribution</td><td>Significance</td></tr></thead><tbody><tr><td>Theology</td><td>First empirical evidence for biological correlates of agape love at gene expression level; demonstration that sacred constructs can be operationalized and studied scientifically</td><td>Supports embodied, incarnational theology; validates contemplative practices; provides new language for theology-science dialogue</td></tr><tr><td>Psychoneuroimmunology</td><td>Extension of CTRA research to positive states; identification of specific genes responding to love/compassion practices; meta-analytic synthesis across multiple datasets</td><td>Expands PNI beyond stress/adversity focus; identifies potential biomarkers; advances understanding of positive psychological influences on immunity</td></tr><tr><td>Mind-Body Medicine</td><td>Molecular mechanisms underlying MBI effects; specific transcriptional targets; comparison across multiple intervention types</td><td>Provides targets for intervention optimization; supports evidence base for integrative medicine; guides development of precision contemplative</td></tr></tbody></table>
<table><thead><tr><th></th><th></th><th>interventions</th></tr></thead><tbody><tr><td>Social Genomics</td><td>Application of social genomics methods to spiritual constructs; integration of theological interpretation with genomic data</td><td>Expands scope of social genomics to include spiritual/religious experiences; demonstrates feasibility of genomic approaches to sacred phenomena</td></tr><tr><td>Interdisciplinary Studies</td><td>Development and testing of QPNIT framework; demonstration of productive theology-science integration; methodology for studying spirituality empirically</td><td>Models interdisciplinary dialogue; provides theoretical foundation for future research; advances methods for empirical spiritual research</td></tr></tbody></table>

*Note.* Table 1 summarizes the key contributions of the dissertation across five disciplinary domains, identifying both the specific contribution and its broader significance for each field.

## Contributions to Theology

For theological scholarship, this dissertation contributes the first empirical evidence that agape love, cultivated through contemplative practice, has measurable biological effects at the level of gene expression. This finding supports an embodied, incarnational theology that takes seriously the unity of spiritual and physical dimensions
of human existence. The Christian tradition has always affirmed that the Word became
flesh, that salvation encompasses the whole person, and that the resurrection involves
bodily transformation. The transcriptional signature of love provides molecular evidence
for this embodied spirituality, showing that spiritual practices leave marks not only on the
soul but on the genome.

The study also demonstrates that theological constructs can be operationalized
and examined empirically without reducing their meaning to measurable components.
While the study did not directly measure agape in its full theological sense, it examined
practices that share core features with agape cultivation—compassion, self-
transcendence, orientation toward others' good—and found consistent biological effects.
This approach provides a model for future empirical theology, showing how sacred
constructs can be studied scientifically while preserving their theological integrity.

***Contributions to Psychoneuroimmunology***

For psychoneuroimmunology, the study extends CTRA research in a crucial
direction: from focusing primarily on adversity and its negative effects to examining
whether positive states, particularly those associated with love, can actively reverse
stress-related transcriptional patterns. Previous CTRA research had demonstrated that
loneliness, grief, and chronic stress produce unfavorable gene expression profiles. This
study provides evidence that the opposite is also true—that practices cultivating love and
compassion may produce favorable profiles characterized by enhanced antiviral
immunity and reduced stress biology.

The identification of specific genes showing consistent effects across datasets—
IFI27, RSAD2, IFIT1, IFIT3, MX2 among interferon genes; FKBP5 among stress-related
genes—provides concrete targets for future research and potential biomarkers for
assessing intervention effects. These genes could be monitored in prospective studies to
evaluate the biological impact of love and compassion interventions, providing more
precise outcome measures than self-report alone.

**Contributions to Mind-Body Medicine**

For mind-body medicine, the study contributes mechanistic insight into how contemplative practices produce health benefits, identifying specific transcriptional pathways that respond to these interventions. This knowledge could inform the development of optimized interventions, the identification of individuals most likely to benefit, and the monitoring of treatment response. The finding that multiple different practices—mindfulness, yoga, relaxation response—produce convergent transcriptional effects suggests common underlying mechanisms that could be targeted more precisely in future interventions.

**Contributions to Interdisciplinary Scholarship**

For interdisciplinary scholarship, the study demonstrates that productive dialogue
between theology and science is possible and fruitful. Rather than the conflict or
independence models that have often characterized theology-science relations, this study
exemplifies an integration model in which both disciplines contribute essential insights.
Theology provides the conceptual framework for understanding love as a transformative
power; biology provides the methods and measurements for detecting its effects. The
QPNIT framework offers a model for how such integration might proceed more broadly,
potentially applicable to other theological constructs such as hope, forgiveness, and
gratitude.
**Implications for Practice**

The findings of this study have significant implications for practice across multiple domains, from clinical healthcare to pastoral care to public health policy. These implications flow from the central finding that love-oriented practices produce measurable, favorable changes in immune gene expression.

**Healthcare and Clinical Practice**

For healthcare practitioners, the findings support the integration of love and compassion-based interventions as adjunctive therapies, particularly for patients experiencing conditions involving chronic inflammation or stress-related immune dysregulation. The specific transcriptional targets identified—enhanced interferon response, reduced FKBP5 expression—could serve as biomarkers for treatment response, enabling more precise assessment of intervention effects. Conditions that might particularly benefit include cardiovascular disease (where inflammation plays a key role), autoimmune disorders (where immune regulation is disrupted), depression (increasingly understood as involving inflammatory processes), and chronic stress-related conditions.

Beyond specific interventions, the findings support a more holistic approach to patient care that addresses relational and spiritual dimensions alongside physical symptoms. The therapeutic relationship itself, characterized by compassion and unconditional positive regard, may have biological effects analogous to those observed in contemplative practice. Healthcare systems might consider integrating pastoral care, chaplaincy services, and contemplative practice programs as components of comprehensive treatment, particularly for patients facing serious or chronic illness.
The findings also have implications for healthcare provider well-being. The same
love and compassion practices that benefit patients may help prevent burnout and
compassion fatigue among clinicians by modulating their own stress-related gene
expression. Healthcare organizations might offer contemplative training programs for
staff as part of wellness initiatives, potentially reducing turnover and improving care
quality.

Pastoral Care and Spiritual Direction

For pastoral care providers, chaplains, and spiritual directors, the study provides scientific support for traditional spiritual practices aimed at cultivating love. The finding that such practices produce measurable biological changes may encourage individuals who might otherwise dismiss spiritual formation as merely subjective or 'all in the mind.' Pastoral care providers can confidently commend practices of loving-kindness meditation, contemplative prayer, and compassion cultivation as beneficial for both spiritual and physical well-being, supported by evidence at the molecular level.

The findings also suggest specific practices that might be emphasized in spiritual
direction. The interventions showing transcriptional effects involved sustained, regular
practice of attention, compassion, and self-transcendence. Spiritual directors might guide
directees toward establishing consistent contemplative practice, emphasizing that the
benefits accumulate through regular engagement rather than occasional intense
experiences. The biological evidence provides additional motivation for perseverance in
practice even when immediate subjective effects are not apparent.
## Religious Communities

Religious communities have long emphasized the centrality of love in spiritual life—'the greatest of these is love' (1 Corinthians 13:13). This study provides empirical validation for these emphases while suggesting specific practices that may be particularly effective in cultivating the biological signature of love. Communities might develop structured programs that systematically train members in loving-kindness meditation, compassion practices, intercessory prayer, and other love-oriented contemplative disciplines.

The findings also have implications for community life more broadly. If love has biological effects, then the quality of relationships within religious communities may affect members' health at the molecular level. Communities characterized by genuine compassion, forgiveness, and mutual care may provide a 'transcriptional environment' conducive to flourishing, while communities marked by judgment, exclusion, or conflict may undermine the very health benefits that spiritual practice is intended to provide. This understanding adds urgency to Jesus's command that his followers love one another (John 13:34)—not only for spiritual reasons but for biological ones as well.

## Public Health Policy

At the population level, the findings suggest that policies promoting social connection, community engagement, and contemplative practice may have measurable biological benefits. Public health initiatives might incorporate love and compassion training as components of stress reduction and health promotion programs, particularly for populations experiencing chronic adversity. School-based programs teaching
emotional regulation and compassion could potentially influence developmental trajectories of immune function, with lifelong health implications.

The findings also support policies that strengthen social bonds and reduce isolation. If loneliness produces unfavorable gene expression (as CTRA research demonstrates) while love produces favorable expression (as this study suggests), then addressing the epidemic of loneliness becomes not merely a social concern but a public health priority. Urban planning that promotes community interaction, workplace policies that support work-life balance, and social services that connect isolated individuals to supportive communities all take on new significance in light of these findings.

## Recommendations

Based on the findings, limitations, and implications of this study, specific recommendations are offered for researchers, practitioners, religious and spiritual leaders, and policymakers.

### Recommendations for Researchers

Future researchers should build on this work through several approaches. First, prospective longitudinal studies are needed that directly measure changes in gene expression before and after love and compassion interventions, with adequate control groups and randomization. Such studies should include validated measures of love, compassion, and related constructs to enable correlation with transcriptional changes and mediation analysis. Second, researchers should explore whether specific components of interventions—such as loving-kindness meditation versus general mindfulness, or devotional versus secular practices—produce distinct transcriptional signatures, enabling optimization of intervention design.
Third, research is needed to examine potential moderators of the relationship
between love practices and gene expression, including individual differences in
spirituality, attachment style, religious background, and genetic polymorphisms affecting
stress responsivity. Fourth, mechanistic studies should examine mediating pathways,
including changes in autonomic nervous system activity, HPA axis function, and
inflammatory markers, to clarify the biological cascade through which love influences
gene expression. Fifth, qualitative research should explore participants' experiences of
love and compassion practices to enrich quantitative findings with phenomenological
insight.

Researchers should also develop better measures of agape love specifically, as
distinct from compassion, attachment love, or general positive affect. Such measures
would enable more precise testing of theological hypotheses about the effects of agape.
Finally, replication studies are essential to confirm the patterns observed in this
secondary analysis with new datasets specifically designed to test the study's hypotheses.

Recommendations for Practitioners

Healthcare practitioners should consider integrating evidence-based mind-body
interventions into treatment plans, particularly for conditions involving chronic
inflammation, stress-related immune dysregulation, or frequent viral infections.
Practitioners should also attend to the relational context of care, recognizing that the
quality of therapeutic relationships may influence biological outcomes through
mechanisms similar to those examined in this study. Training in compassionate
communication and presence may enhance treatment effectiveness across specialties.
Mental health practitioners should consider contemplative practices as adjunctive interventions for depression, anxiety, and stress-related disorders, given the emerging evidence for inflammatory involvement in these conditions. Practitioners working with chronically ill populations should explore partnerships with chaplains, spiritual directors, and contemplative teachers to provide comprehensive care addressing biological, psychological, and spiritual dimensions.

## Recommendations for Religious and Spiritual Leaders

Religious and spiritual leaders should consider incorporating insights from this research into their teaching and pastoral care. The finding that love has biological effects provides a powerful point of contact with contemporary scientific worldviews and may help communicate the relevance of spiritual practice to skeptical or scientifically-oriented audiences. Leaders might emphasize that faith is not opposed to science but illuminated by it—that the ancient wisdom about love's transformative power is being confirmed by modern molecular biology.

Leaders should consider offering structured programs in contemplative practice that systematically cultivate love and compassion, potentially drawing on both Christian contemplative traditions (centering prayer, lectio divina, the Jesus Prayer) and practices from other traditions that have been more extensively studied scientifically (loving-kindness meditation, mindfulness). Ecumenical cooperation in developing such programs could combine the strengths of different contemplative lineages while maintaining appropriate attention to each tradition's distinctive theological commitments.
## Recommendations for Policymakers

Policymakers should consider the health implications of social policies that either promote or undermine experiences of love and connection. Investments in community building, social support programs, family strengthening initiatives, and contemplative education may yield measurable health benefits at the population level. Healthcare policy should support integrative approaches that combine conventional medical treatment with evidence-based mind-body interventions, ensuring appropriate reimbursement and access.

Research funding priorities should include support for interdisciplinary studies at the intersection of theology and biology, recognizing that such research may yield practical health benefits while addressing fundamental questions about human nature and flourishing. Educational policies might incorporate social-emotional learning and contemplative practices in schools, potentially influencing developmental trajectories with lifelong health implications.

## Final Reflections

### The Intersection of Faith and Science

This dissertation represents an attempt to honor both faith and science in the investigation of love. The theological tradition insists that love is ultimately a gift from God, the very nature of divine being (1 John 4:8), and the highest calling of human existence. The tradition describes love as transformative—capable of healing wounds, reconciling enemies, and sanctifying souls. Science, meanwhile, seeks to understand the mechanisms by which all things work, subjecting even the most sacred experiences to empirical investigation.
Rather than viewing these perspectives as competitors—faith versus reason, spirit versus matter, sacred versus secular—this study has sought to show how they might be complementary voices in a larger conversation about what it means to be human. The theological assertion that love transforms finds support in the biological finding that love-oriented practices alter gene expression. The scientific observation that contemplative practice modulates immune function finds meaning in the theological understanding of why love matters and how it should be cultivated. Neither perspective is complete without the other.

The finding that agape love has biological correlates does not reduce love to mere chemistry any more than understanding the neuroscience of vision reduces beauty to mere photons. Rather, it reveals the remarkable coherence of reality—the integration of spiritual and physical dimensions in a unified creation. As the psalmist declared, we are 'fearfully and wonderfully made' (Psalm 139:14), and gene expression research continues to reveal just how wonderful that making is. The molecules of our immune cells, it seems, are responsive to the deepest movements of our hearts.

## Vision for Future Scholarship

Looking forward, I envision a flourishing field of research at the intersection of theology and biology—what might be called 'theological genomics' or 'spiritual biology'—examining not only love but also hope, faith, forgiveness, gratitude, humility, and other spiritual realities that have been central to religious traditions worldwide. The QPNIT framework developed and tested in this dissertation provides one possible foundation for such research, though surely it will be refined, extended, and perhaps superseded as knowledge advances.
My hope is that this work will inspire other researchers to take seriously the
possibility that spiritual realities have biological effects, and that biological research can
illuminate spiritual truths. Such research requires both scientific rigor—careful
methodology, appropriate statistics, replication across samples—and theological
sensitivity—awareness of the deeper meanings and contexts of the constructs being
studied, resistance to reductionism, respect for the transcendent dimensions of human
experience. This combination is challenging but, as this dissertation demonstrates,
achievable.

I also hope that the research will inspire practitioners—healthcare providers, pastors, spiritual directors, educators—to integrate these insights into their work, recognizing that the cultivation of love is not merely a spiritual luxury but a biological necessity, not merely a theological ideal but a health practice. And I hope it will encourage individuals to take their spiritual formation seriously, knowing that the practices of love shape not only their souls but their cells, not only their character but their chromosomes.

**Closing Statement**

The apostle Paul wrote that of faith, hope, and love, 'the greatest of these is love'
(1 Corinthians 13:13). Thomas Aquinas argued that love is the form of all virtues, that
which gives them their life and power and orientation toward the good. Augustine
insisted that we become what we love, that the orientation of our desires shapes the very
structure of our souls. This dissertation suggests that they were right in ways even more
profound than they could have known—that love shapes not only our souls but our cells,
not only our spirits but our genomes, not only our eternal destiny but our everyday immunity.

The transcriptional signature of agape love, revealed in the upregulation of genes that protect us from viral threat and the downregulation of genes that encode chronic stress, represents the molecular inscription of an ancient spiritual truth: that love is life, and that in loving, we flourish. In a world beset by division, isolation, and fear—a world whose genome might be described as 'CTRA-activated'—the message of this research is both scientifically grounded and spiritually hopeful: that the practices of love can write a different transcriptional story, one gene at a time.

May this knowledge inspire both the practice of love and the continued investigation of its mysteries, to the benefit of human health, the advancement of science, and the glory of God who is love.
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APPENDICES
Appendix A: CTRA Gene List

Conserved Transcriptional Response to Adversity (CTRA) Gene List

The Conserved Transcriptional Response to Adversity (CTRA) represents a characteristic pattern of gene expression associated with chronic stress, social isolation, and adverse life circumstances. First identified by Cole and colleagues (2007), the CTRA profile consists of two primary components: (a) upregulation of proinflammatory genes mediated by NF-κB signaling and (b) downregulation of genes involved in Type I interferon antiviral responses. This appendix provides the complete list of 105 CTRA genes used in the present analysis, organized by functional category.

NF-κB/Proinflammatory Gene Set

The proinflammatory component of the CTRA includes 45 genes involved in NF-κB-mediated inflammatory signaling, cytokine production, and innate immune activation. Under conditions of chronic psychosocial stress, these genes show increased expression, contributing to systemic inflammation and elevated disease risk. In the context of agape love and mind-body interventions, favorable outcomes are indicated by relative downregulation of these proinflammatory markers.
<table><caption>Table A1 NF-κB/Proinflammatory CTRA Genes (n = 45)</caption><thead><tr><td>Gene 1</td><td>Gene 2</td><td>Gene 3</td><td>Gene 4</td><td>Gene 5</td></tr></thead><tbody><tr><td>BCL2L1</td><td>BIRC2</td><td>BIRC3</td><td>CCL2</td><td>CCL3</td></tr><tr><td>CCL4</td><td>CCL5</td><td>CFLAR</td><td>COX2</td><td>CXCL1</td></tr><tr><td>CXCL10</td><td>CXCL2</td><td>CXCL8</td><td>ICAM1</td><td>IFNG</td></tr><tr><td>IKBKB</td><td>IKBKG</td><td>IL12A</td><td>IL12B</td><td>IL18</td></tr><tr><td>IL1A</td><td>IL1B</td><td>IL6</td><td>IL8</td><td>JAK2</td></tr><tr><td>MCP1</td><td>MMP2</td><td>MMP9</td><td>NFKB1</td><td>NFKB2</td></tr><tr><td>NFKBIA</td><td>PTGS2</td><td>REL</td><td>RELA</td><td>RELB</td></tr><tr><td>SELE</td><td>SELP</td><td>STAT3</td><td>STAT5A</td><td>STAT5B</td></tr><tr><td>TNF</td><td>TNFA</td><td>TYK2</td><td>VCAM1</td><td>XIAP</td></tr></tbody></table>

Type I Interferon/Antiviral Gene Set

The antiviral component of the CTRA includes 44 genes involved in Type I interferon signaling and antiviral defense mechanisms. Under conditions of chronic psychosocial stress, these genes show decreased expression, potentially compromising host defense against viral pathogens. Conversely, practices associated with agape love, compassion, and positive social connection are hypothesized to enhance expression of these protective antiviral genes.
<table><caption>**Table A2 Type I Interferon/Antiviral CTRA Genes (n = 44)**</caption><thead><tr><td>Gene 1</td><td>Gene 2</td><td>Gene 3</td><td>Gene 4</td><td>Gene 5</td></tr></thead><tbody><tr><td>CXCL10</td><td>CXCL11</td><td>CXCL9</td><td>DDX58</td><td>EIF2AK2</td></tr><tr><td>GBP1</td><td>GBP2</td><td>GBP5</td><td>IFI27</td><td>IFI35</td></tr><tr><td>IFI44</td><td>IFI44L</td><td>IFI6</td><td>IFIH1</td><td>IFIT1</td></tr><tr><td>IFIT2</td><td>IFIT3</td><td>IFIT5</td><td>IFNA1</td><td>IFNA2</td></tr><tr><td>IFNB1</td><td>IFNG</td><td>IRF1</td><td>IRF2</td><td>IRF3</td></tr><tr><td>IRF7</td><td>IRF9</td><td>ISG15</td><td>ISG20</td><td>JAK1</td></tr><tr><td>MDA5</td><td>MX1</td><td>MX2</td><td>OAS1</td><td>OAS2</td></tr><tr><td>OAS3</td><td>OASL</td><td>PKR</td><td>RIG1</td><td>RSAD2</td></tr><tr><td>STAT1</td><td>STAT2</td><td>TYK2</td><td>VIPERIN</td><td></td></tr></tbody></table>

**Additional CTRA-Related Genes**

The CTRA framework also includes 16 additional genes related to glucocorticoid signaling, stress response regulation, and immune modulation. These genes provide context for understanding the broader neuroendocrine-immune interactions that characterize the stress response and its modulation by psychosocial factors.

<table><caption>**Table A3 Additional CTRA-Related Genes (n = 16)**</caption><thead><tr><td>Gene 1</td><td>Gene 2</td><td>Gene 3</td><td>Gene 4</td><td>Gene 5</td></tr></thead><tbody><tr><td>ACTH</td><td>CRH</td><td>CRHR1</td><td>DUSP1</td><td>FKBP5</td></tr><tr><td>GILZ</td><td>IL10</td><td>IL13</td><td>IL4</td><td>NR3C1</td></tr><tr><td>POMC</td><td>SGK1</td><td>TERC</td><td>TERT</td><td>TGFB1</td></tr><tr><td>TSC22D3</td><td></td><td></td><td></td><td></td></tr></tbody></table>
Selected Gene Descriptions

The following provides brief functional descriptions for key genes within each CTRA component that showed significant differential expression in the present analysis.

Key Proinflammatory Genes

**IL1B (Interleukin 1 Beta).** Potent proinflammatory cytokine involved in inflammatory response, fever, and acute phase reactions. Central mediator of innate immunity and implicated in chronic inflammatory conditions.

**IL6 (Interleukin 6).** Pleiotropic cytokine with both pro- and anti-inflammatory properties. Elevated in chronic stress and associated with depression, cardiovascular disease, and metabolic syndrome.

**IL8/CXCL8 (Interleukin 8).** Chemokine that attracts neutrophils to sites of infection or injury. Key mediator of acute inflammatory response and tissue remodeling.

**TNF (Tumor Necrosis Factor).** Master regulator of inflammatory response. Involved in systemic inflammation and implicated in numerous chronic diseases including rheumatoid arthritis and inflammatory bowel disease.

**PTGS2/COX-2 (Prostaglandin-Endoperoxide Synthase 2).** Inducible enzyme producing prostaglandins during inflammation. Target of non-steroidal anti-inflammatory drugs (NSAIDs).

**NFKB1 (Nuclear Factor Kappa B Subunit 1).** Transcription factor central to inflammatory gene expression. Activated by stress, inflammatory signals, and pathogen-associated molecular patterns.
**CCL2/MCP1 (C-C Motif Chemokine Ligand 2)**. Monocyte chemoattractant protein involved in recruiting immune cells to sites of inflammation. Elevated in obesity and metabolic disease.

**ICAM1 (Intercellular Adhesion Molecule 1)**. Cell surface glycoprotein facilitating leukocyte adhesion and transmigration. Marker of endothelial activation and vascular inflammation.

### Key Antiviral/Type I Interferon Genes

**IFI27 (Interferon Alpha Inducible Protein 27)**. Interferon-stimulated gene involved in apoptosis regulation and antiviral defense. Highly responsive to Type I interferons and consistently upregulated in mind-body intervention studies.

**IFIT1 (Interferon Induced Protein with Tetratricopeptide Repeats 1)**. Antiviral protein that inhibits viral replication by binding viral RNA and blocking translation initiation. Key effector of innate antiviral immunity.

**IFIT3 (Interferon Induced Protein with Tetratricopeptide Repeats 3)**. Interferon-stimulated gene with antiviral activity. Forms complexes with other IFIT proteins to enhance antiviral defense.

**MX1 (MX Dynamin Like GTPase 1)**. Interferon-induced GTPase with antiviral activity against RNA viruses including influenza and other negative-strand RNA viruses.

**MX2 (MX Dynamin Like GTPase 2)**. Antiviral protein with activity against HIV-1 and other lentiviruses. Blocks viral capsid uncoating and nuclear import.
**OAS1 (2'-5'-Oligoadenylate Synthetase 1)**. Interferon-induced enzyme that activates RNase L to degrade viral RNA. Key component of innate antiviral defense against diverse viral pathogens.

**RSAD2/Viperin (Radical S-Adenosyl Methionine Domain Containing 2)**. Broad-spectrum antiviral protein induced by Type I interferons. Inhibits replication of multiple virus families including influenza, hepatitis C, and HIV.

**ISG15 (Interferon Stimulated Gene 15)**. Ubiquitin-like modifier conjugated to proteins during antiviral response. Modulates interferon signaling and has direct antiviral activity.

**STAT1 (Signal Transducer and Activator of Transcription 1)**. Transcription factor essential for interferon signaling. Mediates expression of interferon-stimulated genes in response to Type I and Type II interferons.

**IRF7 (Interferon Regulatory Factor 7)**. Master regulator of Type I interferon-dependent immune responses. Essential for amplification of antiviral interferon production.

## Key Stress Response and Regulatory Genes

**FKBP5 (FK506 Binding Protein 5)**. Glucocorticoid receptor co-chaperone that regulates stress hormone sensitivity. Implicated in stress-related psychiatric disorders and shows consistent downregulation with mind-body interventions.

**NR3C1 (Nuclear Receptor Subfamily 3 Group C Member 1)**. Glucocorticoid receptor mediating cortisol effects on gene expression. Central to HPA axis regulation and stress response.
**TSC22D3/GILZ (Glucocorticoid-Induced Leucine Zipper).** Anti-inflammatory protein induced by glucocorticoids. Mediates immunosuppressive effects of cortisol.

**IL10 (Interleukin 10).** Anti-inflammatory cytokine that limits immune responses and prevents tissue damage. Key regulator of inflammatory homeostasis.

**TGFB1 (Transforming Growth Factor Beta 1).** Multifunctional cytokine with immunomodulatory properties. Involved in tissue repair, immune tolerance, and fibrosis.

## Sources

The CTRA gene set used in this analysis was derived from the following primary sources:

Cole, S. W., Hawkley, L. C., Arevalo, J. M., Sung, C. Y., Rose, R. M., & Cacioppo, J. T. (2007). Social regulation of gene expression in human leukocytes. *Genome Biology, 8*(9), R189. https://doi.org/10.1186/gb-2007-8-9-r189

Cole, S. W. (2014). Human social genomics. *PLoS Genetics, 10*(8), e1004601. https://doi.org/10.1371/journal.pgen.1004601

Fredrickson, B. L., Grewen, K. M., Coffey, K. A., Algoe, S. B., Firestine, A. M., Arevalo, J. M., Ma, J., & Cole, S. W. (2013). A functional genomic perspective on human well-being. *Proceedings of the National Academy of Sciences, 110*(33), 13684-13689. https://doi.org/10.1073/pnas.1305419110

Antoni, M. H., Lutgendorf, S. K., Blomberg, B., Carver, C. S., Lechner, S., Diaz, A., Stagl, J., Arevalo, J. M., & Cole, S. W. (2012). Cognitive-behavioral stress management reverses anxiety-related leukocyte transcriptional dynamics.
Biological Psychiatry, 71(4), 366-372.

https://doi.org/10.1016/j.biopsych.2011.10.007

Bower, J. E., Greendale, G., Crosswell, A. D., Garet, D., Sternlieb, B., Ganz, P. A., Irwin, M. R., Olmstead, R., Arevalo, J., & Cole, S. W. (2014). Yoga reduces inflammatory signaling in fatigued breast cancer survivors: A randomized controlled trial. Psychoneuroendocrinology, 43, 20-29.

https://doi.org/10.1016/j.psyneuen.2014.01.019

**Summary Statistics**

Total CTRA genes analyzed: 105

NF-κB/Proinflammatory genes: 45

Type I Interferon/Antiviral genes: 44

Additional regulatory genes: 16

These genes were used to calculate the CTRA composite score as described in Chapter 3 (Methodology), with the composite representing the relative balance between proinflammatory and antiviral gene expression programs. A negative CTRA composite score indicates a favorable shift away from the stress-associated transcriptional profile, characterized by reduced inflammatory signaling and enhanced antiviral capacity.
## Appendix B: GEO Dataset Details

### GEO Dataset Details and Access Information

This appendix provides comprehensive documentation for the four Gene Expression Omnibus (GEO) datasets utilized in the present study. Each dataset entry includes study background, experimental design, sample characteristics, platform information, data processing details, and access instructions. All datasets are publicly available through the National Center for Biotechnology Information (NCBI) GEO repository.

#### Dataset 1: GSE108215

*Mindfulness Awareness Practices (MAPs) Study*

<table><caption>**Table B1 Summary Characteristics for GSE108215**</caption><tr><td>GEO Accession</td><td>GSE108215</td></tr><tr><td>Sample Size</td><td>86</td></tr><tr><td>Platform</td><td>Illumina HumanHT-12 V4.0 Expression BeadChip</td></tr><tr><td>Organism</td><td>Homo sapiens</td></tr><tr><td>Submission Date</td><td>December 2017</td></tr><tr><td>Principal Investigator</td><td>David S. Black, University of Southern California</td></tr><tr><td>Access URL</td><td>https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE108215</td></tr></table>

#### Study Description

This dataset examines transcriptional changes associated with an 8-week Mindfulness Awareness Practices (MAPs) intervention in older adults. The MAPs program is based on
Mindfulness-Based Stress Reduction (MBSR) and includes guided meditation, body awareness exercises, and mindful movement practices. The study employed a randomized controlled design comparing the MAPs intervention to an active control condition.

## Experimental Design

Participants were randomized to either: (a) 8-week MAPs intervention (n=43), consisting of weekly 2-hour group sessions plus daily home practice, or (b) Health Education Program control (n=43), matched for time and attention. Peripheral blood mononuclear cells (PBMCs) were collected at baseline (pre-intervention) and post-intervention (8 weeks). Gene expression was assessed using Illumina microarrays.

## Inclusion/Exclusion Criteria

Adults aged 55-85 years; no prior meditation experience; able to attend weekly sessions; English proficiency; no major psychiatric disorders; no immunomodulatory medications.

## Key Variables

- Intervention group (MAPs vs. Control)

- Time point (Pre vs. Post)

- Age

- Sex

- Baseline inflammatory markers

- Perceived Stress Scale scores

- Loneliness measures

## Data Processing

Raw intensity data were background-corrected and quantile normalized using the lumi package in R. Probes with detection p-value > 0.05 in more than 50% of samples were
removed. Batch effects were adjusted using ComBat. Final dataset includes 12,632
probes mapping to 9,847 unique genes.

Available Files

* GSE108215_series_matrix.txt.gz

* GSE108215_RAW.tar

Primary Publication

Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: A systematic review of randomized controlled trials. Annals of the New York Academy of Sciences, 1373(1), 13-24.

Relevance to Present Study

This dataset is highly relevant to the QPNIT framework as mindfulness practices
cultivate qualities associated with agape love, including compassion, non-judgment, and
present-moment awareness. The study's focus on older adults provides insights into how
contemplative practices may buffer age-related inflammatory processes.

**Dataset 2: GSE44777**

Sudarshan Kriya Yoga (SKY) Breathing Intervention Study
<table><caption>**Table B2 Summary Characteristics for GSE44777**</caption><tr><td>GEO Accession</td><td>GSE44777</td></tr><tr><td>Sample Size</td><td>78</td></tr><tr><td>Platform</td><td>Affymetrix Human Gene 1.0 ST Array</td></tr><tr><td>Organism</td><td>Homo sapiens</td></tr><tr><td>Submission Date</td><td>February 2013</td></tr><tr><td>Principal Investigator</td><td>Fahri Saatcioglu, University of Oslo</td></tr><tr><td>Access URL</td><td>https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE44777</td></tr></table>

## Study Description

This dataset investigates acute and long-term transcriptional changes associated with Sudarshan Kriya Yoga (SKY), a rhythmic breathing practice incorporating specific breathing patterns, meditation, and yoga postures. SKY has been associated with reduced stress, anxiety, and depression, as well as improved immune function.

## Experimental Design

The study employed a within-subjects design examining gene expression changes in long-term SKY practitioners (>2 years of regular practice) before and after a single SKY session. Peripheral blood lymphocytes were collected at three time points: (a) baseline (before SKY session), (b) immediately post-session, and (c) 2 hours post-session.

Additional comparisons were made between experienced practitioners and meditation-naive controls.

## Inclusion/Exclusion Criteria

For practitioners: minimum 2 years of regular SKY practice; practicing at least 3 times per week. For controls: no meditation or yoga experience; matched for age and sex. All
participants: healthy adults aged 25-55; no chronic diseases; no immunomodulatory
medications.

Key Variables

* Practitioner status (Experienced vs. Naive)

- Time point (Pre, Post, 2hr Post)

* Years of practice

- Practice frequency

- Age

- Sex

- Baseline cortisol levels

Data Processing

Raw CEL files were processed using the RMA algorithm in the oligo package. Quality control included array quality metrics and principal component analysis for outlier detection. Probes were annotated using the hugene10sttranscriptcluster.db package. Final dataset includes 21,014 transcript clusters.

Available Files

* GSE44777_series_matrix.txt.gz

- GSE44777_RAW.tar

Primary Publication

Qu, S., Olafsrud, S. M., Meza-Zepeda, L. A., & Saatcioglu, F. (2013). Rapid gene expression changes in peripheral blood lymphocytes upon practice of a comprehensive yoga program. PLoS ONE, 8(4), e61910.
## Relevance to Present Study

SKY practice emphasizes service to others and cultivation of positive emotions aligned with agape love. The breathing techniques are believed to activate parasympathetic nervous system pathways and modulate inflammatory gene expression, providing a physiological mechanism for love-health connections.

## Dataset 3: GSE10041

*Relaxation Response (RR) Gene Expression Study*

<table><caption>**Table B3 Summary Characteristics for GSE10041**</caption><tr><td>GEO Accession</td><td>GSE10041</td></tr><tr><td>Sample Size</td><td>72</td></tr><tr><td>Platform</td><td>Affymetrix Human Genome U133 Plus 2.0 Array</td></tr><tr><td>Organism</td><td>Homo sapiens</td></tr><tr><td>Submission Date</td><td>January 2008</td></tr><tr><td>Principal Investigator</td><td>Herbert Benson & Towia Libermann, Benson-Henry Institute for Mind Body Medicine</td></tr><tr><td>Access URL</td><td>https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10041</td></tr></table>

## Study Description

This landmark dataset examines transcriptional changes associated with the Relaxation Response (RR), a physiological state characterized by decreased oxygen consumption, heart rate, and blood pressure, along with enhanced feelings of well-being. The RR can be elicited through various techniques including meditation, prayer, yoga, and progressive muscle relaxation.
## Experimental Design

The study compared three groups: (a) long-term RR practitioners (M1 group, n=19, practicing 4-20 years), (b) short-term RR trainees (M2 group, n=20, 8 weeks of training), and (c) healthy controls with no RR experience (N group, n=19). For M2 participants, gene expression was assessed before and after the 8-week training period. PBMCs were collected and processed for microarray analysis.

## Inclusion/Exclusion Criteria

Long-term practitioners: minimum 4 years of daily RR practice. Short-term trainees: no prior meditation experience; committed to 8-week program. Controls: no meditation or relaxation training. All groups: healthy adults aged 25-65; no chronic inflammatory conditions; no psychotropic medications.

## Key Variables

- Group (Long-term/Short-term/Control)

- Time point (Pre/Post for trainees)

- Years of practice

- RR technique used

- Age

- Sex

- Psychological measures (anxiety, stress)

## Data Processing

Raw data were normalized using MAS5.0 algorithm. Present/Absent calls were used to filter probes. Differential expression analysis used linear models with empirical Bayes
moderation. Gene set enrichment analysis was performed using GSEA. Final dataset
includes 54,675 probe sets.

Available Files

* GSE10041_series_matrix.txt.gz

* GSE10041_RAW.tar

Primary Publication

Dusek, J. A., Otu, H. H., Wohlhueter, A. L., Bhasin, M., Zerbini, L. F., Joseph, M. G., Benson, H., & Libermann, T. A. (2008). Genomic counter-stress changes induced by the relaxation response. PLoS ONE, 3(7), e2576.

Relevance to Present Study

The Relaxation Response represents a well-characterized physiological state that may serve as a biological substrate for experiences of divine love and contemplative prayer.

Benson's original work documented similar physiological changes across diverse religious and secular practices, supporting the QPNIT framework's emphasis on transcendent experience.

**Dataset 4: GSE55762**

Psychological Well-Being and Gene Expression Study
<table><caption>**Table B4 Summary Characteristics for GSE55762**</caption><tr><td>GEO Accession</td><td>GSE55762</td></tr><tr><td>Sample Size</td><td>122</td></tr><tr><td>Platform</td><td>Illumina HumanHT-12 V4.0 Expression BeadChip</td></tr><tr><td>Organism</td><td>Homo sapiens</td></tr><tr><td>Submission Date</td><td>March 2014</td></tr><tr><td>Principal Investigator</td><td>Barbara L. Fredrickson & Steve W. Cole, University of North Carolina & UCLA</td></tr><tr><td>Access URL</td><td>https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE55762</td></tr></table>

## Study Description

This influential dataset examines the relationship between different types of psychological well-being (hedonic vs. eudaimonic) and gene expression profiles. The study distinguished between well-being derived from pleasure and self-gratification (hedonic) versus well-being derived from meaning, purpose, and contribution to others (eudaimonic)—the latter closely aligned with agape love.

## Experimental Design

Cross-sectional study of healthy adults who completed measures of hedonic well-being (positive affect, life satisfaction) and eudaimonic well-being (purpose, meaning, personal growth, positive relations, self-acceptance). Blood samples were collected for PBMC isolation and gene expression profiling. Participants were stratified into groups based on their well-being profiles.
## Inclusion/Exclusion Criteria

Healthy adults aged 35-64; no chronic diseases; no current psychiatric disorders; no immunomodulatory medications; no current infections. Recruitment targeted diverse well-being profiles.

## Key Variables

* Hedonic well-being score

* Eudaimonic well-being score

* Well-being profile group

* Age

* Sex

* BMI

* Education

* Income

* Social integration measures

* Health behaviors

## Data Processing

Raw data were background-corrected using negative control probes and quantile normalized. Poorly detected probes (detection p > 0.05 in >50% of samples) were removed. Expression values were log2-transformed. CTRA gene set analysis was performed using TELiS promoter-based bioinformatics. Final dataset includes 14,072 probes.

## Available Files

* GSE55762_series_matrix.txt.gz
* GSE55762_non_normalized.txt.gz

**Primary Publication**

Fredrickson, B. L., Grewen, K. M., Coffey, K. A., Algoe, S. B., Firestine, A. M., Arevalo, J. M., Ma, J., & Cole, S. W. (2013). A functional genomic perspective on human well-being. Proceedings of the National Academy of Sciences, 110(33), 13684-13689.

**Relevance to Present Study**

This dataset is central to the present study as it directly operationalizes concepts related to agape love through eudaimonic well-being measures. Fredrickson and Cole's finding that eudaimonic (other-focused) well-being is associated with favorable CTRA profiles while hedonic (self-focused) well-being is not provides key empirical support for the QPNIT framework.

**Data Access Instructions**

To access and download the datasets used in this study, follow these steps:

1. Navigate to the NCBI GEO website: https://www.ncbi.nlm.nih.gov/geo/

2. Enter the GEO accession number (e.g., GSE108215) in the search box.

3. On the dataset page, locate the "Download" section at the bottom.

4. For processed data: Download the Series Matrix File(s), which contain normalized expression values and sample metadata.

5. For raw data: Download the supplementary files or RAW data archive (typically .tar or .tar.gz format).

6. For platform annotation: Navigate to the platform page (GPL number) to download
probe-to-gene mapping files.

7. Import data into R/Bioconductor using the GEOquery package:

```R
# R code for data download
library(GEOquery)

# Download dataset
gse <- getGEO("GSE108215", GSEMatrix = TRUE)

# Extract expression data
exprs_data <- exprs(gse[[1]])

# Extract sample metadata
pheno_data <- pData(gse[[1]])
```

## Integrated Dataset Summary

<table><caption>Table B5 Combined Dataset Characteristics</caption><thead><tr><th>Characteristic</th><th>GSE108215</th><th>GSE44777</th><th>GSE10041</th><th>GSE55762</th><th>Combined</th></tr></thead><tbody><tr><td>Sample Size</td><td>86</td><td>78</td><td>72</td><td>122</td><td>358</td></tr><tr><td>Platform</td><td>Illumina</td><td>Affymetrix</td><td>Affymetrix</td><td>Illumina</td><td>Mixed</td></tr><tr><td>Design</td><td>RCT</td><td>Within-Subj</td><td>Mixed</td><td>Cross-Sect</td><td>—</td></tr><tr><td>Intervention</td><td>MAPs</td><td>SKY</td><td>RR</td><td>—</td><td>MBI</td></tr><tr><td>CTRA Genes Available</td><td>102</td><td>105</td><td>105</td><td>103</td><td>105</td></tr></tbody></table>

Note. RCT = randomized controlled trial; Within-Subj = within-subjects design; Cross-Sect = cross-sectional; MAPs = Mindfulness Awareness Practices; SKY = Sudarshan Kriya Yoga; RR = Relaxation Response; MBI = mind-body intervention.
Ethical Considerations

All datasets used in this study are publicly available through the NCBI GEO repository and contain de-identified data. The original studies received Institutional Review Board (IRB) approval from their respective institutions, and all participants provided informed consent. Secondary analysis of de-identified, publicly available data is generally exempt from IRB review under 45 CFR 46.104(d)(4).