The Contribution of Neuroendocrine-Immune Dysfunction to Common Complex Human Diseases

Neuroendocrine-immune dysfunction – human diseases

Introduction: The Intricate Link Between Neuroendocrine and Immune Systems in Common Complex Diseases

The neuroendocrine and immune systems, traditionally viewed as distinct entities with specialized functions, are now recognized as being engaged in a complex and bidirectional communication network. This integrated system plays a pivotal role in maintaining physiological homeostasis, orchestrating responses to a myriad of internal and external stimuli. The concept of a neuroendocrine-immune axis has emerged, underscoring the profound influence of this intricate interplay on virtually all aspects of human health. A growing body of evidence indicates that dysfunction or aberrant interactions within this axis are fundamental contributors to the pathogenesis and progression of a wide array of common complex human diseases.

This report will delve into the specific roles of neuroendocrine-immune dysregulation in several major categories of human diseases, including Cardiovascular Diseases, Metabolic Diseases, Neurodegenerative and Neurological Diseases, Autoimmune Diseases, Respiratory Diseases, Cancers, and Psychiatric Disorders. By examining the underlying mechanisms of these interactions, a more comprehensive understanding of disease etiology and potential therapeutic targets can be achieved.

Foundational Concepts: Understanding Neuroendocrine-Immune Interactions in Human Health and Disease

The traditional approach in medical research has often focused on dissecting diseases into isolated components, examining individual molecules, cells, or pathways in an attempt to elucidate their etiology. However, the complexity and heterogeneity of many chronic conditions suggest that this reductionist model may fall short in capturing the full picture. A compelling perspective, as highlighted by resources like brainimmune.com ¹, posits that systemic factors, particularly the intricate interplay between the neuroendocrine and immune systems, along with stress-immune interactions, represent critical underpinnings in the development of common complex diseases. This viewpoint necessitates a shift towards understanding diseases not merely as isolated malfunctions but as emergent properties arising from dysregulated network interactions across physiological systems.

Stress, encompassing both physiological challenges such as infection and injury, and psychological pressures like chronic emotional distress, exerts a profound influence as a significant trigger and modulator of neuroendocrine-immune interactions.¹ The hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS) stand as the primary neuroendocrine pathways mediating the body’s response to stress, and their influence extends extensively and diversely to the immune system. Stress activates the hypothalamus, leading to the release of corticotropin-releasing hormone (CRH), which in turn stimulates the pituitary gland to secrete adrenocorticotropic hormone (ACTH). ACTH then prompts the adrenal glands to release cortisol. Simultaneously, the SNS releases catecholamines such as norepinephrine and epinephrine. These hormones have pleiotropic effects on immune cells, altering their proliferation, differentiation, and the production of cytokines. Chronic stress can lead to sustained hormonal changes and immune dysregulation, thereby contributing to a variety of pathological states.

The communication between the neuroendocrine and immune systems is not a unidirectional process but rather a dynamic and reciprocal exchange of information.¹ Immune cells, including lymphocytes, macrophages, and dendritic cells, express a wide array of receptors for neuroendocrine hormones like glucocorticoids and catecholamines, as well as for neuropeptides and neurotransmitters. Conversely, neuroendocrine tissues, such as the hypothalamus, pituitary, and adrenal glands, express receptors for cytokines and other immune mediators.

This constant and multifaceted molecular dialogue involves a diverse range of signaling molecules, including specific hormones (e.g., cortisol, prolactin), neurotransmitters (e.g., norepinephrine, acetylcholine), neuropeptides (e.g., substance P, vasoactive intestinal peptide), and cytokines (e.g., IL-1, IL-6, TNF-α). This intricate crosstalk allows for an exquisitely fine-tuned regulation of a vast array of physiological processes, ensuring a coordinated response to both internal and external stimuli. However, this complexity also presents numerous potential points of failure where dysregulation can occur, ultimately contributing to disease.

The neuroendocrine-immune system plays a crucial role in maintaining overall physiological homeostasis, ensuring stability and adaptation within the internal environment. Disruptions in this delicate equilibrium, whether due to genetic predispositions, environmental factors, chronic stress, or other insults, can lead to a state of dysregulation characterized by either excessive activation or pathological suppression of immune responses, both of which are fundamental contributors to the pathogenesis of a wide range of diseases.¹ Many common complex diseases can be conceptualized as states of disrupted neuroendocrine-immune homeostasis, where the normally protective and regulatory interactions within this axis become maladaptive.

The body’s ability to maintain a stable internal environment despite constant challenges relies heavily on the proper functioning and communication between the neuroendocrine and immune systems. When this intricate balance is perturbed, it can result in chronic inflammation, autoimmunity (where the immune system attacks the body’s own tissues), impaired responses to infections or tissue damage, and metabolic disturbances – all of which are hallmarks of many complex diseases.

Cardiovascular Diseases: The Role of Neuroendocrine-Immune Dysfunction in Pathogenesis

A well-established link exists between chronic stress and an increased risk of cardiovascular diseases. Chronic stress can maintain a pro-inflammatory state, crucial in their pathogenesis.¹ Catecholamine-induced inflammation plays a role in stress-induced cardiomyopathy.¹ Stress activates the sympathetic nervous system, HPA axis, and renin-angiotensin system, leading to the release of stress hormones that promote inflammation.⁶ This chronic inflammation is central to atherosclerosis, involving endothelial dysfunction, macrophage accumulation, and cytokine production.⁶

The HPA axis and the sustained release of cortisol in chronic stress impact blood vessels by promoting vasoconstriction and hypertension.¹¹ Glucocorticoid resistance, occurring during chronic stress, contributes to chronic low-grade inflammation in cardiovascular disease.¹¹ Chronic cortisol elevation also leads to metabolic dysfunction (insulin resistance, abdominal fat, dyslipidemia), key risk factors for cardiovascular disease.¹¹ Conversely, low levels of glucocorticoids during stress can also be detrimental to the cardiovascular system.¹²

Catecholamines (norepinephrine, epinephrine) increase heart contractility and blood pressure.¹³ Immune cells can be a source of catecholamines that regulate local inflammatory responses in the cardiovascular system.¹³ Excessive catecholamine exposure can have toxic effects on the myocardium, leading to cardiomyopathy and arrhythmias.¹⁴ Sympathetic nerve activity is linked to inflammatory cytokine release in cardiovascular disease.⁸

Autonomic nervous system (ANS) dysfunction, particularly increased sympathetic activity and reduced parasympathetic tone, is implicated in cardiovascular disease, including heart failure and arrhythmias.¹⁷ Central nervous system diseases can induce cardiovascular diseases via autonomic dysfunction.¹⁸

Neuroendocrine-immune interactions play specific roles in various cardiovascular conditions:

• Hypertension: Immune cells (T cells, macrophages, dendritic cells, B cells) and cytokines (IL-6, IL-17, TNF-α) promote vascular inflammation and endothelial dysfunction. The sympathetic nervous system and renin-angiotensin system are involved in these interactions.¹⁹
• Atherosclerosis: Stress induces adhesion molecules, macrophage activation, cytokine release, and lipid oxidation, contributing to atherosclerotic plaques. Bidirectional neuroimmune crosstalk occurs in the arterial vessel and bone marrow.²⁴
• Heart Failure: Neuroendocrine activation (SNS, RAAS, AVP) and chronic inflammation contribute to cardiomyocyte death and myocardial fibrosis. Cytokines (TNF-α, IL-1, IL-6) and autonomic imbalance are involved.²⁹
• Anorexia Nervosa-Linked Cardiovascular Diseases: Neuroendocrine (HPA, HPG, HPT axes dysfunction), immune (proinflammatory state), and autonomic nervous system dysregulation contribute to cardiovascular complications.³⁴

Table 1: Summary of Neuroendocrine-Immune Mechanisms in Cardiovascular Diseases

Metabolic Diseases: Neuroendocrine-Immune Interactions in Diabetes and Obesity

The adaptive immune system plays a significant role in diabetes pathogenesis.³⁶ Hormones (growth hormone, insulin-like growth factor-1) and neurotransmitters influence T lymphocyte development and maturation under the metabolic burden of diabetes.³⁶ A local immune-neuroendocrine self-regulating system exists in the pancreas, and its dysfunction can lead to beta-cell damage in type 1 diabetes.³⁷ Complex neuroendocrine-immune interactions are observed in the nonobese diabetic (NOD) mouse model of type 1 diabetes, including the effects of stress, cytokines, and sex hormones.³⁸

Obesity involves a tight coupling of metabolic and immune systems mediated by neuroendocrine peptides, cytokines, and chemokines.⁴⁰ It is a state of chronic low-grade inflammation associated with dysfunctional adipose tissue, which acts as an active endocrine and immune organ.⁴¹ Adipokines (leptin, adiponectin) bridge metabolism and the immune system, and their dysregulation in obesity is significant.⁴¹ There is an interplay between neuroendocrine dysfunctions related to chronic stress and shared biological mechanisms in the pathophysiology of both obesity and depression.⁴² Diet impacts gut microbiota, influencing intestinal neuroendocrine and immune system functions in obesity.⁴³

Metabolic diseases can alter the neuroendocrine stress axis due to rising insulin levels and the release of adipokines and inflammatory cytokines.⁴⁴ Chronic stress due to inflammation may exacerbate these effects, potentially contributing to metabolic syndrome.⁴⁴ Immune system dysfunctions, often manifesting as chronic inflammation, are associated with metabolic diseases.⁴⁵ The interplay between endocrine and immune systems is crucial in the pathogenesis of these conditions.⁴⁵ In chronic fatigue syndrome (CFS), the immune system shows relative resistance to regulation by the neuroendocrine system.⁴⁶ Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation are observed following chronic spinal cord injury.⁴⁷ Exposure to endocrine-disrupting chemicals can induce immune system dysfunction, detrimentally affecting metabolic health.⁴⁸

Neurodegenerative and Neurological Diseases: Disrupted Neuroendocrine-Immune Communication in Alzheimer’s, Parkinson’s, and Multiple Sclerosis

Neurodegeneration involves the loss of neuronal structure and function, often linked to inflammatory processes (neuroinflammation) and oxidative stress.⁴⁹ Immune cells (microglia, astrocytes, T cells) play roles in normal brain function and neuroinflammatory responses, and chronic neuroinflammation can lead to progressive neuron loss.⁵¹

Stress is a risk factor for mild cognitive impairment and dementia.¹ Cytokines like IL-33 may improve memory deficits and reduce β-amyloid accumulation in Alzheimer’s disease.¹ Targeting neuroinflammation, particularly TNF-α, is a research direction.¹ Neuroendocrine and immunological changes are linked in Alzheimer’s.⁵² Neuroinflammation disrupts the brain’s glymphatic system, impairing protein waste clearance.¹ The complement system may be involved in Alzheimer’s pathophysiology.⁵⁴ Overlap exists between metabolic abnormalities and immune dysfunction in Alzheimer’s.⁵³

Peripheral immunity plays a role in cognitive decline during Parkinson’s disease.¹ β2-AR agonists show potential as antiparkinson drugs.¹ Peripheral immunity and gut microbiota are implicated in Parkinson’s pathogenesis and progression.¹ Neuroendocrine abnormalities, including disrupted circadian rhythms and metabolic changes, are common in Parkinson’s.⁵⁶ These abnormalities may serve as biomarkers and therapeutic targets.⁵⁶

In multiple sclerosis, glucocorticoid-resistant IL-17- and IL-22-secreting CD4+ T cells are found, and chronic stress can promote autoimmunity via glucocorticoid resistance.¹ Multiple sclerosis is an autoimmune disease affecting the central nervous system, involving lymphocytes and innate cells.⁵⁹ Bidirectional communication between the neuroendocrine and immune systems is disrupted in multiple sclerosis.⁵ The HPA axis and cortisol play roles in disease susceptibility and relapse recovery.⁶⁰ Hormones like thyroid, melatonin, and sex hormones may have therapeutic effects in multiple sclerosis models.⁶⁰

Unfavorable outcomes after traumatic brain injury (TBI) may result from dysfunctional neuroendocrine-immune communication.⁶² The nature of this dysfunction varies between cortisol trajectory groups.⁶² Neuroinflammation contributes to injury and repair after TBI.⁶³ Posttraumatic neuroendocrine dysfunction (PTHP) is a common sequela, affecting mood, memory, metabolism, and stress response.⁶⁴ The complement system and neurovasculature impairment are involved in post-TBI pathophysiology.⁵⁴

Table 2: Summary of Neuroendocrine-Immune Mechanisms in Neurodegenerative and Psychiatric Disorders

Autoimmune Diseases: The Interplay of Neuroendocrine and Immune Systems in Rheumatoid Arthritis and Lupus

Hormonal effects contribute to the sexual dimorphism of autoimmune processes.¹ Neuroendocrine-immune dysfunction plays a role in the pathogenesis of human autoimmune diseases.⁶⁵ Alterations in neuroendocrine responses can lead to pathologic autoimmunity.⁶⁶ Bidirectional communication exists between the neuroendocrine and immune systems via shared receptors and messenger molecules.⁵ Disruptions in these regulatory systems can cause over-activation or over-suppression of the immune system, contributing to autoimmune diseases.⁵

In rheumatoid arthritis (RA), various hormones are involved in pathogenesis and treatment.¹ RA often improves during pregnancy due to complex endocrine and immunological interactions.¹ Chronic inflammation in RA is accompanied by alterations in endocrine, nervous, and immune system interactions.⁶⁸ Impaired HPA axis activity and inadequate cortisol secretion are seen in RA.⁶⁸ Mental interventions may modulate the neuroendocrine-immune system in RA.⁶⁹ Aberrant production of pro-inflammatory cytokines in RA activates the HPA axis, leading to hormonal imbalances.⁷⁰ Neuroendocrine regulation of inflammatory and immune responses in RA occurs systemically through glucocorticoids and regionally through sympathetic innervation.⁷²

Stress can affect organ-specific autoimmunity, potentially including lupus.¹ Neuroendocrine-immune interactions are fundamental to understanding the pathogenesis and complexity of systemic lupus erythematosus (SLE).⁷³ The HPA axis, central nervous system cytokines, and the sympathetic system are involved in lupus. Hormones (estrogen, prolactin, gonadotropin-releasing hormone, leptin) act as immunomodulatory agents in lupus.⁷³ The nervous and immune systems interact in regulating peripheral inflammation in lupus, linking psychosocial stress with chronic somatic disease.⁷⁴

Respiratory Diseases: Neuroendocrine-Immune Axis Involvement in Asthma and Chronic Obstructive Pulmonary Disease

Neuroimmune recognition and regulation in the respiratory system is a complex and coordinated process.⁷⁵ Pulmonary neuroendocrine cells (PNECs) play a role in respiratory health and disease, including immune regulation.⁷⁶ Increased PNEC numbers are reported in COPD and asthma.⁷⁶ Bidirectional interaction exists between the nervous and immune systems in the lung.⁷⁹ Local neuroimmune interaction in the lung is generally pro-inflammatory, while central regulation aims to limit tissue destruction.⁷⁹

Maternal stress during pregnancy can increase the offspring’s risk of asthma by affecting glucocorticoid release.¹ The beta-adrenergic theory suggests psychological factors influence asthma.¹ Chemical-induced asthma may rely on neuro-immune mechanisms involving airway hyperreactivity.⁸¹ Neuro-immune interactions involving TRPA1, TRPV1 channels, and mast cells are crucial in irritant-induced airway hyperreactivity.⁸¹ The autonomic nervous system is involved in the inflammatory process in asthma.⁸² Sympathetic and parasympathetic nerves regulate airway smooth muscle and mucus secretion in asthma, with immune cell interactions.⁸³ Neuropeptides like CGRP regulate dendritic cell maturation and T cell activation in asthma.⁸⁴

Increased PNEC numbers are reported in COPD.¹ Immune dysfunction and chronic inflammation are central to COPD pathogenesis, involving neutrophils, macrophages, and T cell infiltration.⁸⁵ Prolonged exposure to harmful substances in COPD leads to airway wall thickening and lung function impairment, with interactions between immune cells and oxidative damage.⁸⁵ Cytokine dysregulation (TNF-α, IFN-γ, IL-1β, IL-6) is seen in COPD.⁷⁹ Inflammation in the lung is regulated through neural-immune interaction involving sensory neurons and the central nervous system.⁷⁹

Neuroendocrine-immune interactions may be involved in the association between SARS-CoV-2 infection and impaired mental health.⁸⁷ The “cytokine storm” in severe COVID-19 may link to psychiatric symptoms.⁸⁸ Social isolation during the pandemic has negative impacts on mental health through neuroendocrine-immune changes.⁸⁷

Cancer: Influence of Neuroendocrine-Immune Interactions on Tumor Development and Progression

Neuroendocrine-immune interactions are implicated in various ways in cancer development and progression.¹ Stress and epinephrine can promote leukemia progression, and stress can enhance pre-B cell acute lymphoblastic leukemia progression.¹ Autonomic nerves contribute to prostate cancer growth via adrenergic receptors, and sympathetic neuropathy plays a role in myeloproliferative neoplasms.¹ Stress can activate beta-adrenergic signaling in tumor cells, affecting growth and metastasis, and stress is linked to colorectal cancer progression through a Th2 shift.¹

Sympathetic nervous system activation regulates breast cancer metastasis, increased by stress, and stress hormones like epinephrine may promote breast cancer progression through macrophage M2 polarization.¹ Myeloid-derived suppressor cells (MDSC) in post-operative breast cancer patients can be elevated by stress, facilitating metastasis, and psychological stress is linked to breast cancer development and progression.¹ Beta-blockers have potential as a therapeutic intervention by blocking adrenergic receptors involved in tumor-related immunosuppression.¹ Stress hormones can suppress natural killer (NK) cells, which control cancer.¹ Cytokines of the innate immune response, along with stress, can alter the sleep-wake cycle and disrupt the neuroendocrine system in cancer patients.⁹⁰ SNS and HPA axis dysregulation can promote angiogenesis, tumor cell proliferation, survival, and alter immune responses in the tumor microenvironment.⁹²

Chronic stress can weaken the immune system, making the body more hospitable to cancer, inhibit anoikis, and increase growth factor production, speeding tumor development.⁹³ Stress-induced chronic low-grade inflammation and declined immune surveillance are implicated in cancer development and progression.⁹⁴ Stress hormones can alter neutrophil behavior, potentially reawakening dormant cancer cells.⁹⁵ High cortisol levels may predispose to cancer development, progression, and worse prognosis.⁹⁶ Chronic stress, depression, and social isolation are linked to cancer progression.⁹⁷ Stress can promote angiogenesis in tumors.⁹⁷

An aging immune system can spur tumor growth by promoting harmful inflammation and suppressing anti-tumor immune cells.⁹⁸ Immune cells (T cells, B cells, NK cells) recognize and destroy cancer cells.⁹⁹ Cancer cells can evade immune destruction.⁹⁹ Cancer-associated inflammation can contribute to tumor development and progression.¹⁰² Cancer immunosurveillance involves the immune system identifying and destroying cancerous cells, but tumors can escape this control.¹⁰⁰ The immune system plays a dual role in cancer, both suppressing and promoting tumor growth.¹⁰⁰ Immunotherapy helps the immune system act against cancer.¹⁰¹

Neuroendocrine neoplasms (NENs) are heterogeneous tumors with neuroendocrine differentiation.¹⁰³ A significant proportion of NEN patients experience endocrine imbalances.¹⁰³ Pulmonary NENs are classified into carcinoids and neuroendocrine carcinomas.¹⁰³ Treating metastatic small intestinal neuroendocrine tumors (siNET) with immune checkpoint inhibitors has been challenging, suggesting a need for combination therapy.¹⁰⁴

Psychiatric Disorders: The Neuroendocrine-Immune System’s Contribution to Depression, Anxiety, and Schizophrenia

Depression is linked to chronic inflammation, and the ‘Old Friends’ hypothesis suggests a role for reduced microbial exposure.¹ Interferon-gamma is associated with early CFS, and interleukin-10 deficiency is also noted.¹ TBI-induced neuroendocrine dysregulation can exacerbate posttraumatic morbidity.⁶⁴ Neuroendocrine-immune interactions may be involved in the negative impacts of SARS-CoV-2 infection and social isolation on psychiatric issues.⁸⁷ Bidirectional communication exists between the neuroendocrine and immune systems.² Stress induces the release of pro-inflammatory cytokines, hormones, and neurotransmitters that can contribute to behavioral alterations.¹⁰⁶

Depression in coronary heart disease is associated with high inflammation and low cortisol output.¹ Oxytocin deficit is linked to depression in women and anxiety in children.¹ Interleukin-6 (IL-6) plays a role in stress susceptibility and transferring inflammatory signals to the brain, potentially leading to depressive symptoms.¹ MDD is prevalent in patients with chronic inflammatory conditions, who often exhibit higher levels of circulating pro-inflammatory cytokines.¹⁰⁷ The ‘glucocorticoid resistance model’ suggests reduced glucocorticoid receptor function in depression.¹⁰⁸ Stress can alter the epigenetic landscape, impacting genes involved in stress response and increasing depression susceptibility.¹⁰⁹ Toll-like receptor 4 (TLR4) links neuroimmune signaling and MDD.¹¹⁰ Serum TNF-alpha levels are linked to post-COVID depression.⁸⁹

Low oxytocin levels are linked to anxiety in children.¹ Bidirectional communication exists between the neuroendocrine and immune systems.² Altered neuroendocrine-immune responses in traumatic inflammation may contribute to anxiety disorders.¹¹¹ Anxiety symptoms are prevalent in COVID-19 survivors, potentially linked to inflammation.⁸⁹

Neuroendocrine-immune interactions may play a role in schizophrenia development.¹ Immune system activation could upregulate neuroendocrine pathways affecting tryptophan and tyrosine availability.¹¹² Stress is integrated across the brain and body, with the immune system influencing brain perception in schizophrenia.¹⁰⁵ Inflammation is a response to stress in schizophrenia.¹⁰⁶ Impaired neuroendocrine and immune responses to acute stress are seen in medication-naive patients with a first episode of psychosis.¹¹³

Synthesis of Major Mechanisms: Identifying Common Pathways and Interactions Across Diseases

Chronic stress, through sustained activation of the HPA axis and SNS, leads to inflammation across various diseases, including cardiovascular, metabolic, neurodegenerative, autoimmune, cancer, and psychiatric disorders. Dysregulation of hormones like cortisol, catecholamines, sex hormones, insulin, and adipokines impacts immune cell function and contributes to disease pathogenesis in multiple categories. Altered cytokine profiles (both pro- and anti-inflammatory) are common in the etiology and progression of these complex diseases, with specific cytokines like IL-6, TNF-α, and IL-1β frequently implicated.

Autonomic imbalance, particularly increased sympathetic tone, plays a role in cardiovascular diseases and potentially influences immune responses in other conditions. Glucocorticoid resistance is a recurring theme in autoimmune diseases, chronic inflammatory conditions, and psychiatric disorders, impairing the body’s ability to dampen inflammation. Neuroinflammation within the central nervous system is significant in neurodegenerative and psychiatric disorders, with potential links to systemic diseases. The gut-brain axis and microbiota are emerging as important factors influencing both immune and neuroendocrine systems, with implications for metabolic, neurodegenerative, and psychiatric disorders.

Table 3: Common Neuroendocrine-Immune Mechanisms Across Disease Categories

Conclusion and Future Directions: Implications for Research and Therapeutics

This report has highlighted the critical role of neuroendocrine-immune dysfunction and abnormal interactions in the pathogenesis of a wide array of common complex human diseases. The intricate communication between the nervous, endocrine, and immune systems, mediated by a complex network of hormones, neurotransmitters, neuropeptides, and cytokines, is essential for maintaining physiological homeostasis. Disruptions in this delicate balance, often triggered or exacerbated by chronic stress, can lead to a cascade of maladaptive responses that contribute significantly to the development and progression of cardiovascular diseases, metabolic disorders, neurodegenerative conditions, autoimmune diseases, respiratory illnesses, cancer, and psychiatric disorders.

The understanding of these complex interactions has profound implications for future research. There is a clear need for more integrated and holistic approaches that move beyond the traditional reductionist models to examine the dynamic interplay between the neuroendocrine and immune systems in disease etiology. Future studies should focus on elucidating the specific molecular mechanisms underlying these interactions in different disease contexts, identifying potential biomarkers for early diagnosis and disease monitoring, and exploring the influence of genetic and environmental factors on the neuroendocrine-immune axis.

Furthermore, this knowledge opens up promising therapeutic avenues. Targeting the neuroendocrine-immune axis through various strategies, such as immunomodulatory therapies, stress management techniques, interventions aimed at restoring hormonal balance, and approaches that modulate the gut-brain axis, holds significant potential for treating these complex diseases. The development of personalized medicine approaches that consider an individual’s unique neuroendocrine-immune profile may lead to more effective and targeted interventions, ultimately improving patient outcomes and quality of life.

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113. Impaired Neuroendocrine and Immune Response to Acute Stress in Medication-Naive Patients With a First Episode of Psychosis – ResearchGate
114. Impaired Neuroendocrine and Immune Response to Acute Stress in Medication-Naive Patients With a First Episode of Psychosis – PMC

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