Depression, Anxiety, Asthma, and Chronic Obstructive Pulmonary Disease (COPD)

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Patients with asthma and chronic obstructive pulmonary disease (COPD) often have psychiatric problems including cognitive dysfunction, anxiety, and depression (Bratek et al., 2015).

A recent study investigated the roles of psychiatric symptoms including anxiety, depression, and cognitive dysfunctions among patients with asthma and COPD (Bratek et al., 2015). The researchers observed that 33% of the COPD patients and 29% asthma patients had depression.

In addition, 42 % of the COPD patients and 41% of the asthma patients had elevated anxiety levels (Bratek et al., 2015). The study also found that the emotional and cognitive conditions were associated with tobacco smoke exposure and airway obstruction.

The study confirmed that those with mild to moderate asthma and COPD often have elevated levels of anxiety, depression, and cognitive disorders (Bratek et al., 2015). Environmental factors such as tobacco smoke and airflow obstruction may also be relevant.

Further studies in psychoneuroimmunology (PNI) are needed to measure the influences on the brain and immune systems more accurately. Such input would enable better preventive and therapeutic strategies.


Bratek A, Zawada K, Beil-Gawełczyk J, Beil S, Sozańska E, Krysta K, Barczyk A, Krupka-Matuszczyk I, Pierzchała W. Depressiveness, symptoms of anxiety and cognitive dysfunctions in patients with asthma and chronic obstructive pulmonary disease (COPD): possible associations with inflammation markers: a pilot study. J Neural Transm (Vienna). 2015 Aug;122 Suppl 1:S83-91. doi: 10.1007/s00702-014-1171-9.

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Anxiety, Depression, Diabetes, and High-Fat Diets

Depression and type 2 diabetes (T2D) are often seen together (Dutheil et al., 2016).

What are the mechanisms in psychoneuroimmunology (PNI) associated with these diseases? What are the roles of high-fat diets in anxiety and depression? How can the high-fat diets affect the brain and genetic signaling pathways?

Studies have indicated that having high-fat diets (HFD) for about 4 months may lead to anxiety and depressive problems (Dutheil et al., 2016). At the molecular level, high-fat diets may result in the dysfunctions in the intracellular networks associated with synaptic plasticity and insulin signaling. The changes also affect extracellular signal-regulated kinase (ERK) and P70S6K.

These alterations may affect the glucose homeostasis (Dutheil et al., 2016). In addition, higher corticosterone concentrations and abnormal innate immunity have been observed.

In addition, the higher levels of proinflammatory cytokines including IL-6, IL-1β, and TNFα may be induced (Dutheil et al., 2016). Moreover, drug interventions targeting the innate immunity and inflammation via the suppression of the purinergic P2X7 receptor have been found to ease the anxiety from HFD.

Studies have also observed that the antidepressant ketamine may relieve the anxiety problems from HFD (Dutheil et al., 2016). The drug may work on the ERK and P70S6 kinase signaling pathways in the brain regions including the prefrontal cortex.

Relevant studies have revealed the signaling pathways associated with chronic HFD that can lead to anxiety and depression (Dutheil et al., 2016). These networks can become the potential targets for the prevention and treatment of the comorbidity including anxiety, depression, and diabetes.


Dutheil S, Ota KT, Wohleb ES, Rasmussen K, Duman RS. High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation. Neuropsychopharmacology. 2016 Jun;41(7):1874-87. doi: 10.1038/npp.2015.357.

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Fear, Anxiety, PTSD, GAD, and Inflammation

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Fear- and anxiety-associated problems have been related to inflammation. As evidences, pro-inflammatory biomarkers have been found to be associated with affective behaviors (Michopoulos et al., 2017).

For example, in mental disorders such as posttraumatic stress disorder (PTSD), generalized anxiety disorder (GAD), panic disorder (PD), and phobias, increased levels of inflammatory biomarkers such as cytokines and C-reactive protein (CRP) have been identified (Michopoulos et al., 2017). Stress responses may have critical roles in these disorders, which may result in the alterations in central and peripheral immune functions and cytokine levels.

How about the conditions of inflammation in fear- and anxiety-based disorders?

Studies have demonstrated that the dysfunctions of the stress axis may be correlated with elevated sympathetic tone and suppressed parasympathetic activities (Michopoulos et al., 2017). Such changes in anxiety disorders may lead to the conditions of inflammation and in turn influence the brain areas associated with fear and anxiety. These brain areas include the amygdala, insula, hippocampus, and prefrontal cortex.

Because inflammation and associated alterations in the immune and brain functions are crucial in fear- and anxiety-based disorders, these mechanisms can be targeted for more effective prevention and treatment strategies (Michopoulos et al., 2017). More detailed understanding of the relevant pro-inflammatory biomarkers and pathways would be helpful for the management of anxiety disorders.


Michopoulos V, Powers A, Gillespie CF, Ressler KJ, Jovanovic T. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology. 2017 Jan;42(1):254-270. doi: 10.1038/npp.2016.146.

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Anxiety, Sleep, Fatigue, Inflammation, and Advanced Cancer

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Patients with terminal cancer are often troubled with fatigue (Rodrigues et al., 2016). Studies on the mechanisms would be helpful for improving the quality of life of the patients.

A recent study explored the associations among anxiety and depression, fatigue, sleep quality, inflammatory biomarkers, and quality of life among 51 patients with advanced solid tumors (Rodrigues et al., 2016). In the study, severe fatigue was detected in 19 patients.

Associations were identified between fatigue and the quality of sleep, as well as between the levels of fatigue and the cytokine TNF-α (Rodrigues et al., 2016). In addition, fatigue was also related to anxiety and depression, poor quality of life, and the hemoglobin levels.

In summary, the correlations between fatigue and anxiety, depression, sleep problems, poor quality of life, and inflammation indicate the requests for integrative strategies targeting both mental and physical disorders among the patient group (Rodrigues et al., 2016). Further studies in psychoneuroimmunology (PNI) may help elucidate how to apply the potential strategies for improving the quality of life for the patients.


Rodrigues AR, Trufelli DC, Fonseca F, de Paula LC, Giglio AD. Fatigue in Patients With Advanced Terminal Cancer Correlates With Inflammation, Poor Quality of Life and Sleep, and Anxiety/Depression. Am J Hosp Palliat Care. 2016 Dec;33(10):942-947.

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Anxiety, Inflammation, and Obesity

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Anxiety and depression have been related to the higher levels of inflammation among those with obesity. This group of people may also have the higher risks of cardiovascular disease (CVD) (Pierce et al., 2016).

In a recent study, the associations between anxiety (and depression) with the inflammatory biomarker serum C-reactive protein (CRP) were examined among 100 obese subjects with the mean age of 57.8 years (Pierce et al., 2016). The study found that the levels of anxiety but not depression were related to the biomarker CRP significantly.

The study indicates that anxiety but not depression may be closely associated with inflammation among those with obesity (Pierce et al., 2016). This is an interesting observation as depression has often been related to inflammation in other studies.

More studies in psychoneuroimmunology (PNI) may help reveal the correlations among anxiety, depression, inflammation, obesity, and cardiovascular disease risks. The emotional disorders such as anxiety may also become the possible targets for the prevention and treatment of CVD and obesity-associated disorders.


Pierce GL, Kalil GZ, Ajibewa T, Holwerda SW, Persons J, Moser DJ, Fiedorowicz JG. Anxiety independently contributes to elevated inflammation in humans with obesity. Obesity (Silver Spring). 2017 Feb;25(2):286-289. doi: 10.1002/oby.21698.

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Anxiety and Inflammation in Breast Cancer Survivors

Breast cancer survivors often have continuous psychological disorders such as anxiety and depression. Such mood problems may be caused by stress, and affect the quality of life (Pyter et al., 2017).

Neuroinflammation may have a critical role in the mood disorders among breast cancer survivors. Studies using mice models suggest that neuroinflammation including the genes Cd11b and Cxcl1 may be involved in the behavioral problems following mammary tumor removal (Pyter et al., 2017). The anxiety-like problems were observed together with certain central and peripheral immune biomarkers following tumor resection.

Continuous behavioral disorders such as anxiety in cancer survivors can be caused by the alterations in immune functions that continue to exist following tumor removal (Pyter et al., 2017). Such understanding may be helpful for improving cancer therapies and the effects on mental health and quality of life.


Pyter LM, Suarez-Kelly LP, Carson WE 3rd, Kaur J, Bellasario J, Bever SR. Novel rodent model of breast cancer survival with persistent anxiety-like behavior and inflammation. Behav Brain Res. 2017 May 4. pii: S0166-4328(17)30090-6. doi: 10.1016/j.bbr.2017.05.011.

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Emotional Factors and Fatigue in Adolescents

Fatigue in adolescents may be related to psychological, somatic, and lifestyle factors. In a longitudinal study of 653 adolescent girls, the correlations between the severity of fatigue and psychological conditions such as anxiety and depression were examined (ter Wolbeek et al., 2008).

The study found that about one-fourth of those who had severe fatigue also had continuous fatigue (ter Wolbeek et al., 2008). Factors including the elevated levels of anxiety and depression were associated with continuous fatigue, together with physical inactivity and lack of sleep.

The predictive factors of the onset of fatigue included depression, physical inactivity, and shorter sleep (ter Wolbeek et al., 2008). On the other hand, the lower level of fatigue severity was related to the lower levels of anxiety and depression, and higher levels of physical activity and longer sleep time.

The roles of the emotional factors in the onset and continuance of fatigue in adolescents indicate that integrative interventions targeting anxiety and depression may be helpful for the prevention and treatment of the problem (ter Wolbeek et al., 2008). In addition, physical activities and sleep are also important. Psychoneuroimmunology (PNI) studies may help understand more details among the associations, and how the integrative strategies may be helpful for solving the problem.


ter Wolbeek M, van Doornen LJ, Kavelaars A, Heijnen CJ. Predictors of persistent and new-onset fatigue in adolescent girls. Pediatrics. 2008 Mar;121(3):e449-57. doi: 10.1542/peds.2007-1093.

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Massage Therapy for Pediatric Cancer

Massage therapy has been suggested as a helpful complementary and alternative medicine (CAM) intervention for children with cancer. For example, a meta-analysis of 70 reports showed that massage therapy can be beneficial for alleviating anxiety, depression, constipation, pain, and hypertension (Hughes et al., 2008).

Massage therapy can also be helpful for supporting immune functions during the stages of immune suppression in cancer therapies (Hughes et al., 2008). Specifically, massage approaches with light to medium in pressure have been recommended for pediatric oncology.

In the processes, pediatric oncology nurses have been suggested as critical in the applications of the integrative interventions in addition to conventional therapies (Hughes et al., 2008). The nurses can help manage the interventions toward the optimal effects.

The meta-study suggests that massage is a safe and beneficial intervention among pediatric cancer patients (Hughes et al., 2008). It can be applied as an adjunct therapy for reducing side effects and psychological disorders related to anticancer therapies.

More studies in psychoneuroimmunology (PNI) are needed to understand the mechanisms of how massage therapies may affect the immune and nervous systems, such as the cytokine pathways. Such understanding would be helpful for improving the therapeutic effects.


Hughes D, Ladas E, Rooney D, Kelly K. Massage therapy as a supportive care intervention for children with cancer. Oncol Nurs Forum. 2008 May;35(3):431-42. doi: 10.1188/08.ONF.431-442.

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Psychological Stress and Ovarian Cancer

Ovarian cancer and distress are often seen together. To promote the therapeutic effects and quality of life for the patients, the factors involved in the associations between psychological distress and ovarian cancer need to be found (Arden-Close et al., 2008).

In a meta-analysis of 18 relevant studies, some correlations were found between psychological changes (including anxiety and depression) with the factors of younger age, as well as disease stages and symptoms (Arden-Close et al., 2008). Other factors may include the immune functions.

These studies have demonstrated that among the patient group of ovarian cancer, psychological stress has been related to the demographic factors and disease symptoms (Arden-Close et al., 2008). More studies in psychoneuroimmunology (PNI) would be needed to understand the psychological and immunological interactions in the associated disorders.


Arden-Close E, Gidron Y, Moss-Morris R. Psychological distress and its correlates in ovarian cancer: a systematic review. Psychooncology. 2008 Nov;17(11):1061-72. doi: 10.1002/pon.1363.

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Cytokines, Depression, and Psychoneuroimmunology

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Cytokines such as interferon (IFN)-alpha may cause dopamine depletion and affect the pathways of monoamine metabolism. Their alterations may result in behavioral changes including depression, psychomotor slowing, and fatigue (Miller, 2009).

How can cytokines affect the psychological conditions?

Studies have found that cytokine treatments such as interferon (IFN)-alpha may influence regional brain activities with lower cerebrospinal fluid levels of the dopamine metabolite and homovanillic acid (Miller, 2009). The cytokines may stimulate the neural circuits such as the dorsal anterior cingulate cortex related to anxiety and other behavioral alterations.

In the cytokine-associated psychiatric disorders, serotonin metabolism is important. Serotonin reuptake inhibitors have been used for IFN-alpha-induced depression (Miller, 2009). IFN-alpha may alter the metabolic enzymes such as indoleamine-2,3-dioxygenase (IDO).

In addition, other cytokine signaling pathways may be influenced including the pathways of p38 mitogen activated protein kinase (MAPKs) (Miller, 2009). Such changes may affect the production and reuptake of serotonin.

In summary, cytokine alterations may affect the pathways in the brain and behaviors by influencing the balance in behavioral and immune responses. Further studies in psychoneuroimmunology (PNI) about these pathways may contribute to personalized medicine of the relevant disorders.


Miller AH. Norman Cousins Lecture. Mechanisms of cytokine-induced behavioral changes: psychoneuroimmunology at the translational interface. Brain Behav Immun. 2009 Feb;23(2):149-58. doi: 10.1016/j.bbi.2008.08.006.

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Cytokine Therapies and Psychiatric Disorders

Cytokine therapies including interferon-alpha (IF-alpha) and interleukin-2 (IL-2) have been used for cancers and chronic diseases including melanoma, hepatitis C, and multiple sclerosis. However, they may cause neuropsychiatric side effects (Myint et al., 2009).

These side effects include depression, anxiety, psychosis, hypomanic mood, and cognitive dysfunctions. Some patients may continue to have cognitive problems even after stopping taking the drugs (Myint et al., 2009).

Animal studies have confirmed that the cytokine therapies may result in anxiety, depressive-like, and sickness behaviors, as well as social anhedonia with higher levels of pro-inflammatory cytokines (Myint et al., 2009).

Studies have found that the pro-inflammatory cytokines may stimulate some enzymes such as indoleamine 2-3, dioxygenase (IDO) (Myint et al., 2009). Such changes may promote the tryptophan degradation into kynurenine with lower levels of tryptophan in the brain. As a result, lower levels of the neurotransmitter serotonin may be produced that cannot maintain the normal mood conditions.

The imbalance in the catabolic kynurenine pathway and neurotransmitter-associated networks are critical for abnormal psychophysiological functions (Myint et al., 2009). Such imbalance may be caused by cytokine therapies and result in psychiatric disorders such as anxiety and depression. More studies are needed to find out the possibilities of maintaining the immune balance while using cytokine therapies.

Myint AM, Schwarz MJ, Steinbusch HW, Leonard BE. Neuropsychiatric disorders related to interferon and interleukins treatment. Metab Brain Dis. 2009 Mar;24(1):55-68. doi: 10.1007/s11011-008-9114-5.

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Depression in Older People

Chronic depression and dementia are often seen together in older people. Why do these happen? What are the mechanisms?

Studies have found that chronic stress may lead to the alterations in the hypothalamic-pituitary-adrenal (HPA) axis, as well as serotonergic and immune dysfunctions (Leonard and Myint, 2009). These alterations may in turn result in anxiety and depression disorders.

Specifically, the alterations in the HPA axis and the immune malfunctions may often cause neurodegenerative problems in the hippocampus, prefrontal cortex and amygdalae in the older people (Leonard and Myint, 2009).

Studies in psychoneuroimmunology (PNI) have shown that chronic stress and depression may lead to the increased levels of pro-inflammatory cytokines and glucocorticoids (Leonard and Myint, 2009). Such alterations may in turn result in behavioral symptoms related to depression. These mechanisms may help explain the connections among stress, depression, dementia, and inflammation in the elderly.


Leonard BE, Myint A. The psychoneuroimmunology of depression. Hum Psychopharmacol. 2009 Apr;24(3):165-75. doi: 10.1002/hup.1011.

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Psychoneuroimmunology and Ocular Diseases

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Studies in psychoneuroimmunology (PNI) have revealed the connections between psychosocial stress and depression with immune dysfunctions and various physical problems (Ventura, 2009).

How about ocular diseases?

Studies have shown that psychosocial stress may affect sympathetic adrenomedullary and hypothalamic pituitary axis activation and lead to alterations in the immune functions (Ventura, 2009). Integrative method based on psychoneuroimmunology (PNI) have been recommended for ocular diseases. However, more studies are still needed to understand the mechanisms.

The studies of psychoneuroimmunology may help understand how the psychological conditions including stress, anxiety, and depression can affect the immune functions and cytokine activities in ocular diseases (Ventura, 2009).


Ventura LM. Psychoneuroimmunology: application to ocular diseases. J Ocul Biol Dis Infor. 2009 Jun;2(2):84-93.


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Depression and Skin Disorders

Depressive disorders are often seen together with skin disorders. The rate of the comorbidity of depression and dermatologic diseases is about 30% (Filaković et al., 2009).

The disorders in psychodermatology have been classified into three categories (Filaković et al., 2009). The first category includes the psychophysiological disorders caused by stress experiences. The second category includes the secondary psychiatric diseases caused by skin disorders and therapies. The third category includes primary psychiatric diseases and therapies that may cause skin disorders.

The comorbidity of depression and skin disorders may result from specific immunological factors associated with genetic and adaptive processes (Filaković et al., 2009). The cytokines in the immune responses may be involved in the non-infective inflammatory activities and hormonal productions.

The alterations in such processes may influence the functions of the vegetative and central nervous system (CNS) and result in the “sickness behaviors”. Such behaviors and depression are often manifested as the anxiety, loss of appetite, anhedonia, as well as the reduction of concentration and interest (Filaković et al., 2009).

The complexity in the comorbidity of depressive and skin diseases requests integrative therapeutic strategies targeting various facets of both diseases. The team approaches and the collaboration between the psychological and the physical care have been recommended (Filaković et al., 2009). More studies should be helpful to reveal the relevant pathways in both disorders for more effective treatments.

Filaković P, Petek A, Koić O, Radanović-Grgurić L, Degmecić D. Comorbidity of depressive and dermatologic disorders – therapeutic aspects. Psychiatr Danub. 2009 Sep;21(3):401-10.

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Stress, Immunity, and Breast Cancer Patients

Breast cancer patients after surgery often have higher levels of distress and need psychosocial adaptation to the new conditions. The problems of distress among these patients have been related to cellular immune dysfunctions with the negative impacts on the recovery of the disease (Blomberg et al., 2009).

A study assessed the relationships between psychological adaptation indicators including mood and overall quality of life (QOL), and the cytokine levels of T-helper cell type 1 (Th1) from peripheral mononuclear cells (Blomberg et al., 2009). The study was done among the breast cancer patients after surgery but without adjuvant therapy.

The study found that decreased levels of anxiety were associated with higher levels of the Th1 cytokine interleukin-2 (IL-2) (Blomberg et al., 2009). In addition, higher levels of positive mood were associated with higher levels of the Th1 cytokines IL-12 and interferon-gamma (IFN-gamma). Better QOL was associated with higher levels of the Th1 cytokine tumor necrosis factor-alpha (TNF-alpha).

The study revealed that breast cancer patients after surgery may have individual variances in psychosocial adaptation associated with immunological variables (Blomberg et al., 2009). More investigations are still needed to understand these differences, connections and the relevant pathways.


Blomberg BB, Alvarez JP, Diaz A, Romero MG, Lechner SC, Carver CS, Holley H, Antoni MH. Psychosocial adaptation and cellular immunity in breast cancer patients in the weeks after surgery: An exploratory study. J Psychosom Res. 2009 Nov;67(5):369-76. doi: 10.1016/j.jpsychores.2009.05.016.

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Obesity, Emotional Conditions, Eating Behaviors, and Inflammation

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Obesity has been associated with chronic low-degree inflammation that can result in stress and behavioral problems. A study investigated the correlations among adiposity, low-grade inflammation, eating behaviors, and emotional conditions among obese women going through gastric surgery (Capuron et al., 2011).

The study examined 101 women with severe or morbid obesity before and one year after the gastric surgery (Capuron et al., 2011). The roles of surgery-caused weight loss in the correlations were also assessed.

The study showed that the levels of serum inflammatory biomarkers such as interleukin-6 (IL-6) and high-sensitive C-reactive protein (hsCRP) were related to the depression and anxiety aspects of neuroticism (Capuron et al., 2011). Elevated levels of inflammation predicted increased levels of anxiety and depression. Lower levels of inflammatory biomarkers, especially lower levels of hsCRP were related to lower levels of anxiety and moderate eating behaviors.

The study demonstrated that obesity is tightly related to chronic low-grade inflammation. The body mass index (BMI) has been associated with inflammatory biomarkers and adipokines (Capuron et al., 2011). On the other hand, gastric surgery resulted in weight loss and lower levels of inflammation.

The study confirmed the close correlations among adiposity, inflammation and affectivity in obesity (Capuron et al., 2011). Surgery-caused weight loss has been related to lower levels of inflammation and adipokines including leptin and adiponectin.

In addition, weight loss has been associated with better emotional conditions and eating behaviors (Capuron et al., 2011). The inflammatory conditions may be the critical factors connecting emotional distress and psychological conditions in obesity.


Capuron L, Poitou C, Machaux-Tholliez D, Frochot V, Bouillot JL, Basdevant A, Layé S, Clément K. Relationship between adiposity, emotional status and eating behaviour in obese women: role of inflammation. Psychol Med. 2011 Jul;41(7):1517-28. doi: 10.1017/S0033291710001984.

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Sleep loss, Mood, and Pain in Rheumatoid Arthritis

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Sleep disturbances have been closely related to pain. What are the influences of sleep loss on mood and pain among patients with rheumatoid arthritis (RA)?

In a study of 27 patients with rheumatoid arthritis and 27 controls, the correlations among sleep deprivation, mood symptoms, and pain were analyzed (Irwin et al., 2012). The study found that partial night sleep deprivation resulted in higher levels of fatigue, anxiety, and depression among patients with rheumatoid arthritis.

In addition, higher levels of pain severity and higher number of painful joints were also reported in the same RA group (Irwin et al., 2012). These findings support the connections among sleep loss, mood changes, and arthritis pain.

As sleep disturbances and arthritis pain may have bi-directional interactions, the improvement of sleep quality may be an important strategy for preventing and relieving pain among arthritis patients. Such strategy would also improve the patients’ quality of life. Further studies in psychoneuroimmunology (PNI) are needed to reveal the mechanisms in these interactions.


Irwin MR, Olmstead R, Carrillo C, Sadeghi N, Fitzgerald JD, Ranganath VK, Nicassio PM. Sleep loss exacerbates fatigue, depression, and pain in rheumatoid arthritis. Sleep. 2012 Apr 1;35(4):537-43. doi: 10.5665/sleep.1742.

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Anxiety Disorders and Psychoneuroimmunology

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

The discoveries in psychoneuroimmunology (PNI) need to be translated into clinical care and better quality of life for patients. Such translational efforts are especially meaningful for the treatment of neuropsychiatric disorders with the elucidation of the bidirectional interactions between the central nervous system (CNS) and the immune system (Hou and Baldwin, 2012).

Specifically, the discovery of biomarkers via PNI studies can be applied for more accurate diagnosis and more comprehensive treatments. Because inflammation has the essential roles in psychoneuroimmunology processes, inflammatory biomarkers can be critical in the connections between psychosocial factors and pathological conditions and symptoms.

For example, the alterations in cytokine signaling pathways in the brain may cause behavioral problems (Hou et al., 2013). Cytokines have been found with important roles in major depression (Hou and Baldwin, 2012). Antidepressants have also been observed to have immunomodulating effects. In anxiety disorders, different cytokines may be involved in the neuronal communications associated with various problems (Hou and Baldwin, 2012).

More studies in psychoneuroimmunology are still needed to reveal the reciprocal connections between anxiety disorders and inflammation. The identification of relevant biomarkers would contribute to the discovery of better therapeutic targets for these disorders.


Hou R, Baldwin DS. A neuroimmunological perspective on anxiety disorders. Hum Psychopharmacol. 2012 Jan;27(1):6-14. doi: 10.1002/hup.1259.

Hou R, Tang Z, Baldwin DS. Potential neuroimmunological targets in the treatment of anxiety disorders. Mod Trends Pharmacopsychiatry. 2013;29:67-84. doi: 10.1159/000351965.

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Anxiety, Depression, and Systemic Sclerosis

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Recent studies including those in psychoneuroimmunology (PNI) have collected many evidences on the psychosocial correlations with systemic sclerosis (scleroderma). Systemic sclerosis has been associated with clinical mood disorders including anxiety and depression (Malcarne et al., 2013). It is also often seen with other health problems such as sleep disorders, fatigue, pain, and pruritus.

In addition, studies about the relationships between systemic sclerosis and body image distress have identified the critical factors of alterations in the facial skin and hands (Malcarne et al., 2013). The workplace disability related to systemic sclerosis may be predicted by the factors of breathing problems and fatigue.

Because of the complex mechanisms involved in systemic sclerosis and associated health problems, multidisciplinary care has been suggested helpful for improving the quality of life among the relevant patients (Malcarne et al., 2013). Broader studies at different levels of systemic sclerosis are still needed, especially about the psychosocial factors and associated immune dysfunctions. Such studies would be useful for the prediction, prevention, and treatment of systemic sclerosis and relevant psychological and physiological problems.


Malcarne VL, Fox RS, Mills SD, Gholizadeh S. Psychosocial aspects of systemic sclerosis. Curr Opin Rheumatol. 2013 Nov;25(6):707-13. doi: 10.1097/01.bor.0000434666.47397.c2.

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Psychoneuroimmunology, Meditation, and Stress Management

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Meditation is a mind-body practice that may help with the management of stress. It may reduce the allostatic load and improve the overall well-being both mentally and physically. There are many different approaches or styles of meditation. The practice of PsychoNeuroEndocrinoImmunology-based meditation (PNEIMED) is the integration of philosophical lessons and Buddhist-style meditation (Bottaccioli et al., 2014).

A recent study assessed the influences of the PNEIMED training for four days (or 30 h) on stress among 125 healthy subjects (Bottaccioli et al., 2014). The participants answered questionnaires about stress. Their salivary cortisol levels were examined after awakening and while taking a challenging mental task.

The study found that the PNEIMED training resulted in significantly lower self-rated distress scores (Bottaccioli et al., 2014). The group with training had better psychological well-being and lower cortisol levels upon awakening. This group also had lower amplitudes and durations of the cortisol responses during the challenging tasks.

These results indicate that even brief PNEIMED training may have good effects on relieving stress and anxiety (Bottaccioli et al., 2014). Such practice may be beneficial for those under job-associated stress conditions. However, more studies with larger population groups may be needed to determine the minimum and optimal dosages and components of such trainings in meditation.


Bottaccioli F, Carosella A, Cardone R, Mambelli M, Cemin M, D’Errico MM, Ponzio E, Bottaccioli AG, Minelli A. Brief training of psychoneuroendocrinoimmunology-based meditation (PNEIMED) reduces stress symptom ratings and improves control on salivary cortisol secretion under basal and stimulated conditions. Explore (NY). 2014 May-Jun;10(3):170-9. doi: 10.1016/j.explore.2014.02.002.

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Anxiety and Vaccine Responses in Early Adolescence

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

The field of psychoneuroimmunology (PNI) focuses on the studies of the interactions among psychological activities such as stress, and the nervous and immune systems. Many evidences have been identified through animal or human adult observations.

How about children and adolescents? More PNI studies may be needed for this group of population, especially for personalized medicine. In a study of vaccine response data from 126 children (11-year-olds), the associations between psychosocial risks including anxiety and the immune responses were examined before and after the vaccination (O’Connor et al., 2014).

The study showed that children’s internalizing mood symptoms were related to continuously increased antibody responses (O’Connor et al., 2014). The connections between elevated vaccine response and depressive and anxiety symptoms during the early adolescence indicate the possible differences between adults and children in the interactions between the brain and immune systems.

These findings suggest that personalized studies in psychoneuroimmunology based on different age populations are necessary to establish different PNI models for different patient groups.


O’Connor TG, Moynihan JA, Wyman PA, Carnahan J, Lofthus G, Quataert SA, Bowman M, Caserta MT. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence. Dev Psychopathol. 2014 Nov;26(4 Pt 2):1567-76. doi: 10.1017/S0954579414001242.

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Mindfulness Meditation for Sleep Disorders in Older Adults

Among older adults, sleep disturbances are frequently complained. However, the problems have very limited therapeutic choices. Approaches from mind-body medicine such as mindfulness meditation may help improve sleep quality in this population group with sleep problems.

A randomized clinical trial investigated the effects of mindful awareness practices (MAPs) intervention and sleep hygiene education (SHE) among older adults with the mean age of 66.3 who were having moderate sleep disturbances (Black et al., 2015). The study detected the symptoms of insomnia, stress, anxiety, depression, and fatigue. Some inflammatory signaling factors such as nuclear factor (NF)-κB were also tested.

The study found that those in the MAPs group had better sleep quality in comparison with those in the SHE group (Black et al., 2015). In addition, the MAPs group showed better performance in the measurements of the symptoms of insomnia, depression, and fatigue. Moreover, lower levels of NF-κB were observed in both groups over time.

The findings suggest that the community-accessible MAPs intervention may be more effective on improving sleep quality than a structured SHE intervention (Black et al., 2015). Such findings may have clinical implications for using mindfulness-based interventions to alleviate sleep disorders among older adults for sleep-associated daytime problems and for improving their quality of life.


Black DS, O’Reilly GA, Olmstead R, Breen EC, Irwin MR. Mindfulness meditation and improvement in sleep quality and daytime impairment among older adults with sleep disturbances: a randomized clinical trial. JAMA Intern Med. 2015 Apr;175(4):494 501. doi: 10.1001/jamainternmed.2014.8081.

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Stress, Depression, and Medial Prefrontal Cortex

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

Major depressive disorder (MDD) can be triggered by stress experiences. Studies have shown that stress may change the reward processing (Kumar et al., 2015). What are the effects of stress exposure on the brain, such as those associated with reward processing?

In a recent study of 12 patients with MDD, the influences of acute and chronic life stress were examined. The study showed elevated activation of medial prefrontal cortex (mPFC) to reward feedback in the acute stress conditions among those with higher perceived stressor severity (Kumar et al., 2015).

In addition, those with depression had stronger associations between perceived stressor severity levels and reward-related mPFC activation in the acute stress conditions (Kumar et al., 2015). MDD patients also had lower levels of mPFC gray matter but still had robust functions in those areas.

The study concluded that MDD patients might need more mPFC activation for reward processing under stressful conditions (Kumar et al., 2015). Because the study was done in a relatively small group, more studies with larger groups are necessary to confirm the correlations among stress, depression, and brain functions including the reward-related mPFC activation.


Kumar P, Slavich GM, Berghorst LH, Treadway MT, Brooks NH, Dutra SJ, Greve DN, O’Donovan A, Bleil ME, Maninger N, Pizzagalli DA. Perceived life stress exposure modulates reward-related medial prefrontal cortex responses to acute stress in depression. J Affect Disord. 2015 Jul 15;180:104-11. doi: 10.1016/j.jad.2015.03.035.

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Resilience, Adversity, Gene Expression, and Wellbeing

Chronic social adversity may lead to a “conserved transcriptional response to adversity (CTRA)” with higher levels of pro-inflammatory genes and lower levels of antiviral- and antibody-related genes. Certain psychological resilience factors have been found to alleviate CTRA (Cole et al., 2015).

What are the influences of psychological resilience and adversity factors on CTRA?

A recent study was done to find out the relevant influences of these factors among 108 community-dwelling older adults with the mean age of 73 (Cole et al., 2015). The resilience factors included the well-being with purpose and meaning in life. The adversity factors included perceived social isolation and loneliness.

The study examined the CTRA gene expression in the peripheral blood samples and the correlations with the factors of loneliness and well-being (Cole et al., 2015). The researchers observed elevated levels of CTRA gene expression related to loneliness. On the other hand, lower levels of the gene expression were found to be related to well-being.

In addition, the resilience factors had the effects of alleviation and compensation for the adverse influences of loneliness on the gene expression (Cole et al., 2015). Such associations suggest potential strategies for improving health problems related to social isolation through the strengthen of resilience factors such as purpose and meaning in life.


Cole SW, Levine ME, Arevalo JM, Ma J, Weir DR, Crimmins EM. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology. 2015 Dec;62:11-7. doi: 10.1016/j.psyneuen.2015.07.001.

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Psychoneuroimmunology and Anxiety Disorders

Stress, Chronic Diseases, and Psychoneuroimmunology

Stress, Depression, Inflammation, and Psychoneuroimmunology

The incidence of psychiatric disorders including anxiety, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorders (OCD) is getting higher and higher in the modern world (Furtado and Katzman, 2015). These problems have resulted in severe public and economic problems.

With the development in psychoneuroimmunology (PNI), a question is that “what is the role of the immune system in these conditions”? How can the knowledge be used for psychiatric treatment?

With the detection of the alterations in the cortisol and cytokine concentrations, the stress-associated disorders have been related to the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis (Furtado and Katzman, 2015). Such findings may be used for the discovery of biomarkers and treatment targets.

Further studies in psychoneuroimmunology of the problems such as anxiety and PTSD may help elucidate the complex mechanisms of these disorders (Furtado and Katzman, 2015). The identification of the neuroinflammatory pathways may contribute to the discovery of better therapeutic strategies.


Furtado M, Katzman MA. Neuroinflammatory pathways in anxiety, posttraumatic stress, and obsessive compulsive disorders. Psychiatry Res. 2015 Sep 30;229(1-2):37-48. doi: 10.1016/j.psychres.2015.05.036.

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