Give
News
Substack

Treatment Resistant Depression, The Surprising Connection Most Doctors Miss

Decorative image of multiple pills of different sizes, shapes and colors, spilling from a pill bottle, with a gradient yellow to orange background.

Treatment Resistant Depression; What Your Doctor Wasn’t Taught

Depression is often stigmatized preventing individuals from seeking the help they need. But what happens when you seek treatment only to discover that your prescribed antidepressant doesn’t work?

This is the reality for roughly 30% of patients who find themselves caught in a relentless cycle of tapering off one antidepressant only to begin another that proves equally ineffective.

But what causes treatment-resistant depression?

While many established treatment-resistant depression risk factors have been reported, there is only one risk factor supported by numerous peer-reviewed publications that is not commonly taught in medical schools. It’s the role inflammation plays in a subset of patients with treatment-resistant depression.

Pioneering psychiatrists from Oxford, Emory, Harvard, and Cambridge University are actively trying to change the way health professionals view the role inflammation plays in our mental health.

 But paradigm shifts in medicine take time. 

 Without further ado, let’s begin by defining treatment-resistant depression.

What Is Treatment-Resistant Depression?

Treatment-resistant depression is a type of major depressive disorder that does not respond to at least two different antidepressants even though they are taken at the proper dose and for a proper amount of time. A reduction in depression of less than 25% is often considered an inadequate response to antidepressants.

Treatment-Resistant Depression Causes

.Many well-established risk factors can increase your susceptibility to developing treatment-resistant depression, such as:

  1. Genetics – Genetic variations can influence how the body responds to antidepressants. 
  2. Obesity – Those with a higher BMI have been associated with a reduced response to antidepressants (1).
  3. Adverse childhood experiences – A traumatic event in a child’s life such as abuse, parental separation, tragic death, etc can influence refractory depression (2). 
  4. Chronic stress – Chronic stress can worsen depression and make it harder to treat (3). Learn more about how your hypothalamic-pituitary-adrenal axis (HPA axis) regulates your stress response. 
  5. Other medical conditions – Some medical conditions, such as thyroid disease, heart disease, and chronic pain, can cause or worsen depression (4).
  6. Mental health conditions – Other mental health conditions, such as personality disorders, post-traumatic stress disorder, and substance use disorder, can have similar symptoms to depression (5,6). 
  7. Life issues – Poverty, violence, unresolved grief or loss, family problems, and work stress can make it harder to heal from depression (2). 
  8. Age, gender, and health status – Women and senior citizens are more likely to experience drug-resistant depression (4,7). 
  9. Medication compliance – The level of compliance with the treatment regimen, the amount of time the medication is taken, and the dosage can all affect treatment. 
  10. Subtherapeutic doses – Taking a subtherapeutic dose of antidepressants can cause relative or “pseudo” treatment-resistant depression.

However, there is one cause of treatment-resistant depression in a subgroup of people that your doctor might not mention: chronic inflammation (8,9).

Many of the factors listed above like genetics (10), chronic stress (11), adverse childhood experiences (12,13), medications (14,15), mental health conditions (16-21), and specific life circumstances (3,22) can all cause chronic inflammation or enhance it.

Dr. Golam Khandaker, University of Bristol psychiatrist, aptly explains that “About a third of patients who are resistant to antidepressants show evidence of inflammation… [s]o, anti-inflammatory treatments could be relevant for a large number of people who suffer from depression.”

The link between chronic inflammation and our mental health is backed by more robust scientific studies than the neurotransmitter imbalance theory of depression (23).  

 If that sounds far-fetched then this next section is for you.

Inflammation and Depression: A Comprehensive Guide For Patients and Their Doctors

This 27 page guide contains 118 peer-reviewed sources written for both technical and nontechnical audiences alike. Let your doctor know that chronic inflammation can be associated with treatment-resistant depression by sharing the guide with them.
Learn More

Inflammatory Cytokines In The Blood Predict The Future Onset Of Depression

While the link between chronic inflammation and depression has been observed since the late 1980’s (24) it was unclear whether chronic inflammation causes depression or if depression leads to chronic inflammation. It was the classic ‘chicken or the egg’ conundrum.

Understanding what comes first is done using longitudinal studies. These studies enroll participants and study them for a predefined unit of time into the future instead of studying their past (retrospective study). 

In other words, longitudinal studies allow researchers to ask, “If inflammation spikes in the blood, will depression follow?”

One meta-analysis systematically reviewed the results from 38 different longitudinal studies, consisting of a combined 58,256 participants, to investigate the relationship between chronic systemic inflammation and depression (23). Their results indicate that the pro-inflammatory cytokine, IL-6, and the inflammatory biomarker CRP in the blood predicted the future onset of depression (23).

Combining these 38 studies and running an independent statistical analysis (meta-analysis) significantly strengthens the argument that the pro-inflammatory cytokine IL-6, and the inflammatory biomarker CRP, significantly increase your odds of later developing depression.

Depression Can Cause Inflammation In The Body

Not only can the inflammatory biomarkers IL-6 and CRP predict the future onset of depression, but the severity of depressive symptoms was associated with future increased levels of IL-6 (pro-inflammatory cytokine) and CRP (inflammatory biomarker) (23). In other words, a surge in severe depressive symptoms was followed by a proportional increase in the aforementioned inflammatory biomarkers while a lower increase followed a mild increase in depression in inflammation (23).

This suggests the relationship between inflammation in the body and depression in the brain is not linear, but circular (in a subset of patients).

Why Might Inflammation Affect Our Behavior?

During an acute infection, cytokines cause fatigue by signaling to the hypothalamus (25). This redirects energy toward fighting the infection to keep you alive. The evolutionary explanation for this phenomenon is simple, the inflammation tells your brain to conserve energy so it can be used to fight the infection.

"[C]ytokines, which the body produces to fight certain infections... activate areas of the brain that regulate depression and anxiety” Dr. Todd Gould Professor of Psychiatry, University of Maryland School of Medicine.

But what happens when the inflammation becomes chronic? Well, we know the immune system does not stop communicating with the brain in those with chronic inflammation. The communication however is different, manifesting as depression in some patients.

No Evidence of Low Serotonin Levels In The Depressed Brain

It is widely accepted that an imbalance of serotonin in the brain is to blame for the cause of depression. However, numerous studies have failed to find evidence that serotonin levels are indeed low in the brains of patients with clinical depression (26). In light of this data, or the lack thereof, most modern antidepressants work by boosting serotonin levels in the brain.  

This presents a problem. 

If your first antidepressant doesn’t work, then why would starting a new antidepressant, targeting the same serotonin pathway, work any differently? Sure, there could be patient-to-patient genetic variations that might cause one drug to work better than another, but multiple rounds of different antidepressants is simply illogical. 

Dr. Golam Khandaker, a psychiatrist at the University of Bristol supports this reasoning, “The current approach of a ‘one-size-fits-all’ medicine to treat depression is problematic. All currently available antidepressants target a particular type of neurotransmitter (serotonin), but a third of patients do not respond to these drugs (14).”

Could a different biological mechanism be influencing the cause of depression?

The Link Between Inflammation and Depression: A Historical Perspective

In the late 1980s, oncologists began treating cancer patients with pro-inflammatory cytokines called interferon alpha (IFNɑ) and tumor necrosis factor-alpha (TNFɑ)(24). The oncologists noticed something unexpected. A subset of their patients developed severe depression soon after the cytokines were delivered into their patient’s bloodstream (27).

One could argue that this is a predictable response. After all, they were diagnosed with cancer and were given what could have been toxic amounts of pro-inflammatory cytokines. Wouldn’t that also make you depressed? 

Dr. Andrew Miller of Emory University was one of the first psychiatrists to interview an IFN-ɑ-treated patient. He reported in an interview, “I really expected to see somebody under a blanket who’s shivering and shaking and miserable and toxic, and something that we typically see, and something like sepsis, where somebody’s very sick (28).”

Instead, he observed a “woman was very nicely dressed, makeup was on that looked very nice”, not a deathly ill patient.

Although these patients were not depressed before receiving immunotherapy, they now met the clinical definition of depression. This depression can be prevented by giving the cancer patients an anti-depressant two weeks before starting the immunotherapy (23). 

If delivering pro-inflammatory cytokines into the bloodstream can cause depression then you would predict that patients suffering from chronic inflammatory diseases and infections would be more prone to developing depression. 

Anti-inflammatories And Major Depression

If inflammation is causing mental health conditions in a subset of people then anti-inflammatories should be effective therapies for treating mental illness.

A research analysis (29) aggregated the results from 30 randomized controlled trials (RCTs) involving 1610 participants investigating the effectiveness and safety of using anti-inflammatory agents as a treatment for patients with major depression (30). Anti-inflammatory interventions considered in the analysis included,

  • omega-3 fatty acids (omega-3 FA)
  • N-acetylcysteine (NAC)
  • cytokine inhibitors
  • corticosteroids
  • NSAIDs
  • statins


While the authors noted limitations among a subset of studies, their analysis indicated that anti-inflammatory agents have the potential to safely and efficiently alleviate symptoms associated with major depression (29).

Dr. Golam Khandaker, University of Bristol psychiatrist, suggests that “the future of treating depression might involve identifying otherwise healthy patients for hidden signs of inflammation in the blood followed by [using] anti-inflammatory drugs in psychiatry for certain patients with depression (31).”

Chronic Inflammatory Conditions Increase Your Risk of Treatment-resistant Depression

Patients suffering from chronic inflammatory, infectious, and autoimmune diseases have elevated levels of pro-inflammatory cytokines in their blood (20,23,32-36). This includes the same cytokines (TNFɑ and IFNɑ) previously administered to cancer patients in the late 1980s (23). 

If chronic exposure to pro-inflammatory cytokines can increase your susceptibility to developing clinical depression then one would predict that patients suffering from chronic inflammatory diseases would be more prone to developing depression.

Not only is that true but chronic inflammatory diseases also increase your rate of developing other psychiatric conditions such as anxiety, mood disorders, and schizophrenia to name a few. 

Dr. Tom Pollack psychiatrist at Kings College, London explains, “We have known for some time that having a systemic autoimmune disease can negatively affect one’s mental health. Everyone working in healthcare with these patients should routinely ask about mental well-being, and patients should be supported to speak up without fear of judgment.

Below is a table summarizing the prevalence of psychiatric conditions attributed to not only autoimmune diseases but more generally chronic inflammatory diseases.

Disease/Syndrome Category

Disease Name

Cause

Mental Health Conditions

Autoimmune Disease

Sjögren’s Syndrome

Autoimmune attack on moisture-producing glands (lacrimal and salivary glands)

Depression (37), Anxiety (37), Cognitive Dysfunction (38)

 

Rheumatoid Arthritis

Autoimmune attack on joints

Depression (39), Anxiety (39), Bipolar Disorder (21), Cognitive Impairment (40)

 

Ankylosing Spondylitis

Autoimmune inflammation of the spine and sacroiliac joints

Depression (41), Anxiety (41), Cognitive Dysfunction (42)

 

Juvenile Arthritis

Autoimmune inflammation of the joints in children

Depression (43), Anxiety, Behavioral Problems (44)

 

Psoriatic Arthritis

Autoimmune inflammation of the joints and skin

Depression (45), Anxiety (45), Mood Disorders (46)

 

Lupus

Autoimmune attack on healthy tissues throughout the body

Depression (47), Anxiety (47,48), Mood Disorders (48), Cognitive Dysfunction (49)

 

Psoriasis

Unknown, believed to involve genetic predisposition and dysregulated immune response

Depression (50-52), Anxiety (51), Suicidal Ideation (50)

 

Celiac Disease

Immune reaction to gluten proteins in genetically predisposed individuals

Depression (53,54), Anxiety (53,54), Panic Disorder (53), Cognitive Impairment (55), Schizophrenia (56)

Chronic Disease/Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Unknown, possibly immune system dysfunction or viral infection

Depression (57), Anxiety (58), Cognitive Impairment (59), Sleep Disorders (60)

 

Postural Orthostatic Tachycardia Syndrome (POTS)

Dysfunction of the autonomic nervous system or autoimmune mechanisms

Anxiety (61,62), Depression (61,62), Cognitive Impairment (62), Sleep Disturbances (61)

 

Inflammatory Bowel Diseases & Syndromes

Unknown, a combination of genetic predisposition, environmental factors, and dysregulated immune response

Anxiety (63-65), Depression (63-65), Cognitive Impairment (66), Suicide (67)

 

Mast Cell Activation Syndrome (MCAS)

Inappropriate activation of mast cells

Anxiety (68,69), Panic Attacks (69), Depression (68,69)

 

Ehlers Danlos Syndrome (EDS)

A genetic disorder affecting connective tissue

Anxiety (70-72), Depression (70-72) Suicidal Ideation (72), Bipolar Disorder (72)

Infectious Disease

Long COVID

Persistent symptoms following COVID-19 infection

Depression (73,74), Anxiety (73,74), Cognitive Impairment (75), Fatigue (75), Sleep Disorders (73)

 

Toxoplasmosis

Toxoplasma gondii infection

Schizophrenia (18,35,76-78), Psychosis (76,77), Bipolar Disorder (18), Major Depression (76), Anxiety (76), Autism (76), Obsessive Compulsive Disorder (76)

 

Tuberculosis

Mycobacterium tuberculosis infection

Depression (79), Anxiety (79), Schizophrenia (19)

Chronic Allergic Disease

Chronic Sinusitis

Immune response to allergens

Anxiety (80-83), Depression (80-83), Fatigue (84), Sleep Disturbances (85)

 

Mast Cell Activation Syndrome (MCAS)

Inappropriate activation of mast cells

Anxiety (68,69), Panic Attacks (69), Depression (68,69)

Most of the referenced studies in the table below pool the data from numerous scientific reports, known as a meta-analysis. These meta-analyses provide more robust data sets, strengthening scientific conclusions.

Seemingly Healthy Individuals Suffer From Inflammation-induced Depression

One common misconception about the immune system’s ability to harm the brain is that only patients suffering from chronic inflammatory diseases are susceptible to disruptions in mental health. However, numerous studies suggest that this is simply not true. 

Otherwise healthy individuals with depression (36,39), anxiety (19,39), sleep disorders (39,86), bipolar disorder (32), or mood disorders (36) have all been found to have elevated pro-inflammatory cytokine levels in their blood.

So, what is the trigger that is causing healthy people to develop mental health issues?

Treatment-Resistant Depression and Inflammation

Recent research has highlighted a significant connection between chronic inflammation and treatment-resistant depression. A subset of individuals with TRD exhibit elevated levels of inflammatory markers, such as C-reactive protein (CRP) and proinflammatory cytokines. This inflammation can interfere with neurotransmitter function and reduce the effectiveness of traditional antidepressants (87). If you suspect that chronic inflammation might be contributing to your depression, here are some steps you can take to address it:

Inflammation and Depression: A Comprehensive Guide

Designed to help patients educate health professionals how the immune system causes depression.
2
15
14
4
18
8
20
16
7
- 27 pages
- 118 peer reviewed citations
Emailed straight to your inbox
Give It To Your Doctor

Drug-Resistant Depression Outlook

Understanding the role of chronic inflammation in treatment-resistant depression opens new avenues for effective treatment strategies. By recognizing that inflammation can be a significant factor in this type of drug-resistant depression, patients and healthcare providers can explore targeted therapies that address this underlying issue. 

This holistic approach not only offers hope for those who have struggled with traditional treatments but also underscores the importance of considering the body’s overall health in managing mental health conditions. If you suspect that inflammation may be contributing to your depression, seeking out specialists like immunopsychiatrists or discussing anti-inflammatory treatments with your healthcare provider could be a crucial step towards finding relief and improving your quality of life.

Smiling caucasian male scientist with short brown hair, fair skin, and brown eyes.

Written By

Matthew Menendez, Ph.D.

Director of Science Communication, Brain Inflammation Collaborative

Dr. Menendez has a passion for empowering patients navigating complex chronic diseases. Through innovative educational strategies, he bridges the gap between cutting-edge research and real-world understanding, helping individuals advocate for better care, access timely treatments, and reclaim their quality of life. 

Peer-Reviewed References

  1.     Oskooilar N, Wilcox CS, Tong ML, Grosz DE. Body mass index and response to antidepressants in depressed research subjects. J Clin Psychiatry. Nov 2009;70(11):1609-10. doi:10.4088/JCP.09l05226blu
  2.     Nanni V, Uher R, Danese A. Childhood maltreatment predicts unfavorable course of illness and treatment outcome in depression: a meta-analysis. Am J Psychiatry. Feb 2012;169(2):141-51. doi:10.1176/appi.ajp.2011.11020335
  3.     Cox J. How Stress Affects Mental Health. PsychCentral. Accessed May 31, 2024. https://psychcentral.com/stress/how-stress-affects-mental-health
  4.     Iosifescu DV, Nierenberg AA, Alpert JE, et al. The impact of medical comorbidity on acute treatment in major depressive disorder. Am J Psychiatry. Dec 2003;160(12):2122-7. doi:10.1176/appi.ajp.160.12.2122
  5.     Rush AJ, Wisniewski SR, Warden D, et al. Selecting among second-step antidepressant medication monotherapies: predictive value of clinical, demographic, or first-step treatment features. Arch Gen Psychiatry. Aug 2008;65(8):870-80. doi:10.1001/archpsyc.65.8.870
  6.     Correa R, Akiskal H, Gilmer W, Nierenberg AA, Trivedi M, Zisook S. Is unrecognized bipolar disorder a frequent contributor to apparent treatment resistant depression? J Affect Disord. Dec 2010;127(1-3):10-8. doi:10.1016/j.jad.2010.06.036
  7.     Unützer J, Park M. Older Adults With Severe, Treatment-Resistant Depression. JAMA. 2012;308(9):909-918. doi:10.1001/2012.jama.10690
  8.     Strawbridge R, Hodsoll J, Powell TR, et al. Inflammatory profiles of severe treatment-resistant depression. J Affect Disord. Mar 1 2019;246:42-51. doi:10.1016/j.jad.2018.12.037
  9.     Kappelmann N, Lewis G, Dantzer R, Jones PB, Khandaker GM. Antidepressant activity of anti-cytokine treatment: a systematic review and meta-analysis of clinical trials of chronic inflammatory conditions. Mol Psychiatry. Feb 2018;23(2):335-343. doi:10.1038/mp.2016.167
  10.   Ligthart S, Vaez A, Võsa U, et al. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. Am J Hum Genet. Nov 1 2018;103(5):691-706. doi:10.1016/j.ajhg.2018.09.009
  11.   Gupta A, Agarwal V. Inflammation as a shared mechanism of chronic stress related disorders with potential novel therapeutic targets. Naunyn Schmiedebergs Arch Pharmacol. Jun 8 2024;doi:10.1007/s00210-024-03205-5
  12.   Danese A, Moffitt TE, Harrington H, et al. Adverse childhood experiences and adult risk factors for age-related disease: depression, inflammation, and clustering of metabolic risk markers. Arch Pediatr Adolesc Med. Dec 2009;163(12):1135-43. doi:10.1001/archpediatrics.2009.214
  13.   Mathur A, Li JC, Lipitz SR, Graham-Engeland JE. Emotion Regulation as a Pathway Connecting Early Life Adversity and Inflammation in Adulthood: a Conceptual Framework. Advers Resil Sci. 2022;3(1):1-19. doi:10.1007/s42844-022-00051-3
  14.   Parfitt JR, Driman DK. Pathological effects of drugs on the gastrointestinal tract: a review. Hum Pathol. Apr 2007;38(4):527-36. doi:10.1016/j.humpath.2007.01.014
  15.   Eyre T, Van-Hamel-Parsons V, Wang LM, Hughes KA, Littlewood TJ. An unusual cause of anaemia of chronic disease: induced chronic inflammatory state. Case Rep Hematol. 2011;2011:939080. doi:10.1155/2011/939080
  16.   Peruzzolo TL, Pinto JV, Roza TH, et al. Inflammatory and oxidative stress markers in post-traumatic stress disorder: a systematic review and meta-analysis. Mol Psychiatry. Aug 2022;27(8):3150-3163. doi:10.1038/s41380-022-01564-0
  17.   Fitton R, Sweetman J, Heseltine-Carp W, van der Feltz-Cornelis C. Anti-inflammatory medications for the treatment of mental disorders: A scoping review. Brain Behav Immun Health. Dec 2022;26:100518. doi:10.1016/j.bbih.2022.100518
  18.   Liu T, Gao P, Bu D, Liu D. Association between Toxoplasma gondii infection and psychiatric disorders: a cross-sectional study in China. Scientific Reports. 2022/09/05 2022;12(1):15092. doi:10.1038/s41598-022-16420-y
  19.   Hayward SE, Deal A, Rustage K, et al. The relationship between mental health and risk of active tuberculosis: a systematic review. BMJ Open. Jan 6 2022;12(1):e048945. doi:10.1136/bmjopen-2021-048945
  20.   Fallon BA, Madsen T, Erlangsen A, Benros ME. Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study. Am J Psychiatry. Oct 1 2021;178(10):921-931. doi:10.1176/appi.ajp.2021.20091347
  21.   Charoenngam N, Ponvilawan B, Ungprasert P. Patients with rheumatoid arthritis have a higher risk of bipolar disorder: A systematic review and meta-analysis. Psychiatry Res. Dec 2019;282:112484. doi:10.1016/j.psychres.2019.112484
  22.   Mainous AG, 3rd, Orlando FA, Yin L, Sharma P, Wu V, Saguil A. Inflammation and poverty as individual and combined predictors of 15-year mortality risk in middle aged and older adults in the US. Front Med (Lausanne). 2023;10:1261083. doi:10.3389/fmed.2023.1261083
  23.   Mac Giollabhui N, Ng TH, Ellman LM, Alloy LB. The longitudinal associations of inflammatory biomarkers and depression revisited: systematic review, meta-analysis, and meta-regression. Mol Psychiatry. Jul 2021;26(7):3302-3314. doi:10.1038/s41380-020-00867-4
  24.   Shen J, Xiao Z, Zhao Q, et al. Anti-cancer therapy with TNFα and IFNγ: A comprehensive review. Cell Prolif. Aug 2018;51(4):e12441. doi:10.1111/cpr.12441
  25.   Le Thuc O, Stobbe K, Cansell C, Nahon J-L, Blondeau N, Rovère C. Hypothalamic Inflammation and Energy Balance Disruptions: Spotlight on Chemokines. Review. Frontiers in Endocrinology. 2017-August-14 2017;8doi:10.3389/fendo.2017.00197
  26.   Moncrieff J, Cooper RE, Stockmann T, Amendola S, Hengartner MP, Horowitz MA. The serotonin theory of depression: a systematic umbrella review of the evidence. Molecular Psychiatry. 2023/08/01 2023;28(8):3243-3256. doi:10.1038/s41380-022-01661-0
  27.   McFarland DC, Doherty M, Atkinson TM, et al. Cancer-related inflammation and depressive symptoms: Systematic review and meta-analysis. Cancer. Jul 1 2022;128(13):2504-2519. doi:10.1002/cncr.34193
  28.   Miller A. Health Is Everything. Dr. Andrew Miller: Part 1 – Inflammation, Stress, and Depression.
  29.   Bai S, Guo W, Feng Y, et al. Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials. J Neurol Neurosurg Psychiatry. Jan 2020;91(1):21-32. doi:10.1136/jnnp-2019-320912
  30.   Odelya Gertel Kraybill PD. Anti-inflammatories help major depression. Psychology Today. Accessed May 28th, 2024. https://www.psychologytoday.com/us/blog/expressive-trauma-integration/201911/anti-inflammatories-help-major-depression
  31.   Anti-inflammatory drugs could help treat symptoms of depression, study suggests. University of Cambridge. Accessed March 02, 2024, 2024. https://www.cam.ac.uk/research/news/anti-inflammatory-drugs-could-help-treat-symptoms-of-depression-study-suggests#:~:text=%E2%80%9CThe%20current%20approach%20of%20a%20’one%2Dsize%2Dfits%2Dall’%20medicine,patients%20do%20not%20respond%20to%20these%20drugs.
  32.   Dolsen MR, Soehner AM, Harvey AG. Proinflammatory Cytokines, Mood, and Sleep in Interepisode Bipolar Disorder and Insomnia: A Pilot Study With Implications for Psychosocial Interventions. Psychosom Med. Jan 2018;80(1):87-94. doi:10.1097/psy.0000000000000529
  33.   Johnco C, Kugler BB, Murphy TK, Storch EA. Obsessive-compulsive symptoms in adults with Lyme disease. Gen Hosp Psychiatry. Mar-Apr 2018;51:85-89. doi:10.1016/j.genhosppsych.2018.01.009
  34.   Cocuzza S, Maniaci A, La Mantia I, et al. Obsessive-compulsive disorder in PANS/PANDAS in children: in search of a qualified treatment—a systematic review and metanalysis. Children. 2022;9(2):155.
  35.   Achaw B, Tesfa H, Zeleke AJ, et al. Sero-prevalence of Toxoplasma gondii and associated risk factors among psychiatric outpatients attending University of Gondar Hospital, Northwest Ethiopia. BMC Infect Dis. Jul 4 2019;19(1):581. doi:10.1186/s12879-019-4234-6
  36.   Felger JC. Imaging the Role of Inflammation in Mood and Anxiety-related Disorders. Curr Neuropharmacol. 2018;16(5):533-558. doi:10.2174/1570159×15666171123201142
  37.   Vera Milic MG. Personality, depression and anxiety in primary Sjogren’s syndrome – Association with sociodemographic factors and comorbidity.
  38.   Manzo C, Martinez-Suarez E, Kechida M, Isetta M, Serra-Mestres J. Cognitive Function in Primary Sjögren’s Syndrome: A Systematic Review. Brain Sci. Apr 15 2019;9(4)doi:10.3390/brainsci9040085
  39.   Machin AR, Babatunde O, Haththotuwa R, et al. The association between anxiety and disease activity and quality of life in rheumatoid arthritis: a systematic review and meta-analysis. Clin Rheumatol. May 2020;39(5):1471-1482. doi:10.1007/s10067-019-04900-y
  40.   Pankowski D, Wytrychiewicz-Pankowska K, Janowski K, Pisula E. Cognitive impairment in patients with rheumatoid arthritis: A systematic review and meta-analysis. Joint Bone Spine. May 2022;89(3):105298. doi:10.1016/j.jbspin.2021.105298
  41.   Park JY, Howren AM, Zusman EZ, Esdaile JM, De Vera MA. The incidence of depression and anxiety in patients with ankylosing spondylitis: a systematic review and meta-analysis. BMC Rheumatol. 2020;4:12. doi:10.1186/s41927-019-0111-6
  42.   Vitturi BK, Suriano ES, Pereira de Sousa AB, Torigoe DY. Cognitive Impairment in Patients with Ankylosing Spondylitis. University Press
  43.   Fair DC, Rodriguez M, Knight AM, Rubinstein TB. Depression And Anxiety In Patients With Juvenile Idiopathic Arthritis: Current Insights And Impact On Quality Of Life, A Systematic Review. Open Access Rheumatol. 2019;11:237-252. doi:10.2147/oarrr.s174408
  44.   LeBovidge JS, Lavigne JV, Donenberg GR, Miller ML. Psychological Adjustment of Children and Adolescents With Chronic Arthritis: A Meta-analytic Review. Journal of Pediatric Psychology. 2003;28(1):29-39. doi:10.1093/jpepsy/28.1.29
  45.   Zusman EZ, Howren AM, Park JYE, Dutz J, De Vera MA. Epidemiology of depression and anxiety in patients with psoriatic arthritis: A systematic review and meta-analysis. Semin Arthritis Rheum. Dec 2020;50(6):1481-1488. doi:10.1016/j.semarthrit.2020.02.001
  46.   Cajamarca-Barón J, Guavita-Navarro D, Gallego-Cardona L, et al. Mood disorders in psoriatic arthritis. Revista Colombiana de Reumatología. 2023/07/01/ 2023;30:S97-S104. doi:https://doi.org/10.1016/j.rcreu.2023.02.013
  47.   Zhang L, Fu T, Yin R, Zhang Q, Shen B. Prevalence of depression and anxiety in systemic lupus erythematosus: a systematic review and meta-analysis. BMC Psychiatry. Feb 14 2017;17(1):70. doi:10.1186/s12888-017-1234-1
  48.   Tisseverasinghe A, Peschken C, Hitchon C. Anxiety and mood disorders in systemic lupus erythematosus: current insights and future directions. Current rheumatology reports. 2018;20:1-11.
  49.   Zabala A, Salgueiro M, Sáez-Atxukarro O, Ballesteros J, Ruiz-Irastorza G, Segarra R. Cognitive Impairment in Patients With Neuropsychiatric and Non-neuropsychiatric Systemic Lupus Erythematosus: A Systematic Review and Meta-analysis. University Press
  50.   Singh S, Taylor C, Kornmehl H, Armstrong AW. Psoriasis and suicidality: A systematic review and meta-analysis. J Am Acad Dermatol. Sep 2017;77(3):425-440.e2. doi:10.1016/j.jaad.2017.05.019
  51.   Kamalaraj N, El-Haddad C, Hay P, Pile K. Systematic review of depression and anxiety in psoriatic arthritis. Int J Rheum Dis. Jun 2019;22(6):967-973. doi:10.1111/1756-185x.13553
  52.   Lukmanji A, Basmadjian RB, Vallerand IA, Patten SB, Tang KL. Risk of Depression in Patients With Psoriatic Disease: A Systematic Review and Meta-Analysis. J Cutan Med Surg. May-Jun 2021;25(3):257-270. doi:10.1177/1203475420977477
  53.   Sharma N, Singh K, Senapati S. Celiac disease poses significant risk in developing depression, anxiety, headache, epilepsy, panic disorder, dysthymia: A meta-analysis. Indian Journal of Gastroenterology. 2021:1-10.
  54.   Smith D, Gerdes L. Meta‐analysis on anxiety and depression in adult celiac disease. Acta Psychiatrica Scandinavica. 2012;125(3):189-193.
  55.   Croall ID, Sanders DS, Hadjivassiliou M, Hoggard N. Cognitive deficit and white matter changes in persons with celiac disease: a population-based study. Gastroenterology. 2020;158(8):2112-2122.
  56.   Wijarnpreecha K, Jaruvongvanich V, Cheungpasitporn W, Ungprasert P. Association between celiac disease and schizophrenia: a meta-analysis. Eur J Gastroenterol Hepatol. Apr 2018;30(4):442-446. doi:10.1097/meg.0000000000001048
  57.   Loades ME, Sheils EA, Crawley E. Treatment for paediatric chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) and comorbid depression: a systematic review. BMJ Open. 2016;6(10):e012271. doi:10.1136/bmjopen-2016-012271
  58.   König RS, Paris DH, Sollberger M, Tschopp R. Identifying the mental health burden in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients in Switzerland: A pilot study. Heliyon. Mar 15 2024;10(5):e27031. doi:10.1016/j.heliyon.2024.e27031
  59.   Aoun Sebaiti M, Hainselin M, Gounden Y, et al. Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Scientific reports. 2022;12(1):2157.
  60.   Mohamed AZ, Andersen T, Radovic S, et al. Objective sleep measures in chronic fatigue syndrome patients: A systematic review and meta-analysis. Sleep Medicine Reviews. 2023/06/01/ 2023;69:101771. doi:https://doi.org/10.1016/j.smrv.2023.101771
  61.   Attard A, Attard S, Stanniland C, et al. Management of Psychiatric Conditions in Patients With Comorbid Postural Orthostatic Tachycardia Syndrome: A Literature Review and Case Vignette. Prim Care Companion CNS Disord. Jan 31 2023;25(1)doi:10.4088/PCC.22nr03243
  62.   Anderson JW, Lambert EA, Sari CI, et al. Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS). Front Physiol. 2014;5:230. doi:10.3389/fphys.2014.00230
  63.   Alexakis C, Kumar S, Saxena S, Pollok R. Systematic review with meta‐analysis: the impact of a depressive state on disease course in adult inflammatory bowel disease. Alimentary pharmacology & therapeutics. 2017;46(3):225-235.
  64.   Barberio B, Zamani M, Black CJ, Savarino EV, Ford AC. Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: a systematic review and meta-analysis. The Lancet Gastroenterology & Hepatology. 2021;6(5):359-370.
  65.   Bisgaard TH, Allin KH, Elmahdi R, Jess T. The bidirectional risk of inflammatory bowel disease and anxiety or depression: A systematic review and meta-analysis. General Hospital Psychiatry. 2023;
  66.   Hopkins CW, Powell N, Norton C, Dumbrill JL, Hayee BH, Moulton CD. Cognitive impairment in adult inflammatory bowel disease: a systematic review and meta-analysis. Journal of the Academy of Consultation-Liaison Psychiatry. 2021;62(4):387-403.
  67.   Xiong Q, Tang F, Li Y, et al. Association of inflammatory bowel disease with suicidal ideation, suicide attempts, and suicide: A systematic review and meta-analysis. Journal of psychosomatic research. 2022;160:110983.
  68.   Nicoloro SantaBarbara J, Lobel M. Depression, psychosocial correlates, and psychosocial resources in individuals with mast cell activation syndrome. Journal of health psychology. 2022;27(9):2013-2026.
  69.   Weinstock LB, Nelson RM, Blitshteyn S. Neuropsychiatric Manifestations of Mast Cell Activation Syndrome and Response to Mast-Cell-Directed Treatment: A Case Series. Journal of Personalized Medicine. 2023;13(11):1562.
  70.   Berglund B, Pettersson C, Pigg M, Kristiansson P. Self-reported quality of life, anxiety and depression in individuals with Ehlers-Danlos syndrome (EDS): a questionnaire study. BMC Musculoskeletal Disorders. 2015/04/15 2015;16(1):89. doi:10.1186/s12891-015-0549-7
  71.   Baeza-Velasco C, Gély-Nargeot MC, Bulbena Vilarrasa A, Bravo JF. Joint hypermobility syndrome: problems that require psychological intervention. Rheumatol Int. Sep 2011;31(9):1131-6. doi:10.1007/s00296-011-1839-5
  72.   Cederlöf M, Larsson H, Lichtenstein P, Almqvist C, Serlachius E, Ludvigsson JF. Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings. BMC Psychiatry. Jul 4 2016;16:207. doi:10.1186/s12888-016-0922-6
  73.   Seighali N, Abdollahi A, Shafiee A, et al. The global prevalence of depression, anxiety, and sleep disorder among patients coping with Post COVID-19 syndrome (long COVID): a systematic review and meta-analysis. BMC Psychiatry. Feb 6 2024;24(1):105. doi:10.1186/s12888-023-05481-6
  74.   van der Feltz-Cornelis C, Turk F, Sweetman J, et al. Prevalence of mental health conditions and brain fog in people with long COVID: A systematic review and meta-analysis. Gen Hosp Psychiatry. May-Jun 2024;88:10-22. doi:10.1016/j.genhosppsych.2024.02.009
  75.   Ceban F, Ling S, Lui LMW, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. Mar 2022;101:93-135. doi:10.1016/j.bbi.2021.12.020
  76.   Flegr J, Horáček J. Negative Effects of Latent Toxoplasmosis on Mental Health. Front Psychiatry. 2019;10:1012. doi:10.3389/fpsyt.2019.01012
  77.   Lindgren M, Torniainen-Holm M, Härkänen T, Dickerson F, Yolken RH, Suvisaari J. The association between toxoplasma and the psychosis continuum in a general population setting. Schizophr Res. Mar 2018;193:329-335. doi:10.1016/j.schres.2017.06.052
  78.   Stepanova EV, Kondrashin AV, Sergiev VP, et al. Toxoplasmosis and mental disorders in the Russian Federation (with special reference to schizophrenia). PLoS One. 2019;14(7):e0219454. doi:10.1371/journal.pone.0219454
  79.   Wang XB, Li XL, Zhang Q, et al. A Survey of Anxiety and Depressive Symptoms in Pulmonary Tuberculosis Patients With and Without Tracheobronchial Tuberculosis. Front Psychiatry. 2018;9:308. doi:10.3389/fpsyt.2018.00308
  80.   Fan H, Han Z, Gong X, et al. Prevalence and predictors of depression and anxiety in patients with chronic rhinosinusitis: a systematic review and meta-analysis. BMJ Open. Mar 15 2024;14(3):e079273. doi:10.1136/bmjopen-2023-079273
  81.   Chen F, Liu L, Wang Y, Hu K, Ma B, Chi J. Prevalence of Depression and Anxiety in Patients With Chronic Rhinosinusitis: A Systematic Review and Meta-analysis. Otolaryngology–Head and Neck Surgery. 2022:01945998221082538. doi:10.1177/01945998221082538
  82.   Lin S, Nie M, Wang B, et al. Intrinsic brain abnormalities in chronic rhinosinusitis associated with mood and cognitive function. Original Research. Frontiers in Neuroscience. 2023-March-10 2023;17doi:10.3389/fnins.2023.1131114
  83.   Schlosser RJ, Gage SE, Kohli P, Soler ZM. Burden of illness: A systematic review of depression in chronic rhinosinusitis. Am J Rhinol Allergy. Jul 2016;30(4):250-6. doi:10.2500/ajra.2016.30.4343
  84.   Chester AC. Chronic rhinosinusitis and fatigue: a common but underappreciated association. Am J Med. 2008:e13; author reply e15. vol. 10.
  85.   Fried J, Yuen E, Gudis DA, Schlosser RJ, Nguyen SA, Rowan NR. Changes in Sleep Quality Following Treatment for Chronic Rhinosinusitis: A Systematic Review and Meta-Analysis. Am J Rhinol Allergy. May 2022;36(3):386-396. doi:10.1177/19458924211061442
  86.   Zielinski MR, Gibbons AJ. Neuroinflammation, Sleep, and Circadian Rhythms. Front Cell Infect Microbiol. 2022;12:853096. doi:10.3389/fcimb.2022.853096
  87.   Felger JC. Role of Inflammation in Depression and Treatment Implications. Handb Exp Pharmacol. 2019;250:255-286. doi:10.1007/164_2018_166

More Real Posts About Brain Inflammation

View More Blog Posts
Brain Inflammation Collaborative Logo

EIN: 87-4063264
501(c)(3) Nonprofit Organization

Facebook Instagram Threads Linkedin Youtube
Learn
Engage
Give
unhide®
Research Platform
Sign Up for News
2025 Platinum Transparency Seal from Candid
© Brain Inflammation Collaborative, Inc. 2025

You can mail a check (payable to Brain Inflammation Collaborative, Inc.) with your donation any time to the following address:

Brain Inflammation Collaborative, Inc.
925 Genesee St #180440
Delafield, WI 53018

https://braininflammation.org/wp-content/uploads/2023/06/Unhide_whitepaper_V4.pdf