Bridging Gaps in Research

Through a coordinated research effort involving patients, clinicians and researchers, the Brain Inflammation Collaborative strives to uncover connections between brain inflammation and mental and physical health and make advances in the diagnosis, treatment and prevention of neuroinflammatory illness.

The Unhide Project is an ongoing online clinical study that assembles patient-donated data to help clinicians and researchers accelerate breakthroughs surrounding brain inflammation and mental health.

Join the Movement

The relationship between brain inflammation and mental health is vastly understudied and misunderstood. The Brain Inflammation Collaborative is leading the charge to change that. Discover all the different ways you can support our mission to find long-overdue answers and solutions for patients.

Conditions of Interest

The beginning phase of illnesses we will be investigating include long COVID, OCD, anorexia nervosa, PANDAS, PANS, autoimmune encephalitis, Tourette’s, POTS, narcolepsy, and ME/CFS. Additional illnesses to be explored and added to our platform will include depression, PTSD, concussion, post mortem suicide, anxiety disorders, depression, auto-immune arthritis forms, Ehlers Danlos Syndrome (EDS), mast cell activation syndrome (MCAS), chronic sinusitis, anxiety disorders, small fiber neuropathy, psoriasis, and irritable bowel disease (IBD).

Illness Descriptions of Studied Diagnoses

Anorexia nervosa is an eating disorder where people experience an intense fear of gaining weight and typically hold a distorted perception of weight, which results in caloric restriction that then develops into an abnormally low body weight.

Avoidant restrictive eating disorder (ARFID) is a condition where people have a dramatic restriction in the types and amounts of food eaten. A person with ARFID does not eat enough calories to maintain basic body function. They can be concerned about the texture and appearance of food, or develop selective phobias about foods which can include fear of choking. The limited range of preferred foods can worsen over time. This is a more common issue for children but can pertain to any age group.

Both eating disorders are serious and include psychological issues around depression and anxiety that require supportive treatment. Anorexia nervosa is differentiated from ARFID based on severity of restriction and the potential life-threatening consequences.

People with anorexia use extreme efforts to control their weight and appearance, including calorie restriction, excessive exercising, vomiting after they eat, or misusing laxatives, diet aides, diuretics, or enemas.

Anorexia is characterized by both physical symptoms as well as emotional and behavioral problems. It can be hard to identify the signs of anorexia nervosa as people with anorexia often try to hide their thinness, eating habits, or physical symptoms.

Symptoms can include:

  • Extremely restricted eating
  • Extreme thinness (emaciation)
  • A relentless pursuit of thinness and unwillingness to maintain a normal or healthy weight
  • Intense fear of gaining weight
  • Distorted body image, self-esteem that is heavily influenced by perceptions of body weight and shape, or a denial of the seriousness of low body weight
  • Skin discoloration, brittleness of hair
  • Fatigue
  • Insomnia
  • Abnormal blood counts
  • Irregular heart rhythms
  • Low blood pressure
  • Absence of menstruation
  • Fatigue
Emotional and behavioral symptoms:
 
  • Intense fear of gaining weight, distorted body image
  • Preoccupation with food, including cooking elaborate meals for others but not eating them
  • Frequently skipping meals or refusing to eat
  • Denial of hunger or making excuses for not eating
  • Eating only a few “safe” foods that are usually low in fat and calories
  • Adopting stringent eating rituals like spitting out food after chewing
  • Not wanting to eat in public
  • Lying about how much has been eaten
  • Repeated weighing or measuring the body out of fear of weight gain
  • Checking the mirror frequently for perceived flaws
  • Complaining about being fat or having body parts that are fat
  • Covering up in layers of clothing
  • Lack of emotion
  • Social withdrawal
  • Irritability and depression
  • Reduced interest in sex
 

Diagnosis includes a physical exam, lab tests, and psychological evaluation. In treating anorexia, it’s important to understand that it isn’t really about food but rather the person’s way of coping with other problems. While nutritional counseling, psychotherapy, medication, and lifestyle changes are key to restoring a person to their healthy weight—the first goal in treatment—hospitalization, programs specializing in the treatment of eating disorders, and other medical care may be needed to treat anorexia.

https://www.mayoclinic.org/diseases-conditions/anorexia-nervosa/diagnosis-treatment/drc-20353597

Anyone and everyone can experience anxiety, but anxiety disorders are characterized as intense, excessive, and persistent worry around everyday situations. Panic attacks are a feature of anxiety disorders in which sudden feelings of intense anxiety, fear, or terror peak within minutes.

Anxiety disorders can be generalized, social anxiety disorder, or specific phobias like separation anxiety disorder. Having another medical condition can also result in anxiety around treatment or around a prognosis. Anxiety disorders can interfere with daily life and may cause avoidant behaviors.

After ruling out any underlying medical conditions that require treatment, a mental health provider like a psychiatrist can provide a psychological evaluation. To diagnose anxiety disorders, symptoms will be compared against criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Treatment of anxiety disorders usually involve a combination of medications and psychotherapies.

Inflammation and mental health

The relationship between anxiety disorders and infectious diseases is well studied and their co-occurrence is associated with worse quality of life. Moreover, researchers have found evidence of

Infection in early childhood is also associated with an increased risk of developing depression and anxiety disorders among young people. Mental health may be linked to early immune functioning, for example, a childhood strep infection may trigger an autoimmune response directed at receptors in the brain, causing potential neuropsychiatric symptoms.

https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961

https://www.mayoclinic.org/diseases-conditions/anxiety/diagnosis-treatment/drc-20350967

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095564/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175921/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248872/

https://www.nature.com/articles/1395313

Autoimmune encephalitis (AE) is a collection of serious but rare conditions occurring in around 14 out of 100,000 people. In AE, inflammation of the brain (or encephalitis) occurs when the body makes an antibody that mistakenly attacks the brain. What triggers an autoimmune reaction is not always well understood but can include exposure to certain tumors (e.g. ovarian teratoma), bacteria, and viruses (e.g. herpes simplex and SARS-CoV2).

During inflammation, patients can experience headache, neck pain, light and sound sensitivity, mental confusion, and seizures. AE typically progresses over the course of days to weeks and evolves from initial flu-like symptoms to functional neurologic or psychiatric disorders. There are many different types of AE (and more being discovered all the time), such as:

  • Anti-NMDA receptor encephalitis
  • Hashimoto’s encephalopathy
  • Acute disseminated encephalomyelitis (ADEM)
  • Limbic encephalitis
  • LGI1/CASPR2-antibody encephalitis
  • Anti-GABAA receptor encephalitis
  • Seronegative autoimmune encephalitis
 

Each type of AE has unique features, but common symptoms of AE may include:

  • Memory loss
  • Altered mental status (e.g., confusion, disorientation, irritability, cognitive impairment)
  • Psychiatric symptoms (e.g., anxiety, psychosis, hallucinations, behavioral changes)
  • Movement disorders
  • Difficulty with balance, speech, or vision
  • Sleep problems
  • Weakness or numbness
  • Loss of consciousness or coma
 

Autoimmune encephalitis is easily overlooked, as the signs and symptoms are similar to other more prevalent conditions, including mental health disorders or drug abuse. Discovery of autoantibodies (antibodies directed at the body’s own cells) in blood and cerebrospinal fluid has improved the ability to diagnose AE; however, brain imaging and other tests may be required to confirm an AE diagnosis.

The key to surviving autoimmune encephalitis is early detection and treatment. The approach used to treat AE usually involves a team of care specialists and depends on the underlying cause and symptoms. Treatments for AE include:

  • Immunomodulators (steroids, intravenous antibodies or IVIG, plasma exchange, immune suppression)
  • Antiviral medications and antibiotics (if a viral or bacterial infection is the root cause)
  • Anti-seizure medications
  • Surgery to remove a tumor
 

https://www.hopkinsmedicine.org/health/conditions-and-diseases/encephalitis

https://www.ohsu.edu/brain-institute/autoimmune-encephalitis#:~:text=What%20is%20autoimmune%20encephalitis%3F,that%20mistakenly%20attack%20brain%20ce

https://jamanetwork.com/journals/jamaneurology/fullarticle/2799083

Rheumatoid arthritis (RA), juvenile RA, psoriatic arthritis, and ankylosing spondylitis are all autoimmune forms of arthritis. They cause chronic inflammation starting with the smaller joints like the hands, feet, and spine. Inflammation that goes unchecked can ultimately damage healthy tissues, including other parts of the body like the skin, eyes, lungs, heart, kidneys, vasculature, and nervous system.

Early signs and symptoms of arthritis include tender, warm, swollen joints; joint stiffness in the morning or after inactivity; and fatigue, fever, and loss of appetite. Autoimmune arthritis often affects symmetric joints on both sides of your body. Later stages are characterized by joint deformity, which occurs when swelling from chronic inflammation erodes the bones and causes the joints to shift out of place.

Autoimmune forms of arthritis can be difficult to diagnose in early stages as symptoms mimic other conditions, including  s over time). Physical examination, blood tests looking for inflammatory biomarkers or auto-antibodies, and imaging tests to track disease progression are typical. Treatments target the underlying inflammation and faulty immune processes using specialty medications called disease-modifying anti-rheumatic drugs (DMARDs).

Inflammation and mental health

Chronic inflammation is a hallmark of autoimmune disease, which can lead to constant stimulation of excitatory neurons in the brain. Nonstop production of pro-inflammatory mediators and cytokines ultimately results in cell death and neuronal loss. The brain’s response to chronic pain can actually alter neural pathways, which may exacerbate both physical and psychological difficulties associated with autoimmune arthritis.

An increased prevalence of mental health disorders in these patients may be attributed to the dysregulation of the inflammatory response. Evidence of the neuro-immune interplay is further supported by the effects of biologic therapies, in which reduction in brain inflammation is observed in individuals with autoimmune arthritis well before a reduction of inflammation in the affected joints.

https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/symptoms-causes/syc-20353648

https://www.mayoclinic.org/diseases-conditions/rheumatoid-arthritis/diagnosis-treatment/drc-20353653

https://www.frontiersin.org/articles/10.3389/fnins.2014.00357/full#:~:text=brain%20neuro%2Dinflammation.-,Neuro%2DImmune%20Interaction%20in%20Rheumatoid%20Arthritis,cell%20death%20and%20neuronal%20loss.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449457/

Bipolar disorder, formerly called manic-depression, is a mental illness that causes unusual shifts in mood, energy, and concentration which often make day-to-day tasks difficult. Often diagnosed during teen years or early adulthood, it usually requires lifelong treatment following a prescribed plan.

Characterized by an extreme mood range, people with bipolar disorder can shift from periods of being extremely “up” (elated, irritable, or energized behaviors known as manic episodes) to being very “down” (sad, indifferent, or hopeless behaviors known as depressive episodes). Less severe manic periods are called hypomanic episodes.

Bipolar disorder is categorized into 3 types:

  • Bipolar I disorder – severe manic episodes lasting ≥7 days followed depression lasting ≥2 weeks
  • Bipolar II disorder – periods of depression as well as hypomanic episodes
  • Cyclothymic disorder – recurring hypomanic and depressive symptoms that are not intense enough to qualify as hypomanic or depressive episodes

Bipolar disorder often occurs with other mental health disorders like anxiety, ADHD, addiction, and eating disorders. Similar to other mental illnesses, many factors are likely to contribute to the risk of having bipolar disorder, including genetics and a person’s brain structure and function.

Inflammation and mental health

Recent studies suggest that inflammation plays a prominent role in mood disorders as evidenced by elevated levels of proinflammatory markers in people with bipolar disorder, as well as in other mood disorders. Patients with systemic autoimmune diseases have an increased risk of developing bipolar disorder.

Proinflammatory cytokines (proteins that control activity of immune cells) are believed to mediate mood/behavioral changes associated with illness by activating important immune cells in the brain. Elegant studies on neuroinflammation reported significant activation of these immune cells – called microglial cells – as shown on PET scan in patients with bipolar disorder compared to healthy people.

In bipolar disease, the role of inflammation offers a new therapeutic approach, namely targeting reduction of the proinflammatory state. Anti-inflammatory drugs have been used successfully to treat other mood disorders, particularly depression, and may have promise in bipolar disorder too.

https://www.nimh.nih.gov/health/topics/bipolar-disorder

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054443/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054443/

Celiac disease is a condition in which eating gluten (a protein found in wheat, barley, and rye) triggers an immune response in your small intestine. Over time, this leads to damage of the intestinal villi—the small fingerlike projections lining the small intestine that function to absorb nutrients. This renders the intestine unable to absorb nutrients, which is called malabsorption. At that stage, symptoms include diarrhea, bloating, anemia, fatigue, and weight loss. In children, this can affect growth and development.

Celiac disease can lead to serious health problems if left untreated or undiagnosed. It is estimated that 1 in 100 people are affected by celiac disease, but only about 30% are accurately diagnosed. To diagnose celiac disease, blood work is required to look for antibodies (indicating an immune reaction to gluten) and genetic testing is performed to check for human leukocyte antigens.

If either of these tests indicate celiac disease, an endoscope—a long tube with a tiny camera—will be used to look inside the small intestine and take a tissue sample (biopsy) to study damage to the villi. While there is no cure for celiac disease, people can manage their symptoms by following a strict gluten-free diet. Vitamin and mineral supplements are recommended to make up for nutritional deficiencies.

Inflammation and mental health

Having celiac disease is associated with a lower quality of life and specific mood disorders. Research has shown a relationship between celiac disease and various disorders, including depression, anxiety, eating disorders, autism spectrum disorder, ADHD, bipolar disorder, schizophrenia, and other mood disorders.

In fact, a current study found that 63% of celiac patients reported anxiety and 35% reported depression. Mental distress was most frequently caused by lack of control over their disease, perceived health status, gluten-free diet problems, and impact on daily activities. .

While the relationship between celiac disease and psychiatric symptoms is not well understood, a gluten-free diet can alleviate most neurological and psychiatric symptoms. Gluten, a protein found in wheat, can cause inflammation for some people that leads to joint pain. Researchers have long known that people with autoimmune forms of arthritis, such as rheumatoid arthritis and psoriatic arthritis, are at higher risk for celiac disease.

https://www.mayoclinic.org/diseases-conditions/celiac-disease/symptoms-causes/syc-20352220

https://celiac.org/about-celiac-disease/what-is-celiac-disease/

https://www.mayoclinic.org/diseases-conditions/celiac-disease/diagnosis-treatment/drc-20352225

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984242/

https://www.arthritis.org/health-wellness/healthy-living/nutrition/anti-inflammatory/the-connection-between-gluten-and-arthritis

Sinuses are the spaces or cavities in your head that make mucus which drains to clear your nose of bacteria and allergens. Chronic sinusitis is when your sinuses remain swollen and inflamed for 3 months or longer. Temporary sinus infections (or acute sinusitis) may occur before developing chronic sinusitis, and while they have the same signs and symptoms, the latter may not respond to treatment as readily.

Many factors can contribute to chronic sinusitis, including a deviated septum, respiratory tract infection, nasal polyps, and allergies such as hay fever. Sinusitis can also occur as a complication from medical conditions like cystic fibrosis, HIV, and other immune disorders.

Diagnosing chronic sinusitis involves a physical exam, imaging tests like CT or MRI scans, and using a small camera to look into your sinuses. An allergy test might be recommended to help identify potential triggers or the doctor might swab your nose to check for a bacterial infection. When antibiotics or other medications fail to treat chronic sinusitis, surgery may be considered to enlarge the sinus openings.

Inflammation and mental health

A growing number of studies support the involvement of inflammation in psychiatric illness, and that psychiatric symptoms may arise or worsen following an infection such as sinusitis. In a study evaluating children diagnosed with sinusitis, 10 of 150 patients reported concurrent neuropsychiatric symptoms which resolved once the underlying infection was treated. This research suggests that the identification and treatment of underlying infections can potentially change the trajectory of some neuropsychiatric conditions.

https://my.clevelandclinic.org/health/diseases/17701-sinusitis

https://www.mayoclinic.org/diseases-conditions/chronic-sinusitis/symptoms-causes/syc-20351661

https://pubmed.ncbi.nlm.nih.gov/28012531/

A concussion is a traumatic brain injury often resulting from a blow to the head, a fall, whiplash, or violent shaking of the head and upper body. A concussion results in a temporary loss of normal brain function which can affect memory, speech, judgment, balance, and coordination. Signs of a concussion may not appear immediately and can last for days or weeks; however, most people fully recover.

Common symptoms include confusion, headache, blurred vision, ringing ears, dizziness, nausea, vomiting, drowsiness, and memory loss. Some people experience a temporary loss of consciousness, slurred speech, and delayed response or forgetfulness. Other symptoms can occur days after the injury, such as changes in personality, light sensitivity, loss of smell or taste, and problems sleeping.

If symptoms don’t go away after about two weeks or worsen at any time, patients should seek immediate medical attention. It’s also important to know that a history of multiple concussions or if a patient experiences a second concussion soon after the first one, permanent disability is a risk.

Inflammation and mental health

Altered permeability of the blood-brain barrier (BBB) is a well-known consequence of concussions, which allows the recruitment of blood-born defense mechanisms following a brain injury. However, the neuroimmune response can be delayed hours, days, or even months, and may contribute to long-term neurodegeneration and the demonstrated increase in mental health problems following concussions in youth.

Treatment strategies that focus on managing the neuroinflammatory response may be a more tangible target to protect patients from long-term neural damage and secondary cognitive deficits.

https://www.mayoclinic.org/diseases-conditions/concussion/symptoms-causes/syc-20355594

https://www.aans.org/en/Patients/Neurosurgical-Conditions-and-Treatments/Concussion

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2789683#:~:text=Findings%20This%20cohort%20study%20included,youths%20with%20an%20orthopedic%20injury

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3520152/#:~:text=The%20injured%20brain%2C%20as%20is,following%20CNS%20injury%20remains%20unclear.

Depression, or major depressive disorder, is estimated to affect 1 in 15 adults annually. Depression often appears first in the late teen years to the mid-20s. However, it can affect a person at any age and many people will experience a major depressive episode once in their lifetime. A diagnosis of depression is defined by symptoms lasting at least 2 weeks and a change in the patient’s previous level of functioning.

Symptoms of depression can vary in severity and include:

  • Feeling sad, worthless, or guilty; having a depressed mood
  • Lack of interest in activities previously enjoyed
  • Changes in appetite—weight loss or gain unrelated to dieting
  • Trouble sleeping or sleeping too much
  • Fatigue, loss of energy
  • Inability to sit still, pacing, handwringing
  • Slowed movements or speech
  • Difficulty concentrating or making decisions
  • Thoughts of death or suicide

There are several factors that may contribute to depression such as a person’s brain chemistry, genetics, personality, and environmental factors like continuous exposure to violence, neglect, abuse, or poverty. Note that other medical conditions can mimic symptoms of depression, so it’s important to rule out other possible causes before deciding on treatment.

Inflammation and mental health

Depression can be triggered by a serious infection or autoimmune disease (eg, type 1 diabetes, celiac disease, lupus). A recent study published in JAMA Psychiatry found that severe infection increased the risk of developing a mood disorder by 62% and autoimmune disease increased the risk by 45%.

An infection or autoimmune condition causes localized and/or body-wide inflammation. In some cases, a wayward inflammatory response can target and attack brain cells. In clinical studies, elevated levels of pro-inflammatory cytokines (used to measure inflammation) were found in the development  of depression in adults. Testing anti-inflammatory strategies for reducing or preventing depression will be an important direction in future research.

https://www.psychiatry.org/patients-families/depression/what-is-depression

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.707543/full

https://www.health.harvard.edu/blog/infection-autoimmune-disease-linked-to-depression201306176397#:~:text=An%20autoimmune%20disease%20increased%20the,another%20mood%20disorder%20even%20further

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.642976/full

Ehlers-Danlos syndrome (EDS) is a rare group of genetic disorders affecting the connective tissues, including joints, muscles, skin, and even blood vessels. Joint hypermobility—defined as an unusually large range of movement—is a hallmark of EDS. In children and infants, hypermobility and weak muscle tone can lead to a delay in the development of gross motor skills like sitting, standing, and walking. 

Loose joints are further susceptible to dislocation and chronic pain.  Other signs of EDS include soft, stretchy skin that can bruise easily and abnormal scarring due to the fragile quality of the skin.

In a vascular form of EDS, blood vessels and organ walls can rupture unpredictably, leading to bleeding problems (bruising, internal bleeding, stroke). It can also cause extreme curvature of the spine and other skeletal abnormalities, like bowed limbs and bent joints. Typically, people with EDS have a short stature. Other ways EDS can present include abnormalities of the eyes, teeth, and gums.

EDS is caused by a range of genetic mutations, and diagnosing EDS requires genetic testing. There is no cure for EDS and the goal of treatment is to control blood pressure and pain. Physical therapy can help strengthen muscles and stabilize joints. Braces may be recommended to help prevent joint dislocations.

EDS and mental health

Neurological conditions are increasingly associated with EDS and can have a big impact on daily life. Chronic pain, fatigue, headache, stroke, cerebrovascular disease, brain anomalies, seizures, neuropathy, and developmental delay may be features in hereditary connective tissue disorders. And more studies are exploring the relationship of EDS with mood disorders, personality disorders, addictions, eating disorders, and psychosis.

In a study of hypermobile EDS patients, 70% reported some type of anxiety disorder. Other research has revealed a higher co-occurrence of ADHD and development coordination disorder (DCD) in children diagnosed with EDS compared to typically-developing children. Treatments should consider psychiatric issues and psychiatric evaluation should be part of managing EDS. 

https://www.mayoclinic.org/diseases-conditions/ehlers-danlos-syndrome/diagnosis-treatment/drc-20362149

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4300794/

https://www.ehlers-danlos.com/2017-eds-classification-non-experts/psychiatric-psychological-aspects-ehlers-danlos-syndromes/

Inflammatory bowel disorder (IBD) includes Crohn’s disease and ulcerative colitis. In IBD, the gastrointestinal (GI) tract is damaged due to chronic inflammation. Inflammation can affect any part of the GI tract, but most often occurs in the small or large intestine. Common symptoms of IBD are persistent diarrhea, abdominal pain, rectal bleeding/bloody stools, weight loss, and fatigue.

IBD may be caused by an inappropriate immune response, in which uncontrolled inflammation injures tissues of the GI tract. It’s unknown what causes this, but the immune system may be triggered by a virus or bacterial infection, or there may be a genetic factor causing immune dysfunction.

Diagnosis relies on endoscopy or colonoscopy to see into the GI tract, along with other imaging techniques like MRI and CT. Blood and stool samples will also be tested for inflammatory markers. There are several medications used to treat IBD; surgery may be required to remove damaged parts of the GI tract.

Inflammation and mental health

Depression and anxiety are significant comorbid conditions that people with IBD often experience. Depression and anxiety may be considered consequences of the self-perpetuating cycle of inflammation, a hallmark of IBD. Some studies have even suggested that psychiatric disorders may be predictors of active disease and relapse. Indeed, studies that highlight the impact of mental health on disease-related outcomes recommend mental health screening as an approach to diagnosis and treatment in IBD. 

https://www.cdc.gov/ibd/what-is-IBD.htm#

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361235/

Post-COVID-19 syndrome, also called long-haul COVID, describes a variety of ongoing, new, or returning symptoms experienced by people more than four weeks after getting COVID-19. Long-haul covid can last months or years and may lead to disability. The Household Pulse Survey found that 19% of U.S. adults who had COVID at least 3 months ago are still experiencing symptoms of long COVID, although newer variants may differ and data collection is ongoing.

Symptoms of post-COVID-19 syndrome include:

  • Fatigue
  • Fever
  • Symptoms that get worse after mental or physical effort
  • Respiratory symptoms (e.g., difficulty breathing, shortness of breath, cough)
  • Neurological symptoms (e.g., brain fog, headache, sleep problems, dizziness when standing upright, pin-and-needles feeling, loss of smell or taste, depression or anxiety)
  • Heart symptoms (e.g., chest pain, heart palpitations)
  • Digestive symptoms (e.g., diarrhea, stomach pain)
  • Blood clots and problems affecting the blood vessels
  • Joint or muscle pain
  • Rash
  • Change in menstrual cycle

A person is more likely to experience long-haul COVID if they:

  • have a severe case of COVID-19 (e.g., needed hospitalization or intensive care)
  • are unvaccinated against COVID-19
  • are female
  • smoke
  • are obese
  • have certain medical conditions prior to getting COVID-19
 

It can be difficult to tell if some symptoms are due to long-haul COVID or another condition. Many symptoms are similar to other chronic illnesses that develop following an infection. Increasingly, it appears that long-haul COVID may result from different mechanisms that could help categorize patients for treatment. For instance, people with breathlessness and fatigue from pneumonia damage to their lungs may be very different from those experiencing mostly brain fog and fatigue. A long-haul COVID diagnosis is based on medical history, a prior diagnosis of COVID-19, and clinical examination. Because symptoms vary greatly, a personalized health plan is used to manage post-COVID-19 syndrome.

https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351

https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html

Lupus, or systemic lupus erythematosus, is an autoimmune disease in which the immune response is misdirected at the body’s own tissues, causing sometimes permanent damage to many body systems, including the skin, joints, heart, lung, kidneys, blood vessels, and the brain.

People typically experience lupus as a cycle of episodes, called flares, and periods of remission or wellness. Symptoms often come and go, and new symptoms can develop over time. While no two cases of lupus are exactly the same, specific symptoms depend on the body systems that are affected. The number and severity of symptoms can vary, and may include:

  • Fever
  • Fatigue
  • Arthritis (joint pain, stiffness, and swelling)
  • A “butterfly” rash that appears across the nose and cheeks
  • Round scaly rashes appearing anywhere on the body
  • Skin lesions that worsen with sun exposure
  • Sores in the nose and mouth (often the roof of the mouth)
  • Dry eyes
  • Fingers and toes that turn to blue or white when cold or stressed
  • Headaches, confusion, or memory loss
  • Shortness of breath
  • Chest pain (from inflammation around the lungs or heart)

While the cause of lupus is unknown, factors that can trigger the immune system include infection, certain medications, and even sunlight. In diagnosing lupus, blood and urine tests are used to look for disease markers; physical examination and imaging tests help detect tissue damage; and a kidney or skin biopsy may be taken to study under a microscope. Lupus treatments depend on the symptoms and largely include specialty medications, NSAIDs like ibuprofen, antimalarial drugs, and corticosteroids.

Inflammation and mental health

As an inflammatory autoimmune disorder, lupus affects multiple organ systems, including the central nervous system and brain. In fact, lupus presents with psychiatric symptoms in most patients (up to 39% of patients reported experiencing depression, 24% reported anxiety, and 80% reported cognitive dysfunction). These were often the first symptoms identified before a lupus diagnosis was made.

Unfortunately, mental health symptoms often go undiagnosed and untreated in lupus and most patients with lupus do not receive psychiatric assessment.

https://www.niams.nih.gov/health-topics/lupus

https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789

https://www.mayoclinic.org/diseases-conditions/lupus/diagnosis-treatment/drc-20365790

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9903299/

Mast cell activation syndrome (MCAS) is a condition that describes when a patient experiences repeated episodes of severe allergy-related symptoms, which often affect several body systems. Symptoms typically begin in adulthood and may include hives, swelling, difficulty breathing, low blood pressure, abdominal pain, and severe diarrhea.

Mast cells are the cells responsible for activating an allergic reaction: triggered by an allergen, infection, medication, or mutation, the mast cell releases stored granules (called mediators) that signal an inflammatory response. This is called “secondary activation” because the mast cells are first activated by external stimuli.

The cause of MCAS is unknown and diagnosis often depends on other conditions being excluded first. The mast cell mediators increase during an episode and measuring them can provide clues to an MCAS diagnosis. Treatment goals are to confirm MCAS diagnosis and provide symptom relief. Acute episodes should be treated like anaphylaxis: epinephrine, antihistamines, corticosteroids, and other medications.

Inflammation and mental health

Characterized by its multisystem impact, MCAS presents with extremely diverse s  and range of severity. Neurological symptoms include brain fog, depression, anxiety, insomnia, and sensitivity to a plethora of stimuli. Other symptoms such as severe pain and avoidant behaviors may contribute to mental health burden.

A study found that nearly a third of people diagnosed with MCAS experienced anxiety. Anxiety levels were worse with more frequent and severe physical symptoms.  In studies over the last decade, at least 40–60% of MCAS patients exhibited psychiatric symptoms and findings such as depression, bipolar, anxiety disorders, hallucinations, panic attacks, psychosis, and cognitive issues whereas the prevalence of these in the general population is below 10%.

https://www.mastcellaction.org/assets/2021/09/15/246ac7d9-52ac-4796-8739-3e549cac2c4d.pdf?v=1

https://rarediseases.info.nih.gov/diseases/12981/mast-cell-activation-syndrome

https://www.aaaai.org/conditions-treatments/related-conditions/mcas

https://www.psychologytoday.com/us/blog/holistic-psychiatry/201907/mast-cell-activation-syndrome-alert-psychiatrists

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909465/

Chronic fatigue syndrome, also called myalgic encephalomyelitis or ME/CFS, is a complex disease characterized by chronic fatigue that lasts at least six months. ME/CFS affects neurological, immunological, and metabolic functions. Symptoms do not improve with rest and worsen with even minimal physical or mental activity. Symptoms of ME/CFS include: 

  • Post-exertional fatigue
  • Sleep problems
  • Cognitive issues (problems with memory and thinking)
  • Dizziness that worsens when standing upright
  • Muscle or joint pain
  • Orthostatic intolerance
  • Sensory intolerance
  • Flu-like symptoms
  • Gastrointestinal symptoms
 

ME/CFS is a serious disease and most people who experience ME/CFS never regain their pre-disease level of functioning. According to the CDC, ME/CFS affects up to 2.5 million Americans and is more likely to occur in women than men.

While the underlying cause of ME/CFS is unknown, many people with ME/CFS report symptoms that persist following an acute infection. There is no single diagnostic test to confirm ME/CFS; rather, a diagnosis depends on ruling out other conditions with similar symptoms. No FDA-approved treatment for ME/CFS is currently available and treatment approaches focus on symptom relief.

https://www.nih.gov/mecfs/about-mecfs

https://www.mayoclinic.org/diseases-conditions/chronic-fatigue-syndrome/symptoms-causes/syc-20360490

Narcolepsy is a chronic neurological disorder affecting the sleep-wake cycles and the brain’s ability to control them. People with narcolepsy may unwillingly fall asleep—even in the middle of an activity like eating, talking, or driving. Left untreated, narcolepsy can interfere with cognitive function and development.

Within a normal sleep cycle, people enter REM sleep after 60-90 minutes, whereas in narcolepsy, people enter REM sleep after only 15 minutes. People with narcolepsy can also experience spells of muscle weakness while awake. 

Symptoms typically start in childhood, adolescence, or young adulthood, but are often misdiagnosed. While the causes of narcolepsy are not fully understood, low levels of hypocretin (a chemical that promotes wakefulness and regulates REM sleep) and other factors are thought to be involved (e.g., autoimmune attack on hypocretin-secreting parts of the brain, brain injuries, and genetics). Symptoms include:

  • Excessive daytime sleepiness (EDS) which comes on quickly and may be called a “sleep attack”
  • Cataplexy, the sudden loss of muscle tone while awake, leading to weakness or loss of voluntary muscle control (it is related to the paralysis of muscle activity that occurs during REM sleep)
  • Sleep paralysis, like cataplexy but occurring at the edges of sleep
  • Automatic behaviors, in which a person without conscious awareness automatically continues an action or activity interrupted by a brief sleep episode 
  • Hallucinations, the vivid and sometimes frightening images that accompany sleep paralysis
  • Fragmented sleep and insomnia
 

Diagnosing narcolepsy requires clinical evaluation to rule out other neurological conditions and two specialized tests: polysomnogram (PSG or sleep study) and multiple sleep latency test (MSLT). A doctor may ask the patient to keep a sleep journal to document sleep times and symptoms. There is no cure for narcolepsy, but symptoms can be managed with medication and lifestyle changes. 

https://www.ninds.nih.gov/health-information/disorders/narcolepsy

Obsessive compulsive disorder (OCD) is a condition where a person gets caught in a cycle of obsessions and compulsions. Obsessions are characterized as unwanted intrusive thoughts, images, or urges that trigger intense feelings such as fear, disgust, uncertainty, and doubt. Compulsions are the repetitive behaviors or thoughts used to neutralize, counteract, or get rid of obsessions.

OCD can affect people at any age and most commonly appears between ages 8 and 12 or between late teen years and early adulthood. In the US, it is estimated that 1 in 100 adults and at least 1 in 200 adolescents are currently living with OCD. 

To make an OCD diagnosis, the cycle of obsessions and compulsions must be so extreme and frequent that they take up more than an hour a day, cause intense distress, or get in the way of valued activities like going to school or work or spending time with friends. Common obsessions in OCD include:

  • Contamination obsessions
  • Sexual obsessions
  • Violent obsessions
  • Religious/Moral obsessions
  • Responsibility obsessions
  • Perfectionism-related obsessions
  • Identity obsessions
  • Relationship-related obsessions
  • Existential-themed obsessions
  • Real event/false memory obsessions
 

Common compulsions in OCD include:

  • Avoidance of triggers
  • Excessive washing and cleaning
  • Checking for mistakes or behaviors that could cause harm
  • Checking body parts or conditions
  • Repeating routine activities and body movements
  • Repeating activities in “multiples” (usually to satisfy a “safe” number)
  • Mental compulsions (eg, reviewing events, praying, counting)
  • Arranging or ordering things until they “feel right”
  • Telling, asking, or confessing to get reassurance
 

OCD is typically treated with a combination of cognitive behavioral therapy (CBT) and medication. More specifically, a type of CBT called exposure and response prevention (ERP) can help modify behaviors and thoughts associated with OCD, while a class of drugs called serotonin reuptake inhibitors (SRIs)—a widely used type of antidepressant—are thought to be uniquely effective to treat OCD. 

https://iocdf.org/about-ocd/

https://psychiatry.ufl.edu/patient-care-services/ocd-program/medications-for-ocd/#:~:text=Research%20clearly%20shows%20that%20the,Clomipramine%20(Anafranil)

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, is a condition that affects children, and symptoms seemingly appear “overnight” following a group A streptococcal infection. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a related disorder where the infectious trigger may be other types of infection or not identified. PANDAS/PANS often presents as obsessions or compulsions or restricted eating, and includes at least two other symptoms, including:

  • ADHD symptoms (e.g., hyperactivity, inattention, or fidgeting)
  • Separation anxiety
  • Mood changes (e.g., irritability, sadness, depression, behavioral regression)
  • Trouble sleeping
  • Nighttime bed-wetting
  • Frequent daytime urination
  • Change in motor skills (e.g., handwriting)
  • Decline in cognitive and executive function
  • Motor, sensory, or vocal abnormalities 
  • Joint pain

Initial treatment of PANDAS/PANS should importantly target any underlying infection using antibiotics, antiviral, or related antigen therapeutic. Further symptoms may be managed using a combination of medication, behavioral therapy, and cognitive behavioral therapy. In severe PANDAS, immunotherapy may be considered—research suggests plasma exchange or immunoglobulin (IVIG) can often improve neuropsychiatric symptoms associated with PANDAS.

The diagnosis and treatment of PANDAS/PANS is often difficult, as this is a relatively newly investigated disease. However, with the outbreak of the COVID-19 pandemic and widespread investigation of psychological reactions to coronavirus infection, there is an increase in research into why pathogens can affect the brain of some people but not others. Hopefully in the near future this will aid in making PANS or PANDAS easier to diagnose.

Postural orthostatic tachycardia syndrome (POTS) is a nervous system disorder characterized by specific symptoms that frequently occur when standing upright and are associated with increased heart rate, or tachycardia. These symptoms include:

  • lightheadedness
  • fainting
  • brain fog
  • fatigue
  • exercise intolerance
  • headache
  • blurry vision
  • palpitations
  • tremor
  • nausea

POTS symptoms are usually attributed to a combination of a lower volume of blood in circulation; excess blood pooling below the level of the heart; and elevated hormone levels like adrenaline. POTS is most prevalent in women and in adolescents and young adults. A 10-minute standing test or a tilt table test are typically used to determine a POTS diagnosis.

Treating POTS requires an individualized approach based on the patient’s specific set of symptoms and underlying conditions. There is no cure for POTS, but a combination of diet, physical therapy, and medications have been shown to help manage symptoms.

Inflammation and mental health

While brain fog, forgetfulness, mental fatigue, and fast heart rate on standing are hallmarks of POTS, these symptoms may occur even while seated or lying down. Cognitive dysfunction limits a person’s ability to work or engage in activities and is often cited as the most disabling aspect of POTS. People with POTS often exhibit mild to moderate depression and anxiety, which may be related to living with a chronic illness that negatively impacts their cognition.

Increasing awareness of cognitive and emotional factors as part of the disease burden associated with POTS may lead to new therapeutic targets, helping to optimize a patient’s personalized treatment plan. Future studies should correlate cognitive outcomes with physiological and psychological interventions.

https://www.hopkinsmedicine.org/health/conditions-and-diseases/postural-orthostatic-tachycardia-syndrome-pots

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160364/#:~:text=Psychologically%2C%20patients%20face%20challenges%20congruent,as%20symptoms%20of%20anxiety%20disorders

Psoriasis is a chronic skin condition that appears as a rash with itchy, scaly patches usually on the knees, elbows, torso, or scalp. Psoriasis is the result of an autoimmune reaction and is characterized by unexpected flare ups that last for weeks or months. Infections, cuts or burns, and certain medications can trigger psoriasis in people who are genetically predisposed.

A healthcare provider or dermatologist will perform a physical exam and review of a person’s medical history to diagnose psoriasis. A skin biopsy may be required to confirm the diagnosis. There is no cure for psoriasis but there are several treatments (creams, ointments, etc.) available to manage symptoms. If symptoms persist, light therapy, immunotherapy, or other medications may be recommended.

Inflammation and mental health

Psoriasis can harm a patient’s self-esteem and health-related quality of life. Psoriasis may lead to mental health disorders like anxiety and depression, especially concerning disfigurement and stigmatization associated with having the disease. However, these disorders can also trigger or worsen psoriasis flares.

The prevalence of psychiatric comorbidities was significant among patients with psoriasis—up to 84% reported in one study—higher than in other dermatological diseases. Many studies investigating the mechanisms underlying psoriasis and mental health disorders suggest immune system involvement. Indeed, these were both associated with high levels of pro-inflammatory cytokines in study participants.

Beyond psychiatric disorders, psoriasis is also associated with a number of neurological diseases including, stroke, multiple sclerosis, seizure, migraines, Parkinson’s disease, and Guillain-Barre syndrome, providing further evidence psoriasis is a systemic disease with neuropsychiatric impact.

https://www.mayoclinic.org/diseases-conditions/psoriasis/symptoms-causes/syc-20355840

https://my.clevelandclinic.org/health/diseases/6866-psoriasis

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4928455/

https://pubmed.ncbi.nlm.nih.gov/29509545/

https://pubmed.ncbi.nlm.nih.gov/29509545/

Post-traumatic stress disorder (PTSD) can develop in response to a traumatic event and can affect people of all ages. PTSD is commonly reported among combat veterans or people who have been exposed to physical abuse, sexual assault, an accident, or an event like a natural disaster. While it is completely normal to feel fear or shock following trauma, PTSD is diagnosed when the associated symptoms are sustained over time and interfere with daily life.

PTSD can cause changes to the brain. Activity in the brain’s fear center, the amygdala, increases while activity in areas associated with executive function and memory decrease, upsetting the body’s ability to appropriately respond to stress. An imbalance of important neurotransmitters, including serotonin and norepinephrine, is also reported in PTSD.

PTSD symptoms manifest as intrusive memories, avoidance behaviors, negative changes in thinking or mood, and alterations in arousal and impulsivity. It is prudent to note that approximately 80% of people with PTSD report having comorbid psychiatric disorders, specifically depression, anxiety, and substance abuse/dependency.

Inflammation and mental health

Studies have found a correlation between traumatic stress and immune dysfunction. PTSD has long-term effects on physiological function including that of the immune system, and biomarker testing confirms an altered inflammatory response in patients with PTSD. Dysregulation of normal stress responses can lead to chronic underlying inflammation in the body, which may increase the risk of developing autoimmune disease or contracting a serious infectious disease.

Rather than wait for the clinical signs of stress to emerge, data on a patient’s inflammatory state following trauma may provide new strategies for early prevention and treatment of PTSD.

https://www.nimh.nih.gov/health/topics/post-traumatic-stress-disorder-ptsd 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748176/ 

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.707543/full 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070581/ 

Najavits LM, Ryngala D, Back SE, et al. Treatment of PTSD and comorbid disorders

Najavits LM, Ryngala D, Back SE, et al. Treatment of PTSD and comorbid disordersEffective treatments for PTSD: practice guidelines from the International Society for Traumatic Stress studies. New York: Guilford Press; 2009.

Sjogren’s syndrome is an immune system disorder that is characterized by dry eyes and a dry mouth. It typically affects people who have other autoimmune conditions like rheumatoid arthritis and lupus. In Sjogrens, the immune system mistakenly attacks the body’s own tissues, specifically mucous membranes or glands that secrete moisture. 

In addition to a reduction of tears and saliva, people with Sjogren’s syndrome may report swollen salivary glands, joint swelling and pain, dry skin or a rash, vaginal dryness, persistent dry cough, and fatigue. Because symptoms are similar to other conditions and even mimic some medications’ side effects, Sjogren’s syndrome is difficult to diagnose.

Most diagnostic tests help rule out other diseases. Blood tests are used to identify antibodies associated with Sjogrens and look for evidence of inflammation. Eye tests measure dryness and tear production. Imaging tests are used to check the function of your salivary glands. Finally, a biopsy or small sliver of tissue from your salivary glands may be studied under a microscope.

Inflammation and mental health

Research shows that neurological involvement has been found in up to 80% of adults with Sjogren’s syndrome. Inflammation directed at the brain drives a number of neurological disorders (trouble speaking or understanding speech, vision loss, cognitive dysfunction) but can also manifest in psychiatric disorders (depression, anxiety, cognitive deficits, psychosis), especially in younger people.

In a recent series of case studies, investigators suggested that, in an adolescent population, Sjogren’s syndrome may initially present with psychiatric symptoms, mainly psychosis. In support of this connection, psychiatric symptoms in the participants improved with immunosuppressive medications.

https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/symptoms-causes/syc-20353216

https://www.mayoclinic.org/diseases-conditions/sjogrens-syndrome/diagnosis-treatment/drc-20353221

https://ped-rheum.biomedcentral.com/articles/10.1186/s12969-020-0412-8#:~:text=Neurological%20involvement%20has%20been%20reported,and%20cognitive%20dysfunction%20being%20common

Tourette syndrome is a neurological disorder characterized by unwanted and uncontrolled movements or vocal sounds called tics. Motor or vocal tics are usually rapid and repeated and vary in type, frequency, and severity. Tourette syndrome is more prevalent in boys than girls, and tics usually appear between ages 5 and 10 years and may come and go over time. 

Motor tics typically start by affecting the head and neck and progress to affect muscles of the torso, arms, and legs. Development of vocal tics generally occurs after the presentation of motor tics. Tics are classified as being simple or complex and range from mild to severe. Simple tics are defined as sudden, brief, and repetitive movements, while complex tics are distinct, coordinated patterns of movement. 

Simple motor tics include:

  • Eye movements such as blinking
  • Facial grimacing
  • Shoulder shrugging
  • Head or shoulder jerking

Simple vocal tics include:

  • Repetitive throat clearing
  • Sniffing
  • Barking
  • Grunting

Complex motor tics include:

  • Sniffing or touching an object
  • Hopping
  • Jumping
  • Bending
  • Twisting

Complex vocal tics include:

  • Repeating one’s own words or phrases
  • Repeating others’ words or phrases (called echolalia)
  • Using vulgar, obscene, or swear words (called coprolalia)

Tics can be triggered or worsen with excitement or anxiety, or from certain physical experiences (e.g., hearing someone clear their throat or wearing a tight neck collar). As a neurobehavioral disorder, Tourette syndrome is often accompanied by other conditions, including:

  • Attention deficit hyperactivity disorder (ADHD)
  • Obsessive compulsive disorder or behaviors (OCD/OCB)
  • Anxiety
  • Learning disabilities
  • Behavioral issues
  • Problems sleeping
  • Difficulty with social functioning
  • Sensory processing issues
 

While the cause of Tourette syndrome is unknown, most cases involve the interaction of different genetic variations and environmental factors. Research points to abnormalities in certain regions of the brain, the circuits that connect these regions, and the chemical messengers responsible for communication between nerve cells.

Treatment of Tourette syndrome relies on management of symptoms through medications or behavioral modification or psychotherapy. 

https://www.ninds.nih.gov/health-information/disorders/tourette-syndrome

Need for research: the Unhide™ Project

Our vision is for brain inflammation disorders to be easily diagnosed by medical professionals and to find accessible therapies. 

To support research in this area we developed the Unhide™ Project, a longitudinal and historical research registry and bio repository platform to study the potential immunological mechanisms driving chronic brain inflammation in order to find new therapeutic targets.

Research is critical to evolve current therapies and develop new treatment targets

The Unhide™ Project was established to collect lab samples from patients with diseases characterized by brain inflammation in order to compare and understand common biomarkers.

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