​Abstract

The developmental origins of health and disease (DOHaD) indicate that fetal tissues and organs in critical and sensitive periods of development are susceptible to structural and functional changes due to the adverse environment in utero.

Maternal immune activation (MIA) is one of the phenomena in DOHaD.

Exposure to maternal immune activation is a risk factor for neurodevelopmental disorders, psychosis, cardiovascular diseases, metabolic diseases, and human immune disorders.

It has been associated with increased levels of proinflammatory cytokines transferred from mother to fetus in the prenatal period.

Abnormal immunity induced by MIA includes immune overreaction or immune response failure in offspring. Immune overreaction is a hypersensitivity response of the immune system to pathogens or allergic factor.

Immune response failure could not properly fight off various pathogens.

The clinical features in offspring depend on:
​ the gestation period, inflammatory magnitude, inflammatory type of MIA in the prenatal period, and exposure to prenatal inflammatory stimulation, which might induce epigenetic modifications in the immune system.

​An analysis of epigenetic modifications caused by adverse intrauterine environments might allow clinicians to predict the onset of diseases and disorders before or after birth

It is a long-term (chronic) disease of the central nervous system, which encompasses the brain, spinal cord and optic nerve, and is characterized by inflammation within one or more of those areas.

This inflammation can cause the destruction of the coating (myelin) that surrounds and protects nerve fibers (axons).

As a result, the damage disrupts the normal flow of messages (nerve impulses) from the central nervous system, causing a reduction or loss of body function.

​Mast cells are a part of your immune system.

• 
  They’re made in your bone marrow, then move through your bloodstream into your tissues.
  
  The mature mast cells live in tissues throughout your body to help protect you from hazards around you.
  
  They can help fight infections and regulate your organs.
  
  When your mast cells are overprotective, you may react to harmless things in your environment. This happens in people with seasonal allergies or allergic asthma.
  
  Mast cell activation can sometimes cause anaphylaxis, a serious allergic reaction.

​Mast cell diseases–especially MCAS–are involved with many of the immune issues associated with RCCX/CAPS disorders.

Because mast cells are involved with every system in the body, MCAS symptoms can vary widely as can the severity of the syndrome.

Although many physicians were trained to find systemic mastocytosis, which is the most severe form of mast cell disease, they were not trained to find less severe forms of mast cell disease.

Symptoms of mast cell disease can be wide-ranging. For that reason, physicians and patients are often unable to pin down what caused a particular symptom.

Additionally, tests traditionally used for some of the symptoms of mast cell disease do not test for mast cell disease itself, but rather test for other causes of those symptoms.

. . . Because it appears that mast cell activation problems exist in the gifted population in greater frequency than in the general population, we urge those in the gifted populations with health issues not solved by drugs in those categories to discuss the possibility of mast cell activation problems with their doctors. . . ​

Abstract

​Mast cell activation syndrome (MCAS) is an immune disease with an estimated prevalence of 17%.

Mast cell chemical mediators lead to heterogeneous multisystemic inflammatory and allergic manifestations.

This syndrome is associated with various neurologic and psychiatric disorders, including headache, dysautonomia, depression, generalized anxiety disorder, and many others.

Although MCAS is common, it is rarely recognized, and thus, patients can suffer for decades.

The syndrome is caused by aberrant mast cell reactivity due to the mutation of the controller gene.

A case series is presented herein including eight patients with significant neuropsychiatric disorders that were often refractory to standard medical therapeutics.

Five patients had depression, five had generalized anxiety disorder, and four had panic disorder.

Other psychiatric disorders included attention-deficit hyperactivity disorder, obsessive compulsive disorder, phobias, and bipolar disorder.

All eight patients were subsequently diagnosed with mast cell activation syndrome; six had comorbid autonomic disorders, the most common being postural orthostatic tachycardia syndrome; and four had hypermobile Ehlers-Danlos syndrome.

All patients experienced significant improvements regarding neuropsychiatric and multisystemic symptoms after mast-cell-directed therapy.

In neuropsychiatric patients who have systemic symptoms and syndromes, it is important to consider the presence of an underlying or comorbid MCAS.