​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.

Highlights

• Demyelination plays a key role in major psychiatric and neurological disorders.


• Genetic, environmental, and immune factors drive myelin loss.


•  Arketamine has potential for promoting myelin restoration through TGF-β1 activation.


• Therapies targeting the gut-brain axis through the vagus nerve may support myelin repair.

​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.

​Abstract

Introduction: Postpartum mood disorders are heterogenous disorders and comprise postpartum psychosis and postpartum depression.

Evidence is accumulating that systemic monocyte/macrophage activation, low-grade inflammation and (premature senescence related) T cell defects increase the risk for mood disorders outside pregnancy by affecting the function of microglia and T cells in the emotional brain (the cortico-limbic system) leading to inadequate mood regulation upon stress.

​Areas covered: The evidence in the literature that similar immune dysregulations are present in postpartum mood disorders.

Results: The physiological postpartum period is characterized by a rapid T cell surge and a mild activation of the monocyte/macrophage system.

Postpartum mood disorder patients show a diminished T cell surge (including that of T regulatory cells) and an increase in low grade inflammation, that is, an increased inflammatory state of monocytes/macrophages and higher levels of serum pro-inflammatory cytokines.

Expert opinion: Anti-inflammatory agents (e.g. COX-2 inhibitors) and T cell boosting agents (e.g. low-dose IL-2 therapy) should be further investigated as treatment.

​The hypothesis should be investigated that postpartum mood disorders are active episodes (triggered by changes in the postpartum immuno-endocrine milieu) in ongoing, dynamically fluctuating aberrant neuro-immune-endocrine trajectories leading to mood disorders in women (inheritably) vulnerable to these disorders.

​Conclusion: The process of aging, immune dysregulation, and MDD [Major Depressive Disorder] closely interconnected.

MMP9, IL7R, S100B, and EGF may be used as novel diagnostic biomarkers and potential therapeutic targets for MDD, especially MMP9.

​Highlights
​

• •Neurodevelopmental disorders share a common genetic foundation with immune disorders but exhibit a higher degree of polygenicity.
• •This study identified thirty genomic loci with significant associations in both types of diseases, including eight novel loci.
• •The shared loci were mapped to genes enriched in three classes of pathways.
• •The pleiotropic loci show a significant association with blood cell traits, potentially serving as more accessible and feasible biomarkers for patient stratification.