​Val's Take/Conjecture It's estimated that 90 to 95% of the population have the Epstein-Barr Virus. So the virus itself is far from rare --- what's rare in various diseases and disorders is an ATYPICAL RESPONSE to the Epstein-Barr Virus. Further, Epstein-Barr often becomes a problem for people but often in the context of "Aging." For younger people and re-activated Epstein Barr Virus as well as re-activated Microglia -- this may be a form of premature aging. For people with Neuro-Developmental and Psychiatric Disorders, their Microglia may have been dysregulated IN UTERO and easily re-activated. AUTO-IMMUNE DISEASE Multiple Sclerosis (MS) is now greatly associated with the Epstein-Barr Virus. Further, there is some overlap between MS and Bipolar Disorder. Autoimmune responses to myelin-associated proteins as diagnostic and prognostic biomarkers of relapsing-remitting multiple sclerosis: Associations with human herpesvirus-6 and Epstein-Barr virus reactivation (2025) ​Multiple sclerosis and bipolar disorder: an overlap between soma and psyche (2024) ​"This clinical vignette with literature review is an illustration of the interesting, yet still unknown relationship between MS and affective disorders, where one might be influenced by the other but also have a common pathophysiology. "This highlights that the dividing line between neurology and psychiatry, whose pathophysiology often takes place in the same organ, is often arbitrary." ​​Does Epstein-Barr virus and intracellular Toll-like receptors affect the course of Hashimoto [Thyroiditis] disease? Findings from studies on newly-diagnosed patients (2024)

​Microglia as potential key regulators in viral-induced neuroinflammation (2024) ​Awakening the sleeping giant: Epstein–Barr virus reactivation by biological agents (2024) ​PSYCHIATRIC DISORDERS ​Hypothesis: bipolar disorder is an Epstein-Barr virus-driven chronic autoimmune disease - implications for immunotherapy (2020) ​Microbes and Mental Illness: Past, Present, and Future (2023) ​"Perspectives on the etiology of mental illness have evolved from demonic possession toward multisystem biologically based models that include gene expression, environmental triggers, immune mediators, and infectious diseases. "Microbes are associated with a number of mental disorders, including autism, schizophrenia, bipolar disorder, depressive disorders, and anxiety disorders, as well as suicidality and aggressive or violent behaviors. " ​Atypical immune response to Epstein-Barr virus in major depressive disorder (2020) ​CANCER ​Epstein-Barr virus lytic replication and cancer (2025) ​"Epidemiological studies have provided strong evidence that Epstein-Barr virus (EBV) lytic replication is linked to cancer development."

​Val's Take/Conjecture NOTE:  I am NOT a doctor --- I'm not recommending any treatments. On the other hand, I am recommending we investigate Lactoferrin further. ​This is complicated, of course. There is a study from 1982 showing that people with schizophrenia have MORE LACTOFERRIN. ​At the time, this was thought to reflect an abnormal inflammatory response in people with schizophrenia. Elevated serum levels of lactoferrin and eosinophil cationic protein in schizophrenic patients (1982) ​See also: Global Bibliometric and Visualized Analysis of Research on Lactoferrin from 1978 to 2024 (2024) Lactoferrin deficiency during lactation increases the risk of depressive-like behavior in adult mice (2023) Lactoferrin alleviates Western diet-induced cognitive impairment through the microbiome-gut-brain axis (2023) ​"Thus, Lf [Lactoferrin] intervention alleviated cognitive impairment by inhibiting microglial activation and neuroinflammation through the microbiome-gut-brain axis." The Lactoferrin Phenomenon-A Miracle Molecule (2022) ​Abstract Numerous harmful factors that affect the human body from birth to old age cause many disturbances, e.g., in the structure of the genome, inducing cell apoptosis [programmed cell death] and their degeneration, which leads to the development of many diseases, including cancer. Among the factors leading to pathological processes, microbes, viruses, gene dysregulation and immune system disorders have been described. The function of a protective agent may be played by lactoferrin as a "miracle molecule", an endogenous protein with a number of favorable antimicrobial, antiviral, antioxidant, immunostimulatory and binding DNA properties. The purpose of this article is to present the broad spectrum of properties and the role that lactoferrin plays in protecting human cells at all stages of life.

​Unlocking the power of Lactoferrin: Exploring its role in early life and its preventive potential for adult chronic diseases (2024) ​Abstract Nutrition during the early postnatal period exerts a profound impact on both infant development and later-life health. Breast milk, which contains lactoferrin, a dynamic protein, plays a crucial role in the growth of various biological systems and in preventing numerous chronic diseases. Based on the relationship between early infant development and chronic diseases later in life, this paper presents a review of the effects of lactoferrin in early life on neonates intestinal tract, immune system, nervous system, adipocyte development, and early intestinal microflora establishment, as well as the preventive and potential mechanisms of early postnatal lactoferrin against adult allergy, inflammatory bowel disease, depression, cancer, and obesity. Furthermore, we summarized the application status of lactoferrin in the early postnatal period and suggested directions for future research. Lactoferrin alleviates the adverse effects of early-life inflammation on depression in adults by regulating the activation of microglia (2025) ​"Our findings suggest that lactoferrin intake during lactation protects neurons by regulating microglial activation, thereby effectively reducing depressive symptoms in adults." ​Lactoferrin Attenuates Pro-Inflammatory Response and Promotes the Conversion into Neuronal Lineages in the Astrocytes (2025)

Val's Take/Conjecture With respect to Psychiatric Medications ---- some of them are affecting Microglia both positively and negatively.​ ​ ​The antipsychotic chlorpromazine reduces neuroinflammation by inhibiting microglial voltage-gated potassium channels (2025) *Korean Researchers "This review will provide a summary of the dual role of antipsychotics on neurochemical parameters associated with glial functions and will highlight the potential activity of glio-protective molecules to improve the action of antipsychotics."

Olanzapine, Risperidone and Clozapine prescribing is associated with increased risk for Alzheimer’s Disease reflecting antipsychotic-specific effects on microglial phagocytosis (2023) *UK & Swedish Researchers ​ ​The Janus face of antipsychotics in glial cells: Focus on glio-protection (2023) *Brazilian & German Researchers

Val's Take/ Conjecture It's more complicated than this --- but Microglia are essentially the Brain's Innate Immune Cells. Maternal Immune Activation appears to effect adult behavior by among other things: ​Dysregulating Amoeboid Microglia during pregnancy.  Those Amoeboid Microglia ultimately become Ramified Microglia in the Adult Central Nervous System Astrocytes are another type of glial cell, different than Microglia. Astrocytes do a number of things, including maintaining glutamate homeostasis. Glutamate excitotoxicity is involved with Neuro-Developmental and Psychiatric Disorders. ​Microglial contribution to the pathology of neurodevelopmental disorders in humans (2023) ​Dysfunctional mitochondrial processes contribute to energy perturbations in the brain and neuropsychiatric symptoms (2023) ​Glutamate-Mediated Excitotoxicity in the Pathogenesis and Treatment of Neurodevelopmental and Adult Mental Disorders (2024) ​ "In the current narrative review, we will summarize the role of glutamate-induced excitotoxicity in both the pathophysiology and therapeutic interventions of neurodevelopmental and adult mental diseases with a focus on autism spectrum disorders, substance abuse, and psychiatric disorders. "Indeed, glutamatergic drugs are under preclinical and clinical development for the treatment of different mental diseases that share glutamatergic neuroplasticity dysfunctions."

​ ​"Our mission: to help accelerate the next breakthrough in drug discovery, diagnostics and basic research." Microglia subtype markers  (2022) Amoeboid microglia ​Amoeboid microglia are associated with the developing CNS. In rats, amoeboid microglia have been shown to appear late in gestation and disappear soon after birth. Ultimately, amoeboid microglia grow long crenulated processes and transform into ramified microglia found in the adult CNS. Ramified microglia Reactive microglia Like macrophages, reactive microglia secrete inflammatory mediators, which orchestrate the cerebral immune response. ​Chronic microglial activation is associated with neurological disorders including Alzheimer's disease, multiple sclerosis, and delayed neuronal death occurring after ischaemia. ​In these instances, the persistent activation of microglia accompanied by the sustained secretion of inflammatory mediators is thought to have a deleterious effect on neuronal function and survival, thereby exacerbating disease processes. CD45 - microglia CD45 - macrophage CD11b CD68 - microglia CD68 - macrophage ​Astrocytes Maintain Glutamate Homeostasis in the CNS by Controlling the Balance between Glutamate Uptake and Release (2019)