Late-stage borreliosis and substance abuse.

Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by Borrelia infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide. Methods: Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence in situ hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue. Results: Autopsy tissue evaluation demonstrated Borrelia in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by Borrelia-induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia. Conclusions: Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.

Microbes and Mental Illness: Past, Present, and Future.

A review of the association between microbes and mental illness is performed, including the history, relevant definitions, infectious agents associated with mental illnesses, complex interactive infections, total load theory, pathophysiology, psychoimmunology, psychoneuroimmunology, clinical presentations, early-life infections, clinical assessment, and treatment. 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. Specific microbes that have been associated or potentially associated with at least one of these conditions include Aspergillus, Babesia, Bartonella, Borna disease virus, Borrelia burgdorferi (Lyme disease), Candida, Chlamydia, coronaviruses (e.g., SARS-CoV-2), Cryptococcus neoformans, cytomegalovirus, enteroviruses, Epstein-Barr virus, hepatitis C, herpes simplex virus, human endogenous retroviruses, human immunodeficiency virus, human herpesvirus-6 (HHV-6), human T-cell lymphotropic virus type 1, influenza viruses, measles virus, Mycoplasma, Plasmodium, rubella virus, Group A Streptococcus (PANDAS), Taenia solium, Toxoplasma gondii, Treponema pallidum (syphilis), Trypanosoma, and West Nile virus. Recognition of the microbe and mental illness association with the development of greater interdisciplinary research, education, and treatment options may prevent and reduce mental illness morbidity, disability, and mortality.

Adverse Childhood Events, Post-Traumatic Stress Disorder, Infectious Encephalopathies and Immune-Mediated Disease.

Adverse Childhood Events (ACE), Post-Traumatic Stress Disorder (PTSD), and infectious encephalopathies are associated with immune-mediated diseases. Data supporting this are reviewed, and an integrated hypothesis is provided. All three can be associated with intrusive symptoms and temporal lobe pathology. ACE and PTSD are accompanied by an impaired mental capacity to differentiate external danger vs. safety. Infectious encephalopathies are accompanied by a failure of adaptive immunity and an impaired immune capacity to differentiate internal danger vs. safety. All three conditions are associated with impairments to differentiate danger vs. safety and adapt effectively. There are reciprocal interactions between ACE, PTSD, and infectious encephalopathies with accompanying persistent immune activation. This is associated with immune dysregulation, chronic hyperarousal, activation of the stress response, and impairments of the fear recognition and response neural circuits, hypothalamic-pituitary-adrenal axis, amygdala, and hippocampus. The pathophysiological processes can result in a broad spectrum of chronic neuropsychiatric and somatic symptoms and diseases. Understanding the psychodynamic, neurological, neuroimmune, inflammatory and autoimmune components of this interactive process expands the effective treatment opportunities.

A Clinical Diagnostic System for Late-Stage Neuropsychiatric Lyme Borreliosis Based upon an Analysis of 100 Patients.

Many late-stage chronic Lyme disease clinical findings are neuropsychiatric. A total clinical assessment is critical in diagnosis, especially since controversy surrounds the reliability of laboratory testing. The clinical findings of one hundred Lyme disease patients with chronic neuropsychiatric symptoms were entered into a database. The prevalence of each clinical finding pre-infection and post-infection was compared and calculated within the 95% confidence interval. Patients had minimal symptoms pre-infection, but a high post-infection prevalence of a broad spectrum of acquired multisystem symptoms. These findings included impairments of attention span, memory, processing, executive functioning, emotional functioning, behavior, psychiatric syndromes, vegetative functioning, neurological, musculoskeletal, cardiovascular, upper respiratory, dental, pulmonary, gastrointestinal, genitourinary, and other symptoms. The most prevalent symptoms included sustained attention impairments, brain fog, unfocused concentration, joint symptoms, distraction by frustration, depression, working memory impairments, decreased school/job performance, recent memory impairments, difficulty prioritizing multiple tasks, fatigue, non-restorative sleep, multitasking difficulties, sudden mood swings, hypersomnia, mental apathy, decreased social functioning, insomnia, tingling, word finding difficulties, name retrieval, headaches, sound hypersensitivity, paresis, anhedonia, depersonalization, cold intolerance, body temperature fluctuations, light sensitivity and dysfluent speech. The average patient had five symptoms pre-infection and 82 post-infection. Pattern recognition is critical in making a diagnosis. This study was used to develop three clinical assessment forms.

Differentiating Psychosomatic, Somatopsychic, Multisystem Illnesses, and Medical Uncertainty.

There is often difficulty differentiating between psychosomatic, somatopsychic, multisystem illness, and different degrees of medical uncertainty. Uncommon, complex, and multisystem diseases are commonly misdiagnosed. Two case histories are described, and relevant terms differentiating psychosomatic, somatopsychic, and multisystem illnesses are identified, reviewed, and discussed. Adequate differentiation requires an understanding of the mind/body connection, which includes knowledge of general medicine, psychiatry, and the systems linking the body and the brain. A psychiatric diagnosis cannot be given solely based upon the absence of physical, laboratory, or pathological findings. Medically unexplained symptoms, somatoform disorder, and compensation neurosis are outdated and/or inaccurate terms. The terms subjective, nonspecific, and vague can be used inaccurately. Conversion disorders, functional disorders, psychogenic illness, factitious disorder imposed upon another (Munchausen's syndrome by proxy), somatic symptom disorder, psychogenic seizures, psychogenic pain, psychogenic fatigue, and delusional parasitosis can be over-diagnosed. Bodily distress disorder and bodily distress syndrome are scientifically unsupported and inaccurate. Many "all in your head" conditions may be related to the microbiome and the immune system. Better education concerning the interface between medicine and psychiatry and the associated diagnostic nomenclature as well as utilizing clinical judgment and thorough assessment, exercising humility, and maintaining our roots in traditional medicine will help to improve diagnostic accuracy and patient trust.

Proposed Lyme Disease Guidelines and Psychiatric Illnesses.

The Infectious Disease Society of America, American Academy of Neurology, and American Academy of Rheumatology jointly proposed Lyme disease guidelines. Four areas most relevant to psychiatry were reviewed-the disclaimer, laboratory testing, and adult and pediatric psychiatric sections. The disclaimer and the manner in which these guidelines are implemented are insufficient to remove the authors and sponsoring organizations from liability for harm caused by these guidelines. The guidelines and supporting citations place improper credibility upon surveillance case definition rather than clinical diagnosis criteria. The guidelines fail to address the clear causal association between Lyme disease and psychiatric illnesses, suicide, violence, developmental disabilities and substance abuse despite significant supporting evidence. If these guidelines are published without very major revisions, and if the sponsoring medical societies attempt to enforce these guidelines as a standard of care, it will directly contribute to increasing a national and global epidemic of psychiatric illnesses, suicide, violence, substance abuse and developmental disabilities and the associated economic and non-economic societal burdens. The guideline flaws could be improved with a more appropriate disclaimer, an evidence-based rather than an evidence-biased approach, more accurate diagnostic criteria, and recognition of the direct and serious causal association between Lyme disease and psychiatric illnesses.

The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders.

Chronic infectious diseases, including tick-borne infections such as Borrelia burgdorferi may have direct effects, promote other infections and create a weakened, sensitized and immunologically vulnerable state during fetal development and infancy leading to increased vulnerability for developing autism spectrum disorders. A dysfunctional synergism with other predisposing and contributing factors may contribute to autism spectrum disorders by provoking innate and adaptive immune reactions to cause and perpetuate effects in susceptible individuals that result in inflammation, molecular mimicry, kynurenine pathway changes, increased quinolinic acid and decreased serotonin, oxidative stress, mitochondrial dysfunction and excitotoxicity that impair the development of the amygdala and other neural structures and neural networks resulting in a partial Klüver-Bucy Syndrome and other deficits resulting in autism spectrum disorders and/or exacerbating autism spectrum disorders from other causes throughout life. Support for this hypothesis includes multiple cases of mothers with Lyme disease and children with autism spectrum disorders; fetal neurological abnormalities associated with tick-borne diseases; similarities between tick-borne diseases and autism spectrum disorder regarding symptoms, pathophysiology, immune reactivity, temporal lobe pathology, and brain imaging data; positive reactivity in several studies with autistic spectrum disorder patients for Borrelia burgdorferi (22%, 26% and 20-30%) and 58% for mycoplasma; similar geographic distribution and improvement in autistic symptoms from antibiotic treatment. It is imperative to research these and all possible causes of autism spectrum disorders in order to prevent every preventable case and treat every treatable case until this disease has been eliminated from humanity.

Neuropsychiatric Lyme Borreliosis: An Overview with a Focus on a Specialty Psychiatrist's Clinical Practice.

There is increasing evidence and recognition that Lyme borreliosis (LB) causes mental symptoms. This article draws from databases, search engines and clinical experience to review current information on LB. LB causes immune and metabolic effects that result in a gradually developing spectrum of neuropsychiatric symptoms, usually presenting with significant comorbidity which may include developmental disorders, autism spectrum disorders, schizoaffective disorders, bipolar disorder, depression, anxiety disorders (panic disorder, social anxiety disorder, generalized anxiety disorder, posttraumatic stress disorder, intrusive symptoms), eating disorders, decreased libido, sleep disorders, addiction, opioid addiction, cognitive impairments, dementia, seizure disorders, suicide, violence, anhedonia, depersonalization, dissociative episodes, derealization and other impairments. Screening assessment followed by a thorough history, comprehensive psychiatric clinical exam, review of systems, mental status exam, neurological exam and physical exam relevant to the patient's complaints and findings with clinical judgment, pattern recognition and knowledgeable interpretation of laboratory findings facilitates diagnosis. Psychotropics and antibiotics may help improve functioning and prevent further disease progression. Awareness of the association between LB and neuropsychiatric impairments and studies of their prevalence in neuropsychiatric conditions can improve understanding of the causes of mental illness and violence and result in more effective prevention, diagnosis and treatment.

Aggressiveness, violence, homicidality, homicide, and Lyme disease.

BACKGROUND: No study has previously analyzed aggressiveness, homicide, and Lyme disease (LD). MATERIALS AND METHODS: Retrospective LD chart reviews analyzed aggressiveness, compared 50 homicidal with 50 non-homicidal patients, and analyzed homicides. RESULTS: Most aggression with LD was impulsive, sometimes provoked by intrusive symptoms, sensory stimulation or frustration and was invariably bizarre and senseless. About 9.6% of LD patients were homicidal with the average diagnosis delay of 9 years. Postinfection findings associated with homicidality that separated from the non-homicidal group within the 95% confidence interval included suicidality, sudden abrupt mood swings, explosive anger, paranoia, anhedonia, hypervigilance, exaggerated startle, disinhibition, nightmares, depersonalization, intrusive aggressive images, dissociative episodes, derealization, intrusive sexual images, marital/family problems, legal problems, substance abuse, depression, panic disorder, memory impairments, neuropathy, cranial nerve symptoms, and decreased libido. Seven LD homicides included predatory aggression, poor impulse control, and psychosis. Some patients have selective hyperacusis to mouth sounds, which I propose may be the result of brain dysfunction causing a disinhibition of a primitive fear of oral predation. CONCLUSION: LD and the immune, biochemical, neurotransmitter, and the neural circuit reactions to it can cause impairments associated with violence. Many LD patients have no aggressiveness tendencies or only mild degrees of low frustration tolerance and irritability and pose no danger; however, a lesser number experience explosive anger, a lesser number experience homicidal thoughts and impulses, and much lesser number commit homicides. Since such large numbers are affected by LD, this small percent can be highly significant. Much of the violence associated with LD can be avoided with better prevention, diagnosis, and treatment of LD.

Suicide and Lyme and associated diseases.

PURPOSE: The aim of this paper is to investigate the association between suicide and Lyme and associated diseases (LAD). No journal article has previously performed a comprehensive assessment of this subject. INTRODUCTION: Multiple case reports and other references demonstrate a causal association between suicidal risk and LAD. Suicide risk is greater in outdoor workers and veterans, both with greater LAD exposure. Multiple studies demonstrate many infections and the associated proinflammatory cytokines, inflammatory-mediated metabolic changes, and quinolinic acid and glutamate changes alter neural circuits which increase suicidality. A similar pathophysiology occurs in LAD. METHOD: A retrospective chart review and epidemiological calculations were performed. RESULTS: LAD contributed to suicidality, and sometimes homicidality, in individuals who were not suicidal before infection. A higher level of risk to self and others is associated with multiple symptoms developing after acquiring LAD, in particular, explosive anger, intrusive images, sudden mood swings, paranoia, dissociative episodes, hallucinations, disinhibition, panic disorder, rapid cycling bipolar, depersonalization, social anxiety disorder, substance abuse, hypervigilance, generalized anxiety disorder, genital-urinary symptoms, chronic pain, anhedonia, depression, low frustration tolerance, and posttraumatic stress disorder. Negative attitudes about LAD from family, friends, doctors, and the health care system may also contribute to suicide risk. By indirect calculations, it is estimated there are possibly over 1,200 LAD suicides in the US per year. CONCLUSION: Suicidality seen in LAD contributes to causing a significant number of previously unexplained suicides and is associated with immune-mediated and metabolic changes resulting in psychiatric and other symptoms which are possibly intensified by negative attitudes about LAD from others. Some LAD suicides are associated with being overwhelmed by multiple debilitating symptoms, and others are impulsive, bizarre, and unpredictable. Greater understanding and a direct method of acquiring LAD suicide statistics is needed. It is suggested that medical examiners, the Centers for Disease Control and Prevention, and other epidemiological organizations proactively evaluate the association between LAD and suicide.

The psychoimmunology of lyme/tick-borne diseases and its association with neuropsychiatric symptoms.

Disease progression of neuropsychiatric symptoms in Lyme/tick-borne diseases can be better understood by greater attention to psychoimmunology. Although there are multiple contributors that provoke and weaken the immune system, infections and persistent infections are significant causes of pathological immune reactions. Immune mediated ef-fects are a significant contributor to the pathophysiological processes and disease progression. These immune effects in-clude persistent inflammation with cytokine effects and molecular mimicry and both of these mechanisms may be present at the same time in persistent infections. Sickness syndrome associated with interferon treatment and autoimmune limbic encephalopathies are models to understand inflammatory and molecular mimicry effects upon neuropsychiatric symp-toms. Progressive inflammatory reactions have been proposed as a model to explain disease progression in depression, psychosis, dementia, epilepsy, autism and other mental illnesses and pathophysiological changes have been associated with oxidative stress, excitotoxicity, changes in homocysteine metabolism and altered tryptophan catabolism. Lyme dis-ease has been associated with the proinflammatory cytokines IL-6, IL-8, IL-12, IL-18 and interferon-gamma, the chemokines CXCL12 and CXCL13 and increased levels proinflammatory lipoproteins. Borrelia burgdorferi surface gly-colipids and flagella antibodies appear to elicit anti-neuronal antibodies and anti-neuronal antibodies and Borrelia burgdorferi lipoproteins can disseminate from the periphery to inflame the brain. Autism spectrum disorders associated with Lyme/tick-borne diseases may be mediated by a combination of inflammatory and molecular mimicry mechanisms. Greater interaction is needed between infectious disease specialists, immunologists and psychiatrists to benefit from this awareness and to further understand these mechanisms.

Morgellons disease, illuminating an undefined illness: a case series.

INTRODUCTION: This review of 25 consecutive patients with Morgellons disease (MD) was undertaken for two primary and extremely fundamental reasons. For semantic accuracy, there is only one "proven" MD patient: the child first given that label. The remainder of inclusive individuals adopted the label based on related descriptions from 1544 through 1884, an internet description quoted from Sir Thomas Browne (1674), or was given the label by practitioners using similar sources. Until now, there has been no formal characterization of MD from detailed examination of all body systems. Our second purpose was to differentiate MD from Delusions of Parasitosis (DP), another "informal" label that fit most of our MD patients. How we defined and how we treated these patients depended literally on factual data that would determine outcome. How they were labeled in one sense was irrelevant, except for the confusing conflict rampant in the medical community, possibly significantly skewing treatment outcomes. CASE PRESENTATION: Clinical information was collected from 25 of 30 consecutive self-defined patients with Morgellons disease consisting of laboratory data, medical history and physical examination findings. Abnormalities were quantified and grouped by system, then compared and summarized, but the numbers were too small for more complex mathematical analysis. The quantification of physical and laboratory abnormalities allowed at least the creation of a practical clinical boundary, separating probable Morgellons from non-Morgellons patients. All the 25 patients studied meet the most commonly used DP definitions. CONCLUSIONS: These data suggest Morgellons disease can be characterized as a physical human illness with an often-related delusional component in adults. All medical histories support that behavioral aberrancies onset only after physical symptoms. The identified abnormalities include both immune deficiency and chronic inflammatory markers that correlate strongly with immune cytokine excess. The review of 251 current NLM DP references leads us to the possibility that Morgellons disease and DP are grossly truncated labels of the same illness but with the reversal of the cause-effect order. Further, the patients' data suggest that both illnesses have an infectious origin.