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\setlength{\parindent}{0pt}\raggedright \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}} \vskip16pt \textcolor{GJBlue}{\large\bfseries\abstractname\space} }{% \vskip8pt \textcolor{GJMediumGrey}{\rule{\textwidth}{2pt}} \vskip16pt } \usepackage[absolute,overlay]{textpos} \makeatother \usepackage{lineno} \linenumbers \begin{document} \author[1]{Daniel A. Kinderlehrer} \author[2]{Nancy Brown} \renewcommand\Authands{ and } \date{\small \em Received: 12 June 2021 Accepted: 1 July 2021 Published: 15 July 2021} \maketitle \begin{abstract} The incidence of mental health disorders in adolescents continues to rise. The cause of the increase in mental illness is multifactorial, including both environmental and biological causes. To investigate the latter, ten adolescents at a psychiatric residential treatment center in Colorado with the DSM-5 diagnosis of major depressive disorder (MDD), of whom seven were additionally diagnosed with generalized anxiety disorder (GAD), were chosen at random for further serologic study. Testing revealed exposure to group A Streptococcus (GAS) in 3 of 10 (30%); Borrelia burgdorferi sensu lato (Bbsl) in 2 of 10 (20%); and Bartonella spp. in 3 of 10 (30%). In addition, 9 of 10 (90%) subjects had abnormal Cunningham Panels, which measures levels of antineuronal antibodies that have been associated with psychiatric disturbances. Given the degree of psychological dysfunction in these adolescents requiring intensive residential treatment, this case series lends support to the hypothesis that exposure to infectious agents may play a role, perhaps by autoimmune mechanisms, in the significant and ongoing rise in the rate of neuropsychiatric illness in adolescents. This preliminary report adds to this premise and requires further investigation. \end{abstract} \keywords{PANDAS, PANS, autoimmune, neuroinflammation, streptococcus, lyme, bartonella, cunningham panel, mental illness, adolescents.} \begin{textblock*}{18cm}(1cm,1cm) % {block width} (coords) \textcolor{GJBlue}{\LARGE Global Journals \LaTeX\ JournalKaleidoscope\texttrademark} \end{textblock*} \begin{textblock*}{18cm}(1.4cm,1.5cm) % {block width} (coords) \textcolor{GJBlue}{\footnotesize \\ Artificial Intelligence formulated this projection for compatibility purposes from the original article published at Global Journals. However, this technology is currently in beta. \emph{Therefore, kindly ignore odd layouts, missed formulae, text, tables, or figures.}} \end{textblock*} \begin{textblock*}{10cm}(1.05cm,3cm) {{\textit{CrossRef DOI of original article:}} \underline{10.34257/GJMRAVOL21IS1PG1}} \end{textblock*}\let\tabcellsep& \section[{Introduction}]{Introduction}\par cited as a significant factor \hyperref[b3]{[5]}. Common sources of Corresponding Author ?: e-mail: kinderlehrer@gmail.com stress in adolescence include social stress/peer pressure, academic pressure, isolation, dysfunctional home environment, physical or sexual abuse, bullying, low self-esteem and substance abuse. Compounding these issues, adolescents who spend more time on social media and electronic devices such as smartphones are more likely to report mental health issues, and an increase in screen time is associated with a decrease in in-person social interaction and an increase in depressive episodes \hyperref[b0]{[1]}.\par It is clear that biological issues also have a significant role in mental health disorders. Neuropsychiatric symptoms can be caused by multiple organic issues including heavy metal toxicity \hyperref[b4]{[6]}, allergy to gluten \hyperref[b5]{[7]}, thyroid disorders \hyperref[b6]{[8]}, and autoimmune illness \hyperref[b7]{[9]}. In addition, the medical literature is replete with the identification of neuropsychiatric disorders caused by infection \hyperref[b7]{[9,}\hyperref[b8]{10]}.\par Autoimmune mechanisms may underly the linkage between infection and neuropsychiatric disorders. In 1994, Swedo et.al. described mental health issues associated with group A Streptococcus (GAS) infections \hyperref[b39]{[38]}. Based on the first fifty children who met the clinical description of neuropsychiatric disorders following streptococcal infections, Swedo outlined five diagnostic criteria for this diagnosis and coined the term pediatric autoimmune neuropsychiatric disorders ental health problems among adolescents are increasing \hyperref[b0]{[1]}. The most common mental health disorder in this age group is anxiety. Anxiety disorders occur in approximately 32\% of adolescents 13 to 18 years of age, and 8.3\% had severe impairment \hyperref[b1]{[2]}. The number of adolescents who experienced major depressive disorder (MDD) was 21.48\% in 2015 and increased by nearly a third from 2009/2010 to 2015 \hyperref[b0]{[1]}; 13.3\% of youth aged 12 to 17 report suffering from at least one major depressive episode in 2017 {\ref [3]}. The suicide rate among persons aged 10 to 24 has increased 56\% between 2007 and 2017; since 2014 suicide has replaced homicide as the second most common cause of death for teenagers ages 10 to 19 in the United States \hyperref[b2]{[4]}.\par The cause of mental health disorders in adolescents is multifactorial, including both biological and environmental causes. Stress issues have been \section[{M}]{M}\par Other tick-borne infections can also cause neuropsychiatric illness. Infections with Bartonella spp. have been associated with anxiety, panic disorder, depression, obsessive compulsive disorder (OCD), phobias, eating disorders, alcohol and drug abuse, psychosis and personality disorders \hyperref[b18]{[18]}\hyperref[b19]{[19]}\hyperref[b20]{[20]}\hyperref[b21]{[21]}\hyperref[b22]{[22]}. Bartonella henselae (B. henselae) is also associated with a wide spectrum of autoimmune conditions \hyperref[b23]{[23]}\hyperref[b25]{[24]}\hyperref[b26]{[25]}\hyperref[b27]{[26]}\hyperref[b28]{[27]}\hyperref[b29]{[28]}\hyperref[b30]{[29]}\hyperref[b31]{[30]}\hyperref[b32]{[31]}\hyperref[b33]{[32]}\hyperref[b34]{[33]}\hyperref[b35]{[34]}\hyperref[b36]{[35]}\hyperref[b37]{[36]}\hyperref[b38]{[37]}, including pediatric acute-onset neuropsychiatric syndrome (PANS) \hyperref[b22]{[22]}.\par Infections transmitted by ticks have been linked to a spectrum of mood and behavioral disorders. Borrelia burgdorferi sensu lato (Bbsl), the pathogen that causes Lyme disease, is responsible for a wide range of mental health disorders, including anxiety disorders, depression, schizoaffective disorders, bipolar disorder, eating disorders, addiction, suicide, violence, anhedonia, depersonalization and dissociative episodes \hyperref[b10]{[11]}\hyperref[b12]{[12]}\hyperref[b13]{[13]}\hyperref[b14]{[14]}\hyperref[b16]{[15]} {\ref [16]}\hyperref[b17]{[17]}.\par Abstract-The incidence of mental health disorders in adolescents continues to rise. The cause of the increase in mental illness is multifactorial, including both environmental and biological causes. To investigate the latter, ten adolescents at a psychiatric residential treatment center in Colorado with the DSM-5 diagnosis of major depressive disorder (MDD), of whom seven were additionally diagnosed with generalized anxiety disorder (GAD), were chosen at random for further serologic study. Testing revealed exposure to group A Streptococcus (GAS) in 3 of 10 (30\%); Borrelia burgdorferi sensu lato (Bbsl) in 2 of 10 (20\%); and spp. in 3 of 10 (30\%). In addition, 9 of 10 (90\%) subjects had abnormal Cunningham Panels, which measures levels of antineuronal antibodies that have been associated with psychiatric disturbances. Given the degree of psychological dysfunction in these adolescents requiring intensive residential treatment, this case series lends support to the hypothesis that exposure to infectious agents may play a role, perhaps by autoimmune mechanisms, in the significant and ongoing rise in the rate of neuropsychiatric illness in adolescents. This preliminary report adds to this premise and requires further investigation.\par Bartonella associated with streptococcal infections (PANDAS) \hyperref[b40]{[39]}. These criteria include OCD or tic disorder (as defined by DSM IV, American Psychiatric Association, 2000), prepubertal age of onset, an abrupt onset with relapsing or remitting course, neurological abnormalities during exacerbations (such as involuntary, choreiform movements or motor hyperactivity), and a temporal association between streptococcal infections and neuropsychiatric symptom exacerbations.\par In recognition of the finding that multiple microbes in addition to GAS can trigger autoimmune encephalitis and autoimmune encephalopathies or PANDAS-like syndromes, this condition is now referred to as pediatric acute-onset neuropsychiatric syndrome (PANS), and criteria have been developed for this diagnosis. Children must have the abrupt onset of OCD or severely restricted food intake; there must be no known neurologic or medical disorder that would account for the symptoms; and include at least two of the following seven conditions: anxiety, emotional lability and/or depression; irritability, aggression, and/or severe oppositional behaviors; behavioral (developmental) regression; sudden deterioration in school performance; motor or sensory abnormalities; somatic signs and symptoms, including sleep disturbances, enuresis, or urinary frequency \hyperref[b41]{[40]}. Multiple microbes have been documented as triggering PANS including herpes simplex virus, influenza A virus, varicella zoster virus, Epstein-Barr virus, HIV, recurrent sinusitis, the common Immune cross-reactivity between microbes and host tissues has been well documented and is attributed to molecular mimicry \hyperref[b44]{[43,}\hyperref[b45]{44]}. Children with PANS-like conditions exhibit elevated levels of antineuronal antibodies against dopamine receptors \hyperref[b46]{[45]}\hyperref[b47]{[46]}\hyperref[b49]{[47]}, lysoganglioside \hyperref[b50]{[48]}, and tubulin \hyperref[b51]{[49]}. Antineuronal antibodies crossing the blood-brain barrier can activate calcium calmodulin-dependent protein kinase II (CaMKII), a multifunctional enzyme highly concentrated in the brain, which mediates many different learning, memory, and developmental cell pathways. CaMKII alters dopamine neurotransmission, leading to neuropsychiatric symptoms of OCD as well as tics, and youths with OCD and tics have elevations in CaMKII activity \hyperref[b52]{[50]}.The Cunningham Panel was developed to assess patients with PANS-like syndromes, and includes levels of these antibodies as well as CaMKII activity.\par autoimmune induced neuroinflammation as a possible cause of their disorders. \section[{II.}]{II.} \section[{Methods}]{Methods}\par Subjects were randomly selected patients at a residential adolescent treatment center. The severity of their mental health issues prevented them from living at home and attending school. All were suffering from depression, and some also suffered from anxiety. Informed consent was reviewed and approved by the Western Institutional Review Board (WIRB). Consent was obtained from all subjects and their guardians. \section[{III.}]{III.} \section[{Results}]{Results}\par The subjects ranged from fourteen to seventeen years of age. There were six females and four males. All ten satisfied DSM-5 criteria for MDD, and seven additionally satisfied DSM-5 criteria for GAD. Three of the subjects were diagnosed with Attention Deficit Disorder (ADD), three subjects had made serious suicide attempts, four subjects had behavior associated with non-suicidal self-injury disorder (NSSID) in the form of cutting, and one had tics. One subject had previously been diagnosed with celiac disease, but the remaining nine had no known medical disorder. See Table \hyperref[tab_0]{1}. cold, Mycoplasma pneumonia and B. henselae \hyperref[b22]{[22,}\hyperref[b42]{41,}\hyperref[b43]{42]}.\par Serum testing included Lyme ImmunoBlot IgM and IgG for evidence of exposure to Bbsl; Bartonella Multi-species Western Blot IgM and IgG for evidence of exposure to Bartonella spp.; Anti-DNase B (ADB) for evidence of exposure to GAS; and the Cunningham Panel for evidence of autoimmune neuroinflammation. The Cunningham Panel includes five assays performed on serum that measure human IgG levels by enzymelinked immunosorbent assay (ELISA) directed against the Dopamine D1 Receptor, Dopamine D2L Receptor, Lysoganglioside-GM1, and Tubulin, as well as a cell stimulation assay which measures the ability of a person's serum IgG to stimulate CaMKII activity in human neuronal cells.\par This exploratory study has two aims. First, to examine whether adolescents with serious mental health disorders have a higher rate of exposure to GAS, Bbsl, and Bartonella spp. than the general population. Secondly, to evaluate whether adolescents with significant mental health disorders have elevations in antineuronal antibody levels, consistent with Nine of ten subjects (90\%) had abnormalities in the Cunningham Panel with elevations in anti-neuronal antibodies and five of ten (50\%) subjects with elevations in CaMKII activity. See Table \hyperref[tab_3]{5}. \section[{Discussion}]{Discussion}\par In this case series, three of ten subjects (30\%) had positive titers to ADB consistent with exposure to GAS. ADB titers become positive one week to one month after streptococcal infection and usually stay positive for months. However, in some individuals ADB titers stay positive longer than one year, including in some with streptococcal carrier states \hyperref[b53]{[51,}\hyperref[b54]{52]}. ADB titers are positive in the majority of patients with streptococcal induced autoimmune illnesses including rheumatic fever and post-streptococcal glomerulonephritis, as well as in patients with PANDAS \hyperref[b53]{[51]}\hyperref[b54]{[52]}\hyperref[b55]{[53]}. Fujikawa et. al. found that only 8\% of a noncarrier control population had elevations in ADB titers \hyperref[b54]{[52]}. The finding that 30\% of the subjects in this study had elevations in ADB levels suggests the possibility that GAS may have played a role in their mental health issues.\par In this case series, 2 of 10 (20\%) subjects showed evidence of exposure to or current infection with Bbsl. The Lyme immunoblot assay, which utilizes pure While neuroinflammation has been documented in both acute and persistent infection with Bbsl \hyperref[b65]{[63]}\hyperref[b66]{[64]}\hyperref[b67]{[65]}, this pathogen has not as yet been documented as a singular cause of PANS. Cross et.al. described the case of a pre-pubescent female who developed PANS with a positive Cunningham Panel, was serologically positive for Streptococcus but also for several tick-borne infections including Bbsl, B. henselae, and Babesia recombinant proteins as test antigens, is more sensitive and specific than the Lyme ELISA and the Lyme Western Blot \hyperref[b57]{[54]}\hyperref[b58]{[55]}\hyperref[b59]{[56]}. While cross-reactivity of some Borrelia proteins with antigens from other bacteria and viruses is well known \hyperref[b41]{[40]}, the presence of IgG antibodies at 23-kdA (outer surface protein [Osp]C), 34-kdA (OspB) and at 39-kdA are considered specific and therefore diagnostic for B. burgdorferi \hyperref[b60]{[57]}\hyperref[b61]{[58]}\hyperref[b62]{[59]}\hyperref[b63]{[60]}. Subjects 3 and 6 demonstrated IgG reactivity at Bands 23, 34 and/or 39. While these results do not meet the Centers for Disease Control and Prevention (CDC) criteria for reporting Lyme disease, the CDC criteria were established for surveillance purposes only, not for clinical diagnosis {\ref [61,}\hyperref[b64]{62]}. \section[{Bbsl ImmunoBlot positive}]{Bbsl ImmunoBlot positive} \section[{Medical Research}]{Medical Research}\par Volume XXI Issue I Version I( D D D D ) A © 2021 Global Journals\par Microbial Induced Autoimmune Inflammation as a Cause of Mental Illness in Adolescents: A Case Series duncani, and responded to broad spectrum antimicrobial therapy \hyperref[b69]{[66]}. Many of the neuropsychiatric symptoms of neuroborreliosis parallel or overlap with those of PANS, including anxiety disorders, depression, OCD and tics \hyperref[b10]{[11]}\hyperref[b12]{[12]}\hyperref[b13]{[13]}\hyperref[b14]{[14]}\hyperref[b16]{[15]} {\ref [16]}\hyperref[b17]{[17]}\hyperref[b70]{67]}.\par illness in humans, including autoimmune and psychiatric illness as noted above. There is an abundance of data on infections in animals with B. vinsonii and B. elizabethae, but in humans it is limited. There are reports that both species can cause infective endocarditis \hyperref[b86]{[82]}\hyperref[b87]{[83]}\hyperref[b88]{[84]}, and B. vinsonii has additionally been reported to cause neurological abnormalities \hyperref[b89]{[85,}\hyperref[b90]{86]}. There are no reports of neuropsychiatric complications with these two Bartonella species. However, these infections need to be considered emerging illnesses at this time; few laboratories are equipped to identify these potential pathogens and correlate them with clinical syndromes.\par There is also the possibility of cross-reactivity among different species of Bartonella \hyperref[b92]{[87]}. The relevance of positive Bartonella spp. IgG in three adolescents in this study is unclear.\par In this case series, 9 of 10 (90\%) subjects demonstrated the presence of anti-neuronal antibodies and 5 of 10 (50\%) had CaMKII activation. The utility of the Cunningham Panel has been demonstrated in the assessment of PANDAS/PANS by Shimasaki et. al. They evaluated 58 patients meeting the diagnostic criteria for PANDAS/PANS who were tested pre-and posttreatment. Patients were categorized as "Improved/ Resolved" (n=34) or "Not-Improved/Worsened" (n=24). The changes in assays of the Cunningham Panel paralleled changes in patient symptoms following treatment with an accuracy of 90\%, a sensitivity of 88\% and a specificity of 92\% \hyperref[b94]{[88]}. Chain et.al. compared 35 acute onset PANDAS patients with 28 healthy controls and found that 32 sera (91.4\%) in the PANDAS group were positive for one or more of the antineuronal autoantibodies compared with 9 of 28 healthy controls (32.1\%) \hyperref[b95]{[89]}. Likewise, Connery et.al. found that the Cunningham Panel accurately predicted significant responses in aberrant behavior and social responsiveness in children with autism \hyperref[b96]{[90]}. Multiple other studies have found an association between autoimmune neuropsychiatric disorders such as PANDAS/PANS and the biomarkers included in the Cunningham Panel \hyperref[b46]{[45]}\hyperref[b47]{[46]}\hyperref[b49]{[47]}\hyperref[b50]{[48]}\hyperref[b51]{[49]}\hyperref[b52]{[50]}\hyperref[b97]{[91]}\hyperref[b98]{[92]}\hyperref[b100]{[93]}\hyperref[b101]{[94]}\hyperref[b103]{[95]}\hyperref[b104]{[96]}. Antineuronal antibodies crossing the blood brain barrier and activating CaMKII may underlie the serious mental health issues in the subjects in this case series.\par Hesselmark and Bejerot have challenged the utility of using the Cunningham panel to diagnose PANS \hyperref[b105]{[97]}.Their study found both low sensitivity and specificity of the Cunningham panel, and did not find a statistical difference between patients with PANS and healthy controls. But their findings have been challenged because, among other issues, they used invalid serum collection tubes-they used gold top tubes that contain both a clot activator and a serum gel separator rather than glass red top tubes that have no additives \hyperref[b106]{[98]}.\par The rates of infections with GAS \hyperref[b107]{[99,}\hyperref[b109]{100]} and tick-borne pathogens \hyperref[b110]{[101]} are increasing, and perhaps molecular mimicry resulting in immune cross-reactivity underlies the rise in autoimmune illnesses \hyperref[b111]{[102]}. Nonmicrobial factors that underlie the development of autoimmunity are also increasing, including occupational exposures such as pesticides \hyperref[b112]{[103,}\hyperref[b113]{104]}, dietary changes and their impact on the microbiome B. henselae causes a wide spectrum of clinical Some of the chronic symptoms in patients with post-treatment Lyme disease syndrome (PTLDS) are attributed to autoimmunity \hyperref[b71]{[68,}\hyperref[b72]{69]}, and Chandra et. al. found anti-neuronal antibody levels 41 of 83 (49.4\%) PTLDS patients who continued to suffer from chronic symptoms of pain, fatigue, and impaired cognition; antibodies against Bbsl cross-reacted with several neural proteins \hyperref[b65]{[63]}. Likewise, Fallon et.al. found higher levels of antibodies against Lysoganglioside-GM1, Tubulin, and Dopamine D1-Receptor as well as well as elevated activity of CaMKII in patients with a prior history of Lyme borreliosis but not in those without that history \hyperref[b73]{[70]}. Osp A has a protein sequence similar to GAS \hyperref[b74]{[71]}, and OspA is associated with autoimmune reactivity \hyperref[b72]{[69]}. It is not unlikely that Bbsl is yet another microbe that can trigger PANS-like syndromes. The finding that 20\% of subjects in this case series had evidence of exposure to Bbsl raises the possibility that this microbe is playing a role in their mental health issues.\par In this case series, 3 of 10 (30\%) subjects showed evidence of exposure to or current infection with Bartonella spp. B. henselae, an intracellular gramnegative pleomorphic bacillus, is the causative agent of cat scratch disease (CSD) transmitted via the cat flea. In addition to transmission via fleas, sandflies and lice, B. henselae can be transmitted via the Ixodes tick \hyperref[b75]{[72,}\hyperref[b77]{73]}. Co-occurrence of Bartonella spp. with known tick-borne pathogens such as Bbsl is not uncommon. A survey by Adelson et. al. of Ixodes ticks in northern New Jersey found B. burgdorferi present in 35\% while 34\% harbored Bartonella spp. \hyperref[b78]{[74]}. Additional surveys have confirmed the high incidence of Bartonella spp. in Ixodes ticks \hyperref[b79]{[75,}\hyperref[b80]{76]}. The Bartonella bacillus is difficult to grow; therefore, culture is not recommended \hyperref[b81]{[77]}. While polymerase chain reaction (PCR) in serum or tissue specimens is the most definitive way to diagnose infection with Bartonella, PCR detection lacks sensitivity (43-76\%) \hyperref[b82]{[78]}. ELISA and Indirect immunoflourescence assays (IFA) are the standard tools to diagnose bartonellosis, however increased sensitivity is associated with decreased specificity with both these antibody assays \hyperref[b83]{[79,}\hyperref[b84]{80]}. There is preliminary evidence that Western blot testing for Bartonella as performed in this case series is both more sensitive and specific than either IFA or ELISA testing \hyperref[b85]{[81]}. Microbial Induced Autoimmune Inflammation as a Cause of Mental Illness in Adolescents: A Case Series \hyperref[b114]{[105,}\hyperref[b115]{106]}, and stress-related disorders such as posttraumatic stress disorder (PTSD) \hyperref[b116]{[107,}\hyperref[b118]{108]}. Indeed, all these factors can alter epigenetics \hyperref[b119]{[109]}\hyperref[b122]{[110]}\hyperref[b123]{[111]}\hyperref[b124]{[112]}\hyperref[b125]{[113]} {\ref [114]}, and epigenetics is crucial to the development of autoimmunity {\ref [115]}. Therefore, it is possible that multiple factors are contributing to autoimmunity and are cumulative in succeeding generations.\par V. \section[{Conclusion}]{Conclusion}\par The increasing incidence of mental health disorders in adolescents is multifactorial. Stress issues and an increase in screen time on electronic devices has appropriately received attention, but less attention has been given to the role of organic disorders. This case series documented exposure to GAS, Bbsl and Bartonella spp. in 5 of 10 (50\%) subjects, raising the possibility that these microbes may be playing a causative role in the subjects' mental illness. In addition, 9 of 10 (90\%) subjects had evidence of autoimmune neuroinflammation as evidenced by their positive Cunningham Panels. The high percentage incidence of antineuronal antibodies and CaMKII activation in this group of ten subjects may not necessarily be indicative of all patients in this facility due to the small sample size, but it is possible that neuroinflammation is an important contributor to the increasingly high incidence of mental health disorders in the adolescent population.\par Given the serious and increasing morbidity and mortality of mental illness in the adolescent population, the implications are significant for promoting future research. Further studies in a larger cohort of patients compared with a healthy control population that would help elucidate the roles of GAS, Bbsl and Bartonella along with autoimmune neuroinflammation in the etiology of mental health issues in the adolescent population is warranted. \begin{figure}[htbp] \noindent\textbf{1} \par \begin{longtable}{P{0.4864457831325301\textwidth}P{0.0588855421686747\textwidth}P{0.04096385542168675\textwidth}P{0.03328313253012048\textwidth}P{0.025602409638554216\textwidth}P{0.04608433734939759\textwidth}P{0.04096385542168675\textwidth}P{0.04864457831325301\textwidth}P{0.012801204819277108\textwidth}P{0.05632530120481928\textwidth}} Subject\tabcellsep Age\tabcellsep Gender\tabcellsep MDD\tabcellsep GAD\tabcellsep Suicide attempt\tabcellsep Eating Disorder\tabcellsep NSSID (Cutting)\tabcellsep Tics\tabcellsep Medical Disorder\\ 1\tabcellsep 16\tabcellsep M\tabcellsep +\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep Celiac\\ 2\tabcellsep 16\tabcellsep F\tabcellsep +\tabcellsep \tabcellsep +\tabcellsep \tabcellsep +\tabcellsep \tabcellsep \\ 3\tabcellsep 14\tabcellsep M\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ 4\tabcellsep 15\tabcellsep F\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep +\tabcellsep +\tabcellsep +\tabcellsep \\ 5\tabcellsep 15\tabcellsep F\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ 6\tabcellsep 16\tabcellsep F\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ 7\tabcellsep 15\tabcellsep M\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ 8\tabcellsep 17\tabcellsep F\tabcellsep +\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep +\tabcellsep \tabcellsep \\ 9\tabcellsep 17\tabcellsep M\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ 10\tabcellsep 15\tabcellsep F\tabcellsep +\tabcellsep \tabcellsep \tabcellsep \tabcellsep +\tabcellsep \tabcellsep \\ \multicolumn{3}{l}{MDD, Major depressive disorder}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ \multicolumn{3}{l}{GAD, Generalized anxiety disorder}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ \multicolumn{4}{l}{NSSID, Non-suicidal self-injury disorder}\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ \multicolumn{7}{l}{Three of ten subjects (30\%) had elevated levels of ADB. See Table 2.}\tabcellsep \tabcellsep \tabcellsep \end{longtable} \par \caption{\label{tab_0}Table 1 :}\end{figure} \begin{figure}[htbp] \noindent\textbf{2} \par \begin{longtable}{P{0.4008361204013378\textwidth}P{0.042642140468227424\textwidth}P{0.10944816053511705\textwidth}P{0.0014214046822742473\textwidth}P{0.011371237458193979\textwidth}P{0.08812709030100334\textwidth}P{0.0028428093645484947\textwidth}P{0.07391304347826086\textwidth}P{0.11939799331103677\textwidth}} \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Year 2021\\ \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 3\\ \tabcellsep \tabcellsep \multicolumn{2}{l}{Subject 1 2 3 4 5 6 7 8 9}\tabcellsep \tabcellsep Anti-DNase B (RR:0-170) 286 125 <78 <78 324 113 <78 238 163\tabcellsep \tabcellsep \tabcellsep Volume XXI Issue I Version I\\ \tabcellsep \tabcellsep \multicolumn{4}{l}{10 Elevated levels are highlighted and in bold <78}\tabcellsep \tabcellsep \tabcellsep ( D D D D ) A\\ \multicolumn{8}{l}{Table 3 summarizes the results of the Lyme ImmunoBlot IgM and IgG testing. Two of ten subject (20\%) had antibodies to IgG specific bands P23, P34 and P39. Table 3: Results of Lyme ImmunoBlot testing Subject P93 P66 P58 P45 P41 P39 P34 P31 P30 P28 P23 P18 Results IgG ++ + NEG}\tabcellsep Medical Research\\ 1 2\tabcellsep IgM IgG IgM IgG\tabcellsep +\tabcellsep \tabcellsep + -+\tabcellsep +\tabcellsep +\tabcellsep NEG NEG NEG POS\tabcellsep Global Journal of\\ 3\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ \tabcellsep IgM\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep NEG\\ 4\tabcellsep IgG\tabcellsep +\tabcellsep +\tabcellsep +\tabcellsep \tabcellsep \tabcellsep NEG\\ \tabcellsep IgM\tabcellsep \tabcellsep \tabcellsep +\tabcellsep \tabcellsep \tabcellsep NEG\\ \tabcellsep IgG\tabcellsep \tabcellsep \tabcellsep +\tabcellsep ++\tabcellsep +\tabcellsep NEG\\ 5\tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \\ \tabcellsep IgM\tabcellsep \tabcellsep \tabcellsep +\tabcellsep \tabcellsep \tabcellsep NEG\\ \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep © 2021 Global Journals\end{longtable} \par \caption{\label{tab_1}Table 2 :}\end{figure} \begin{figure}[htbp] \noindent\textbf{4} \par \begin{longtable}{P{0.4188995215311005\textwidth}P{0.13624401913875597\textwidth}P{0.22775119617224882\textwidth}P{0.06710526315789474\textwidth}} \multicolumn{4}{l}{Microbial Induced Autoimmune Inflammation as a Cause of Mental Illness in Adolescents: A Case Series}\\ Year 2021\tabcellsep \tabcellsep \tabcellsep \\ 4\tabcellsep \tabcellsep \tabcellsep \\ Volume XXI Issue I Version I\tabcellsep Subject 1\tabcellsep \multicolumn{2}{l}{Bartonella Western blots IgG IgM NEG NEG}\\ D D D D ) A\tabcellsep 2\tabcellsep NEG\tabcellsep NEG\\ (\tabcellsep \tabcellsep \tabcellsep \\ Medical Research Global Journal of\tabcellsep 3 4 5 6 7 8 9\tabcellsep POS B. elizabethae NEG NEG POS B. vinsonii NEG NEG POS B. henselae\tabcellsep NEG NEG NEG NEG NEG NEG NEG\\ \tabcellsep 10\tabcellsep NEG\tabcellsep NEG\\ \tabcellsep \multicolumn{2}{l}{IgG, Immunoglobulin G}\tabcellsep \\ \tabcellsep \multicolumn{2}{l}{IgM, Immunoglobulin M}\tabcellsep \\ © 2021 Global Journals\tabcellsep \tabcellsep \tabcellsep \end{longtable} \par {\small\itshape [Note: B. elizabethiae, Bartonella elizabethiae B. vinsonii, Bartonella vinsonii B. heneslae, Bartonella henselae Three of ten subjects (30\%) had antibodies to either B. henselae, Bartonella elizabethae (B. elizabethae) or Bartonella vinsonii (B. vinsonii). See Table 4.]} \caption{\label{tab_2}Table 4 :}\end{figure} \begin{figure}[htbp] \noindent\textbf{5} \par \begin{longtable}{P{0.19333333333333333\textwidth}P{0.14833333333333332\textwidth}P{0.15166666666666667\textwidth}P{0.125\textwidth}P{0.13999999999999999\textwidth}P{0.09166666666666667\textwidth}} Subject\tabcellsep Anti-Dopamine D1 RR:500-2000\tabcellsep Anti-Dopamine D2L RR:2000-8000\tabcellsep Anti-Lysoganglioside RR:80-320\tabcellsep Anti-Tubulin RR:250-1000\tabcellsep CaMKII Activity RR:53-130\\ 1\tabcellsep 1:8000\tabcellsep 1:8000\tabcellsep 1:80\tabcellsep 1:2000\tabcellsep 125\\ 2\tabcellsep 1:4000\tabcellsep 1:8000\tabcellsep 1:160\tabcellsep 1:4000\tabcellsep 137\\ 3\tabcellsep 1:4000\tabcellsep 1:8000\tabcellsep 1:160\tabcellsep 1:4000\tabcellsep 133\\ 4\tabcellsep 1:4000\tabcellsep 1:8000\tabcellsep 1:160\tabcellsep 1:8000\tabcellsep 159\\ 5\tabcellsep 1:4000\tabcellsep 1:8000\tabcellsep 1:160\tabcellsep 1:4000\tabcellsep 130\\ 6\tabcellsep 1:2000\tabcellsep 1:4000\tabcellsep 1:80\tabcellsep 1:2000\tabcellsep 121\\ 7\tabcellsep 1:4000\tabcellsep 1:2000\tabcellsep 1:40\tabcellsep 1:2000\tabcellsep 123\\ 8\tabcellsep 1:16000\tabcellsep 1:16000\tabcellsep 1:320\tabcellsep 1:4000\tabcellsep 134\\ 9\tabcellsep 1:2000\tabcellsep 1:4000\tabcellsep 1:80\tabcellsep 1:1000\tabcellsep 113\\ 10\tabcellsep 1:4000\tabcellsep 1:8000\tabcellsep 1:80\tabcellsep 1:4000\tabcellsep 118\\ \multicolumn{3}{l}{Abnormal results are highlighted and in bold}\tabcellsep \tabcellsep \tabcellsep \\ \multicolumn{3}{l}{CaMKII, Calcium calmodulin-dependent protein kinase II}\tabcellsep \tabcellsep \tabcellsep \end{longtable} \par \caption{\label{tab_3}Table 5 :}\end{figure} \begin{figure}[htbp] \noindent\textbf{6} \par \begin{longtable}{} \end{longtable} \par \caption{\label{tab_4}Table 6}\end{figure} \begin{figure}[htbp] \noindent\textbf{6} \par \begin{longtable}{P{0.20923076923076925\textwidth}P{0.08826923076923077\textwidth}P{0.009807692307692307\textwidth}P{0.13730769230769233\textwidth}P{0.13730769230769233\textwidth}P{0.26807692307692305\textwidth}} \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Year 2021\\ \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep 5\\ Subject 1 2 3 4 5 6 7 8\tabcellsep Anti-DNase B positive + + +\tabcellsep + +\tabcellsep Bartonella spp. Western Blot positive + +\tabcellsep Cunningham Panel positive + + + + + + + +\tabcellsep Volume XXI Issue I Version I D D D D )\\ 9\tabcellsep \tabcellsep \tabcellsep +\tabcellsep \tabcellsep (\\ \multicolumn{2}{l}{10 Bbsl, Borrelia burgdorferi sensuolato}\tabcellsep \tabcellsep \tabcellsep +\tabcellsep Medical Research\\ \tabcellsep \tabcellsep \tabcellsep \tabcellsep \tabcellsep Global Journal of\end{longtable} \par {\small\itshape [Note: A © 2021 Global Journals Microbial Induced Autoimmune Inflammation as a Cause of Mental Illness in Adolescents: A Case Series IV.]} \caption{\label{tab_5}Table 6 :}\end{figure} \backmatter \subsection[{Acknowledgments}]{Acknowledgments}\par The authors wish to acknowledge the cooperation of the administration of the Fire Mountain Treatment Center near Estes Park, Colorado; IGeneX laboratory that performed serological testing for Borrelia burgdorferi and Bartonella; Moleculera Labs that performed Cunningham Panel tests; and Dr. Rosalie Greenberg for her assistance in the preparation of this manuscript. \subsection[{Funding}]{Funding}\par This research received no external funding. \subsection[{Author contributions}]{Author contributions}\par D.A.K. conceived the premise of this research and secured IRB approval. 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