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Les lectures partagées constituent une forme particulière de discours adressé aux enfants. Nous inscrivant dans les approches basées sur l’usage, nous défendons l’idée de l’importance de cette pratique dans la construction du langage chez l’enfant et dans la perspective de son entrée dans la littératie. A partir du module « Livres pour enfants » du corpus ESLO, nous observerons l’usage des liaisons au regard des caractéristiques du lecteur, des enfants, des types d’albums lus et d’un ensemble de facteurs internes. Cette étude est exploratoire dans la mesure où la taille de notre corpus nous permet d’observer seulement certains de ces facteurs. Les premières tendances obtenues et les réflexions sur les aspects méthodologiques à creuser constituent un point d’étape important pour de futurs travaux autour de la lecture partagée et de l’usage des liaisons dans le domaine de l’acquisition du langage.

Background: Clinician-administered measures to assess severity of illness anxiety and response to treatment are few. The authors evaluated a modified version of the hypochondriasis-Y-BOCS (H-YBOCS-M), a 19-item, semistructured, clinician-administered instrument designed to rate severity of illness-related thoughts, behaviors, and avoidance.Methods: The scale was administered to 195 treatment-seeking adults with DSM-IV hypochondriasis. Test-retest reliability was assessed in a subsample of 20 patients. Interrater reliability was assessed by 27 interviews independently rated by four raters. Sensitivity to change was evaluated in a subsample of 149 patients. Convergent and discriminant validity was examined by comparing H-YBOCS-M scores to other measures administered. Item clustering was examined with confirmatory and exploratory factor analyses.Results: The H-YBOCS-M demonstrated good internal consistency, interrater and test-retest reliability, and sensitivity to symptom change with treatment. Construct validity was supported by significant higher correlations with scores on other measures of hypochondriasis than with nonhypochondriacal measures. Improvement over time in response to treatment correlated with improvement both on measures of hypochondriasis and on measures of somatization, depression, anxiety, and functional status. Confirmatory factor analysis did not show adequate fit for a three-factor model. Exploratory factor analysis revealed a five-factor solution with the first two factors consistent with the separation of the H-YBOCS-M items into the subscales of illness-related avoidance and compulsions.Conclusions: H-YBOCS-M appears to be valid, reliable, and appropriate as an outcome measure for treatment studies of illness anxiety. Study results highlight "avoidance" as a key feature of illness anxiety-with potentially important nosologic and treatment implications. [ABSTRACT FROM AUTHOR]

The obsessive-compulsive (OC) spectrum has been discussed in the literature for two decades. Proponents of this concept propose that certain disorders characterized by repetitive thoughts and/or behaviors are related to obsessive-compulsive disorder (OCD), and suggest that such disorders be grouped together in the same category (i.e. grouping, or "chapter") in DSM. This article addresses this topic and presents options and preliminary recommendations to be considered for DSM-V. The article builds upon and extends prior reviews of this topic that were prepared for and discussed at a DSM-V Research Planning Conference on Obsessive-Compulsive Spectrum Disorders held in 2006. Our preliminary recommendation is that an OC-spectrum grouping of disorders be included in DSM-V. Furthermore, we preliminarily recommend that consideration be given to including this group of disorders within a larger supraordinate category of "Anxiety and Obsessive-Compulsive Spectrum Disorders." These preliminary recommendations must be evaluated in light of recommendations for, and constraints upon, the overall structure of DSM-V. [ABSTRACT FROM AUTHOR]

Abstract Background The most effective way to provide support to caregivers with infants in order to promote good health, social, emotional and developmental outcomes is the subject of numerous debates in the literature. In Canada, each province adopts a different approach which range from universal to targeted programs. Nonetheless, each year a group of vulnerable infants is identified to the child welfare system with concerns about their well-being and safety. This study examines maltreatment-related investigations in Canada involving children under the age of one year to identify which factors determine service provision at the conclusion of the investigation. Methods A secondary analysis of the Canadian Incidence Study of Reported Child Abuse and Neglect CIS-2008 (PHAC, 2010) dataset was conducted. Multivariate analyses were conducted to understand the profile of investigations involving infants (n=1,203) and which predictors were significant in the decision to transfer a case to ongoing services at the conclusion of the investigation. Logistic Regression and Classification and Regression Trees (CART) were conducted to examine the relationship between the outcome and predictors. Results The results suggest that there are three main sources that refer infants to the Canadian child welfare system: hospital, police, and non-professionals. Infant maltreatment-related investigations involve young caregivers who struggle with poverty, single-parenthood, drug/solvent and alcohol abuse, mental health issues, lack of social supports, and intimate partner violence. Across the three referral sources, primary caregiver risk factors are the strongest predictor of the decision to transfer a case to ongoing services. Conclusions Multivariate analyses indicate that the presence of infant concerns does not predict ongoing service provision, except when the infant is identified with positive toxicology at birth. The opportunity for early intervention and the need to tailor interventions for specific caregiver risk factors is discussed.

Flaviviruses such as dengue virus (DENV), Zika virus (ZIKV), and yellow fever virus (YFV) are spread by mosquitoes and cause human disease and mortality in tropical areas. In contrast, Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The potential role of pathogens, particularly vector-transmitted infectious agents, as a cause of psychosis has not been intensively investigated. We have reported a potential link between Bartonella spp. bacteremia and neuropsychiatric symptoms, including pediatric acute onset neuropsychiatric syndrome and schizophrenia. The purpose of this study was to further assess whether Bartonella spp. exposure or infection are associated with psychosis., Methods: In a blinded manner, we assessed the presence of anti- Bartonella antibodies by indirect immunofluorescence assays (IFA), and infection by amplification of bacterial DNA from blood by quantitative polymerase chain reaction (qPCR), digital PCR (dPCR), and droplet digital PCR (ddPCR) in 116 participants. Participants were categorized into one of five groups: 1) controls unaffected by psychosis ( n = 29); 2) prodromal participants ( n = 16); 3) children or adolescents with psychosis ( n = 7); 4) adults with psychosis ( n = 44); and 5) relatives of a participant with psychosis ( n = 20)., Results: There was no significant difference in Bartonella spp. IFA seroreactivity between adults with psychosis and adult controls unaffected by psychosis. There was a higher proportion of adults with psychosis who had Bartonella spp. DNA in the bloodstream (43.2%) compared to adult controls unaffected by psychosis (14.3%, p = 0.021). The Bartonella species was determined for 18 of the 31 bacteremic participants, including infection or co-infection with Bartonella henselae (11/18), Bartonella vinsonii subsp. b erkhoffii (6/18), Bartonella quintana (2/18), Bartonella alsatica (1/18), and Bartonella rochalimae (1/18)., Discussion: In conjunction with other recent research, the results of this study provide justification for a large national or international multi-center study to determine if Bartonella spp. bacteremia is more prevalent in adults with psychosis compared to adults unaffected by psychosis. Expanding the investigation to include a range of vector-borne and other microbial infections with potential CNS effects would enhance knowledge on the relationship between psychosis and infection., Competing Interests: In conjunction with Dr. S. Sontakke and North Carolina State University, EB holds US Patent No. 7,115,385 Media and Methods for Cultivation of Microorganisms, which was issued on October 3rd, 2006. He is a co-founder, shareholder and Chief Scientific Officer for Galaxy Diagnostics, a company that provides advanced diagnostic testing for the detection of Bartonella spp. infections. RM is a co-founder and the Chief Technical Officer for Galaxy Diagnostics Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Delaney, Robveille, Maggi, Lashnits, Kingston, Liedig, Murray, Fallon and Breitschwerdt.)

Introduction: Lyme disease (LD) affects ∼476,000 people each year in the United States. Symptoms are variable and include rash and flu-like symptoms. Reasons for the wide variation in disease outcomes are unknown. Powassan virus (POWV) is a tick-borne flavivirus that causes disease ranging from asymptomatic infection to encephalitis, neurologic damage, and death. POWV and LD geographic case distributions overlap, with Ixodes species ticks as the common vectors. Clinical ramifications of coinfection or sequential infection are unknown. Objectives: This study's primary objective was to determine the prevalence of POWV-reactive antibodies in sera samples collected from previously studied cohorts of individuals with self-reported LD history residing in the Northeastern United States. As a secondary objective, we studied clinical differences between people with self-reported LD history and low versus high POWV antibody levels. Methods: We used an enzyme-linked immunosorbent assay (ELISA) to quantify IgG directed at the POWV envelope (E) protein domain III in 538 samples from individuals with self-reported LD history and 16 community controls. The samples were also tested with an ELISA assay to quantify IgG directed at the POWV NS1 protein. Results: The percentage of individuals with LD history and possible evidence of POWV exposure varied depending on the assay utilized. We found no significant difference in clinical symptoms between those with low or high POWV IgG levels in the in-house assay. Congruence of the EDIII and NS1 assays was low with only 12% of those positive in the in-house EDIII ELISA testing positive in the POWV NS1 ELISA. Conclusions: The results highlight the difficulty in flavivirus diagnostic testing, particularly in the retrospective detection of flavivirus exposure. The findings suggest that a prospective study with symptomatic patients using approved clinical testing is necessary to address the incidence and clinical implications of LD and POWV co-infection or sequential infection.

Objective: To examine factors associated with COVID-19 vaccination (time to vaccination and vaccination status) among healthy young children participating in primary healthcare., Methods: A cohort study was conducted between November 2021 and September 2022 through the TARGet Kids! primary care research network in Toronto, Canada. Sociodemographic information, child and parent health characteristics, parental vaccine beliefs and child COVID-19 vaccine uptake were collected through parent-reported questionnaires. The primary outcome was time to child COVID-19 vaccination, measured as the time between vaccine availability date and parent-reported child COVID-19 vaccination date. Interval-censored proportional hazard models were used., Results: A total of 267 children age 0 to 13 years were included. The mean child age was 7.6 years, 52.8% (n = 141) were male, 66.5% (n = 141) had mothers of European ethnicity (with missingness), and 68.2% (n = 182) of the children were vaccinated. All parents of vaccinated children had received the COVID-19 vaccination themselves. The rate of vaccination for children was 2% higher with each one-month increase in child age (adjusted HR = 1.02, 95%CI = 1.01-1.03, p < 0.001). Compared to children whose parents had uncertain beliefs, those whose parents had positive beliefs about the importance and safety of COVID-19 vaccination for their children had higher rates of vaccination (adjusted HR = 8.29, 95%CI = 4.25-16.17, p < 0.001; adjusted HR = 5.09, 95%CI = 3.17-8.17, p < 0.001)., Conclusion: Older child age, parental COVID-19 vaccination, and positive parental beliefs about COVID-19 vaccination were statistically significantly associated with COVID-19 vaccination among healthy young children. Our findings may help to inform policies, practices, and research which aim to strengthen parental vaccine confidence and promote child COVID-19 vaccination., (© 2023. The Author(s) under exclusive license to The Canadian Public Health Association.)

Lyme disease, the most common tick-borne disease in the United States, is caused by infection with the spirochete Borrelia burgdorferi . While most patients with acute Lyme disease recover completely if treated with antibiotics shortly after the onset of infection, approximately 10-30% experience post-treatment symptoms and 5-10% have residual symptoms with functional impairment (post-treatment Lyme disease syndrome or PTLDS). These patients typically experience pain, cognitive problems, and/or fatigue. This narrative review provides a broad overview of Lyme disease, focusing on neuropsychiatric manifestations and persistent symptoms. While the etiology of persistent symptoms remains incompletely understood, potential explanations include persistent infection, altered neural activation, and immune dysregulation. Widely recognized is that new treatment options are needed for people who have symptoms that persist despite prior antibiotic therapy. After a brief discussion of treatment approaches, the article focuses on vagus nerve stimulation (VNS), a neuromodulation approach that is FDA-approved for depression, epilepsy, and headache syndromes and has been reported to be helpful for other diseases characterized by inflammation and neural dysregulation. Transcutaneous VNS stimulates the external branch of the vagus nerve, is minimally invasive, and is well-tolerated in other conditions with few side effects. If well-controlled double-blinded studies demonstrate that transcutaneous auricular VNS helps patients with chronic syndromes such as persistent symptoms after Lyme disease, taVNS will be a welcome addition to the treatment options for these patients.

Objective: Recent neurocognitive studies of patients with post-treatment Lyme disease syndrome (PTLDS) find consistent deficits in memory and processing speed. Language fluency deficits are observed as well but may be secondary to poor memory and slowing rather than an independent deficit., Method: This study performed a secondary analysis of data presented previously, including individuals with PTLDS and comparison samples of healthy volunteers (HC) and patients with major depressive disorder (MDD), to determine if language fluency deficits could be accounted for by poor performance in these other neurocognitive domains., Results: Basic verbal abilities, memory, and processing speed were all significantly associated with fluency performance. MDD patients' fluency deficits relative to HC were accounted for by these covariates. However, PTLDS patients' poorer fluency performance relative to both other groups was not., Conclusions: Language fluency appears to be an independent area of neurocognitive deficit within the constellation of PTLDS symptoms., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Infection with severe acute respiratory syndrome coronavirus 2 associates with diverse symptoms, which can persist for months. While antiviral antibodies are protective, those targeting interferons and other immune factors are associated with adverse coronavirus disease 2019 (COVID-19) outcomes. Here we discovered that antibodies against specific chemokines were omnipresent post-COVID-19, were associated with favorable disease outcome and negatively correlated with the development of long COVID at 1 yr post-infection. Chemokine antibodies were also present in HIV-1 infection and autoimmune disorders, but they targeted different chemokines compared with COVID-19. Monoclonal antibodies derived from COVID-19 convalescents that bound to the chemokine N-loop impaired cell migration. Given the role of chemokines in orchestrating immune cell trafficking, naturally arising chemokine antibodies may modulate the inflammatory response and thus bear therapeutic potential., (© 2023. The Author(s).)

Background : Since disulfiram's discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods : For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were "disulfiram" and "Antabuse". Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results : In total, 196 sources addressing our research focus spanning 1948-2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions : While disulfiram has promise as a "repurposed" agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications.

In North America, Lyme disease (LD) is primarily caused by the spirochetal bacterium Borrelia burgdorferi, transmitted to humans by Ixodes species tick bites, at an estimated rate of 476,000 patients diagnosed per year. Acute LD often manifests with flu-like symptoms and an expanding rash known as erythema migrans (EM) and less often with neurologic, neuropsychiatric, arthritic, or cardiac features. Most acute cases of Lyme disease are effectively treated with antibiotics, but 10-20% of individuals may experience recurrent or persistent symptoms. This chapter focuses on the neuropsychiatric aspects of Lyme disease, as these are less widely recognized by physicians and often overlooked. Broader education about the potential complexity, severity, and diverse manifestations of tick-borne diseases is needed., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Abstract: One prior study suggests that traumatic events before Lyme disease play an important role in symptom severity. We examined this hypothesis among 60 individuals with persistent symptoms after Lyme disease using validated measures of trauma history, mental and physical symptoms, and functional status. Analysis of variance with Tukey-Kramer multiple comparisons test revealed that a greater number of traumatic events were significantly associated with greater symptom severity on the scales of mood (stress, depression, and anxiety), cognition, multisystem symptom burden, and functional status (mental and physical), but not on measures of pain and fatigue. The effect sizes-meaningful but not large (0.17-0.29)-were mostly produced by comparison with individuals reporting multiple prior traumatic events, representing half of the posttreatment Lyme disease syndrome (PTLDS) group. In conclusion, although PTLDS may be exacerbated by past trauma, trauma plays a role in only a subgroup of PTLDS. Whether addressing prior trauma can improve outcomes in this subgroup requires study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Health anxiety may exist with or without prominent somatic symptoms, but the impact of somatic symptoms on treatment response is unclear. The study objective was to examine this question further as symptom burden may impact choice of type of treatment. Methods: This exploratory study used a unique database from a prior trial of 193 individuals with DSM-IV hypochondriasis who had been randomly assigned to either cognitive behavioral therapy, fluoxetine, combined therapy, or placebo. Two subgroups were newly defined-no/low somatic burden ( n = 42) and prominent somatic burden ( n = 151). Response was defined by ≥30% improvement in hypochondriasis. Results: Among high somatic hypochondriacal participants, compared to placebo, the odds of being a responder were significantly greater among those who received fluoxetine, either alone (OR = 4.46; 95% CI: 1.38, 14.41) or with cognitive behavioral therapy (OR = 3.56; 95% CI: 1.19, 10.68); the estimated odds were not significantly different for those receiving cognitive behavioral therapy alone (OR = 1.81; 95% CI: 0.59, 5.54). In contrast, among low somatic hypochondriacal participants, compared to placebo, the observed odds of being a responder were similar in magnitude and direction for those who received cognitive behavioral therapy, either alone (OR = 3.00; 95% CI: 0.38, 23.68) or in combination with fluoxetine (OR = 3.60; 95% CI: 0.62, 21.03), compared to the odds for those receiving fluoxetine alone (OR = 0.90; 95% CI: 0.14, 5.65). High somatic hypochondriacal individuals assigned to any fluoxetine group had significantly greater odds of being a responder than those who had not received fluoxetine (OR = 2.70; 95% CI: 1.33, 5.48). Low somatic hypochondriacal individuals assigned to any cognitive behavioral therapy group had significantly greater odds of being a responder than those who had not received cognitive behavioral therapy (OR = 8.03; 95% CI: 1.41, 45.67). Conclusion: These findings indicate that somatic symptom burden may be important in guiding treatment selection among individuals with marked health anxiety, as hypochondriacal individuals with high somatic burden responded more often to fluoxetine while those with low somatic burden responded more often to cognitive behavioral therapy. Systematic replication with larger studies is needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Fallon, Basaraba, Pavlicova, Ahern and Barsky.)

Objective: Lyme borreliosis is a tick-borne infectious disease that may confer an increased risk of mental disorders, but previous studies have been hampered by methodological limitations, including small sample sizes. The authors used a nationwide retrospective cohort study design to examine rates of mental disorders following Lyme borreliosis., Methods: Using Denmark's National Patient Register and the Psychiatric Central Research Register, and including all persons living in Denmark from 1994 through 2016 (N=6,945,837), the authors assessed the risk of mental disorders and suicidal behaviors among all individuals diagnosed with Lyme borreliosis in inpatient and outpatient hospital contacts (N=12,156). Incidence rate ratios (IRRs) were calculated by Poisson regression analyses., Results: Individuals with Lyme borreliosis had higher rates of any mental disorder (IRR=1.28, 95% CI=1.20, 1.37), of affective disorders (IRR=1.42, 95% CI=1.27, 1.59), of suicide attempts (IRR=2.01, 95% CI=1.58, 2.55), and of death by suicide (IRR=1.75, 95% CI=1.18, 2.58) compared with those without Lyme borreliosis. The 6-month interval after diagnosis was associated with the highest rate of any mental disorder (IRR=1.96, 95% CI=1.53, 2.52), and the first 3 years after diagnosis was associated with the highest rate of suicide (IRR=2.41, 95% CI=1.25, 4.62). Having more than one episode of Lyme borreliosis was associated with increased incidence rate ratios for mental disorders, affective disorders, and suicide attempts, but not for death by suicide., Conclusions: Individuals diagnosed with Lyme borreliosis in the hospital setting had an increased risk of mental disorders, affective disorders, suicide attempts, and suicide. Although the absolute population risk is low, clinicians should be aware of potential psychiatric sequelae of this global disease.

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges., Competing Interests: AGR is a scientific advisor to NeonMind Biosciences and ETHA Natural Botanicals. In conjunction with Dr. S. Sontakke and North Carolina State University, EBB holds US Patent No. 7,115,385; Media and Methods for Cultivation of Microorganisms, which was issued on October 3rd, 2006. He is a co-founder, shareholder and Chief Scientific Officer for Galaxy Diagnostics, a company that provides advanced diagnostic testing for the detection of Bartonella spp. and Borrelia infections. RM is a co-founder, shareholder and the Chief Technical Officer for Galaxy Diagnostics. RTM is a paid consultant/speaker for Zoetis and receives license related income from Zoetis. MJS serves on the Scientific Advisory Board for the Global Lyme Alliance and has been issued a patent [US Patent No. 10 481 165] for “Elevated CCL19 after completion of therapy for acute Lyme disease identifies patients at risk for development of post-treatment Lyme disease syndrome who will benefit from further antibiotic therapy”. AO has pending patent applications on the development of Lyme disease diagnostic tests. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bobe, Jutras, Horn, Embers, Bailey, Moritz, Zhang, Soloski, Ostfeld, Marconi, Aucott, Ma'ayan, Keesing, Lewis, Ben Mamoun, Rebman, McClune, Breitschwerdt, Reddy, Maggi, Yang, Nemser, Ozcan, Garner, Di Carlo, Ballard, Joung, Garcia-Romeu, Griffiths, Baumgarth and Fallon.)

The complex etiology of neurodegenerative disease has prompted studies on multiple mechanisms including genetic predisposition, brain biochemistry, immunological responses, and microbial insult. In particular, Lyme disease is often associated with neurocognitive impairment with variable manifestations between patients. We sought to develop methods to reliably detect Borrelia burgdorferi , the spirochete bacteria responsible for Lyme disease, in autopsy specimens of patients with a history of neurocognitive disease. In this report, we describe the use of multiple molecular detection techniques for this pathogen and its application to a case study of a Lyme disease patient. The patient had a history of Lyme disease, was treated with antibiotics, and years later developed chronic symptoms including dementia. The patient's pathology and clinical case description was consistent with Lewy body dementia. B. burgdorferi was identified by PCR in several CNS tissues and by immunofluorescent staining in the spinal cord. These studies offer proof of the principle that persistent infection with the Lyme disease spirochete may have lingering consequences on the CNS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gadila, Rosoklija, Dwork, Fallon and Embers.)

Eighty-two patients seeking consultation for long-term sequalae after suspected tick-borne illness were consecutively tested for Borrelia miyamotoi antibodies using a recombinant glycerophosphodiester phosphodiesterase (GlpQ) enzyme immunoassay. Twenty-one of the 82 patients (26%) tested positive on the GlpQ IgG ELISA. Nearly all of the patients (98%) had no prior B. miyamotoi testing, indicating that clinicians rarely test for this emerging tick-borne pathogen. Compared to patients who solely tested positive for Lyme disease antibodies, patients with B. miyamotoi antibodies presented with significantly more sleepiness and pain. A prospective study is needed to ascertain the relationship between the presence of B. miyamotoi antibodies and persistent symptoms., (Copyright © 2020 Delaney, Murray, Aasen, Bennett, Brown and Fallon.)

In recent decades, an evolving conversation among religion, psychiatry, and neuroscience has been taking place, transforming how we conceptualize religion and how that conceptualization affects its relation to psychiatry. In this article, we review several dimensions of the dialogue, beginning with its history and the phenomenology of religious experience. We then turn to neuroscientific studies to see how they explain religious experience, and we follow that with two related areas: the benefits of religious beliefs and practices, and the evolutionary foundation of those benefits. A final section addresses neuroscientific and evolutionary accounts of the transcendent, that is, what these fields make of the claim that religious experience connects to a transcendent reality. We conclude with a brief summary, along with the unresolved questions we have encountered.

Background: Molecular mimicry targeting neural tissue has been reported after Borrelia burgdorferi ( Bb ) infection. Herein, we investigate whether antineuronal autoantibodies are increased and whether antibody-mediated signaling of neuronal cells is elevated in a cohort of symptomatic adults with a history of Lyme Disease (LD)., Methods: Participants (n ​= ​179) included 24 with recent Erythema Migrans (EM) without prior LD, 8 with recent EM and prior LD (EM ​+ ​prior LD), 119 with persistent post-treatment LD symptoms (PTLS), and 28 seronegative endemic controls with no prior LD history. Antineuronal immunoglobulin G (IgG) titers were measured by standard ELISA and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was identified in serum., Results: EM ​+ ​prior LD cases had higher antibody titers than controls for anti-lysoganglioside GM1 (p ​= ​0.002), anti-tubulin (p ​= ​0.03), and anti-D1R (p ​= ​0.02), as well as higher expression in the functional antibody-mediated CaMKII Assay (p ​= ​0.03). The EM cases with no prior history showed no significant differences on any measures. The PTLS cases demonstrated significantly higher titers (p ​= ​0.01) than controls on anti-lysoganglioside GM1, but not for the other measures., Conclusion: The finding of elevated anti-neuronal autoantibodies in our small sample of those with a prior history of Lyme disease but not in those without prior Lyme disease, if replicated in a larger sample, suggests an immune priming effect of repeated infection; the CaMKII activation suggests that antineuronal antibodies have functional significance. The elevation of anti-lysoganglioside antibodies among those with PTLS is of particular interest given the established role of anti-ganglioside antibodies in peripheral and central neurologic diseases. Future prospective studies can determine whether these autoantibodies emerge after Bb infection and whether their emergence coincides with persistent neurologic or neuropsychiatric symptoms., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: None for B. Fallon, B. Strobino, S.Reim or J. Stoner. Madeleine Cunningham is chief scientific officer and co-founder with financial interest in Moleculera Labs, a commercial laboratory for diagnostic testing of autoantibodies against the heart and brain., (© 2019 The Author(s).)

Objective: Chronic pain is highly prevalent among patients with mood, anxiety, personality, and somatic symptom disorders; and patients with chronic pain often suffer from persistent interpersonal distress. However, the neural mechanisms underlying this phenomenon and its possible role in the etiology of chronic pain are not yet understood. Based on our Developmental Theory of Centralized/Somatoform Pain, and prior research suggesting the existence of a shared neural system subserving interpersonal emotions and pain, we aimed to identify the neural basis for modulation of pain by feelings of interpersonal rejection and the role of the early interpersonal environment in development of this shared neural system., Methods: During fMRI scanning, 22 healthy participants received moderately painful thermal stimuli in 3 interpersonal contexts: Acceptance, Rejection, and Reacceptance (modified Cyberball paradigm). Early interpersonal environment was assessed using the Parental Bonding Instrument., Results: Interpersonal context modulated activity in pain neural systems during rejection and during accepting interactions with previously rejecting others. Moreover, the subjective perception of rejection, even when rejection was not occurring, correlated positively with reported pain severity and neural activity in the insula. The magnitude of neural modulation in pain circuits by feelings of rejection was associated with the quality of early interpersonal experience with caregivers., Conclusions: Results suggest that interpersonal emotions play an important role in the development and functioning of the pain system, supporting our Developmental Theory of predisposition to chronic centralized pain. These findings have direct implications for clinical practice, including the importance of treating interpersonal distress to alleviate pain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The multi-system symptoms accompanying acute and post-treatment Lyme disease syndrome pose a challenge for time-limited assessment. The General Symptom Questionnaire (GSQ-30) was developed to fill the need for a brief patient-reported measure of multi-system symptom burden. In this study we assess the psychometric properties and sensitivity to change of the GSQ-30. Materials and Methods: 342 adult participants comprised 4 diagnostic groups: Lyme disease (post-treatment Lyme disease syndrome, n = 124; erythema migrans, n = 94); depression, n = 36; traumatic brain injury, n = 51; healthy, n = 37. Participants were recruited from clinical research facilities in Massachusetts, Maryland, and New York. Validation measures for the GSQ-30 included the Patient Health Questionnaire-4 for depression and anxiety, visual analog scales for fatigue and pain, the Sheehan Disability Scale for functional impairment, and one global health question. To assess sensitivity to change, 53 patients with erythema migrans completed the GSQ-30 before treatment and 6 months after 3 weeks of treatment with doxycycline. Results: The GSQ-30 demonstrated excellent internal consistency (Cronbach α = 0.95). The factor structure reflects four core domains: pain/fatigue, neuropsychiatric, neurologic, and viral-like symptoms. Symptom burden was significantly associated with depression ( r s = 0.60), anxiety ( r s = 0.55), pain ( r s = 0.75), fatigue ( r s = 0.77), functional impairment ( r s = 0.79), and general health ( r s = -0.58). The GSQ-30 detected significant change in symptom burden before and after antibiotic therapy; this change correlated with change in functional impairment. The GSQ-30 total score significantly differed for erythema migrans vs. three other groups (post-treatment Lyme disease syndrome, depression, healthy controls). The GSQ-30 total scores for traumatic brain injury and depression were not significantly different from post-treatment Lyme disease syndrome. Conclusions and Relevance: The GSQ-30 is a valid and reliable instrument to assess symptom burden among patients with acute and post-treatment Lyme disease syndrome and is sensitive in the detection of change after treatment among patients with erythema migrans. The GSQ-30 should prove useful in clinical and research settings to assess multi-system symptom burden and to monitor change over time. The GSQ-30 may also prove useful in future precision medicine studies as a clinical measure to correlate with disease-relevant biomarkers., (Copyright © 2019 Fallon, Zubcevik, Bennett, Doshi, Rebman, Kishon, Moeller, Octavien and Aucott.)

Introduction: HIV-associated neurocognitive disorder (HAND) may affect 30%-50% of people ageing with HIV. HAND may increase stress and anxiety, and impede coping. Psychosocial group therapy may ameliorate HAND's symptoms, yet the ideal intervention is unclear. This protocol outlines a pilot randomised controlled trial (RCT)-designed using community-based participatory research-to pilot cognitive remediation group therapy (CRGT) against an active comparator., Methods and Analysis: This is a pilot, parallel design, two-arm RCT that will recruit participants diagnosed with the mild neurocognitive disorder form of HAND from a neurobehavioural research unit at a tertiary care hospital in Toronto, Canada. Eligibility criteria include age ≥40 years, known HIV status for 5+ years, English fluency, able to consent and able to attend 8 weeks of group therapy. Eligible participants will be randomised to one of two treatment arms, each consisting of eight-session group interventions delivered once weekly at 3 hours per session. Arm 1 (novel) is CRGT, combining mindfulness-based stress reduction with brain training activities. Arm 2 (active control) is mutual aid group therapy. The primary outcomes are feasibility, measured by proportions of recruitment and completion, and acceptability, determined by a satisfaction questionnaire. The secondary outcome is intervention fidelity, where content analysis will be used to assess facilitator session reports. A between-group analysis will be conducted on exploratory outcomes of stress, anxiety, coping and use of intervention activities that will be collected at three time points., Ethics and Dissemination: Ethical approval was obtained from the Research Ethics Boards of St. Michael's Hospital and the University of Toronto. Findings will be disseminated through peer-reviewed publications, conference presentations and community reporting. This study could provide insight into design (eg, recruitment, measures) and intervention considerations (eg, structure, content) for a larger trial to lessen the burden of cognitive decline among people ageing with HIV., Trial Registration Number: NCT03483740; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Neurocognitive dysfunction in patients with residual or emergent symptoms after treatment for Lyme Disease is often attributed to comorbid depression. In this study, patients with Post-Treatment Lyme Disease Syndrome (PTLDS) were compared to patients with Major Depressive Disorder (MDD), as well as healthy comparison subjects (HC), on neurocognitive measures administered through the same laboratory, to determine if patterns of performance were similar., Methods: Two analyses were conducted. First, performance on the Wechsler Adult Intelligence Scale (WAIS-III) and on subtests from the Wechsler Memory Scale (WMS-III) was compared among the groups. Second, comparable subgroups of PTLDS and MDD patients with at least one low WMS-III score were compared on an additional set of measures assessing motor function, psychomotor performance, attention, memory, working memory, and language fluency, to determine if the overall profile of performance was similar in the two subgroups., Results: In the first analysis, PTLDS patients performed more poorly than both MDD and HC on tasks assessing verbal abilities, working memory, and paragraph learning. Processing speed in the two patient groups, however, was equally reduced. In the second analysis, MDD patients with low WMS-III exhibited concomitantly greater difficulties in psychomotor speed and attention, while low-WMS-III PTLDS patients exhibited greater difficulties in language fluency., Conclusions: MDD and PTLDS can be confused neuropsychologically because both exhibit similar levels of psychomotor slowing. However, problems on memory-related tasks, though mild, are more pronounced in PTLDS. PTLDS patients with poorer memory also exhibit poorer language fluency, and less deficit in processing speed and attention compared to MDD., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Depression has been reported in 8-45% of patients with posttreatment Lyme symptoms (PTLS), but little is known about suicidal ideation in these patients., Method: Depression and suicidal ideation were assessed using the Beck Depression Inventory (BDI-II). Scores from the PTLS group (n = 81) were compared to those from 2 other groups: HIV+ patients being treated for fatigue (n = 70), and a nonpatient comparison group (NPCG; n = 44). ANOVA and t-tests were used to compare groups; logistic regression was used to identify the strongest correlates of suicidal ideation., Results: Mean BDI-II scores fell in the mildly depressed range for PTLS and HIV+ patients, with both groups having higher depression scores than the NPCG. Suicidal ideation was reported by 19.8% of the PTLS patients and 27.1% of the HIV+ patients, a nonsignificant difference. Among those with mild or no depression, suicidal ideation was uncommon (6.5% PTLS and 11.9% HIV+). Among the patients with moderate-to-severe depression, suicidal ideation was more common (63.2% of 19 PTLS and 50% of 28 HIV+); among these, 2 with PTLS and 1 with HIV+ expressed suicidal intent. Further, 4.5% (n = 2) of the NPCG had suicidal ideation, each had scores in the moderate-to-severe depression range. Higher scores on the cognitive symptoms subscale of the BDI-II predicted greater likelihood of suicidal ideation across patient groups., Conclusion: As expected, suicidal ideation is increased among patients who are depressed. The fact that 1 in 5 patients with PTLS reported suicidal ideation highlights the importance of screening for depression and suicidality to optimize patient care., (Copyright © 2018 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

The objective was to examine the prevalence of Borrelia antibodies among symptomatic individuals with recent and past Lyme disease in endemic communities using standard assays and novel assays employing next-generation antigenic substrates. Single- and two-tiered algorithms included different anti- Borrelia ELISAs and immunoblots. Antibody prevalence was examined in sera from 32 individuals with recent erythema migrans (EM), 335 individuals with persistent symptoms following treatment for Lyme disease (PTLS), and 41 community controls without a history of Lyme disease. Among convalescent EM cases, sensitivity was highest using the C6 ELISA (93.8%) compared to other single assays; specificity was 92.7% for the C6 ELISA vs. 85.4⁻97.6% for other assays. The two-tiered ELISA-EUROLINE IgG immunoblot combinations enhanced case detection substantially compared to the respective ELISA-IgG Western blot combinations (75.0% vs. 34.4%) despite similar specificity (95.1% vs. 97.6%, respectively). For PTLS cohorts, two-tier ELISA-IgG-blot positivity ranged from 10.1% to 47.4%, depending upon assay combination, time from initial infection, and clinical history. For controls, the two-tier positivity rate was 0⁻14.6% across assays. A two-tier algorithm of two-ELISA assays yielded a high positivity rate of 87.5% among convalescent EM cases with specificity of 92.7%. For convalescent EM, combinations of the C6 ELISA with a second-tier ELISA or line blot may provide useful alternatives to WB-based testing algorithms.

Objective: Prior studies of hypochondriasis demonstrated benefits for pharmacotherapy and for cognitive-behavioral therapy (CBT). This study examined whether joint treatment offers additional benefit., Method: Patients with DSM-IV hypochondriasis (N=195) were randomly assigned to one of four treatments-placebo, CBT, fluoxetine, or joint treatment with both fluoxetine and CBT. Evaluations assessed hypochondriasis, other psychopathology, adverse events, functional status, and quality of life. The primary analysis assessed outcome at week 24 among the intent-to-treat sample, with responders defined as having a 25% or greater improvement over baseline on both the Whiteley Index and a modified version of the Yale-Brown Obsessive Compulsive Scale for hypochondriasis (H-YBOCS-M). The Cochran-Armitage trend test assessed the hypothesized pattern of response: joint treatment > CBT or fluoxetine treatment > placebo treatment., Results: The predicted pattern of response was statistically significant, as shown by the following responder rates: joint treatment group, 47.2%; single active treatment group, 41.8%; and placebo group, 29.6%. Responder rates for each active treatment were not significantly different from the rate for placebo. Secondary analyses of the Whiteley Index as a continuous measure revealed that, compared with placebo, fluoxetine (but not CBT) was significantly more effective at week 24 in reducing hypochondriasis and had a significantly faster rate of improvement over 24 weeks. Fluoxetine also resulted in significantly less anxiety and better quality of life than placebo. Dropout rates did not differ between groups, and treatment-emergent adverse events were evenly distributed., Conclusions: This study supports the safety, tolerance, and efficacy of fluoxetine for hypochondriasis. Joint treatment provided a small incremental benefit. Because approximately 50% of patients did not respond to the study treatments, new or more intensive approaches are needed.

Unlabelled: The DSM-5 diagnosis of illness anxiety disorder adds avoidance as a component of a behavioral response to illness fears - one that was not present in prior DSM criteria of hypochondriasis. However, maladaptive avoidance as a necessary or useful criterion has yet to be empirically supported., Methods: 195 individuals meeting DSM-IV criteria for hypochondriasis based on structured interview completed a variety of self-report and clinician-administered assessments. Data on maladaptive avoidance were obtained using the six-item subscale of the clinician-administered Hypochondriasis - Yale Brown Obsessive Compulsive Scale - Modified. To determine if avoidance emerged as a useful indicator in hypochondriasis, we compared the relative fit of continuous latent trait, categorical latent class, and hybrid factor mixture models., Results: A two-class factor mixture model fit the data best, with Class 1 (n=147) exhibiting a greater level of severity of avoidance than Class 2 (n=48). The more severely avoidant group was found to have higher levels of hypochondriacal symptom severity, functional impairment, and anxiety, as well as lower quality of life., Conclusion: These results suggest that avoidance may be a valid behavioral construct and a useful component of the new diagnostic criteria of illness anxiety in the DSM-5, with implications for somatic symptom disorder., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Individuals with questions about their health often turn to the Internet for information about their symptoms, but the degree to which health anxiety is related to online checking, and clinical variables, remains unclear. The clinical profiles of highly anxious Internet checkers, and the relationship to checking behavior itself, have not previously been reported., Objective: In this article, we test the hypothesis, derived from cognitive-behavioral models, that individuals with higher levels of illness anxiety would recall having experienced worsening anxiety after reassurance-seeking on the Internet., Method: Data from 731 volunteers who endorsed engaging in online symptom-searching were collected using an online questionnaire. Severity of health anxiety was assessed with the Whiteley Index, functional impairment with the Sheehan Disability Scale, and distress recall during and after searching with a modified version of the Clinician׳s Global Impairment scale. Multiple regression analyses were conducted to determine variables contributing to distress during and after Internet checking., Results: Severity of illness anxiety on the Whiteley Index was the strongest predictor of increase in anxiety associated with, and consequent to, online symptom-searching. Individuals with high illness anxiety recalled feeling worse after online symptom-checking, whereas those with low illness anxiety recalled relief. Longer-duration online health-related use was associated with increased functional impairment, less education, and increased anxiety during and after checking., Conclusion: Because individuals with moderate-high levels of illness anxiety recall experiencing more anxiety during and after searching, such searching may be detrimental to their health. If replicated in controlled experimental settings, this would suggest that individuals with illness anxiety should be advised to avoid using the Internet for illness-related information., (Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Though the phenotype of anxiety about medical illness has long been recognized, there continues to be debate as to whether it is a distinct psychiatric disorder and, if so, to which diagnostic category it belongs., Objective: Our objective was to investigate the pattern of psychiatric comorbidity in hypochondriasis (HC) and to assess the relationship of health anxiety to anxiety, depressive, and somatoform disorders., Methods: Data were collected as part of a clinical trial on treatment methods for HC. In all, 194 participants meeting criteria for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) HC were assessed by sociodemographic variables, results of structured diagnostic interviews, and validated instruments for assessing various symptom dimensions of psychopathology., Results: Most of the individuals with HC had comorbid psychiatric illness; the mean number of comorbid diagnoses was 1.4, and 35.1% had HC as their only diagnosis. Participants were more likely to have only comorbid anxiety disorders than only comorbid depressive or somatoform disorders. Multiple regression analysis of continuous measures of symptoms revealed the strongest correlation of health anxiety with anxiety symptoms, and a weaker correlation with somatoform symptoms; in multiple regression analysis, there was no correlation between health anxiety and depressive symptoms., Conclusion: Our findings suggest that the entity of health anxiety (HC in DSM-IV and illness anxiety disorder in DSM-5) is a clinical syndrome distinct from other psychiatric disorders. Analysis of comorbidity patterns and continuous measures of symptoms suggest that its appropriate classification is with anxiety rather than somatoform or mood disorders., (Copyright © 2016 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: As the incidence of Lyme disease (LD) has increased, a number of "Lyme specialty laboratories" have emerged, claiming singular expertise in LD testing. We investigated the degree of interlaboratory variability of several LD serologic tests-whole cell sonicate (WCS) enzyme-linked immunosorbent assay (ELISA), immunoglobulin M (IgM) and immunoglobulin G (IgG) Western blots (WBs), and an ELISA based on the conserved sixth region of variable major protein-like sequence expressed (C6)-that were performed at 1 university laboratory, 1 commercial laboratory, and 2 laboratories that specialize in LD testing., Methods: Serum samples from 37 patients with posttreatment Lyme syndrome, as well as 40 medically healthy controls without prior LD, were tested independently at the 4 laboratories., Results: In general, there was little difference among the laboratories in the percentage of positive test results on the ELISAs and IgG WBs, although the number of discordant results was often high. When in-house criteria for positivity were used at the 2 specialty laboratories, specificity at 1 laboratory declined considerably on both the IgM and IgG WBs. The Centers for Disease Control and Prevention (CDC) 2-tiered criteria improved overall concordance. At the 2 laboratories that performed the C6 ELISA, the percentage of positive tests was comparable to that of the WCS ELISA while providing higher specificity. The IgM WB performed poorly in our patient population of individuals with later-stage illness, a result consistent with previous studies., Conclusions: Although there was surprisingly little difference among the laboratories in percentage of positive results on most assays using CDC criteria, interlaboratory variability was considerable and remains a problem in LD testing., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Low-frequency repetitive transcranial magnetic stimulation (rTMS) to supplementary motor area (SMA) showed clinical benefit in obsessive-compulsive disorder (OCD). Here we tested whether clinical improvement was associated with enhanced cortical inhibition as measured by single and paired-pulse TMS variables. In 18 OCD patients receiving 4 weeks of either active or sham rTMS in a double-blind randomized trial, we assessed bilateral resting and active motor thresholds (RMT and AMT), cortical silent period (CSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF). We tested correlations between changes in Yale-Brown Obsessive Compulsive Scale-Self-report (Y-BOCS-SR), Clinical Global Impression-Severity subscale (CGI-S) and cortical excitability measures. Active rTMS increased right hemisphere RMT whose change correlated with Y-BOCS-SR improvement. Baseline RMT hemispheric asymmetry, defined as the difference between left and right hemispheres RMT, and its normalization after active rTMS correlated with Y-BOCS-SR and CGI-S improvements. Active rTMS also increased right hemisphere SICI whose change correlated with Y-BOCS-SR and CGI-S at week 4, and with normalization of baseline RMT hemispheric asymmetry. Treatment-induced changes in cortical excitability measures are consistent with an inhibitory action of SMA rTMS on dysfunctional motor circuits in OCD. Correlations of neurophysiology measures with therapeutic outcome are supportive of the role of SMA in the modulation of OCD symptoms., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Marked functional impairment has been reported by patients with post-treatment Lyme disease syndrome (PTLDS)., Objective: We sought to identify the clinical features that contribute most strongly to the impaired health status associated with PTLDS., Methods: Enrolled patients had a well-documented history of Lyme disease, prior treatment with at least 3 weeks with intravenous ceftriaxone, a positive IgG Western blot, and objective problems with memory. An index score to capture aggregate cognitive functioning, Short-Form 36 physical and mental component summary scores, and scores on other clinical and demographic measures were examined. Multiple linear regressions were performed to determine significant predictors of perceptions of impaired life functioning as delineated by the Short-Form 36., Results: Fatigue was the most important contributor to perceived impairments in overall physical functioning, and fatigue and depression significantly predicted perceived impairments in overall mental functioning., Conclusions: Because fatigue and depression contribute prominently to reports of impaired physical functioning and mental functioning among patients with PTLDS, clinicians should assess patients for these symptoms and consider targeting these symptoms in the selection of treatment interventions. Future controlled studies should examine the effectiveness of such agents for patients with PTLDS., (© 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Central sensitization is a process that links a variety of chronic pain disorders that are characterized by hypersensitivity to noxious stimuli and pain in response to non-noxious stimuli. Among these disorders, treatments that act centrally may have greater efficacy than treatments acting peripherally. Because many individuals with post-treatment Lyme syndrome (PTLS) have a similar symptom cluster, central sensitization may be a process mediating or exacerbating their sensory processing. This article reviews central sensitization, reports new data on sensory hyperarousal in PTLS, explores the potential role of central sensitization in symptom chronicity, and suggests new directions for neurophysiologic and treatment research.

Following antibiotic treatment for Lyme disease, some patients report persistent or relapsing symptoms of pain, fatigue, and/or cognitive deficits. Factors other than active infection, including immune abnormalities, have been suggested, but few clues regarding mechanism have emerged. Furthermore, the effect of antibiotic treatment on immune response in affected individuals remains unknown. In this study, a longitudinal analysis of specific immune markers of interest was carried out in patients with a history of Lyme disease and persistent objective memory impairment, prior to and following treatment with either ceftriaxone or placebo. IFNα activity was measured by detection of serum-induced changes in specific target genes, using a functional cell-based assay and quantitative real-time PCR. Level and pattern of antibody reactivity to brain antigens and to Borrelia burgdorferi proteins were analyzed by ELISA and immunoblotting. Sera from the patient cohort induced significantly higher expression of IFIT1 and IFI44 target genes than those from healthy controls, indicating increased IFNα activity. Antibody reactivity to specific brain and borrelial proteins was significantly elevated in affected patients. IFNα activity and antibody profile did not change significantly in response to ceftriaxone. The heightened antibody response implies enhanced immune stimulation, possibly due to prolonged exposure to the organism prior to the initial diagnosis and antibiotic treatment of Lyme disease. The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Emotions elicited by interpersonal versus non-interpersonal experiences have different effects on neurobiological functioning in both animals and humans. However, the extent to which the brain circuits underlying interpersonal and non-interpersonal emotions are distinct still remains unclear. The goal of our study was to assess whether different neural circuits are implicated in the processing of arousal and valence of interpersonal versus non-interpersonal emotions. During functional magnetic resonance imaging, participants imagined themselves in emotion-eliciting interpersonal or non-interpersonal situations and then rated the arousal and valence of emotions they experienced. We identified (1) separate neural circuits that are implicated in the arousal and valence dimensions of interpersonal versus non-interpersonal emotions, (2) circuits that are implicated in arousal and valence for both types of emotion, and (3) circuits that are responsive to the type of emotion, regardless of the valence or arousal level of the emotion. We found extensive recruitment of limbic (for arousal) and temporal-parietal (for valence) systems associated with processing of specifically interpersonal emotions compared to non-interpersonal ones. The neural bases of interpersonal and non-interpersonal emotions may, therefore, be largely distinct.

Objective: Symptoms of hypochondriasis are sometimes attributed to personality psychopathology by health care providers. The goals of this study were to assess the prevalence of personality disorder (PD) comorbidity in hypochondriasis (HYP) and to compare the PD comorbidity profile of patients with HYP with that found among patients with other disorders characterized by intrusive thoughts and fears., Methods: Structured Clinical Interview for DSM-IV Axis I and Axis II Disorders (SCID-I and SCID-II) were administered to 179 individuals: 62 with HYP, 46 with obsessive-compulsive disorder (OCD), and 71 with social anxiety disorder (SAD). For group contrasts, the samples were "purified" of the comparison comorbid disorders. General linear models were used to test the combined effect of group (HYP, OCD, SAD), age, and gender on the PD outcome variables., Results: 59.7% of HYP subjects had no Axis II comorbidity. The most common PDs in HYP were paranoid (19.4%), avoidant (17.7%), and obsessive-compulsive (14.5%). HYP significantly differed from SAD in the likelihood of a cluster C disorder, whereas no significant difference was noted for HYP vs. OCD. The proportion of subjects having at least two PDs was not significantly different for HYP vs. OCD or for HYP vs. SAD., Conclusion: Although 40% of patients with hypochondriasis have PD comorbidity as assessed by the SCID-II, the amount of PD comorbidity is not significantly different than found among individuals with two comparison anxiety disorders. Therefore, health providers should be aware that PD may complicate the clinical profile of HYP, but they should avoid assuming that PD psychopathology is the primary source of hypochondriacal distress., (Copyright © 2012 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Unlabelled: Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence., Methods: The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated., Results: 2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures., Conclusions: Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.