Development of a self-report screening instrument for emotional dysregulation: the Reactivity, Intensity, Polarity and Stability questionnaire, screening version (RIPoSt-SV).

BACKGROUND: Emotional dysregulation (ED) refers to the inability to manage emotional experiences or expressions hindering goal-oriented behavior. Moderate impairment on at least two domains among temper control, affective lability, and emotional over-reactivity has been proposed to identify ED in adults with attention-deficit/hyperactivity disorder (ADHD). No screening measure designed for use in diverse psychiatric samples exists. We aimed to develop a self-report screening tool for ED based on the 40-item version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-40). METHODS: 150 adult outpatients with non-psychotic conditions were enrolled between February and July 2023 at the Second Psychiatry Unit of Pisa University Hospital. Clinically significant ED (CSED) was defined based on the previously suggested approach for ADHD. Differences between patients with and without CSED were tested. To develop our screening instrument, a decision tree algorithm was trained by hyperparameter tuning through 5-fold cross-validation in 120 subjects and tested on the remaining 30. RESULTS: 75 subjects met criteria for CSED (50 %). CSED was associated with lower age and higher prevalence of psychiatric conditions, including minor mood disorders, ADHD, cannabis use disorders, and eating disorders. We identified a decision tree consisting of six items from RIPoSt-40 that effectively detected CSED, with accuracy, sensitivity, specificity, positive and negative predictive values of 80 % or higher in both the training and testing sets. LIMITATIONS: Tertiary-level; no consensus on criteria; sample size. CONCLUSION: The screening version of the Reactivity, Intensity, Polarity, and Stability questionnaire (RIPoSt-SV) demonstrates promise as a valuable tool for ED screening in clinical settings.

History of Childhood/Adolescence Referral to Speciality Care or Treatment in Adult Patients with Attention-Deficit/Hyperactivity Disorder: Mutual Relations with Clinical Presentation, Psychiatric Comorbidity and Emotional Dysregulation.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition that only rarely remits in adulthood. While several studies underlined differences between child and adult ADHD, the relationship between adult clinical presentation and early referral/treatment has been rarely investigated. In our study, 100 adults with ADHD were recruited and subdivided according to a history of referral to speciality care or treatment with methylphenidate (MPH) during childhood/adolescence. The early referral was associated with a history of disruptive behaviors during childhood/adolescence. Current ADHD symptoms were more pronounced in patients first referred during childhood/adolescence but never treated with MPH. Early MPH treatment was associated with lower rates of mood disorders and lower severity of emotional dysregulation at the time of assessment. Negative emotionality mediated the relationship between MPH treatment and mood disorders comorbidity. ADHD patients first referred during childhood/adolescence are characterized by more externalizing features than those first referred in adulthood. MPH treatment during the developmental age may have a role in preventing mood disorders in patients with ADHD, possibly by reducing emotional dysregulation.

Long-term treatment of adult ADHD in a naturalistic setting: Clinical predictors of attrition, medication choice, improvement, and response.

OBJECTIVES: The aim of this study was to identify clinical predictors of treatment attrition, medication choice, improvement and response to pharmacotherapy in adult attention-deficit/hyperactivity disorder (ADHD). METHODS: 150 ADHD patients were enrolled and naturalistically followed-up for at least 4 months. Conners' Adult ADHD Rating Scales-Observer: Screening Version (CAARS-O:SV) were used to measure ADHD severity. RESULTS: 58 subjects (38.7%) were lost at follow-up, while 75 (50%) completed follow-up assessment, on average after 26.05 ± 11.99 weeks; 35 were treated with atomoxetine (ATX) and 40 with methylphenidate (MPH). Treatments were moderately effective (d = 0.72) and 37 patients (49.3%) were responders (≥30% CAARS-O:SV decrease). Patients lost at follow-up had lower inattentive symptoms, less generalised anxiety and family history of bipolar disorder, more amphetamine use disorder than follow-up completers. Compared to ATX-treated subjects, MPH-treated patients had greater severity of hyperactivity/impulsivity and were more frequently diagnosed with alcohol use disorder. While MPH and ATX showed similar efficacy, more pronounced improvements were observed in patients with combined ADHD, anxiety and substance use disorders. ADHD severity and comorbid substance use positively predicted response. CONCLUSIONS: Consensus-based hierarchical treatment of ADHD comorbidity is not consistently supported. Comorbid anxiety, mood and substance use disorders should not discourage the treatment of adult ADHD.

Treatment adherence and tolerability of immediate- and prolonged-release lithium formulations in a sample of bipolar patients: a prospective naturalistic study.

The aim of this study was to compare treatment adherence and tolerability of different lithium formulations in 70 bipolar patients receiving lithium therapy for the first time. During the 1-year follow-up, information was collected regarding patient's clinical course, therapeutic adherence, side effects of the treatment and serum levels of lithium, creatinine and thyroid-stimulating hormone. At baseline, 30 patients (43%) were on prolonged-release lithium formulations and 40 (57%) on immediate-release formulations. At the final evaluation, 37 patients (53%) were considered lost to follow-up. Both prolonged- and immediate-release patients showed significant improvement in the Functioning Assessment Short Test and in the Clinical Global Impressions for Bipolar Disorder scores during the follow-up. At the first follow-up visit, the mean plasma lithium level of prolonged-release patients was higher than immediate-release patients (0.61 vs. 0.47, respectively; P = 0.063), as well as the therapeutic adherence (85 vs. 64%, respectively; P = 0.089). Fine tremor and gastrointestinal symptoms were more frequent in immediate-release patients than in prolonged-release patients at each follow-up visit, with the sole exception of gastrointestinal symptoms at the last evaluation. Prolonged-release lithium therapy could provide potential advantages over immediate-release formulations. Future naturalistic studies and clinical trials with a longer follow-up duration are needed.

Comparison of Emotional Dysregulation Features in Cyclothymia and Adult ADHD.

Background and Objectives: Emotional dysregulation is central to the problem of the overlap between attention-deficit/hyperactivity disorder (ADHD) and cyclothymia. The aim of the study was to evaluate comorbidity rates between ADHD and cyclothymic disorder and to explore demographic and clinical differences among the groups, focusing on affective temperament and emotional dysregulation. Materials and Methods: One hundred sixty-five outpatients attending the Second Psychiatry Unit at the Santa Chiara University Hospital (Pisa) were consecutively recruited: 80 were diagnosed with ADHD, 60 with cyclothymic disorder, and 25 with both conditions. Temperament Evaluation of Memphis, Pisa, Paris, and San Diego (TEMPS-M) and the 40-item version of Reactivity, Intensity, Polarity, and Stability questionnaire (RI-PoSt-40) were administered. Results: Cyclothymic patients were more frequently female and older with respect to the ADHD groups. Both comorbid and non-comorbid ADHD patients showed significantly lower educational attainment and more frequently had substance use disorders. Panic disorder was common in non-comorbid cyclothymic patients, who showed significantly higher rates of familial panic disorder, major depressive disorder and suicide attempts in comparison with patients only diagnosed with ADHD. Cyclothymic patients without ADHD were also characterized by fewer hyperthymic temperamental traits, higher depressive and anxious dispositions, and a greater negative emotionality. No significant differences among groups were observed for cyclothymic temperament and overall negative emotional dysregulation, but comorbid patients with both conditions scored the highest in these subscales. This group also showed significantly higher affective instability with respect to ADHD patients without cyclothymia and was less frequently diagnosed with bipolar disorder type II than patients from both the other groups. Conclusions: ADHD and cyclothymia often co-occur and show similar levels of emotional dysregulation. However, cyclothymic patients may be more prone to negative emotionality in clinical settings. Subjects with "sunny" cyclothymic features might escape the attention of clinicians unless ADHD is present.

Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection.

BACKGROUND: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. METHODS: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated cell wall in controlling viral induced inflammation using a murine model of influenza infection. We monitored mortality and morbidity over a 10-day period and viral load, differential broncho alveolar lavage (BAL) fluid inflammatory cell counts, Lung tissue histology, BAL and serum cytokines, markers of vascular damage and cell death were quantified. FINDINGS: Intranasal administration of Bifidobacterium longum35624® or its isolated cell wall prior to virus inoculation significantly reduced viral load within the lungs and significantly improved survival. Reduced viral load was associated with reduced lung injury as suggested by cell death and vascular leakage markers, a shift from neutrophil to macrophage recruitment, reduced inflammatory cytokine levels (including IL-6), reduced type 1 and 2 interferon levels, but increased levels of interferon-λ and surfactant protein D. These protective effects were maintained when the bifidobacterial cell wall preparation was administered 24 h after viral inoculation. The protective effects were also observed for the Bifidobacterium longumPB-VIR™ strain. INTERPRETATION: Exposure to these bifidobacterial strains protect against the inflammatory sequelae and damage associated with uncontrolled viral replication within the lung. FUNDING: This work has been funded, in part, by a research grant from GlaxoSmithKline, PrecisionBiotics Group Ltd., Swiss National Science Foundation grants (project numbers CRSII3_154488, 310030_144219, 310030_127356 and 310030_144219) and Christine Kühne - Center for Allergy Research and Education (CK-CARE).

Relationships Among Delayed Sleep Phase Disorder, Emotional Dysregulation, and Affective Temperaments in Adults With Attention Deficit Hyperactivity Disorder and Cyclothymia.

This study aims to explore the relationships between delayed sleep phase disorder (DSPD) and emotional dysregulation in 240 patients (134 with cyclothymia, 81 with attention deficit hyperactivity disorder [ADHD] and 25 with both conditions). DSPD was assessed using the Morningness-Eveningness Questionnaire, followed by a clinical evaluation. Affective temperaments and emotional dysregulation were also investigated through the brief version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego and the Reactivity, Intensity, Polarity, Stability questionnaires, respectively. Clinical variables were compared in patients with and without DSPD, and a logistic regression model was used to identify the predictive value of the clinical characteristics on the presence of DSPD. DSPD patients (19% of the total sample) were significantly younger than patients without DSPD, showed an about 4 times higher lifetime history of comorbid ADHD and cyclothymia, and reported higher scores in the irritable and cyclothymic temperamental subscales and in the affective instability and impulsivity dimensions. In the multiple logistic regression, we found a negative predictive value of increasing age on the presence of DSPD, whereas comorbid cyclothymia and ADHD and cyclothymic temperament seem to represent risk factors for DSPD.

Resveratrol plus carboxymethyl-ß-glucan in infants with common cold: A randomized double-blind trial.

OBJECTIVES: To evaluate effectiveness of a nasal resveratrol/carboxymethyl-ß-glucan solution compared to nasal saline solution: a) on common cold symptoms by means of a validated measure scale (CARIFS score), b) on Rhinovirus infection and CCL2, CCL5, IL8, IL6, CXCL10 and TLR2 expression in nasal swabs, c) on frequency of relapses after 30 days of follow-up. METHODS: 89 infants with respiratory infection symptoms were randomly assigned to receive either a nasal resveratrol/carboxymethyl-ß-glucan solution or nasal saline solution.All patients were evaluated with CARIFS score at enrollment, after 48 h, 7 and 30 days by physicians and parents. Nasal swabs were obtained at enrollment, after 48 h and after one week. RESULTS: CARIFS score improved in both groups. Episodes of sneezing and cough were fewer in study group after 7 days of follow-up (p < 0.05). No significant differences were found on nasopharyngeal swabs in Rhinovirus detection and cytokines expression after 48 h, nor in 30 days relapses. TLR2 expression was significantly higher in Rhinovirus infected children of the study group. No adverse effects occurred. CONCLUSIONS: These data suggest that a solution containing resveratrol plus carboxymethyl-ß-glucan might have a positive impact on both clinical and socio-economic burden due to infant common cold.

Toxoplasmosis in a Cohort of Italian Patients With Bipolar and Psychotic Disorders: How Infection May Affect Clinical Features?

This study investigated the seroprevalence of Toxoplasma gondii in a cohort of 101 Italian inpatients affected by mood or schizophrenia-spectrum disorders and compared clinical features between seronegative and seropositive subjects. Patients diagnosed according to DSM-5 criteria underwent clinical assessments and blood collection to test parasite-specific IgG/IgM serum levels. Twenty-eight patients (27.7%) had IgG anti-T. gondii, and none had IgM antibodies. We found higher prevalence rate in patients aged 40 years or older, as compared with younger. No significant association was detected between T. gondii and a specific diagnostic category; however, bipolar disorder (BD)-II showed the highest positivity rate (40.9%). The seropositive status was significantly associated with a lower presence of psychotic symptoms, higher number of total episodes of predominant excitatory polarity, longer illness duration, and lower severity of current episode, particularly anxiety, depressive, and withdrawal/retardation symptoms. These preliminary results seem to point out an association between chronic toxoplasmosis and a specific subtype of BD.

Reactivity, Intensity, Polarity and Stability questionnaire (RIPoSt-40) assessing emotional dysregulation: Development, reliability and validity.

BACKGROUND: Emotional dysregulation (ED) is a heterogenous construct with great relevance in psychiatric research and clinical practice. In the present study, we validated a 40-items version of the Reactivity, Intensity, Polarity and Stability questionnaire (RIPoSt-40), a self-report measure of ED. METHODS: A non-clinical sample (N = 396) and two clinical samples of patients with cyclothymia (N = 120) and ADHD (N = 54) were recruited. Items were selected and subscales were derived based on inter-item correlations and PCA with promax rotation in the non-clinical sample. Test-retest reliability was assessed in a subsample (N = 60). Internal consistency and concurrent validity with TEMPS-M factors were evaluated in each sample. The three groups results were compared to ascertain discriminant validity. RESULTS: Four subscales were identified as measures of affective instability, emotional impulsivity, negative and positive emotionality. The first three subscales also sum up to a negative ED score comprising thirty items. Measures of reliability (test-retest r = 0.71-0.84) and internal consistency (Cronbach's α = 0.72-0.95) were generally high. Concurrent validity was supported by correlations with TEMPS-M factors. Discriminant validity was significant (p < 0.001) with cyclothymic and ADHD patients showing higher scores for each subscale, except for positive emotionality. LIMITATIONS: The non-clinical sample was recruited through a web-survey and mainly included young and highly educated subjects. Mood and anxiety comorbidity of the clinical samples were not taken into consideration. CONCLUSION: RIPoSt-40 questionnaire has proved to be a valid, reliable and useful tool to assess ED both in clinical and non-clinical contexts.

A prophylactic multi-strain probiotic treatment to reduce the absorption of toxic elements: In-vitro study and biomonitoring of breast milk and infant stools.

Potential exposure to toxic elements initially occurs during gestation and after birth via breast milk, which is the principal source of nutrients for infants during the first months of life. In this study, we evaluated whether maternal oral supplementation with a multi-strain probiotic product can protect infants from exposure to arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) via breast milk. In-vitro studies of the bacterial strains present in this probiotic product showed a high bacterial tolerance for As, Cd, Hg, and Pb, and good binding capacity for Cd, Hg, and Pb (72%, 81%, and 64%, respectively) within 1 h of contact. We evaluated concentrations (5 mg L-1 for Cd and Pb, and 2 mg L-1 for Hg) that largely exceeded the provisional tolerable weekly intake of these toxic elements via food or water applicable for human consumption. Changes in the levels of these elements in breast milk and newborn stools were evaluated in the control (orally supplemented with placebo) and experimental (orally supplemented with probiotic) groups at birth (t0), 15 days (t15), and 30 days (t30) after delivery. Elemental analysis of breast milk did not show significant differences between the control and experimental groups at different stages of lactation; however, stool samples obtained from newborns of mothers supplemented with the probiotic product showed that Cd levels were significantly reduced (by 26%) at t15 compared with the levels of the controls. Our data did not show an association between concentration of toxic elements in breast milk and that in newborn stools. Indeed, the concentration of Cd, Hg, and Pb in breast milk decreased during the lactation period, whereas the levels of these elements in newborn stools were stable over time. Although our in-vitro data indicate that the consortium of these probiotic strains can absorb toxic compounds, this study was limited by its small sample size and potential uncontrolled confounding effects, such as maternal diet and lifestyle. Therefore, we could not confirm whether prophylactic use of this probiotic product can reduce the absorption of toxic elements. The risk assessment in the studied population evidenced a margin of exposure (MOE) of 1, or between 1 and 10 for Pb, and lower than 50 for As. This poses a potential risk for breastfed infants, indicating that interventions aimed to avoid breastfeeding-related health risks remain a major challenge in public health.

High levels of butyrate and propionate in early life are associated with protection against atopy.

BACKGROUND: Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short-chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti-inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma. METHODS: We analyzed SCFA levels by high-performance liquid chromatography (HPLC) in fecal samples from 301 one-year-old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation. RESULTS: Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation. CONCLUSION: Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.

Optimization and validation of a fast digestion method for the determination of major and trace elements in breast milk by ICP-MS.

Breast milk guarantees all the nutrients required by infants during their first few months of life and remains the most important food source for their health and growth. However, the mother may transfer potentially toxic chemicals to the suckling infant through breastfeeding. The aim of this study was to optimize and validate a fast method for the determination of a total content of 34 elements (Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cs, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, P, Pb, Rb, Sb, Se, Si, Sn, Sr, Te, Ti, Tl, U, V, and Zn) in liquid and lyophilized breast milk. The samples were subjected to HNO3:H2O2 (2:1) digestion in an open vessel heated in a water bath (WBD; 80 °C) and subsequently analysed by quadrupole inductively coupled plasma mass spectrometry equipped with a collision-reaction interface. The performance of the proposed method was evaluated in terms of selectivity, detection and quantification limits, linearity, accuracy, and robustness by using standard reference materials and filed samples of breast milk. Compared to microwave-assisted acid digestion, the proposed open vessel digestion allows a significant reduction in treatment time and sample manipulation, while maintaining a similar analytical performance. Masses of 0.5 g of breast milk were efficiently digested with the WBD treatment allowing a residual carbon content lower than 60 mg L-1 and a residual acidity lower than 0.87 mol L-1 in final digested samples. Thus, it shows great potential for application to routine analysis. The method provides satisfactory detection limits and good performance (trueness and recovery percentages 80-111%; coefficient of variation <10%; and relative repeatability <15%) and allows a high sample throughput for multi-elemental determination in human biomonitoring studies.

Role of Lactobacilli and Lactoferrin in the Mucosal Cervicovaginal Defense.

The innate defense system of the female mucosal genital tract involves a close and complex interaction among the healthy vaginal microbiota, different cells, and various proteins that protect the host from pathogens. Vaginal lactobacilli and lactoferrin represent two essential actors in the vaginal environment. Lactobacilli represent the dominant bacterial species able to prevent facultative and obligate anaerobes outnumber in vaginal microbiota maintaining healthy microbial homeostasis. Several mechanisms underlie the protection exerted by lactobacilli: competition for nutrients and tissue adherence, reduction of the vaginal pH, modulation of immunity, and production of bioactive compounds. Among bioactive factors of cervicovaginal mucosa, lactoferrin, an iron-binding cationic glycoprotein, is a multifunctional glycoprotein with antibacterial, antifungal, antiviral, and antiparasitic activities, recently emerging as an important modulator of inflammation. Lactobacilli and lactoferrin are largely under the influence of female hormones and of paracrine production of various cytokines. Lactoferrin is strongly increased in lower genital tract mucosal fluid of women affected by Neisseria gonorrheae, Chlamydia trachomatis, and Trichomonas vaginalis infections promoting both innate and adaptive immune responses. In vaginal dysbiosis characterized by low amounts of vaginal lactobacilli and increased levels of endogenous anaerobic bacteria, the increase in lactoferrin could act as an immune modulator assuming the role normally played by the healthy microbiota in vaginal mucosa. Then lactoferrin and lactobacilli may be considered as biomarkers of altered microbial homeostasis at vaginal level. Considering the shortage of effective treatments to counteract recurrent and/or antibiotic-resistant bacterial infections, the intravaginal administration of lactobacilli and lactoferrin could be a novel efficient therapeutic strategy and a valuable tool to restore mucosal immune homeostasis.

Exposure to nonmicrobial N-glycolylneuraminic acid protects farmers' children against airway inflammation and colitis.

BACKGROUND: Childhood exposure to a farm environment has been shown to protect against the development of inflammatory diseases, such as allergy, asthma, and inflammatory bowel disease. OBJECTIVE: We sought to investigate whether both exposure to microbes and exposure to structures of nonmicrobial origin, such as the sialic acid N-glycolylneuraminic acid (Neu5Gc), might play a significant role. METHODS: Exposure to Neu5Gc was evaluated by quantifying anti-Neu5Gc antibody levels in sera of children enrolled in 2 farm studies: the Prevention of Allergy Risk factors for Sensitization in Children Related to Farming and Anthroposophic Lifestyle (PARSIFAL) study (n = 299) and the Protection Against Allergy Study in Rural Environments (PASTURE) birth cohort (cord blood [n = 836], 1 year [n = 734], 4.5 years [n = 700], and 6 years [n = 728]), and we associated them with asthma and wheeze. The effect of Neu5Gc was examined in murine airway inflammation and colitis models, and the role of Neu5Gc in regulating immune activation was assessed based on helper T-cell and regulatory T-cell activation in mice. RESULTS: In children anti-Neu5Gc IgG levels correlated positively with living on a farm and increased peripheral blood forkhead box protein 3 expression and correlated inversely with wheezing and asthma in nonatopic subjects. Exposure to Neu5Gc in mice resulted in reduced airway hyperresponsiveness and inflammatory cell recruitment to the lung. Furthermore, Neu5Gc administration to mice reduced the severity of a colitis model. Mechanistically, we found that Neu5Gc exposure reduced IL-17+ T-cell numbers and supported differentiation of regulatory T cells. CONCLUSIONS: In addition to microbial exposure, increased exposure to non-microbial-derived Neu5Gc might contribute to the protective effects associated with the farm environment.

Is Toxoplasma gondii a Trigger of Bipolar Disorder?

Toxoplasma gondii, a ubiquitous intracellular parasite, has a strong tropism for the brain tissue, where it forms intracellular cysts within the neurons and glial cells, establishing a chronic infection. Although latent toxoplasmosis is generally assumed to be asymptomatic in immunocompetent individuals, it is now clear that it can induce behavioral manipulations in mice and infected humans. Moreover, a strong relation has emerged in recent years between toxoplasmosis and psychiatric disorders. The link between T. gondii and schizophrenia has been the most widely documented; however, a significant association with bipolar disorder (BD) and suicidal/aggressive behaviors has also been detected. T. gondii may play a role in the etiopathogenesis of psychiatric disorders affecting neurotransmitters, especially dopamine, that are implicated in the emergence of psychosis and behavioral Toxoplasma-induced abnormalities, and inducing brain inflammation by the direct stimulation of inflammatory cytokines in the central nervous system. Besides this, there is increasing evidence for a prominent role of immune dysregulation in psychosis and BD. The aim of this review is to describe recent evidence suggesting a link between Toxoplasma gondii and BD, focusing on the interaction between immune responses and this infectious agent in the etiopathogenesis of psychiatric symptoms.

Bipolar Disorder With Psychotic Features and Ocular Toxoplasmosis: A Possible Pathogenetic Role of the Parasite?

Recent evidence suggests the involvement of Toxoplasma gondii infection in the emergence of psychotic and affective disorders. In this report, we describe the case of a young Brazilian woman affected by recurrent ocular toxoplasmosis and presenting with a manic episode with psychotic features in the context of a diagnosis of Bipolar Disorder (BD), type I. We observed a relationship between ocular manifestations and the clinical course of bipolar illness, confirmed by molecular analyses (nested-PCR), as well as by the high level of T. gondii specific IgG. This case report is the first showing the presence of circulating parasite DNA at the time of occurrence of psychiatric symptoms, thus providing further support for a possible role of the parasite in the pathogenesis of some cases of BD.

The Surface-Associated Exopolysaccharide of Bifidobacterium longum 35624 Plays an Essential Role in Dampening Host Proinflammatory Responses and Repressing Local TH17 Responses.

The immune-modulating properties of certain bifidobacterial strains, such as Bifidobacterium longum subsp. longum 35624 (B. longum 35624), have been well described, although the strain-specific molecular characteristics associated with such immune-regulatory activity are not well defined. It has previously been demonstrated that B. longum 35624 produces a cell surface exopolysaccharide (sEPS), and in this study, we investigated the role played by this exopolysaccharide in influencing the host immune response. B. longum 35624 induced relatively low levels of cytokine secretion from human dendritic cells, whereas an isogenic exopolysaccharide-negative mutant derivative (termed sEPSneg) induced vastly more cytokines, including interleukin-17 (IL-17), and this response was reversed when exopolysaccharide production was restored in sEPSneg by genetic complementation. Administration of B. longum 35624 to mice of the T cell transfer colitis model prevented disease symptoms, whereas sEPSneg did not protect against the development of colitis, with associated enhanced recruitment of IL-17+ lymphocytes to the gut. Moreover, intranasal administration of sEPSneg also resulted in enhanced recruitment of IL-17+ lymphocytes to the murine lung. These data demonstrate that the particular exopolysaccharide produced by B. longum 35624 plays an essential role in dampening proinflammatory host responses to the strain and that loss of exopolysaccharide production results in the induction of local TH17 responses. IMPORTANCE: Particular gut commensals, such as B. longum 35624, are known to contribute positively to the development of mucosal immune cells, resulting in protection from inflammatory diseases. However, the molecular basis and mechanisms for these commensal-host interactions are poorly described. In this report, an exopolysaccharide was shown to be decisive in influencing the immune response to the bacterium. We generated an isogenic mutant unable to produce exopolysaccharide and observed that this mutation caused a dramatic change in the response of human immune cells in vitro In addition, the use of mouse models confirmed that lack of exopolysaccharide production induces inflammatory responses to the bacterium. These results implicate the surface-associated exopolysaccharide of the B. longum 35624 cell envelope in the prevention of aberrant inflammatory responses.

Genome Analysis and Characterisation of the Exopolysaccharide Produced by Bifidobacterium longum subsp. longum 35624™.

The Bifibobacterium longum subsp. longum 35624™ strain (formerly named Bifidobacterium longum subsp. infantis) is a well described probiotic with clinical efficacy in Irritable Bowel Syndrome clinical trials and induces immunoregulatory effects in mice and in humans. This paper presents (a) the genome sequence of the organism allowing the assignment to its correct subspeciation longum; (b) a comparative genome assessment with other B. longum strains and (c) the molecular structure of the 35624 exopolysaccharide (EPS624). Comparative genome analysis of the 35624 strain with other B. longum strains determined that the sub-speciation of the strain is longum and revealed the presence of a 35624-specific gene cluster, predicted to encode the biosynthetic machinery for EPS624. Following isolation and acid treatment of the EPS, its chemical structure was determined using gas and liquid chromatography for sugar constituent and linkage analysis, electrospray and matrix assisted laser desorption ionization mass spectrometry for sequencing and NMR. The EPS consists of a branched hexasaccharide repeating unit containing two galactose and two glucose moieties, galacturonic acid and the unusual sugar 6-deoxy-L-talose. These data demonstrate that the B. longum 35624 strain has specific genetic features, one of which leads to the generation of a characteristic exopolysaccharide.