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Previous evidence connects periodontal disease, a modifiable condition affecting a majority of Americans, with metabolic and cardiovascular morbidity and mortality. This review focuses on the likely mediation of these associations by immune activation and their potential interactions with mental illness. Future longitudinal, and ideally interventional studies, should focus on reciprocal interactions and cascading effects, as well as points for effective preventative and therapeutic interventions across diagnostic domains to reduce morbidity, mortality and improve quality of life.

BackgroundAlongside affective episodes, cognitive dysfunction is a core symptom of bipolar disorder. The intracellular parasite T. gondii has been positively associated with both, the diagnosis of bipolar disorder and poorer cognitive performance, across diagnostic boundaries. This study aims to investigate the association between T. gondii seropositivity, serointensity, and cognitive function in an euthymic sample of bipolar disorder.MethodsA total of 76 participants with bipolar disorder in remission were tested for T. gondii-specific IgG and IgM antibodies and for cognitive performance using neuropsychological test battery. Cognitive parameters were categorized into three cognitive domains (attention and processing speed, verbal memory, and executive function). Statistical analysis of associations between continuous indicators of cognitive function as dependent variables in relationship to T. gondii, included multivariate analyses of co-variance for seropositivity, and partial correlations with IgG serointensity in IgG seropositives. All analyses were controlled for age and premorbid IQ.ResultsIn seropositives (n = 27), verbal memory showed significant inverse partial correlations with IgG antibody levels (short delay free recall (r=–0.539, p = 0.005), long delay free recall (r=–0.423, p = 0.035), and immediate recall sum trial 1–5 (r=–0.399, p = 0.048)). Cognitive function did not differ between IgG seropositive and seronegative individuals in any of the cognitive domains (F (3,70) = 0.327, p = 0.806, n = 76). IgM positives (n = 7) were too few to be analyzed.ConclusionsThis investigation is the first to show an association between T. gondii IgG serointensity and memory function in a well-diagnosed bipolar disorder sample. It adds to the existing literature on associations between latent T. gondii infection and cognition in bipolar disorder, while further research is needed to confirm and expand our findings, eliminate potential sources of bias, and establish cause-effect relationships.

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Purpose of Review This review focuses on recent advances in our understanding of the interactions between psychological stress, the immune system, and periodontitis, including the dynamic role of host stress responses in altering immune function, altering the oral microbiome and biofilm formation, and promoting local and systemic disease progression. Recent Findings Within the context of periodontal health and disease, stress leads to an impairment of effective antimicrobial defense, shifts in oral microbiome profiles toward more pathogenic gene expression and taxa composition, increased translocation, and biofilm formation. The link between stress and periodontitis is multiform and includes hypothalamic–pituitary–adrenal (HPA) axis and catecholamine activation, production of immune mediators of inflammation and, clinically, syndromes of depression, bipolar disorder, anxiety disorders, and sleep-wake disorders. Summary Psychological stress appears to be an important modifiable risk factor for the development and progression of periodontitis and other periodontal diseases.

Background: Toxoplasma gondii (T. gondii) has been associated with acute food-borne illness, chronic low-grade inflammation, neuropsychiatric conditions and reactivation of chronic latent infection in immunocompetent hosts. Primary infection with T. gondii in pregnant women can lead to congenital toxoplasmosis. In addition to well-known oral tissue-cyst or oocyst ingestion, we hypothesized that the very high prevalence of T. gondii in certain populations exposed to agricultural dust could be, in part, a consequence of airborne infection with oocysts. Methods: We collected environmental dust samples from an area with a reportedly high T. gondii seroprevalence in the Old Order Amish population, in Lancaster, Pennsylvania. Samples included: a) air filters from air-conditioning units; b) swabs of settled dust; and c) vacuum filters containing airborne field dust. Pools of the swabs and shredded sub-samples of the air filters were fed to pigs, with inoculation into mice of heart tissue from seroconverted pigs. We also investigated the presence of T. gondii DNA using PCR amplification. Results: Only one pig seroconverted. However, bioassay of pig heart tissue further inoculated into mice showed no evidence of T. gondii infection. Consistently, no evidence of T. gondii DNA was revealed in any sample. Conclusions: No evidence of airborne transmission was found in the environmental samples that were examined.

Background: Evidence links Toxoplasma gondii (T. gondii), a neurotropic parasite, with schizophrenia, mood disorders and suicidal behavior, all of which are associated and exacerbated by disrupted sleep. Moreover, low-grade immune activation and dopaminergic overstimulation, which are consequences of T. gondii infection, could alter sleep patterns and duration. Methods: Sleep data on 833 Amish participants [mean age (SD) = 44.28 (16.99) years; 59.06% women] were obtained via self-reported questionnaires that assessed sleep problems, duration and timing. T. gondii IgG was measured with ELISA. Data were analyzed using multivariable logistic regressions and linear mixed models, with adjustment for age, sex and family structure. Results: T. gondii seropositives reported less sleep problems (p < 0.005) and less daytime problems due to poor sleep (p < 0.005). Higher T. gondii titers were associated with longer sleep duration (p < 0.05), earlier bedtime (p < 0.005) and earlier mid-sleep time (p < 0.05). Conclusions: It seems unlikely that sleep mediates the previously reported associations between T. gondii and mental illness. Future longitudinal studies with objective measures are necessary to replicate our findings.

) IgG seropositivity and serointensity have been previously associated with suicidal self-directed violence (SSDV). Although associations with unipolar depression have also been investigated, the results have been inconsistent, possibly as a consequence of high heterogeneity. We have now studied this association in a more homogeneous population, [that is (i.e.) Old Order Amish (OOA)] with previously reported high seroprevalence. In 306 OOA with a mean age of 46.1±16.7 years, including 191 (62.4%) women in the Amish Wellness Study, we obtained both IgG titers (by enzyme-linked immunosorbent assay [ELISA]), and depression screening questionnaires (Patient Health Questionnaire [PHQ-9] [n=280] and PHQ-2 [n=26]). Associations between IgG and dysphoria/hopelessness and anhedonia scores on depression screening questionnaires were analyzed using multivariable linear methods with adjustment for age and sex. Serointensity was associated with both current dysphoria/hopelessness (p=0.045) and current combined anhedonia and dysphoria/hopelessness (p=0.043), while associations with simple anhedonia and past/lifelong (rather than current) phenotypes were not significant. These results indicate the need for larger longitudinal studies to corroborate the association between dysphoria/hopelessness and IgG-titers. Current hopelessness is a known risk factor for SSDV which responds particularly well to cognitive behavioral therapy, and may be a focused treatment target for -positive individuals at high-risk for SSDV.

Seasonal changes in non-human animals and seasonal affective disorder (SAD) in humans are associated with immune activation in winter relative to summer. We intended to measure seasonal variation in neopterin, a marker of cellular immunity, and its interactions with gender and seasonality of mood. We studied 320 Amish from Lancaster, PA, USA (men=128; 40%) with an average age [Standard deviation (SD)] of 56.7 (13.9) years. Blood neopterin level was measured with enzyme-linked immunosorbent assay (ELISA). Seasonality was measured with Seasonal Pattern Assessment Questionnaire (SPAQ). Statistical analysis included analysis of covariance (ANCOVAs) and multivariate linear regression. We also investigated interactions of seasonal differences in neopterin with gender, seasonality scores and estimation of SAD diagnosis. We found a significantly higher neopterin level in winter than in summer (p=0.006). There were no significant gender or seasonality interactions. Our study confirmed the hypothesized higher neopterin level in winter. A cross sectional design was our major limitation. If this finding will be replicated by longitudinal studies in multiple groups, neopterin could be used to monitor immune status across seasons in demographically diverse samples, even if heterogeneous in gender distribution, and degree of seasonality of mood.

Introduction Sleep problems and periodontal disease have a bidirectional relationship and are independently linked with depression, dementia, and metabolic disease. Inadequate sleep can worsen inflammation, a hallmark of periodontal disease, and the activation of the immune system can alter sleep/wake cycles. A key player in periodontal disease is Porphyromonas gingivalis, a bacteria that can translocate to the brain and induce miRNA’s. Antibodies to P. gingivalis capsular virulence factors, K1-7, have been used to estimate P. gingivalis virulence. This study was conducted to explore cross-sectional associations between seropositivity of K serotypes of P. gingivalis and measures of self-reported impairment in sleep. If identified, these links would provide a rationale to initiate causality and mediation studies. We hypothesized that sleep impairment is positively associated with P. gingivalis K IgG serointensity. Methods 880 Old Order Amish aged 44.8 (SD: 17.2 years); 360 men (40.91%), 520 women (59.09%) responded to an adapted Pittsburgh-Sleep-Quality-Index questionnaire. IgG serointensity to 7 K-capsular P. gingivalis serotypes were measured with ELISAs. We tested for the association of log-transformed serotype IgG intensity and positivity (successively defined as within the top 5% and 25% for each serotype) with sleep parameters (as binary and continuous variables) using linear and logistic regressions, adjusting for age and sex. Results We confirmed no hypothesized associations between any of the sleep problems on the PSQI and K serotype serointensity and seropositivity. Exploratory analysis returned a negative association of log-transformed K3 IgG with daytime sleepiness (p=0.01); however, this did not resist adjustment for multiple comparisons and was inconsistent with the direction of the hypothesis. Conclusion Strengths of the study include the reduced smoking prevalence in the Amish and the relatively homogenous lifestyle, reducing confounding. The results imply P. gingivalis serotypes are not associated with sleep disturbance. Limitations are self-reporting of sleep, cross-sectional approach and limited generalizability. Results do not support an association between P. gingivalis K serotypes and sleep-problems. Support (if any) MVM-CoRE

Markers of chronic infection Toxoplasma gondii (Nicolle et Manceaux, 1908) have been associated with suicidal self-directed violence (SSDV). We present the results of the first study relating T. gondii IgG serology with suicide attempts and suicidal ideation in United States Veterans, known to have higher suicide rates than members of the general population. We also related T. gondii serology to SSDV risk factors, including valid and reliable measures of trait impulsivity, aggression, self-reported depression, and sleep disturbance. We recruited 407 Veterans enrolled at three Veterans Affairs Medical Centers with mean (S.D.) age = 45.6 (11.6) years; 304 men (74.7%); 203 with a history of SSDV and 204 with no history of any self-directed violence (SDV). Seropositivity and serointensity, categorised as high (top quartile) or low (lower three quartiles), were analysed in relationship to SSDV, suicidal ideation and clinical risk factors using age and gender-adjusted linear and logistic methods, after transformations and nonparametric tests when appropriate. Associations between seropositivity and SSDV and its risk factors were not significant in all groups. High serointensity, while not associated with SSDV or repeat suicide attempts, was positively associated with suicidal ideation, depression, impulsivity, and daytime dysfunction due to sleepiness (p < 0.05), but only in Veterans with a history of SSDV. In Veterans without a history of SDV, no associations were significant. These associations remained significant after adjustment for certain socioeconomic factors (i.e., income, homelessness, military rank). Including education in the model downgraded the statistical significance of suicidal ideation and depression to statistical trends, but the significance of associations with impulsivity and daytime dysfunction due to sleepiness remained. Major limitations include the cross-sectional design, overall low seropositivity within the sample, and potentially spurious results due to multiple comparisons. Thus, the results of this report need to be replicated in larger samples, ideally longitudinally.