Electroconvulsive Treatment Utilization for Inpatient Management of Catatonia in Adolescents With Schizophrenia Spectrum Disorders.

OBJECTIVE: The aim of this study was to determine rates of electroconvulsive therapy (ECT) use for catatonia in schizophrenia spectrum disorders, stratified by patient demographics and hospital characteristics, and its impact on inpatient length of stay and cost. METHODS: We found 155 adolescents (aged 12-18 years) with principal discharge diagnosis of schizophrenia spectrum disorders with catatonia from the National Inpatient Sample. They were subgrouped into ECT (n = 20) and non-ECT (n = 135) groups. We used descriptive statistics to evaluate the utilization of ECT for catatonia and independent-sample t test for continuous variables with statistical significance at P ≤ 0.05. RESULTS: The overall utilization rate of ECT in adolescents for catatonia was 12.9%. A high rate of ECT use was evident for Whites (30.8%) compared with the other race/ethnicities and also was seen in private health insurance beneficiaries (20%). The rate of ECT use varied by the region, with highest for the Northeast (20%), followed by the South (18.2%), and the West (14.3%). Adolescent inpatients with catatonia in public and teaching type, and large bed-size hospitals were more likely to receive ECT than their counterparts. The mean number of ECT sessions required during the inpatient stay was 5.2 (range, 1-15), and the mean number of days from admission to initial ECT was 2.5 (range, 0-6). CONCLUSIONS: Electroconvulsive therapy is used for approximately only 13% of adolescents with catatonia when comorbid schizophrenia spectrum disorders are present, suggesting that many patients may not get evidence-based treatment. Future studies in this area are needed.

Toxoplasma gondii IgG associations with sleep-wake problems, sleep duration and timing.

BACKGROUND: Evidence links Toxoplasmagondii (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) 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.

No evidence for airborne transmission of Toxoplasma gondii in a very high prevalence area in Lancaster County.

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: Wo 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.

Periodontal, metabolic, and cardiovascular disease: Exploring the role of inflammation and mental health.

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.

Seasonality of blood neopterin levels in the Old Order Amish.

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.

Positive association between Toxoplasma gondii IgG serointensity and current dysphoria/hopelessness scores in the Old Order Amish: a preliminary study.

Toxoplasma gondii (T. gondii) 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 T. gondii 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 T. gondii 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 T. gondii 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 T. gondii 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 T. gondii-positive individuals at high-risk for SSDV.

Decreasing Tryptophan and Increasing Neopterin Plasma Levels During Pregnancy are Associated with High First Trimester Porphyromonas gingivalis K-Serotype IgG Serointensity in a Cohort of Hispanic Women.

BACKGROUND: Immune activation or high levels of stress may lead to increased metabolism of tryptophan during pregnancy. Porphyromonas gingivalis (Pg), the "keystone" periodontal pathogen, induces immune and indoleamine 2,3-dioxygenase (IDO) activation. Thus, we hypothesized that larger gestational decreases in tryptophan and elevations in neopterin and kynurenine would occur in pregnant women with elevated IgG antibodies to Pg capsular (K) serotypes. METHODS: Venous blood of 52 Hispanic pregnant women with a mean age (SD) of 31.8 (5.9) years was sampled once per trimester of pregnancy (V1, V2, V3), and plasma was obtained and stored. ELISAs were used to measure Pg capsular (K) serotype IgG serointensity (V1 only) and neopterin levels (V1-V3). Tryptophan and kynurenine (V1-V3) were measured with high-performance liquid chromatography. The participants having IgG serointensity for any of the seven Pg K serotypes in the highest quartile were defined as the "High PgK_IgG" group and those having IgG serointensity for all K serotypes in the lowest three quartiles were defined as the "Low PgK_IgG" group. Statistics included multivariable linear and nonparametric methods. RESULTS: Significant decreases in plasma tryptophan levels and increases in neopterin during gestation were found in "High PgK_IgG" women but not in "Low PgK_IgG" women. Kynurenine changes were not significantly different between the two groups. CONCLUSION: If replicated in larger studies and further characterized clinically, radiologically, and microbiologically, our results may potentially lead to novel interventional targets, as well as the development of more complete prognostic and predictive interactive biomarkers for adverse obstetrical outcomes and peripartum depression, and their prevention.

Toxoplasma gondii, Suicidal Behavior, and Intermediate Phenotypes for Suicidal Behavior.

Within the general literature on infections and suicidal behavior, studies on Toxoplasma gondii (T. gondii) occupy a central position. This is related to the parasite's neurotropism, high prevalence of chronic infection, as well as specific and non-specific behavioral alterations in rodents that lead to increased risk taking, which are recapitulated in humans by T. gondii's associations with suicidal behavior, as well as trait impulsivity and aggression, mental illness and traffic accidents. This paper is a detailed review of the associations between T. gondii serology and suicidal behavior, a field of study that started 15 years ago with our publication of associations between T. gondii IgG serology and suicidal behavior in persons with mood disorders. This "legacy" article presents, chronologically, our primary studies in individuals with mood disorders and schizophrenia in Germany, recent attempters in Sweden, and in a large cohort of mothers in Denmark. Then, it reviews findings from all three meta-analyses published to date, confirming our reported associations and overall consistent in effect size [ranging between 39 and 57% elevation of odds of suicide attempt in T. gondii immunoglobulin (IgG) positives]. Finally, the article introduces certain links between T. gondii and biomarkers previously associated with suicidal behavior (kynurenines, phenylalanine/tyrosine), intermediate phenotypes of suicidal behavior (impulsivity, aggression) and state-dependent suicide risk factors (hopelessness/dysphoria, sleep impairment). In sum, an abundance of evidence supports a positive link between suicide attempts (but not suicidal ideation) and T. gondii IgG (but not IgM) seropositivity and serointensity. Trait impulsivity and aggression, endophenotypes of suicidal behavior have also been positively associated with T. gondii seropositivity in both the psychiatrically healthy as well as in patients with Intermittent Explosive Disorder. Yet, causality has not been demonstrated. Thus, randomized interventional studies are necessary to advance causal inferences and, if causality is confirmed, to provide hope that an etiological treatment for a distinct subgroup of individuals at an increased risk for suicide could emerge.

Predictors of civil and forensic inpatient psychiatric readmissions at a Public Mental Health Hospital.

Inpatient psychiatric readmissions are increasingly prevalent and associated with worse prognostic outcomes and high economic costs, regardless of the medicolegal ramifications that necessitate them. Unlike most general medical readmissions, psychiatric readmissions are commonly warranted for both medical and legal purposes. However, studies focusing on analyzing the predictors of inpatient psychiatric readmission and their relationship to civil versus forensic readmission are limited. The purpose of this study was to examine the predictors of psychiatric readmission among civil and forensic patients admitted to a psychiatric hospital. In this retrospective chart review, we extrapolated data from medical records of 741 patients admitted from 2012 to 2017 with follow up until 2019. Analyses involved chi-square tests for comparing the distribution of demographic and clinical variables between forensic and civil readmission, and Cox regression to determine predictors of time to first readmission. Our results show that race, diagnosis, restraint/seclusion, type of admission, and disposition are significantly associated with an increased risk of psychiatric readmission. This study has important implications for healthcare providers and policy makers in revising mental health policies and improving systems-based practices for the mental health system. Future efforts in improving community psychiatric services and enhancing inpatient therapeutic environment may reduce psychiatric readmissions.

Inflammation in Traumatic Brain Injury.

There is an increasing evidence that inflammation contributes to clinical and functional outcomes in traumatic brain injury (TBI). Many successful target-engaging, lesion-reducing, symptom-alleviating, and function-improving interventions in animal models of TBI have failed to show efficacy in clinical trials. Timing and immunological context are paramount for the direction, quality, and intensity of immune responses to TBI and the resulting neuroanatomical, clinical, and functional course. We present components of the immune system implicated in TBI, potential immune targets, and target-engaging interventions. The main objective of our article is to point toward modifiable molecular and cellular mechanisms that may modify the outcomes in TBI, and contribute to increasing the translational value of interventions that have been identified in animal models of TBI.

Periodontal Pathogens and Neuropsychiatric Health.

Increasing evidence incriminates low-grade inflammation in cardiovascular, metabolic diseases, and neuropsychiatric clinical conditions, all important causes of morbidity and mortality. One of the upstream and modifiable precipitants and perpetrators of inflammation is chronic periodontitis, a polymicrobial infection with Porphyromonas gingivalis (P. gingivalis) playing a central role in the disease pathogenesis. We review the association between P. gingivalis and cardiovascular, metabolic, and neuropsychiatric illness, and the molecular mechanisms potentially implicated in immune upregulation as well as downregulation induced by the pathogen. In addition to inflammation, translocation of the pathogens to the coronary and peripheral arteries, including brain vasculature, and gut and liver vasculature has important pathophysiological consequences. Distant effects via translocation rely on virulence factors of P. gingivalis such as gingipains, on its synergistic interactions with other pathogens, and on its capability to manipulate the immune system via several mechanisms, including its capacity to induce production of immune-downregulating micro-RNAs. Possible targets for intervention and drug development to manage distal consequences of infection with P. gingivalis are also reviewed.

Traumatic Brain Injury and Suicidal Behavior: A Review.

Given the increasing rate of death by suicide in the United States, it is imperative to examine specific risk factors and to identify possible etiologies of suicidal behavior in at-risk clinical subpopulations. There is accumulating evidence to support an elevated risk of death by suicide in individuals with a history of traumatic brain injury (TBI). In this review article, after defining terms used in suicidology, we discuss the associations of TBI with death by suicide, suicide attempt, and suicidal ideation. A model for repetitive TBIs, leading to chronic traumatic encephalopathy, is also discussed as a neuroinflammatory process, with discussion about its possible link with suicide. The review concludes with an overview of interventions to prevent suicidal behavior.

Moderation of the relationship between Toxoplasma gondii seropositivity and trait impulsivity in younger men by the phenylalanine-tyrosine ratio.

Previously, we reported that Toxoplasma gondii (T. gondii)-seropositivity is associated with higher impulsive sensation seeking in younger men. As dopaminergic and serotonergic signaling regulate impulsivity, and as T. gondii directly and indirectly affects dopaminergic signaling and induces activation of the kynurenine pathway leading to the diversion of tryptophan from serotonin production, we investigated if dopamine and serotonin precursors or the tryptophan metabolite kynurenine interact with the T. gondii-impulsivity association. In 950 psychiatrically healthy participants, trait impulsivity scores were related to T. gondii IgG seropositivity. Interactions were also identified between categorized levels of phenylalanine (Phe), tyrosine (Tyr), Phe:Tyr ratio, kynurenine (Kyn), tryptophan (Trp) and Kyn:Trp ratio, and age and gender. Only younger T. gondii-positive men with a high Phe:Tyr ratio, were found to have significantly higher impulsivity scores. There were no significant associations in other demographic groups, including women and older men. No significant effects or interactions were identified for Phe, Tyr, Kyn, Trp, or Kyn:Trp ratio. Phe:Tyr ratio, therefore, may play a moderating role in the association between T. gondii seropositivity and impulsivity in younger men. These results could potentially lead to individualized approaches to reduce impulsivity, based on combined demographic, biochemical and serological factors.

Automatic implantable cardiac defibrillator implantation may precipitate effort-induced thrombosis in young athletes: a case report and literature review.

Upper extremity deep vein thrombosis (DVT) is a common finding after implantation of an automatic implantable cardiac defrillator (AICD). We describe the case of a patient who developed a left upper extremity DVT 4.5 months after implantation of an AICD and was found to have a lead-induced stenosis with possible underlying Paget-Schroetter syndrome (PSS) in the midbrachiocephalic vein on venography. While his symptoms resolved after the combination of pharmacomechanical thrombolysis, angioplasty, and anticoagulation, his long-term management is complicated by the presence of both PSS and lead-induced stenosis. Herein, we discuss his presentation, treatment, and future management options.