Plasma Soluble P-selectin, Interleukin-6 and S100B Protein in Patients with Schizophrenia: a Pilot Study.

Microglial activation has long been posited to be involved in the neurobiology of schizophrenia. However, recent studies indicate that schizophrenia is associated with astrocytic activation, rather than microglia activation. Moreover, elevated levels of peripheral inflammatory cytokines associated with schizophrenia could induce or reflect brain inflammation. Therefore, based on: 1) findings of a periphery-to-brain communication pathway involving the cell adhesion molecule, P-selectin, in animal models; 2) dysregulated interleukin-6 (IL-6) and elevated levels of the astrocytic marker, S100B protein, in patients with schizophrenia, we sought to determine correlations between plasma soluble P-selectin (sP-selectin), S100B and IL-6 respectively. We recruited 106 patients with schizophrenia (mean age 33 years, 71.60% male) from the inpatient. sP-selectin, S100B and IL-6 were measured in fasting plasma. We calculated Pearson's and partial correlations between sP-selectin, S100B and IL-6. After controlling for potential confounders, sP-selectin positively correlated with S100B (r=0.31, p=0.004) and IL-6 (r=0.28, P=0.046). The correlation between IL-6 and S100B (r=0.28, p=0.066) did not reach statistical significance. We propose that in some patients with schizophrenia, immune activation in the periphery is associated with P-selectin-mediated trafficking of inflammation into the brain (most likely via leukocytes), which might be associated with astrocytic activation. Future studies should include healthy controls and first episode/early-onset psychosis patients. Importantly, in vivo imaging of neuroinflammation should be correlated with sP-selectin, IL-6 and S100B in the periphery and the CSF. Finally, the utility of combining sP-selectin, IL-6 and S100B as biomarkers for subtyping patients with schizophrenia, treatment selection and prognosis, should be evaluated in longitudinal studies.

Biological and Psychological Factors Determining Neuropsychiatric Outcomes in COVID-19.

PURPOSE OF REVIEW: We present biological and psychological factors implicated in psychiatric manifestations of SARS-CoV-2, as well as its neuroinvasive capability and immune pathophysiology. RECENT FINDINGS: Preexisting mental illness leads to worse clinical outcomes in COVID-19. The presence of the virus was reported in the cerebrospinal fluid (CSF) and brain tissue post-mortem. Most common psychiatric manifestations include delirium, mood disorders, anxiety disorders, and posttraumatic stress disorder. "Long-COVID" non-syndromal presentations include "brain-fogginess," autonomic instability, fatigue, and insomnia. SARS-CoV-2 infection can trigger prior vulnerabilities based on the priming of microglia and other cells, induced or perpetuated by aging and mental and physical illnesses. COVID-19 could further induce priming of neuroimmunological substrates leading to exacerbated immune response and autoimmunity targeting structures in the central nervous system (CNS), in response to minor immune activating environmental exposures, including stress, minor infections, allergens, pollutants, and traumatic brain injury.

Plasma soluble P-selectin correlates with triglycerides and nitrite in overweight/obese patients with schizophrenia.

BACKGROUND: Soluble P-selectin (sP-selectin) is associated with risk factors for cardiovascular disease (CVD) but this association has not been evaluated in patients with schizophrenia. This study primarily evaluated the association of sP-selectin with plasma lipids and nitrite (NO2-) respectively in overweight/obese adults with schizophrenia. METHODS: One-hundred and six patients with schizophrenia (mean age 32.9 years; 71.60% male) were recruited from a psychiatric hospital. Participants completed a structured interview and provided a fasting blood sample. Body mass index (BMI) was used to divide the sample into normal weight and overweight/obese groups. Pearson's and partial correlation coefficients (controlling for age, sex, race, education, and inflammation) were calculated to examine the association of sP-selectin with plasma lipids, and NO2- in the overweight/obese patients (primary analysis), as well as in the normal weight patients and the total sample (exploratory analyses). RESULTS: After controlling for potential confounders, sP-selectin positively correlated with triglycerides (r = 0.38, p = 0.01) and NO2- (r = 0.40, p < 0.01) in the overweight/obese group only. CONCLUSIONS: Future longitudinal studies should evaluate the utility of sP-selectin as a biomarker of CVD in overweight/obese adults with schizophrenia (for example, by relating sP-selectin to incidence of cardiovascular events).

Correlations between Body Mass Index, Plasma High-Sensitivity C-Reactive Protein and Lipids in Patients with Schizophrenia.

High prevalence of obesity in individuals with schizophrenia, associated with metabolic syndrome, leads to high rate of premature deaths from cardiovascular disease (CVD) in this population. Body mass index (BMI) and C-reactive protein (CRP) are correlated in the general population but this relationship has not been fully elucidated in patients with schizophrenia. We aimed to evaluate the correlation between BMI and CRP while relating both variables to plasma lipids in patients with schizophrenia. BMI, fasting high sensitivity CRP (hs-CRP), cotinine, and lipids were measured in 106 patients with schizophrenia (diagnosis confirmed with MINI). Pearson's and partial correlations (adjusting for age, sex, race, education and cotinine) between BMI, hs-CRP and lipids were calculated. Based on BMI, the patients were divided into normal-weight vs. overweight/obese and t-tests and linear regression were done to compare hs-CRP and lipids in the 2 groups. BMI positively correlated with hs-CRP (r = 0.29, p = 0.004). BMI and hs-CRP negatively correlated with HDL in the total sample (r = -0.29, p = 0.004; r = -0.37, p < 0.001 respectively). Furthermore, hs-CRP negatively correlated with HDL in overweight/obese patients (r = -0.41, p = 0.003), but not in normal-weight patients. hs-CRP and triglycerides were higher (1.62 ± 0.09 mg/L vs. 0.56 ± 0.08 mg/L, p < 0.001; 121.77 ± 8.96 mg/dL vs. 91.23 ± 6.52 mg/dL, p = 0.008 respectively) and HDL lower (39.55 ± 1.48 mg/dL vs. 50.68 ± 2.24 mg/dL, p < 0.001) in overweight/obese patients. Being overweight/obese is associated with increased inflammation and dyslipidemia in patients with schizophrenia. Effective interventions to prevent weight gain in schizophrenia are urgently needed.

Elevated Plasma S100B, Psychotic Symptoms, and Cognition in Schizophrenia.

S100B is a calcium binding protein mainly produced by glial cells. Previous studies have shown elevated levels of S100B in patients with schizophrenia. We measured S100B levels in fasting plasma of 39 patients with schizophrenia and 19 adult healthy controls. We used linear regression to compare S100B between patients and controls. In patients only, we also investigated the relationship between S100B levels and psychotic symptoms (assessed by the Positive and Negative Syndrome Scale), and cognitive function (assessed by the NIH Toolbox Cognition Battery), respectively by calculating Pearson's correlation coefficients. Mean plasma S100B was significantly higher in the patient group than in the control group. There were no significant correlations between plasma S100B and psychotic symptoms or cognition.

Knowledge and Attitude Towards Pharmacological Management of Acute Agitation: A Survey of Psychiatrists, Psychiatry Residents, and Psychiatric Nurses.

OBJECTIVE: The authors compared the current knowledge and attitude of psychiatrists, psychiatry residents, and psychiatric nurses towards the pharmacological management of acute agitation. METHODS: Questionnaires were electronically distributed to all attending psychiatrists, psychiatry residents, and psychiatric nurses who were either employed by the University Department of Psychiatry and Behavioral Sciences or were staff at a 250-bed affiliated Psychiatric Hospital. Where possible, Fisher's exact test was used to compare responses to questions based on designation. RESULTS: Of the 250 questionnaires distributed, 112 were returned (response rate of 44.8%), of which 64 (57.1%) were psychiatric nurses, 27 (24.1%) were attending psychiatrists, and 21 (18.8%) were psychiatry residents. A significantly higher percentage of attending psychiatrists and psychiatric nurses compared to psychiatry residents thought that newer second- generation antipsychotics (SGAs) are not as effective as older first-generation antipsychotics (FGAs) for managing acute agitation (55.6, 48.4, and 9.5% respectively, p = 0.008). The combination of intramuscular haloperidol, lorazepam, and diphenhydramine was the most preferred option chosen by all designations for the psychopharmacological management of severe agitation. Furthermore, a larger percentage of the psychiatric nurses, in comparison to attending psychiatrists, also chose the combination of intramuscular chlorpromazine, lorazepam, and diphenhydramine as an option for managing severe agitation; no psychiatry resident chose this option. CONCLUSION: Knowledge of evidence-based psychopharmacological management of agitation differs among attending psychiatrists, psychiatry residents and psychiatric nurses. Although the management of agitation should be individualized and context specific, monotherapy should be considered first where applicable.

Kynurenine and Tryptophan Levels in Patients With Schizophrenia and Elevated Antigliadin Immunoglobulin G Antibodies.

OBJECTIVE: Several studies have reported an association between nonceliac gluten sensitivity and schizophrenia. Immune and kynurenine (KYN) pathways have also been implicated in the pathophysiology of schizophrenia, and certain proinflammatory immune mediators may increase KYN and reduce tryptophan (TRP) levels. METHODS: We measured serum antigliadin immunoglobulin G (IgG), KYN, and TRP in 950 patients with schizophrenia. Patients with antibody level at the 90th percentile or higher of control participants (21.9% of all patients) were classified as having elevated antigliadin IgG. Independent t tests and linear regression models were used to compare TRP, KYN, and KYN-TRP ratio (indicator of TRP metabolism) between patients with and those without elevated antigliadin IgG. The correlation between antigliadin IgG and TRP, KYN, and the ratio was also evaluated in the patients. RESULTS: KYN and KYN-TRP ratio were higher in patients with elevated antigliadin IgG (geometric mean [standard deviation {SD}] = 2.65 [0.25] µmol/L versus 2.25 [0.23] µmol/L [p < .001] and 0.05 [0.26] versus 0.04 [0.25; p = .001] respectively), findings robust to adjustment for potential demographic and clinical confounders. Antigliadin IgG positively correlated with KYN and KYN-TRP ratio (r = 0.12, p < .001; r = 0.11, p = .002). TRP did not differ between the two groups and did not correlate with antigliadin IgG. CONCLUSIONS: Our results connect nonceliac gluten sensitivity with the KYN pathway of TRP metabolism in psychotic illness and hint toward potential individualized treatment targets.

Mortality associated with anxiolytic and hypnotic drugs-A systematic review and meta-analysis.

BACKGROUND: Use of hypnotics or anxiolytic drugs is common and various studies have reported increased mortality with hypnotics or anxiolytic use. OBJECTIVE: To consolidate the evidence on mortality risk associated with hypnotics or anxiolytic use METHODS: Major databases were searched through April 2014 for studies reporting mortality risk associated with hypnotics or anxiolytics use. A pooled hazard ratio with 95% confidence interval was estimated using random-effects model. RESULTS: After screening 2188 articles, 25 studies (24 cohort, 1 case-control) enrolling 2,350,093 patients with 59% females (age 18-102 years) were included in the meta-analysis. Hypnotics or anxiolytic users had 43% higher risk of mortality than non-users (hazard ratio, 1.43; 95% confidence interval, [1.12, 1.84]). Eight studies reported risk estimates for each gender category and pooled results from these studies showed increased risk of mortality among men (hazard ratio = 1.60, 95% confidence interval = [1.29,1.99]) and women (hazard ratio = 1.68, 95% confidence interval = [1.38, 2.04]). Pooled results from 10 studies showed higher mortality among benzodiazepine users compared to non-users (hazard ratio = 1.60, 95% confidence interval = [1.03, 2.49]), while pooled results from five studies showed an increased risk of mortality with Z-drugs use although the effect could not reach statistical significance (hazard ratio = 1.73, 95% confidence interval = [0.95, 3.16]). Significant heterogeneity was observed in the analyses and the quality of included studies was good. CONCLUSION: This meta-analysis suggests that hypnotics or anxiolytics drugs use is associated with increased mortality and hence should be used with caution. Future studies focused on underlying mechanism of increased mortality with hypnotics or anxiolytics use are required.

A Study of the Impact of Cannabis on Doses of Discharge Antipsychotic Medication in Individuals with Schizophrenia or Schizoaffective Disorder.

Patients with schizophrenia or schizoaffective disorder have a high prevalence of comorbid cannabis use disorder (CUD). CUD has been associated with poorer outcomes in patients. We compared doses of antipsychotic medications at the time of discharge from hospital among inpatients with schizophrenia or schizoaffective disorder with or without concurrent cannabis use. We reviewed the medical records of patients (N = 8157) with schizophrenia or schizoaffective disorder discharged from the hospital between 2008 and 2012. The patients were divided into two groups; those with urine drug tests positive for cannabis and those negative for cannabis. Doses of antipsychotic medications were converted to chlorpromazine equivalents. Bivariate analyses were done with Student's t test for continuous variables and χ 2 test for categorical variables. Linear regression was carried out to adjust for potential confounders. Unadjusted analysis revealed that the cannabis positive group was discharged on lower doses of antipsychotic medication compared with the cannabis negative group (geometric mean chlorpromazine equivalent doses 431.22 ± 2.20 vs 485.18 ± 2.21; P < 0.001). However, the difference in geometric mean chlorpromazine equivalent doses between the two groups was no longer significant after adjusting for sex, age, race, and length of stay (geometric mean difference 0.99; 95 % CI 0.92-1.10). Though limited by lack of information on duration, amount and severity of cannabis use, as well as inability to control for other non-antipsychotic medications, our study suggests that cannabis use did not significantly impact on doses of antipsychotics required during the periods of acute exacerbation in patients with schizophrenia or schizoaffective disorder.

Hospital length of stay in individuals with schizophrenia with and without cocaine-positive urine drug screens at hospital admission.

Despite the high prevalence of cocaine use disorder (CUD) in individuals with schizophrenia, current understanding of the effect of cocaine on psychiatric hospital length of stay (LOS) in individuals with schizophrenia is limited. We therefore retrospectively examined the medical records of 5106 hospital admissions due to exacerbation of schizophrenia. Linear regression and t-test were used to compare LOS between individuals with schizophrenia with cocaine-positive urine drug test results and those with negative test results. Individuals with schizophrenia who were also positive for cocaine had shorter LOS from both unadjusted (geometric mean LOS, 8.07 ± 1.92 vs. 11.83 ± 1.83 days; p < 0.001) and adjusted (ß = 0.69; confidence interval, 0.63-0.76; p < 0.001) analyses. Our results suggest that individuals with schizophrenia who also have comorbid CUD may require shorter inpatient treatment during periods of exacerbation of symptoms. Replication of this finding has relevance in treatment planning and resource allocation for the subpopulation of individuals with schizophrenia who also have stimulant use disorders.

Antipsychotic medication-induced dysphoria: its meaning, association with typical vs. atypical medications and impact on adherence.

Antipsychotic medication-induced dysphoria is a relatively under-recognized and understudied effect of antipsychotic medication. Although the term is encountered in clinical practice and in the literature, there is no consensus regarding its exact meaning. This article is a narrative review of the literature on antipsychotic medication and dysphoria based on a pubmed database search. We found that antipsychotic medication-induced dysphoria is a term used to describe a negative and unpleasant affective state which seems to be more often associated with high potency first-generation antipsychotics and could potentially lead to medication non-adherence. Though it is plausible to expect antipsychotic medication-induced dysphoria to be related to extrapyramidal symptoms, most especially akathisia, the nature of the association remains unspecified. Furthermore, there is some evidence that dopamine blockade maybe involved in the pathogenesis of antipsychotic medication-induced dysphoria. However, the limited methods of the currently available studies make it impossible to conclusively address the question of which class of antipsychotic (first- or second-generation) has a higher prevalence and severity of the syndrome.

Smoking, hypercholesterolaemia and hypertension as risk factors for cognitive impairment in older adults.

BACKGROUND: the prevalence of all types of cognitive impairment, including dementia, is increasing but knowledge of aetiological factors is still evolving. OBJECTIVE: this study aimed to evaluate the association between cardiovascular risk factors and cognitive function in older persons. DESIGN, SETTING AND SUBJECTS: a population-based cohort design involving 2,312 men and women (aged 50-75) enrolled in the University of Edinburgh Aspirin for Asymptomatic Atherosclerosis trial. METHODS: cognitive tests included the Mill Hill Vocabulary Scale, auditory verbal learning test (AVLT), digit symbol test, verbal fluency test (VFT), Raven's Progressive Matrices and the trail making test. A 'g' score (measure of general intelligence) was computed for each subject. Regression analysis was used to evaluate the association between relevant variables. RESULTS: higher diastolic BP was negatively associated with AVLT (ß = -0.153, P < 0.01), and with an estimated decline on AVLT (ß = -0.125, P < 0.01). Smoking was negatively associated with all the cognitive variables except VFT. The total cholesterol level was not associated with cognitive function or estimated decline. CONCLUSIONS: smoking and elevated blood pressure may be risk factors for cognitive decline, and thus potential targets for preventive and therapeutic interventions.

Reading increases ocular illuminance during light treatment.

BACKGROUND: Bright-light treatment is a safe and effective treatment for the management of winter seasonal affective disorder (SAD). In a recent study, we found that the relative duration of reading was positively associated with likelihood of remission after six weeks of light treatment. METHODS: Two technicians measured the illuminance of a light box with a light meter directed towards the center of reading material that was placed on a table in front of the light box. The measurement was also performed after reading material was removed. The two measurements were performed in a randomized order. Friedman analysis of variance with Wilcoxon post-hoc tests were used to compare illuminance with vs. without reading. RESULTS: The presence of the reading material increased illuminance by 470.93 lux (95% CI 300.10-641.75), p<0.0001. LIMITATIONS: This is a technical report done under conditions intended to mimic those of typical ambulatory light treatment as much as possible. CONCLUSIONS: As reading materials reflect light from the light box, reading during light therapy increases ocular illuminance. If confirmed by future studies using continuous recordings in randomized design, instructing SAD patients to read during light therapy may contribute to a more complete response to light treatment. The downside of specific relevance for students, is that reading, in particular, with bright light in the late evening/early night may induce or worsen circadian phase delay, adversely affecting health and functioning.

Challenges and Considerations in Treating Negative and Cognitive Symptoms of Schizophrenia Spectrum Disorders.

Background: The prototypical patient with schizophrenia spectrum disorders (SSDs) is often thought to possess positive symptoms. However, patients with SSDs can present with predominantly negative and cognitive symptoms, which can create diagnostic and treatment challenges. Case Presentation: A 33-year-old female veteran presented to the emergency department with diminished speech output, markedly blunted affect, tangential speech, was not oriented to situation, and appeared to be responding to internal stimuli. Following inpatient admission, the veteran was diagnosed with schizoaffective disorder, which was misdiagnosed as major depressive disorder and borderline personality disorder during her military service. She was initially treated with olanzapine injections and psychotherapy but continued to experience worsening symptoms, resulting in multiple hospitalizations. After starting clozapine, she demonstrated marked improvement and continued with outpatient mental health care. Conclusions: Predominant negative and cognitive symptom presentations of SSDs require unique considerations to accurately identify and provide optimal treatment for the patient. Clozapine is a promising treatment for addressing these symptoms. This case demonstrates how careful multidisciplinary evaluations, review of health records, collateral information from family members, and other diagnostic and treatment considerations in patients with predominant negative and cognitive symptoms of SSDs can refine and enhance the clinical care offered to such patients.

History of Suicide Attempt and Clozapine Treatment in Veterans With Schizophrenia or Schizoaffective Disorder.

Objective: To evaluate whether a history of suicide attempt increases the odds of receiving clozapine treatment in veterans with schizophrenia or schizoaffective disorder.Methods: Electronic health record data were obtained for veterans with schizophrenia or schizoaffective disorder treated at any US Veterans Affairs Medical Center between January 1, 2000, and January 31, 2021 (N = 134,692). Logistic regression (adjusted and unadjusted) was applied to estimate odds ratios (ORs) for clozapine treatment in suicide attempters relative to nonattempters.Results: 3,407 patients had a documented history of suicide attempt, while 6,867 patients had received clozapine treatment. Also, 9.4% (n = 321) of suicide attempters versus 5.0% (n = 6546) of nonattempters had received clozapine treatment. The odds of being treated with clozapine was approximately 2-fold in patients with a history of suicide attempt in unadjusted (OR = 1.98, 95% CI, 1.76-2.22) and adjusted (OR = 1.91, 95% CI, 1.67-2.15) analyses.Conclusions: Despite the higher odds of clozapine treatment in suicide attempters with schizophrenia or schizoaffective disorder, clozapine was underutilized in the current sample of veterans. Concerted efforts should be made to expand the use of clozapine in patients with schizophrenia or schizoaffective disorder, especially those with a history of suicide attempt.

Digital Medicine System in Veterans With Severe Mental Illness: Feasibility and Acceptability Study.

BACKGROUND: Suboptimal medication adherence is a significant problem for patients with serious mental illness. Measuring medication adherence through subjective and objective measures can be challenging, time-consuming, and inaccurate. OBJECTIVE: The primary purpose of this feasibility and acceptability study was to evaluate the impact of a digital medicine system (DMS) among Veterans (patients) with serious mental illness as compared with treatment as usual (TAU) on medication adherence. METHODS: This open-label, 2-site, provider-randomized trial assessed aripiprazole refill adherence in Veterans with schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder. We randomized 26 providers such that their patients either received TAU or DMS for a period of 90 days. Semistructured interviews with patients and providers were used to examine the feasibility and acceptability of using the DMS. RESULTS: We enrolled 46 patients across 2 Veterans Health Administration sites: 21 (46%) in DMS and 25 (54%) in TAU. There was no difference in the proportion of days covered by medication refill over 3 and 6 months (0.82, SD 0.24 and 0.75, SD 0.26 in DMS vs 0.86, SD 0.19 and 0.82, SD 0.21 in TAU, respectively). The DMS arm had 0.85 (SD 0.20) proportion of days covered during the period they were engaged with the DMS (mean 144, SD 100 days). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient findings described the positive impact of the DMS on medication adherence, challenges with the DMS patch connectivity and skin irritation, and challenges with the DMS app that affected overall use. Providers described an overall interest in using a DMS as an objective measure to support medication adherence in their patients. However, providers described challenges with the DMS dashboard and integrating DMS data into their workflow, which decreased the usability of the DMS for providers. CONCLUSIONS: There was no observed difference in refill rates. Among those who engaged in the DMS arm, the proportion of days covered by refills were relatively high (mean 0.85, SD 0.20). The qualitative analyses highlighted areas for further refinement of the DMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT03881449; https://clinicaltrials.gov/ct2/show/NCT03881449.

Repetitive Transcranial Magnetic Stimulation: A Potential Treatment for Obesity in Patients with Schizophrenia.

Obesity is highly prevalent in patients with schizophrenia and, in association with metabolic syndrome, contributes to premature deaths of patients due to cardiovascular disease complications. Moreover, pharmacologic, and behavioral interventions have not stemmed the tide of obesity in schizophrenia. Therefore, novel effective interventions are urgently needed. Repetitive transcranial magnetic stimulation (rTMS) has shown efficacy for inducing weight loss in obese non-psychiatric samples but this promising intervention has not been evaluated as a weight loss intervention in patients with schizophrenia. In this narrative review, we describe three brain mechanisms (hypothalamic inflammation, dysregulated mesocorticolimbic reward system, and impaired prefrontal cortex function) implicated in the pathogenesis and pathophysiology of obesity and emphasize how the three mechanisms have also been implicated in the neurobiology of schizophrenia. We then argue that, based on the three overlapping brain mechanisms in obesity and schizophrenia, rTMS would be effective as a weight loss intervention in patients with schizophrenia and comorbid obesity. We end this review by describing how deep TMS, relative to conventional TMS, could potentially result in larger effect size for weight loss. While this review is mainly conceptual and based on an extrapolation of findings from non-schizophrenia samples, our aim is to stimulate research in the use of rTMS for weight loss in patients with schizophrenia.

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.

History of Suicide Attempts and COVID-19 Infection in Veterans with Schizophrenia or Schizoaffective Disorder: Moderating Effects of Age and Body Mass Index.

INTRODUCTION: Relative to the general population, patients with schizophrenia or schizoaffective disorder have higher rates of suicide attempts and mortality from COVID-19 infection. Therefore, determining whether a history of suicide attempt is associated with COVID-19 in patients with schizophrenia or schizoaffective disorder has implications for COVID-19 vulnerability stratification in this patient population. METHODS: We carried out cross-sectional analyses of electronic health records of veterans with a diagnosis of schizophrenia or schizoaffective disorder that received treatment at any United States Veterans Affairs Medical Center between January 1, 2020, and January 31, 2021. We used logistic regression to estimate unadjusted and adjusted (including age, sex, race, marital status, body mass index (BMI), and a medical comorbidity score) odds ratios (ORs) for COVID-19 positivity in suicide attempters relative to nonattempters. RESULTS: A total of 101,032 veterans (mean age 56.67 ± 13.13 years; males 91,715 [90.8%]) were included in the analyses. There were 2,703 (2.7%) suicide attempters and 719 (0.7%) patients were positive for COVID-19. The association between history of suicide attempt and COVID-19 positivity was modified by age and BMI, such that the relationship was only significant in patients younger than 59 years, and in obese (BMI ≥30) patients (adjusted OR 3.42, 95% CI 2.02-5.79 and OR 2.85, 95% CI 1.65-4.94, respectively). CONCLUSIONS: Higher rates of COVID-19 in young or obese suicide attempters with a diagnosis of schizophrenia or schizoaffective disorder might be due to the elevated risk for the infection in this subgroup of patients.

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.