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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.

IntroductionSchizophrenia is a severe psychiatric condition associated with cognitive impairment and premature dementia. Furthermore, metabolic syndrome (MetS)—combined central obesity, diabetes, dyslipidemia and hypertension—is highly prevalent in patients with schizophrenia and is believed to contribute to cognitive impairment and premature dementia in patients with schizophrenia. However, the mechanisms by which MetS contributes to cognitive impairment in patients with schizophrenia is unclear. Based on the association of MetS with platelet activation and the ability of activated platelets to impact blood-brain-barrier function, we tested the hypothesis that platelet activation is associated with both MetS and cognitive impairment in two independent pilot samples of patients with schizophrenia.MethodsIn the first pilot sample (sample A) we recruited 13 veterans with either schizophrenia or schizoaffective disorder with MetS (MetS+, n=6), and without MetS (MetS-, n=7). We administered the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) on all 13 veterans and assessed platelet activation using flow cytometry. In the second pilot sample (sample B), we identified 10 non-veteran MetS+ patients with schizophrenia and 10 age-, and sex-matched MetS-patients with schizophrenia from previously collected data on 106 patients enrolled in a non-MetS study. Participants in sample B had data on the NIH Toolbox cognitive battery (NIH Toolbox) and plasma soluble P-selectin (sP-selectin), a marker of platelet activation. We compared flow cytometry platelet activation in MetS+ and MetS- using the Mann Whitney test and the median test to compare sP-selectin and cognitive measures. We also measured the correlation between platelet activation and cognition using Spearman’s rho correlation.ResultsPlatelet activation was significantly higher in MetS+ than MetS- (mean rank 8.60 vs. 3.83, p=0.017). Median score for the picture vocabulary test (language ability) was significantly lower in MetS+ relative to MetS- (82.35 vs. 104, p=0.015). In addition, platelet activation correlated negatively (rho = −0.74, p= 0.009) with the Wechsler Memory Scale: Spatial Span (nonverbal working memory) and plasma sP-selectin correlated negatively (rho = −0.55, p= 0.029) with the List Sorting Working Memory Test.ConclusionOur preliminary findings suggest that platelet activation is involved in the association of MetS with cognitive impairment in patients with schizophrenia. Future studies are needed to elucidate the role of platelets in MetS-related cognitive impairment in patients with schizophrenia.

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.

BACKGROUND Suboptimal medication adherence is a significant problem for patients with serious mental illness (SMI). Measuring medication adherence through subjective and objective measures can be challenging, time consuming and inaccurate. OBJECTIVE We evaluated a digital medicine system (DMS) compared to treatment as usual (TAU) on adherence to oral aripiprazole and patient and provider perspectives on the feasibility and acceptability of a DMS. 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. Semi-structured interviews with patients and providers were used to examine feasibility and acceptability of using the DMS. RESULTS We enrolled 46 patients across 2 Veterans Affairs (VA) sites: (21 in DMS and 25 in TAU). There was no difference in medication refill over 3 and 6 months, respectively (82% and 75% DMS vs. 86% and 82% TAU). The DMS arm had 85% days covered during the period they were engaged with the DMS (144 days on average). Interviews with patients (n=14) and providers (n=5) elicited themes salient to using the DMS. Patient themes included: pre-enrollment adherence strategies and interest in the DMS, positive impact on medication adherence, system usability challenges, support needs, and suggested design/functionality improvements. Provider themes included: concerns for patient medication adherence and interest in the DMS, concerns with the DMS, DMS dashboard usability, challenges of the DMS, and suggestions to increase provider use. CONCLUSIONS There was no observed difference in refill rates. Among those who engaged in the DMS arm, refill rates were relatively high (85%). The qualitative analyses highlighted areas for further refinement of the DMS. CLINICALTRIAL NCT03881449

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

ImportanceAs patients with schizophrenia or schizoaffective disorder have a high risk of suicide, and a history of suicide attempt is a strong predictor of suicide, determining whether history of suicide attempt is associated with COVID-19 in patients with schizophrenia or schizoaffective disorder has implications for suicide prevention in this patient population.ObjectiveTo determine whether a history of suicide attempt is associated with COVID-19 in Veterans with schizophrenia or schizoaffective disorder.DesignCross-sectional analyses of nation-wide electronic health records (EHR).SettingUnited States Veterans Health Administration.ParticipantsVeterans with a diagnosis of schizophrenia or schizoaffective disorder that received treatment at any United States Veterans Affairs Medical Center from January 1, 2020 to January 31, 2021.ExposureHistory of suicide attempt.Main OutcomeAdjusted and unadjusted odds ratios (ORs) for COVID-19 positivity in suicide attempters relative to non-attempters. Adjusted analyses included age, sex, race, marital status, BMI, and a medical comorbidity score.ResultsA 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. There was effect modification by age and BMI in the association of history of suicide attempt with COVID-19 positivity such that the association was only significant in obese (BMI ≥ 30) patients and patients younger than 59 years respectively. In the entire sample, the unadjusted OR for COVID-19 positivity in attempters was 1.42 (95% CI 0.97 to 2.10) and the adjusted odds ratio was 1.90 (95% CI 1.28 to 2.80). In patients younger than 59 years, and in the obese patients respectively, history of suicide attempt was associated with COVID-positive status in unadjusted analyses [OR 3.53 (95% CI 2.10 to 5.94); OR 2.22 (95% CI 1.29 to 3.81)] and adjusted analyses [OR 3.42 (95% CI 2.02 to 5.79); OR 2.85 (95% CI 1.65 to 4.94)].Conclusions and RelevanceYoung or obese suicide attempters with a diagnosis of schizophrenia or schizoaffective disorders have higher rates of COVID-19 diagnosis; due to possible long-term neuropsychiatric sequelae of infection with SARS-CoV-2, such patients should be monitored closely.

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.

OBJECTIVE: The use of synthetic cannabinoid (SC) products has become popular in recent years, but data regarding their impact on hospital stays are limited. The impact of SC and cannabis use on hospital length of stay and doses of antipsychotics at discharge was assessed in this study. METHOD: The sample consisted of inpatients with discharge diagnoses of bipolar disorder, schizophrenia, or other psychotic disorders. Medical records of patients with self-reported SC use and negative urine drug screens (SC group, n = 77), with cannabis use confirmed by urine drug screen (cannabis group, n = 248), and with no drug use confirmed by urine drug screen (no-drug group, n = 1,336) were examined retrospectively. RESULTS: Length of stay (mean [SD] days) significantly differed (p < .001) among the SC (8.29 [4.29]), cannabis (8.02 [5.21]), and no-drug groups (10.19 [9.08]). Antipsychotic doses (chlorpromazine milligram equivalent doses) also significantly differed (p = .002) among the SC (254.64 [253.63]), cannabis (219.16 [216.71]), and no-drug groups (294.79 [287.85]). Unadjusted and adjusted pairwise comparisons showed that the cannabis group had a shorter length of stay (p < .001) and received lower doses of antipsychotics (p = .003) than the no-drug group. SC users did not differ significantly from the other two groups in either length of stay or doses of antipsychotics. CONCLUSIONS: Our findings suggest that acute SC exposure is not predictive of a more prolonged time for response to antipsychotic medications or of a need for larger doses of these medications compared with cannabis users.

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. Summary 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.

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).

U.S. Hispanics, now the single largest minority group in the country, face unique mental health disparities. The current study utilizes Andersen's Behavioral Model of Health Service Use to examine ethnic disparities in receiving a schizophrenia or mood disorder diagnosis at psychiatric hospital admission. Our retrospective cohort study examined electronic health record data at an academic safety-net psychiatric hospital for adult patients (n = 5571) admitted between 2010 and 2013. Logistic regression with block-wise entry of predisposing, enabling and need variables was used to examine ethnic disparities in receiving a schizophrenia diagnosis at admission. The block of need factors was the strongest predictor of receiving a schizophrenia diagnosis compared to predisposing and enabling factors. Compared to non-Hispanic whites, Hispanics and African Americans had a greater likelihood of receiving a schizophrenia diagnosis at admission. Additionally, patients diagnosed with schizophrenia had elevated positive and negative symptoms and were more likely to be male, single/unmarried, homeless, high inpatient service utilizers, involuntarily hospitalized, and to exhibit functional impairment at psychiatric hospital admission. To address elevated positive and negative symptoms of schizophrenia, functional impairment, social withdrawal, and high inpatient service utilization, promising psychosocial interventions should be adapted for racial and ethnic minority populations and utilized as an adjuvant to antipsychotic medication.

Background: Vitamin D deficiency and immune dysregulation are reciprocally linked In turn, associations between Vitamin D deficiency and the course of several infections, including influenza, as well as certain cancers and metabolic conditions have been previously reported African-Americans are known to have a higher prevalence of Vitamin D deficiency than Caucasians We are now analyzing racial differences in 25-OH-D deficiency in US Veterans, who have a more homogeneous access to laboratory testing and Vitamin D supplementation than the general population Methods: The study is based on analysis of electronic medical records In a sample of 2,399,411 Veterans [age (SD)= 62 2(15)} who had at least one blood 25-OH-D result during FY2001-FY2014, the lowest level was seasonally adjusted and analyzed Odds of having a seasonally adjusted blood level of 25-OH-D level

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.

ObjectiveSeveral 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 trypt

Background Several epidemiological studies have found that the prevalence of bipolar disorder (BD) is significantly higher in obese population than non-obese population. However, no meta-analysis has been published to quantitatively summarize the related literature. Methods In this study, we conducted a meta-analysis to explore the association between obesity and BD by combining 9 cross-sectional studies with a total of 12,259 BD cases and 615,490 non-BD controls. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled odds ratio (OR), while the heterogeneity was assessed using I2 and Q statistic. Results Our meta-analysis suggests that obesity is associated with increased prevalence of BD by a random-effect model (OR=1.77, 95% CI: 1.40–2.23; Q=44.62, P Limitation Without prospective studies, we cannot determine whether obesity increased the risk of developing BD or vice-versa. Conclusion Obesity is positively associated with BD.

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

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.

Peripheral and CNS-localized inflammatory processes are hypothesized to contribute to the complex pathophysiology of schizophrenia. Elevated levels of the acute phase reactant C-reactive protein (CRP) have been observed in schizophrenia, yet relatively few studies have investigated the association between this inflammatory biomarker and psychotic symptoms in schizophrenia. This study is a pilot cross-sectional analysis investigating the relation of plasma CRP levels and the positive and negative symptoms of schizophrenia (the primary aim), assessed by the Positive and Negative Syndrome Scale (PANSS). A secondary analysis was also performed evaluating the potential association of CRP with cognitive function using the NIH Toolbox Cognitive Test Battery. After adjusting for age, sex, race, and body mass index, a positive correlation was observed between CRP and PANSS negative symptoms (rho = 0.37, p = 0.05). There was no correlation between plasma CRP and any of the NIH Toolbox measures of cognitive function in the unadjusted or adjusted analyses. Though limited by a relatively small sample size and the unavailability of longitudinal data, the correlation between CRP and psychopathology in this sample of patients supports a role for inflammation in the pathophysiology of schizophrenia.

Neurodegenerative processes may be involved in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF), the most widely distributed neurotrophin and oxidative stress (OS) may be critical for several pathological manifestations of neurodegenerative disorders. Accumulating evidence suggests that both BDNF and OS may be involved in the pathophysiology of schizophrenia. However, the possible interaction between BDNF and OS has been under-investigated. Serum BDNF, plasma malondialdehyde (MDA) levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were analyzed using established procedures in 164 chronic medicated schizophrenia and 50 healthy controls. Schizophrenic symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) with cognitive and depressive factors derived from the five factor model of the PANSS. Compared to the control group, the patients exhibited a significant decrease in BDNF levels, in the activities of SOD and GSH-Px but a significant increase in MDA levels. In patients, but not in controls, we observed a significant negative correlation between BDNF and SOD. Furthermore, the interaction between BDNF and CAT was associated with the PANSS cognitive factor, and the interaction between BDNF and GSH-Px with the PANSS depressive factor. Both decreased BDNF levels and OS may be implicated in the pathophysiology of chronic schizophrenia. Their inverse association only in the schizophrenia group may reflect a pathological mechanism involving an interaction of oxidative damage and neurotrophin dysfunction. Moreover, OS may interact with the BDNF system to influence the clinical symptoms and cognitive impairment in schizophrenia, which is line with the neurodevelopmental hypothesis of schizophrenia.

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 (β = 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.

Synthetic cannabinoid products have become popular and have led to an increased number of patients presenting to emergency departments and psychiatric hospitals. The purpose of this study was to evaluate the impact of synthetic cannabinoid use at admission on length of stay and doses of antipsychotics at discharge in individuals with bipolar disorder, schizophrenia and other psychotic disorders. We retrospectively examined medical records of 324 inpatients admitted from January 2014 to July 2015. We found that synthetic cannabinoid use predicted length of stay and antipsychotic dose using structural equation modeling. Further, the association of synthetic cannabinoid use with length of stay was partly mediated by antipsychotic dose. These associations were independent of specific diagnosis. In conclusion, patients with bipolar disorder, schizophrenia, or other psychotic disorders who reported synthetic cannabinoid use at admission had shorter length of stay and received lower doses of antipsychotics, irrespective of clinical diagnoses.

Objectives: Brain maturation differs depending on the area of the brain and sex. Girls show an earlier peak in maturation of the prefrontal cortex. Although differences between adult females and males with schizophrenia have been widely studied, there has been less research in girls and boys with psychosis. The purpose of this study was to examine differences in verbal and visual memory, verbal working memory, auditory attention, processing speed, and cognitive flexibility between boys and girls. Methods: We compared a group of 80 boys and girls with first-episode psychosis to a group of controls. Results: We found interactions between group and sex in verbal working memory (p = 0.04) and auditory attention (p = 0.01). The female controls showed better working memory (p = 0.01) and auditory attention (p = 0.001) than males. However, we did not find any sex differences in working memory (p = 0.91) or auditory attention (p = 0.93) in the psychosis group. Conclusions: These results are consistent with the presence of sex-modulated cognitive profiles at first presentation of early-onset psychosis.

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.

There is a dearth of information on the association of atopy with schizophrenia. The few available studies used population-based registers to classify the atopy status of the patients but this strategy is not reliable. This study measured seropositivity with a multiallergen screen of allergen specific IgE antibodies in schizophrenia patients versus healthy controls. A subset of 66 schizophrenia patients and 34 healthy controls were randomly selected from a large comparative study of schizophrenia patients and controls. The Phadiatop multi-allergen screen was performed on sera from all the participants to assess their atopic status. Logistic regression was used to calculate the odds ratio for the association of schizophrenia with Phadiatop seropositivity as a measure of atopy. The prevalence of Phadiatop seropositivity was significantly lower (χ2 4.59, p = 0.032) and there was a reduced odds ratio for atopy in schizophrenia patients relative to controls (OR 0.40; 95% CI 0.17 to 0.94, p = 0.036). Though limited by a relatively small sample size and potentially confounded by anti-psychotic medications, this study suggests that the prevalence of atopy is lower in patients with schizophrenia. Replicating these results in larger samples could add to our growing understanding of immunological implications in mental illness.

Immune dysfunction has been implicated in the pathophysiology of schizophrenia. Leukocyte migration to the site of inflammation is a fundamental step of immune response which involves P-, E-, and L-selectins. Elevated selectin levels have been reported in un-medicated first-episode patients with schizophrenia but not in medicated patients with multi-episode schizophrenia. We measured fasting plasma soluble P-, E-, and L-selectin in 39 medicated patients with multi-episode schizophrenia and 19 healthy controls. In patients, psychotic symptom severity and cognitive function were assessed with the Positive and Negative Syndrome Scale (PANSS) and the NIH Toolbox Cognitive Test Battery respectively. C-reactive protein (CRP) and Body Mass Index (BMI) were measured in patients and controls. Comparison of selectin levels between patients and controls was done with t-tests and linear regression. Pearson correlation coefficients between plasma selectins and PANSS and cognitive measures were calculated. Geometric mean plasma soluble L-selectin level was lower in patients compared to controls from unadjusted (606.7 ± 1.2 ng/ml vs. 937.7 ± 1.15 ng/ml, p < 0.001) and adjusted analyses (β = 0.59; CI 0.41 to 0.88, p = 0.011). There was a trend towards higher plasma soluble P-selectin in patients compared to controls (90.4 ± 1.2ng/ml vs. 71.8 ± 1.2ng/ml, p = 0.059) in the unadjusted analysis. There was no association between the selectins and psychotic symptoms or cognitive function in the patients. In addition, the selectins were not significantly associated with CRP or BMI. The limitations of this study include small sample size and unavailability of information on medications and blood cell counts. The potential utility of soluble L-selectin as a biomarker of antipsychotic exposure in patients with schizophrenia and the concomitant change in immune response with the use of antipsychotics should be further evaluated.

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 (β= −0.153, P< 0.01), and with an estimated decline on AVLT ( β= −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.

We aimed to replicate, in a larger sample and in a different geographical location, the previously reported elevation of anti-gliadin IgG antibodies in schizophrenia.A total of 950 adults with schizophrenia (severity assessed by PANSS) and 1000 healthy controls were recruited in the Munich metropolitan area. Anti-gliadin IgG antibodies were analyzed with ELISA. χ(2)-tests and logistic regression were used to analyze the association of schizophrenia with elevated anti-gliadin IgG. A multivariable general linear model was used to compare anti-gliadin IgG levels between patients and controls.The odds ratio of having elevated anti-gliadin IgG antibodies in the schizophrenia group was 2.13 (95% CI 1.57 to 2.91, p0.0001). Mean anti-gliadin IgG levels were higher in schizophrenia patients (0.81 ± 0.79 vs. 0.52 ± 0.56, t = 9.529, df = 1,697, p0.0001) and the difference persisted after adjusting for potential confounders.Our study, limited by its cross sectional design, confirmed an association between anti-gliadin IgG antibodies and schizophrenia. Replication in longitudinal studies, clinical trials of gluten free diet and mechanistic investigation could lead to novel treatment targets, preventive and therapeutic considerations in schizophrenia.

The goal of this review was to consolidate the evidence concerning the efficacy of botulinum toxin type A (onabotulinumtoxinA) in depression.We searched MEDLINE, EMBASE, Cochrane, and Scopus through May 5, 2014, for studies evaluating the efficacy of botulinum toxin A in depression. Only randomized controlled trials were included in the meta-analysis. A pooled mean difference in primary depression score, and pooled odds ratio for response and remission rate with 95% confidence interval (CI) were estimated using the random-effects model. Heterogeneity was assessed using Cochran Q test and χ statistic.Of the 639 articles that were initially retrieved, 5 studies enrolling 194 subjects (age 49±9.6 y) were included in the systematic review, and 3 randomized controlled trials enrolling 134 subjects were included in the meta-analysis. The meta-analysis showed a significant decrease in mean primary depression scores among patients who received botulinum toxin A compared with placebo (-9.80; 95% CI, -12.90 to -6.69) with modest heterogeneity between the studies (Cochran Q test, χ=70). Response and remission rates were 8.3 and 4.6 times higher, respectively, among patients receiving botulinum toxin A compared with placebo, with no heterogeneity between the studies. The 2 studies excluded from the meta-analysis also found a significant decrease in primary depression scores in patients after receiving botulinum toxin A. A few subjects had minor side effects, which were similar between the groups receiving botulinum toxin and those receiving placebo.This study suggests that botulinum toxin A can produce significant improvement in depressive symptoms and is a safe adjunctive treatment for patients receiving pharmacotherapy for depression. Future trials are needed to evaluate the antidepressant effect per se of botulinum toxin A and to further elucidate the underlying antidepressant mechanism of botulinum toxin A.

Background The relationship between Toxoplasma gondii infection and the development of bipolar disorder (BD) has long been investigated, yet to date it is still poorly understood and documented. The aim of this review is to derive a summary estimate of the strength of the association between infection with T. gondii and BD from the available published studies. Methods A systematic review was performed using PubMed, LILACS, PsycINFO, and Embase databases. Studies which included a proportion of seropositive BD patients and controls were further examined in a meta-analysis. Results One hundred eighteen citations were initially retrieved. Thirteen studies were included in our systematic review. Eight out of these thirteen studies were included in our meta-analysis. Statistical analyses showed that T. gondii infection is associated with with BD (OR=1.26). Limitations Small sample size was the major limitation among the studies that carried out serological analyses. In addition, the available studies did not have enough information on disease status/severity or type of bipolar disorder. Also, it was not possible to analyze pregnancy status or perinatal infection. Future studies addressing the aforementioned topics are clearly needed. Conclusions Despite heterogeneous results, patients with BD are more likely to be infected by T. gondii than controls. Early T. gondii infection might predispose the development of BD. T.gondii infection is becoming clinically relevant in psychiatric disorders and future mechanistic studies are required to elucidate the underlying pathophysiological mechanisms.

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

A seasonal suicide peak in spring is highly replicated, but its specific cause is unknown. We reviewed the literature on suicide risk factors which can be associated with seasonal variation of suicide rates, assessing published articles from 1979 to 2011. Such risk factors include environmental determinants, including physical, chemical, and biological factors. We also summarized the influence of potential demographic and clinical characteristics such as age, gender, month of birth, socioeconomic status, methods of prior suicide attempt, and comorbid psychiatric and medical diseases. Comprehensive evaluation of risk factors which could be linked to the seasonal variation in suicide is important, not only to identify the major driving force for the seasonality of suicide, but also could lead to better suicide prevention in general.

Toxoplasma gondii (T. gondii) a widespread neurotropic parasite, has been previously associated with schizophrenia and more recently with suicidal behavior. However, no previous study has examined the association of T. gondii with suicidal behavior in schizophrenia patients. 950 individuals diagnosed with schizophrenia by SCID were recruited from the Munich area of Germany. Solid-enzyme immunoassay methods were used to measure IgG plasma antibodies to T. gondii, other neurotropic pathogens and gliadin. Logistic regression models were developed to analyze the association of T. gondii seropositivity or serointensity with history of suicidal behavior. In those younger than the median age of the sample, 38, T. gondii serointensity was associated with history of suicidal behavior (p = 0.02), while in the older patients the relationship was not significant (p = 0.21). Seropositivity was also associated with history of suicide attempt in younger patients, odds ratio 1.59 (95% CI 1.06 to 2.40), p = 0.03. Seropositivity for CMV (p = 0.22), HSV-1 (p = 0.36) and gliadin (p = 0.92) was not related to history of suicide attempt in the entire sample or any age subgroup. T. gondii serology might become, with interaction with vulnerability genes, a candidate biomarker for a subgroup of schizophrenia patients prone to attempting suicide.

Mrs. M is a 30-year-old, married, African-American woman with no prior history of mental illness who was initially admitted to a general hospital due to changes in behavior. Mrs. M’s husband reported that during the 2 days prior to her admission, she seemed to have difficulty paying attention and registering information; she would sometimes talk excessively and at other times would stare blankly and not engage in any conversation with her husband. She also experienced insomnia and was intermittently restless. When she initially arrived at the general hospital, she was agitated and was given a one-time dose of ziprasidone 20 mg orally to calm her down. While at the general hospital, the patient was also selectively mute. The initial medical work-up in