Clozapine, neutropenia and Covid-19: should clinicians be concerned? 3 months report.

BACKGROUND: Clozapine is among the most effective antipsychotics used for treatment resistant schizophrenia. Adverse reactions to clozapine include neutropenia. In March 2020, at the start of the Coronavirus -19 pandemic, clinicians raised concerns regarding continuation of antipsychotic treatment, and specifically of clozapine, in patients with coronavirus disease. We aimed here at providing a short report focusing on the association between neutropenia and clozapine in a case series of psychiatric inpatients diagnosed with COVID-19. PATIENTS & METHODS: We retrospectively inspected data of 10 patients on clozapine, admitted to Highgate Mental Health Centre, Camden & Islington NHS Foundation Trust, between March and July 2020; selection was based on their COVID-19 positive PCR test. We used a linear regression model to estimate whether there was a significant drop in the neutrophil count during SARS-CoV-2 infection.The analysis was done in R using a linear regression to the origin. RESULTS: Data were collected on 10 patients, of which 7 were males. During COVID-19 infection, neutrophils' count (ANC) was 4.13 â€‹× â€‹109/l (SD â€‹= â€‹2.70) which constituted a significant drop from a baseline value of 5.2 â€‹× â€‹109/l (SD â€‹= â€‹2.24). The mean relative reduction in ANC was -0.2729 (SD â€‹= â€‹0.1666). The beta value of 0.8377 obtained with the linear regression showed that ANC values during SARS-CoV-2 infection were 83.77% of the baseline ANC showing that within the two time points there was a decrease of 16.23%. The linear regression had a pvalue â€‹= â€‹8.96 â€‹× â€‹10-8 and an adjusted R2 of 95.94% which shows that the variability of the data is very well explained by the model. We also compared baseline ANC with ANC values approximately a month after resolution of the infection and results indicate that ANC values return to a 95% of baseline. CONCLUSIONS: Clinicians should bear in mind that a significant drop in neutrophils' count may occur in patients taking clozapine and affected from a SARS-CoV-2 infectionand that this drop is only transitory.

Inflammation in Mental Disorders: Is the Microbiota the Missing Link?

Research suggests that inflammation is important in the pathophysiology of mental disorders. In addition, a growing body of evidence has led to the concept of the microbiota-gut-brain axis. To understand the potential interactions, we begin by exploring the liaison between the immune system and mental disorders, then we describe the evidence that the microbiota impact the immune response in the developing brain. Next, we review the literature that has documented microbiome alterations in major mental disorders. We end with a summary of therapeutic applications, ranging from psycho-biotics to immunomodulatory drugs that could affect the microbiota-gut-brain axis, and potential treatments to alleviate the adverse effects of antipsychotics. We conclude that there is promising evidence to support the position that the microbiota plays an important role in the immunological pathophysiology of mental disorders with an emphasis on psychotic disorders and mood disorders. However, more research is needed to elucidate the mechanisms.

Estudio comparativo sobre las causas de mortalidad entre personas con trastorno bipolar y una muestra control en Costa Rica entre 1995 y 2005 / Comparative study of mortality causes between subjects with bipolar disorder and a control sample between 1995 and 2005

Resumen Justificación: el trastorno afectivo bipolar afecta entre un 1 % y un 2 % de la población mundial. Se ha descrito que se acompaña de un aumento en la mortalidad por causas tanto violentas como no violentas. Existen pocos estudios en el país acerca de las causas de muerte en esta población. Este estudio tiene como objetivo analizar las causas de muerte de personas con trastorno afectivo bipolar y compararlas con las de controles sanos. Métodos: de los sujetos con trastorno afectivo bipolar previamente reclutados para estudios genéticos del Centro de Investigación en Biología Celular y Molecular de la UCR, se seleccionó a las 154 personas que habían fallecido entre 1993 y 2005. Se eligieron 154 controles apareados por sexo, que hubiesen nacido y fallecido en el mismo periodo que el sujeto, con una diferencia no mayor a tres meses. El análisis estadístico consistió en una prueba exacta de Fisher con 1000 simulaciones del valor de p con Monte Carlo. Resultados: de los 154 sujetos, un 50 % (n=77) fueron mujeres. No hubo diferencia en la causa de muerte entre sexos. Se encontró diferencia significativa en las principales causas de muerte entre casos y controles (p<0,05). Se observó una diferencia significativa en las categorías de "lesiones autoinflingidas" (χ2 (1)=11.0, p<0,05) y "cáncer" (χ2(1)= 4,1, p= 0,04). No se documentó diferencia en enfermedad cardiovascular (χ2(1)=0,3, p= 0,61), neumonía (χ2(1)=3,1, p= 0,07) y accidentes (χ2(1)= 2,0, p= 0,16). Conclusión: como se ha documentado en bibliografía internacional, las lesiones autoinfligidas son la causa de muerte de mayor importancia en la población afectada con trastorno afectivo bipolar.

Abstract Background: Bipolar disorder affects 1% to 2% of the world population. It has been described that it is accompanied by an increase in mortality from both violent and non-violent causes. Few studies have been published in our country about causes of death in this particular population. The objective of our study is to analyze the causes of death of subjects with bipolar disorder and compare them to healthy controls. Methods: From the pool of subjects with bipolar disorder previously recruited for genetic studies conducted at the Cellular and Molecular Biology Research Centre of the UCR, we recruited the 154 subjects who had died between 1993 and 2005. Controls of the same sex who were born and died in the same period as the subject, with a difference no greater than three months, were selected. For the statistical analysis we ran a Fisher's exact test with 1000 simulations of the p-value with Monte Carlo. Results: Of 154 subjects, 50% (n=77) were women. We found no difference in the cause of death between sexes among the cases. A significant difference in the main causes of death was found between cases and controls (p<0.05). A significant difference was observed in the categories of "self-inflicted lesions" (χ2 (1)=11.0, p<0.05) and "cancer" (χ2(1)= 4.1, p= 0.04). No difference was documented in cardiovascular disease, (χ2(1)=0.3, p= 0.61), pneumonia (χ2(1)=3.1, p= 0.07) nor accidents (χ2(1)= 2.0, p= 0.16). Conclusion: Self-inflicted lesions, as has been documented in international literature, are a cause of death of major importance in the population affected with bipolar disorder.