Purpose: This meta-analysis provides a longitudinal assessment of depression and cognitive impairment induced by taxane-based chemotherapy in women with breast cancer after 6 months of treatment. We highlighted the incidence and prevalence, the cognitive pattern in neuropsychological studies, and the relationship between chemotherapy-induced cognitive impairment and different risk factors. We estimated the effect sizes on each cognitive domain and differentiated effect sizes by each method of comparison of effects (i.e., baseline data, or control groups).Methods: The databases MEDLINE and Embase were searched for publications about taxane-related cognitive changes in patients with breast cancer published from 1980 to 2019. Cross-sectional and self-reported outcomes studies were excluded except for the depression item. Included studies were assessed for risk of bias with the Newcastle–Ottawa Scale. We estimated effect sizes for each cognitive domain and differentiated effect sizes by each method of comparison of effects. The review is reported in compliance with the PRISMA Statement; it was registered prospectively in PROSPERO as CRD42020163255.Results: Eleven studies meeting the criteria were analyzed, which resulted in a sample of 1,057 patients with breast cancer who received chemotherapy including 820 patients (77%) who received taxane-based chemotherapy. Attention and concentration, depression, and executive function domains had significant chemotherapy-induced impairment across all comparison types. Statistically significant improvement was found in language and verbal memory when comparing chemotherapy patients' test scores with baseline or matched controls. Taxane-based chemotherapy had a non-significant effect on processing speed, visual memory, visuospatial, and motor function domains.Conclusions: The occurrence of chemotherapy-induced cognitive impairment 6 months or more after the course of treatment in people with breast cancer is frequent in the domains of attention, executive function, and depression. Other domains appear stable or improve with time after treatment cessation.

The COVID-19 pandemic is a public health emergency. As we write, the world counts more than 10 million positive cases and more than 500 thousand deaths. The difficult conditions faced by healthcare workers helping with the COVID-19 pandemic are leading to severe adverse mental health consequences.The aim of this review is to summarize and analyze the mental health issues that healthcare workers are experiencing during the COVID-19 outbreak. We conduct a systematic literature review to investigate the healthcare workforce’s mental health disorders. About 145 articles were retrieved for the period between January 1, 2020 and April 30, 2020. After screening, 27 articles were selected for full-text examination, 13 were included in the review. Of the studies included, 69% (9/13) and 61% (8/13) investigated depression and anxiety, respectively, although other mental health disorders such as insomnia, distress, stress, and fear were also assessed. Most of the healthcare workers in the studies reported high levels of stress, anxiety, and severe symptoms of depressions.Caregivers are working under high levels of pressure, in a high-risk environment, and are dealing with many physical and psychological challenges. Appropriate actions and well-timed psychological support to protect medical workers’ mental health should be considered.

Dramatic improvements in cancer survival have occurred in the last decade, but the quality of life for many survivors is compromised due to severe, long-lasting, and often irreversible side effects of chemotherapy. The neurological side effects, chemotherapy induced peripheral neuropathy (CIPN) and cancer related/induced cognitive impairment (CRCI/CICI), are under-recognized and can occur after chemotherapy, immunotherapy, or radiation. The cellular mechanisms underlying these neurological side effects are poorly understood and there are no effective treatments or preventions, other than reduction or termination of cancer therapy. In our preliminary prospective, non-interventional study to examine the side effects of chemotherapy in patients with breast cancer (NCT03872141), patients with breast cancer who received standard of care single agent weekly taxane-based chemotherapy were assessed at baseline, midpoint, and end of treatment for neurological and cognitive changes and for blood levels of potential protein biomarkers (n = 13). CIPN and CRCI both showed an increase in severity with accumulating taxane and these changes were compared to protein alternations over the course of treatment. Using peripheral blood collected from patients (n = 10) during chemotherapy and tested with an antibody array curated by the MD Anderson RPPA Core), we found that 19 proteins were increased, and 12 proteins decreased over 12 weeks of treatment. Among those downregulate were proteins known to be critical for neuronal viability and function including GRB2 (growth factor receptor-bound protein 2) and NCS1 (neuronal calcium sensor 1). Concurrently, proteins associated with apoptosis, including BAK1 (Bcl-1 homologous antagonist/killer), were upregulated. These results support the proposal that CIPN and CRCI increase with increasing taxane exposure, and identified several proteins that are altered with taxane exposure that could be implicated in their pathogenesis. In conclusion, our study provides evidence for progressive neurological changes and the rationale to investigate the molecular basis for these changes with the goal of target identification for mitigation of these neurological side effects.

Wolfram Syndrome is a rare autosomal recessive disease characterized by early-onset diabetes mellitus, neurodegeneration, and psychological disorders. Mutations in the gene WFS1, coding for the protein wolframin, cause Wolfram Syndrome and are associated with bipolar disorder and schizophrenia. This report aims to connect WFS1 mutations to their impact on protein expression and structure, which ultimately translates to altered cell function and behavioral alterations of an individual.Methods: Published data were used to compile WFS1 mutations associated with psychiatric symptoms, both in homozygous patients and heterozygous carriers of WFS1 mutations. These mutations were evaluated in silico using SNAP2, PolyPhen-2, and PROVEAN to predict the effects of sequence variants. Statistical analysis was performed to assess the correlation between the locations of the mutations and the damage prediction scores.Results: Several mutations, clustering in the center and C-terminus of the WFS1 polypeptide, such as A559T and R558C, are found in individuals with psychiatric diseases and appear particularly impactful on protein structure. Our analysis showed that mutations in all regions of wolframin were present in patients with schizophrenia whereas only cytoplasmic and ER luminal mutations were reported in patients with manic episodes and bipolar disorders. According to Poly-Phen-2 predictions, 82.4% of the ER lumen mutations and 85.7% of the membrane mutations are damaging.Conclusion: We propose mood disorders in Wolfram Syndrome and heterozygous carriers of WFS1 mutations are the consequence of specific mutations in WFS1 that alter the structure of wolframin, resulting in intracellular calcium dysregulations and impaired cell signaling, Understanding the effect of WFS1 mutations on bipolar disorder and schizoprenia is integral to designing clinically targeted treatments for both diseases, which need more specialized treatments.