Are cytokine profiles associated with the cognitive performance of adults with severe major depression?

Cognitive impairment often occurs in major depressive disorder (MDD). Studies suggest that these cognitive deficits may be associated with inflammatory biomarkers, but data are limited. Therefore, this study aims to investigate the relationship between 48 peripheral blood cytokines and cognitive performance in patients with severe depressive disorder. One hundred consecutive hospitalized adult patients with severe depression who participated in the Depression long-term Augsburg (DELTA) study were included in the present analysis. To test working memory (WM) the Wechsler Adult Intelligence Scale (WAIS) IV and to assess interference control (IC) the Stroop Color and Word Test (SCWT) were performed. The serum concentrations of the biomarkers were measured using the Bio-Plex Pro™ Human Cytokine Screening Panel 1. Multiple linear regression models adjusted for possible confounders were fitted to examine associations. WM was impaired in 11% of the patients. IC was impaired in 1%-3% of the cases depending on the subtest. Eotaxin, IL-1ß, IL-4, MCP-1, G-CSF, and PGF-BB were negatively associated with the WM. Eotaxin, IL-1ß, IL-4, IL-16, IL-18, MCP-1, G-CSF, SCF, and MIP-1α were negatively associated with IC. None of these associations remained significant after adjustment for multiple testing. The present study identified eotaxin, IL-1ß, IL-4, IL-16, IL-18, MCP-1, G-CSF, SCF, PGF-BB and MIP-1α as being associated with cognitive performance. After confirmation of these results in further studies, these cytokines may be potential targets for new treatments.

Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection.

Studies on cognitive problems of persons with mild COVID-19 courses are still lacking. This study aimed to determine the frequency and associated factors of subjective and objective cognitive problems after COVID-19 in non-hospitalized persons. Study participants were examined at the University Hospital of Augsburg from 04/11/2020 to 26/05/2021. The Wechsler Adult Intelligence Scale (WAIS) IV digit span, Stroop Color and Word Test (SCWT), Regensburger verbal fluency test (RWT) and, subjective ratings of memory and concentration were applied. Of the 372 participants (mean age 46.8 ± 15.2 years, 54.3% women, median time after infection 9.1 months), 24.9% reported concentration and 21.9% memory problems. Overall, 55.6% of the participants had at least a mild negative alteration in any cognitive test. The strongest impairments were found regarding memory functions (41.1% mild alterations, 6.2% distinct impairments) and verbal fluency (12.4% mild alterations, 5.4% distinct impairments). SCWT showed negative alterations in no more than 3.0% of the participants. Level of school education, age, and depressiveness emerged as significantly related to the cognitive tests. The number of complaints and depressiveness were significantly associated with subjective memory and concentration problems. It is important to identify mild cognitive impairment in non-hospitalized COVID-19 patients early to offer them effective interventions.

Serial Analysis of Gene Mutations and Gene Expression during First-Line Chemotherapy against Metastatic Colorectal Cancer: Identification of Potentially Actionable Targets within the Multicenter Prospective Biomarker Study REVEAL.

Most metastatic colorectal cancer (mCRC) patients succumb to refractory disease due to secondary chemotherapy resistance. To elucidate the molecular changes associated with secondary resistance, we recruited 64 patients with mCRC and hepatic metastases before standard first-line chemotherapy between 2014 and 2018. We subjected DNA from primary tumor specimens (P), hepatic metastasis specimens after treatment (M), and liquid biopsies (L) taken prior to (pre), during (intra), and after (post) treatment to next generation sequencing. We performed Nanostring expression analysis in P and M specimens. Comparative bioinformatics and statistical analysis revealed typical mutational patterns with frequent alterations in TP53, APC, and KRAS in P specimens (n = 48). P and pre-L (n = 42), as well as matched P and M (n = 30), displayed a similar mutation spectrum. In contrast, gene expression profiles classified P (n = 31) and M (n = 23), distinguishable by up-regulation of immune/cytokine receptor and autophagy programs. Switching of consensus molecular subtypes from P to M occurred in 58.3% of cases. M signature genes SFRP2 and SPP1 associated with inferior survival, as validated in an independent cohort. Molecular changes during first-line treatment were detectable by expression profiling rather than by mutational tumor and liquid biopsy analyses. SFRP2 and SPP1 may serve as biomarkers and/or actionable targets.