Clinical characteristics of cognitive deficits in major depressive disorder: a 6-month prospective study

Background: Previous studies have shown that major depressive disorder (MDD) is associated with a variety of cognitive deficits, which can persist even in remitted states. Nevertheless, the relationship between the cognitive and affective symptoms in depression remains obscure. The aim of the present study was to explore the clinical characteristics and correlates of the cognitive deficits in patients with MDD. Methods: Clinical and neuropsychological assessments were conducted at baseline and 6-month follow-ups. The severity of the disease and the effect of treatment were assessed with the Hamilton Depression Scale-17. Neuropsychological tests, including the digital symbol substitution test and digit span test, were administered to 67 depressed patients and 56 healthy participants. Results: MDD patients showed impairments in memory, attention, and executive function at baseline. After the 6-month treatment phase, patients in remission showed significant alleviation of these cognitive deficits, although impairments in attention and executive function were still present when compared to controls. Discussion: Significant cognitive deficits are present in MDD. The speed of remission of cognitive functions seems to be slower than and inconsistent with emotional symptoms, which provides new support for the argument that cognitive deficits are independent factors from the emotional symptoms in MDD

Psychometric property study of the Affective Lability Scale-short form in Chinese patients with mood disorders

IntroductionThis study aimed to investigate the psychometric properties of the Affective Lability Scale-short form (ALS-SF) among Chinese patients with mood disorders, and to compare ALS-SF subscale scores between patients with major depressive disorder (MDD) and patients with bipolar disorder (BD) depression.MethodsA total of 344 patients with mood disorders were included in our study. Participants were measured through a set of questionnaires including the Chinese version of ALS-SF, Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-item (GAD-7), and NEO-Five Factor Inventory (NEO-FFI). Exploratory factor analysis and confirmatory factor analysis were applied to examine the psychometric properties of ALS-SF. Besides, correlation and regression analyses were performed to explore the relationship between affective lability and depression, anxiety, and neuroticism. Independent samples t-tests were used to compare the subscale scores of ALS-SF between the MDD and BD depression groups.ResultsResults of factor analysis indicated that the model of ALS-SF was consistent with ALS-SF. The ALS-SF showed a solid validity and high internal consistency (Cronbach’s alpha = 0.861). In addition, each subscale of ALS-SF was significantly correlated with PHQ-9, GAD-7, and NEO-FFI neuroticism subscale, except for the anger subscale showed no significant correlation with PHQ-9. Besides, the depression/elation and anger factor scores in patients with BD depression were higher than in patients with MDD.ConclusionOur study suggests that the Chinese version of ALS-SF has good reliability and validity for measuring affective lability in Chinese patients with mood disorders. Assessing affective lability would assist clinicians to distinguish between MDD and BP depression and may decrease the risks of misdiagnosis

Structural and Lipidomic Alterations of Striatal Myelin in 16p11.2 Deletion Mouse Model of Autism Spectrum Disorder

Myelin abnormalities have been observed in autism spectrum disorder (ASD). In this study, we seek to discover myelin-related changes in the striatum, a key brain region responsible for core ASD features, using the 16p11.2 deletion (16p11.2±) mouse model of ASD. We found downregulated expression of multiple myelin genes and decreased myelin thickness in the striatum of 16p11.2± mice versus wild type controls. Moreover, given that myelin is the main reservoir of brain lipids and that increasing evidence has linked dysregulation of lipid metabolism to ASD, we performed lipidomic analysis and discovered decreased levels of certain species of sphingomyelin, hexosyl ceramide and their common precursor, ceramide, in 16p11.2± striatum, all of which are major myelin components. We further identified lack of ceramide synthase 2 as the possible reason behind the decrease in these lipid species. Taken together, our data suggest a role for myelin and myelin lipids in ASD development

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies

Molecular characterization and clinical relevance of metabolic expression subtypes in human cancers.

Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently correlated with worse prognosis, whereas subtypes with upregulated lipid metabolism showed the opposite. Metabolic subtypes correlated with diverse somatic drivers but exhibited effects convergent on cancer hallmark pathways and were modulated by highly recurrent master regulators across cancer types. As a proof-of-concept example, we demonstrated that knockdown of SNAI1 or RUNX1—master regulators of carbohydrate metabolic subtypes-modulates metabolic activity and drug sensitivity. Our study provides a system-level view of metabolic heterogeneity within and across cancer types and identifies pathway cross-talk, suggesting related prognostic, therapeutic, and predictive utility

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Influence of comorbid anxiety symptoms on cognitive deficits in patients with major depressive disorder

Background: Major depressive disorder (MDD) patients with comorbid anxiety symptoms showed obvious cognitive deficits. However, it remains unclear whether comorbid anxiety symptoms will make a specific contribution to cognitive deficits in MDD. Methods: Executive function, processing speed, attention and memory were assessed in 162 MDD patients, and 142 healthy controls (HCs) by a comprehensive neuropsychological battery. 14-item Hamilton Anxiety Rating Scale (HAM-A) was used for anxiety symptoms and MDD patients with HAM-A total score >14 were classified into MDD with comorbid anxiety (MDDA) group. A multivariate analysis of covariance and regression models was conducted to evaluate the effects of anxiety symptoms on cognitive deficits. Results: There were no significantly differences in all 4 cognitive domains between MDD alone and MDDA patients (all p < 0.05). In MDDA subgroup, HAM-A total score contributed to executive function and memory (both p < 0.05), while HAM-A psychic symptoms contributed to all 4 domains (all p < 0.05). Moreover, after controlling for the severity of depression, either anxiety symptoms shown as HAMA total score or psychic anxiety symptoms only contributed significantly to the executive function performance. Limitations: The cross-sectional design made it hard to acquire a cognitive performance trajectory accompanied by the fluctuations in anxiety symptoms. Conclusion: Our findings suggest that there is no significant difference in cognitive performance between MDD alone and MDDA patients. However, comorbid anxiety, especially psychic anxiety may contribute to extensive cognitive deficits in MDDA patients. Notably, anxiety symptoms only independently triggered executive dysfunction when eliminating effect of the severity of depression

Prevalence and predictors of post-traumatic stress disorder in patients with cured coronavirus disease 2019 (COVID-19) one month post-discharge

Background: Coronavirus disease 2019 (COVID-19) can place an immense psychological strain on the infected patient. The psychological distress can linger after the initial recovery from the infection. Objective: This study aimed to evaluate the prevalence and predictors of provisional post-traumatic stress disorder (PTSD) in patients with cured COVID-2019. Methods: The baseline survey was conducted from 10 to 25 February 2020 in patients with COVID-19 in a designated hospital. Demographic and clinical characteristics were acquired, and depression and anxiety levels were assessed, using the 9-item Patient Health Questionnaire and 7-item Generalized Anxiety Disorder scale, respectively. A follow-up survey was conducted 1 month post-discharge. PTSD symptoms were measured by the Impact of Event Scale-6 (IES-6) and patients’ perception of supportive care during hospitalization was investigated using a self-developed questionnaire. Results: In total, 114 patients completed both the baseline and follow-up surveys. Of these, 41 (36.0%) met the cut-off score for provisional PTSD diagnosis according to the IES-6. Female gender [odds ratio (OR) = 4.69, 95% confidence interval (CI) 1.54–14.37], educational level of high school or below (OR = 15.49, 95% CI 1.13–212.71), higher anxiety levels (OR = 1.34, 95% CI 1.12–1.61) and lower perceptions of emotional support during hospitalization (OR = 0.41, 95% CI 0.17–0.96) predicted a higher risk for provisional PTSD. Conclusions: PTSD is commonly seen in patients with COVID-19 1 month post-discharge. Female patients, and patients with lower educational levels, higher anxiety levels and lower perceptions of emotional support during hospitalization may be more likely to develop PTSD in the near future. Enhancing emotional support during hospitalization could help to prevent PTSD in patients with COVID-19

The effects of childhood trauma on the onset, severity and improvement of depression: The role of dysfunctional attitudes and cortisol levels

Background: Childhood trauma is an important early social risk factor for the development of the major depressive disorder (MDD). Both childhood trauma and depression are associated with dysfunctional attitudes and dysregulation in stress hormones. We aimed to clarify the path from childhood trauma to depression and identify potential predictors of antidepressant treatment outcomes. Objectives: One hundred and thirty-nine MDD patients and 112 healthy controls were included at baseline. Depressive symptoms were assessed with both self-reported and expert-rated scales. Childhood trauma and dysfunctional attitudes were evaluated and blood cortisol levels were assayed. Patients received an open-label antidepressant trial with paroxetine and their depressive symptoms were monitored by the Hamilton Depression Rating Scale (HAMD) during 6 months of treatment. After 6 months, 94 patients received the same assessments as the baseline. Results: At baseline, the influence of childhood trauma on depression diagnosis was mediated by dysfunctional attitudes. In patients with MDD, the influence of childhood trauma on depression severity was mediated by both dysfunctional attitudes and cortisol levels. Baseline childhood trauma predicted the antidepressant treatment outcome during early treatment phase and baseline cortisol levels predicted the antidepressant treatment outcome at later treatment phase. After 6-month antidepressant treatment, a significant remission by time effect was found on dysfunctional attitudes and depression severity but not on cortisol levels. Conclusion: Effect of childhood trauma on depression onset was mediated by dysfunctional attitudes. The relationship between childhood trauma and depressive symptoms was mediated by dysfunctional attitudes and cortisol levels in MDD patients. Baseline childhood trauma and cortisol levels may be moderators for antidepressant treatment response at different treatment phase