Neurocognitive deficits in depression: a systematic review of cognitive impairment in the acute and remitted state

Previous research suggests a broad range of deficits in major depressive disorder. Our goal was to update the current assumptions and investigate the extent of cognitive impairment in depression in the acute and remitted state. A systematic review of the existing literature between 2009 and 2019 assessing the risk of bias within the included studies was performed. Of the 42 articles reviewed, an unclear risk of bias was shown overall. The risk of bias mainly concerned the sample selection, inadequate remedial measures, as well as the lack of blinding the assessors. In the acute phase, we found strong support for impairment in processing speed, learning, and memory. Follow-up studies and direct comparisons revealed less pronounced deficits in remission, however, deficits were still present in attention, learning and memory, and working memory. A positive correlation between the number of episodes and cognitive deficits as well as depression severity and cognitive deficits was reported. The results also demonstrate a resemblance between the cognitive profiles in bipolar disorder and depression. Comparisons of depression with schizophrenia led to unclear results, at times suggesting an overlap in cognitive performance. The main findings support the global deficit hypothesis and align with results from prior meta-analyses and reviews. Recommendations for future research are also presented

Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies

Kindliche Verhaltensauffälligkeiten im ersten Lebensjahr und mütterliche Belastung in der Zeit der COVID-19-Pandemie

Theoretischer Hintergrund: Die COVID-19-Pandemie stellte in vielen Bereichen eine Belastung für Familien dar, insbesondere durch die einschneidenden Beschränkungen zu Beginn. Fragestellung: Wie wirkte sich dies auf die Belastung von Müttern mit Kindern im ersten Lebensjahr und auf die kindliche Verhaltensregulation aus? Methode: In einer Online-Befragung schätzten 577 Mütter das Schrei-‍, Schlaf- und Fütter-/Essverhalten ihrer Kinder (M = 7.3; 0 – 12 Mon., SD = 3.25) und ihre eigene Belastung ein, zudem Stresserleben, depressive Symptomatik, Partnerschaftszufriedenheit und Bonding. Ergebnisse: Schlafprobleme traten bei 21.7 %, schwer tröstbares und häufiges Schreien bei 12.3 % und exzessives Schreien bei 1.6 % der Kinder auf. Mindestens jede fünfte Mutter fühlte sich durch Schreien oder Schlafprobleme belastet. Mehr Stress, beeinträchtigtes Bonding und weniger Partnerschaftszufriedenheit erklärten 17 – 21 % der Varianz der mütterlichen Belastung durch Schrei- und Schlafverhalten. In der Zeit der stärksten Beschränkungen zeigte sich signifikant mehr Belastung in der Gruppe von Müttern, die von vermehrtem Schreien und verlängerter Einschlaflatenz berichteten, sowie mit mindestens einem weiteren Kind im Haushalt (MANOVA). Diskussion und Schlussfolgerung: Pandemiebedingt belastend für Mütter im ersten Jahr scheinen eingeschränkter Zugang zum Versorgungssystem, die Betreuung von mehr als einem Kind sowie das Alter des Kindes zu sein, während eine gute Beziehung zum Kind (Bonding) und/oder zum Partner (Partnerschaftszufriedenheit) abmildernd wirken.Theoretical background: The COVID-19 pandemic placed a burden on families in several respects, particularly because of the severe confinement imposed at its beginning. The confinement in spring 2020 led to social disruption and a reduction of supportive structures. In the first year of an infant’s life, the psychological well-being of a mother–child dyad is particularly susceptible to external stressful changes. Research question: How did the restrictions from the pandemic affect families with children in the first year of the infant’s life, particularly infant regulatory problems and related maternal stress? Methods: In an online survey, N = 577 mothers reported on their infants’ behavior (0 – 12 months of age, M = 7.3 months, SD = 3.3) regarding their crying, sleeping, and feeding/eating behavior as well as the respective distress experienced during the restrictions. Measures of current maternal well-being included overall perceived stress, depressivity, relationship satisfaction, and maternal bonding. Frequency/duration of infantile crying, sleep latency as well as night awakenings and feeding/eating problems were surveyed following clinical criteria (DC: 0 – 5) and percentile scores, respectively. The association of infant behavior and maternal distress was examined using linear regression and MANOVA. Results: Overall, at least one in five mothers felt burdened by her child’s regulatory problems during the time of severe restrictions. More than one in four mothers reported being highly or very highly distressed by her child’s crying. Sleeping problems, such as prolonged sleep latency (> 90th percentile) or several nightly awakenings, were reported for 21.7 % of the children. Difficulty to console and frequent crying were reported for 12.3 % and excessive crying for 1.6 % of the children. Higher levels of stress as well as increased impairment in maternal bonding and less relationship satisfaction explained 17 – 21 % of the variance of maternal distress from crying and sleeping problems. Significantly more distress was evident in the group of mothers who reported increased crying and prolonged latency to fall asleep (> 45 min) and with more than one child in the household during the period of most severe restrictions (MANOVA). A lack of medical, psychotherapeutic, and other means of care was reported by nearly a quarter of the respondents and was the only restriction that was significantly related to the perception of more stressful child behavior. Discussion and conclusion: Pandemic-related stressors for first-year mothers appear to be enhanced by limited access to the care system, caring for more than one child, the increasing age of the child, while a good relationship with the child (bonding) and/or partner (relationship) satisfaction provide buffers

Obesity, metabolic factors and risk of different histological types of lung cancer: A Mendelian randomization study.

BACKGROUND: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. METHODS AND FINDINGS: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79-1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. CONCLUSIONS: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior

Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Neurocognitive Deficits in First-Episode and Chronic Psychotic Disorders: A Systematic Review from 2009 to 2022

Cognitive impairment in patients suffering from schizophrenia spectrum disorders has been discussed as a strong predictor for multiple disease outcome variables, such as response to psychotherapy, stable relationships, employment, and longevity. However, the consistency and severity of cognitive deficits across multiple domains in individuals with first-episode and chronic psychotic disorders is still undetermined. We provide a comprehensive overview of primary research from the years 2009 to 2022. Based on a Cochrane risk assessment, a systematic synthesis of 51 out of 3669 original studies was performed. Impairment of cognitive functioning in patients diagnosed with first-episode psychotic disorders compared with healthy controls was predicted to occur in all assessed cognitive domains. Few overall changes were predicted for chronically affected patients relative to those in the first-episode stage, in line with previous longitudinal studies. Our research outcomes support the hypothesis of a global decrease in cognitive functioning in patients diagnosed with psychotic disorders, i.e., the occurrence of cognitive deficits in multiple cognitive domains including executive functioning, memory, working memory, psychomotor speed, and attention. Only mild increases in the frequency of cognitive impairment across studies were observed at the chronically affected stage relative to the first-episode stage. Our results confirm and extend the outcomes from prior reviews and meta-analyses. Recommendations for psychotherapeutic interventions are provided, considering the broad cognitive impairment already observed at the stage of the first episode. Based on the risk of bias assessment, we also make specific suggestions concerning the quality of future original studies