Although the early antidepressant trials which included severely ill and hospitalized patients showed substantial drug‐placebo differences, these robust differences have not held up in the trials of ...the past couple of decades, whether sponsored by pharmaceutical companies or non‐profit agencies. This narrowing of the drug‐placebo difference has been attributed to a number of changes in the conduct of clinical trials. First, the advent of DSM‐III and the broadening of the definition of major depression have led to the inclusion of mildly to moderately ill patients into antidepressant trials. These patients may experience a smaller magnitude of antidepressant‐placebo differences. Second, drug development regulators, such as the U.S. Food and Drug Administration and the European Medicines Agency, have had a significant, albeit underappreciated, role in determining how modern antidepressant clinical trials are designed and conducted. Their concerns about possible false positive results have led to trial designs that are poor, difficult to conduct, and complicated to analyze. Attempts at better design and patient selection for antidepressant trials have not yielded the expected results. As of now, antidepressant clinical trials have an effect size of 0.30, which, although similar to the effects of treatments for many other chronic illnesses, such as hypertension, asthma and diabetes, is less than impressive.
Abstract Background Low levels of physical activity (PA) and sedentary behavior (SB) are independent risk factors for cardiovascular disease and premature mortality in people with major depressive ...disorder (MDD). Aims Investigate levels of PA and SB and their predictors in people with MDD. Methods Electronic databases were searched from inception till 04/2016 for articles measuring PA and SB with a self-report questionnaire (SRQ) or objective measure (e.g. accelerometer) in people with MDD. Random-effects meta-analyses and meta-regression analyses were conducted. Results Twenty-four eligible studies were identified including 2,901 people with MDD (78.4% female, mean age=54 years; range: 21 to 77 years). People with MDD spent 126.0 min (95%CI=91.9–160.1) per day engaging in all types of PA and spent 8.5 hours (95%CI=7.51–9.62) during their waking day being sedentary. Compared to controls, people with MDD spent less time in total PA (SMD=-0.25, 95%CI=-0.03–0.15) and moderate to vigorous PA (SMD=-0.30, 95%CI=-0.40-0.21) and engaged in higher levels of SB (SMD=0.09, 95%CI=0.01–0.18). The proportion of people with MDD not meeting the recommended PA guidelines was 67.8% (n=13 studies), which was higher in studies relying on objective versus self-report measures (85.7% v 62.1%, p=0.04). People with MDD were less likely than controls to meet recommended PA guidelines (OR=-1.50, 95%CI=-1.10--2.10). Limitations Heterogeneity was evident in most analyses. Conclusions Adults with MDD engage in low levels of PA and high levels of SB. PA and SB are independent predictors of mortality, therefore, future lifestyle interventions targeting both the prevention of SB and adoption and maintenance of PA are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•COVID-19 is accompanied by chest CT scan anomalies (CCTAs), lowered SpO2 and immune activation.•The immune activation is characterized by increased IL-6, IL-10, CRP, sRAGEs, and lower albumin and ...calcium.•Increased CCTAs and lowered SpO2 are significantly associated with immune activation.•Increased CCTAs and lowered SpO2 are significantly associated with depression, anxiety and physiosomatic symptoms.•The effects of CCTAs/SpO2 on these neuropsychiatric symptoms are mediated by immune activation.
COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like and physiosomatic symptoms.
To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest computed tomography scan anomalies (CCTAs), oxygen saturation (SpO2), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs).
The above biomarkers were assessed in 60 COVID-19 patients and 30 healthy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales.
Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors. One common “infection-immune-inflammatory (III) core” underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms.
Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Over the past decade, the interpersonal theory of suicide has contributed to substantial advances in the scientific and clinical understanding of suicide and related conditions. The interpersonal ...theory of suicide posits that suicidal desire emerges when individuals experience intractable feelings of perceived burdensomeness and thwarted belongingness and near-lethal or lethal suicidal behavior occurs in the presence of suicidal desire and capability for suicide. A growing number of studies have tested these posited pathways in various samples; however, these findings have yet to be evaluated meta-analytically. This paper aimed to (a) conduct a systematic review of the unpublished and published, peer-reviewed literature examining the relationship between interpersonal theory constructs and suicidal thoughts and behaviors, (b) conduct meta-analyses testing the interpersonal theory hypotheses, and (c) evaluate the influence of various moderators on these relationships. Four electronic bibliographic databases were searched through the end of March, 2016: PubMed, Medline, PsycINFO, and Web of Science. Hypothesis-driven meta-analyses using random effects models were conducted using 122 distinct unpublished and published samples. Findings supported the interpersonal theory: the interaction between thwarted belongingness and perceived burdensomeness was significantly associated with suicidal ideation; and the interaction between thwarted belongingness, perceived burdensomeness, and capability for suicide was significantly related to a greater number of prior suicide attempts. However, effect sizes for these interactions were modest. Alternative configurations of theory variables were similarly useful for predicting suicide risk as theory-consistent pathways. We conclude with limitations and recommendations for the interpersonal theory as a framework for understanding the suicidal spectrum.
Public Significance Statement
This meta-analysis generally found support for the interpersonal theory of suicide-thwarted belongingness and perceived burdensomeness were significant correlates of suicidal ideation severity, and thwarted belongingness, perceived burdensomeness, and capability for suicide were significantly associated with suicide attempt history. Effect sizes for these relationships were weak-to-moderate, suggesting potentially modest clinical significance. However, there was insufficient research on the theory's specific hypotheses, including its capacity for predicting death by suicide and the role of viewing thwarted belongingness and perceived burdensomeness as intractable in suicidal desire.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ, UPUK
Introduction and purpose: The problem of major depression disorder (MDD) affects more and more people. In a few years, it may become the most common disease after cardiovascular diseases and cancer. ...MDD are manifested by a depressed mood, decreased energy, loss of interest and the ability to enjoy life, as well as a number of other additional symptoms. Untreated MDD can lead to disability. This entails not only consequences for the sick person but also increased social costs. That is why it is so important to know the causes of its formation and to look for new therapeutic methods.
State of knowledge: The development of MDD is influenced by genetic factors, inflammatory factors and hormonal disorders, changes in the structure of the brain, disorders in neurotransmission. The microbiome-gut-brain axis affects mood regulation and neurotransmission in the brain. Bacteria such as Escherichia, Shigella, Enterococcus, Streptococccus, Alistipes, Parabacterioides, Veillonella have been identified as having a potential negative effect on the development of MDD and response to treatment. The use of probiotics containing Lactobacillus helveticus R0052, Bifidobacterium longum and Clostridium butyricum MIYAIRI 588 may help reduce the symptoms of MDD. In recent years, the US Food and Drug Administration (FDA) has approved the intranasal preparation of esketamine for the treatment of treatment-resistant depression and major depressive disorder with severe suicidal thoughts. Unlike other antidepressants, it has a quick effect on reducing symptoms.
Summary: Due to the global problem of MDD, further research is needed to better understand the mechanisms of its formation. Particular attention should be paid to the influence of microbiota.
Abstract Background Depression severity is assessed in numerous research disciplines, ranging from the social sciences to genetics, and used as a dependent variable, predictor, covariate, or to ...enroll participants. The routine practice is to assess depression severity with one particular depression scale, and draw conclusions about depression in general, relying on the assumption that scales are interchangeable measures of depression. The present paper investigates to which degree 7 common depression scales differ in their item content and generalizability. Methods A content analysis is carried out to determine symptom overlap among the 7 scales via the Jaccard index (0=no overlap, 1=full overlap). Per scale, rates of idiosyncratic symptoms, and rates of specific vs. compound symptoms, are computed. Results The 7 instruments encompass 52 disparate symptoms. Mean overlap among all scales is low (0.36), mean overlap of each scale with all others ranges from 0.27–0.40, overlap among individual scales from 0.26–0.61. Symptoms feature across a mean of 3 scales, 40% of the symptoms appear in only a single scale, 12% across all instruments. Scales differ regarding their rates of idiosyncratic symptoms (0%–33%) and compound symptoms (22%–90%). Limitations Future studies analyzing more and different scales will be required to obtain a better estimate of the number of depression symptoms; the present content analysis was carried out conservatively and likely underestimates heterogeneity across the 7 scales. Conclusion The substantial heterogeneity of the depressive syndrome and low overlap among scales may lead to research results idiosyncratic to particular scales used, posing a threat to the replicability and generalizability of depression research. Implications and future research opportunities are discussed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
IMPORTANCE: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions ...that better suit them. OBJECTIVE: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. DATA SOURCES: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. STUDY SELECTION: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. DATA EXTRACTION AND SYNTHESIS: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. MAIN OUTCOMES AND MEASURES: Patient Health Questionnaire–9 (PHQ-9) scores. RESULTS: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference MD in posttreatment PHQ-9 scores, −0.8; 95% CI, −1.4 to −0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. CONCLUSIONS AND RELEVANCE: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.
Since the first cases of the novel coronavirus disease SARS-CoV-2 were reported in December 2019 in China, the virus has spread in most countries. The aim of the present study was to assess initial ...data on the mental health burden of the German public during the COVID-19 pandemic.
A cross-sectional study was conducted in Germany and collected complete datasets from 15 704 German residents aged 18 years and over. Besides demographics, generalized anxiety (GAD-7), depression (PHQ-2) and psychological distress (DT) were assessed. Furthermore, COVID-19-related fear, trust in governmental actions to face COVID-19 and the subjective level of information regarding COVID-19 were covered.
Significantly increased symptoms were highly prevalent in all dimensions: generalized anxiety (44.9%), depression (14.3%), psychological distress (65.2%) and COVID-19-related fear (59%). Females and younger people reported higher mental burden. Trust in governmental actions to face COVID-19 and the subjective level of information regarding COVID-19 are negatively associated with mental health burden. However, the subjective level of information regarding COVID-19 is positively associated with increased COVID-19-related fear.
The provision of appropriate psychological interventions for those in need and the provision of transparency and comprehensible information are crucial during the current pandemic.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Patients with major depressive disorder (MDD) show attention bias to the negative emotional stimuli. We aimed at studying the EEG-correlates of unconscious expectation of angry human faces in MDD ...patients compared to healthy controls.
128-channel EEG was recorded in MDD (23 female and 7 male) and in healthy volunteers (22 female and 8 male) while they categorized pictures as humans or animals. Half of the pictures were neutral and half were showing the faces of angry humans or animals. The pictures were preceded by cues (one for each category), which meaning was not explained to the participants. We performed the wavelet analysis of EEG recorded during the face expectation period: 1000–2000ms from the cue onset.
We found the emotional modulation (EM) in EEG rhythms during the expectation of angry vs. neutral faces in both groups. Statistical comparison of the spectral power using 2×2 factorial design showed that the EM differences (p<.05) between the groups were in the left parietal locations in 9Hz and in 16–18Hz, in the right parietal locations in 27–28Hz, and in the right frontal area in 30–31Hz.
The unconscious expectation of angry vs. neutral faces resulted in EM differences between the MDD and healthy controls in the right frontal and bilateral parietal areas mostly in beta range, and also in alpha and gamma.
The EEG from the parietal locations can be a better indicator for the differences between MDD and healthy controls.
Unconscious emotional processing in patients may become a prospective biomarker for depression.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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