COVID-19 risk, course and outcome in people with mental disorders: a systematic review and meta-analyses.

AIMS: It has been suggested that people with mental disorders have an elevated risk to acquire severe acute respiratory syndrome coronavirus 2 and to be disproportionally affected by coronavirus disease 19 (COVID-19) once infected. We aimed to analyse the COVID-19 infection rate, course and outcome, including mortality and long COVID, in people with anxiety, depressive, neurodevelopmental, schizophrenia spectrum and substance use disorders relative to control subjects without these disorders. METHODS: This study constitutes a preregistered systematic review and random-effects frequentist and Bayesian meta-analyses. Major databases were searched up until 27 June 2023. RESULTS: Eighty-one original articles were included reporting 304 cross-sectional and prospective effect size estimates (median n per effect-size = 114837) regarding associations of interest. Infection risk was not significantly increased for any mental disorder that we investigated relative to samples of people without these disorders. The course of COVID-19, however, is relatively severe, and long COVID and COVID-19-related hospitalization are more likely in all patient samples that we investigated. The odds of dying from COVID-19 were high in people with most types of mental disorders, except for those with anxiety and neurodevelopmental disorders relative to non-patient samples (pooled ORs range, 1.26-2.57). Bayesian analyses confirmed the findings from the frequentist approach and complemented them with estimates of the strength of evidence. CONCLUSIONS: Once infected, people with pre-existing mental disorders are at an elevated risk for a severe COVID-19 course and outcome, including long COVID and mortality, relative to people without pre-existing mental disorders, despite an infection risk not significantly increased.

SARS-CoV-2 susceptibility and COVID-19 illness course and outcome in people with pre-existing neurodegenerative disorders: systematic review with frequentist and Bayesian meta-analyses.

BACKGROUND: People with neurodegenerative disease and mild cognitive impairment (MCI) may have an elevated risk of acquiring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may be disproportionally affected by coronavirus disease 2019 (COVID-19) once infected. AIMS: To review all eligible studies and quantify the strength of associations between various pre-existing neurodegenerative disorders and both SARS-CoV-2 susceptibility and COVID-19 illness course and outcome. METHOD: Pre-registered systematic review with frequentist and Bayesian meta-analyses. Systematic searches were executed in PubMed, Web of Science and preprint servers. The final search date was 9 January 2023. Odds ratios (ORs) were used as measures of effect. RESULTS: In total, 136 primary studies (total sample size n = 97 643 494), reporting on 268 effect-size estimates, met the inclusion criteria. The odds for a positive SARS-CoV-2 test result were increased for people with pre-existing dementia (OR = 1.83, 95% CI 1.16-2.87), Alzheimer's disease (OR = 2.86, 95% CI 1.44-5.66) and Parkinson's disease (OR = 1.65, 95% CI 1.34-2.04). People with pre-existing dementia were more likely to experience a relatively severe COVID-19 course, once infected (OR = 1.43, 95% CI 1.00-2.03). People with pre-existing dementia or Alzheimer's disease were at increased risk for COVID-19-related hospital admission (pooled OR range: 1.60-3.72). Intensive care unit admission rates were relatively low for people with dementia (OR = 0.54, 95% CI 0.40-0.74). All neurodegenerative disorders, including MCI, were at higher risk for COVID-19-related mortality (pooled OR range: 1.56-2.27). CONCLUSIONS: Our findings confirm that, in general, people with neurodegenerative disease and MCI are at a disproportionally high risk of contracting COVID-19 and have a poor outcome once infected.

COVID-19-related changes in eating disorder pathology, emotional and binge eating and need for care: a systematic review with frequentist and Bayesian meta-analyses.

PURPOSE: The COVID-19 pandemic has been a leading cause of stress and feelings of loss of control, both of which have been related to eating disorder (ED) pathology onset and deterioration. We aim to estimate the magnitude of changes in the prevalence rates of, and indicators for, ED psychopathology in the face of the COVID-19 pandemic. METHOD: Pre-registered systematic review with frequentist and Bayesian meta-analyses. Searches for eligible studies were performed in PubMed, Web of Science and pre-print servers until January 15 2023. RESULTS: Our searches yielded 46 eligible studies reporting on a total of 4,688,559 subjects. These data provide strong evidence indicating increased rates of diagnosed and self-reported ED's and a concordant increased need for care in the face of the pandemic. ED symptom severity scores in patients were not elevated during the pandemic, except for those related to anorexia nervosa. On average, people in the general population report relatively high levels of emotional and binge eating during the pandemic, although the evidential strength for these associations is only anecdotal to moderate. Moderators of between-study heterogeneity were not detected. CONCLUSIONS: Altogether, our results suggest that the COVID-19 pandemic is associated with a wide spread negative effect on ED pathology in patient samples and the general population. The development of online prevention and intervention programs for EDs during stressful times like a pandemic is encouraged. A limitation is that the results reported here may be prone to biases, amongst others, self-report bias. LEVEL OF EVIDENCE: Level I, systematic review and meta-analysis. PREREGISTRATION: Prospero [ https://www.crd.york.ac.uk/prospero ] ID: CRD42022316105.

Linguistic Analysis of Online Domestic Violence Testimonies in the Context of COVID-19.

Worldwide, an increase in cases and severity of domestic violence (DV) has been reported as a result of social distancing measures implemented to decrease the spreading of the Coronavirus Disease (COVID-19). As one's language can provide insight in one's mental health, this pre-registered study analyzed word use in a DV online support group, aiming to investigate the impact of the COVID-19 pandemic on DV victims in an ex post facto research design. Words reflecting social support and leisure activities were investigated as protective factors against linguistic indicators of depression in 5,856 posts from the r/domesticviolence subreddit and two neutral comparison subreddits (r/changemyview & r/femalefashionadvice). In the DV support group, the average number of daily posts increased significantly by 22% from pre- to mid-pandemic. Confirmatory analysis was conducted following a registered pre-analysis plan. DV victims used significantly more linguistic indicators of depression than individuals in the comparison groups. This did not change with the onset of COVID-19. The use of negative emotion words was negatively related to the use of social support words (Spearman's rho correlation coefficient [rho] = -0.110) and words referring to leisure activities (rho = -0.137). Pre-occupation with COVID-19 was associated with the use of negative emotion words (rho = 0.148). We conclude that language of DV victims is characterized by indicators of depression and this characteristic is stable over time. Concerns with COVID-19 could contribute to negative emotions, whereas social support and leisure activities could function to some degree as protective factors. A potential weakness of this study is its cross-sectional design and the lack of experimental control. Future studies could make use of natural language processing and other advanced methods of linguistic analysis to learn about the mental health of DV victims.

The incubus phenomenon: Prevalence, frequency and risk factors in psychiatric inpatients and university undergraduates.

Background: The incubus phenomenon is a paroxysmal sleep-related disorder characterized by the visuotactile sensation of a person or entity exerting pressure on one's thorax during episodes of sleep paralysis and (apparent) wakefulness. This terrifying phenomenon is relatively unknown even though a previous meta-analysis indicated a lifetime prevalence of 0.11 for individuals in the general population and of 0.41 for selected at-risk groups, including people diagnosed with schizophrenia and students. Since the studies reviewed did not always make a strict distinction between the incubus phenomenon and isolated sleep paralysis, we carried out a cross-sectional study in a contemporary patient and student sample to attain current, more detailed data on the incubus phenomenon. Materials and methods: In a cross-sectional design, we used the Waterloo Unusual Sleep Experience Questionnaire (WUSEQ) to screen patients with severe psychiatric disorders and university undergraduates to establish and compare prevalence rates, frequencies of occurrence, and risk factors for the incubus phenomenon. Results: Having interviewed 749 people, comprising 606 students and 143 patients with a schizophrenia spectrum or related disorder who had been acutely admitted to a secluded nursing ward, we computed a reported lifetime prevalence of 0.12 and 0.09, respectively, which rates were not statistically different. In both groups, the phenomenon was more common in people with a non-Western European background. Risk factors noted for the students were the use of psychotropic medication and the lifetime presence of an anxiety disorder, eating disorder, or sleeping disorder. We found no associations with age or gender in either group. Conclusion: The 0.09 and 0.12 lifetime prevalence rates we recorded for the incubus phenomenon in students and psychiatric inpatients is substantially lower than the 0.41 found in an earlier meta-analysis. We tentatively attribute this difference to an overgeneralization in previous studies but also discuss alternative explanations. The elevated prevalence among non-Western European participants may well be due to the fact that the topic continues to be part of the cultural and religious heritage of many non-Western countries.

Forced swim stressor: Trends in usage and mechanistic consideration.

The acquired immobility response during the "forced swim test (FST)" is not a rodent model of depression, but the test has some validity in predicting a compound's antidepressant potential. Nevertheless, 60% of the about 600 papers that were published annually the past 2 years label the rodent's immobility response as depression-like behaviour, but the relative contribution per country is changing. When the Editors-in-Chief of 5 journals publishing most FST papers were asked for their point of view on labelling immobility as depression-like behaviour and despair, they responded that they primarily rely on the reviewers regarding scientific merit of the submission. One Editor informs authors of the recent NIMH notice (https://grants.nih.gov/grants/guide/notice-files/NOT-MH-19-053.html) which encourages investigators to use animal models "for" addressing neurobiological questions rather than as model "of" specific mental disorders. The neurobiological questions raised by use of the FST fall in two categories. First, research on the role of endocrine and metabolic factors, with roots in the 1980s, and with focus on the bottom-up action of glucocorticoids on circuits processing salient information, executive control and memory consolidation. Second, recent findings using novel technological and computational advances that have allowed great progress in charting top-down control in the switch from active to passive coping with the inescapable stressor executed by neuronal ensembles of the medial prefrontal cortex via the peri-aquaductal grey. It is expected that combining neural top-down and endocrine bottom-up approaches will provide new insights in the role of stress-coping and adaptation in pathogenesis of mental disorders.

Impact of review method on the conclusions of clinical reviews: A systematic review on dietary interventions in depression as a case in point.

BACKGROUND: The recommendations of experts who write review articles are a critical determinant of the adaptation of new treatments by clinicians. Several types of reviews exist (narrative, systematic, meta-analytic), and some of these are more vulnerable to researcher bias than others. Recently, the interest in nutritional interventions in psychiatry has increased and many experts, who are often active researchers on this topic, have come to strong conclusions about the benefits of a healthy diet on depression. In a young and active field of study, we aimed to investigate whether the strength of an author's conclusion is associated with the type of review article they wrote. METHODS: Systematic searches were performed in PubMed, Web of Science, Cochrane Database of Systematic Reviews, and Google Scholar for narrative reviews and systematic reviews with and without meta-analyses on the effects of diet on depression (final search date: May 30th, 2020). Conclusions were extracted from the abstract and discussion section and rated as strong, moderate, or weak by independent raters who were blind to study type. A benchmark on legitimate conclusion strength was based on a GRADE assessment of the highest level of evidence. This systematic review was registered with PROSPERO, number CRD42020141372. FINDINGS: 24 narrative reviews, 12 systematic reviews, and 14 meta-analyses were included. In the abstract, 33% of narrative reviews and 8% of systematic reviews came to strong conclusions, whereas no meta-analysis did. Narrative reviews were 8.94 (95% CI: 2.17, 36.84) times more likely to report stronger conclusions in the abstract than systematic reviews with and without meta-analyses. These findings were similar for conclusions in the discussion section. Narrative reviews used 45.6% fewer input studies and were more likely to be written by authors with potential conflicts of interest. A study limitation is the subjective nature of the conclusion classification system despite high inter-rater agreements and its confirmation outside of the review team. CONCLUSIONS: We have shown that narrative reviews come to stronger conclusions about the benefits of a healthy diet on depression despite inconclusive evidence. This finding empirically underscores the importance of a systematic method for summarizing the evidence of a field of study. Journal editors may want to reconsider publishing narrative reviews before meta-analytic reviews are available.

Anxiety, depression and post-traumatic stress disorder in refugees resettling in high-income countries: systematic review and meta-analysis.

BACKGROUND: The number of refugees is at its highest since the Second World War and on the rise. Many refugees suffer from anxiety, depression and post-traumatic stress disorder (PTSD), but exact and up-to-date prevalence estimates are not available. AIMS: To report the pooled prevalence of anxiety and mood disorders and PTSD in general refugee populations residing in high-income countries and to detect sources of heterogeneity therein. METHOD: Systematic review with meta-analyses and meta-regression. RESULTS: Systematic searches (final search date 3 August 2019) yielded 66 eligible publications that reported 150 prevalence estimates (total sample N = 14 882). Prevalence rates were 13 and 42% (95% CI 8-52%) for diagnosed and self-reported anxiety, 30 and 40% (95% CI 23-48%) for diagnosed and self-reported depression, and 29 and 37% (95% CI 22-45%) for diagnosed and self-reported PTSD. These estimates are substantially higher relative to those reported in non-refugee populations over the globe and to populations living in conflict or war settings, both for child/adolescent and adult refugees. Estimates were similar over different home and resettlement areas and independent of length of residence. CONCLUSIONS: Our data indicate a challenging and persisting disease burden in refugees due to anxiety, mood disorders and PTSD. Knowing this is relevant for the development of public health policies of host countries. Scalable interventions, tailored for refugees, should become more readily available.

The Effects of Physical Exercise on Functional Outcomes in the Treatment of ADHD: A Meta-Analysis.

Objective: An increasing number of studies suggest possible beneficial effects of exercise in alleviating ADHD functional outcomes. The current study provides a quantitative meta-analysis of the available studies investigating this relationship. Method: Studies reporting on the effects of physical exercise on motor skills and executive functions in children with ADHD were identified through Cochrane, PsycInfo, PubMed, Web of Science databases. Ten publications were selected. Random-effects model was used to calculate effect sizes. Results: There was a significant effect of exercise on ADHD functional outcomes (g = 0.627). Longer exercise intervention duration was consistently associated with larger effect sizes. Effect sizes were not related to exercise intensity, mean age of participants, or gender distribution. Conclusion: Results suggest that exercise has a modest positive impact on ADHD functional outcomes, such as executive functions and motor skills, with longer interventions yielding better results.

Anxiety in Children with Selective Mutism: A Meta-analysis.

This study evaluates the current conceptualization of selective mutism (SM) as an anxiety disorder in the DSM-5 using a meta-analytic approach. In the absence of any systematic assessment of anxiety in the field of SM, we pooled prevalence data of comorbid anxiety disorders in a random-effects meta-analysis. On the basis of 22 eligible studies (N = 837), we found that 80% of the children with SM were diagnosed with an additional anxiety disorder, notably social phobia (69%). However, considerable heterogeneity was present, which remained unexplained by a priori specified moderators. The finding that SM is often diagnosed in combination with anxiety disorders, indicates that these disorders are not discrete, separable categories. Moreover, this finding does not help to elucidate the relation between SM and anxiety as an etiological mechanism or symptomatic feature. Broadening our research strategies regarding the assessment of anxiety is paramount to clarify the role of anxiety in SM, and allow for proper classification.

Coping with the forced swim stressor: Current state-of-the-art.

The forced swim test (FST) for rodents does not model despair or helplessness. It also is not a read-out for depression, anxiety, psychomotor retardation or autism, because these are anthropomorphic interpretations of the rodent's acquired immobility. Rather, the transition from swimming to immobility allows to examine the mechanistic underpinning of coping with inescapable stressors. However, in a recent detailed analysis of the FST application over the past 40 years, we noted a dramatic surge in the use of this test to phenotype animals as 'depressed'. As a follow up to that report, we now present an analysis of the use of the FST over the past three years. This literature analysis shows that the popularity of the FST is still increasing and that the majority of researchers qualifies the rodent's floating response as depressive-like behavior. However, over the past few years we also note a trend to interpret immobility rather as the expression of a coping strategy. In view of this result, we have sent a poll to the relevant authors to learn how consistent they are in naming FST behavior. Remarkably, we find a dramatic inverse correlation between their first qualification of acquired immobility as depressive-like behavior towards their current interpretation as coping strategy. In this contribution we have embedded our literature analysis and poll results in an update on the management of coping with inescapable stressors by processing in prefrontal cortical circuitry and glucocorticoid feedback.

The SMILES trial: do undisclosed recruitment practices explain the remarkably large effect?

The SMILES trial showed substantial improvement of depressive symptoms following seven consultations on healthy dieting. The very large effect size on depression reduction seems remarkable and we suggest that selectively induced expectancy and a loss of blinding have contributed to the observed effect.

Magnesium and mood disorders: systematic review and meta-analysis.

BACKGROUND: Magnesium (Mg2+) has received considerable attention with regards to its potential role in the pathophysiology of the mood disorders, but the available evidence seems inconclusive.AimsTo review and quantitatively summarise the human literature on Mg2+ intake and Mg2+ blood levels in the mood disorders and the effects of Mg2+ supplements on mood. METHOD: Systematic review and meta-analyses. RESULTS: Adherence to a Mg2+-rich diet was negatively associated with depression in cross-sectional (odds ratio = 0.66) but not in prospective studies. Mg2+ levels in bodily fluids were on average higher in patients with a mood disorder (Hedge's g = 0.19), but only in patients treated with antidepressants and/or mood stabilisers. There was no evident association between Mg2+ levels and symptom severity. Mg2+ supplementation was associated with a decline in depressive symptoms in uncontrolled (g = -1.60) but not in placebo-controlled trials (g = -0.21). CONCLUSION: Our results provide little evidence for the involvement of Mg2+ in the mood disorders.Declaration of interestNone.

Diet quality and depression risk: A systematic review and dose-response meta-analysis of prospective studies.

BACKGROUND: It has been claimed that the quality of a diet is associated with the incidence of depressive disorders. We sought to investigate the evidence for this claim. METHODS: Systematic searches were performed up to March 6th, 2017 in order to identify prospective cohort studies that reported on exposure to dietary patterns or food groups and the incidence of depression/depressive symptoms. Data from 24 independent cohorts (totalling 1,959,217 person-years) were pooled in random-effects meta-analyses. RESULTS: Adherence to a high-quality diet, regardless of type (i.e., healthy/prudent or Mediterranean), was associated with a lower risk of depressive symptoms over time (odds ratios ranged 0.64-0.78 in a linear dose-response fashion [P < 0.01]). A relatively low dietary inflammatory index was also associated with a somewhat lower incidence of depressive symptom (odds ratio = 0.81), although not in a dose-response fashion. Similar associations were found for the consumption of fish and vegetables (odds ratios 0.86 and 0.82 respectively) but not for other high quality food groups (e.g., fruit). Studies that controlled for depression severity at baseline or that used a formal diagnosis as outcome did not yield statistically significant findings. Adherence to low quality diets and food groups was not associated with higher depression incidence. LIMITATIONS: Our ability to detect confounders was only limited. CONCLUSION: There is evidence that a higher quality of a diet is associated with a lower risk for the onset of depressive symptoms, but not all available results are consistent with the hypothesis that diet influences depression risk. Prospective studies that control for relevant confounders such as obesity incidence and randomized controlled prevention trials are needed to increase the validity of findings in this field.

Prevalence Rates of the Incubus Phenomenon: A Systematic Review and Meta-Analysis.

BACKGROUND: The incubus phenomenon is a paroxysmal sleep-related disorder characterized by compound hallucinations experienced during brief phases of (apparent) wakefulness. The condition has an almost stereotypical presentation, characterized by a hallucinated being that exerts pressure on the thorax, meanwhile carrying out aggressive and/or sexual acts. It tends to be accompanied by sleep paralysis, anxiety, vegetative symptoms, and feelings of suffocation. Its prevalence rate is unknown since, in prior analyses, cases of recurrent isolated sleep paralysis with/without an incubus phenomenon have been pooled together. This is unfortunate, since the incubus phenomenon has a much greater clinical relevance than isolated sleep paralysis. METHODS: PubMed, Embase, and PsycINFO were searched for prevalence studies of the incubus phenomenon, and a meta-analysis was performed. RESULTS: Of the 1,437 unique records, 13 met the inclusion criteria, reporting on 14 (k) independent prevalence estimates (total N = 6,079). The pooled lifetime prevalence rate of the incubus phenomenon was 0.19 [95% confidence interval (CI) = 0.14-0.25, k = 14, N = 6,079] with heterogeneous estimates over different samples. In selected samples (e.g., patients with a psychiatric disorder, refugees, and students), prevalence rates were nearly four times higher (0.41, 95% CI = 0.25-0.56, k = 4, n = 1,275) than in the random samples (0.11, 95% CI = 0.08-0.14, k = 10, n = 4,804). This difference was significant (P < 0.001). CONCLUSION: This review and meta-analysis yielded a lifetime prevalence of the incubus phenomenon in the general population of 0.11 and, in selected samples, of 0.41. This is slightly higher than the prevalence rates in previous analyses that included cases of recurrent isolated sleep paralysis without an incubus phenomenon. Based on the condition's robust clinical presentation and the relatively high prevalence rates, we advocate inclusion of the incubus phenomenon as a diagnostic category in major classifications such as the International Classification of Diseases and Related Health Problems and the Diagnostic and Statistical Manual of Mental Disorders. Recommendations are also made for clinical practice and future research.

Associations between chronotypes and psychological vulnerability factors of depression.

Chronotypes have been associated with psychopathology. The eveningness chronotype has been consistently linked with depressed states or depressive disorder, but the underlying mechanism remains unclear. Prior studies have shown associations between chronotype and personality traits that are linked to depression (e.g. neuroticism), but other psychological vulnerability factors have not been previously investigated in relation to chronotypes. The aim of this study was to examine the association between chronotypes, depression and psychological risk factors of depression (namely, cognitive reactivity and worry), in a large cohort of depressed patients and healthy individuals. We used data from the Netherlands Study of Depression and Anxiety (n = 1654), which includes 1227 clinically diagnosed individuals with a lifetime diagnosis of depression and 427 healthy controls. We assessed cognitive reactivity (Leiden Index of Depression Sensitivity-Revised) and trait worry (Penn State Worry Questionnaire). We controlled for sociodemographic factors as well as for insomnia and neuroticism. We found that the evening type is associated with higher cognitive reactivity scores, especially with increased rumination. Cognitive reactivity also mediated the relationship between chronotype and depression status, even when controlling for neuroticism and insomnia. Trait worry was not associated with chronotype. Our findings show that depressogenic cognitions are more prevalent in evening types and perhaps mediate the association between chronotype and depression. Further prospective research is needed to determine the timeline of the association. Nevertheless, results imply that targeting depressogenic cognitive processes, perhaps in combination with chronotherapeutic treatments, may be particularly useful in evening types.

The association of childhood maltreatment with depression and anxiety is not moderated by the oxytocin receptor gene.

BACKGROUND: The oxytocin receptor (OXTR) gene may be involved in resilience or vulnerability towards stress, and hence in the development of stress-related disorders. There are indications that OXTR single nucleotide polymorphisms (SNPs) interact with early life stressors in predicting levels of depression and anxiety. To replicate and extend these findings, we examined whether three literature-based OXTR SNPs (rs2254298, rs53576, rs2268498) interact with childhood maltreatment in the development of clinically diagnosed depression and anxiety disorders. METHODS: We included 2567 individuals from the Netherlands Study of Depression and Anxiety. This sample consisted of 387 healthy controls, 428 people with a current or past depressive disorder, 243 people with a current or past anxiety disorder, and 1509 people with both lifetime depression and anxiety diagnoses. Childhood maltreatment was measured with both an interview and via self-report. Additional questionnaires measured depression and anxiety sensitivity. RESULTS: Childhood maltreatment was strongly associated with both lifetime depression and anxiety diagnoses, as well as with depression and anxiety sensitivity. However, the OXTR SNPs did not moderate these associations nor had main effects on outcomes. CONCLUSIONS: The three OXTR gene SNPs did not interact with childhood maltreatment in predicting lifetime depression and anxiety diagnoses or sensitivity. This stresses the importance of replication studies with regard to OXTR gene variants in general populations as well as in clearly established clinical samples.