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The upsurge in the number of people affected by the COVID-19 is likely to lead to increased rates of emotional trauma and mental illnesses. This article systematically reviewed the available data on the benefits of interventions to reduce adverse mental health sequelae of infectious disease outbreaks, and to offer guidance for mental health service responses to infectious disease pandemic. PubMed, Web of Science, Embase, PsycINFO, WHO Global Research Database on infectious disease, and the preprint server medRxiv were searched. Of 4278 reports identified, 32 were included in this review. Most articles of psychological interventions were implemented to address the impact of COVID-19 pandemic, followed by Ebola, SARS, and MERS for multiple vulnerable populations. Increasing mental health literacy of the public is vital to prevent the mental health crisis under the COVID-19 pandemic. Group-based cognitive behavioral therapy, psychological first aid, community-based psychosocial arts program, and other culturally adapted interventions were reported as being effective against the mental health impacts of COVID-19, Ebola, and SARS. Culturally-adapted, cost-effective, and accessible strategies integrated into the public health emergency response and established medical systems at the local and national levels are likely to be an effective option to enhance mental health response capacity for the current and for future infectious disease outbreaks. Tele-mental healthcare services were key central components of stepped care for both infectious disease outbreak management and routine support; however, the usefulness and limitations of remote health delivery should also be recognized.
Antidepressants are amongst the most commonly prescribed classes of drugs and their use continues to grow. Adverse outcomes are part of the landscape in prescribing medications and therefore management of safety issues need to be an integral part of practice.
We have developed consensus guidelines for safety monitoring with antidepressant treatments.
To present an overview of screening and safety considerations for pharmacotherapy of clinical depressive disorders and make recommendations for safety monitoring.
Data were sourced by a literature search using Medline and a manual search of scientific journals to identify relevant articles. Draft guidelines were prepared and serially revised in an iterative manner until all co-authors gave final approval of content.
A guidelines document was produced after approval by all 19 co-authors. The final document gives guidance on; the decision to treat, baseline screening prior to commencement of treatment, and ongoing monitoring during antidepressant treatment. The guidelines state or reference screening protocols that may detect medical causes of depression as well as screening and monitoring protocols to investigate specific adverse effects associated with antidepressant treatments that may be reduced or identified earlier by baseline screening and agent-specific monitoring after commencing treatment.
The implementation of safety monitoring guidelines for treatment of clinical depression may significantly improve outcome, by improving a patient's overall physical health status.
Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS).
We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium.
There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia (β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation.
These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
Background: Observational studies have reported an association between childhood obesity and a higher risk of multiple sclerosis (MS). However, the difficulties to fully account for confounding and long recall periods make causal inference from these studies challenging. The objective of this study was to assess the contribution of childhood obesity to the development of MS through Mendelian randomization, which uses genetic associations to minimize the risk of confounding. Methods: We selected 23 independent genetic variants strongly associated with childhood body mass index (BMI) in a genome-wide association study (GWAS) which included 47,541 children. The corresponding effects of these variants on risk of MS were obtained from a GWAS of 14,802 MS cases and 26,703 controls. Standard two-sample Mendelian randomization methods were performed, with additional sensitivity analyses to assess the likelihood of bias from genetic pleiotropy. Results: The inverse-variance weighted MR analysis revealed that one standard deviation increase in childhood BMI increased odds of MS by 26% (odds ratio=1.26, 95% confidence interval 1.10-1.45, p=0.001). There was no significant heterogeneity across the individual estimates. Sensitivity analyses were consistent with the main findings and provided no evidence of pleiotropy. Conclusions: This study provides genetic support of a role for increased childhood BMI in the development of MS.
Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.
To study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals.
In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging.
Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety–threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC.
Poor vmPFC safety–threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.
Higher cognitive ability is associated with favourable health characteristics. The relation between ability and alcohol consumption, and their interplay with other health characteristics, is unclear. We aimed to assess the relationship between cognitive ability and alcohol consumption and to assess whether alcohol consumption relates differently to health characteristics across strata of ability.
For 63 120 Norwegian males, data on cognitive ability in early adulthood were linked to midlife data on alcohol consumption frequency (times per month, 0–30) and other health characteristics, including cardiovascular risk factors and mental distress. Relations were assessed using linear regression and reported as unstandardised beta coefficients [95% confidence interval (CI)].
The mean ± s.d. frequency of total alcohol consumption in the sample was 4.0 ± 3.8 times per month. In the low, medium, and high group of ability, the frequencies were 3.0 ± 3.3, 3.7 ± 3.5, and 4.7 ± 4.1, respectively. In the full sample, alcohol consumption was associated with physical activity, heart rate, fat mass, smoking, and mental distress. Most notably, each additional day of consumption was associated with a 0.54% (0.44–0.64) and 0.14% (0.09–0.18) increase in the probability of current smoking and mental distress, respectively. In each strata of ability (low, medium, high), estimates were 0.87% (0.57–1.17), 0.48% (0.31–0.66) and 0.49% (0.36–0.62) for current smoking, and 0.44% (0.28–0.60), 0.10% (0.02–0.18), and 0.09% (0.03–0.15) for mental distress, respectively.
Participants with low cognitive ability drink less frequently, but in this group, more frequent alcohol consumption is more strongly associated with adverse health characteristics.
Observational associations between cannabis and schizophrenia are well documented, but ascertaining causation is more challenging. We used Mendelian randomization (MR), utilizing publicly available data as a method for ascertaining causation from observational data.
We performed bi-directional two-sample MR using summary-level genome-wide data from the International Cannabis Consortium (ICC) and the Psychiatric Genomics Consortium (PGC2). Single nucleotide polymorphisms (SNPs) associated with cannabis initiation (p < 10−5) and schizophrenia (p < 5 × 10−8) were combined using an inverse-variance-weighted fixed-effects approach. We also used height and education genome-wide association study data, representing negative and positive control analyses.
There was some evidence consistent with a causal effect of cannabis initiation on risk of schizophrenia [odds ratio (OR) 1.04 per doubling odds of cannabis initiation, 95% confidence interval (CI) 1.01–1.07, p = 0.019]. There was strong evidence consistent with a causal effect of schizophrenia risk on likelihood of cannabis initiation (OR 1.10 per doubling of the odds of schizophrenia, 95% CI 1.05–1.14, p = 2.64 × 10−5). Findings were as predicted for the negative control (height: OR 1.00, 95% CI 0.99–1.01, p = 0.90) but weaker than predicted for the positive control (years in education: OR 0.99, 95% CI 0.97–1.00, p = 0.066) analyses.
Our results provide some that cannabis initiation increases the risk of schizophrenia, although the size of the causal estimate is small. We find stronger evidence that schizophrenia risk predicts cannabis initiation, possibly as genetic instruments for schizophrenia are stronger than for cannabis initiation.
Negative mood states are composed of symptoms of depression and anxiety, and by a third factor related to stress, tension and irritability. We sought to clarify the nature of the relationships between the factors by studying twin pairs.
A total of 503 monozygotic twin pairs completed the Depression Anxiety Stress Scales (DASS), an instrument that assesses symptoms of depression, anxiety and stress–tension. We applied a recently developed twin regression methodology – Inference about Causation from Examination of FAmiliaL CONfounding (ICE FALCON) – to test for evidence consistent with the existence of ‘causal’ influences between the DASS factors.
There was evidence consistent with the stress–tension factor having a causal influence on both the depression (p < 0.0001) and anxiety factors (p = 0.001), and for the depression factor having a causal influence on the anxiety factor (p < 0.001).
Our findings suggest a critical role for stress–tension in the structure of negative mood states, and that interventions that target it may be particularly effective in reducing depression and anxiety symptoms.
Studies have suggested both adverse and protective associations of obesity with depressive symptoms. We examined the contribution of environmental and heritable factors in this association. Participants were same-sex twin pairs from two population-based twin cohort studies, the Older Finnish Twin Cohort (n = 8,215; mean age = 44.1) and the US Midlife Development in the United States (MIDUS; n = 1,105; mean age = 45.1). Body mass index (BMI) was calculated from self-reported height and weight. Depressive symptoms were assessed using Beck's Depression Inventory (BDI; Finnish Twin Cohort), and by negative and positive affect scales (MIDUS). In the Finnish Twin Cohort, higher BMI was associated with higher depressive symptoms in monozygotic (MZ) twins (B = 2.01, 95% CI = 1.0, 3.0) and dizygotic (DZ) twins (B = 1.17, 0.5, 1.9) with BMI >22. This association was observed in within-pair analysis in DZ twins (B = 1.47, CI = 0.4, 2.6) but not in within-pair analysis of MZ twins (B = 0.03, CI = -1.9, 2.0). Consistent with the latter result, a bivariate genetic model indicated that the association between higher BMI and higher depressive symptoms was largely mediated by genetic factors. The results of twin-pair analysis and bivariate genetic model were replicated in the MIDUS sample. These findings suggest an association between obesity and higher depressive symptoms, which is largely explained by shared heritable biological mechanisms.
There is increasing evidence that hyperenergetic diets have an impact on memory in rodents. However, it is largely unknown how diets, such as a cafeteria diet (CD), that mimic a Western-type diet act on learning and memory, in particular when fed during early stages of development. Here, we fed lactating dams a CD and exposed both male and female offspring to a novel object discrimination (NOD) task, a two-trial test of recognition memory in which rats exposed to two identical objects during a training/familiarisation trial can discriminate a novel from a familiar object during the subsequent choice trial. The choice trial was performed following inter-trial interval (ITI) delays of up to 4 h. Maternal diet did not have an impact on exploration of the objects by either sex during the familiarisation trial. Control males discriminated the novel from the familiar object, indicating intact memory with an ITI of 1 h, but not 2 or 4 h. The CD delayed this natural forgetting in male rats such that discrimination was also evident after a 2 h ITI. In contrast, control females exhibited discrimination following both 1 and 2 h ITI, but the CD impaired performance. In summary, the present study shows that maternal exposure to the CD programmes NOD in the adult. In better-performing females, dietary programming interferes with NOD, whereas NOD was improved in males after lactational CD feeding.
The amygdala and subgenual anterior cingulate cortex (sACC) are key brain regions for the generation of negative affect. In this longitudinal fMRI study of adolescents we investigated how amygdala–sACC connectivity was correlated with negative affectivity (NA) both cross-sectionally and longitudinally, and examined its relationship to the onset of first-episode depression.
Fifty-six adolescents who were part of a larger longitudinal study of adolescent development were included. They had no history of mental illness at the time of their baseline scan (mean age 16.5 years) and had a follow-up scan 2 years later (mean age 18.8 years). We used resting-state functional-connectivity MRI to investigate whether cross-sectional and change measures of amygdala–sACC connectivity were (i) correlated with NA and its change over time, and (ii) related to the onset of first-episode depression.
The magnitude of amygdala connectivity with sACC showed significant positive correlation with NA at both time-points. Further analysis confirmed that change in amygdala–sACC connectivity between assessments was correlated with change in NA. Eight participants developed a first episode of depression between the baseline and follow-up assessments: they showed increased amygdala–sACC connectivity at follow-up.
Amygdala–sACC connectivity is associated with NA in adolescence, with change in connectivity between these regions showing positive correlation with change in NA. Our observation that the onset of depression was associated with an increase in connectivity between the regions provides support for the neurobiological ‘scar’ hypothesis of depression.
Preterm birth confers risk for poor outcome, including mental health problems. Survival of extremely preterm (EP; <28 weeks' gestation) or extremely low birthweight (ELBW; <1000 g) infants increased in the 1990s but psychiatric outcomes in older adolescents born preterm since 1990 are not well documented. This study aimed to characterize mental health and personality traits in a prospective geographical cohort of adolescents born EP/ELBW in Victoria, Australia in 1991 and 1992.
At age 18 years, 215 EP/ELBW and 157 normal birthweight (>2499 g) control adolescents completed the Structured Clinical Interview for DSM-IV Disorders, Axis 1 Non-Patient version (SCID-I/NP), the Children's Interview for Psychiatric Syndromes (ChIPS) attention deficit hyperactivity disorder (ADHD) module, and questionnaires assessing recent depression and anxiety symptoms and personality traits.
ADHD prevalence was significantly elevated in EP/ELBW adolescents compared with controls [15% v. 7%; odds ratio (OR) 2.67, 95% confidence interval (CI) 1.08–6.58]. Aside from ADHD, however, EP/ELBW and control adolescents reported very similar outcomes, with other lifetime diagnoses identified in 23% of EP/ELBW and 21% of controls. These were predominantly mood and anxiety disorders (21% EP/ELBW, 20% controls). The groups did not differ in recent depression or anxiety symptoms assessed using questionnaires, and personality traits were also similar.
ADHD was more prevalent in EP/ELBW adolescents than controls, which is consistent with some, but not all, reports on preterm survivors born before the 1990s, and younger preterm children born in the 1990s. The high rates of anxiety and mood disorders were similar in both groups, and comparable with population-based estimates.
The relationship between prenatal tobacco exposure and hyperactivity remains controversial. To mitigate limitations of prior studies, we used a strategy involving comparison of maternal and paternal smoking reports in a historical sample where smoking during pregnancy was common.
Data were drawn from a longitudinally followed subsample of the Child Health and Development Study (n = 1752), a population-based pregnancy cohort ascertained in 1961–1963 in California. Maternal prenatal smoking was common (33.4%). Maternal and paternal smoking patterns were assessed at three time points by mother report. Hyperactivity was assessed at the mean of age of 10 years based on mother report to a personality inventory.
Unadjusted, maternal smoking during pregnancy was associated with offspring hyperactivity [β = 0.22, 95% confidence interval (CI) 0.11–0.33] and, to a similar degree, when the father smoked (β = 0.18, 95% CI 0.07–0.30). After adjustment, maternal smoking remained robustly predictive of offspring hyperactivity (β = 0.25, 95% CI 0.09–0.40) but father smoking was not (β = 0.02, 95% CI −0.20 to 0.24). When examined among the pairs matched on propensity score, mother smoking was robustly related to offspring hyperactivity whether the father smoked (β = 0.26, 95% CI 0.03–0.49) or did not smoke (β = 0.30, 95% CI 0.04–0.57). By number of cigarettes, associations with hyperactivity were present for 10–19 and 20+ cigarettes per day among mothers.
In a pregnancy cohort recruited in a time period in which smoking during pregnancy was common, we document associations between prenatal smoking exposure and offspring hyperactivity. Novel approaches to inferring causality continue to be necessary in describing the potential adverse consequences of prenatal smoking exposure later in life.
Cigarette smoking is strongly associated with mental illness but the causal direction of the association is uncertain. We investigated the causal relationship between smoking and symptoms of anxiety and depression in the Norwegian HUNT study using the rs1051730 single nucleotide polymorphism (SNP) variant located in the nicotine acetylcholine receptor gene cluster on chromosome 15 as an instrumental variable for smoking phenotypes. Among smokers, this SNP is robustly associated with smoking quantity and nicotine dependence.
In total, 53 601 participants were genotyped for the rs1051730 SNP and provided information on smoking habits and symptoms of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS).
Self-reported smoking was positively associated with the prevalence of both anxiety and depression, and the measured polymorphism was positively associated with being a current smoker and the number of cigarettes smoked in current smokers. In the sample as a whole, risk of anxiety increased with each affected T allele [odds ratio (OR) 1.06, 95% confidence interval (CI) 1.02–1.09, p = 0.002] but there was no association with depression (p = 0.31). However, we found no clear association of the polymorphism with either anxiety (OR 1.03, 95% CI 0.97–1.09, p = 0.34) or depression (OR 1.02, 95% CI 0.95–1.09, p = 0.62) among smokers.
As there was no association of the smoking-related rs1051730 SNP with anxiety and depression among smokers, the results suggest that smoking is not a cause of anxiety and depression.
Depression has been associated with functional alterations in several areas of the cingulate cortex. In this study we have taken a systematic approach to examining how alterations in functional connectivity vary across the functionally diverse subregions of the rostral cingulate cortex.
Eighteen patients with major depressive disorder, aged 15 to 24 years, were matched with 20 healthy control participants. Using resting-state functional connectivity magnetic resonance imaging (fcMRI), we systematically investigated the functional connectivity of four subregions of the rostral cingulate cortex. Voxelwise statistical maps of each subregion's connectivity with other brain areas were compared between the patient and control groups.
The depressed participants showed altered patterns of connectivity with ventral cingulate subregions. They showed increased connectivity between subgenual anterior cingulate cortex (ACC) and dorsomedial frontal cortex, with connectivity strength showing positive correlation with illness severity. Depressed participants also showed increased connectivity between pregenual ACC and left dorsolateral frontal cortex, and decreased connectivity between pregenual ACC and the caudate nucleus bilaterally.
The results reinforce the importance of subgenual ACC for depression, and show a close link between brain regions that support self-related processes and affective visceromotor function. The pregenual ACC also has an important role, with its increased connectivity with dorsolateral frontal cortex suggesting heightened cognitive regulation of affect; and reduced connectivity with the caudate nucleus potentially underlying symptoms such as anhedonia, reduced motivation and psychomotor dysfunction.
Abnormalities in cortico-striatal-pallidal-thalamic (CSPT) circuits have been implicated in major depressive disorder (MDD). However, the robustness of these findings across studies is unclear, as is the extent to which they are influenced by demographic, clinical and pharmacological factors.
With the aim of clarifying these questions, we conducted a meta-analysis to map the volumetric abnormalities that were most robustly identified in CSPT circuits of individuals with MDD. A systematic search identified 41 studies meeting our inclusion criteria.
There were significant volume reductions in prefrontal (especially orbitofrontal) and anterior cingulate cortices, and also in subcortical structures such as the caudate nucleus and putamen, with effect sizes ranging from small to moderate. The subgenual anterior cingulate and orbitofrontal cortices were significantly smaller in antidepressant-free samples compared to medicated patients. Late-life depression (LLD) tended to be associated with smaller volumes in circumscribed frontal and subcortical structures, with the most robust differences being found in thalamic volume.
Individuals with major depression demonstrate volumetric abnormalities of CSPT circuits. However, these observations may be restricted to certain subgroups, highlighting the clinical heterogeneity of the disorder. On the basis of this meta-analysis, CSPT abnormalities were more prominent in those with LLD whereas antidepressant use seemed to normalize certain cortical volumetric abnormalities.
Preterm (PT) birth and low birth weight (LBW) are high-prevalence events that are associated with adverse outcomes in the longer term, with vulnerability increasing as maturity at birth decreases. Psychiatric symptomatology appears heightened in PT/LBW survivors, though there are some discordant findings from studies using questionnaire measures, particularly with respect to anxiety and depressive symptoms.
This article synthesises findings from research using clinical psychiatric diagnostic criteria in PT/LBW individuals aged 10–25 years compared with term-born peers. Key outcomes of interest were the rates of individuals receiving any psychiatric diagnosis and the number of diagnoses of anxiety or depressive disorders.
A literature search for studies reporting prevalence of ‘any diagnosis’ yielded five studies that met inclusion criteria, with a total of 565 PT/LBW and 533 control individuals. Also, five studies were found that reported rates of anxiety/depression (692 PT/LBW and 605 control individuals). The risk of these outcomes was increased for PT/LBW individuals compared with controls [any diagnosis: odds ratio (OR) 3.66, 95% confidence interval (CI) 2.57–5.21; anxiety or depressive disorder: OR 2.86, 95% CI 1.73–4.73].
The studies reviewed here indicate that, in addition to monitoring and management of medical and cognitive sequelae, the psychological well-being of PT/LBW individuals should be a key part of ongoing care.