There has been a limited number of systematic reviews conducted to summarize the overview of the relationship between DNA methylation and depression, and to critically appraise the roles of major ...study characteristics in the accuracy of study findings. This systematic review aims to critically appraise the impact of study characteristics on the association between DNA methylation and depression, and summarize the overview of this association. Electronic databases and gray literatures until December 2017 were searched for English-language studies with standard diagnostic criteria of depression. A total of 67 studies were included in this review along with a summary of their study characteristics. We grouped the findings into etiological and treatment studies. Majority of these selected studies were recently published and from developed countries. Whole blood samples were the most studied common tissues. Bisulfite conversion, along with pyrosequencing, was widely used to test the DNA methylation level across all the studies. High heterogeneity existed among the studies in terms of experimental and statistical methodologies and study designs. As recommended by the Cochrane guideline, a systematic review without meta-analysis should be undertaken. This review has, in general, found that DNA methylation modifications were associated with depression. Subgroup analyses showed that most studies found BDNF and SLC6A4 hypermethylations to be associated with MDD or depression in general. In contrast, studies on NR3C1, OXTR, and other genes, which were tested by only few studies, reported mixed findings. More longitudinal studies using standardized experimental and laboratory methodologies are needed in future studies to enable more systematical comparisons and quantitative synthesis.
In this article we have provided a perspective on the importance and value of youth mental health services for society and argued that advancing youth mental health services should be the number one ...priority of health services in Canada. Using the age period of 12–25 years for defining youth, we have provided justification for our position based on scientific evidence derived from clinical, epidemiological and neurodevelopmental studies. We have highlighted the early onset of most mental disorders and substance abuse as well as their persistence into later adulthood, the long delays experienced by most help seekers and the consequence of such delays for young people and for society in general. We have also provided a brief review of the current gross inadequacies in access and quality of care available in Canada. We have argued for the need for a different conceptual framework of youth mental disorders as well as for a transformation of the way services are provided in order not only to reduce the unmet needs but also to allow a more meaningful exploration of the nature of such problems presenting in youth and the best way to treat them. We have offered some ideas based on previous work completed in this field as well as current initiatives in Canada and elsewhere. Any transformation of youth mental health services in Canada must take into consideration the significant geographic, cultural and political diversity across the provinces, territories and indigenous peoples across this country.
COVID-19 was declared a pandemic in March 2020, by the World Health Organization. The pandemic has had unprecedented worldwide implications, in particular on marginalized populations.
The aim of this ...study is to review the impact of the pandemic on patients with schizophrenia spectrum disorders.
A number of databases were searched for this review, including PubMed, EMBASE, PsycINFO and Google Scholar. Search terms included psychosis and COVID-19, schizophrenia and COVID-19, and severe mental illness and COVID-19. We included all English language papers and preprints. The final search was done on 15 July 2020.
Forty-seven relevant studies were identified and included in this review. Studies were summarised into five main subcategories: potential impact of the COVID-19 pandemic on physical health outcomes of patients with schizophrenia spectrum disorders, impact on mental health outcomes, review of case reports and case series to date, treatment recommendation guidelines and risk of increased prevalence of psychosis.
Patients with schizophrenia spectrum disorders may be vulnerable to the effects of the COVID-19 pandemic. This patient population has a number of risk factors, including psychosocial adversities and illness related factors. Continuous monitoring and long-term studies of the impact of the pandemic on this patient population are required.
As outlined earlier, publication of negative findings is essential to interpreting the overall significance of a field of research. However, papers with negative findings are less likely to be highly ...cited than papers with positive findings and less likely overall to be noticed in the scientific commun - ity.
Summary Introduction Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose–response relation between intranasal oxytocin ...administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We therefore examined the effects of 24IU and 48IU of intranasal oxytocin on the cortisol response to vigorous exercise. Method Seventeen males participated in a randomized, placebo-controlled, double-blind, and within-subject experiment. Participants engaged in vigorous exercise for 60 min following the administration of placebo or intranasal oxytocin on three occasions. Saliva samples and mood ratings were collected at eight intervals across each session. Results Salivary cortisol concentrations changed over time, peaking after 60 min of exercise (quadratic: F (1,16) = 7.349, p = .015, partial η2 = .32). The 24IU dose of oxytocin attenuated cortisol levels relative to placebo ( F (1,16) = 4.496, p = .05, partial η2 = .22) and the 48IU dose, although the latter fell just short of statistical significance ( F (1,16) = 3.054, p = .10, partial η2 = .16). There was no difference in the cortisol response to exercise in participants who were administered 48IU of intranasal oxytocin relative to placebo. Intranasal oxytocin had no effect on mood. Conclusion This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress. Future research using exogenous oxytocin will need to consider the possibility of dose–response relations.
Childhood-onset schizophrenia (COS), defined by the onset of illness before age 13 years, is a rare severe neurodevelopmental disorder of unknown etiology. Recently, sequencing studies have ...identified rare, potentially causative de novo variants in sporadic cases of adult-onset schizophrenia and autism. In this study, we performed exome sequencing of 17 COS trios in order to test whether de novo variants could contribute to this disease. We identified 20 de novo variants in 17 COS probands, which is consistent with the de novo mutation rate reported in the adult form of the disease. Interestingly, the missense de novo variants in COS have a high likelihood for pathogenicity and were enriched for genes that are less tolerant to variants. Among the genes found disrupted in our study, SEZ6, RYR2, GPR153, GTF2IRD1, TTBK1 and ITGA6 have been previously linked to neuronal function or to psychiatric disorders, and thus may be considered as COS candidate genes.
Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental psychiatric disorder. Genome-wide association studies (GWAS) have identified several loci associated with ADHD. However, ...understanding the biological relevance of these genetic loci has proven to be difficult. Here, we conduct an ADHD transcriptome-wide association study (TWAS) consisting of 19,099 cases and 34,194 controls and identify 9 transcriptome-wide significant hits, of which 6 genes were not implicated in the original GWAS. We demonstrate that two of the previous GWAS hits can be largely explained by expression regulation. Probabilistic causal fine-mapping of TWAS signals prioritizes KAT2B with a posterior probability of 0.467 in the dorsolateral prefrontal cortex and TMEM161B with a posterior probability of 0.838 in the amygdala. Furthermore, pathway enrichment identifies dopaminergic and norepinephrine pathways, which are highly relevant for ADHD. Overall, our findings highlight the power of TWAS to identify and prioritize putatively causal genes.
Accurate automated quantification of subcortical structures is a greatly pursued endeavour in neuroimaging. In an effort to establish the validity and reliability of these methods in defining the ...striatum, globus pallidus, and thalamus, we investigated differences in volumetry between manual delineation and automated segmentations derived by widely used FreeSurfer and FSL packages, and a more recent segmentation method, the MAGeT-Brain algorithm. In a first set of experiments, the basal ganglia and thalamus of thirty subjects (15 first episode psychosis FEP, 15 controls) were manually defined and compared to the labels generated by the three automated methods. Our results suggest that all methods overestimate volumes compared to the manually derived “gold standard”, with the least pronounced differences produced using MAGeT. The least between-method variability was noted for the striatum, whereas marked differences between manual segmentation and MAGeT compared to FreeSurfer and FSL emerged for the globus pallidus and thalamus. Correlations between manual segmentation and automated methods were strongest for MAGeT (range: 0.51 to 0.92; p<0.01, corrected), whereas FreeSurfer and FSL showed moderate to strong Pearson correlations (range 0.44–0.86; p<0.05, corrected), with the exception of FreeSurfer pallidal (r=0.31, p=0.10) and FSL thalamic segmentations (r=0.37, p=0.051). Bland-Altman plots highlighted a tendency for greater volumetric differences between manual labels and automated methods at the lower end of the distribution (i.e. smaller structures), which was most prominent for bilateral thalamus across automated pipelines, and left globus pallidus for FSL.
We then went on to examine volume and shape of the basal ganglia structures using automated techniques in 135 FEP patients and 88 controls. The striatum and globus pallidus were significantly larger in FEP patients compared to controls bilaterally, irrespective of the method used. MAGeT-Brain was more sensitive to shape-based group differences, and uncovered widespread surface expansions in the striatum and globus pallidus bilaterally in FEP patients compared to controls, and surface contractions in bilateral thalamus (FDR-corrected). By contrast, after using a recommended cluster-wise thresholding method, FSL only detected differences in the right ventral striatum (FEP>Control) and one cluster of the left thalamus (Control>FEP).
These results suggest that different automated pipelines segment subcortical structures with varying degrees of variability compared to manual methods, with particularly pronounced differences found with FreeSurfer and FSL for the globus pallidus and thalamus.
•Manual segmentation of subcortical structure is evaluated against 3 automated tools.•Correspondence with manual labels was greatest with MAGeT-Brain.•Greatest between-method variability was noted for FreeSurfer and FSL-FIRST.•Larger striatum and pallidum were found in first episode psychosis across methods.•Subcortical shape profiles in patients vs. controls differed between MAGeT and FSL.
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