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.
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.
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.
Functional recovery remains the primary goal following treatment of a psychotic disorder, especially after a first episode. Evidence regarding relative contributions of predictors of functional ...outcome, including symptoms and cognition, remains equivocal. The objective of the study was to determine the relative contribution of cognition, in particular verbal memory, and symptomatic remission to social and occupational functioning while controlling for established predictors of functioning in a large sample of patients presenting with a first episode of a schizophrenia spectrum or affective psychosis.
Patients (aged 14-35 years) met DSM-IV criteria for a first episode of a schizophrenia spectrum or affective psychosis and had been admitted to the Prevention and Early Intervention Program for Psychoses, Montreal, Quebec, Canada, between 2003 and 2009 for treatment and follow-up for 2 years. Established predictors (duration of untreated psychosis, medication adherence, age at onset, substance use, premorbid adjustment), verbal memory, and length of positive and negative symptom remission were regressed on functioning (using the Strauss Carpenter Scale) at 1 (n = 208) and 2 (n = 159) years. Regressions were conducted with established predictors in the first step, followed by verbal memory and consecutive months of combined positive and negative symptom remission in the third step. Regressions were then repeated with length of positive and negative symptom remission, respectively.
Length of combined positive and negative symptom remission explained the most variance in functioning at 1 (R² adjusted = 0.35, F₉,₁₂₉ = 9.33, P < .001) and 2 (R² adjusted = 0.38, F₉,₉₇ = 8.21, P < .001) years, and verbal memory contributed only slightly to such outcome. While length of remission of negative symptoms was a stronger predictor of functioning than remission of positive symptoms at 1 year, length of positive symptom remission also made a large contribution at 2 years.
These results highlight the importance of achieving and maintaining remission of both negative and positive symptoms for longer periods in patients with a first episode of a psychotic disorder and the need for effective interventions to do so.
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