Canadian Network for Mood and Anxiety Treatments (CANMAT) Task Force Report: A Systematic Review and Recommendations of Cannabis use in Bipolar Disorder and Major Depressive Disorder.

BACKGROUND: Given the increasing acceptability and legalization of cannabis in some jurisdictions, clinicians need to improve their understanding of the effect of cannabis use on mood disorders. OBJECTIVE: The purpose of this task force report is to examine the association between cannabis use and incidence, presentation, course and treatment of bipolar disorder and major depressive disorder, and the treatment of comorbid cannabis use disorder. METHODS: We conducted a systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, searching PubMed, Embase, PsycINFO, CINAHL and Cochrane Central Register of Controlled Trials from inception to October 2020 focusing on cannabis use and bipolar disorder or major depressive disorder, and treatment of comorbid cannabis use disorder. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach was used to evaluate the quality of evidence and clinical considerations were integrated to generate Canadian Network for Mood and Anxiety Treatments recommendations. RESULTS: Of 12,691 publications, 56 met the criteria: 23 on bipolar disorder, 21 on major depressive disorder, 11 on both diagnoses and 1 on treatment of comorbid cannabis use disorder and major depressive disorder. Of 2,479,640 participants, 12,502 were comparison participants, 73,891 had bipolar disorder and 408,223 major depressive disorder without cannabis use. Of those with cannabis use, 2,761 had bipolar disorder and 5,044 major depressive disorder. The lifetime prevalence of cannabis use was 52%-71% and 6%-50% in bipolar disorder and major depressive disorder, respectively. Cannabis use was associated with worsening course and symptoms of both mood disorders, with more consistent associations in bipolar disorder than major depressive disorder: increased severity of depressive, manic and psychotic symptoms in bipolar disorder and depressive symptoms in major depressive disorder. Cannabis use was associated with increased suicidality and decreased functioning in both bipolar disorder and major depressive disorder. Treatment of comorbid cannabis use disorder and major depressive disorder did not show significant results. CONCLUSION: The data indicate that cannabis use is associated with worsened course and functioning of bipolar disorder and major depressive disorder. Future studies should include more accurate determinations of type, amount and frequency of cannabis use and select comparison groups which allow to control for underlying common factors.

Clinical correlates of late-onset versus early-onset bipolar disorder in a global sample of older adults.

OBJECTIVES: Late-onset bipolar disorder (LOBD) represents a significant subgroup of bipolar disorder (BD). However, knowledge for this group is mostly extrapolated from small studies in subjects with early/mixed age of illness onset. In this global sample of older adults with BD (OABD: ≥50 years old) we aim to characterize the sociodemographic and clinical presentation of LOBD (≥40 years at BD onset) compared to early-onset BD (EOBD: <40 years at BD onset). METHODS: The Global Aging and Geriatric Experiments in Bipolar Disorder consortium provided international data on 437 older age bipolar disorder participants. We compared LOBD versus EOBD on depression, mania, functionality, and physical comorbidities. Exploratory analyses were performed on participants with BD onset ≥50 years old. RESULTS: LOBD (n = 105) did not differ from EOBD (n = 332) on depression, mania, global functioning, nor employment status (p > 0.05). Late-onset bipolar disorder was associated with higher endocrine comorbidities (odds ratio = 1.48, [95%CI = 1.0,12.1], p = 0.03). This difference did not remain significant when subjects with BD onset ≥50 years old were analyzed. LIMITATIONS: This study is limited by the retrospective nature of the variable age of onset and the differences in evaluation methods across studies (partially overcame by harmonization processes). CONCLUSION: The present analysis is in favor of the hypothesis that LOBD might represent a similar clinical phenotype as classic EOBD with respect to core BD symptomatology, functionality, and comorbid physical conditions. Large-scale global collaboration to improve our understanding of BD across the lifespan is needed.

Sex-specific associations in verbal memory brain circuitry in early psychosis.

Hippocampal circuitry and related cortical connections are altered in first episode psychosis (FEP) and are associated with verbal memory deficits, as well as positive and negative symptoms. There are robust sex differences in the clinical presentation of psychosis, including poorer verbal memory in male patients. Consideration of sex differences in hippocampal-cortical circuitry and their associations with different behavioral dimensions may be useful for understanding the underlying pathophysiology of verbal memory deficits and related symptomatology in psychosis. Here, we use a data-driven approach to simultaneously capture the complex links between sex, verbal memory, symptoms, and cortical-hippocampal brain metrics in FEP. Structural magnetic resonance imaging and behavioral data were acquired from 100 FEP patients (75 males, 25 females) and 87 controls (55 males, 32 females). Multivariate brain-behavior associations were examined in FEP using partial least squares to map sociodemographic, verbal memory, and clinical data onto brain morphometry. The analysis identified two sex-dependent patterns of verbal memory, symptoms, and brain structure. In male patients, verbal memory deficits and core psychotic symptoms were associated with both increased and decreased frontal and temporal cortical thickness and reductions in CA2/3 hippocampal subfield and fornix volumes. In female patients, fewer negative/depressive symptoms were associated with a more attenuated cortical thickness pattern and more diffuse reductions in hippocampal white matter regions. Taken together, the results contribute towards better understanding the underlying pathophysiology of psychosis by highlighting the unique contribution of specific hippocampal subfields and surrounding white matter and their connections with broader cortical networks in a sex-dependent manner.

Annotating unknown species of urban microorganisms on a global scale unveils novel functional diversity and local environment association.

In urban ecosystems, microbes play a key role in maintaining major ecological functions that directly support human health and city life. However, the knowledge about the species composition and functions involved in urban environments is still limited, which is largely due to the lack of reference genomes in metagenomic studies comprises more than half of unclassified reads. Here we uncovered 732 novel bacterial species from 4728 samples collected from various common surface with the matching materials in the mass transit system across 60 cities by the MetaSUB Consortium. The number of novel species is significantly and positively correlated with the city population, and more novel species can be identified in the skin-associated samples. The in-depth analysis of the new gene catalog showed that the functional terms have a significant geographical distinguishability. Moreover, we revealed that more biosynthetic gene clusters (BGCs) can be found in novel species. The co-occurrence relationship between BGCs and genera and the geographical specificity of BGCs can also provide us more information for the synthesis pathways of natural products. Expanded the known urban microbiome diversity and suggested additional mechanisms for taxonomic and functional characterization of the urban microbiome. Considering the great impact of urban microbiomes on human life, our study can also facilitate the microbial interaction analysis between human and urban environment.

Minds@Work: A New Manualized Intervention to Improve Job Tenure in Psychosis Based on Scoping Review and Logic Model.

Introduction A significant proportion of people experiencing psychosis are unemployed, despite a strong desire to work. Current supported employment programs appear effective in helping them obtain employment, yet job tenure remains an arduous challenge. The objective of this study was to review the literature and model the results to inform the development of a new manualized group psychosocial intervention-'Minds@Work'-aimed specifically at improving job tenure in psychosis. Methods The study was registered on the Open Science Framework platform ( https://osf.io/he68z ). The literature was searched in Medline, Embase, PsycInfo and Cochrane Library databases for studies examining predictors of job tenure in psychosis and existing occupational psychosocial interventions. Data were extracted using a pre-established form and synthesized using logic models. Results A total of 94 studies were included and their findings were modeled using different categories: intervention typologies, mechanisms of action, predictors of job tenure, outcomes and contextual factors. The 'Minds@Work' program was built based on these modeled findings and aimed to target specific predictors of job tenure while addressing some of the limitations of existing interventions. The program uses evidence-based techniques and is divided into 9 modules covering 4 themes: positive psychology (motivation, character strengths, self-compassion), neurocognitive remediation (attention, memory, problem-solving), cognitive biases training (jumping to conclusions, defeatists beliefs, theory of mind, attributional styles) and socioemotional coping skills (emotion regulation, communication). Conclusions Once validated, this new program is meant to be used either as a stand-alone intervention or integrated in supported employment initiatives, by employment specialists or healthcare workers.

Biowarfare, bioterrorism and biocrime: A historical overview on microbial harmful applications.

Microbial Forensics is a field that continues to grow in interest and application among the forensic community. This review, divided into two sections, covers several topics associated with this new field. The first section presents a historic overview concerning the use of microorganisms (or its product, i.e. toxins) as harmful biological agents in the context of biological warfare (biowarfare), bioterrorism, and biocrime. Each case is illustrated with the examination of case reports that span from prehistory to the present day. The second part of the manuscript is devoted to the role of MF and highlights the necessity to prepare for the pressing threat of the harmful use of biological agents as weapons. Preventative actions, developments within the field to ensure a timely and effective response and are discussed herein.

Classification of STR allelic variation using massively parallel sequencing and assessment of flanking region power.

The application of massively parallel sequencing (MPS) to forensic genetics has led to improvements in multiple aspects of DNA analysis, however, additional complexities are concurrently associated with these advances. In relation to short tandem repeat (STR) typing, the move to sequence rather than length-based methodologies has highlighted the extent to which previous allelic variation was masked - both within and outside of the repeat regions (the flanking regions). In order to fully implement MPS for autosomal STR analysis, sequence-based allelic frequencies must be available, and concordance with previous typing techniques needs to be assessed. In this work, a series of samples (n = 1007) from five different population groups were genotyped using the MiSeq FGx™ Forensic Genomics System. Results were compared to those obtained using capillary electrophoresis (CE), and sequence variation has been characterised both within and outside STR repeat regions, with allelic frequencies provided for all variants observed within this database. Analysing and characterising flanking region sequence is currently less straightforward than studying repeat region variation alone, and the added value of doing so remains largely unexplored - this paper provides data to show that the gain in polymorphism achieved when analysing flanking regions is less than might be expected. In the White British population for example, including the sequence variation within repeat regions of 26 autosomal STRs made the average combined random match probability (RMP) over 700 times lower than with length-based alleles alone. Including the sequence variation within the flanking regions only resulted in a combined RMP that was a further 4 times lower.

Sex Differences in Verbal Memory Predict Functioning Through Negative Symptoms in Early Psychosis.

Verbal memory (VM) is one of the most affected cognitive domains in first-episode psychosis (FEP) and is a robust predictor of functioning. Given that healthy females demonstrate superior VM relative to males and that female patients show less-severe illness courses than male patients, this study examined whether normative sex differences in VM extend to FEP and influence functioning. Four hundred and thirty-five patients (299 males, 136 females) with affective or nonaffective psychosis were recruited from a catchment-based specialized FEP intervention service and 138 nonclinical controls (96 males, 42 females) were recruited from the same community. One of the two neurocognitive batteries comprising six cognitive domains (VM, visual memory, working memory, attention, executive function, processing speed) were administered at baseline. In patients, positive and negative symptoms were evaluated at baseline and functioning was assessed at 1-year follow-up. Patients were more impaired than controls on all cognitive domains, but only VM showed sex differences (both patient and control males performed worse than females), and these results were consistent across batteries. In patients, better baseline VM in females was related to better functioning after 1 year, mediated through fewer baseline negative symptoms. Supplemental analyses revealed these results were not driven by affective psychosis nor by age and parental education. Thus, normative sex differences in VM are preserved in FEP and mediate functioning at 1-year follow-up via negative symptoms. This study highlights the importance of investigating sex effects for understanding VM deficits in early psychosis and suggests that sex may be a disease-modifying variable with important treatment implications.

Concordance of the ForenSeq™ system and characterisation of sequence-specific autosomal STR alleles across two major population groups.

By using sequencing technology to genotype loci of forensic interest it is possible to simultaneously target autosomal, X and Y STRs as well as identity, ancestry and phenotypic informative SNPs, resulting in a breadth of data obtained from a single run that is considerable when compared to that generated with standard technologies. It is important however that this information aligns with the genotype data currently obtained using commercially available kits for CE-based investigations such that results are compatible with existing databases and hence can be of use to the forensic community. In this work, 400 samples were typed using commercially available STR kits and CE, as well as using the Ilumina ForenSeq™ DNA Signature Prep Kit and MiSeq® FGx to assess concordance of autosomal STRs and population variability. Results show a concordance rate between the two technologies exceeding 99.98% while numerous novel sequence based alleles are described. In order to make use of the sequence variation observed, sequence specific allele frequencies were generated for White British and British Chinese populations.