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BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression.METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits).RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; PCONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints.METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function.RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures.LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin.CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

When first introduced, invasive species typically evade detection; DNA barcoding coupled with high-throughput sequencing (HTS) may be more sensitive and accurate than morphology-based taxonomy and thereby improve invasive (or rare) species detection. We quantified the relative error of species detection between morphology-based and HTS-based taxonomic identification of ichthyoplankton collections from the Port of Duluth, Minnesota, an aquatic non-native species introduction “hot-spot” in the Laurentian Great Lakes. We found HTS-based taxonomy identified 28 species and morphology-based taxonomy identified 30 species, of which 27 were common to both. Among samples, 76% of family-level taxonomic assignments agreed; however, only 42% of species assignments agreed. Most errors were attributed to morphology-based taxonomy, whereas HTS-based taxonomy error was low. For this study system, for most non-native fishes, the detection probability by randomized survey for larvae was similar to that by a survey that is optimized for non-native species early detection of juveniles and adults. We conclude that classifying taxonomic errors by comparing HTS results against morphology-based taxonomy is an important step toward incorporating HTS-based taxonomy into biodiversity surveys.

This paper examines a head coach’s enactment of their hybrid role (i.e., it was comprised of leadership, management, and coaching responsibilities) in an elite level sport organisation. A methodological bricolage comprising a) participant observation and reflexive field notes, b) ethnographic film, and c) semi-structured and stimulated recall interviews was used to generate data during 20 months of ethnographic fieldwork with an international rugby union team. Data were iteratively analysed using Crossley’s (2011) relational theorising. The head coach was found to strategically manage nuanced relations with, and between, more and less trusted collaborators in the organisation. This positioned her to maintain oversight and to influence the support, capital, resources and information flowing through relational networks towards the organisation’s key mission. Strategic interaction that responded to others’ thoughts, feelings and interests was used to generate buy-in, space and time to carry out the manager’s agendas. The findings highlight the importance for researchers, policy makers, sport organisations, educators and practitioners of further engaging with management as an ongoing exercise in collective behaviour, which includes micropolitical struggles and exchange.

Background Women diagnosed with substance use disorders (SUDs) have higher rates of major medical conditions compared to women without SUDs. Cervical cancer is the second leading cause of cancer death in women aged 20–39 years worldwide and women with SUDs have an increased risk of cervical cancer compared to women without SUD. The National Drug Treatment Centre (NDTC) cervical screening programme, derived from the national CervicalCheck programme, offers free cervical screening to patients attending for treatment of SUDs. Aims This study aimed to audit adherence to the NDTC Cervical Screening guidelines before and after the implementation of an awareness-raising educational intervention. Methods The electronic clinical records of women aged between 25 and 60 years attending the lead consultant’s (M.S.) outpatient clinic were reviewed for documentary evidence indicating that information about the cervical screening programme had been discussed. This was completed before and one month after the implementation of an awareness-raising educational intervention. Results All women (n = 46, mean age 36.3 (SD = 6.5) years) had an opioid use disorder; 85% had a benzodiazepine use disorder, and 24% had an alcohol use disorder. Of these, 80% had at least one chronic medical condition, 76% had a psychiatric disorder, and 59% were homeless. Adherence to the NDTC cervical screening guideline, as indicated by documentary evidence in clinical records, was 33% (14/43) at baseline, and rose to 88% (36/41) (p < 0.0001) one month after the intervention. Conclusions This completed audit cycle shows that an awareness-raising educational intervention can significantly improve adherence to a cervical screening programme in women with SUDs.

Sport has been a major strategic cultural practice used by Western allies to encourage citizens to support and “thank” their governments’ military actors. This increasingly visible intersection of sport and militarism occurred simultaneously alongside the development of propaganda departments by the American and Canadian governments seeking to use sport (and other popular cultural activities) to communicate consent for their respective military actors and actions. United Kingdom (UK) has witnessed many of these campaigns being replicated with a wide range of popular culture practices being utilized to provide public performances of support for its nation’s military personnel. This article critically analyzes “support the troops” rhetoric in UK by discussing a selection of official sporting and political articulations. Of significance is the extent to which those coordinating numerous support strategies for military-related violence (and its political rationale) have incorporated the language and symbolism of UK military-related remembrance, which historically has been viewed as a sorrowful and sombre reflection on the mass slaughter of millions during two world wars. The significance and centrality of on-the-surface-apolitical communication in and of sport as a form of ideological inculcation is illustrated.

The medium- to long-term consequences of COVID-19 are not yet known, though an increase in mental health problems are predicted. Multidisciplinary strategies across socio-economic and psychological levels may be needed to mitigate the mental health burden of COVID-19. Preliminary evidence from the rapidly progressing field of psychedelic science shows that psilocybin therapy offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and maladaptive habitual patterns of cognition and behaviour, notably depression, addiction and obsessive compulsive disorder. The COMPASS Pathways (COMPASS) phase 2b double-blind trial of psilocybin therapy in antidepressant-free, treatment-resistant depression (TRD) is underway to determine the safety, efficacy and optimal dose of psilocybin. Results from the Imperial College London Psilodep-RCT comparing the efficacy and mechanisms of action of psilocybin therapy to the selective serotonin reuptake inhibitor (SSRI) escitalopram will soon be published. However, the efficacy and safety of psilocybin therapy in conjunction with SSRIs in TRD is not yet known. An additional COMPASS study, with a centre in Dublin, will begin to address this question, with potential implications for the future delivery of psilocybin therapy. While at a relatively early stage of clinical development, and notwithstanding the immense challenges of COVID-19, psilocybin therapy has the potential to play an important therapeutic role for various psychiatric disorders in post-COVID-19 clinical psychiatry.

Service liability interconnections among globally networked IT- and IoT-driven service organizations create potential channels for cascading service disruptions worth billions of dollars, due to modern cyber-crimes such as DDoS, APT, and ransomware attacks. A natural question that arises in this context is: What is the likelihood of a cyber-blackout? , where the latter term is defined as the probability that all (or a major subset of) organizations in a service chain become dysfunctional in a certain manner due to a cyber-attack at some or all points in the chain. The answer to this question has major implications to risk management businesses such as cyber-insurance when it comes to designing policies by risk-averse insurers for providing coverage to clients in the aftermath of such catastrophic network events. In this article, we investigate this question in general as a function of service chain networks and different cyber-loss distribution types. We show somewhat surprisingly (and discuss the potential practical implications) that, following a cyber-attack, the effect of (a) a network interconnection topology and (b) a wide range of loss distributions on the probability of a cyber-blackout and the increase in total service-related monetary losses across all organizations are mostly very small. The primary rationale behind these results are attributed to degrees of heterogeneity in the revenue base among organizations and the Increasing Failure Rate property of popular (i.i.d/non-i.i.d) loss distributions, i.e., log-concave cyber-loss distributions. The result will enable risk-averse cyber-risk managers to safely infer the impact of cyber-attacks in a worst-case network and distribution oblivious setting.

In 1967, in Lisbon, Celtic Football Club, won the European Cup becoming the first club outside of Portugal, Spain and Italy to win it. The win was and is totemic for the Irish Catholic immigrant community in Scotland that has historically supported Celtic. We suggest the significance of the win reveals intersections of ethnicity, religion, nationalism, and the politics of ‘sectarianism’ in Scotland. During a period of discriminatory practices and attitudes towards Irish descended Catholics in Scotland, this iconic win for a Scottish based club born of Irish Catholics personified for this diaspora that (on one level) their day had arrived. This article explores the socio-cultural significance and legacy of ‘Lisbon 67ʹ for insider and outsider groups in Scotland. We reveal that soccer remains a central component of group memory connecting the past, present and future. We suggest Celtic’s win offered confidence and hope to a marginalized group within Scotland.

The gut microbiota, acting via the gut-brain axis, modulates key neurobiological systems that are dysregulated in stress-related disorders. Preclinical studies show that the gut microbiota exerts an influence over neuroimmune and neuroendocrine signaling pathways, in addition to epigenetic modification, neurogenesis, and neurotransmission. In humans, preliminary evidence suggests that the gut microbiota profile is altered in depression. The full impact of microbiota-based treatments, at different neurodevelopmental time points, has yet to be fully explored. The integration of the gut microbiota, as a mediator, in the complex trajectory of depression, may enhance the possibility of personalized precision psychiatry.

This research examines the masculine identities and experiences of males within the subject of PE. Specifically, it examines the masculine identities of two groups of boys in the Scottish secondary physical education (PE) context: Secondary 1 (S1: age 12-13) and Secondary 4 (S4: age 15-16). Drawing from Hegemonic Masculinity Theory and Inclusive Masculinity Theory, this research set out to explore how masculine identities co-exist and develop within the same context, building on previous research that has examined masculine identities in the Scottish PE context. To do so, guided by key principles of ethnography and using qualitative methods, S1 and S4 boys were observed in their PE lessons for a period of 3 months. In the third month, 4 pupils in each class volunteered to take part in semi-structured group interviews. The results from our thematic analysis indicated that both groups performed different masculine identities. The S1 boys that were observed and interviewed adopted inclusive masculinities, where they seemed able to display a range of gendered behaviours without fear of stigmatisation or marginalisation. Conversely, the majority of the S4 boys observed and all of the boys that were interviewed embodied an exclusive form of masculinity, using their bodies to allow them to enact a range of masculine behaviours, while maintaining their superior position in the social hierarchy. This article highlights the need for more research into the construction of masculine identities as pupils navigate PE and school. We also suggest that teachers can be more pro-active in maintaining broad, inclusive and critical conceptions of PE as pupils progress from the junior to the senior years.

Depression is the leading contributor to the burden of disease worldwide. Stigma and negative attitudes to depression can act as barriers to treatment and to social inclusion. Understanding attitudes to depression and treatment has implications for individual outcomes and societal mental health.To explore public attitudes to, and management of depression, including lifestyle factors, medication, and psychotherapy.A nationally representative online population survey of Irish adults was conducted by RED C.Nine hundred ninety-one people completed the survey. The majority thought that depression was a medical illness (90%), was different to sadness or stress (89%), and that awareness of depression was increasing (89%), while stigma was reducing (69%). Self-reported lifetime depression rates were high and were significantly higher in younger people (18-34 yrs) (63% vs 55%, p = 0.017), and in urban areas (60% vs 44%, p 0.0001). Younger people were less likely to contact their GP (46% vs 61%, p = 0.034) and reported more stigma around antidepressants (ADTs) compared to older people ( 55 years) (74% vs 58%, p 0.0001). There were negative attitudes to ADTs and a preference for talking therapies and lifestyle changes. Males were more likely to hold negative attitudes to ADTs.Stigma around depression is reducing and public awareness is improving. However, the very high self-reported lifetime rates of depression may reflect milder forms or emotional/psychological distress, rather than clinical depression. Negative attitudes and stigma towards ADTs remains high. A collaborative, sustained effort is required to advance public appreciation of mood and its management, across the severity spectrum, in tandem with destigmatising the targeted use of ADTs.

Introduction Despite the rapid advance of psychedelic science and possible translation of psychedelic therapy into the psychiatric clinic, very little is known about mental health service user attitudes. Objectives To explore mental health service user attitudes to psychedelics and psilocybin therapy. Methods A questionnaire capturing demographics, diagnoses, previous psychedelic and other drug use, and attitudes to psychedelics and psilocybin therapy was distributed to mental health service users. Results Ninety-nine participants completed the survey (52% female, mean age 42 years). The majority (72%) supported further research, with 59% supporting psilocybin as a medical treatment. A total of 27% previously used recreational psilocybin, with a male preponderance (p = 0.01). Younger age groups, those with previous psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin. A total of 55% of the total sample would accept as a treatment if doctor recommended, whereas 20% would not. Fewer people with depression/anxiety had used recreational psychedelics (p = 0.03) but were more likely to support government funded studies (p = 0.02). A minority (5%) of people with conditions (psychosis and bipolar disorder) that could be exacerbated by psilocybin thought it would be useful for them. One fifth of the total sample viewed psychedelics as addictive and unsafe even under medical supervision. Concerns included fear of adverse effects, lack of knowledge, insufficient research, illegality, and relapse if medications were discontinued. Conclusions The majority supported further research into psilocybin therapy. Younger people, those with previous recreational psychedelic experience, and those with non-religious beliefs were more likely to have favourable attitudes towards psilocybin therapy.

Background Antipsychotics (APs) increase weight, metabolic syndrome, diabetes and cardiovascular disease. Guidelines recommend cardio-metabolic monitoring at initial assessment, at 3 months and then annually in people prescribed APs. Aim To determine the rates of cardio-metabolic monitoring in AP treated early and chronic psychosis and to assess the impact of targeted improvement strategies. Methods Medical records were reviewed in two cohorts of first-episode psychosis (FEP) patients before and after the implementation of a physical health parameter checklist and electronic laboratory order set. In a separate group of patients with chronic psychotic disorders, adherence to annual monitoring was assessed before and 3 months after an awareness-raising educational intervention. Results In FEP, fasting glucose (39% vs 67%, p=0.05), HbA1c (0% vs 24%, p=0.005) and prolactin (18% vs 67%, p=0.001) monitoring improved. There were no significant differences in weight (67% vs 67%, p=1.0), BMI (3% vs 10%, p=0.54), waist circumference (3% vs 0%, p=1.0), fasting lipids (61% vs 76% p=0.22) or ECG monitoring (67% vs 67%, p=1.0). Blood pressure (BP) (88% vs 57%, p=0.04) and heart rate (91% vs 65%, p=0.03) monitoring dis-improved. Diet (0%) and exercise (

Electoral politics is strongly influenced by unfolding events, some of them leading to major shifts in alignment. There has been renewed interest in the ‘floating voter’ in contemporary Europe, not least because of increased electoral support for right-wing political parties. In Scotland, however, the clearest example of realignment is to be found not so much in support for specific political parties, although that should not be ignored, but rather in a shift of sections of the population from UK unionism towards support for Scottish independence, despite the result of the 2014 Scottish independence referendum. We explore past contentions from certain authors that the ethno-religious, socio-economic and political stratification of supporters of the two largest football clubs in Scotland, Celtic and Rangers, may be linked to their personal voting dispositions with regards to the issue of Scottish independence. These past findings are discussed in light of our interviews with fans of Scottish football teams which explore their perceptions of the interconnection between football club support, nationalism, unionism, and political voting in contemporary Scotland. Our interviewees suggest that the shifting dynamics of contemporary Scottish politics in an era of constitutional evolution has been reflected in shifting political and social affiliations of Scottish football clubs: although the traditional political allegiances of Celtic and Rangers were argued to persist to a degree, consensus emerged that these traditional allegiances have been destabilised by broader political, socio-economic and ideological developments.

Reclining on the lyra of the fornix, the dorsal hippocampal commissure (DHC) facilitates communication between the left and right hippocampi. Despite being a key commissural fiber bundle of the hippocampus, the DHC remains relatively underexplored in humans. Using high-resolution T1 and T2 magnetic resonance imaging in conjunction with High Angular Resolution Diffusion Imaging and Constrained Spherical Deconvolution tractography, we investigated if there are differences between the DHC of a sample of 54 healthy controls and 38 patients diagnosed with Major Depressive Disorder (MDD). After isolating the DHC using an anatomically derived protocol, segmented volumes of the left and right temporal pole, amygdala, hippocampus and parahippocampal gyrus extracted. In both controls and MDD patients, DHC fibers were spread across each of these four regions, with the parahippocampal gyri contributing the most to the volume of this white matter tract. Furthermore, diffusion metrics showed no effect of aging or sex on the integrity of the DHC in either group. This study is the first to investigate the DHC in MDD and the first to demonstrate that the DHC connects with the amygdala and temporal pole on both sides of the brain. Our data shows that the human DHC, rather than simply connecting the left and right hippocampi, allows connections between each hippocampus and the contralateral temporal pole, amygdala and parahippocampal gyrus. This suggests that the human temporal lobe, and the parahippocampal gyrus, may exert more influence on the contralateral limbic system via the DHC than previously thought.

Online social interaction has become integral to contemporary social life, adding new dimensions to how young people learn, interact, and perceive themselves and one another. This paper presents theoretical insights from a year-long ethnographic study within a Scottish secondary school, where participant observation and qualitative interviews were used to explain pupils’ informal social relationships. Here, pupils aged 11-18 constructed and negotiated a hyper-surveillanced social space within which many became (or strived to become) visible and ‘known’ amongst others and where online presentations of self were highly important. This facilitated a celebrity-esque culture amongst the pupil population whereby pupils learnt from and emulated macro celebrity culture and often framed social interactions as entertainment. Central to these practices, was a continual desire to “make gains in distinction” by demonstrating high social status amongst peers. The paper explores the resulting implications for teaching, learning and pupil wellbeing within contemporary educational environments.

It has been customary to think of the rivalry between Heart of Midlothian FC (Hearts) and Hibernian FC (Hibs) in Scotland’s capital city as a less well-known and diluted imitation of the rivalry between Glasgow’s so-called Old Firm of Celtic and Rangers with both rivalries being located within the context of sectarian identity politics. In fact, as argued in this article, the early history of the two Edinburgh clubs reveals a considerably closer association with sectarianism than is to be found in the initial years of the Old Firm. In support of this claim, evidence is drawn here from Hibs’ exclusively Catholic origins and from Hearts’ militaristic connections at the time of the First World War. On the other hand, as we further demonstrate, the contemporary rivalry between Hearts and Hibs owes less to religious and ethnic division than to spatial factors, or at the very least to the imagining of place, and to perceptions centred on the comparable images of the two clubs, both on and off the field of play, not least in relation to social class. With specific reference to place, while Hearts supporters are eager to celebrate their club as ‘the talk o’ the toon (town)’, one is increasingly obliged to consider which Edinburgh imaginary is implied in their famous old song and also what Hibs supporters’ celebration of the city’s district of Leith tell us about the current rivalry. Furthermore, while the Hearts-Hibs rivalry has entered a post-sectarian phase, sectarian elements do remain a feature of both clubs although these tend to manifest themselves when they are in opposition to one or other of Glasgow’s Old Firm clubs for specific political and ethnic reasons.

Following decades of ecologic and economic impacts from a growing list of nonindigenous and invasive species, government and management entities are committing to systematic early- detection monitoring (EDM). This has reinvigorated investment in the science underpinning such monitoring, as well as the need to convey that science in practical terms to those tasked with EDM implementation. Using the context of nonindigenous species in the North American Great Lakes, this article summarizes the current scientific tools and knowledge - including limitations, research needs, and likely future developments - relevant to various aspects of planning and conducting comprehensive EDM. We begin with the scope of the effort, contrasting target-species with broad-spectrum monitoring, reviewing information to support prioritization based on species and locations, and exploring the challenge of moving beyond individual surveys towards a coordinated monitoring network. Next, we discuss survey design, including effort to expend and its allocation over space and time. A section on sample collection and analysis overviews the merits of collecting actual organisms versus shed DNA, reviews the capabilities and limitations of identification by morphology, DNA target markers, or DNA barcoding, and examines best practices for sample handling and data verification. We end with a section addressing the analysis of monitoring data, including methods to evaluate survey performance and characterize and communicate uncertainty. Although the body of science supporting EDM implementation is already substantial, research and information needs (many already actively being addressed) include: better data to support risk assessments that guide choice of taxa and locations to monitor; improved understanding of spatiotemporal scales for sample collection; further development of DNA target markers, reference barcodes, genomic workflows, and synergies between DNA-based and morphology-based taxonomy; and tools and information management systems for better evaluating and communicating survey outcomes and uncertainty.

Relationships between total soil or bioaccessible lead (Pb), measured using an in vitro bioaccessibility assay, and children’s blood lead levels (BLL) were investigated in an urban neighborhood in Philadelphia, Pennsylvania, USA, with a history of soil Pb contamination. Soil samples from 38 homes were analyzed to determine whether accounting for the bioaccessible Pb fraction improves statistical relationships with children’s BLLs. Total soil Pb ranged from 58 to 2,821 mg/kg; the bioaccessible Pb fraction ranged from 47 to 2,567 mg/kg. Children’s BLLs ranged from 0.3 to 9.8 μg/dL. Hierarchical models were used to compare relationships between total or bioaccessible Pb in soil and children’s BLLs. Total soil Pb as the predictor accounted for 25% of the variability in child BLL; bioaccessible soil Pb as the predictor accounted for 28% of BLL variability. A bootstrapping analysis confirmed a significant increase in R2 for the model using bioaccessible soil Pb as the predictor with 99.3% of bootstraps showing a positive increase. Estimated increases of 1.4 μg/dL and 1.6 μg/dL in BLL per 1,000 mg/kg Pb in soil were observed for this study area using total and bioaccessible Pb, respectively. Children’s age did not contribute significantly to the prediction of BLLs.

The psychedelic research renaissance is gaining traction. Preliminary clinical studies of the hallucinogenic fungi, psilocybin, with psychological support, have indicated improvements in mood, anxiety and quality of life. A seminal, open-label study demonstrated marked reductions in depression symptoms in participants with treatment-resistant depression (TRD). The associated neurobiological processes involve alterations in brain connectivity, together with altered amygdala and default mode network activity. At the cellular level, psychedelics promote synaptogenesis and neural plasticity. Prompted by the promising preliminary studies, a randomized, double-blind trial has recently been launched across Europe and North America to investigate the efficacy of psilocybin in TRD. One of these centres is based in Ireland – CHO Area 7 and Tallaght University Hospital. The outcome of this trial will determine whether psilocybin with psychological support will successfully translate into the psychiatric clinic for the benefit of patients.

The gut microbiota, acting via the gut-brain axis, modulates key neurobiological systems that are dysregulated in stress-related disorders. Preclinical studies show that the gut microbiota exerts an influence over neuroimmune and neuroendocrine signaling pathways, in addition to epigenetic modification, neurogenesis, and neurotransmission. In humans, preliminary evidence suggests that the gut microbiota profile is altered in depression. The full impact of microbiota-based treatments, at different neurodevelopmental time points, has yet to be fully explored. The integration of the gut microbiota, as a mediator, in the complex trajectory of depression, may enhance the possibility of personalized precision psychiatry.

Schizophrenia is a heterogeneous neurodevelopmental disorder involving the convergence of a complex and dynamic bidirectional interaction of genetic expression and the accumulation of prenatal and postnatal environmental risk factors. The development of the neural circuitry underlying social, cognitive and emotional domains requires precise regulation from molecular signalling pathways, especially during critical periods or "windows", when the brain is particularly sensitive to the influence of environmental input signalling. Many of the brain regions involved, and the molecular substrates sub-serving these domains are responsive to life-long microbiota-gut-brain (MGB) axis signalling. This intricate microbial signalling system communicates with the brain via the vagus nerve, immune system, enteric nervous system, enteroendocrine signalling and production of microbial metabolites, such as short-chain fatty acids. Preclinical data has demonstrated that MGB axis signalling influences neurotransmission, neurogenesis, myelination, dendrite formation and blood brain barrier development, and modulates cognitive function and behaviour patterns, such as, social interaction, stress management and locomotor activity. Furthermore, preliminary clinical studies suggest altered gut microbiota profiles in schizophrenia. Unravelling MGB axis signalling in the context of an evolving dimensional framework in schizophrenia may provide a more complete understanding of the neurobiological architecture of this complex condition and offers the possibility of translational interventions.