Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

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; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: 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.).

Lost in translation? The potential psychobiotic Lactobacillus rhamnosus (JB-1) fails to modulate stress or cognitive performance in healthy male subjects.

BACKGROUND: Preclinical studies have identified certain probiotics as psychobiotics - live microorganisms with a potential mental health benefit. Lactobacillus rhamnosus (JB-1) has been shown to reduce stress-related behaviour, corticosterone release and alter central expression of GABA receptors in an anxious mouse strain. However, it is unclear if this single putative psychobiotic strain has psychotropic activity in humans. Consequently, we aimed to examine if these promising preclinical findings could be translated to healthy human volunteers. OBJECTIVES: To determine the impact of L. rhamnosus on stress-related behaviours, physiology, inflammatory response, cognitive performance and brain activity patterns in healthy male participants. METHODS: An 8week, randomized, placebo-controlled, cross-over design was employed. Twenty-nine healthy male volunteers participated. Participants completed self-report stress measures, cognitive assessments and resting electroencephalography (EEG). Plasma IL10, IL1ß, IL6, IL8 and TNFα levels and whole blood Toll-like 4 (TLR-4) agonist-induced cytokine release were determined by multiplex ELISA. Salivary cortisol was determined by ELISA and subjective stress measures were assessed before, during and after a socially evaluated cold pressor test (SECPT). RESULTS: There was no overall effect of probiotic treatment on measures of mood, anxiety, stress or sleep quality and no significant effect of probiotic over placebo on subjective stress measures, or the HPA response to the SECPT. Visuospatial memory performance, attention switching, rapid visual information processing, emotion recognition and associated EEG measures did not show improvement over placebo. No significant anti-inflammatory effects were seen as assessed by basal and stimulated cytokine levels. CONCLUSIONS: L. rhamnosus was not superior to placebo in modifying stress-related measures, HPA response, inflammation or cognitive performance in healthy male participants. These findings highlight the challenges associated with moving promising preclinical studies, conducted in an anxious mouse strain, to healthy human participants. Future interventional studies investigating the effect of this psychobiotic in populations with stress-related disorders are required.

Early detection monitoring for aquatic non-indigenous species: Optimizing surveillance, incorporating advanced technologies, and identifying research needs.

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.

Can a rapid underwater video approach enhance the benthic assessment capability of the national coastal condition assessment in the great lakes?

Over 400 sites were sampled in the nearshore of the U.S. Great Lakes during the U.S. National Coastal Condition Assessment (NCCA) field survey in summer 2010. Underwater video images were recorded in addition to routine NCCA benthic assessment measures. This paper has two objectives: (1) to develop a process to evaluate video performance with acceptance criteria, exploring reasons for poor images, and (2) to use acceptable videos in an example application with invasive mussels, evaluating the enhancement potential of video to supplement traditional grab sampling. A standard hierarchical protocol was developed to rank video performance based on quality and clarity. We determined controllable and uncontrollable factors affecting video performance. Moreover, specific thresholds limiting video were identified: >0.5/m for light extinction and >3.5 µg/L for chlorophyll a concentration. To demonstrate the utility and enhancement potential of video sampling, observed dreissenid presence from excellent (221 of 362 videos) videos was compared with NCCA benthic taxonomy, in the context of the statistically based NCCA survey. Including video increased the overall area estimate of the U.S. Great Lakes nearshore with invasive mussels by about 15% compared to PONAR alone; 44% (7570 km(2)) of the surveyed region had mussels. The proportion of the nearshore area having mussels varied from low (3.5%) in Lake Superior to >50% in the lower lakes. PONAR and video have unique strengths and weaknesses as sampling tools in the Great Lakes nearshore environment, but when paired were complimentary and thus provided a more thorough benthic condition assessment at lake and regional scales.

Amid magic and menace: psychiatrists' attitudes to psilocybin therapy.

OBJECTIVES: Understanding variations in knowledge and attitudes of psychiatrists to psilocybin therapy is important for the collective discourse about the potential impact on clinical practice and public health in Ireland. METHODS: A 28-item questionnaire was designed based on previous studies and distributed to psychiatrists in Ireland via online mailing lists and at in-person academic events. RESULTS: 151 psychiatrists completed the questionnaire (73.3% were under 40 years of age, 76.0% were trainees, and 49.0% were female). In the total sample, 81.5% agreed that psilocybin therapy shows promise in the treatment of psychiatric disorders and 86.8% supported funding research, 86.8% would be willing to refer a patient if it was licensed and indicated, and 78.1% would consider the treatment for themselves, if indicated. Conversely, 6.6% agreed that psilocybin therapy was unsafe even under medical supervision, and 21.9% thought it was potentially addictive. 15.9% of the total sample reported at least one concern including, lack of robust evidence, long-term effectiveness, superiority to current interventions, potential harmful effects, cost and accessibility, and impartiality. Less than half of respondents felt knowledgeable (40.0%) and 9.9% felt adequately prepared to participate in psilocybin therapy. Consultant psychiatrists trended towards less optimism for a potential role in bipolar depression and emotionally unstable personality disorder compared to trainee psychiatrists. CONCLUSION: Overall psychiatrists in Ireland held positive attitudes towards psilocybin therapy. However, there was a lack of knowledge evident. Addressing the knowledge gap and aligning with the best available evidence will be key if psychedelic therapy is to prevail in a clinical setting.

Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis.

Moving towards a systems psychiatry paradigm embraces the inherent complex interactions across all levels from micro to macro and necessitates an integrated approach to treatment. Cortical 5-HT2A receptors are key primary targets for the effects of serotonergic psychedelics. However, the therapeutic mechanisms underlying psychedelic therapy are complex and traverse molecular, cellular, and network levels, under the influence of biofeedback signals from the periphery and the environment. At the interface between the individual and the environment, the gut microbiome, via the gut-brain axis, plays an important role in the unconscious parallel processing systems regulating host neurophysiology. While psychedelic and microbial signalling systems operate over different timescales, the microbiota-gut-brain (MGB) axis, as a convergence hub between multiple biofeedback systems may play a role in the preparatory phase, the acute administration phase, and the integration phase of psychedelic therapy. In keeping with an interconnected systems-based approach, this review will discuss the gut microbiome and mycobiome and pathways of the MGB axis, and then explore the potential interaction between psychedelic therapy and the MGB axis and how this might influence mechanism of action and treatment response. Finally, we will discuss the possible implications for a precision medicine-based psychedelic therapy paradigm.

Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication.

Psilocybin is being investigated as a treatment in adults with treatment-resistant depression (TRD). Withdrawal from serotonergic antidepressant drugs is a common prerequisite for taking part in trials of psilocybin due to the possibility of ongoing antidepressant drugs altering the psychedelic effect. This phase II, exploratory, international, fixed-dose, open-label study explored the safety, tolerability, and efficacy of a synthetic form of psilocybin (investigational drug COMP360) adjunct to a selective serotonin reuptake inhibitor in participants with TRD. Participants received a single 25 mg dose of psilocybin alongside psychological support and were followed-up for 3 weeks. The primary efficacy end point was change in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score from Baseline at Week 3. Secondary end points were safety, including treatment-emergent adverse events (TEAEs), the proportion of responders and remitters at Week 3, and the change from Baseline to Week 3 in Clinical Global Impression-Severity (CGI-S) score. Nineteen participants were dosed and the mean Baseline MADRS total score was 31.7 (SD = 5.77). Twelve (63.2%) participants had a TEAE, most of which were mild and resolved on the day of onset. There were no serious TEAEs or indication of increased suicidal ideation or behavior. At Week 3, mean change from Baseline in MADRS total score was -14.9 (95% CI, -20.7 to -9.2), and -1.3 (SD = 1.29) in the CGI-S. Both response and remission were evident in 8 (42.1%) participants. Larger, comparator-controlled trials are necessary to understand if this paradigm can optimize treatment-outcome where antidepressant drug withdrawal would be problematic.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

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.

Water quality and plankton in the United States nearshore waters of Lake Huron.

Our goal in the development of a nearshore monitoring method has been to evaluate and refine an in situ mapping approach to assess the nearshore waters across the Great Lakes. The report here for Lake Huron is part of a broader effort being conducted across all five Great Lakes. We conducted an intensive survey for the United States nearshore of Lake Huron along a continuous shoreline transect (523 km) from Port Huron, Michigan, to Detour Passage. A depth contour of 20 m was towed with a conductivity-temperature depth profiler, fluorometer, transmissometer, and laser optical plankton counter. Multiple cross-contour tows (10-30 m) on the cruise dates were used to characterize the variability across a broader range of the nearshore. The cross-contour tows were comparable with the alongshore contour indicating that the 20-m contour does a good job of representing the nearshore region (10-30 m). Strong correlations were observed between water quality and spatially associated watershed land use. A repeat tow separated by several weeks investigated temporal variability in spatial patterns within a summer season. Strong correlations were observed across each variable for the temporal repeat across broad- and fine-scale spatial dimensions. The survey results for Lake Huron nearshore are briefly compared with a similar nearshore survey in Lake Superior. The biomass concentrations of lower food web components of Lake Huron were notably approximately 54-59 % of those in Lake Superior. The towed instrumentation survey supported the recent view of a change in Lake Huron to an ultra-oligotrophic state, which has been uncharacteristic in recent history.

Psychedelic perceptions: mental health service user attitudes to psilocybin therapy.

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.

Minding metabolism: targeted interventions to improve cardio-metabolic monitoring across early and chronic psychosis.

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 (<15%) assessment was poor. In chronic psychotic disorders, BP monitoring improved (20% vs 41.4%, p=0.05), whereas weight (17.0% vs 34.1%, p=0.12), BMI (9.7% vs 12.1%, p=1.0), fasting glucose (17% vs 24.3%, p=0.58) and fasting lipids remained unchanged (17% vs 24.3%, p=0.58). CONCLUSIONS: Targeted improvement strategies resulted in a significant improvement in a limited number of parameters in early and chronic psychotic disorders. Overall, monitoring remained suboptimal.

The role of the gut microbiome in the development of schizophrenia.

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.

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective.

Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

Amygdala substructure volumes in Major Depressive Disorder.

The role of the amygdala in the experience of emotional states and stress is well established. Connections from the amygdala to the hypothalamus activate the hypothalamic-pituitaryadrenal (HPA) axis and the cortisol response. Previous studies have failed to find consistent whole amygdala volume changes in Major Depressive Disorder (MDD), but differences may exist at the smaller substructural level of the amygdala nuclei. High-resolution T1 and T2-weighted-fluid-attenuated inversion recovery MRIs were compared between 80 patients with MDD and 83 healthy controls (HC) using the automated amygdala substructure module in FreeSurfer 6.0. Volumetric assessments were performed for individual nuclei and three anatomico-functional composite groups of nuclei. Salivary cortisol awakening response (CAR), as a measure of HPA responsivity, was measured in a subset of patients. The right medial nucleus volume was larger in MDD compared to HC (p = 0.002). Increased right-left volume ratios were found in MDD for the whole amygdala (p = 0.004), the laterobasal composite (p = 0.009) and in the central (p = 0.003) and medial (p = 0.014) nuclei. The CAR was not significantly different between MDD and HC. Within the MDD group the left corticoamygdaloid transition area was inversely correlated with the CAR, as measured by area under the curve (AUCg) (p ≤ 0.0001). In conclusion, our study found larger right medial nuclei volumes in MDD compared to HC and relatively increased right compared to left whole and substructure volume ratios in MDD. The results suggest that amygdala substructure volumes may be involved in the pathophysiology of depression.

An audit of the cervical screening programme in the National Drug Treatment Centre (NDTC).

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.

Mood and Microbes: Gut to Brain Communication in Depression.

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.

Mood matters: a national survey on attitudes to depression.

BACKGROUND: 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. AIMS: To explore public attitudes to, and management of depression, including lifestyle factors, medication, and psychotherapy. METHODS: A nationally representative online population survey of Irish adults was conducted by RED C. RESULTS: 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. CONCLUSIONS: 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.

Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis

Moving towards a systems psychiatry paradigm embraces the inherent complex interactions across all levels from micro to macro and necessitates an integrated approach to treatment. Cortical 5-HT2A receptors are key primary targets for the effects of serotonergic psychedelics. However, the therapeutic mechanisms underlying psychedelic therapy are complex and traverse molecular, cellular, and network levels, under the influence of biofeedback signals from the periphery and the environment. At the interface between the individual and the environment, the gut microbiome, via the gut-brain axis, plays an important role in the unconscious parallel processing systems regulating host neurophysiology. While psychedelic and microbial signalling systems operate over different timescales, the microbiota-gut-brain (MGB) axis, as a convergence hub between multiple biofeedback systems may play a role in the preparatory phase, the acute administration phase, and the integration phase of psychedelic therapy. In keeping with an interconnected systems-based approach, this review will discuss the gut microbiome and mycobiome and pathways of the MGB axis, and then explore the potential interaction between psychedelic therapy and the MGB axis and how this might influence mechanism of action and treatment response. Finally, we will discuss the possible implications for a precision medicine-based psychedelic therapy paradigm. (AU)

Sensitivity and accuracy of high-throughput metabarcoding methods for early detection of invasive fish species.

High-throughput DNA metabarcoding has gained recognition as a potentially powerful tool for biomonitoring, including early detection of aquatic invasive species (AIS). DNA based techniques are advancing, but our understanding of the limits to detection for metabarcoding complex samples is inadequate. For detecting AIS at an early stage of invasion when the species is rare, accuracy at low detection limits is key. To evaluate the utility of metabarcoding in future fish community monitoring programs, we conducted several experiments to determine the sensitivity and accuracy of routine metabarcoding methods. Experimental mixes used larval fish tissue from multiple "common" species spiked with varying proportions of tissue from an additional "rare" species. Pyrosequencing of genetic marker, COI (cytochrome c oxidase subunit I) and subsequent sequence data analysis provided experimental evidence of low-level detection of the target "rare" species at biomass percentages as low as 0.02% of total sample biomass. Limits to detection varied interspecifically and were susceptible to amplification bias. Moreover, results showed some data processing methods can skew sequence-based biodiversity measurements from corresponding relative biomass abundances and increase false absences. We suggest caution in interpreting presence/absence and relative abundance in larval fish assemblages until metabarcoding methods are optimized for accuracy and precision.

Cross Talk: The Microbiota and Neurodevelopmental Disorders.

Humans evolved within a microbial ecosystem resulting in an interlinked physiology. The gut microbiota can signal to the brain via the immune system, the vagus nerve or other host-microbe interactions facilitated by gut hormones, regulation of tryptophan metabolism and microbial metabolites such as short chain fatty acids (SCFA), to influence brain development, function and behavior. Emerging evidence suggests that the gut microbiota may play a role in shaping cognitive networks encompassing emotional and social domains in neurodevelopmental disorders. Drawing upon pre-clinical and clinical evidence, we review the potential role of the gut microbiota in the origins and development of social and emotional domains related to Autism spectrum disorders (ASD) and schizophrenia. Small preliminary clinical studies have demonstrated gut microbiota alterations in both ASD and schizophrenia compared to healthy controls. However, we await the further development of mechanistic insights, together with large scale longitudinal clinical trials, that encompass a systems level dimensional approach, to investigate whether promising pre-clinical and initial clinical findings lead to clinical relevance.