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The revival of psilocybin in psychopharmacological research heralds a potential paradigm shift for treating mood and anxiety disorders, and other psychiatric conditions beyond the psychotic spectrum. This critical review evaluates current evidence on psilocybin’s efficacy, juxtaposing potential benefits with the practical aspects of psychedelic-assisted psychotherapy (PAP) and the methodological constraints of existing research.
An electronic literature search was conducted using PubMed/MEDLINE, selecting studies published up to December 2023 that explored the clinical use of psilocybin in mood and anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and substance use disorder. Despite promising preliminary results suggesting psilocybin’s efficacy in alleviating depression and anxiety, as well as obsessions, compulsions, and addictive behaviors, significant evidence gaps persist. These include evaluating the efficacy of psilocybin compared to standard antidepressants or anxiolytic molecules and identifying patient subpopulations that might benefit most from PAP. Concerns about psilocybin’s safety, long-term efficacy, and optimal dosage remain unclear due to previous trials’ limitations. Real-world implementation faces challenges, including infrastructural requirements, personnel training, and unresolved legal and ethical issues. This paper argues for further research to substantiate the evidence base, emphasizing the need for larger studies that overcome current methodological limitations and explore psilocybin’s full therapeutic potential. While psilocybin holds promise for psychiatry, its successful translation from research to clinical practice demands more robust evidence on efficacy, safety, and methodological rigor. In addition, other factors, such as cultural stigma and legal/ethical issues, need to be successfully addressed to facilitate psilocybin’s implementation in healthcare systems.
The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.
Methods
Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.
Results
In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.
Conclusions
Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.
To identify the patients who are most likely to participate in discussions about palliative care (PC) and advance care planning (ACP), and to determine their preferred timing and approach of discussion.
Methods
The study included women aged 18–75 years diagnosed with breast cancer. In the quantitative phase, sociodemographic and clinical characteristics, knowledge, decision-making, and stigmas were evaluated. The qualitative phase included questions about patients’ understanding, timing, and method of discussing PC and ACP, which were analyzed by Bardin’s content analysis.
Results
In Phase 1, a total of 115 participants were included, with 53.04% completing both phases and 46.96% declining further participation. Those who completed both phases exhibited higher rates of marriage and educational attainment, while those who declined Phase 2 had a higher prevalence of advanced-stage cancer and palliative treatment. Completion of both phases was associated with a greater knowledge of reality and increased awareness of PC and ACP. Furthermore, the qualitative analysis revealed 5 convergent themes: timing, demystification, patient empowerment, misconception elimination, and open communication. These themes informed the development of a conceptual model that provides a framework for discussing PC and ACP with patients at different stages of cancer diagnosis and treatment, highlighting appropriate and inappropriate approaches and timing.
Significance of results
Early discussion is beneficial, but withholding information or infringing on autonomy should be avoided. The study reveals that married and highly educated individuals tend to be more receptive to these discussions. However, patients with late-stage cancer tend to decline participation. Patients value open communication, demystification of PC, and empowering discussions that eliminate misunderstandings. Efforts should be made to reach patients with limited familiarity, particularly those with late-stage cancer, to increase their receptiveness to enable well-informed decision-making.
Image-processing pipelines require the design of complex workflows combining many different steps that bring the raw acquired data to a final result with biological meaning. In the image-processing domain of cryo-electron microscopy single-particle analysis (cryo-EM SPA), hundreds of steps must be performed to obtain the three-dimensional structure of a biological macromolecule by integrating data spread over thousands of micrographs containing millions of copies of allegedly the same macromolecule. The execution of such complicated workflows demands a specific tool to keep track of all these steps performed. Additionally, due to the extremely low signal-to-noise ratio (SNR), the estimation of any image parameter is heavily affected by noise resulting in a significant fraction of incorrect estimates. Although low SNR and processing millions of images by hundreds of sequential steps requiring substantial computational resources are specific to cryo-EM, these characteristics may be shared by other biological imaging domains. Here, we present Scipion, a Python generic open-source workflow engine specifically adapted for image processing. Its main characteristics are: (a) interoperability, (b) smart object model, (c) gluing operations, (d) comparison operations, (e) wide set of domain-specific operations, (f) execution in streaming, (g) smooth integration in high-performance computing environments, (h) execution with and without graphical capabilities, (i) flexible visualization, (j) user authentication and private access to private data, (k) scripting capabilities, (l) high performance, (m) traceability, (n) reproducibility, (o) self-reporting, (p) reusability, (q) extensibility, (r) software updates, and (s) non-restrictive software licensing.
While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.
Methods
We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.
We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.
Results
Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.
Conclusions
Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.
Consumption of high-energy-yielding diets, rich in fructose and lipids, is a factor contributing to the current increase in non-alcoholic fatty liver disease prevalence. Gut microbiota composition and short-chain fatty acids (SCFAs) production alterations derived from unhealthy diets are considered putative underlying mechanisms. This study aimed to determine relationships between changes in gut microbiota composition and SCFA levels by comparing rats featuring diet-induced steatohepatitis with control counterparts fed a standard diet. A high-fat high-fructose (HFHF) feeding induced higher body, liver and mesenteric adipose tissue weights, increased liver triglyceride content and serum transaminase, glucose, non-HDL-c and MCP-1 levels. Greater liver malondialdehyde levels and glutathione peroxidase activity were also observed after feeding the hypercaloric diet. Regarding gut microbiota composition, a lowered diversity and increased abundances of bacteria from the Clostridium sensu stricto 1, Blautia, Eubacterium coprostanoligenes group, Flavonifractor, and UBA1819 genera were found in rats featuring diet-induced steatohepatitis, as well as higher isobutyric, valeric and isovaleric acids concentrations. These results suggest that hepatic alterations produced by a hypercaloric HFHF diet may be related to changes in overall gut microbiota composition and abundance of specific bacteria. The shift in SCFA levels produced by this unbalanced diet cannot be discarded as potential mediators of the reported hepatic and metabolic alterations.
The relationship between schizophrenia and violence is complex. The aim of this multicentre case–control study was to examine and compare the characteristics of a group of forensic psychiatric patients with a schizophrenia spectrum disorders and a history of significant interpersonal violence to a group of patients with the same diagnosis but no lifetime history of interpersonal violence.
Method
Overall, 398 patients (221 forensic and 177 non-forensic patients) were recruited across five European Countries (Italy, Germany, Poland, Austria and the United Kingdom) and assessed using a multidimensional standardised process.
Results
The most common primary diagnosis in both groups was schizophrenia (76.4%), but forensic patients more often met criteria for a comorbid personality disorder, almost always antisocial personality disorder (49.1 v. 0%). The forensic patients reported lower levels of disability and better social functioning. Forensic patients were more likely to have been exposed to severe violence in childhood. Education was a protective factor against future violence as well as higher levels of disability, lower social functioning and poorer performances in cognitive processing speed tasks, perhaps as proxy markers of the negative syndrome of schizophrenia. Forensic patients were typically already known to services and in treatment at the time of their index offence, but often poorly compliant.
Conclusions
This study highlights the need for general services to stratify patients under their care for established violence risk factors, to monitor patients for poor compliance and to intervene promptly in order to prevent severe violent incidents in the most clinically vulnerable.
Fructose (C6H12O6), also known as levulose, is a hexose. Chronic consumption of fructose may be associated with increased intrahepatic fat concentration and the development of insulin resistance as well as an increase in the prevalence of nonalcoholic fatty liver disease and hyperlipidemia during pregnancy. Despite the existence of many studies regarding the consumption of fructose in pregnancy, its effects on fetuses have not yet been fully elucidated. Therefore, the objective of this study was to evaluate the genetic and biochemical effects in offspring (male and female) of female mice treated with fructose during pregnancy and lactation. Pairs of 60-day-old Swiss mice were used and divided into three groups; negative control and fructose, 10%/l and 20%/l doses of fructose groups. After offspring birth, the animals were divided into six groups: P1 and P2 (males and females), water; P3 and P4 (males and females) fructose 10%/l; and P5 and P6 (males and females) fructose 20%/l. At 30 days of age, the animals were euthanized for genetic and biochemical assessments. Female and male offspring from both dosage groups demonstrated genotoxicity (evaluated through comet assay) and oxidative stress (evaluated through nitrite concentration, sulfhydril content and superoxide dismutase activity) in peripheral and brain tissues. In addition, they showed nutritional and metabolic changes due to the increase in food consumption, hyperglycemia, hyperlipidemia, and metabolic syndrome. Therefore, it is suggested that high consumption of fructose by pregnant female is harmful to their offspring. Thus, it is important to carry out further studies and make pregnant women aware of excessive fructose consumption during this period.
We investigated the habitat use and feeding ecology of 10 cetacean species encountered along the south-eastern coast of Brazil (24–26°S) using carbon (δ13C) and nitrogen (δ15N) stable isotopes. Hierarchical cluster analysis distinguished two main groups based on their isotopic patterns. One group included migratory baleen whales (Megaptera novaeangliae and Eubalaena australis) with the lowest δ13C and δ15N values, reflecting baseline isotopic values of their Subantarctic feeding grounds and consumption of lower trophic level prey. Resident species and those occasionally occurring in Brazilian coastal waters highly differed from the migratory whales in their isotopic values. In this group, Tursiops truncatus had the highest δ13C and δ15N values, indicating coastal habits and relatively higher trophic position. Similar δ13C values were observed in Sotalia guianensis, Pontoporia blainvillei, Orcinus orca and Steno bredanensis. However, the former two species had lower δ15N values than the latter two, indicating different trophic positions. The relatively lower δ13C values observed in Stenella frontalis suggest greater influence of pelagic prey in their diet. Furthermore, the lower δ13C values observed in Delphinus delphis and Balaenoptera edeni were associated with upwelling events that occur along the region, affecting the isotopic values of their main prey. Juvenile M. novaeangliae had higher δ13C and δ15N than the adults, which may indicate feeding in areas with different isoscapes and consumption of pelagic schooling fish with relatively higher trophic levels than krill. This study provides preliminary information that are useful to understand the habitat use and coexistence of cetacean species occurring in south-eastern Brazil.
Epigenetic age acceleration (AA) has been associated with adverse environmental exposures and many chronic conditions. We estimated, in the NINFEA birth cohort, infant saliva epigenetic age, and investigated whether parental socio-economic position (SEP) and pregnancy outcomes are associated with infant epigenetic AA. A total of 139 saliva samples collected at on average 10.8 (range 7–17) months were used to estimate Horvath’s DNA methylation age. Epigenetic AA was defined as the residual from a linear regression of epigenetic age on chronological age. Linear regression models were used to test the associations of parental SEP and pregnancy outcomes with saliva epigenetic AA. A moderate positive association was found between DNA methylation age and chronological age, with the median absolute difference of 6.8 months (standard deviation [SD] 3.9). The evidence of the association between the indicators of low SEP and epigenetic AA was weak; infants born to unemployed mothers or with low education had on average 1 month higher epigenetic age than infants of mothers with high education and employment (coefficient 0.78 months, 95% confidence intervals [CIs]: −0.79 to 2.34 for low/medium education; 0.96, 95% CI: −1.81 to 3.73 for unemployment). There was no evidence for association of gestational age, birthweight or caesarean section with infant epigenetic AA. Using the Horvath’s method, DNA methylation age can be fairly accurately predicted from saliva samples already in the first months of life. This study did not reveal clear associations between either pregnancy outcomes or parental socio-economic characteristics and infant saliva epigenetic AA.
This study evaluated the feeding habits of the franciscana dolphin (Pontoporia blainvillei) in south-eastern Brazil. Stomach contents were collected from a total of 145 dead specimens found incidentally caught by fishing vessels or stranded between 2005 and 2015. Fish otoliths, cephalopod beaks and whole non-digested prey were used for prey species identification. A total of 9337 prey items were identified, including 26 species of teleost fishes and three species of cephalopods. The most important prey families were Sciaenidae among fish and Loliginidae among cephalopods. Franciscana dolphins tended to feed on small fish (mean = 5.25 cm) and cephalopods (mean = 8.57 cm). The index of relative importance (IRI) showed that Pellona harroweri and Doryteuthis plei were the most important prey for both males and females. The PERMANOVA test confirmed that there is no significant difference between the feeding habits of different sexes, but detected a significant difference among seasons. Overall, our results show that franciscana dolphins are predominantly ichthyophagous and non-selective in relation to the type of prey, feeding on pelagic, demersal and pelagic-demersal prey.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
Aims
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Method
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
Results
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
Conclusions
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
We present a dynamical proof of the well-known fact that the Néron–Tate canonical height (and its local counterpart) takes rational values at points of an elliptic curve over a function field $k=\mathbb{C}(X)$, where $X$ is a curve. More generally, we investigate the mechanism by which the local canonical height for a map $f:\mathbb{P}^{1}\rightarrow \mathbb{P}^{1}$ defined over a function field $k$ can take irrational values (at points in a local completion of $k$), providing examples in all degrees $\deg f\geq 2$. Building on Kiwi’s classification of non-archimedean Julia sets for quadratic maps [Puiseux series dynamics of quadratic rational maps. Israel J. Math.201 (2014), 631–700], we give a complete answer in degree 2 characterizing the existence of points with irrational local canonical heights. As an application we prove that if the heights $\widehat{h}_{f}(a),\widehat{h}_{g}(b)$ are rational and positive, for maps $f$ and $g$ of multiplicatively independent degrees and points $a,b\in \mathbb{P}^{1}(\bar{k})$, then the orbits $\{f^{n}(a)\}_{n\geq 0}$ and $\{g^{m}(b)\}_{m\geq 0}$ intersect in at most finitely many points, complementing the results of Ghioca et al [Intersections of polynomials orbits, and a dynamical Mordell–Lang conjecture. Invent. Math.171 (2) (2008), 463–483].
An important effort has been recently made to detect spectroscopically galaxies at z ~ 6 and higher where the cosmic reionization is thought to occur. The drop of the fraction of Lyman Alpha Emitters (LAEs) at z>6 is currently interpreted as an effect of the increasing neutral hydrogen density.
We present preliminary results from the latest VLT/FORS2 programs, combined with ESO archival data, to perform a large census of z ~ 6 galaxies. We derive their physical properties as stellar mass and dust attenuation with an SED fitting tool including nebular emission which is of primeval importance because IRAC channels are strongly contaminated by emission lines at those redshifts. We take a special care to derive with precision the redshift of non LAEs to perform a comparison of their properties with the LAE population and derive as accurately as possible the fraction of LAEs. In particular, we compare the UV beta slope with the Lyα equivalent width which are known to correlate at lower redshift.
We also report the detection of few peculiar z ~ 6 galaxies with extremely blue UV β slope (~−3), which can be a signature of unusual stellar populations (e.g., very hot and massive stars).
We show that the weak limit of the maximal measures for any degenerating sequence of rational maps on the Riemann sphere ${\hat{{\mathbb{C}}}} $ must be a countable sum of atoms. For a one-parameter family $f_t$ of rational maps, we refine this result by showing that the measures of maximal entropy have a unique limit on $\hat{{\mathbb{C}}}$ as the family degenerates. The family $f_t$ may be viewed as a single rational function on the Berkovich projective line $\mathbf{P}^1_{\mathbb{L}}$ over the completion of the field of formal Puiseux series in $t$, and the limiting measure on $\hat{{\mathbb{C}}}$ is the ‘residual measure’ associated with the equilibrium measure on $\mathbf{P}^1_{\mathbb{L}}$. For the proof, we introduce a new technique for quantizing measures on the Berkovich projective line and demonstrate the uniqueness of solutions to a quantized version of the pullback formula for the equilibrium measure on $\mathbf{P}^1_{\mathbb{L}}$.
We study the postcritically finite maps within the moduli space of complex polynomial dynamical systems. We characterize rational curves in the moduli space containing an infinite number of postcritically finite maps, in terms of critical orbit relations, in two settings: (1) rational curves that are polynomially parameterized; and (2) cubic polynomials defined by a given fixed point multiplier. We offer a conjecture on the general form of algebraic subvarieties in the moduli space of rational maps on ${ \mathbb{P} }^{1} $ containing a Zariski-dense subset of postcritically finite maps.
Contrary to concerns that fructose may have adverse metabolic effects, there is evidence that small, ‘catalytic’ doses ( ≤ 10 g/meal) of fructose decrease the glycaemic response to high-glycaemic index meals in human subjects. To assess the longer-term effects of ‘catalytic’ doses of fructose, we undertook a meta-analysis of controlled feeding trials. We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library. Analyses included all controlled feeding trials ≥ 7 d featuring ‘catalytic’ fructose doses ( ≤ 36 g/d) in isoenergetic exchange for other carbohydrates. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean differences (MD) with 95 % CI. Heterogeneity was assessed by the Q statistic and quantified by I2. The Heyland Methodological Quality Score assessed study quality. A total of six feeding trials (n 118) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD − 0·40, 95 % CI − 0·72, − 0·08) and fasting glucose (MD − 0·25, 95 % CI − 0·44, − 0·07). This benefit was seen in the absence of adverse effects on fasting insulin, body weight, TAG or uric acid. Subgroup and sensitivity analyses showed evidence of effect modification under certain conditions. The small number of trials and their relatively short duration limit the strength of the conclusions. In conclusion, this small meta-analysis shows that ‘catalytic’ fructose doses ( ≤ 36 g/d) may improve glycaemic control without adverse effects on body weight, TAG, insulin and uric acid. There is a need for larger, longer ( ≥ 6 months) trials using ‘catalytic’ fructose to confirm these results.