Side-effects of mdma-assisted psychotherapy: a systematic review and meta-analysis.

Evidence suggests that MDMA-assisted psychotherapy (MDMA-AP) has therapeutic potential for treatment of psychiatric illness. We conducted the first comprehensive systematic review and meta-analysis of the side effects of MDMA-AP across indications. We also assessed the quality of side effects-reporting in published trials of MDMA-AP. PubMed, EMBASE, PsycINFO, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) were systematically searched. Phase 2 and 3 MDMA-AP studies were included; Phase 1 studies, which assessed MDMA without psychotherapy, were not. Quality of side effects-reporting was assessed against the CONSORT Harms 2022 guidelines. We also compared numbers of adverse events reported in publications to those recorded in ClinicalTrial.gov registers. Thirteen studies were included, with eight contributing to the meta-analysis. In Phase 2 studies, MDMA-AP was associated with increased odds of any side effect during medication sessions (OR = 1.67, 95%CI (1.12, 2.49)) and in the 7 days following (OR = 1.59, 95%CI (1.12, 2.24)) relative to control conditions. In Phase 3 studies, MDMA-AP was associated with increased odds of any adverse event during the treatment period relative to placebo-assisted psychotherapy (OR = 3.51, 95%CI (2.76, 4.46)). The majority of RCTs were rated as having high risk of bias. Certainty of the evidence was rated as very low to moderate according to the GRADE framework. No included RCT had adequate adherence to the CONSORT Harms 2022 recommendations and reporting rates were also low. Compared to placebo, MDMA-AP was associated with increased odds of side effects, which were largely transient and mild or moderate in severity. However, identified limitations in existing evidence indicate that further investigation is needed to better characterize the safety profile of MDMA-AP and guide implementation.

Self-motion induced environmental kinetopsia and pop-out illusion - Insight from a single case phenomenology.

Stable visual perception, while we are moving, depends on complex interactions between multiple brain regions. We report a patient with damage to the right occipital and temporal lobes who presented with a visual disturbance of inward movement of roadside buildings towards the centre of his visual field, that occurred only when he moved forward on his motorbike. We describe this phenomenon as "self-motion induced environmental kinetopsia". Additionally, he was identified to have another illusion, in which objects displayed on the screen, appeared to pop out of the background. Here, we describe the clinical phenomena and the behavioural tasks specifically designed to document and measure this altered visual experience. Using the methods of lesion mapping and lesion network mapping we were able to demonstrate disrupted functional connectivity in the areas that process flow-parsing such as V3A and V6 that may underpin self-motion induced environmental kinetopsia. Moreover, we suggest that altered connectivity to the regions that process environmental frames of reference such as retrosplenial cortex (RSC) might explain the pop-out illusion. Our case adds novel and convergent lesion-based evidence to the role of these brain regions in visual processing.

Development of a real-time PCR assay for detection of hemp russet mite (Aculops cannabicola).

Of the many arthropod species affecting hemp (Cannabis sativa L.) cultivation in the United States, one species of particular importance is the hemp russet mite (Aculops cannabicola, HRM). Hemp russet mite is a microscopic arthropod which feeds on all parts of hemp plants. Due to its minute size, HRM can proliferate undetected for a long time, complicating management efforts and causing serious economic losses. DNA sequencing and PCR assays can facilitate accurate identification and early detection of HRM in infested-plants. Therefore, a real-time SYBR Green based species-specific PCR assay (quantitative PCR, qPCR) was developed for the identification of HRM DNA by amplification of a 104 bp Internal Transcribed Spacer 1 (ITS1) sequence. The detection limit was estimated to be approximately 48 copies of the HRM marker gene sequence. The real-time-PCR assay is rapid, detects all life stages of mite under 2 hours. A 10-fold serial dilution of the plasmid DNA containing the ITS1 insert were used as standards in the real-time PCR assay. The quantification cycle (Cq) value of the assay showed a strong linear relationship with HRM DNA with R2 of 0.96. The assay was tested against several commonly found hemp pests including two-spotted spider mite and western flower thrips to determine specificity of the assay and to show that no non-target species DNA was amplified. The outcomes of this research will have important applications for agricultural biosecurity through accurate identification of HRM, early detection and timely deployment of management tactics to manage and prevent pest outbreaks.

Biology and management of hemp russet mite (Acari: Eriophyidae).

Hemp is rapidly becoming a crop of global agricultural importance, and one of the more serious pests of this crop is hemp russet mite (HRM) Aculops cannabicola (Acari: Eriophyidae). Significant knowledge gaps presently exist regarding critical aspects of pest biology, quantification of crop damage, and efficacy of pesticides. Here we assessed the role of cannabidiol (CBD) on HRM performance, efficacy of sulfur treatments in field trials, and effect of hot water immersion with and without surfactants in reducing HRM counts on hemp cuttings. We found that HRM fecundity was reduced on a high-CBD cultivar compared with a low-CBD cultivar in detached leaf assays. In contrast, HRM fecundity and survival were not impacted when reared on high-CBD diet in artificial feeding assays. This suggests that cannabinoids other than CBD may aid in reduction of mite populations on the high-CBD cultivar. Sulfur sprays reduced HRM populations by up to 98% with the greatest effects seen in plants receiving dual applications, one during the vegetative period in July and the second at the initiation of flowering in August. Yields of plants treated with sulfur increased by up to 33%, and there was a further increase in cannabinoid production by up to 45% relative to untreated plants. Hot water immersion treatments with and without surfactant solution reduced HRM on infested hemp cuttings, and no phytotoxicity was observed. This study provides novel approaches to mitigating HRM at multiple stages in hemp production.

Agency in schizophrenia and autism: a systematic review.

Introduction: Previous research suggests that altered experiences of agency are an underlying vulnerability in both schizophrenia and autism. Here, we explore agency as a potential transdiagnostic factor by conducting a systematic review of existing literature investigating agency in autism and schizophrenia individually and together. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted three systematic searches on PsycINFO, Embase, Medline, PubMed and Web of Science to identify studies that investigated (1) agency in schizophrenia, (2) agency in autism, and (3) agency in both schizophrenia and autism. Results: A total of 31 articles met eligibility criteria for inclusion and data extraction, with 24 measuring agency in schizophrenia, 7 investigating agency in autism, and no articles comparing the two. Results show that, compared to control populations, agency is significantly different in every identified schizophrenia study and generally not significantly different in autism. Discussion: Importantly, we identified a lack of studies using common tasks and a disproportionate number of studies investigating different dimensions of agency across the two conditions, resulting in limited grounds for valid comparison. Systematic review registration: Prospero, CRD42021273373.

Cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but not schizotypy.

Well characterised cognitive and perceptual impairments in schizophrenia may not be diagnostically specific with some studies suggesting no significant differences between psychotic disorders. This transdiagnostic ambiguity is paralleled in the boundary distinctions between psychotic disorders and the sub-threshold symptomatology of schizotypy. The current study used the CNTRACS test battery to explore if performance deficits in visual integration, relational memory and goal maintenance were specific to schizophrenia or extend to other psychotic disorders; and if task performance varied between individuals with schizophrenia and schizotypy in healthy adults. The sample consisted of healthy controls, and patients who met DSM-IV criteria for schizophrenia, other psychotic disorders and non-psychotic disorders who were tested in person; and an online sample of self-assessed healthy adults. No significant differences were found in performance between patients with schizophrenia and other psychotic disorders in contrast to non-psychotic disorders and healthy controls. The high schizotypy group performed better on the tasks compared to the other psychoses and schizophrenia groups. There were no differences in the healthy control group between individuals with high versus low schizotypy or between in-person and online task performance. These findings support the notion that cognitive and perceptual impairments in schizophrenia extend to other psychotic disorders but are discontinuous with schizotypy. This study provides insights into similarities between schizophrenia and other psychotic disorders with regards to the potential neural substrates underpinning these functions and supports the use of online tools for assessing domains of cognition and perception.

Meta-analysis of dichotomous and ordinal tests with an imperfect gold standard.

Standard methods for the meta-analysis of medical tests, without assuming a gold standard, are limited to dichotomous data. Multivariate probit models are used to analyse correlated dichotomous data, and can be extended to model ordinal data. Within the context of an imperfect gold standard, they have previously been used for the analysis of dichotomous and ordinal test data from a single study, and for the meta-analysis of dichotomous tests. However, they have not previously been used for the meta-analysis of ordinal tests. In this article, we developed a Bayesian multivariate probit latent class model for the simultaneous meta-analysis of ordinal and dichotomous tests without assuming a gold standard, which also allows one to obtain summary estimates of joint test accuracy. We fitted the models using the software Stan, which uses a state-of-the-art Hamiltonian Monte Carlo algorithm, and we applied the models to a dataset in which studies evaluated the accuracy of tests, and test combinations, for deep vein thrombosis. We demonstrate the issues with dichotomising ordinal test accuracy data in the presence of an imperfect gold standard, before applying and comparing several variations of our proposed model which do not require the data to be dichotomised. The models proposed will allow researchers to more appropriately meta-analyse ordinal and dichotomous tests without a gold standard, potentially leading to less biased estimates of test accuracy. This may lead to a better understanding of which tests, and test combinations, should be used for any given medical condition.

Gene duplication and rate variation in the evolution of plastid ACCase and Clp genes in angiosperms.

While the chloroplast (plastid) is known for its role in photosynthesis, it is also involved in many other metabolic pathways essential for plant survival. As such, plastids contain an extensive suite of enzymes required for non-photosynthetic processes. The evolution of the associated genes has been especially dynamic in flowering plants (angiosperms), including examples of gene duplication and extensive rate variation. We examined the role of ongoing gene duplication in two key plastid enzymes, the acetyl-CoA carboxylase (ACCase) and the caseinolytic protease (Clp), responsible for fatty acid biosynthesis and protein turnover, respectively. In plants, there are two ACCase complexes-a homomeric version present in the cytosol and a heteromeric version present in the plastid. Duplications of the nuclear-encoded homomeric ACCase gene and retargeting of one resultant protein to the plastid have been previously reported in multiple species. We find that these retargeted homomeric ACCase proteins exhibit elevated rates of sequence evolution, consistent with neofunctionalization and/or relaxation of selection. The plastid Clp complex catalytic core is composed of nine paralogous proteins that arose via ancient gene duplication in the cyanobacterial/plastid lineage. We show that further gene duplication occurred more recently in the nuclear-encoded core subunits of this complex, yielding additional paralogs in many species of angiosperms. Moreover, in six of eight cases, subunits that have undergone recent duplication display increased rates of sequence evolution relative to those that have remained single copy. We also compared substitution patterns between pairs of Clp core paralogs to gain insight into post-duplication evolutionary routes. These results show that gene duplication and rate variation continue to shape the plastid proteome.

Long-read transcriptome and other genomic resources for the angiosperm Silene noctiflora.

The angiosperm genus Silene is a model system for several traits of ecological and evolutionary significance in plants, including breeding system and sex chromosome evolution, host-pathogen interactions, invasive species biology, heavy metal tolerance, and cytonuclear interactions. Despite its importance, genomic resources for this large genus of approximately 850 species are scarce, with only one published whole-genome sequence (from the dioecious species Silene latifolia). Here, we provide genomic and transcriptomic resources for a hermaphroditic representative of this genus (S. noctiflora), including a PacBio Iso-Seq transcriptome, which uses long-read, single-molecule sequencing technology to analyze full-length mRNA transcripts. Using these data, we have assembled and annotated high-quality full-length cDNA sequences for approximately 14,126 S. noctiflora genes and 25,317 isoforms. We demonstrated the utility of these data to distinguish between recent and highly similar gene duplicates by identifying novel paralogous genes in an essential protease complex. Furthermore, we provide a draft assembly for the approximately 2.7-Gb genome of this species, which is near the upper range of genome-size values reported for diploids in this genus and threefold larger than the 0.9-Gb genome of Silene conica, another species in the same subgenus. Karyotyping confirmed that S. noctiflora is a diploid, indicating that its large genome size is not due to polyploidization. These resources should facilitate further study and development of this genus as a model in plant ecology and evolution.

Exercise alone impacts short-term adult visual neuroplasticity in a monocular deprivation paradigm.

Adult homeostatic visual plasticity can be induced by short-term patching, heralded by a shift in ocular dominance in favor of the deprived eye after monocular occlusion. The potential to boost visual neuroplasticity with environmental enrichment such as exercise has also been explored; however, the results are inconsistent, with some studies finding no additive effect of exercise. Studies to date have only considered the effect of patching alone or in combination with exercise. Whether exercise alone affects typical outcome measures of experimental estimates of short-term visual neuroplasticity is unknown. We therefore measured binocular rivalry in 20 healthy young adults (20-34 years old) at baseline and after three 2-hour interventions: patching (of the dominant eye) only, patching with exercise, and exercise only. Consistent with previous work, the patching interventions produced a shift in ocular dominance toward the deprived (dominant) eye. Mild- to moderate-intensity exercise in the absence of patching had several effects on binocular rivalry metrics, including a reduction in the dominant eye percept. The proportion of mixed percept and the time to first switch (onset rivalry) did not change from baseline across all interventions. Thus, we demonstrate that exercise alone can impact binocular rivalry outcomes measures. We did not observe a synergistic effect between patching and exercise in our data.

Dynamic face processing impairments are associated with cognitive and positive psychotic symptoms across psychiatric disorders.

Impairments in social cognition-including recognition of facial expressions-are increasingly recognised as a core deficit in schizophrenia. It remains unclear whether other aspects of face processing (such as identity recognition) are also impaired, and whether such deficits can be attributed to more general cognitive difficulties. Moreover, while the majority of past studies have used picture-based tasks to assess face recognition, literature suggests that video-based tasks elicit different neural activations and have greater ecological validity. This study aimed to characterise face processing using video-based stimuli in psychiatric inpatients with and without psychosis. Symptom correlates of face processing impairments were also examined. Eighty-six psychiatric inpatients and twenty healthy controls completed a series of tasks using video-based stimuli. These included two emotion recognition tasks, two non-emotional facial identity recognition tasks, and a non-face control task. Symptoms were assessed using the Positive and Negative Syndrome Scale. Schizophrenia and bipolar disorder groups were significantly impaired on the emotion-processing tasks and the non-face task compared to healthy controls and patients without psychosis. Patients with other forms of psychosis performed intermediately. Groups did not differ in non-emotional face processing. Positive symptoms of psychosis correlated directly with both emotion-processing performance and non-face discrimination across patients. We found that identity processing performance was inversely associated with cognition-related symptoms only. Findings suggest that deficits in emotion-processing reflect symptom pathology independent of diagnosis. Emotion-processing deficits in schizophrenia may be better accounted for by task-relevant factors-such as attention-that are not specific to emotion processing.

Neuroplasticity in older adults revealed by temporary occlusion of one eye.

Occluding one eye for several hours alters visual experience. Specifically, occluding one eye shifts the balance of ocular dominance to favour the recently deprived eye, which can be measured using binocular rivalry. This ocular dominance shift demonstrates homeostatic neuroplasticity within the visual system and has been explored in detail in younger adults. Here we measure whether the strength and general features of neuroplasticity revealed by monocular patching are maintained in older adults. Thirty younger (18-35 years) and 30 older adults (60-81 years) participated. Binocular rivalry features were measured before and after 2 h of occlusion. Post-patching, perceptual dominance of the non-patched eye decreased (p < .001) in both age groups. The effect of occlusion on all features of binocular rivalry did not significantly differ between groups. The older visual system maintains the ability to rapidly adjust to changes in perceptual experience induced by eye occlusion. This preservation of neuroplasticity suggests that visual training methods designed to improve visual performance based on eye occlusion should maintain effectiveness into older age.

Medicinal psychedelics for mental health and addiction: Advancing research of an emerging paradigm.

The medical use of psychedelic substances (e.g. psilocybin, ayahuasca, lysergic acid diethylamide and 3,4-methylenedioxymethamphetamine) is attracting renewed interest, driven by a pressing need for research and development of novel therapies for psychiatric disorders, as well as promising results of contemporary studies. In this Viewpoint, we reflect upon the 'Clinical Memorandum on Psychedelics' recently released by the Royal Australian and New Zealand College of Psychiatrists and note subsequent developments including the application for down-scheduling of psilocybin and 3,4-methylenedioxymethamphetamine presently being considered by the Therapeutic Goods Administration and approvals for access via the Special Access Scheme. We suggest that this field is worthy of rigorous research to assess potential benefits, address safety parameters and clarify therapeutic mechanisms. To this end, we outline recent research findings, provide an overview of current knowledge relating to mechanisms of action and discuss salient aspects of the psychedelic-assisted psychotherapy treatment model. The sum of this research points towards medicinal psychedelics as a potential new class of psychiatric treatments when used within a medically supervised framework with integrated psychotherapeutic support. However, before widespread translation into clinical use can occur, appropriately designed and sufficiently powered trials are required to detect both potential positive and negative outcomes. Unique safety and regulatory challenges also need to be addressed. As for any new medical therapy, psychedelic research needs to be conducted in a rigorous manner, through the dispassionate lens of scientific enquiry. Carte blanche availability to practitioners, without specific protocols and appropriate training, would be potentially harmful to individuals and detrimental to the field.

Stronger Top-Down and Weaker Bottom-Up Frontotemporal Connections During Sensory Learning Are Associated With Severity of Psychotic Phenomena.

Recent theories in computational psychiatry propose that unusual perceptual experiences and delusional beliefs may emerge as a consequence of aberrant inference and disruptions in sensory learning. The current study investigates these theories and examines the alterations that are specific to schizophrenia spectrum disorders vs those that occur as psychotic phenomena intensify, regardless of diagnosis. We recruited 66 participants: 22 schizophrenia spectrum inpatients, 22 nonpsychotic inpatients, and 22 nonclinical controls. Participants completed the reversal oddball task with volatility manipulated. We recorded neural responses with electroencephalography and measured behavioral errors to inferences on sound probabilities. Furthermore, we explored neural dynamics using dynamic causal modeling (DCM). Attenuated prediction errors (PEs) were specifically observed in the schizophrenia spectrum, with reductions in mismatch negativity in stable, and P300 in volatile, contexts. Conversely, aberrations in connectivity were observed across all participants as psychotic phenomena increased. DCM revealed that impaired sensory learning behavior was associated with decreased intrinsic connectivity in the left primary auditory cortex and right inferior frontal gyrus (IFG); connectivity in the latter was also reduced with greater severity of psychotic experiences. Moreover, people who experienced more hallucinations and psychotic-like symptoms had decreased bottom-up and increased top-down frontotemporal connectivity, respectively. The findings provide evidence that reduced PEs are specific to the schizophrenia spectrum, but deficits in brain connectivity are aligned on the psychosis continuum. Along the continuum, psychotic experiences were related to an aberrant interplay between top-down, bottom-up, and intrinsic connectivity in the IFG during sensory uncertainty. These findings provide novel insights into psychosis neurocomputational pathophysiology.

Clinical differences between patients with psychogenic nonepileptic seizures and functional motor disorder.

OBJECTIVES: Why a patient might present with psychogenic nonepileptic seizures (PNES) as opposed to another functional neurological symptom is unknown. A recent review suggested that patients with PNES and functional motor disorders (FMD) differ on demographic and clinical factors of potential aetiological and mechanistic significance, arguing they might represent different disorders, though direct comparisons are limited. We sought to determine whether these factors differed in patients presenting with FMD and PNES at our clinic, as well as whether preceding medical complaints would differ between the two, particularly those affecting the limbs or head. METHODS: A retrospective chart review of all presentations with FMD or PNES patients to a functional neurology clinic, collecting demographic and clinical data, including medical and surgical history. RESULTS: Fifty-six patients with FMD and 52 with PNES were included. Significantly more patients with FMD had functional somatic syndromes (46% vs 27%, p = 0.036) and preceding medical events that affected their limbs than patients with PNES (34% vs 14%, p = 0.013); significantly more patients with PNES had dissociative symptoms (31% vs 4%, p < 0.001) and lifetime suicidal ideation (56% vs 32%, p = 0.013). SIGNIFICANCE: These results highlight the substantial comorbidities affecting FMD and PNES, but find clinical differences between the two groups that may be of aetiological or mechanistic significance.

Silence in Shamatha, Transcendental, and Stillness Meditation: An Evidence Synthesis Based on Expert Texts.

Shamatha, Transcendental, and Stillness Meditation are said to aim for "contentless" experiences, where mental content such as thoughts, perceptions, and mental images is absent. Silence is understood to be a central feature of those experiences. The main source of information about the experiences is texts by experts from within the three traditions. Previous research has tended not to use an explicit scientific method for selecting and reviewing expert texts on meditation. We have identified evidence synthesis as a robust and transparent method that is suitable for this purpose. In this paper we use evidence synthesis based on expert texts to examine silence/quietness as a feature of the contentless experiences in the three practices. Objective criteria were used to select a sample of 135 expert texts. A database containing the expert descriptions of the meditation techniques and experiences was produced by extracting the relevant material from the publications and coding that material to differentiate individual features. The database, which forms part of the Supplementary Material for this paper, identifies each feature of the contentless experiences referred to in the expert texts, including silence/quietness. Our key finding is that the experts indicate silence/quietness has a particular connection with stillness, and the absence of concepts, mental activity/noise, thoughts, and disturbance. Further analysis leads to the following insights. The silence/quietness reflects the absence of thoughts and sounds, and this fits neatly with a conception of silence/quietness as the absence of internal and external noise. In some cases the terms silence and quietness may also reflect the absence of other disturbances such as non-auditory perceptions, mental images, and negative feelings. That would fit with a conception of silence/quietness as complete calm or absence of disturbance. It is not clear from the expert texts how silence/quietness is distinct from other features such as stillness that also reflect the absence of disturbances. As a separate matter, silence/quietness has connections with all the other features of the contentless experiences, but the closeness of the connections varies. Our work uncovers fine distinctions and ambiguities which lead to new research questions that can be explored in future studies.

Aberrant connectivity in auditory precision encoding in schizophrenia spectrum disorder and across the continuum of psychotic-like experiences.

BACKGROUND: The ability to generate a precise internal model of statistical regularities is impaired in schizophrenia. Predictive coding accounts of schizophrenia suggest that psychotic symptoms may be explained by a failure to build precise beliefs or a model of the world. The precision of this model may vary with context. For example, in a noisy environment the model will be more imprecise compared to a model built in an environment with lower noise. However compelling, this idea has not yet been empirically studied in schizophrenia. METHODS: In this study, 62 participants engaged in a stochastic mismatch negativity paradigm with high and low precision. We included inpatients with a schizophrenia spectrum disorder (N = 20), inpatients with a psychiatric disorder but without psychosis (N = 20), and healthy controls (N = 22), with comparable sex ratio and age distribution. Bayesian mapping and dynamic causal modelling were employed to investigate the underlying microcircuitry of precision encoding of auditory stimuli. RESULTS: We found strong evidence (exceedance P > 0.99) for differences in the underlying connectivity associated with precision encoding between the three groups as well as on the continuum of psychotic-like experiences assessed across all participants. Critically, we show changes in interhemispheric connectivity between the two inpatient groups, with some connections further aligning on the continuum of psychotic-like experiences. CONCLUSIONS: While our results suggest continuity in backward connectivity alterations with psychotic-like experiences regardless of diagnosis, they also point to specificity for the schizophrenia spectrum disorder group in interhemispheric connectivity alterations.

Perceptual rivalry across animal species.

This review in memoriam of Jack Pettigrew provides an overview of past and current research into the phenomenon of multistable perception across multiple animal species. Multistable perception is characterized by two or more perceptual interpretations spontaneously alternating, or rivaling, when animals are exposed to stimuli with inherent sensory ambiguity. There is a wide array of ambiguous stimuli across sensory modalities, ranging from the configural changes observed in simple line drawings, such as the famous Necker cube, to the alternating perception of entire visual scenes that can be instigated by interocular conflict. The latter phenomenon, called binocular rivalry, in particular caught the attention of the late Jack Pettigrew, who combined his interest in the neuronal basis of perception with a unique comparative biological approach that considered ambiguous sensation as a fundamental problem of sensory systems that has shaped the brain throughout evolution. Here, we examine the research findings on visual perceptual alternation and suppression in a wide variety of species including insects, fish, reptiles, and primates. We highlight several interesting commonalities across species and behavioral indicators of perceptual alternation. In addition, we show how the comparative approach provides new avenues for understanding how the brain suppresses opposing sensory signals and generates alternations in perceptual dominance.