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Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.

Abstract Aims A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings.

Aims: A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods: This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

This article provides an overview of the current views on psychedelics and explores their connection to well-being based on scientific research and anecdotal evidence. The article begins by examining the historical context of psychedelics. It then delves into the subsequent prohibition and resurgence of scientific interest in psychedelics, highlighting key studies that have shaped our understanding of their effects. The discussion then shifts to contemporary research on psychedelics, particularly focusing on their therapeutic potential in treating mental health conditions such as depression and anxiety. Studies utilizing psychedelics have shown promising results in facilitating transformative experiences and catalyzing lasting psychological benefits. Moreover, the article examines the neurobiological mechanisms underlying the effects of psychedelics, shedding light on how they modulate brain activity and alter perception. In addition to clinical applications, the article explores the growing interest in the potential of psychedelics to enhance well-being in healthy individuals. Anecdotal reports and preliminary research suggest that these substances may induce positive changes in personality traits, attitudes, and behaviors, leading to increased life satisfaction and a greater sense of connectedness with oneself, others, and the natural world. Lastly, the article discusses the public perception of psychedelic substances, the challenges, and the future directions in psychedelic research, including the need for rigorous clinical trials, the development of safe and responsible guidelines for their use, and the exploration of novel therapeutic approaches that integrate psychedelic experiences into psychotherapy. [ABSTRACT FROM AUTHOR]

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.

Mitochondrial metabolism can contribute to nuclear histone acetylation among other epigenetic mechanisms. A central aspect of this signaling pathway is acetyl-L-carnitine (LAC), a pivotal mitochondrial metabolite best known for its role in fatty acid oxidation. Work from our and other groups suggested LAC as a novel epigenetic modulator of brain plasticity and a therapeutic target for clinical phenotypes of depression linked to childhood trauma. Aberrant mitochondrial metabolism of LAC has also been implicated in the pathophysiology of Alzheimer's disease. Furthermore, mitochondrial dysfunction is linked to other processes implicated in the pathophysiology of both major depressive disorders and Alzheimer's disease, such as oxidative stress, inflammation, and insulin resistance. In addition to the rapid epigenetic modulation of glutamatergic function, preclinical studies showed that boosting mitochondrial metabolism of LAC protects against oxidative stress, rapidly ameliorates insulin resistance, and reduces neuroinflammation by decreasing proinflammatory pathways such as NFkB in hippocampal and cortical neurons. These basic and translational neuroscience findings point to this mitochondrial signaling pathway as a potential target to identify novel mechanisms of brain plasticity and potential unique targets for therapeutic intervention targeted to specific clinical phenotypes. [ABSTRACT FROM AUTHOR]

The identification of a blood marker of brain pathology that is sensitive to substance-induced neurotoxicity and dynamically responds to longitudinal changes in substance intake would substantially improve clinical monitoring in the field of substance use and addiction. Here, we explored the hypothesis that plasma levels of neurofilament light chain (NfL), a promising marker of neuroaxonal pathology, are elevated in chronic cocaine users and longitudinally associated with changes in cocaine use. Plasma NfL levels were determined using single molecule array (SIMOA) technology at baseline and at a 4-month follow-up. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples. In a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in cocaine users (n=35) compared to stimulant-naïve healthy controls (n=35). A positive correlation between cocaine hair concentration and NfL levels was also found. Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up, indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the neurotoxic cocaine adulterant levamisole) and NfL levels were found. Our findings demonstrate that NfL is a sensitive marker for assessing cocaine-related neuroaxonal pathology, supporting the utility of blood NfL analysis in addiction research but also suggesting the detailed assessment of substance use in neurological studies and diagnostics. [ABSTRACT FROM AUTHOR]

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes. [ABSTRACT FROM AUTHOR]

While alterations in the locus coeruleus-noradrenergic system are present during early stages of neuropsychiatric disorders, it is unclear what causes these changes and how they contribute to other pathologies in these conditions. Data suggest that the onset of major depressive disorder and schizophrenia is associated with metal dyshomeostasis that causes glial cell mitochondrial dysfunction and hyperactivation in the locus coeruleus. The effect of the overactive locus coeruleus on the hippocampus, amygdala, thalamus, and prefrontal cortex can be responsible for some of the psychiatric symptoms. Although locus coeruleus overactivation may diminish over time, neuroinflammation-induced alterations are presumably ongoing due to continued metal dyshomeostasis and mitochondrial dysfunction. In early Alzheimer's and Parkinson's diseases, metal dyshomeostasis and mitochondrial dysfunction likely induce locus coeruleus hyperactivation, pathological tau or α-synuclein formation, and neurodegeneration, while reduction of glymphatic and cerebrospinal fluid flow might be responsible for β-amyloid aggregation in the olfactory regions before the onset of dementia. It is possible that the overactive noradrenergic system stimulates the apoptosis signaling pathway and pathogenic protein formation, leading to further pathological changes which can occur in the presence or absence of locus coeruleus hypoactivation. Data are presented in this review indicating that although locus coeruleus hyperactivation is involved in pathological changes at prodromal and early stages of these neuropsychiatric disorders, metal dyshomeostasis and mitochondrial dysfunction are critical factors in maintaining ongoing neuropathology throughout the course of these conditions. The proposed mechanistic model includes multiple pharmacological sites that may be targeted for the treatment of neuropsychiatric disorders commonly. [ABSTRACT FROM AUTHOR]

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.

Cognition in extended brain-body music systems becomes especially agile during psychedelic experience, necessitating a sonic rhetoric emphasizing transformative agency. Rooted in the recursive listening spaces of dub, three forms of psychedelic electronica -- ambient house, trip-hop and glitch -- foster an echological sensibility unique to records made largely from the bits and pieces of other recordings. In this article, longform albums representing each of these genres are offered as sonic pharmakomedia, pharmacologically activated non-human agencies that sustain psychedelic mind-machine systems. Managing the psychedelic experience by mediating set and setting through music selection is adopted in psychedelic research, therapy sessions and personal practices alike. I consider set and setting in terms of their contributions to a liminal sonic substance that facilitates encounters with non-human agencies. Putting indigenous shamanic practices in conversation with contemporary neuropsychopharmacology, sound studies and psychedelic music production, this article offers a diagnostic inventory of the effects of the sonic substance. [ABSTRACT FROM AUTHOR]

Background: Prepulse-induced startle modulation occurs when a weak sensory stimulus ('prepulse') is presented before a startling sensory stimulus ('pulse'), producing an inhibited (Prepulse Inhibition, PPI) or facilitated (Prepulse Facilitation, PPF) startle response. We recently identified several gaps and outlined future lines of enquiry to enable a fuller understanding of the neurobiology of PPI and PPF in healthy and clinical populations. However, before embarking on these studies, it is important to consider how task and population characteristics affect these phenomena in healthy humans. Methods: We examined PPI and PPF in separate tasks, with counterbalanced task order across participants in one session, using a range of stimulus onset asynchronies (SOAs), in 48 healthy adults (23 men, 25 women; 10 hormonal contraceptive users) to determine which SOAs produce the strongest PPI and PPF and also explored how sex and hormonal contraception might influence PPI and PPF under these experimental conditions. Results: Both PPI and PPF were affected by SOA, with greatest PPI observed at 60 and 120 ms, and greatest PPF at 4500 and 6000 ms. PPI was influenced by sex (more PPI in men than women) and hormonal contraception, whereas PPF was affected by task order (greater PPF when the PPF task followed, rather than preceded, the PPI task). Conclusions: Our findings indicate that studies of PPI and PPF need to consider, not only sex and hormonal status of study participants, but also task characteristics and presentation order to reduce variance and increase replicability across studies. [ABSTRACT FROM AUTHOR]

The association between autism spectrum disorders (ASD) and epilepsy has been extensively documented, and the estimated prevalence varies depending upon the selected population and the clinical characteristics. Currently, there are a lack of studies assessing the patient care pathways in ASD, particularly for comorbidity with epilepsy, despite its personal, familial, and economic impacts. Genetic abnormalities are likely implicated in the association of ASD and epilepsy, although they are currently detectable in only a small percentage of patients, and some known genetic and medical conditions are associated with ASD and epilepsy. There is no specificity of seizure type to be expected in children and adolescents with ASD compared with other neurodevelopmental disorders or epileptic syndromes. Treatment options include antiepileptic drugs (AED) and developmentally-based early interventions for ASD. Carbamazepine and lamotrigine are the most used AED, but further studies are needed to more precisely define the most suitable medications for this specific group of children with ASD. [ABSTRACT FROM AUTHOR]

Zebrafish are a dynamic research model in the domains of neuropsychopharmacology, biological psychiatry and behaviour. Working with larvae ≤4 days post-fertilisation (dpf) offers an avenue for high-throughput investigation whilst aligning with the 3Rs principles of animal research. The light/dark assay, which is the most widely used behavioural assay for larval neuropharmacology research, lacks experimental reliability and standardisation. This study aimed to formulate a robust, reproducible and standardised light/dark behavioural assay using 4 dpf zebrafish larvae. Considerable between-batch and inter-individual variability was found, which we rectified with a normalisation approach to ensure a reliable foundation for analysis. We then identified that 5-min light/dark transition periods are optimal for locomotor activity. We also found that a 30-min acclimation in the light was found to produce significantly increased dark phase larval locomotion. Next, we confirmed the pharmacological predictivity of the standardised assay using ethanol which, as predicted, caused hyperlocomotion at low concentrations and hypolocomotion at high concentrations. Finally, the assay was validated by assessing the behavioural phenotype of hyperactive transgenic (adgrl3.1 −/− ) larvae, which was rescued with psychostimulant medications. Our standardised assay not only provides a clear experimental and analytical framework to work with 4 dpf larvae, but also facilitates between-laboratory collaboration using our normalisation approach. • The light/dark assay establishes 4 dpf zebrafish as robust neuropsychopharmacology models. • Our unique normalisation analysis protocol facilitates researcher collaboration. • Predictable pharmacological effects were seen in 4 dpf larvae with ethanol exposure. • Hyperactive phenotypes of ADHD transgenic larvae were rescued with ATO and MPH. [ABSTRACT FROM AUTHOR]

Prospective memory (PM) impairment in recreational drug users has been documented in recent years. However, most studies on the effects of drugs on PM contain several methodological challenges, such as small sample size (< 100 participants), unrepresentative sample type (e.g., student or patient), short abstinence period (< 7 days), and lack of control of potential confounds (e.g., sleep and IQ). The present study investigated the possible consequences of recreational drug use on prospective memory, using self-report and lab-based prospective memory measures while overcoming the methodological challenges. The sample was composed of 47 non-users (27 females, age range from 18 to 50 +) and 53 drug users (21 females, age range from 18 to 50 +). Recreational drug users reported significantly more deficits in the long-term episodic, short-term habitual, and internally cued PM failures subscales of the Prospective Memory Questionnaire. However, these deficits were eliminated after controlling for covariates (e.g., age, sleep quality, general health, alcohol usage). Recreational drug users also performed worse than non-users in the short-term, long-term, event-based, and time-based PM subscales of the Royal Prince Alfred Prospective Memory Test. These results remained significant after controlling for the covariates. Drug users demonstrated greater impairments on time-based and long-term PM tasks thought to be linked with executive functioning. Taken together, the present study provides further support for recreational drug-related deficits in PM and highlights a dissociation between self-report and lab-based PM measures. [ABSTRACT FROM AUTHOR]

Schizophrenia is characterized by neurochemical, morphological, bioelectrical, and behavioral changes in the body, which overall produce a system of mutually interacting pathophysiological theories. This review considers the neurochemical theory of the pathogenesis of schizophrenia through the prism of neuropsychopharmacology with the aim of explaining and understanding the mechanisms of action of antipsychotic drugs. The interactions of neurochemical processes with the genetic and immunological underpinnings of schizophrenia are described. Current data on the ligands, receptor targets, and second messengers involved in the pathogenesis of schizophrenia and psychoses are presented with a detailed explanation of their physiological role and connections at the neurochemical, anatomical, functional, and effector levels of the connective organization of the brain. [ABSTRACT FROM AUTHOR]

Psilocybin (a serotonin 2A, or 5-HT2A, receptor agonist) has shown preliminary efficacy as a treatment for mood and substance use disorders. The current report utilized positron emission tomography (PET) with the selective 5-HT2A receptor inverse agonist radioligand [11C]MDL 100,907 (a.k.a. M100,907) and cortical regions of interest (ROIs) derived from resting-state functional connectivity-based brain parcellations in 4 healthy volunteers (2 females) to determine regional occupancy/target engagement of 5-HT2A receptors after oral administration of a psychoactive dose of psilocybin (10 mg/70 kg). Average 5-HT2A receptor occupancy across all ROIs was 39.5% (± 10.9% SD). Three of the ROIs with greatest occupancy (between 63.12 and 74.72% occupancy) were within the default mode network (subgenual anterior cingulate and bilateral angular gyri). However, marked individual variability in regional occupancy was observed across individuals. These data support further investigation of the relationship between individual differences in the acute and enduring effects of psilocybin and the degree of regional 5-HT2A receptor occupancy.

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS., Competing Interests: GM reported a conflict of receiving research support and scientific consulting fees from Noema. GaG received a research grant from Diamond Therapeutics, Toronto (ON), Canada. DD was a consultant for Diamond Therapeutics, Toronto (ON), Canada. GaG and DD were inventors of a patent on the use of psychedelics. GuG was Chief Medical Officer at Compass pathways, holds shares and options in Compass pathways and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, Ocean Neuroscience, P1Vital, Sage, Servier, and Takeda. DE was a paid advisor for Aya Biosciences, Clerkenwell Health, and Mindstate Design Lab. RC-H reported receiving consulting fees from COMPASS Pathways, Entheon Biomedical, Mydecine, Synthesis Institute, Tryp Therapeutics, and Usona Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pasculli, Busan, Jackson, Alm, De Gregorio, Maguire, Goodwin, Gobbi, Erritzoe and Carhart-Harris.)

Objective: There are only a few treatment algorithms for first‐episode schizophrenia. Moreover, all the algorithms apply to acute treatment, but not maintenance treatment. Therefore, we aimed to develop acute and maintenance treatment algorithms for first‐episode schizophrenia. Methods: The algorithm committee of the Japanese Society of Clinical Neuropsychopharmacology developed pharmacological treatment algorithms for the acute phase, agitation, and maintenance phase of first‐episode schizophrenia. Results: The acute treatment algorithm focuses on drug‐naïve patients with first‐episode schizophrenia who are not old or very agitated and recommends first‐line treatment with aripiprazole, second‐ or third‐line treatment with risperidone/paliperidone or olanzapine, and fourth‐line treatment with clozapine. Long‐acting injection of the current antipsychotic agent can be used for poor medication adherence or based on patient preference. The agitation treatment algorithm recommends first‐line treatment with lorazepam and second‐ or third‐line treatment with quetiapine or levomepromazine and clearly instructs that the medication used for agitation should be reduced and then discontinued after remission of agitation. The maintenance treatment algorithm recommends the gradual reduction of antipsychotics to the minimum effective dose after remission of positive symptoms. Conclusions: We hope that our unique algorithms will be used broadly and will contribute to minimizing patients' burden related to antipsychotic treatment. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications are the first-line treatment for schizophrenia. However, non-adherence is frequent despite its negative impact on the course of the illness. In response, we aimed to investigate social media posts about antipsychotics to better understand the online environment in this regard.Methods: We collected tweets containing mentions of antipsychotic medications posted between January 1st 2019 and October 31st 2020. The content of each tweet and the characteristics of the users were analyzed as well as the number of retweets and likes generated.Results: Twitter users, especially those identified as patients, showed an interest in antipsychotic medications, mainly focusing on the topics of sexual dysfunction and sedation. Interestingly, paliperidone, despite being among one of the newest antipsychotics, accounted for a low number of tweets and did not generate much interest. Conversely, retweet and like ratios were higher in those tweets asking for or offering help, in those posted by institutions and in those mentioning cognitive complaints. Moreover, health professionals did not have a strong presence in tweet postings, nor did medical institutions. Finally, trivialization was frequently observed.Conclusion: This analysis of tweets about antipsychotic medications provides insights into experiences and opinions related to this treatment. Twitter user perspectives therefore constitute a valuable input that may help to improve clinicians' knowledge of antipsychotic medications and their communication with patients regarding this treatment.

Objective: Schizophrenia is a chronic, debilitating psychiatric disorder with a high risk of relapse. Nonadherence to medication is a significant contributor to poor outcomes. Although long-acting injectable (LAI) antipsychotics prevent the relapse of schizophrenia, several factors present obstacles to the use of LAI antipsychotics, and clinical guidelines for LAI antipsychotics remain limited. To provide clinical recommendations, the Taiwanese Society of Biological Psychiatry and Neuropsychopharmacology (TSBPN) developed consensus statements for the effectiveness, target populations, initiation timing, and particular clinical situations for the use of LAI antipsychotics in patients with schizophrenia.Methods: After a systematic literature review, a working group drafted consensus statements for the selected clinical topics and determined the levels of evidence-based recommendation based on the latest World Federation of Societies of Biological Psychiatry grading system. A scientific committee evaluated the draft statements and decided the final recommendations regarding the grades by anonymous voting after incorporating clinical experience and practice into the evidence from research.Results: The TSBPN proposed ten consensus statements for the application of LAI antipsychotics. The current evidence supported that LAI antipsychotics could be a treatment option for all schizophrenia patients, including first-episode patients. LAI antipsychotics could be initiated both during an acute psychotic episode and when patients are stable. The consensus also gave recommendations for particular clinical situations with insufficient scientific data, such as for use in elderly or adolescent patients, patients with treatment-resistant schizophrenia, and breakthrough psychosis, and strategies to assist patients/caregivers with decision making.Conclusions: The consensus statements developed by the TSBPN provide evidence-based clinical recommendations and could give clinicians more confidence when prescribing LAI antipsychotics to treat schizophrenia, thereby improving treatment outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Cerebral palsy (CP) is one of the leading causes of child disability, which profoundly affects the lives of whole families and contributes to the burden of health care. Despite the extensive rehabilitative, surgical and other therapeutic efforts of an array of specialists, a significant proportion of patients remain severely disabled. Transcranial magnetic stimulation (TMS) is a non-invasive diagnostic tool in various diseases of the cerebral cortex and cortico-spinal tract (CST). Repetitive TMS (rTMS) is able to induce a long-lasting cerebral plasticity, which is associated with a therapeutic effect in a number of psychiatric and neurological diseases. This article reviews the diagnostic findings gained with TMS in CP as well as therapeutic trials performed with rTMS. Views: The absence of responses in the motor cortex in the first months of life, as revealed by TMS, may predict the development of CP in children at risk. In a proportion of children with the unilateral form of CP, TMS documents the pathological preservation of ipsilateral, cortico-spinal connections from the non-lesioned hemisphere, which is associated with poor outcome. rTMS seems to be a safe method with significant therapeutic potential in CP. The data published so far reveals an almost unanimously significant therapeutic benefit in motor performance over placebo. However, the studies conducted to date have almost without exception involved children with unilateral palsy, and have focused nearly exclusively on therapy for motor symptoms. Conclusions: Magnetic stimulation brings significant diagnostic and therapeutic effects in CP. However, more studies that go beyond the limits specified above are still awaited. [ABSTRACT FROM AUTHOR]

Purpose: Presentation of the role of the dopaminergic system and microRNAs in the development of depression after glucocorticoids (GCs) therapy. Views: GCs are steroid hormones secreted by the adrenal glands, and their synthesis is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. The secretion of GCs (cortisol in humans and corticosterone in rodents) is dependent directly on corticotropin, secreted from the pituitary gland and indirectly on the corticotropin-releasing factor, a hormone released from the paraventricular nuclei of the hypothalamus. Prolonged treatment with GCs disrupts the functions of the HPA axis, impairs the dopaminergic system, suppresses hippocampal neurogenesis and sensitizes the amygdala, leading to an increased susceptibility to depression. This is an important problem because GCs are commonly prescribed for a broad range of medical conditions, including inflammatory and autoimmune disorders. The action of GCs may be at least partially regulated by epigenetic mechanisms (microRNAs), in addition to which microRNAs modulate GCs production and cellular response to GCs. Conclusions: The administration of GCs may lead to changes in dopaminergic system activity (e.g. D2 receptors activity), which significantly contribute to the predisposition to depression. Additionally, GCs therapy may cause changes in the activity of micro-RNAs (e.g. miR-124), which exacerbates symptoms of depression. Searching for specific changes in microRNA expression will provide clinically practical and easily applicable biomarkers of depression risk and new forms of pharmacotherapy in GC-induced depression. [ABSTRACT FROM AUTHOR]

Neuropharmacology is the science that studies the effects of drugs on the central nervous system. Examining the recent history of neuropharmacology allows us to identify future challenges and to project into the future. The contemporary history of neuropharmacology begins with the empirical use of psychotropic alkaloids in barbiturate preparations. Then the discovery of neuroleptics in the 1950s truly opened up the field of pharmacological science, with psychopharmacological clinical exploration in psychiatry, complemented by the contributions of neurochemists and biochemists discovering and exploring neurotransmission. These studies also contributed to the development of dopaminergic and serotonergic drugs used in neurology. The more recent period brought the advent of neuropsychopharmacology, sharing therapeutic targets in neurology and psychiatry on the one hand, and a translational research approach on the other. Moreover, the pharmacology of brain drugs is still a growing discipline in 2020. Despite emerging pharmacological concepts (biased agonists, glial targeting, epigenetic therapeutics, etc.), entire areas of brain‐based therapeutics need to be renewed, particularly in psychiatry, offering great challenges to a new generation of pharmacologists and clinicians. [ABSTRACT FROM AUTHOR]

Introduction: Anatomical Therapeutic Chemical (ATC) indication-based classification system is the World Health Organization (WHO) drug classification system and it is widely used in clinical and researh practice, however there has been questions around the scientific base of this (1, 2). Neuroscience-based Nomenclature (NbN) has been developed by representatives from 5 international organizations, with specific expertise in psychopharmacology, to address the issues around neuropsychopharmacological drug classification and improve the focus on pharmacological domains and mode of action: ECNP  – European College of Neuropsychopharmacology ACNP  – American College of Neuropsychopharmacology AsCNP  – Asian College of Neuropsychopharmacology CINP  – International College of Neuropsychopharmacology IUPHAR – International Union of Basic and Clinical Pharmacology References: 1. Nutt DJ. Beyond psychoanaleptics - can we improve antidepressant drug nomenclature? [published correction appears in J Psychopharmacol. 2009 Sept;23(7):861].  J Psychopharmacol. 2009;23(4):343-345. doi:10.1177/0269881109105498 2. Zohar J, Stahl S, Moller HJ, et al. A review of the current nomenclature for psychotropic agents and an introduction to the Neuroscience-based Nomenclature.  Eur Neuropsychopharmacol. 2015;25(12):2318-2325. doi:10.1016/j.euroneuro.2015.08.019 Objectives: As NbN is a novel classification system that can be used as a teaching tool as well as for other purposes, we aimed to understand the experience, views and needs of the psychiatric trainees and early career psychiatrists who will shape the future of psychiatry, around drug classification systems. Methods: The ethical clearance of the study was obtained from King's College London. We prepared an online survey (https://forms.gle/FCSdVTFH4U5QNn5t8) with a multinational group of early career pscyhiatrists who met through the CINP and EFPT, and test-run the survey with a small group of psychiatric trainees. The online survey was then disseminated via emailing lists and groups of early careers psychiatrists as well as through social media. Results: At the time of this abstract submission, the data collection is ongoing. Results will include analyses of the experience with different drug classifcations systems, awareness, views and attainment of NbN, stratified according to the demographic data (country, careers status, main work setting). Conclusions: The findings from this study will shed light on the views and needs of early career psychiatrists on the topic from clinical and academic aspects, a previously unexplored perspective on drug classification systems. The findings can inform the planning of various strategies to address areas to improve the use and teaching of these tools. Disclosure of Interest: None Declared [ABSTRACT FROM AUTHOR]

The purpose of this paper is to describe and present applications of fuzzy logic in analysis of certain neuropsychopathological symptoms. These symptoms have been linked to conditions relating to occupational hazards. Our method of data analysis which is based on Hamacher operation on picture fuzzy sets is then applied to analyse such occupational hazards. Our result proves to be effective and applicable in medical decision processes especially in situations where such neuro-psychopathological symptoms are detectable by first-aid diagnostic machines. [ABSTRACT FROM AUTHOR]

This article seeks to situate pharmacological cognitive enhancement as part of a broader relationship between cultural understandings of the body-brain and the political economy. It is the body of the worker that forms the intersection of this relationship and through which it comes to be enacted and experienced. In this article, we investigate the imaginaries that both inform and are reproduced by representations of pharmacological cognitive enhancement, drawing on cultural sources such as newspaper articles and films, policy documents, and pharmaceutical marketing material to illustrate our argument. Through analysis of these diverse cultural sources, we argue that the use of pharmaceuticals has come to be seen not only as a way to manage our brains, but through this as a means to manage our productive selves, and thereby to better manage the economy. We develop three analytical themes. First, we consider the cultural representations of the brain in connection with the idea of plasticity – captured most graphically in images of morphing – and the representation of enhancement as a desirable, inevitable, and almost painless process in which the mind-brain realizes its full potential and asserts its will over matter. Following this, we explore the social value accorded to productive employment and the contemporary (biopolitical) ethos of working on or managing oneself, particularly in respect of improving one's productive performance through cognitive enhancement. Developing this, we elaborate a third theme by looking at the moulding of the worker's productive body-brain in relation to the demands of the economic system. [ABSTRACT FROM AUTHOR]

Prevalence and symptoms of most psychiatric and neurological disorders differ in men and women and there is substantial evidence that their neurobiological basis and treatment also differ by sex. This special issue sought to bring together a series of empirical papers and targeted reviews to highlight the diverse impact of sex in neuroscience and neuropsychopharmacology. This special issue emphasizes the diverse impact of sex in neuroscience and neuropsychopharmacology, including 9 review papers and 17 research articles highlighting investigation in different species (zebrafish, mice, rats, and humans). Each contribution covers scientific topics that overlap with genetics, endocrinology, cognition, behavioral neuroscience, neurology, and pharmacology. Investigating the extent to which sex differences can impact the brain and behavior is key to moving forward in neuroscience research. [ABSTRACT FROM AUTHOR]

Objectives: To understand the therapeutic mechanisms of bipolar disorder (BD) drugs at molecular and cellular levels. Methods: Next generation sequencing was used to determine the transcriptional effects of a combination of four commonly prescribed BD drugs (lithium, valproate, lamotrigine and quetiapine) or vehicle (0.2% DMSO) in NT2-N (human neuronal) cells and rats. Differential expression of genes and pathway analysis were performed using edgeR in R and Gene Set Enrichment Analysis software respectively. Free cholesterol levels and neurite outgrowth were quantified in NT2-N cells following combination and individual BD drug treatments. Results: Pathway analysis showed up-regulation of many elements of the cholesterol biosynthesis pathway in NT2-N cells and oxidative phosphorylation in rat brains. Intracellular cholesterol transport genes were upregulated (NPC1, NPC2 and APOE), while the cholesterol efflux gene (ABCA1) was downregulated. BD drug combination tended to increase intracellular cholesterol levels and neurite outgrowth, but these effects were not seen for the drugs when used individually. Conclusions: These data suggest that BD drug combination is increasing cholesterol biosynthesis and the newly synthesised cholesterol is being utilised within the cells, possibly for synthesis of new membranes to facilitate neurite outgrowth. This mechanism possibly underpins clinical efficacy in individuals with BD treated with polypharmacy. [ABSTRACT FROM AUTHOR]

Alterations in the integration of perception and action have been proposed as a core cognitive characteristic of GTS. However, to date it is unknown how neuropharmacological interventions used to treat GTS affect the neural systems related to perception and action integration. Here, we introduce an integrated neuropsychopharmacological perspective to address this question. Specifically, we consider the relevant abnormalities in cortico-striato-thalamo-cortical circuits. Furthermore, we highlight how GTS medication might affect the integration of perception and action in the context of event file coding. [ABSTRACT FROM AUTHOR]

The growing acceptance of cannabis use for medical and recreational purposes across the world has sparked interest in evaluation of the therapeutic potential of the drug. While the beneficial effects of cannabis use to treat physical pain are well-known, its efficacy as a treatment for mental health disorders has not been as extensively investigated. As the most prominent and widespread of these disorders, depression and anxiety have been diagnosed in individuals across the world. Despite the wide range of severity for these disorders, tricyclic antidepressants and selective serotonin reuptake inhibitors are predominately prescribed to treat any case. However, these compounds are not always effective treatments, which leaves a need to investigate alternative treatment options for depression and anxiety. This review article aims to identify prominent research studies focused on evaluating the potential of the human endocannabinoid system, which consists of two main cannabinoid receptor subtypes (CB1 and CB2). Prior studies have focused on the use of exogenous cannabinoids such as oleamide or phytocannabinoids such as delta-9- THC, but this review gives more consideration to endocannabinoids that are produced by the human body. In addition to experiments testing the independent capacity of endocannabinoid receptor ligands as antidepressants, the additive and synergistic potentials of these ligands have been examined in conjunction with cholinergic receptor ligands through the use of mice FST. Recent studies have also indicated that certain genetic variants within the endocannabinoid system such as the CB1 rs1049353 G allele have been linked to increased prevalence of mental health disorders and provide a rationale for gender discrepancies in disorder incidence. Although current research into the prospective use of endocannabinoids as antidepressants is limited, this review details the field’s most salient advancements toward potential clinical applications.

Introduction: Psychiatry is one of the medical disciplines that suffers most from a lack of innovation in its therapeutic arsenal. Many failures in drug candidate trials can be explained by pharmacological properties that have been poorly assessed upstream, in terms of brain passage, brain target binding and clinical outcomes. Positron emission tomography can provide pharmacokinetic and pharmacodynamic data to help select candidate-molecules for further clinical trials., Areas Covered: This review aims to explain and discuss the various methods using positron-emitting radiolabeled molecules to trace the cerebral distribution of the drug-candidate or indirectly measure binding to its therapeutic target. More than an exhaustive review of PET studies in psychopharmacology, this article highlights the contributions this technology can make in drug discovery applied to psychiatry., Expert Opinion: PET neuroimaging is the only technological approach that can, in vivo in humans, measure cerebral delivery of a drug candidate, percentage and duration of target binding, and even the pharmacological effects. PET studies in a small number of subjects in the early stages of the development of a psychotropic drug can therefore provide the pharmacokinetic/pharmacodynamic data required for subsequent clinical evaluation. While PET technology is demanding in terms of radiochemical, radiopharmacological and nuclear medicine expertise, its integration into the development process of new drugs for psychiatry has great added value.

Melatonin (MLT), a neuromodulator mainly acting through two G-protein coupled receptors MT 1 and MT 2 , regulates many brain functions, including circadian rhythms, mood, pain and sleep. MLT and non-selective MT 1 /MT 2 receptor agonists are clinically used in neuropsychiatric and/or sleep disorders. However, the selective roles of the MT 1 and MT 2 receptors need to be clarified. Here, we review the role of the MT 1 receptor in neuropsychopharmacology, describe the anatomical localization of MT 1 receptors in the brain, discuss the medicinal chemistry, biochemistry and molecular aspects of the receptor, and explore the findings linking MT 1 receptors to psychiatric and neurological disorders. MT 1 receptors are localized in brain regions which regulate circadian rhythms, sleep, and mood, such as the suprachiasmatic nucleus, cortex, hippocampus, dorsal raphe nucleus and lateral hypothalamus. Their activation modulates intracellular signaling pathways also targeted by psychoactive drugs, including antidepressants and mood stabilizers. MT 1 receptor knockout mice display increased anxiety, a depressive-like phenotype, increased propensity to reward and addiction, and reduced Rapid-Eye-Movement sleep. These behavioral dysfunctions are associated with altered serotonergic and noradrenergic neurotransmissions. Several studies indicate that the MT 1 , rather than MT 2 , receptor is implicated in circadian rhythm regulation. The involvement of MT 1 receptors in Alzheimer's and Huntington diseases has also been proposed. Postmortem studies in depressed patients have further confirmed the possible involvement of MT 1 receptors in depression. Overall, there is substantial evidence indicating a role for MT 1 receptor in modulating brain function and mood. Consequently, this MLT receptor subtype deserves to be further examined as a novel target for neuropsychopharmacological drug development. [ABSTRACT FROM AUTHOR]

Today’s technological progress allows for precise and effective human enhancement, based on technological devices, and based on pharmacological means - via biologically active compounds. This then raises a multitude of philosophical, legal, ethical and biomedical questions. The breakthrough in psychopharmacology and biotechnology came in the middle of the 20th century, and since then, thousands of active compounds have been synthesized and successfully applied in clinical practice. The article focuses on philosophical aspects (including ethical, biomedical and genetic) of contemporary human cognitive neuroenhancement based on neuro-psychopharmacological (i.e. psychotropic and nootropic) agents in the era of cognitive science. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is common in youth and treatment options are limited. We evaluated the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in adolescents and transitional aged youth with treatment resistant MDD. Methods: Thirty-two outpatients with moderate to severe, treatment-resistant MDD, aged 13–21 years underwent a three-week, open-label, single center trial of rTMS (ClinicalTrials.gov identifier NCT01731678). rTMS was applied to the left dorsolateral prefrontal cortex (DLPFC) using neuronavigation and administered for 15 consecutive week days (120% rest motor threshold; 40 pulses over 4 s [10 Hz]; inter-train interval, 26 s; 75 trains; 3,000 pulses). The primary outcome measure was change in the Hamilton Depression Rating Scale (Ham-D). Treatment response was defined as a >50% reduction in Ham-D scores. Safety and tolerability were also examined. Results: rTMS was effective in reducing MDD symptom severity (t = 8.94, df = 31, p < 0.00001). We observed 18 (56%) responders (≥ 50% reduction in Ham-D score) and 14 non-responders to rTMS. Fourteen subjects (44%) achieved remission (Ham-D score ≤ 7 post-rTMS). There were no serious adverse events (i.e., seizures). Mild to moderate, self-limiting headaches (19%) and mild neck pain (16%) were reported. Participants ranked rTMS as highly tolerable. The retention rate was 91% and compliance rate (completing all study events) was 99%. Conclusions: Our single center, open trial suggests that rTMS is a safe and effective treatment for youth with treatment resistant MDD. Larger randomized controlled trials are needed. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01731678 [ABSTRACT FROM AUTHOR]

Abstract The laws governing cannabis are evolving worldwide and associated with changing patterns of use. The main psychoactive drug in cannabis is Δ9-tetrahydrocannabinol (THC), a partial agonist at the endocannabinoid CB 1 receptor. Acutely, cannabis and THC produce a range of effects on several neurocognitive and pharmacological systems. These include effects on executive, emotional, reward and memory processing via direct interactions with the endocannabinoid system and indirect effects on the glutamatergic, GABAergic and dopaminergic systems. Cannabidiol, a non-intoxicating cannabinoid found in some forms of cannabis, may offset some of these acute effects. Heavy repeated cannabis use, particularly during adolescence, has been associated with adverse effects on these systems, which increase the risk of mental illnesses including addiction and psychosis. Here, we provide a comprehensive state of the art review on the acute and chronic neuropsychopharmacology of cannabis by synthesizing the available neuroimaging research in humans. We describe the effects of drug exposure during development, implications for understanding psychosis and cannabis use disorder, and methodological considerations. Greater understanding of the precise mechanisms underlying the effects of cannabis may also give rise to new treatment targets. [ABSTRACT FROM AUTHOR]

Research shows that various pharmaceuticals can offer modest cognition enhancing effects for healthy individuals. These finding have caused some academics to support liberal use of pharmacological cognitive enhancement (PCE) in schools and universities. This approach partially arises from arguments implying there is little moral justification for regulating such drugs. In this paper, I argue against the liberal use of PCE on epistemic grounds. According to Charles Taylor, emotions and behaviour are epistemically valuable because they tell us meaningful things about reality. Hence, an accurate interpretation of students' emotions and behaviour in context is crucial to support an effective and ethical educational process. This paper supports the assertion that PCE might alter emotions and behaviour, and thereby distort the interpretation of the educational situation by students, educators and policy makers. Therefore, when discussing whether or not to regulate PCE we should be mindful of these epistemic concerns. [ABSTRACT FROM AUTHOR]

The growing acceptance of cannabis use for medical and recreational purposes across the world has sparked interest in evaluation of the therapeutic potential of the drug. While the beneficial effects of cannabis use to treat physical pain are well-known, its efficacy as a treatment for mental health disorders has not been as extensively investigated. As the most prominent and widespread of these disorders, depression and anxiety have been diagnosed in individuals across the world. Despite the wide range of severity for these disorders, tricyclic antidepressants and selective serotonin reuptake inhibitors are predominately prescribed to treat any case. However, these compounds are not always effective treatments, which leaves a need to investigate alternative treatment options for depression and anxiety. This review article aims to identify prominent research studies focused on evaluating the potential of the human endocannabinoid system, which consists of two main cannabinoid receptor subtypes (CB1 and CB2). Prior studies have focused on the use of exogenous cannabinoids such as oleamide or phytocannabinoids such as delta-9- THC, but this review gives more consideration to endocannabinoids that are produced by the human body. In addition to experiments testing the independent capacity of endocannabinoid receptor ligands as antidepressants, the additive and synergistic potentials of these ligands have been examined in conjunction with cholinergic receptor ligands through the use of mice FST. Recent studies have also indicated that certain genetic variants within the endocannabinoid system such as the CB1 rs1049353 G allele have been linked to increased prevalence of mental health disorders and provide a rationale for gender discrepancies in disorder incidence. Although current research into the prospective use of endocannabinoids as antidepressants is limited, this review details the field's most salient advancements toward potential clinical applications. [ABSTRACT FROM AUTHOR]

The consumption of substances for the purpose of abuse and among them medicaments has increased worldwide, which is a serious health problem and a cause of concern for health professionals because of the damage they cause in the consumers. The medicaments that are consumed for non-chemical medical purposes are chemical substances, which modify the functioning of neurotransmitters such as dopamine, serotonin, noradrenaline, GABA, glutamate, producing cognitive, emotional, motivational and behavioral changes in the person that consume it. We describe the neurobiological factors that condition the addictive behavior of drugs for non-medical purposes. A bibliographic review was made on the medicaments consume for the purpose of abuse and neurobiology. The starting point was the telephone consultations, the medical guard, the Research Center, the Information on Drugs and Toxicology of Angola, and the diagnosis of intoxication. [ABSTRACT FROM AUTHOR]