Shared genetic mechanisms underlying association between sleep disturbances and depressive symptoms.

OBJECTIVES: Polygenic scores (PGS) for sleep disturbances and depressive symptoms in an epidemiological cohort were contrasted. The overlap between genes assigned to variants that compose the PGS predictions was tested to explore the shared genetic bases of sleep problems and depressive symptoms. METHODS: PGS analysis was performed on the São Paulo Epidemiologic Sleep Study (EPISONO, N = 1042), an adult epidemiological sample. A genome wide association study (GWAS) for depression grounded the PGS calculations for Beck Depression Index (BDI), while insomnia GWAS based the PGS for Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI). Pearson's correlation was applied to contrast PGS and clinical scores. Fisher's Exact and Benjamin-Hochberg tests were used to verify the overlaps between PGS-associated genes and the pathways enriched among their intersections. RESULTS: All PGS models were significant when individuals were divided as cases or controls according to BDI (R2 = 1.2%, p = 0.00026), PSQI (R2 = 3.3%, p = 0.007) and ISI (R2 = 3.4%, p = 0.021) scales. When clinical scales were used as continuous variables, the PGS models for BDI (R2 = 1.5%, p = 0.0004) and PSQI scores (R2 = 3.3%, p = 0.0057) reached statistical significance. PSQI and BDI scores were correlated, and the same observation was applied to their PGS. Genes assigned to variants that compose the best-fit PGS predictions for sleep quality and depressive symptoms were significantly overlapped. Pathways enriched among the intersect genes are related to synapse function. CONCLUSIONS: The genetic bases of sleep quality and depressive symptoms are correlated; their implicated genes are significantly overlapped and converge on neural pathways. This data suggests that sleep complaints accompanying depressive symptoms are not secondary issues, but part of the core mental illness.

Preliminary investigation of the administration of biperiden to reduce relapses in individuals with cocaine/crack user disorder: A randomized controlled clinical trial.

BACKGROUND: Several studies have demonstrated that ACh modulates the dopaminergic circuit in the nucleus accumbens, and its blockade appears to be associated with the inhibition of the reinforced effect or the increase in dopamine caused by cocaine use. The objective of this study was to evaluate the effect of biperiden (a muscarinic receptor antagonist with a relatively higher affinity for the M1 receptor) on crack/cocaine use relapse compared to a control group that received placebo. METHODS: This study is a double-blind, randomized, placebo-controlled clinical trial. The intervention group received 2 mg of biperiden, 3 times a day, for a period of 3 months. The control group received identical placebo capsules, at the same frequency and over the same period. All participants were followed for a period of six months. RESULTS: The sample comprised 128 people, with 61 in the control group and 67 in the biperiden group. Lower substance consumption was observed in the group that received biperiden treatment two (bT2 = -2.2 [-3.3; -1.0], p < 0.001) and six months (bT4 = -6, 2 [-8.6; -3.9], p < 0.001) after the beginning of the intervention. The biperiden group had a higher latency until a possible first day of consumption, in the same evaluation periods (bT2 = 0.26 [0.080; 0.44], p = 0.004; bT4 = 0.63 [0.32; 0.93], p < 0.001). CONCLUSIONS: Despite the major limitations of the present study, the group that received biperiden reduced the number of days of cocaine/crack use and showed an increase in the latency time for relapse. More studies are needed to confirm the utility of this approach.

Neuroscience-Based Nomenclature (NbN): the Portuguese version of the new classification for psychopharmacological drugs.

Neuroscience-Based Nomenclature (NbN) is a proposal to provide a nomenclature based on neuroscience and pharmacology instead of the old disease-based classification. NbN is based on the mechanism of action and pharmacological target and aims to assist in rational prescription, reduce stigma, and increase treatment adherence. Currently, NbN is endorsed by many psychiatric associations, adopted by several relevant journals, and included in major psychiatry textbooks. Therefore, it is important that NbN is known to psychiatrists.

Biperiden reverses the increase in 50-kHz ultrasonic vocalizations but not the increase in locomotor activity induced by cocaine.

Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.

Current strategies for tapering psychiatric drugs: Differing recommendations, impractical doses, and other barriers.

While effective ways to prevent withdrawal symptoms from psychiatric drugs remain unclear, a highly accepted clinical approach for treatment discontinuation is to gradually reduce doses over time. The objective of this review is to gather the current strategies for tapering of psychiatric drugs described in the literature and guidelines in an attempt to identify the most promising one. Literature review and search for practice guidelines provided by government agencies and medical organizations were performed. Different strategies for tapering were found: linear tapering, hyperbolic tapering (by exponential dose reduction and pre-established dose-response curves), extended dosing, and substitution for a long half-life drug. The use of guidelines offers support for patients and prescribers, increasing the likelihood of achieving effective drug discontinuation. Nevertheless, the lack of standardization found among the guidelines makes any attempt to reduce or stop the drug very difficult for prescribers. Hyperbolic tapering by exponential dose reduction appears to be the most promising strategy for psychiatric drug discontinuation. Yet, we still face a constant challenge: how to safely obtain flexible doses for the discontinuation of drugs, particularly during the last steps in which lower doses are required. Further studies are needed to reduce the barriers associated with psychiatric drug discontinuation.

Religious and secular spirituality: Methodological implications of definitions for health research.

The importance of spirituality as a research topic has been increasingly recognized, which has led to several studies on the topic. Areas including psychology, medicine, and nursing have produced studies on spirituality under a plurality of definitions and methods, which reveals the complexity of the theme. However, this has resulted in a range of potential problems, including: (1) the use of overlapping and contradictory terms between studies, or even within the same study, (2) research methodologies that do not fit the definitions (sometimes unreflectively) assumed by the authors, (3) difficulties, or even the impossibility, of comparing the results of studies, (4) controversies in respect of the inclusion/exclusion of secular groups in research on spirituality, and (5) ambiguous measurements, often being exclusively dependent on each participant's individual interpretation of what spirituality means. This article discusses these problems, recommends theoretical and methodological alternatives and presents taxonomy of definitions of spirituality.

A Systematic Review on Alcohol Consumption among Non-Religious and Religious Adults.

Background: Research has suggested that religiosity is a protective factor in alcohol use, but this is an area that could be further explored. Objective: To undertake a systematic review of the literature on drinking patterns and their relationship with religiosity and non-religiosity in adult populations. Methods: We searched for relevant studies using the PubMed, LILACS, Web of Science, Scopus, and Psych-INFO databases. This review included only studies of people aged 18 and over which had a non-religious group as a comparison measure. Results: Fifty-one studies met the inclusion criteria. The present review showed that religious people tend to have lower alcohol consumption compared to those with no religion. However, this difference appears only when religions are analyzed together without differentiating between religious affiliations (Catholicism, Buddhism, Evangelicalism, etc.). Some religious affiliations, such as Buddhism, Catholicism and Lutheranism, appear to be risk factors for alcohol consumption. Definitions of risk consumption showed high heterogeneity, ranging from eight to 21 or more doses per week, a difference of 13 doses of alcohol between studies. Conclusions: The present review showed that religious people tend to have lower alcohol consumption compared to non-religious people. However, the results are contradictory when religious affiliations are analyzed separately and compared with non-religious participants. Adequately understanding which dimensions of religiosity and non-religiosity (e.g., group processes, engagement, meaning, rules of behavior) are protective in adulthood is fundamental to the construction of more effective interventions in this age group.

Mindfulness-based interventions in inpatient treatment for Substance Use Disorders: A systematic review.

Inpatient treatment for Substance Use Disorder (SUD), such as Therapeutic Communities and Residential Treatment has been used to test the effect of Mindfulness-Based Interventions (MBI) over different outcomes. Although there is evidence of the effectiveness of MBIs, little is known about the particularities that the place may have in the outcomes. The main objective of this Systematic Review was to evaluate the effectiveness of MBIs for SUDs performed in the inpatient context. PubMed, Web of Science and PsycInfo were used for the search. Quantitative and qualitative studies with no control, usual treatment or other active comparator intervention for SUDs inpatient treatment from 1980 to 2020 were included. From 21 selected studies, 18 were quantitative and 3 qualitative; 12 studies were RCT. Most samples were comprised with women. Based on characteristics of outcomes, we were able to divide them into: Substance Use and Associated Outcomes, Stress, Impulsivity e Evaluation of the MBI protocol. Results suggest that stress assessment is a determining factor for treatment success in these settings. Regarding substance use, although several outcomes have been assessed, the most remarkable results were craving reduction and improvement in treatment adherence. There is evidence that MBIs in inpatient settings benefited those who participated in the experimental groups on some outcomes, such as stress and substance use. Little is mentioned about the impact of the environment over the outcomes and short follow-ups were a relevant limitation of most of the studies. Future assessments must increase follow-up time and evaluate the relationship between the context and the MBI.

Omega-3 for the Prevention of Alcohol Use Disorder Relapse: A Placebo-Controlled, Randomized Clinical Trial.

Background: Recent studies have sought to identify the possible benefits of the intake of omega-3, an important component of neuronal membranes, for the treatment of alcohol use disorder. Aim: The objective of the present study was to evaluate whether omega-3 supplementation is protective against alcohol use disorder relapse after hospital discharge. Methods: A randomized, double-blind, placebo-controlled study was carried out with severe alcohol dependence. Male inpatients were randomized to treatment with omega-3 (n = 59) or placebo (n = 52) for 3 months, participants were assessed after discharge at 1 month (T1), 2 months (T2), 3 months (T3), and 6 months (T4) with assessments made using self-report instruments. The primary outcomes were the possible reduction with assessments made using self-report instruments. The primary outcomes were the possible reduction in the number, intensity of relapses, amount of consumption in each relapse and number of days of consumption during relapses; as secondary outcomes were assessed symptoms of anxiety, depression, degree of dependence, compulsion, and craving. Results: The groups were similar regarding consumption amount parameters and propensity to relapse; however, an effect of treatment with omega-3 was found on the number of days of drinking at 2 months [B = 0.65 (0.09; 1, 21), p = 0.01] and 3 months [B = 2.6 (1.61; 3.58), p < 0.001] after discharge, favoring the intervention group. The effect was not maintained at follow up of 6 months. No differences were found in psychiatric symptoms and severity of addiction. Conclusion: Despite the major limitations of the present study, the group that received omega-3 had a lower number of days of consumption of standard doses of alcohol in the evaluations of 60 and 90 days after discharge. More robust studies are needed to confirm or refute these findings. Brazilian Registry of Clinical Trials: n° RBR-48mkgz7 (URL: https://ensaiosclinicos.gov.br/rg/RBR-48mkgz7).

Drug Use Frequency Variation and Mental Health During the COVID-19 Pandemic: an Online Survey.

In December 2019, a new disease caused by a coronavirus was first identified in China and quickly spread across the world, causing a large number of deaths. Quarantine has been implemented in many countries as a measure to prevent the spread of the disease. The impact of this situation on drug use and mental health is still poorly understood. Therefore, this cross-sectional study sought to assess possible associations between quarantine, the use of psychoactive substances, and symptoms of depression and anxiety. The assessment instruments used were the Patient Health Questionnaire-9 (PHQ-9); the General Anxiety Disorder-7 (GAD-7) scale; and an adaptation of the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). The sample consisted of 2398 participants who met the following inclusion criteria: being in quarantine, aged 18 years or older, and living in Brazil. There was a decrease in the frequency of use of practically all drugs investigated in the evaluated sample. However, some factors were associated with less variations in the frequency of substance use before and during quarantine. These factors were being male, single, and having an occupation different from homemaker.

Sleep, psychiatric and socioeconomic factors associated with substance use in a large population sample: A cross-sectional study.

Multiple elements modulate drug use, including sleep, which is increasingly being considered as an important contributor to substance use and abuse. The present study aimed to evaluate the association between sleep, psychiatric and socioeconomic/demographic factors and substance use in a large-scale representative sample from the city of São Paulo, Brazil. Data from the 2007 São Paulo Epidemiological Sleep Study (EPISONO) database were used. In the EPISONO study, volunteers underwent a polysomnographic exam and completed a series of questionnaires to assess objective and subjective sleep quality and associated comorbidities. Drug use was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Linear (univariate and multivariate) and logistic regressions were performed to identify factors associated with the use of the 4 most commonly used substances in the sample (tobacco, alcohol, cannabis and cocaine/crack). Structural equation models were used to establish theoretical networks to explain the relationship between sleep, psychiatric and socioeconomic factors and use of these substances. The logistic regression results showed that psychiatric symptoms, lower income, and poorer subjective sleep were the main factors associated with tobacco consumption; gender and occupational status with alcohol intake; age and occupation with cannabis use; and education with cocaine/crack use. The structural equation models partially supported these findings and identified significant effects of psychiatric symptoms on tobacco consumption, both directly and mediated by sleep. Our results reinforce previous findings concerning factors associated with generally misused substances and suggest that sleep should be considered as an important element in future substance use disorder studies.

Standardization for obtaining blood viscosity: A systematic review.

INTRODUCTION: There is evidence to suggest that blood viscosity (BV) is involved in several pathological processes. In this review, we evaluated the different methods of BV acquisition, analyzing the sample storage time, the storage temperature, the acquisition time, the acquisition temperature, sample volume, and shear rates, in order to standardize this technique. METHODS: We selected 50 articles with methods of obtaining BV, evaluating pathologies through BV, comparing rheological equipment, monitoring, and regulating BV. RESULTS AND CONCLUSION: Measurements should be obtained as soon as possible, to reduce hemorheological changes. It is necessary to refrigerate them at 4°C when the storage time is long. The acquisition time is related to the equipment used. BV measurements at 37°C will represent the real BV in vivo more faithfully. In order to understand the BV phenomena, the shear rates must be between 0.1 and 1000 s-1. There is a wide variety of equipment available for measuring the BV.

Effects of biperiden (cholinergic muscarinic m1/m4 receptor antagonist) on ethanol conditioned place preference in mice.

BACKGROUND: Previous studies suggest that muscarinic cholinergic receptors might act upon the dopamine release in the mesolimbic system and alter drug-reinforcing values related to drug craving. AIMS: We examined the effects of systemic biperiden administration, a muscarinic cholinergic (M1/M4) receptor antagonist, on ethanol (dose of 2 g/Kg) conditioned place preference (CPP), neuronal activation, dopamine and its metabolites levels in the nucleus accumbens. METHODS: Thirty minutes before the ethanol-induced CPP test, mice received saline or biperiden at doses of 1.0, 5.0, or 10.0 mg/kg. The time spent in each compartment was recorded for 15 min. After the CPP protocol, animals were euthanized, and we investigated the activation of the nucleus accumbens by immunohistochemistry for Fos. We also quantified dopamine, homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) levels in the nucleus accumbens by high-performance liquid chromatography (HPLC). Additionally, the rotarod was employed to evaluate the effects of biperiden on motor coordination. RESULTS: Biperiden at different doses (1.0, 5.0, and 10.0 mg/kg) blocked the expression of ethanol-induced CPP. These biperiden doses increased the number of Fos-positive cells and the dopamine turnover in the nucleus accumbens. None of the doses affected the motor coordination evaluated by the rotarod. CONCLUSIONS: Our results show that biperiden can modulate the effect of alcohol reward, and its mechanism of action may involve a change in dopamine and cholinergic mesolimbic neurotransmission.

Effects of Risperidone in Autistic Children and Young Adults: A Systematic Review and Meta-Analysis.

There are several studies investigating the effects of risperidone on autism, but many of these studies are contradictory or inconclusive. This systematic review and meta-analysis investigated the effects of risperidone on five domains of the Aberrant Behaviour Checklist (ABC) scale on Autism Spectrum Disorder (ASD), as well as weight gain and waist circumference. The protocol for the present systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO). For this study, we analysed articles (2,459), selecting them according to the PICOS strategy (Population, Intervention, Comparison, Outcome, Study design). Although risperidone is effective for the treatment of lethargy and inadequate speech, concerns about the association between weight gain, waist circumference and risperidone require a need for evaluation of the risk-benefit ratio in its use. There was a significant association between weight gain, waist circumference and risperidone. In conclusion, it was possible to suggest the efficacy of risperidone for the treatment of lethargy and inadequate speech. Finally, we emphasize that the risk-benefit in its use should be evaluated (Protocol number CRD42019122316).