Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

[Appropriate Use and Abuse of Sedative-Hypnotic Drugs].

The incidence of insomnia has been increasing in recent years. In addition, due to the impact of the COVID-19 pandemic, more and more people are experiencing a variety of insomniac problems, including having difficulty in sleep initation, waking up too early, and short sleep duration. Chronic insomnia may seriously affect patients' life and work, increase their risks of developing physical and mental illnesses, and cause crushing social and economic burdens. Sedative-hypnotics, including benzodiazepine agonists, melatonin receptor agonists, orexin receptor antagonists, and antidepressants with hypnotic effects, are widely used to treat most patients suffering from insomnia. However, there is the phenomenon of the non-medical use and abuse of sedative-hypnotic drugs, especially benzodiazepine receptor agonists. The abuse of sedative-hypnotic drugs may lead to mental and physical dependence, cognitive impairment, depression and anxiety, as well as an increased risks of falls and death. Therefore, drug regulatory authorities in China and other countries have issued relevant policies to reinforce regulation. Herein, we reviewed the prevalent use and safety of sedative-hypnotic drugs and proposed suggestions concerning their appropriate use. Both the efficacy and safety of sedative-hypnotic drugs should be carefully considered so that patients suffering from insomnia receive thorough and prompt treatment and the problem of potential abuse of sedative-hypnotic drugs is assessed in an objective and scientific manner. We also hope to provide references for the standardized clinical use of insomnia drugs.

Efficacy and tolerability of pharmacological treatments for insomnia in adults: A systematic review and network meta-analysis.

Insomnia is one of the most common and burdensome disorders in adults. We compared and ranked insomnia medication on the basis of their efficacy and tolerability. We performed a systematic review and network meta-analysis of placebo-controlled or head-to-head randomized controlled trials for primary insomnia in adults comparing 20 drugs. We searched eight databases and seven trial registers from inception to March 1st, 2022. Primary outcomes included sleep latency (SL), awake time after sleep onset (WASO) and discontinuation for adverse events (AED), and secondary outcomes included total sleep time (TST), sleep efficiency (SE), sleep quality (SQ) and adverse events (ADE). Pooled standardized mean differences or odds ratios with 95% credible intervals were estimated using pairwise and network meta-analysis with random-effects. Differences among trial findings were explored in subgroup and sensitivity analyses. Confidence in evidence was assessed using GRADE. The PROSPERO registered number is CRD42020182144. We identified 22,538 records and included 69 studies (17,319 patients). Orexin receptor antagonists (ORAs) are more efficacious than benzodiazepine-like drugs (Z-drugs) and placebo for WASO and SE, and better than melatonin receptor agonists (MRAs) for SL, WASO and SE. ORAs ranked the best in SL (SUCRA value: 0.84), WASO (0.93), TST (0.86) and SE (0.96). Lemborexant and daridorexant (two ORAs) showed greater efficacy than placebo for SL, WASO, and TST, with good tolerability. Z-drugs were more efficacious than placebo for SL, WASO, TST and SE, but with higher risk to safety. Zaleplon and eszopiclone had better efficacy than placebo for TST and SQ respectively. MRAs may also be efficacious for sleep-onset insomnia with good safety. However, the long-term adverse effects of all medications are unclear. Insomnia medications differ in their efficacy and tolerability. ORAs have superior efficacy and tolerability. These findings should aid clinicians in matching risk/benefits of drugs available in their countries to insomnia symptoms.

Common and distinguishing genetic factors for substance use behavior and disorder: an integrated analysis of genomic and transcriptomic studies from both human and animal studies.

BACKGROUND AND AIMS: Genomic and transcriptomic findings greatly broaden the biological knowledge regarding substance use. However, systematic convergence and comparison evidence of genome-wide findings is lacking for substance use. Here, we combined all the genome-wide findings from both substance use behavior and disorder (SUBD) and identified common and distinguishing genetic factors for different SUBDs. METHODS: Systemic literature search for genome-wide association (GWAS) and RNA-seq studies of alcohol/nicotine/drug use behavior (partially meets or not reported diagnostic criteria) and alcohol use behavior and disorder (AUBD), nicotine use behavior and disorder (NUBD) and drug use behavior and disorder (DUBD) was performed using PubMed and the GWAS catalog. Drug use was focused upon cannabis, opioid, cocaine and methamphetamine use. GWAS studies required case-control or case/cohort samples. RNA-seq studies were based on brain tissues. The genes which contained significant single nucleotide polymorphism (P ≤ 1 × 10-6 ) in GWAS and reported as significant in RNA-seq studies were extracted. Pathway enrichment was performed by using Metascape. Gene interaction networks were identified by using the Protein Interaction Network Analysis database. RESULTS: Total SUBD-related 2910 genes were extracted from 75 GWAS studies (2 773 889 participants) and 17 RNA-seq studies. By overlapping the genes and pathways of AUBD, NUBD and DUBD, four shared genes (CACNB2, GRIN2B, PLXDC2 and PKNOX2), four shared pathways [two Gene Ontology (GO) terms of 'modulation of chemical synaptic transmission', 'regulation of trans-synaptic signaling', two Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of 'dopaminergic synapse', 'cocaine addiction'] were identified (significantly higher than random, P < 1 × 10-5 ). The top shared KEGG pathways (Benjamini-Hochberg-corrected P-value < 0.05) in the pairwise comparison of AUBD versus DUBD, NUBD versus DUBD, AUBD versus NUBD were 'Epstein-Barr virus infection', 'protein processing in endoplasmic reticulum' and 'neuroactive ligand-receptor interaction', respectively. We also identified substance-specific genetic factors: i.e. ADH1B and ALDH2 were unique for AUBD, while CHRNA3 and CHRNA4 were unique for NUBD. CONCLUSIONS: This systematic review identifies the shared and unique genes and pathways for alcohol, nicotine and drug use behaviors and disorders at the genome-wide level and highlights critical biological processes for the common and distinguishing vulnerability of substance use behaviors and disorders.

Global prevalence of digital addiction in general population: A systematic review and meta-analysis.

The present meta-analytic review aimed to synthesize the global prevalence characteristics of digital addiction in the general population. We searched PubMed, Embase, Cochrane Library, and PsycINFO for studies reporting prevalence of various subtypes of digital addiction published before October 31, 2021. Studies were eligible if they were published in peer-reviewed journals, used a validated tool to assess digital addiction, and passed the qualify assessment. In total, 498 articles with 507 studies were included in systematic review, and the meta-analysis included 495 articles with 504 studies covering 2,123,762 individuals from 64 countries. Global pooled prevalence estimates were 26.99% (95% CI, 22.73-31.73) for smartphone addiction, 17.42% (95% CI, 12.42-23.89) for social media addiction, 14.22% (95% CI, 12.90-15.65) for Internet addiction, 8.23% (95% CI, 5.75-11.66) for cybersex addiction, and 6.04% (95% CI, 4.80-7.57) for game addiction. Higher prevalence of digital addiction was found in Eastern Mediterranean region and low/lower-middle income countries. Males had higher risk for Internet and game addiction. An increasing trend of digital addiction during the past two decades was found, which dramatically worsened during COVID-19 pandemic. This study provides the first and comprehensive estimation for the global prevalence of multiple subtypes of digital addiction, which varied between regions, economic levels, time periods of publication, genders, and assessment scales. PROSPERO ID: CRD42020171117.

Internet Addiction Increases in the General Population During COVID-19: Evidence From China.

BACKGROUND AND OBJECTIVES: COVID-19-related quarantine and stress have likely escalated the crisis of Internet addiction. This study aimed to determine the impact of the COVID-19 pandemic on Internet use and related risk factors among the general public in China. METHODS: A large-sample cross-sectional online survey was conducted from March 24 to April 30, 2020, in China, and 20,472 participants completed the survey. We investigated the prevalence and severity of Internet addiction based on the Internet Addiction Test (IAT), and explored the risk factors related to increases in time spent on Internet use and severity of Internet addiction, as well as severe Internet addiction. RESULTS: The overall prevalence of Internet addiction was 36.7% among the general population during the pandemic, and that of severe Internet addiction was 2.8%, according to IAT scores. Time spent on recreational Internet use had significantly increased during the pandemic, and almost half of participants reported increases in the severity of Internet addiction. Risk factors for increases in time spent on Internet use and severity of Internet addiction and severe Internet addiction included having fewer social supporters, perceiving pressure and impact on mental health status due to COVID-19, and being over-engaged in playing videogames. DISCUSSION AND CONCLUSIONS: The COVID-19 pandemic adversely impacted Internet use and increased the prevalence and severity of Internet addiction among the general population in China, especially in vulnerable populations. SCIENTIFIC SIGNIFICANCE: This study provides evidence for policymakers to refine public health policies to control the pandemic and make efforts to provide population-specific prevention and interventions for people at risk of developing Internet addiction. (Am J Addict 2021;00:00-00).

Identification of novel risk loci with shared effects on alcoholism, heroin, and methamphetamine dependence.

Different substance dependences have common effects on reward pathway and molecular adaptations, however little is known regarding their shared genetic factors. We aimed to identify the risk genetic variants that are shared for substance dependence (SD). First, promising genome-wide significant loci were identified from 3296 patients (521 alcoholic/1026 heroin/1749 methamphetamine) vs 2859 healthy controls and independently replicated using 1954 patients vs 1904 controls. Second, the functional effects of promising variants on gene expression, addiction characteristics, brain structure (gray and white matter), and addiction behaviors in addiction animal models (chronic administration and self-administration) were assessed. In addition, we assessed the genetic correlation among the three SDs using LD score regression. We identified and replicated three novel loci that were associated with the common risk of heroin, methamphetamine addiction, and alcoholism: ANKS1B rs2133896 (Pmeta = 3.60 × 10-9), AGBL4 rs147247472 (Pmeta = 3.40 × 10-12), and CTNNA2 rs10196867 (Pmeta = 4.73 × 10-9). Rs2133896 in ANKS1B was associated with ANKS1B gene expression and had effects on gray matter of the left calcarine and white matter of the right superior longitudinal fasciculus in heroin dependence. Overexpression of anks1b gene in the ventral tegmental area decreased addiction vulnerability for heroin and methamphetamine in self-administration rat models. Our findings could shed light on the root cause for substance dependence and will be helpful for the development of cost-effective prevention strategies for general addiction disorders.

Risk factors and an early prediction model for persistent methamphetamine-related psychiatric symptoms.

Methamphetamine (MA)-related psychiatric symptoms (MAP) are serious comorbidities of MA use and result in many social problems such as violence and suicide. We investigated the sociodemographic and genetic risk factors for persistent MAP of MA users (MUs) and constructed an early MAP prediction model. Derivation and replication samples had 1734 and 905 MUs, respectively. Symptom Checklist 90, Childhood Trauma Questionnaire, Attention-Deficit Hyperactivity Disorder (ADHD) Rating Scale-IV, and Social Support Rating Scale were used to assess the past-year prevalence of general MAP and life events retrospectively. Genome-wide association study (GWAS) was used to analyze MAP-related genetic factors. The prediction model was constructed by integrating the risk life events and clinical and genetic features using logistic regression. Of the 2639 MUs, 1293 (48.83%) had past-year MAP. The severity of MA addiction (SMA), childhood trauma, childhood ADHD symptoms, and social support were reliable risk factors for persistent MAP. By integrating these risk factors and the polygenic risk score from GWAS from derivation samples, the area under the curve (AUC) of the predictive model for MAP was 0.754 (95% CI 0.717~0.771). The risk factors and prediction model were also verified in replication samples. In addition, SMA, ADHD, and social support were mediators for the effect of the risk genetic factor on persistent MAP. Our study identified several risk factors for persistent MAP and will be helpful for developing scalable tools for the prevention of persistent and general MAP.

A Review of Risk Factors for Methamphetamine-Related Psychiatric Symptoms.

The illegal use of methamphetamine (MA) is a growing public health concern globally and results in a series of negative effects. The prominent detrimental effect of MA use is MA-related psychiatric symptoms (MAP) and is observed at a much higher incidence compared to the general population. MAP often includes multiple dimensions of cognitive impairment and induces adverse consequences such as, violence and suicide. However, the assessment methods for MAP are not standardized. Hence, it is necessary to investigate factors that affect the progression of psychiatric symptoms in individuals who use MA. A review of published studies was performed by searching the following databases: PubMed, EMBASE, and PsycINFO from inception to 31 May, 2018. The search strategy included methamphetamine, dependence, psychiatric symptoms, and risk factor terms. We reviewed the different features of MAP and the various types of assessment instruments and summarized MAP risk factors from MA use-related factors, socio-demographic characteristics, life events, and genetic factors. We found that MAP was consistently and causally associated with MA use, particularly as it relates to the frequency and amount of MA use. Other MAP-related risk factors like life events and genetics were relatively inconsistent in their association with MAP. Hence, causal and longitudinal studies that focus on multilateral comparisons are required. This review provides high quality evidence for MAP risk factors and would be helpful for developing early prevention and treatment strategies for MAP.