Addiction Psychiatry

Virtual mindfulness may be helpful for individuals with intellectual disabilities in the context of COVID-related disruptions of in-person programming, such as Special Olympics (SO). This study examined the feasibility of a virtual mindfulness intervention for SO athletes and their caregivers.

Technological addiction refers to behavior characterized by excessive and prolonged use of technological devices; reactions of anger, frustration, or panic when unable to use them; and unsuccessful attempts to reduce the time spent on them [...].

Attention-Deficit/Hyperactivity Disorder (ADHD), characterized by clinical diversity, poses diagnostic challenges often reliant on subjective assessments. Metabolomics presents an objective approach, seeking biomarkers for precise diagnosis and targeted interventions. This review synthesizes existing metabolomic insights into ADHD, aiming to reveal biological mechanisms and diagnostic potentials. A thorough PubMed and Web of Knowledge search identified studies exploring blood/urine metabolites in ADHD-diagnosed or psychometrically assessed children and adolescents. Synthesis revealed intricate links between ADHD and altered amino acid metabolism, neurotransmitter dysregulation (especially dopamine and serotonin), oxidative stress, and the kynurenine pathway impacting neurotransmitter homeostasis. Sleep disturbance markers, notably in melatonin metabolism, and stress-induced kynurenine pathway activation emerged. Distinct metabolic signatures, notably in the kynurenine pathway, show promise as potential diagnostic markers. Despite limitations like participant heterogeneity, this review underscores the significance of integrated therapeutic approaches targeting amino acid metabolism, neurotransmitters, and stress pathways. While guiding future research, this overview of the metabolomic findings in ADHD suggests directions for precision diagnostics and personalized ADHD interventions.

Vitamin D deficiency is a risk factor for liver disease, insulin resistance, and beta cell dysfunction. Individuals with alcohol use disorder (AUD) have many comorbidities, with a heavy burden of liver disease and metabolic complications, including type 2 diabetes mellitus (T2DM).

Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD.

Cancer is the leading cause of death in Canada, and living with cancer generates psychological demands, including depression and anxiety among cancer survivors and caregivers. Text4Hope-Cancer Care SMS text messaging-based service was provided to people with cancer and caregivers during the COVID-19 pandemic to support their mental health.

Opioid withdrawal is common among hospitalized patients. Those with substance use disorders exhibit higher rates of patient-directed discharge. The literature lacks information regarding the patient perspective on opioid withdrawal in the hospital setting. In this study, we aimed to capture the patient-reported experience of opioid withdrawal during hospitalization and its impact on the desire to continue treatment for opioid use disorder after discharge. We performed a single-center qualitative study involving semi-structured interviews of hospitalized patients with opioid use disorder (OUD) experiencing opioid withdrawal. Investigators conducted in-person interviews utilizing a combination of open-ended and dichotomous questions. Interview transcripts were then analyzed with open coding for emergent themes. Nineteen interviews were performed. All participants were linked to either buprenorphine (79%) or methadone (21%) at discharge. Eight of nineteen patients (42%) reported a patient-directed discharge during prior hospitalizations. Themes identified from the interviews included: (1) opioid withdrawal was well-managed in the hospital; (2) patients appreciated receiving medication for opioid use disorder (MOUD) for withdrawal symptoms; (3) patients valued and felt cared for by healthcare providers; and (4) most patients had plans to follow-up for opioid use disorder treatment after hospitalization. In this population with historically high rates of patient-directed discharge, patients reported having a positive experience with opioid withdrawal management during hospitalization. Amongst our hospitalized patients, we observed several different individualized MOUD induction strategies. All participants were offered MOUD at discharge and most planned to follow-up for further treatment.

Alcohol Use Disorder (AUD) is a persistent condition linked to neuroinflammation, neuronal oxidative stress, and neurodegenerative processes. While the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has demonstrated effectiveness in reducing liver inflammation associated with alcohol, its impact on the brain remains largely unexplored. This study aimed to assess the effects of alirocumab, a monoclonal antibody targeting PCSK9 to lower systemic low-density lipoprotein cholesterol (LDL-C), on central nervous system (CNS) pathology in a rat model of chronic alcohol exposure. Alirocumab (50 mg/kg) or vehicle was administered weekly for six weeks in 32 male rats subjected to a 35 % ethanol liquid diet or a control liquid diet (n = 8 per group). The study evaluated PCSK9 expression, LDL receptor (LDLR) expression, oxidative stress, and neuroinflammatory markers in brain tissues. Chronic ethanol exposure increased PCSK9 expression in the brain, while alirocumab treatment significantly upregulated neuronal LDLR and reduced oxidative stress in neurons and brain vasculature (3-NT, p22phox). Alirocumab also mitigated ethanol-induced microglia recruitment in the cortex and hippocampus (Iba1). Additionally, alirocumab decreased the expression of pro-inflammatory cytokines and chemokines (TNF, CCL2, CXCL3) in whole brain tissue and attenuated the upregulation of adhesion molecules in brain vasculature (ICAM1, VCAM1, eSelectin). This study presents novel evidence that alirocumab diminishes oxidative stress and modifies neuroimmune interactions in the brain elicited by chronic ethanol exposure. Further investigation is needed to elucidate the mechanisms by which PCSK9 signaling influences the brain in the context of chronic ethanol exposure.

Heavy substance use (SU) and substance use disorders (SUD) have complex etiologies and often severe consequences. Certain personality traits have been associated with an increased risk for SU(D), but far less is known about personality changes related to SU(D). This review aims to synthesize the existing literature on this research question. A systematic literature search was conducted from November 2022 to February 2023 in PubMed, EbscoHost, and Web of Science. Peer-reviewed original papers on SU(D)-related personality changes were included. Of 55 included studies, 38 were observational population-based studies and 17 were intervention studies. Overall, personality and SU measures, samples, study designs, and statistical approaches were highly heterogenous. In observational studies, higher SU was most consistently related to increases in impulsivity-related traits and (less so) neuroticism, while interventions in the context of SU(D) were mostly associated with increases in conscientiousness and self-efficacy and lasting decreases in neuroticism. Findings for traits related to extraversion, openness, conscientiousness, and agreeableness were mixed and depended on SU measure and age. Studies on bidirectional associations suggest that personality and SU(D) both influence each other over time. Due to their strong association with SU(D), impulsivity-related traits may be important target points for interventions. Future work may investigate the mechanisms underlying personality changes related to SU(D), distinguishing substance-specific effects from general SU(D)-related processes like withdrawal, craving, and loss of control. Furthermore, more research is needed to examine whether SU(D)-related personality changes vary by developmental stage and clinical features (e.g. initial use, onset, remission, and relapse).

Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event.

Mental health (MH) problems in youth are prevalent, burdening, and frequently persistent. Despite the existence of effective treatment, the uptake of professional help is low, particularly due to attitudinal barriers.

In the UK, smoking prevalence in people with depression (34%) and anxiety (29%) is more than double that of the general population (13%). People who stop smoking improve their mental health with comparable effect sizes found for antidepressants. In England, online psychological therapy is a standard treatment for depression and anxiety. Online therapy is an acceptable setting for smoking cessation support; however, integrated smoking and mental health support is not available. This novel study aims to assess the acceptability and feasibility of an online smoking cessation intervention, and trial procedures, offered alongside online mental health treatment as it offers increased reach to people with common mental health difficulties who smoke.

We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns.

Intrapersonal parental factors play a significant role in the development of problematic gaming in children. However, few studies have explored parental perspectives on their relationship with a child engaged in problematic gaming, as well as the need for support parents perceive in relation to the child's gaming. We conducted semi-structured interviews with 12 parents (83.3% women) of 11 children (81.8% boys, Mage = 15 ± 2) to examine how parents of children with problematic gaming behavior perceive the parent-child relationship and their need for additional support. We analyzed qualitative accounts using thematic analysis to identify themes and subthemes while drawing on the theoretical frameworks of Aaron Antonovsky's theory of sense of coherence (SOC) and Jürgen Habermas' theory of logic. Participants described difficulties regarding all three components of SOC (meaningfulness, comprehensibility, and manageability) in relation to their child's gaming, with the most significant challenge being manageability. Parents primarily sought assistance from institutions and organizations, such as mental health services, to enhance manageability. The findings emphasize parents' need for relational and practical support tailored to their unique context, as well as their wish to be more involved in the treatment of their children.

Drugs of abuse are thought to promote addiction in part by "hijacking" brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type-specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified as a molecular substrate that regulates cell type-specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.

Opioids are a first-line treatment for severe cancer pain. However, clinicians may be reluctant to prescribe opioids for patients with concurrent substance use disorders (SUD) or clinical concerns about non-prescribed substance use.

Globally, mental health conditions pose a substantial burden of disease. Despite the availability of evidence-based pharmacological and psychological treatments, the symptoms of a substantial subgroup of patients do not respond to these interventions, and only a minority of patients have access to them. This study aimed to assess the efficacy of ImPuls, a 6-month transdiagnostic group exercise intervention, plus treatment-as-usual, compared with treatment-as-usual alone in outpatients with various mental disorders.

Over the past decade, treatment for opioid use disorder has expanded to include long-acting injectable and implantable formulations of medication for opioid use disorder (MOUD), and integrated treatment models systematically addressing both behavioral and physical health. Patient preference for these treatment options has been underexplored. Gathering data on OUD treatment preferences is critical to guide the development of patient-centered treatment for OUD. This cross-sectional study assessed preferences for long-acting MOUD and integrated treatment using an online survey.

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Clinicians are often hesitant to prescribe psychostimulants in bipolar disorder (BD) due to concerns of inducing (hypo)mania, despite limited published evidence on associations between prescribed psychostimulant use and recurrence of mood episodes in BD. The current systematic review and meta-analysis evaluated the emergence of (hypo)manic symptoms in patients with BD receiving prescribed psychostimulants or other pro-cognitive medications in euthymic or depressive states.

Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson's disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Hospitalization presents an opportunity to begin people with opioid use disorder (OUD) on medications for opioid use disorder (MOUD) and link them to care after discharge; regrettably, people admitted to the hospital with an underlying OUD typically do not receive MOUD and are not connected with subsequent treatment for their condition. To address this gap, we launched a multi-site randomized controlled trial to test the effectiveness of a hospital-based addiction consultation team (the Substance Use Treatment and Recovery Team (START)) consisting of an addiction medicine specialist and care manager team that provide collaborative care and a specified intervention to people with OUD during the inpatient stay. Successful implementation of new practices can be impacted by organizational context, though no previous studies have examined context prior to implementation of addiction consultation services (ACS). This study assessed pre-implementation context for implementing a specialized ACS and tailoring it accordingly.

Smartphone addiction (SA) is increasing worldwide. The aim of this study is to determine the level of SA in athletes affiliated to the Turkish Handball Federation in Izmir and to examine its relationship with factors such as sociodemographic status, health status, eating attitude, and body perception. This cross-sectional study was conducted in March-April 2021 in Izmir Province. The sample of the study consisted of 212 licensed handball athletes. The short SA scale, three-factor nutrition scale, and body perception scale were used. A chi-square test was used for bivariate comparisons and logistic regression analysis was used for multivariate comparisons. The study was completed with 202 individuals (the coverage rate was 95.3%). The prevalence of SA was found to be 27.7%. The risk of SA increased 2.49-fold (CI: 1.17-5.31, = 0.018) in female participants, 2.01-fold (CI: 1.01-4.06, = 0.048) in participants with alcohol use, 2.17-fold (CI: 1.04-4.58, = 0.042) in participants with low nutritional scores, 2.65-fold (CI: 1.15-6.10, = 0.022) in individuals with high-income status, and 2.66-fold (CI: 1.07-6.64, = 0.036) in individuals with high body perception scale score. In total, 27.7% of the athlete sample had scores above the SA threshold. These results point out that a behavioral addiction such as SA can occur even in professionals of an activity such as sports, known for beneficial effects in terms of healthy life.

Methamphetamine (METH) use disorder has risen dramatically over the past decade, and there are currently no FDA-approved medications due, in part, to gaps in our understanding of the pharmacological mechanisms related to METH action in the brain.

Stigma is a public health concern. Stigmatizing attitudes toward persons with substance use disorders (SUDs) can adversely impact clinical care and outcomes. Beliefs about SUD, prior experience and familiarity to persons with SUD, and educational curricula drive attitudes among health-care workers. In 2019, nursing and nursing assistant students were recruited through an online survey platform. Participants completed an SUD knowledge test and a survey assessing education, beliefs, personal experience, and confidence in recognizing the signs and symptoms of SUD. One hundred and ten health-care students (nursing students,  = 67 and nursing assistant students,  = 43) completed the survey. Among nursing assistant students, endorsing a disease model of addiction ((2, 40) = 5.83,  < .001,  = .23), and personal familiarity with SUD ((2, 40) = 4.46,  < .001,  = .18), were significantly positively predictive of positive regard toward working with persons with SUD. For nursing students, endorsing a disease model of addiction, educational curricula involving persons with SUD, and personal familiarity were significantly positively predictive of positive regard toward working with persons with SUDs ((2, 61) = 11.52,  < .001, R = .36). Interventions to mitigate drug-related stigma among health-care students should center students with personal familiarity, promote the disease concept of addiction, and incorporate contact-based training.

Methamphetamine (METH, "Crystal Meth") and 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") share structural-chemical similarities but have distinct psychotropic profiles due to specific neurochemical actions. Previous research has suggested that their impact on social cognitive functions and social behaviour may differ significantly, however, direct comparisons of METH and MDMA users regarding social cognition and interaction are lacking. Performances in cognitive and emotional empathy (Multifaceted Empathy Test) and emotion sensitivity (Face Morphing Task), as well as aggressive social behaviour (Competitive Reaction Time Task) were assessed in samples of n = 40 chronic METH users, n = 39 chronic MDMA users and n = 86 stimulant-naïve controls (total N = 165). Self-reports and hair samples were used to obtain subjective and objective estimates of substance use patterns. METH users displayed diminished cognitive and emotional empathy towards positive stimuli, elevated punitive social behaviour regardless of provocation, and self-reported heightened trait anger relative to controls. MDMA users diverged from the control group only by exhibiting a distinct rise in punitive behaviour when faced with provocation. Correlation analyses indicated that both higher hair concentrations of MDMA and METH may be associated with reduced cognitive empathy. Moreover, greater lifetime MDMA use correlated with increased punitive behaviour among MDMA users. Our findings confirm elevated aggression and empathy deficits in chronic METH users, while chronic MDMA users only displayed more impulsive aggression. Dose-response correlations indicate that some of these deficits might be a consequence of use. Specifically, the dopaminergic mechanism of METH might be responsible for social-cognitive deficits.

Tobacco use remains a leading cause of death in the U.S. Varenicline is a preferred medication for tobacco cessation, and a prior report in the literature showed its use fell dramatically after the voluntary recall of Chantix (name-brand varenicline) in July 2021.

Ageing is a heterogeneous multisystem process involving different rates of decline in physiological integrity across biological systems. The current study dissects the unique and common variance across body and brain health indicators and parses inter-individual heterogeneity in the multisystem ageing process. Using machine-learning regression models on the UK Biobank data set (N = 32,593, age range 44.6-82.3, mean age 64.1 years), we first estimated tissue-specific brain age for white and gray matter based on diffusion and T1-weighted magnetic resonance imaging (MRI) data, respectively. Next, bodily health traits, including cardiometabolic, anthropometric, and body composition measures of adipose and muscle tissue from bioimpedance and body MRI, were combined to predict 'body age'. The results showed that the body age model demonstrated comparable age prediction accuracy to models trained solely on brain MRI data. The correlation between body age and brain age predictions was 0.62 for the T1 and 0.64 for the diffusion-based model, indicating a degree of unique variance in brain and bodily ageing processes. Bayesian multilevel modelling carried out to quantify the associations between health traits and predicted age discrepancies showed that higher systolic blood pressure and higher muscle-fat infiltration were related to older-appearing body age compared to brain age. Conversely, higher hand-grip strength and muscle volume were related to a younger-appearing body age. Our findings corroborate the common notion of a close connection between somatic and brain health. However, they also suggest that health traits may differentially influence age predictions beyond what is captured by the brain imaging data, potentially contributing to heterogeneous ageing rates across biological systems and individuals.

Research has largely focused on how attentional bias to smoking-related cues and impulsivity independently influence the development and maintenance of cigarette smoking, with limited exploration of the relationship between these mechanisms. The current experiments systematically assessed relationships between multiple dimensions of impulsivity and attentional bias, at different stages of attention, in smokers varying in nicotine dependency and deprivation. Nonsmokers (NS; n = 26), light-satiated smokers (LS; n = 25), heavy-satiated smokers (HS; n = 23) and heavy 12-hour nicotine-deprived smokers (HD; n = 30) completed the Barratt Impulsivity Scale, delayed discounting task, stop-signal task, information sampling task and a visual dot-probe assessing initial orientation (200 ms) and sustained attention (2000 ms) toward smoking-related cues. Sustained attention to smoking-related cues was present in both HS and LS, while initial orientation bias was only evident in HS. HS and LS also had greater levels of trait motor and nonplanning impulsivity and heightened impulsive choice on the delay discounting task compared with NS, while heightened trait attentional impulsivity was only found in HS. In contrast, in HD, nicotine withdrawal was associated with no attentional bias but heightened reflection impulsivity, poorer inhibitory control and significantly lower levels of impulsive choice relative to satiated smokers. Trait and behavioral impulsivity were not related to the extent of attentional bias to smoking-related cues at any stage of attention, level of nicotine dependency or state of deprivation. Findings have both clinical and theoretical implications, highlighting the unique and independent roles impulsivity and attentional bias may play at different stages of the nicotine addiction cycle.

This study aims to explore the association between the implementation of the adverse event reporting system (AERS), burnout, and job satisfaction among psychiatric nurses, with a focus on examining the mediating effect of workplace violence from patients.

With increases in cannabis use and potency, there is a need to improve our understanding of the impact of use on cognitive function. Previous research indicates long-term cannabis use may have a negative effect on executive function. Few studies have examined persistence of it in protracted abstinence, and there is limited evidence of predictors of worse cognitive function in current and former users. In this study, we aim to evaluate the associations between cannabis use status (current, former, and never use) and self-report cognition. Further, we investigate if cannabis use characteristics predict self-report cognitive function.

: Most studies on the impact of COVID-19 have shown a decrease or no change in unassisted suicide rates, but effects on assisted suicide have not been studied. We aimed to estimate the association between the COVID-19 pandemic and both types of suicide. : Between 2017 and 2021, 1280 assisted suicides and 535 unassisted suicides were recorded in three Swiss cantons. We conducted descriptive and time series analyses on monthly suicide rates, categorized by gender. : Among women, a decrease in assisted suicide rates was found during the acute phases of the pandemic. Among men, assisted suicide rates increased gradually from the onset of the pandemic. Regarding unassisted suicide rates, no significant change was observed in women, while in men, there was a decrease, which was larger at the end than at the onset. : COVID-19 had contrasting effects on assisted and unassisted men and women suicide rates.

The response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial. The models incorporated pre-treatment sMRI, clinical, sociodemographic, and polygenic risk score (PRS) data. Patients were randomly assigned to receive active (N = 45) or sham (N = 47) rTMS treatment. The prediction target was individual response, defined as ≥20% reduction in pre-treatment negative symptom sum scores of the Positive and Negative Syndrome Scale. Our multimodal sequential prediction workflow achieved a balanced accuracy (BAC) of 94% (non-responders: 92%, responders: 95%) in the active-treated group and 50% in the sham-treated group. The clinical, clinical + PRS, and sMRI-based classifiers yielded BACs of 65%, 76%, and 80%, respectively. Apparent sadness, inability to feel, educational attainment PRS, and unemployment were most predictive of non-response in the clinical + PRS model, while grey matter density reductions in the default mode, limbic networks, and the cerebellum were most predictive in the sMRI model. Our sequential modelling approach provided superior predictive performance while minimising the diagnostic burden in the clinical setting. Predictive patterns suggest that rTMS responders may have higher levels of brain grey matter in the default mode and salience networks which increases their likelihood of profiting from plasticity-inducing brain stimulation methods, such as rTMS. The future clinical implementation of our models requires findings to be replicated at the international scale using stratified clinical trial designs.

Adherence to dietary guidelines is critical for optimizing health and weight outcomes after metabolic and bariatric surgery, yet many patients have difficulty. The purpose of this study was to identify the types and frequency of post-surgery non-adherent dietary behaviors and to determine pre-surgery predictors of adherence at 1-year post-surgery.

The surge in digital media consumption, coupled with the ensuing consequences of digital addiction, has witnessed a rapid increase, particularly after the initiation of the COVID-19 pandemic. Despite some studies exploring specific technological addictions, such as internet or social media addiction, in Bangladesh, there is a noticeable gap in research focusing on digital addiction in a broader context. Thus, this study aims to investigate digital addiction among students taking the university entrance test, examining its prevalence, contributing factors, and geographical distribution using GIS techniques.

Methamphetamine (MA) abuse has resulted in a plethora of social issues. Sleep disturbance is a prominent issue about MA addiction, which serve as a risk factor for relapse, and the gut microbiota could play an important role in the pathophysiological mechanisms of sleep disturbances. Therefore, improving sleep quality can be beneficial for treating methamphetamine addiction, and interventions addressing the gut microbiota may represent a promising approach.

Less than half of community pharmacies in the United States stock buprenorphine products indicated for the treatment of opioid use disorder. This lack of access to buprenorphine in community pharmacies is a significant barrier to care. To address this issue, this protocol outlines a comprehensive approach to develop a practice guideline aimed at improving access to safe and effective opioid use disorder treatment in community pharmacies.

Tobacco smoking is highly prevalent among alcohol and other drugs (AOD) service clients and, despite interest in quitting, abstinence is rarely sustained. Nicotine products may assist after discharge from residential treatment services, but little is known about client receptivity to them. This study examined AOD withdrawal service clients' experiences of two types of nicotine products for smoking cessation post-discharge, combination nicotine replacement therapy (cNRT) and nicotine vaping products (NVP).

Understanding the function of BRAF mutants is crucial for determining the best treatment strategy. This study aimed to characterize a rare variant, , which was identified in a patient with lung adenocarcinoma (LUAD) by comprehensive genomic profiling.

The limbic system, particularly the NAc, shows a high concentration of metabotropic glutamate receptors (mGluRs). Recent evidence suggests the significant involvement of mGluRs in mental disorders, including substance abuse and addiction. The objective of this study was to examine the involvement of mGlu8 receptors in the NAc in the mechanisms underlying the extinction and reinstatement of conditioned place preference (CPP) induced by morphine. Male Wistar rats underwent surgical implantation of bilateral cannulas in the NAc and were assessed in a CPP protocol. In study 1 at the same time as the extinction phase, the rats were given varying doses of S-3,4-DCPG (0.03, 0.3, and 3 μg/0.5 μl). In study 2, rats that had undergone CPP extinction were given S-3,4-DCPG (0.03, 0.3, and 3 μg/0.5 μl) five minutes prior to receiving a subthreshold dose of morphine (1 mg/kg) in order to reactivate the previously extinguished morphine response. The findings demonstrated that administering S-3,4-DCPG directly into the accumbens nucleus resulted in a decrease in the duration of the CPP extinction phase. Moreover, dose-dependent administration of S-3,4-DCPG into the NAc inhibited CPP reinstatement. The observations imply that microinjection of S-3,4-DCPG as a potent orthosteric agonist with high selectivity for the mGlu8 receptor into the NAc promotes the process of extinction while concurrently exerting inhibitory effects on the reinstatement of morphine-induced CPP. This effect may be associated with the modulation of glutamate engagement within the NAc and the plasticity of reward pathways at the synaptic level.

Here, we report recurrent focal deletions of the chr14q32.31-32 locus, including , a negative regulator of NF-κB signaling, in de novo diffuse large B cell lymphoma (DLBCL) (24/324 cases). Integrative analysis revealed an association between copy number loss with accumulation of NIK, the central noncanonical (NC) NF-κB kinase, and increased NC NF-κB pathway activity. Accordingly, TRAF3 genetic ablation in isogenic DLBCL model systems caused upregulation of NIK and enhanced NC NF-κB downstream signaling. Knockdown or pharmacological inhibition of NIK in TRAF3-deficient cells differentially impaired their proliferation and survival, suggesting an acquired onco-addiction to NC NF-κB. TRAF3 ablation also led to exacerbated secretion of the immunosuppressive cytokine IL-10. Coculturing of TRAF3-deficient DLBCL cells with CD8+ T cells impaired the induction of Granzyme B and interferon (IFN) γ, which were restored following neutralization of IL-10. Our findings corroborate a direct relationship between genetic alterations and NC NF-κB activation, and highlight NIK as a potential therapeutic target in a defined subset of DLBCL.

The precise roles of screen media activity (SMA) and sleep problems in relation to child/adolescent psychopathology remain ambiguous. We investigated temporal relationships among sleep problems, SMA, and psychopathology and potential involvement of thalamus-prefrontal-cortex (PFC)-brainstem structural covariation.

Recovery from addiction is frequently equated with abstinence. However, some individuals who resolve an addiction continue to use substances, including via substitution (i.e., increased use of one substance after eliminating/ reducing another). Substitution may play a distinct role during early recovery (≤ 1 year), as this period is marked by dramatic change and adjustment. Cannabis is one of the most used substances and is legal for medical and recreational use in an increasing number of states. Consequently, cannabis an increasingly accessible substitute for substances, like fentanyl, heroin, cocaine and methamphetamine, with higher risk profiles (e.g., associated with risk for withdrawal, overdose, and incarceration).

Cancer cells exhibit heightened secretory states that drive tumor progression. Here, we identify a chromosome 3q amplicon that serves as a platform for secretory regulation in cancer. The 3q amplicon encodes multiple Golgi-resident proteins, including the scaffold Golgi integral membrane protein 4 (GOLIM4) and the ion channel ATPase Secretory Pathway Ca2+ Transporting 1 (ATP2C1). We show that GOLIM4 recruits ATP2C1 and Golgi phosphoprotein 3 (GOLPH3) to coordinate calcium-dependent cargo loading and Golgi membrane bending and vesicle scission. GOLIM4 depletion disrupts the protein complex, resulting in a secretory blockade that inhibits the progression of 3q-amplified malignancies. In addition to its role as a scaffold, GOLIM4 maintains intracellular manganese (Mn) homeostasis by binding excess Mn in the Golgi lumen, which initiates the routing of Mn-bound GOLIM4 to lysosomes for degradation. We show that Mn treatment inhibits the progression of multiple types of 3q-amplified malignancies by degrading GOLIM4, resulting in a secretory blockade that interrupts pro-survival autocrine loops and attenuates pro-metastatic processes in the tumor microenvironment. Potentially underlying the selective activity of Mn against 3q-amplified malignancies, ATP2C1 co-amplification increases Mn influx into the Golgi lumen, resulting in a more rapid degradation of GOLIM4. These findings show that functional cooperativity between co-amplified genes underlies heightened secretion and a targetable secretory addiction in 3q-amplified malignancies.

Community treatment orders have been introduced in many jurisdictions with increasing use over time. We conducted a rapid umbrella review to synthesise the quantitative and qualitative evidence from systematic reviews and/or meta-analyses of their potential harms and benefits.

Maternal smoking during pregnancy (MSDP) may impact offspring biological (e.g., deoxyribonucleic acid methylation [DNAm]) and behavioral (e.g., attention-deficit/hyperactivity disorder hyperactive/impulsive [ADHD-HI] symptoms) development. There has been consistency in findings of differential methylation in global DNAm, and the specific genes and in relation to MSDP. The current study aims to (a) replicate the associations of MSDP and DNAm in prior literature in middle childhood-adolescence (cross-sectionally) using a sibling-comparison design where siblings were discordant for MSDP ( = 328 families; Sibling 1 = 13.02; Sibling 2 = 10.20), adjusting for prenatal and postnatal covariates in order to isolate the MSDP exposure on DNAm. We also (b) cross-sectionally explored the role of DNAm in the most robust MSDP-ADHD associations (i.e., with ADHD-HI) previously found in this sample. We quantified smoking exposure severity for each sibling reflecting time and quantity of MSDP, centered relative to the sibling pair's average (i.e., within-family centered, indicating child-specific effects attributable MSDP exposure) and controlling for the sibling average MSDP (i.e., between-family component, indicating familial confounding related to MSDP). We found that child-specific MSDP was associated with global DNAm, and and methylation after covariate adjustment, corroborating emerging evidence for a potentially causal pathway between MSDP and DNAm. There was some evidence that child-specific and methylation partially explained associations between MSDP and ADHD-HI symptoms, though only on one measure (of two). Future studies focused on replication of these findings in a longitudinal genetic design could further solidify the associations found in the current study. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

This longitudinal cohort study aims to investigate the relationship between self-reported childhood maltreatment (CM) and the retrospective trajectory of substance use, mental health, and satisfaction with life in individuals with substance use disorders.

Patients with Parkinson's disease (PD) experience changes in behavior, personality, and cognition that can manifest even in the initial stages of the disease. Previous studies have suggested that mild behavioral impairment (MBI) should be considered an early marker of cognitive decline. However, the precise neurostructural underpinnings of MBI in early- to mid-stage PD remain poorly understood.

The COVID-19 pandemic raised concerns regarding increased suicide-related behaviours. We compared characteristics and counts of Emergency Department (ED) presentations for self-harm, an important suicide-related outcome, during versus prior to the pandemic's first year. We included patients presenting with self-harm to the ED of two trauma centres in Toronto, Canada. Time series models compared intra-pandemic (March 2020-February 2021) presentation counts to predictions from pre-pandemic data. The self-harm proportion of ED presentations was compared between the intra-pandemic period and preceding three years. A retrospective chart review of eligible patients seen from March 2019-February 2021 compared pre- vs. intra-pandemic patient and injury characteristics. While monthly intra-pandemic self-harm counts were largely within expected ranges, the self-harm proportion of total presentations increased. Being widowed (OR=9.46; 95 %CI=1.10-81.08), employment/financial stressors (OR=1.65, 95 %CI=1.06-2.58), job loss (OR=3.83; 95 %CI=1.36-10.76), and chest-stabbing self-harm (OR=2.50; 95 %CI=1.16-5.39) were associated with intra-pandemic presentations. Intra-pandemic self-harm was also associated with Intensive Care Unit (ICU) admission (OR=2.18, 95 %CI=1.41-3.38). In summary, while the number of self-harm presentations to these trauma centres did not increase during the early pandemic, their proportion was increased. The association of intra-pandemic self-harm with variables indicating medically severe injury, economic stressors, and being widowed may inform future suicide and self-harm prevention strategies.

Cannabis is a pharmacologically complex plant consisting of hundreds of potentially active compounds. One class of compounds present in cannabis that has received little attention are terpenes. Traditionally thought to impart aroma and flavor to cannabis, it has become increasingly recognized that terpenes might exert therapeutic effects themselves. Several recent reports have also indicated terpenes might behave as cannabinoid type 1 (CB1) receptor agonists. This study aimed to investigate whether several terpenes present in cannabis produce discriminative stimulus effects similar to or enhance the effects of Δ9-tetrahydrocannabinol (THC). Subsequent experiments explored other potential cannabimimetic effects of these terpenes. Rats were trained to discriminate THC from vehicle while responding under a fixed-ratio 10 schedule of food presentation. Substitution testing was performed with the CB receptor agonist JWH-018 and the terpenes linalool, limonene, γ-terpinene and α-humulene alone. Terpenes were also studied in combination with THC. Finally, THC and terpenes were tested in the tetrad assay to screen for CB1-receptor agonist-like effects. THC and JWH-018 dose-dependently produced responding on the THC-paired lever. When administered alone, none of the terpenes produced responding predominantly on the THC-paired lever. When administered in combination with THC, none of the terpenes enhanced the potency of THC, and in the case of α-humulene, decreased the potency of THC to produce responding on the THC-paired lever. While THC produced effects in all four tetrad components, none of the terpenes produced effects in all four components. Therefore, the terpenes examined in this report do not have effects consistent with CB1 receptor agonist properties in the brain.

The ongoing overdose and drug toxicity crisis in North America has contributed momentum to the emergence of safer supply prescribing and programs in Canada as a means of providing an alternative to the highly volatile unregulated drug supply. The implementation and scale-up of safer supply have been met with a vocal reaction on the part of news media commentators, conservative politicians, recovery industry representatives, and some prominent addiction medicine physicians. This reaction has largely converged around several narratives, based on unsubstantiated claims and anecdotal evidence, alleging that safer supply programs are generating a "new opioid epidemic", reflecting an emerging alignment among key institutional and political actors. Employing situational analysis method, and drawing on the policy studies and social science scholarship on moral panics, this essay examines news media coverage from January to July 2023, bringing this into dialogue with other existing empirical sources on safer supply (e.g. Coroner's reports, program evaluations, debates among experts in medical journals). We employ eight previously established criteria delineating moral panics to critically appraise public dialogue regarding safer supply, diverted medication, and claims of increased youth initiation to drug use and youth overdose. In detailing the emergence of a moral panic regarding safer supply, we trace historic continuities with earlier drug scares in Canadian history mobilized as tools of racialized poverty governance, as well as previous backlashes towards healthcare interventions for people who use drugs (PWUD). The essay assesses the claims of moral entrepreneurs against the current landscape of opioid use, diversion, and overdose among youth, notes the key role played by medical expertise in this and previous moral panics, and identifies what the convergence of these narratives materialize for PWUD and healthcare access, as well as the broader policy responses such narratives activate.

Background and aims Problematic Social Network Sites Use (PSNSU) mirrors substance use disorders with regard to symptoms (e.g., diminished control). Recent theoretical advances in the addiction research field recognize a central role of affective and cognitive processes in the development of addictive behaviors. For example, the metacognitive model of addictive behaviors sustains that cognitive processes like extended thinking, disruption in metacognitive monitoring, and thought suppression are associated with addictive behaviors leading to increased craving. The current study aims to test the mediating role of extended thinking (i.e., worry, rumination, and desire thinking) in the relationship between psychological distress and PSNSU. Methods A community sample of 548 individuals (F = 68.5%, M 29.29 ± 12.04 years) completed an online survey. Structural Equation Modeling (SEM) was utilized to analyze the relationships among the variables under study. Results The assessed structural model adequately fits the data, accounting for 89% of PSNSU variance. Psychological distress predicted PSNSU through the mediation of desire thinking and rumination and the serial mediation of (i) worry and craving (ii) desire thinking and craving The model is gender invariant. Conclusions The current findings provide preliminary evidence for the role of extended thinking in PSNSU. Worry, rumination and desire thinking may be central cognitive processes in eliciting craving and PSNSU for individuals who experience psychological distress.

The devastating health, economic, and social consequences of COVID-19 may harm the already vulnerable groups, particularly people with severe psychiatric disorders (SPDs). The present study was conducted to investigate the anxiety response of patients with SPDs during the COVID-19 pandemic.

Novel psychoactive substances (NPS) represent a broad class of drugs new to the illicit market that often allow passing drug-screening tests. They are characterized by a variety of structures, rapid transience on the drug scene and mostly unknown metabolic profiles, thus creating an ever-changing scenario with evolving analytical targets. The present study aims at developing an indirect screening strategy for NPS monitoring, and specifically for new synthetic opioids (NSOs), based on assessing changes in endogenous urinary metabolite levels as a consequence of the systemic response following their intake. The experimental design involved in-vivo mice models: 16 animals of both sex received a single administration of morphine or fentanyl. Urine was collected before and after administration at different time points; the samples were then analysed with an untargeted metabolomics LC-HRMS workflow. According to our results, the intake of opioids resulted in an elevated energy demand, that was more pronounced on male animals, as evidenced by the increase in medium and long chain acylcarnitines levels. It was also shown that opioid administration disrupted the pathways related to catecholamines biosynthesis. The observed alterations were common to both morphine and fentanyl: this evidence indicate that they are not related to the chemical structure of the drug, but rather on the drug class. The proposed strategy may reinforce existing NPS screening approaches, by identifying indirect markers of drug assumption.

Alcohol use disorder (AUD) is a severe, yet not fully understood, mental health problem. It is associated with liver, pancreatic, and gastrointestinal diseases, thereby highly increasing the morbidity and mortality of these individuals. Currently, there is no effective and safe pharmacological therapy for AUD. Therefore, there is an urgent need to increase our knowledge about its neurophysiological etiology to develop new treatments specifically targeted at this health condition. Recent findings have shown an upregulation in the histaminergic system both in alcohol dependent individuals and in animals with high alcohol preference. The use of H3 histaminergic receptor antagonists has given promising therapeutic results in animal models of AUD. Interestingly, astrocytes, which are ubiquitously present in the brain, express the three main histamine receptors (H1, H2 and H3), and in the last few years, several studies have shown that astrocytes could play an important role in the development and maintenance of AUD. Accordingly, alterations in the density of astrocytes in brain areas such as the prefrontal cortex, ventral striatum, and hippocampus that are critical for AUD-related characteristics have been observed. These characteristics include addiction, impulsivity, motor function, and aggression. In this work, we review the current state of knowledge on the relationship between the histaminergic system and astrocytes in AUD and propose that histamine could increase alcohol tolerance by protecting astrocytes from ethanol-induced oxidative stress. This increased tolerance could lead to high levels of alcohol intake and therefore could be a key factor in the development of alcohol dependence.

Menthol and filter ventilation (FV) contribute to cigarette appeal. This observational study examines the US prevalence of menthol versus non-menthol cigarette use by FV and how harm perceptions, cigarettes per day and biomarkers of exposure vary.

Negative life events (NLE) have been associated with increased alcohol use (AU) during adolescence. However, whether this risk association may be modified by leisure activities such as sports participation (SP) remains poorly understood. This study examined whether accumulated family-specific NLE in particular were associated with greater AU, and if so, whether SP moderated this association to reduce AU among high-NLE adolescents. We examined five annual assessments from a nationwide cohort of 3,422 Norwegian adolescents (13-15 year-olds; 55.3 % girls at baseline) who participated in the MyLife study. At each assessment, adolescents reported their AU on the Alcohol Use Disorders Identification Test-Concise (AUDIT-C), the number of family-specific NLE in the past 12 months, SP days in the past 30 days, and multiple sociodemographic and individual-level characteristics (covariates). Changes over time in AU as a function of NLE, SP, and their interaction (NLExSP) were examined with a set of partially nested growth curve models. AU increased non-linearly over time in all models. The fully adjusted best-fitting model showed significant NLExSP interactions (estimate = -0.013, 95% CI [-0.02, -0.006]), such that the initial AUDIT-C scores were lower for high-NLE adolescents with high SP and greater for high-NLE adolescents with low SP. Further, linear increases in AU over time were marginally steeper for high-NLE adolescents with high SP (NLExSPxTime estimate = 0.034, 95% CI [-0.0002, 0.007]). Thus, SP appeared to have a protective role in reducing AU for high-NLE youth primarily during middle school years. Prevention efforts thus may utilize organized sports for youth facing family-specific NLE as a resource early on.

Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice.

Few interventions for food addiction (FA) report on dietary intake variables. The present study comprised a three-arm randomised controlled trial in adults with symptoms of FA. The aim was to evaluate dietary intake, sleep and physical activity resulting from a dietitian-led telehealth intervention at 3 months.

To characterise and understand the untreated high-risk opioid user population in Finland, and to determine the reasons why these people do not enter treatment. The study setting was a half-year cross-sectional survey in Finland during 2021-2022. An electronic questionnaire with 24 structured questions was concluded in 16 needle exchange units. Participants were opioid-dependent people without opioid agonist treatment (OAT), and they answered the survey voluntarily and anonymously. Of the 167 respondents, 62% were men, 53% were aged ≤34 years, 66% had used opioids for >6 years, and 78% used drugs intravenously (IV) daily. The most used opioid (95%) was buprenorphine. Most respondents used opioids as self-medication for withdrawal symptoms (75%), or to treat psychological symptoms (59%) or pain (43%). Of them, 70% also used other substances for recreational purposes. The most common named reasons to stay outside OAT were as follows: seeking treatment is too difficult (37%); treatment is too binding (36%); and fear of actions from authorities (23%). For opioid-dependent respondents who would be eligible for OAT in Finland, treatment awareness is limited. These high-risk opioid users also think that the treatment would be too binding. In conclusion, there is a need for increase in general information about, accessibility to, acceptance for and individualisation of OAT.

People with severe mental illness, such as schizophrenia-spectrum disorder and bipolar disorder, face poorer health outcomes from multiple chronic illnesses. Physical multimorbidity, the coexistence of two or more chronic physical conditions, and psychiatric multimorbidity, the coexistence of three or more psychiatric disorders, are both emerging concepts useful in conceptualising disease burden. However, the prevalence of physical and psychiatric multimorbidity in this cohort is unknown. This study aimed to estimate the absolute prevalence of both physical and psychiatric multimorbidity in people with severe mental illness, and also compare the odds of physical multimorbidity prevalence against people without severe mental illness.

The impact of the COVID-19 pandemic on young people with eating disorders (EDs) and their families was profound, with surging rates of hospitalizations and referrals reported internationally. This paper provides an account of the additional health and social costs of ED care for young people living in Canada incurred during the COVID-19 pandemic, drawing attention to the available data to inform these estimates while noting gaps in data capacities to account for a full view of the ED system of care.

The global market of flavour capsule cigarettes (FCCs) has grown significantly over the past decade; however, prevalence data exist for only a few countries. This study examined prevalence and perceptions of FCCs among adults who smoke across five countries.

Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia (TRS). Although a large body of evidence supports its efficacy and favorable risk-benefit ratio in individuals who have failed two or more antipsychotics, clozapine remains underused. However, variations in clozapine utilization across geographic and clinical settings suggest that it could be possible to improve its use. In this narrative review and expert opinion, we summarized information available in the literature on the mechanisms of action, effectiveness, and potential adverse events of clozapine. We identified barriers leading to discouragement in clozapine prescription internationally, and we proposed practical solutions to overcome each barrier. One of the main obstacles identified to the use of clozapine is the lack of appropriate training for physicians: we highlighted the need to develop specific professional programs to train clinicians, both practicing and in residency, on the relevance and efficacy of clozapine in TRS treatment, initiation, maintenance, and management of potential adverse events. This approach would facilitate physicians to identify eligible patients and offer clozapine as a treatment option in the early stage of the disease. We also noted that increasing awareness of the benefits of clozapine among healthcare professionals, people with TRS, and their caregivers can help promote the use of clozapine. Educational material, such as leaflets or videos, could be developed and distributed to achieve this goal. The information provided in this article may be useful to improve disease burden and support healthcare professionals, patients, and caregivers navigating the complex pathways to TRS management.

We introduce the concept of harm reduction capital (HRCap) as the combination of knowledge, resources, and skills related to substance use risk reduction, which we hypothesize to predict MOUD use and opioid overdose. In this study, we explored the interrelationships between ethnicity, HRCap, nonfatal overdose, and MOUD use among PWUD.

Obacunone, a natural triterpenoid, is an active component of the herbs Turcz. and Rupr, and an indicator of the herbs' quality. Owing to its multiple health benefits, several studies have investigated the multi-targeting potential action mechanisms of obacunone. To summarize recent developments on the pharmacological actions of obacunone and focus on the underlying molecular mechanisms and signaling networks, we searched PubMed, Europe PMC, Wiley Online Library, Web of Science, Google Scholar, Wanfang Medical Network, and China National Knowledge Infrastructure for articles published prior to March 2024. Existing research indicates obacunone has great potential to become a promising therapeutic option against tumors, fibrotic diseases, bone and cholesterol metabolism diseases, and infections of pathogenic microorganisms, among others. The paper contributes to providing up-to-date references for further research and clinical applications of obacunone.

Recreational cannabis legalization (RCL) is expanding rapidly. RCL's effects on mental health issues are of particular concern because cannabis use is more frequent among people receiving psychiatric care and is associated with several psychiatric disorders. The authors conducted a scoping review to examine the evidence and discern gaps in the literature concerning the effects of RCL on mental health and to assess the factors responsible for an observed heterogeneity in research results.

Naloxone is an effective medication used to reverse opioid overdoses. Distributing naloxone directly to those at risk, therefore, reduces the risk of opioid-related deaths. New legislation in Australia means a prescription is no longer required to access naloxone. Whilst acknowledging the benefits of increased access, we aim to evaluate the impact psychiatrists can have on naloxone provision due to their unique position as doctors often working with those who may be at risk.

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. HCC incidence is on the rise, while treatment options remain limited. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the Activator Protein-1 (AP-1) (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens (Fra-) 1 and 2 is unknown. Here, we show that hepatocyte-restricted expression of a single chain c-Jun~Fra-2 protein, which functionally mimics the c-Jun/Fra-2 AP-1 dimer, results in spontaneous HCC formation in c-Jun~Fra-2 mice. Several hallmarks of human HCC, such as cell cycle dysregulation and the expression of HCC markers are observed in liver tumors arising in c-Jun~Fra-2 mice. Tumorigenesis occurs in the context of mild inflammation, low-grade fibrosis, and Pparγ-driven dyslipidemia. Subsequent analyses revealed increased expression of c-Myc, evidently under direct regulation by AP-1 through a conserved distal 3' enhancer. Importantly, c-Jun~Fra-2-induced tumors revert upon switching off transgene expression, suggesting oncogene addiction to the c-Jun~Fra-2 transgene. Tumors escaping reversion maintained c-Myc and c-Myc target gene expression, likely due to increased c-Fos. Interfering with c-Myc in established tumors using the Bromodomain and Extra-Terminal motif inhibitor JQ-1 diminished liver tumor growth in c-Jun~Fra-2 mutant mice. Thus, our data establish c-Jun~Fra-2 mice as a model to study liver tumorigenesis and identify the c-Jun/Fra-2-Myc interaction as a potential target to improve HCC patient stratification and/or therapy.

Nicotine use produces psychoactive effects, and chronic use is associated with physiological and psychological symptoms of addiction. However, chronic nicotine use is known to decrease food intake and body weight gain, suggesting that nicotine also affects central metabolic and appetite regulation. We recently showed that acute nicotine self-administration in nicotine-dependent animals produces a short-term increase in food intake, contrary to its long-term decrease of feeding behavior. As feeding behavior is regulated by complex neural signaling mechanisms, this study aimed to test the hypothesis that nicotine intake in animals exposed to chronic nicotine may increase activation of pro-feeding regions and decrease activation of pro-satiety regions to produce the acute increase in feeding behavior. FOS immunohistochemistry revealed that acute nicotine intake in nicotine self-administering animals increased activation of the pro-feeding arcuate and lateral hypothalamic nuclei and decreased activation of the pro-satiety parabrachial nucleus. Regional correlational analysis also showed that acute nicotine changes the functional connectivity of the hunger/satiety network. Further dissection of the role of the arcuate nucleus using electrophysiology found that putative POMC neurons in animals given chronic nicotine exhibited decreased firing following acute nicotine application. These brain-wide central signaling changes may contribute to the acute increase in feeding behavior we see in rats after acute nicotine and provide new areas of focus for studying both nicotine addiction and metabolic regulation.

This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.

We investigated whether defense mechanisms in patients with borderline personality disorder (BPD) predict treatment response of dialectical behavior therapy (DBT) and whether they moderate outcome in different treatment lengths.

Dual diagnosis is used in addiction medicine to refer to the co-occurrence of an addiction-related disorder and another psychiatric disorder in the same individual. Adolescence is a key period for the development of both mental disorders and addictions.

To evaluate the effects of a multi-component intervention for smokers hospitalized for atherosclerotic cardiovascular disease (ASCVD) on the participation rate in community-based cessation programmes and the use of cessation drugs. Additionally, to explore the impact on the cessation rates at 6 months.

Methamphetamine is a highly stimulating psychoactive drug that causes life-threatening addictions and affects millions of people around the world. Its effects on the brain are complex and include disturbances in the neurotransmitter systems and neurotoxicity. There are several known treatment methods, but their effectiveness is moderate. It must be emphasised that no drugs have been approved for treatment. For this reason, there is an urgent need to develop new, effective, and safe treatments for methamphetamine. One of the potential treatments is mindfulness meditation. In recent years, this technique has been researched extensively in the context of many neurological and psychiatric disorders.

(1) Objective: This systematic review explores the intricate relationship between cyberbullying and non-suicidal self-injury (NSSI) in adolescents, acknowledging the dynamic nature of these phenomena in the evolving landscape of technology and social norms. (2) Methods: PubMed/MEDLINE, Web of Science, and EMBASE were searched, and 14 studies were selected based on the eligibility criteria, focusing on participants aged 10 to 19, cyberbullying roles, and NSSI as the predictor and outcome variables, respectively. (3) Results: Internalizing symptoms, specifically depression and anxiety, emerged as the most prominent mediators. However, factors such as externalizing symptoms, stress, and negative emotional responses (emotion reactivity, negative emotions) were also identified to play a significant role in the relationship between cyberbullying and NSSI. On the other hand, protective factors against the negative impact of cyberbullying on NSSI risk, such as strong peer connections and school engagement, were identified. (4) Discussions: This review underscores the multidimensional nature of the cyberbullying-NSSI association, emphasizing the roles of potential risk factors such as internalizing and externalizing symptoms, stress, and negative emotional response. Internalizing symptoms played a central role as pathways between cyberbullying victimization and NSSI. Additionally, social factors, including peer connections and school engagement, were found to act as protective elements. (4) Conclusion: Continuous investigation is crucial in order to adapt interventions to the evolving technological and social landscape. The study advocates for targeted interventions that prioritize positive social connections to mitigate the impact of cyberbullying on adolescent well-being.

Synthetic cathinones, derived from cathinone found in the plant Catha edulis, represent the second largest and most frequently seized group of new psychoactive substances. They are considered as β-keto analogs of amphetamine, sharing pharmacological effects with amphetamine and cocaine. This review describes the neurotoxic properties of synthetic cathinones, encompassing their capacity to induce neuroinflammation, dysregulate neurotransmitter systems, and alter monoamine transporters and receptors. Additionally, it discusses the rewarding and abuse potential of synthetic cathinones drawing from findings obtained through various preclinical animal models, contextualized with other classical psychostimulants. The review also offers an overview of current abuse trends of synthetic cathinones on the illicit drug market, specifying the aspects covered, and underscores the risks they pose to public health. Finally, the review discusses public health initiatives and efforts to reduce the hazards of synthetic cathinones, including harm reduction methods, education, and current clinical management strategies.

Central neurological disorders are significant contributors to morbidity, mortality, and long-term disability globally in modern society. These encompass neurodegenerative diseases, ischemic brain diseases, traumatic brain injury, epilepsy, depression, and more. The involved pathogenesis is notably intricate and diverse. Ferroptosis and neuroinflammation play pivotal roles in elucidating the causes of cognitive impairment stemming from these diseases. Given the concurrent occurrence of ferroptosis and neuroinflammation due to metabolic shifts such as iron and ROS, as well as their critical roles in central nervous disorders, the investigation into the co-regulatory mechanism of ferroptosis and neuroinflammation has emerged as a prominent area of research. This paper delves into the mechanisms of ferroptosis and neuroinflammation in central nervous disorders, along with their interrelationship. It specifically emphasizes the core molecules within the shared pathways governing ferroptosis and neuroinflammation, including SIRT1, Nrf2, NF-κB, Cox-2, iNOS/NO·, and how different immune cells and structures contribute to cognitive dysfunction through these mechanisms. Researchers' findings suggest that ferroptosis and neuroinflammation mutually promote each other and may represent key factors in the progression of central neurological disorders. A deeper comprehension of the common pathway between cellular ferroptosis and neuroinflammation holds promise for improving symptoms and prognosis related to central neurological disorders.

The pandemic caused by SARS-CoV-2 is still a major health problem. Newly emerging variants and long-COVID-19 represent a challenge for the global health system. In particular, individuals in developing countries with insufficient health care need easily accessible, affordable and effective treatments of COVID-19. Previous studies have demonstrated the efficacy of functional inhibitors of acid sphingomyelinase against infections with various viruses, including early variants of SARS-CoV-2. This work investigated whether the acid sphingomyelinase inhibitors fluoxetine and sertraline, usually used as antidepressant molecules in clinical practice, can inhibit the replication of the former and recently emerged SARS-CoV-2 variants in vitro. Fluoxetine and sertraline potently inhibited the infection with pseudotyped virus-like particles and SARS-CoV-2 variants D614G, alpha, delta, omicron BA.1 and omicron BA.5. These results highlight fluoxetine and sertraline as priority candidates for large-scale phase 3 clinical trials at different stages of SARS-CoV-2 infections, either alone or in combination with other medications.

In a digitally oriented society, smartphones provide continual online accessibility to daily life while simultaneously predisposing adolescents to engage in prolonged connections for various purposes, thus escalating the risk of Internet addiction (IA). Cognitive processes such as multitasking and attentional shifting are frequently associated with smartphone activities. Additionally, online engagements may serve as emotional strategies for regulating negative states (e.g., boredom and distress), redirecting attention towards more gratifying activities, such as social media contents. This study delves into cognitive-emotional processes (i.e., emotion regulation, attention impulsiveness, online vigilance, and multitasking) and emotional/behavioural factors (i.e., emotional problems, conduct problems, hyperactivity/inattention, peer relationships, and prosocial behaviours) that may be implicated in smartphone activities and technology addiction among adolescents. A community sample of Italian high school students (N = 676; 42.2% females) completed the Smartphone Distraction Scale (SDS), the Strength and Difficulties Questionnaire (SDQ) for internalising/externalising symptoms and the Internet Addiction Test (IAT) to assess the presence and severity of IA. The scores on the SDS were found to be positively associated with IA levels. Furthermore, students exhibiting higher internalising/externalising symptoms, particularly those with traits of attention deficit hyperactivity disorder (ADHD), are more likely to manifest problematic smartphone usage. The implications for screening adolescents more susceptible to developing IA symptoms and for implementing preventive interventions are discussed.

Among the most vulnerable to the health-harming effects of heat are people experiencing homelessness. However, during the 2021 Heat Dome, the deadliest extreme heat event (EHE) recorded in Canada to date, people experiencing homelessness represented the smallest proportion of decedents (n = 3, 0.5%)-despite the impacted region (British Columbia) having some of the highest rates of homelessness in the country. Thus, we sought to explore the 2021 Heat Dome as a media-based case study to identify potential actions or targeted strategies that were initiated by community support agencies, individuals and groups, and communicated in the news during this EHE that may have aided in the protection of this group or helped minimize the mortality impacts. Using media articles collated for a more extensive investigation into the effects of the 2021 Heat Dome (n = 2909), we identified a subset which included content on people experiencing homelessness in Canada (n = 274, 9%). These articles were thematically analysed using NVivo. Three main themes were identified: (i) public warnings issued during the 2021 Heat Dome directly addressed people experiencing homelessness, (ii) community support services explicitly targeting this population were activated during the heat event, and (iii) challenges and barriers faced by people experiencing homelessness during extreme heat were communicated. These findings suggest that mass-media messaging and dedicated on-the-ground initiatives led by various organizations explicitly initiated to support individuals experiencing homelessness during the 2021 Heat Dome may have assisted in limiting the harmful impacts of the heat on this community.

Despite the legal acceptance of homosexuality in India, it remains a social taboo, resulting in various challenges being faced by homosexual males. These challenges mainly include issues such as addiction/drug use and inconsistent and/ or incorrect condom usage which increase the risk of acquiring sexually transmitted infections (STIs) and HIV among them. This study was thus conducted with the objective of studying the patterns of addiction/drug use and condom usage among homosexual males.

Substance use disorder (SUD) remains a significant public health issue, with a high relapse rate even after detoxification treatment. Family dysfunction has been identified as a closely related factor contributing to relapse in individuals with SUD. The objective of this study was to investigate the mediating role of family climate in the relapse tendency among patients with SUD.

Substance abuse remains a challenging public health issue, especially among young people. It has been shown that poor sleep and substance abuse may have mutual intensifying effects. This study aimed to evaluate the rates of substance abuse, cigarette smoking, and alcohol consumption and their association with sleep disturbances among university students in 2021.

Pregnant people with comorbid posttraumatic stress disorder (PTSD) and substance use disorder (SUD) constitute a highly vulnerable population. PTSD and SUD confer risks to both the pregnant person and the fetus, including a host of physical and mental health consequences. When PTSD and SUD co-occur, potential negative impacts are amplified, and the symptoms of each may exacerbate and maintain the other. Pregnancy often increases engagement in the healthcare system, presenting a unique and critical opportunity to provide PTSD and SUD treatment to birthing people motivated to mitigate risks of losing custody of their children. This paper presents implementation process outcomes of Written Exposure Therapy (WET), a brief, scalable, and sustainable evidence-based PTSD treatment delivered to pregnant persons receiving care in an integrated obstetrical-addiction recovery program at Boston Medical Center. Trial participants (N = 18) were mostly White, non-Hispanic (61.1%), not currently working (77.8%), had a high school or lower level of education (55.5%), had an annual household income less than $35,000 (94.4%), and were living in a substance use residential program (55.6%). We examined intervention feasibility, acceptability, appropriateness, adoption; barriers and facilitators to implementation; and feedback on supporting uptake and sustainability of the intervention using coded qualitative sources (consultation field notes [N = 47] and semi-structured interviews [N = 5]) from providers involved in trial planning and treatment delivery. Results reflected high acceptability, appropriateness, and adoption of WET. Participants described system-, provider-, and patient-level barriers to implementation, offered suggestions to enhance uptake, but did not raise concerns about core components of the intervention. Findings suggest that WET is an appropriate and acceptable PTSD treatment for this difficult-to-reach, complex population, and has the potential to positively impact pregnant persons and their children.

The use of standard protocols in studies supports consistent data collection, improves data quality, and facilitates cross-study analyses. Funded by the National Institutes of Health, the PhenX (consensus measures for otypes and eposures) Toolkit is a catalog of recommended measurement protocols that address a wide range of research topics and are suitable for inclusion in a variety of study designs. In 2020, a PhenX Working Group of smoking cessation experts followed a well-established consensus process to identify and recommend measurement protocols suitable for inclusion in smoking cessation and smoking harm reduction studies. The broader scientific community was invited to review and provide feedback on the preliminary recommendation of the Working Group. Fourteen selected protocols for measuring smoking cessation, harm reduction, and biomarkers research associated with smoking cessation were released in the PhenX Toolkit ( https://www.phenxtoolkit.org) in February 2021. These protocols complement existing PhenX Toolkit content related to tobacco regulatory research, substance use and addiction research, and other measures of smoking-related health outcomes. Adopting well-established protocols enables consistent data collection and facilitates comparing and combining data across studies, potentially increasing the scientific impact of individual studies.

Impulsivity and decision-making are key factors in addiction. However, little is known about how gender and time sensitivity affect impulsivity in internet gaming disorder (IGD).

In China, a significant number of undergraduates are experiencing poor sleep quality. This study was designed to investigate the prevalence of poor sleep quality and identify associated factors among undergraduates in Jiangsu Province, China.

The influence of mindfulness-based intervention (MBI) programs on behavioural problems among community youth is largely understudied. While technology continues to evolve and the prevalence of screen-based activities is rising, limited studies have accounted for screen time when examining the efficacy of an MBI. Accordingly, this study investigated the impact of MBI on conduct problems and hyperactivity among community youth, accounting for sociodemographic characteristics and four types of screen time.

Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women.

The COVID-19 pandemic caused multiple stressors that may lead to symptoms of adjustment disorder. We longitudinally examined relationships between risk and protective factors, pandemic-related stressors and symptoms of adjustment disorder during the COVID-19 pandemic, as well as whether these relationships differed by the time of assessment. The European Society for Traumatic Stress Studies (ESTSS) ADJUST Study included = 15,169 participants aged 18 years and above. Participants from 11 European countries were recruited and screened three times at 6-month intervals from June 2020 to January 2022. Associations between risk and protective factors (e.g. gender), stressors (e.g. fear of infection), and symptoms of adjustment disorder (AjD, ADNM-8) and their interaction with time of assessment were examined using mixed linear regression. The following predictors were significantly associated with higher AjD symptom levels: female or diverse gender; older age; pandemic-related news consumption >30 min a day; a current or previous mental health disorder; trauma exposure before or during the pandemic; a good, satisfactory or poor health status (vs. very good); burden related to governmental crisis management and communication; fear of infection; restricted social contact; work-related problems; restricted activity; and difficult housing conditions. The following predictors were associated with lower AjD levels: self-employment or retirement; working in healthcare; and face-to-face contact ≥ once a week with loved ones or friends. The effects of the following predictors on AjD symptoms differed by the time of assessment in the course of the pandemic: a current or previous mental disorder; burden related to governmental crisis management; income reduction; and a current trauma exposure. We identified risk factors and stressors predicting AjD symptom levels at different stages of the pandemic. For some predictors, the effects on mental health may change at different stages of a pandemic.