Search Results (264)

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background: Anabolic–androgenic steroids (AASs) are commonly used for performance enhancement but have been linked to significant neurobiological consequences. This review explores the impact of AASs on neurochemical pathways, cognitive function, and psychiatric disorders, highlighting their potential neurotoxicity. Methods: A narrative review of current literature was conducted to examine AASs-induced alterations in neurotransmitter systems, structural and functional brain changes, and associated psychiatric conditions. The interplay between AASs use and other substances was also considered. Results: Chronic AASs exposure affects serotonin and dopamine systems, contributing to mood disorders, aggression, and cognitive deficits. Structural and functional changes in the prefrontal cortex and limbic regions suggest long-term neurotoxicity. AASs use is associated with increased risks of depression, anxiety, and psychosis, potentially driven by hormonal dysregulation and neuroinflammation. Co-occurring substance use exacerbates neurocognitive impairments and behavioral disturbances. Discussion: While evidence supports the link between AASs use and neurotoxicity, gaps remain in understanding the precise mechanisms and long-term effects. Identifying biomarkers of brain damage and developing targeted interventions are crucial for mitigating risks. Increased awareness among medical professionals and policymakers is essential to address AASs-related neuropsychiatric consequences. Conclusions: AASs abuse poses significant risks to brain health, necessitating further research and prevention efforts. Evidence-based strategies are needed to educate the public, enhance early detection, and develop effective interventions to reduce the neuropsychiatric burden of AASs use. Full article

Background and Objectives: The worldwide shift toward psychiatric deinstitutionalization has aimed to enhance patient autonomy, social integration, and overall quality of life. However, limited studies have examined how concurrent substance use—particularly alcohol, marijuana, and inhalable drugs—affects clinical outcomes in these populations. This study aimed to evaluate psychiatric patients with varying degrees of institutionalization and investigate whether substance use complicates or exacerbates treatment outcomes. We hypothesized that individuals using substances would demonstrate worse psychosocial functioning, higher healthcare costs, and increased readmission rates. Methods: We performed a cross-sectional study of 95 participants recruited from long-term care facilities. Participants completed the SF-36 survey validated in Romanian. Financial data were collected to gauge direct and indirect healthcare expenditures. Results: Results indicated that 34.7% of participants reported alcohol use, 12.6% used marijuana, and 9.5% used inhalable substances. Substance-using patients experienced higher mean hospitalization costs of approximately USD 3251.8, compared to non-users (USD 2743.6, p = 0.032). Quality-of-life scores were significantly lower among substance users (mean SF-36 score 58.4 vs. 66.7, p = 0.027). Rates of relapse and readmission were also notably higher in the substance-using cohort (42.1%) relative to non-users (29.8%, p = 0.041). Conclusions: To our knowledge, this is the first Romanian study—and one of only a handful in Europe—to quantify how specific substance-use profiles simultaneously alter quality of life and direct healthcare costs in a deinstitutionalized psychiatric population. Our findings highlight the need for integrated interventions targeting both mental health and substance abuse. Full article

Background and objectives. Symptoms of Attention Deficit Hyperactivity Disorder (ADHD) are frequently present in university students, even without a clinical diagnosis, and may be aggravated by various factors. This study analyzes the relationship between these symptoms and the use of alcohol, tobacco, cannabis, and other drugs by young university students. Materials and methods. A cross-sectional study was conducted with 397 university students using an anonymous online questionnaire. ADHD symptoms were assessed with the Adult ADHD Self-Report Scale (ASRS), alcohol use with the Alcohol Use Disorders Identification Test (AUDIT-C), nicotine dependence with the Fagerström test, cannabis use with the Cannabis Abuse Screening Test (CAST), and the use of other substances with an adaptation of the latter. Results. The mean age was 21.4 years, and most participants (76.6%) were women. Of the participants, 46.1% presented symptoms compatible with ADHD according to the ASRS. The most frequent items were difficulty maintaining attention during boring tasks (77.3%), avoiding tasks that require mental effort (76.8%), and being easily distracted by noise or external activity (73.8%). Significant differences were found between ASRS scores and gender, with scores being higher and more consistent among those students who identified themselves as non-binary gender (male or female) (p < 0.01). A significant association was also found between smoking and a higher ASRS score (p < 0.01). Although no significant associations with body mass index were detected, a trend toward greater symptomatology was observed in obese individuals. In multivariate analysis, still gender and smoking significantly (p = 0.12 and p = 0.031, respectively) predicted ADHD symptoms (ASRS score). The model R = 0.228 (R squared = 0.052, F = 1.62, p = 0.077). No statistically significant differences were found between ADHD symptoms and the use of alcohol, cannabis, or other substances in either bivariate or multivariate analyses. Conclusions. This study underscores the importance of early detection of ADHD symptoms in the university setting, considering factors such as gender and smoking habit. Future research should focus on aggravating factors such as academic stress and problematic technology use. Full article

Introduction: Cannabis use disorder (CUD) is being increasingly diagnosed in the United States, but access to treatment remains unequal, particularly in New York. Identifying the factors that contribute to disparities in receiving treatment for CUD among different population groups is essential for ensuring effective and targeted interventions. This study explores the sociodemographic factors influencing treatment utilization for CUD in New York. Methods: Data for this study were retrieved from the 2018 Treatment Episode Data Set—Discharges (TEDS-D) of the U.S. Substance Abuse and Mental Health Services Administration (SAMHSA). Sample size for the study is 422,319 people with CUD. Logistic regression analysis was performed to examine the odds of receiving treatment for CUD based on demographic and socioeconomic factors, as well as the type of treatment setting. Results: The results revealed significant disparities in treatment utilization. Asians/Pacific Islanders and Hawaiian Natives had lower odds of receiving treatment compared to African Americans (OR = 0.367, 95% CI 0.341–0.394). Similarly, Caucasians had the lowest odds of receiving treatment (OR = 0.270, 95% CI 0.266–0.275). Females were less likely to receive treatment compared to males (OR = 0.756, 95% CI 0.744–0.768). Those with higher educational attainment (over four years of college) had the lowest odds of receiving treatment, while individuals with 9–11th grade education had the highest odds. Employment status also influenced treatment access, with the unemployed having the highest odds, and full-time employees having the lowest. Additionally, individuals with no source of income had significantly lower odds of receiving treatment. Conclusions: This study highlights significant disparities in the provision of treatment for CUD in New York, influenced by sociodemographic factors such as race, gender, age, education, and employment status. These findings emphasize the need for targeted interventions to reduce these disparities and improve treatment access for underserved populations. Full article

Background/Objectives: Anxiety disorders are the most prevalent mental illnesses worldwide and in Portugal, often resulting in chronicity and disability. The objective of this study is to evaluate the sociodemographic and health-related factors associated with anxiety in the Portuguese adult population. Methods: This study included participants aged 18 to 65 years from the nationwide, population-based EpiDoC cohort, who were followed from 2011 to 2021 (n = 2927). Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS). A mixed logistic regression analysis was performed using a prospective analytical approach. Two strategies were used to adjust the mixed models: (i) model with only complete observations (n = 1950) and (ii) model with imputation of the category “No” in missing self-reported diseases (n = 2554). Results: The proportion of anxiety symptoms decreased from 2011–2013 to 2021 (12.5% vs. 8.5%). Experienced anxiety symptoms were positively associated (OR > 1, p < 0.05) with being female; having a high school, 2nd and 3rd cycle (6–9 years of studies), or primary/no education; being unemployed; seeking the first job; and not working or being temporarily unable to work. Additionally, anxiety symptoms were positively associated (OR > 1, p < 0.05) with smoking daily, lack of physical exercise, and medication use. Digestive diseases, multimorbidity, and region were also positively associated (OR > 1, p < 0.05) with anxiety symptoms. Moreover, age was negatively associated (OR < 1, p < 0.05) with experiencing anxiety symptoms. Conclusions: Some determinants are modifiable and preventable through economic, social, and health policies. Measures to promote healthy lifestyles, like physical exercise, reduce substance abuse, prevent chronic diseases, increase employability, and increase schooling and health literacy, are necessary to reduce the anxiety rate in Portugal. Full article

Brain organoids are self-organized, three-dimensional (3D) aggregates derived from human embryonic stem cells, induced pluripotent stem cells, or primary organs with cell types and cellular architectures resembling those of the developing human brain. Recent studies have shown the use of region-specific brain organoids for modeling various diseases ranging from neurodevelopmental and neurodegenerative diseases to different brain cancers, which have numerous applications in fundamental research and the development of new drugs, personalized treatment, and regenerative medicine. Consequently, the use of brain organoids in drug discovery is complex and challenging and still an emerging area in this field. This review article summarizes the primary stem cells used in brain organoid generation, region-specific brain organoids, and the functional assays used in their characterization. In addition, we discuss the use of brain organoids in modeling neurodevelopmental and neurodegenerative diseases and pediatric brain cancers, as well as the application of organoids, assembloids, and tumoroids in cancer neuroscience. We further explore the recent advances in using brain organoids in high-throughput screening to improve their use for drug discovery. Full article

Background: Intimate partner femicide (IPF) is the most common form of femicide and a severe expression of gender-based violence, highlighting persistent gender inequality worldwide. Addressing this major public health concern requires a comprehensive synthesis of existing evidence to inform prevention strategies. This review aims to identify risk factors for IPF and explore the demographic, behavioral, and psychosocial characteristics of victims and perpetrators. Methods: A narrative review was conducted using a systematic literature search in Scopus, Web of Science, and PubMed, following PRISMA guidelines. Studies were selected based on predefined inclusion and exclusion criteria. Out of 1200 identified records, 51 met the criteria and were included. Data extraction and analysis were conducted independently by two reviewers. Findings are presented narratively. Results: The review identified multiple risk factors for IPF. Victims were more likely to be married, with a history of psychological and physical abuse as well as substance use. Perpetrators were typically older, with higher rates of unemployment, psychiatric disorders, and substance use. Common precipitating factors included jealousy, separation, and recurrent conflicts. Weapon use—particularly knives and firearms—and “overkill” were frequent. Perpetrators often exhibited stalking behaviors and a history of intimate partner violence. Compared to other homicide offenders, IPF perpetrators were generally older, more often employed, and less likely to have a criminal background, but more likely to engage in intimate partner violence and hold patriarchal beliefs. Conclusions: IPF is not an unpredictable act. Despite the heterogeneity among perpetrators, identifiable risk indicators can inform effective prevention and intervention efforts. Full article

Specific gut microorganisms and their metabolic by-products have been identified as key regulators of host physiology, contributing to the modulation of the immune system, inflammatory processes, brain function, and behavior, which highlights the gut microbiome as a potential modulator of the neurobiological mechanisms involved in substance use disorders. This narrative review provides an updated overview of how drugs of abuse influence the composition and dynamics of the human gut microbiome and how bacterial dysbiosis may be a contributing factor to substance use disorders by modulating the communication between the gut and the brain. Thus, by examining commonly abused substances such as alcohol, psychostimulants, opioids, cannabinoids, and nicotine, this review aimed to deepen the understanding of the bidirectional relationship between the gut microbiome and substance use. There is evidence indicating that gut microbiome alterations may influence addiction through changes in gut-brain signaling. Furthermore, changes in the gut microbiome and its metabolites may not only result from substance use disorders, but could also modulate behavioral responses to drugs of abuse. Although the exact mechanisms by which the gut microbiome modulates behavioral responses to drugs of abuse are not fully understood, microbial products such as short-chain fatty acids, tryptophan metabolites, bile acids, and neurotransmitters have been suggested to play a role in this process by influencing the blood–brain barrier permeability, host immune activation, neural signaling, and gene expression. Therefore, manipulating the gut microbiome or its by-products may represent a promising approach for enhancing substance use disorder treatments, identifying individuals at increased risk of pathological drug use, and elucidating its role in substance-related behaviors. Full article

Substance Use Disorders (SUDs) are frequently associated with impairments in emotional regulation and behavioural control. Among the most prevalent substances of abuse, alcohol and cocaine are known to exert distinct effects on neuropsychological functioning. This study aimed to compare individuals with Alcohol Use Disorder (AUD) and Cocaine Use Disorder (CUD) in terms of impulsivity and alexithymia, and to examine the clinical implications of poly-substance use involving both alcohol and cocaine. Participants completed standardized psychometric assessments, including the Barratt Impulsiveness Scale (BIS-11), the Brief Psychiatric Rating Scale (BPRS), and the Toronto Alexithymia Scale (TAS-20). Group comparisons were conducted using non-parametric tests, and logistic regression models were applied to control for demographic covariates. The findings showed that impulsivity levels were comparable across groups, whereas alexithymia scores were significantly higher in individuals with AUD and in those with poly-substance use, relative to CUD-only participants. These findings underscore the relevance of targeting emotional regulation difficulties, particularly alexithymia, in the assessment and treatment of SUDs. Integrating emotion-focused interventions may enhance treatment outcomes, especially for individuals with co-occurring substance use patterns. Future research is needed to clarify the underlying neuropsychological mechanisms contributing to these differences and to inform more personalized approaches to addiction care. Full article

Introduction: Social sustainability is deeply connected to the well-being of marginalized groups, and it is important to highlight how mental health impacts the social inclusion of homeless individuals, particularly veterans. Homelessness is a growing global issue, disproportionately affecting U.S. veterans, with mental health challenges playing a significant role in its onset and perpetuation. Purpose: This study aims to compare the sociodemographic and clinical characteristics of homeless veterans and non-veterans in the U.S. Method: Using public data (N = 6295), this quantitative study applies descriptive and inferential statistical analyses. Results: Homeless veterans are more likely than non-veterans to be older, male, and identify as Caucasian or African American. They are more frequently high school graduates or have higher education, and report being divorced, widowed, married, or in varied employment statuses (full-time, part-time, or unemployed). Veterans exhibit higher rates of severe mental illnesses, schizophrenia, trauma- and stressor-related disorders, ADHD, bipolar disorder, personality disorders, depression, anxiety, and substance or alcohol use disorders. However, they are less likely than non-veterans to report substance-induced disorders, intoxication, dependence, or abuse involving cocaine, cannabis, opioids, and other substances. Conclusions: Psychosocial interventions for homeless veterans should prioritize mental health-related concerns, whereas efforts for homeless non-veterans should focus on addressing substance use. Future research should develop tailored interventions, explore the sociodemographic factors influencing homelessness, and investigate the interplay between trauma, mental health, and substance use. Addressing these issues can contribute to a more resilient, inclusive, and sustainable society by providing long-term support and integration opportunities for those most affected. The novelty of this study lies in distinguishing between mental health issues prevalent in veterans and substance use disorders more common in non-veterans, offering insights for tailored interventions. It also connects these findings to social sustainability, suggesting that addressing these issues can promote a more inclusive and resilient society. Full article

The potential contribution of the ion channels that control the excitability of the midline and intralaminar nuclei of the thalamus to the modulation of behaviors has not been well studied. In this study, we used both global genetic deletion (knock-out, KO) and thalamus-specific molecular knock-down (KD) approaches to investigate the role of thalamic Ca_V3.1 T-type calcium channels (T-channels) in fear learning and fear responses. Previously, we have shown that the dominant subtype of T-channels in the central medial nucleus of the thalamus (CMT) is the Ca_V3.1 isoform and that CMT neurons from Ca_V3.1 KO animals have decreased burst firing. By specifically knocking down Ca_V3.1 T-channels in the CMT using the shRNA approach, we also reduced burst firing without affecting the tonic firing mode of the transfected neurons. We report that global Ca_V3.1 KO animals showed stronger freezing behaviors during both the conditioning and testing phases of contextual fear conditioning, while CMT-specific Ca_V3.1 KD mice only had stronger fear responses during testing. In contrast, the cue-mediated fear responses were similar between Ca_V3.1 KO and Ca_V3.1 KD mice and the controls. Our findings validate thalamic Ca_V3.1 T-channels as a potential new target for the development or treatment of different psychiatric diseases, such as post-traumatic stress disorder, schizophrenia, anxiety, and substance abuse disorders. Full article

Background/Objectives: This review examines the role of pharmacogenomics in individual responses to the pharmacotherapy of various drugs of abuse, including alcohol, cocaine, and opioids, to identify genetic variants that contribute to variability in substance use disorder treatment outcomes. In addition, it explores the pharmacomicrobiomic aspects of substance use, highlighting the impact of the gut microbiome on bioavailability, drug metabolism, pharmacodynamics, and pharmacokinetics. Results: Research on pharmacogenetics has identified several promising genetic variants that may contribute to the individual variability in responses to existing pharmacotherapies for substance addiction. However, the interpretation of these findings remains limited. It is estimated that genetic factors may account for 20–95% of the variability in individual drug responses. Therefore, genetic factors alone cannot fully explain the differences in drug responses, and factors such as gut microbiome diversity may also play a significant role. Drug microbial biotransformation is produced by microbial exoenzymes that convert low molecular weight organic compounds into analogous compounds by oxidation, reduction, hydrolysis, condensation, isomerization, unsaturation, or by the introduction of heteroatoms. Despite significant advances in pharmacomicrobiomics, challenges persist including the lack of standardized methodologies, inter-individual variability, limited understanding of drug biotransformation mechanisms, and the need for large-scale validation studies to develop microbiota-based biomarkers for clinical use. Conclusions: Progress in the pharmacogenomics of substance use disorders has provided biological insights into the pharmacological needs associated with common genetic variants in drug-metabolizing enzymes. The gut microbiome and its metabolites play a pivotal role in various stages of drug addiction including seeking, reward, and biotransformation. Therefore, integrating pharmacogenomics with pharmacomicrobiomics will form a crucial foundation for significant advances in precision and personalized medicine. Full article

Depressive disorder during pregnancy is a common condition, affecting approximately 10–15% of pregnant women, and is associated with adverse pregnancy outcomes such as inadequate prenatal care, substance abuse, and fetal growth restriction. Beyond neurotransmitter disturbances, increasing evidence suggests that infectious agents may play a role in the pathophysiology of depression through immune system modulation. Toxoplasma gondii infection has been linked to various mental disorders in the general population, including depression and anxiety. This study aimed to investigate whether depressive disorder during pregnancy is associated with chronic T. gondii infection by analyzing cytokine levels involved in inflammatory response modulation. Serum levels of TNF, IFN-γ, TGF-β1, IL-6, IL-8, IL-10, and MIF were measured in 79 pregnant women (18–40 years old) during the third trimester of an uncomplicated pregnancy. Participants were divided into four groups: Group I—depressive disorder and T. gondii seropositive (n = 19); Group II—no depressive disorder and T. gondii seropositive (n = 20); Group III—depressive disorder and T. gondii seronegative (n = 20); and Group IV—no depressive disorder and T. gondii seronegative (n = 20). Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) during routine prenatal visits, and blood samples were collected during standard prenatal examinations. Significant differences in cytokine levels were observed among the study groups. Notably, the group with both depressive disorder and chronic T. gondii infection exhibited a distinct cytokine profile characterized by significantly elevated TNF, IL-6, and IL-10 levels and significantly reduced IL-8 and MIF levels compared to the other groups. These findings suggest that pregnant women with depressive disorder and chronic T. gondii infection exhibit an altered balance of pro- and anti-inflammatory cytokines. This is the first study to investigate the association between serum cytokine levels, depressive disorder, and chronic T. gondii infection in pregnant women. Further research is needed to evaluate the potential of these immunobiomarkers as diagnostic tools or for monitoring therapeutic and prognostic strategies in this context. Full article

Background/Objectives: The present systematic review analyses the neuroradiological findings in subjects with axis I psychiatric disorders (i.e., bipolar, major depressive, schizophrenic, anxiety, and post-traumatic stress disorders) and comorbid substance use disorder in order to elucidate the organic changes that occur in the brains of people suffering from both conditions. Methods: We analysed and compared the different neuroimaging findings extracted from 93 studies and 10,823 patients; articles were obtained from three databases (Scopus, PubMed [Medline], and the Cochrane Controlled Register of Trials [Central]) and subjected to specific eligibility criteria. We selected articles that assessed patients with axis I psychiatric conditions and a comorbid substance abuse disorder; articles had to report relevant neuroimaging findings and bias was assessed via the Newcastle–Ottawa scale. Results: Significant findings were found on the structure or function of psychiatric patients’ brains with comorbid substance abuse, with certain key areas that were further affected by substance use, especially in areas involved in reward processing, with reductions in volume and connectivity and the augmentation of stimuli-related activity. Conclusions: These results present important implications on the current understanding of psychiatric disorders and comorbid substance use, on the importance of neuroradiological tools in the diagnosis and treatment of these disorders, and on the search for potential new targets for the treatment of psychiatric disease and substance addiction. Full article