Exploring Predictors of Treatment Response to GLP-1 Receptor Agonists for Smoking Cessation.

Introduction: Understanding predictors of smoking cessation medication efficacy facilitates the ability to enhance treatment effectiveness. In our pilot trial, exenatide, a glucagon-like peptide-1 receptor agonist, adjunct to nicotine patch improved smoking abstinence compared to nicotine patch alone. This secondary analysis explores potential baseline characteristics associated with differential treatment response to exenatide.

Fitness consequences of depressive symptoms vary between generations: Evidence from a large cohort of women across the 20th century.

Depression has strong negative impacts on how individuals function, leading to the assumption that there is strong negative selection on this trait that should deplete genetic variation and decrease its prevalence in human populations. Yet, depressive symptoms remain common. While there has been a large body of work trying to resolve this paradox by mapping genetic variation of this complex trait, there have been few direct empirical tests of the core assumption that there is consistent negative selection on depression in human populations.

Lipidomic and Proteomic Insights from Extracellular Vesicles in Postmortem Dorsolateral Prefrontal Cortex Reveal Substance Use Disorder-Induced Brain Changes.

Substance use disorder (SUD) significantly increases the risk of neurotoxicity, inflammation, oxidative stress, and impaired neuroplasticity. The activation of inflammatory pathways by substances may lead to glial activation and chronic neuroinflammation, potentially mediated by the release of extracellular particles (EPs), such as extracellular condensates (ECs) and extracellular vesicles (EVs). These particles, which reflect the physiological, pathophysiological, and metabolic states of their cells of origin, might carry molecular signatures indicative of SUD.

Cell type-specific Multi-Omics Analysis of Cocaine Use Disorder in the Human Caudate Nucleus.

Structural and functional alterations in the brain's reward circuitry are present in cocaine use disorder (CocUD), but their molecular underpinnings remain unclear. To investigate these mechanisms, we performed single-nuclei multiome profiling on postmortem caudate nucleus tissue from six individuals with CocUD and eight controls. We profiled 31,178 nuclei, identifying 13 cell types including D1- and D2-medium spiny neurons (MSNs) and glial cells.

Neuroecological links of the exposome and One Health.

This NeuroView assesses the interplay among exposome, One Health, and brain capital in health and disease. Physical and social exposomes affect brain health, and green brain skills are required for environmental health strategies. Ibanez et al.

Neuronal alterations in AKT isotype expression in schizophrenia.

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia.

Identifying novel gene dysregulation associated with opioid overdose death: A meta-analysis of differential gene expression in human prefrontal cortex.

Only recently have human postmortem brain studies of differential gene expression (DGE) associated with opioid overdose death (OOD) been published; sample sizes from these studies have been modest (N = 40-153). To increase statistical power to identify OOD-associated genes, we leveraged human prefrontal cortex RNAseq data from four independent OOD studies and conducted a transcriptome-wide DGE meta-analysis (N = 285). Using a unified gene expression data processing and analysis framework across studies, we meta-analyzed 20 098 genes and found 335 significant differentially expressed genes (DEGs) by OOD status (false discovery rate < 0.

Prenatal cocaine exposure and its influence on pediatric epigenetic clocks and epigenetic scores in humans.

The investigation of the effects of prenatal cocaine exposure (PCE) on offspring has been inconsistent, with few studies investigating biological outcomes in humans. We profiled genome-wide DNA methylation (DNAm) of umbilical cord blood (UCB) from newborns with (n = 35) and without (n = 47) PCE. We used DNAm data to (1) assess pediatric epigenetic clocks at birth and (2) to estimate epigenetic scores (ES) for lifetime disorders.

Types of Traumatic Experiences in Drug Overdose-Related Deaths: An Exploratory Latent Class Analysis.

Aim: Drug overdose related-deaths in the US are increasing, with over 100,000 deaths occurring in 2020, an increase of 30% from the previous year and the highest number recorded in a single year. It is widely known that experiences of trauma and substance use very often co-occur, but little is known about the role of trauma in the context of drug overdose-related deaths. Latent class analysis (LCA) was used to classify drug overdose-related deaths based on type of traumatic experiences and individual, social, and substance use characteristics.

A human stem cell-derived neuronal model of morphine exposure reflects brain dysregulation in opioid use disorder: Transcriptomic and epigenetic characterization of postmortem-derived iPSC neurons.

Introduction: Human-derived induced pluripotent stem cell (iPSC) models of brain promise to advance our understanding of neurotoxic consequences of drug use. However, how well these models recapitulate the actual genomic landscape and cell function, as well as the drug-induced alterations, remains to be established. New models of drug exposure are needed to advance our understanding of how to protect or reverse molecular changes related to substance use disorders.

MicroRNA-mRNA networks are dysregulated in opioid use disorder postmortem brain: Further evidence for opioid-induced neurovascular alterations.

Introduction: To understand mechanisms and identify potential targets for intervention in the current crisis of opioid use disorder (OUD), postmortem brains represent an under-utilized resource. To refine previously reported gene signatures of neurobiological alterations in OUD from the dorsolateral prefrontal cortex (Brodmann Area 9, BA9), we explored the role of microRNAs (miRNA) as powerful epigenetic regulators of gene function.

Methods: Building on the growing appreciation that miRNAs can cross the blood-brain barrier, we carried out miRNA profiling in same-subject postmortem samples from BA9 and blood tissues.

The UT health Psychological Autopsy Interview Schedule (UTH- PAIS) - Description and reliability of diagnoses and transdiagnostic personality measures.

Few studies have used psychological autopsies to evaluate large and diverse populations on transdiagnostically relevant variables such as personality, temperament, and trauma exposure; rather, they tend to focus on specific psychiatric disorders or manner of death. We therefore developed the UT Health Psychological Autopsy Interview Schedule (UTH-PAIS). The measure is described, and our results show that the PAIS diagnoses and dimensions can be reliably assessed.

Within subject cross-tissue analyzes of epigenetic clocks in substance use disorder postmortem brain and blood.

There is a possible accelerated biological aging in patients with substance use disorders (SUD). The evaluation of epigenetic clocks, which are accurate estimators of biological aging based on DNA methylation changes, has been limited to blood tissue in patients with SUD. Consequently, the impact of biological aging in the brain of individuals with SUD remains unknown.

Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits.

Private companies have begun offering services to allow parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This procedure, called polygenic embryo screening, raises several difficult scientific and ethical issues, as discussed in this Personal View. Polygenic embryo screening depends on the statistical properties of polygenic risk scores, which are complex and not well studied in the context of this proposed clinical application.

Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder.

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls.

Nuclear βII-Tubulin and its Possible Utility in Cancer Diagnosis, Prognosis and Treatment.

Microtubules are organelles that usually occur only in the cytosol. Walss et al. (1999) discovered the βII isotype of tubulin, complexed with , in the nuclei of certain cultured cells, in non-microtubule form.