Exploring the potential link between ΔFosB and -acetylcysteine in craving/relapse dynamics: can -acetylcysteine stand out as a possible treatment candidate?

From a neuroscientific point of view, one of the unique archetypes of substance use disorders is its road to relapse, in which the reward system plays a crucial role. Studies on the neurobiology of substance use disorders have highlighted the central role of a protein belonging to the Fos family of transcription factors, ΔFosB. Relying on the roles ΔFosB plays in the pathophysiology of substance use disorders, we endeavour to present some evidence demonstrating that -acetylcysteine, a low-cost and well-tolerated over-the-counter medicine, may influence the downstream pathway of ΔFosB, thereby serving as a treatment strategy to mitigate the risk of relapse in cases of substance use.

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.

Sex differences in sensitivity to fentanyl effects in mice: Behavioral and molecular findings during late adolescence.

Purpose: Sex differences play a crucial role in understanding vulnerability to opioid addiction, yet there have been limited preclinical investigations of this effect during the transition from adolescence to adulthood. The present study compared the behaviors of male and female rodents in response to fentanyl treatment and targeted molecular correlates in the striatum and medial prefrontal cortex.

Materials And Methods: Thirty adolescent C57BL/6J mice underwent a 1-week fentanyl treatment with an escalating dose.

Consortium Profile: The Methylation, Imaging and NeuroDevelopment (MIND) Consortium.

Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults.

The cortical thickness of tricenarian cocaine users assembles features of an octogenarian brain.

It has been suggested that substance use disorders could lead to accelerated biological aging, but only a few neuroimaging studies have investigated this hypothesis so far. In this cross-sectional study, structural neuroimaging was performed to measure cortical thickness (CT) in tricenarian adults with cocaine use disorder (CUD, n  = 30) and their age-paired controls (YC, n  = 30), and compare it with octogenarian elder controls (EC, n  = 20). We found that CT in the right fusiform gyrus was similar between CUD and EC, thinner than the expected values of YC.

Proposing an integrative, dynamic and transdiagnostic model for addictions: dysregulation phenomena of the three main modes of the predostatic mind.

Several theories have been proposed to explain the complex diagnostic aspects related to addiction disorders and their development. Recent frameworks tend to focus on dimensional perspectives of symptoms rather than categorical systems, since substance use disorders are frequently comorbid with other psychiatric and especially personality disorders. However, useful transdiagnostic models that could integrate clinical evaluation derived from neuroscientific theories are lacking.

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.

Examining predictors of cocaine withdrawal syndrome at the end of detoxification treatment in women with cocaine use disorder.

Background: Detoxification is frequently recommended as a treatment for moderate to severe Cocaine Use Disorder (CUD). However, the response to detoxification varies among patients, and previous studies have focused mostly on patterns of drug use behavior to test associations with treatment outcomes, overlooking the potential impact of psychosocial factors, other clinical variables, and individual life experiences. In this study we comprehensively examined several variables aiming to find the most relevant predictors to classify patients with severe versus non-severe cocaine withdrawal symptoms at the end of detoxification.

A single dose of cocaine raises SV2A density in hippocampus of adolescent rats.

Objective: Cocaine is a highly addictive psychostimulant that affects synaptic activity with structural and functional adaptations of neurons. The transmembrane synaptic vesicle glycoprotein 2A (SV2A) of pre-synaptic vesicles is commonly used to measure synaptic density, as a novel approach to the detection of synaptic changes. We do not know if a single dose of cocaine suffices to affect pre-synaptic SV2A density, especially during adolescence when synapses undergo intense maturation.

A cross-sectional study of the association between exposure to violence, intelligence, and executive function in Brazilian youths.

We carried out an exploratory study of the association between exposure to violence, intelligence, and executive functions in Brazilian preadolescents. The study included 56 participants (31 males) aged 8 to 14 years old (mean = 11.3, SD = 1.

Rethinking treatment-resistant depression to quasi-tenacious depression.

With almost one-third of patients with major depression not adequately responsive to treatments, the management of treatment-resistant depression (TRD) has continued to be challenging. Recently, an essential step was taken to replace TRD with difficult-to-treat depression (DTD), pointing to some drawbacks associated with this terminology and identifying addressable barriers. In line with the DTD concept, we discuss why terming this population of patients as TRD could be semantically and clinically misleading.

Gender differences in progression to crack-cocaine use and the role of sexual and physical violence.

Objective: This study aimed to evaluate whether progression from first drug use to crack-cocaine use differs according to gender, and whether the report of sexual or physical violence impacts the time of progression.

Methods: We interviewed 896 crack-cocaine users (548 men; 348 women) from addiction treatment units. Cox regression models evaluated the time of progression from first drug use to crack use.

A systematic review and meta-analysis of epigenetic clocks in schizophrenia.

Introduction: Evidence suggests that schizophrenia (SZ) is associated with accelerated biological aging. DNA methylation can be used as an indicator of biological aging by means of epigenetic clock estimates.

Objective: The aim of this systematic review and meta-analysis was to investigate the association between SZ and different epigenetic clocks.

Effects of early life stress on brain cytokines: A systematic review and meta-analysis of rodent studies.

Exposure to early life stress (ELS) may lead to long-lasting neurobiological and behavioral impairments. Alterations in the immune system and neuroinflammatory state induced by ELS exposure are considered risk factors for developing psychiatric disorders. Here, we performed a systematic review and meta-analysis of rodent studies investigating the short and long-term effects of ELS exposure on anti and pro-inflammatory cytokines in brain tissues.

The Perceptions of Women About Their High Experience of Using Crack Cocaine.

Introduction: The aim of this study was to explore the perceptions of women about their experience in using crack cocaine, discussing their motivations for using it and the repercussions in their lives.

Objective: To investigate these experiences, a qualitative exploratory study was conducted, using the inductive thematic analyses of the content.

Methods: Eight female crack cocaine users took part in this study.