Neuroscience Psychopharmacology

Recent studies have sparked renewed interest in the therapeutic potential of psychedelics for treating depression and other mental health conditions. Simultaneously, the novel psychoactive substances (NPS) phenomenon, with a huge number of NPS emerging constantly, has changed remarkably the illicit drug market, being their scientific evaluation an urgent need. Thus, this study aims to elucidate the impact of amino-terminal modifications to the 5-MeO-DMT molecule on its interactions with serotonin receptors and transporters, as well as its psychoactive and thermoregulatory properties...

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BACKGROUND: Understanding the biological processes underlying individual differences in emotion regulation and stress responsivity is a key challenge for translational neuroscience. The gene FKBP5 is a core regulator in molecular stress signaling that is implicated in the development of psychiatric disorders. Yet it remains unclear how FKBP5 DNA methylation (DNAm) in peripheral blood relates to individual differences in measures of neural structure and function, and their relevance to daily-life stress responsivity...

AIM: Widely used second-generation antipsychotics are associated with adverse metabolic effects, contributing to increased cardiovascular mortality. To develop strategies to prevent or treat adverse metabolic effects, preclinical models have a clear role in uncovering underlying molecular mechanisms. However, with few exceptions, preclinical studies have been performed in healthy animals, neglecting the contribution of dysmetabolic features inherent to psychotic disorders. METHODS: In this study, methylazoxymethanol acetate (MAM) was prenatally administered to pregnant Sprague-Dawley rats at gestational day 17 to induce a well-validated neurodevelopmental model of schizophrenia mimicking its assumed pathogenesis with persistent phenotype...

AIM: Large language models (LLMs) have been suggested to play a role in medical education and medical practice. However, the potential of their application in the psychiatric domain has not been well-studied. METHOD: In the first step, we compared the performance of ChatGPT GPT-4, Bard, and Llama-2 in the 2022 Taiwan Psychiatric Licensing Examination conducted in traditional Mandarin. In the second step, we compared the scores of these three LLMs with those of 24 experienced psychiatrists in 10 advanced clinical scenario questions designed for psychiatric differential diagnosis...

Cerebral cortex is found only in mammals and most prominently present in humans. Various rodent models with fully or partially ablated cortex are commonly used to probe the role of cortex in brain functions and its multiple subcortical projections, including pallium, thalamus and the limbic system. Various rodent models are traditionally used to study the role of cortex in brain functions. A small teleost fish, the zebrafish (Danio rerio), has gained popularity in neuroscience research, and albeit (like other fishes), lacks cortex, its brain performs well some key functions (e...

The significant heterogeneity in smoking behavior among smokers, coupled with the inconsistent efficacy of approved smoking cessation therapies, supports the presence of individual variations in the mechanisms underlying smoking. This emphasizes the need to shift from standardized to personalized smoking cessation therapies. However, informed precision medicine demands precision fundamental research. Tobacco smoking is influenced and sustained by diverse psychopharmacological interactions between nicotine and environmental stimuli...

Functional changes in dopamine transporter (DAT) are related to various psychiatric conditions, including bipolar disorder (BD) symptoms. In experimental research, the inhibition of DAT induces behavioral alterations that recapitulate symptoms found in BD patients, including mania and depressive mood. Thus, developing novel animal models that mimic BD-related conditions by pharmacologically modulating the dopaminergic signaling is relevant. The zebrafish (Danio rerio) has been considered a suitable vertebrate system for modeling BD-like responses, due to the well-characterized behavioral responses and evolutionarily conservation of the dopaminergic system of this species...

Although mental effort is a frequently used term, it is poorly defined and understood. Consequently, its usage is frequently loose and potentially misleading. In neuroscience research, the term is used to mean both the cognitive 'work' that is done in meeting task demands, and the subjective experience of performing that work. We argue that conflating these two meanings hampers progress in understanding cognitive impairments in neuropsychiatric conditions, because cognitive work and the subjective experience of it have distinct underlying mechanisms...

In recent years, psychedelics have generated considerable excitement and interest as potential novel therapeutics for an array of conditions, with the most advanced evidence base in the treatment of certain severe and/or treatment-resistant psychiatric disorders. An array of clinical and pre-clinical evidence has informed our current understanding of how psychedelics produce profound alterations in consciousness. Mechanisms of psychedelic action include receptor binding and downstream cellular and transcriptional pathways, with long-term impacts on brain structure and function-from the level of single neurons to large-scale circuits...

BACKGROUND: Resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in psychiatric disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across them. METHODS: To uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of dysconnectivity findings reported separately in MDD, BD and SZ...

Introduction: The use of medical Cannabis remains unregulated in several countries due to the scarcity of clinical studies with high scientific evidence that establish safety and efficacy of Cannabis products. This study aimed to comprehensively analyze how knowledge has been created in this field, as well as perform a bibliographic mapping to identify knowledge gaps, and investigate key authors and journals that have significantly contributed to advancing our understanding of Cannabis . Method: The study protocol was registered in the International Prospective Register of Systematic Review (CRD42020223084)...

Exposure-response prevention is an effective approach to treat anxiety disorders. Virtual reality exposure therapy (VRET) is a promising treatment for patients with posttraumatic stress disorder (PTSD). New research has helped refine and update VRET. In this study, we introduce a form of VRET developed for patients suffering from PTSD after a traffic accident, and present two cases treated using this protocol. After 6 weeks of VRET treatment, the two participants not only improved their PTSD symptoms, but also improved their depressed mood, anxiety, and insomnia symptoms...

Trichotillomania (or hair pulling disorder) is a habitual condition in which patients constantly pull their hair. Although psychotherapies such as behavioral therapy and pharmacotherapy have shown relative effectiveness for trichotillomania, some patients fail to respond to these interventions or show only partial responses. Recently, noninvasive brain stimulation techniques such as transcranial direct current stimulation have shown promise in the treatment of psychiatric disorders. We designed a new protocol that included intensified and repeated during 16 sessions, every other day, 2 sessions one day, current intensity of 2 mA for 20 minutes, which regions dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA): Anodal (F3) and cathodal (SMA) were selected as stimulation target areas...

OBJECTIVE: : This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in out-patients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. METHODS: : This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3-12 weeks; 3-week interval)...

OBJECTIVE: : Cognitive reserve has emerged as a concept to explain the variable expression of clinical symptoms in the pathology of Alzheimer's disease (AD). The association between years of education, a proxy of cognitive reserve, and resting-state functional connectivity (rFC), a representative intermediate phenotype, has not been explored in the preclinical phase, considering risk factors for AD. We aimed to evaluate whether the relationship between years of education and rFC in cognitively preserved older adults differs depending on amyloid-beta deposition and APOE ε4 carrier status as effect modifiers...

OBJECTIVE: : Treatment Resistant Depression (TRD) is commonly defined as the lack of response to two or more anti-depressants with different mechanisms of action. Up to 30% of patients diagnosed with major depressive disorder might be considered to present TRD. The objective of this study was to assess the effectiveness and tolerability of esketamine in patients diagnosed with TRD, who were referred to our program after exhausting all available treatments. A secondary objective consisted in researching the relationship between response and previous use of electroconvulsive therapy...

OBJECTIVE: : This study investigated the association between non-suicidal self-injury (NSSI) and quantified electroencephalogram (QEEG) in patients with depression. We aimed to identify clinical features of NSSI and differences in QEEG findings. METHODS: : This retrospective study used the medical records of 52 inpatients with major depressive episodes, aged from 15 to 30. The patients were categorized according to their history of NSSI. Their main diagnosis and sex were also considered...

OBJECTIVE: : Recent evidence suggests that oxidative stress contributes to the pathophysiology of schizophrenia. This study aimed to compare thiol-disulphide homeostasis in acute and stable phases of schizophrenia for the first time. METHODS: : Among the patients with schizophrenia, 61 in the acute-phase and 61 in the stable phase of their illness were enrolled in the study. Native thiol (NT), total thiol (TT), disulphide (SS), disulphide/native thiol, disulphide/total thiol, and native thiol/total thiol for thiol-disulphide homeostasis were compared between the groups...

OBJECTIVE: : Microtubule (MT) stability in neurons is vital for brain development; instability is associated with neuropsychiatric disorders. The present study examined the effects of social defeat stress (SDS) on MT-regulating proteins and tubulin polymerization. METHODS: : After 10 days of SDS, defeated mice were separated into susceptible (Sus) and unsusceptible (Uns) groups based on their performance in a social avoidance test. Using extracted brain tissues, we measured the expression levels of α-tubulin, acetylated α-tubulin, tyrosinated α-tubulin, MT-associated protein-2 (MAP2), stathmin (STMN1), phospho stathmin serine 16 (p-STMN1 [Ser16]), phospho stathmin serine 25 (p-STMN1 [Ser25]), phospho stathmin serine 38 (p-STMN1 [Ser38]), stathmin2 (STMN2), phospho stathmin 2 serine 73 (p-STMN2 [Ser73]), 78-kDa glucose-regulated protein (GRP-78), and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) using Western blot assay...