Facile synthesis of Eu3+-doped niobium carbide MXene quantum dots for parallel detection of hypoxanthine and fluoxetine via fluorescence quenching and enhancement mechanisms.

A hydrothermal synthetic method is established to produce blue fluorescent Eu3+-doped niobium carbide MXene quantum dots (Eu3+-Nb2C MQDs). The synthesized Eu3+-Nb2C MQDs demonstrated a quantum yield of 20.61% and a maximum emission intensity at 405 nm. The as-prepared Eu3+-Nb2C MQDs acted as a sensor for the rapid and sensitive detection of hypoxanthine through fluorescence quenching, and of fluoxetine through fluorescence enhancement mechanisms. The emission peak of Eu3+-Nb2C MQDs at 405 nm exhibited a linear response for hypoxanthine and fluoxetine in the ranges of 0.5-25 µM and 0.125-2.5 µM, with detection limits of 15.0 and 3.7 nM, respectively. The newly developed probe was effectively used for the selective detection of hypoxanthine and fluoxetine in biofluids and pharmaceutical samples. Remarkably, the Eu3+-Nb2C MQDs exhibited minimal cytotoxicity towards A549 lung cancer cells and showed great potential as imaging agent for imaging of Saccharomyces cerevisiae cells.

Fluoxetine, but not paroxetine, alters the jaw-closing muscle activity during non-rapid eye movement sleep in mice.

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00-08:00 and 08:00-14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Comparative Efficacy of Animal Depression Models and Antidepressant Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Animal models are critical tools in the study of psychiatric disorders; however, none of the current models fully reflect human stress-related disorders, even though most of the knowledge about the mechanisms of depression comes from animal studies. Animal studies are useful in pharmacological research, whereby we can obtain results that translate into patient treatment by controlling environmental factors, especially in behavioural research. The authors systematically reviewed this issue since medical databases provide access to many primary studies. METHODS: A systematic review and meta-analysis were conducted based on 25 primary studies. The studies were identified in databases such as PubMed, Embase, and Web of Science (December 2022) according to the inclusion and exclusion criteria established at the beginning of the research and published in the form of a protocol, following the PRISMA and Cochrane Collaboration methodology for secondary studies and CAMARADES (CAMARADES Berlin, QUEST-BIH Charité) for secondary studies on animals. Forest plot analyses were performed (data presented as Mean Difference, Random Model, Inverse Variance), Risk of Bias assessment (Systematic Review Center for Laboratory animal Experimentation (SYRCLE) evaluation), quality assessment of included studies (Animal research: Reporting of In Vivo Experiments (ARRIVE)), and a range of data from source publications were compiled in tabular form. The study analysed the popularity of both animal depression models (ADM) and rat strains used in pharmacological research to test the efficacy of antidepressant drugs based on the immobility time (IT) factor (Forced Swimming Test). The study examined selective serotonin reuptake inhibitors, namely fluoxetine, sertraline, paroxetine, citalopram, and escitalopram. Additionally, the study addressed issues concerning the "data availability statement" because precise IT data analysis was impossible in the case of 212 papers. RESULTS: Our data confirm that the Chronic Unpredictable Mild Stress (CUMS) model is the most popular and versatile model used in preclinical depression research, while the two most popular rat strains were Wistar and Sprague-Dawley. The quality of included papers based on the ARRIVE assessment showed a ratio value equal to 0.63, meaning that studies were of intermediate overall quality. The Risk of Bias assessment based on the SYRCLE tool revealed a high risk related to the blinding and the random outcome assessment. In the meta-analysis, the results indicate that all analysed drugs demonstrated efficacy in reducing IT, and the most analysed drug was fluoxetine (confirmed based on 17 studies (19 models)). The analysis of the efficacy of ADMs showed that the most effective models were CUMS, Flinders Sensitive Line (genetic model), Social Isolation, Restraint Stress, and Low-dose Lipopolysaccharide (pharmacological model). Only 2.35% (5 out of 212) of corresponding authors responded to our data request. CONCLUSIONS: The study highlights the dominance of the CUMS model and the Wistar and Sprague-Dawley rat strains in preclinical depression research, affirming the efficacy of SSRIs, particularly fluoxetine, in reducing IT. The findings underscore the need for better data availability and methodological improvements despite intermediate overall study quality and notable bias risks. Enhanced transparency and rigorous assessment standards are essential for advancing the reliability of animal models in depression research.

Environmental fluoxetine promotes skin cell proliferation and wound healing.

This study investigates the effects of environmentally-relevant concentrations of fluoxetine (FLX, commercial name: Prozac) on wound healing. Pollution of water systems with pharmaceutical and personal care products, including antidepressants such as FLX and other selective serotonin reuptake inhibitors, is a growing environmental concern. Environmentally-relevant FLX concentrations are known to impact physiological functions and behaviour of aquatic animals, however, the effects of exposure on humans are currently unknown. Using a combination of human skin biopsies and a human keratinocyte cell line, we show that exposure to environmental FLX promotes wound closure. We show dose-dependent increases in wound closure with FLX concentrations from 125 ng/l. Using several -omics and pharmaceutical approaches, we demonstrate that the mechanisms underlying enhanced wound closure are increased cell proliferation and serotonin signalling. Transcriptomic analysis revealed 350 differentially expressed genes after exposure. Downregulated genes were enriched in pathways related to mitochondrial function and metabolism, while upregulated genes were associated with cell proliferation and tissue morphogenesis. Kinase profiling showed altered phosphorylation of kinases linked to the MAPK pathway. Consistent with this, phosphoproteomic analyses identified 235 differentially phosphorylated proteins after exposure, with enriched GO terms related to cell cycle, division, and protein biosynthesis. Treatment of skin biopsies and keratinocytes with ketanserin, a serotonin receptor antagonist, reversed the increase in wound closure observed upon exposure. These findings collectively show that exposure to environmental FLX promotes wound healing through modulating serotonin signalling, gene expression and protein phosphorylation, leading to enhanced cell proliferation. Our results justify a transition from the study of behavioural effects of environmental FLX in aquatic animals to the investigation of effects of exposure on wound healing in aquatic and terrestrial animals, including direct impacts on human health.

Pegylated chitosan nanoparticles of fluoxetine enhance cognitive performance and hippocampal brain derived neurotrophic factor levels in a rat model of local demyelination.

Cognitive impairment is a common feature in neurodegenerative diseases such as multiple sclerosis (MS). This study aims to explore the potential of enhancing the beneficial effects of fluoxetine (FLX), a neuroprotective agent known for its ability to increase neural plasticity by utilizing nanoparticles. The study specifically focuses on the synthesis and evaluation of PEGylated chitosan nanoparticles of FLX and its effect on demyelination and the subsequent cognitive impairment (CI) in the hippocampus of rats induced by local injection of lysophosphatidylcholine (LPC). Chitosan/polyethylene glycol nanoparticles were synthesized, and their properties were analyzed. Demyelination was induced in rats via hippocampal injections of lysolecithin. Behavioral assessments included open field maze, elevated plus maze, and novel object recognition memory (NORM) tests. Hippocampal levels of insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) were measured using enzyme-linked immunoassay (ELISA). The extent of remyelination was quantified using Luxol fast blue staining. Nanoparticle size measured 240.2 nm with 53 % encapsulation efficacy. Drug release exhibited a slow pattern, with 76 % released within 4 h. Nanoparticle-treated rats displayed reduced anxiety-like behavior, improved memory, increased BDNF levels, and a reduced extent of demyelination, with no change in IGF- levels. In addition, FLX -loaded chitosan nanoparticles had better effect on cognitive improvement, BDNF levels in the hippocampus that FLX. Altering pharmacokinetics and possibly pharmacodynamics. These findings highlight the potential of innovative drug delivery systems, encouraging further research in this direction.

Fluoxetine accelerates epileptogenesis and magnifies disease severity in a rat model of acquired epilepsy.

OBJECTIVE: Many people with epilepsy experience comorbid anxiety and depression, and antidepressants remain a primary treatment for this. Emerging evidence suggests that these agents may modulate epileptogenesis to influence disease severity. Here, we assessed how treatment with the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine impacts epileptogenic, behavioral, and pathological sequelae following status epilepticus. METHODS: Male Wistar rats received kainic acid to induce status epilepticus (SE) or vehicle (sham). Animals then received either fluoxetine (10 mg/kg/day) or vehicle for 8 weeks via subcutaneous osmotic pump. Video-electroencephalography was recorded continuously until behavioral testing at day 56, including assessments of anxiety- and depression-like behavior and spatial cognition. Postmortem immunocytochemistry studies examined mossy fiber sprouting. RESULTS: Fluoxetine treatment significantly accelerated epileptogenesis following SE, reducing the average period to the first spontaneous seizure (from 32 days [vehicle] to 6 days [fluoxetine], p < .01). Also, fluoxetine exposure magnified the severity of the resultant epilepsy, increasing seizure frequency compared to vehicle (p < .01). Exposure to fluoxetine was associated with improved anxiety- and depression-like behaviors but significantly worsened cognition. Mossy fiber sprouting was more pronounced in fluoxetine-treated rats compared to vehicle (p < .0001). SIGNIFICANCE: Our studies demonstrate that, using a model exhibiting spontaneous seizures, epileptogenesis is accelerated and magnified by fluoxetine, an effect that may be related to more severe pathological neuroplasticity. The differential influence of fluoxetine on behavior indicates that different circuitry and mechanisms are responsible for these comorbidities. These findings suggest that caution should be exercised when prescribing SSRI antidepressants to people at risk of developing epilepsy.

The Antidepressant Action of Fluoxetine Involves the Inhibition of Dlx5/6 in Cortical GABAergic Neurons through a TrkB-Dependent Pathway.

Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. DLX5 and DLX6 (DLX5/6) encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA DLX6-AS1, which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of Dlx5/6 in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in Dlx5, Dlx6 and Dlx6-AS1 expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental Dlx5 overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in Dlx5/6 expression in GABAergic neurons, which, in turn, has direct consequences on PV expression and on behavioural profiles. Variants in the DLX5/6 regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment.

Inhibition of Ionic Currents by Fluoxetine in Vestibular Calyces in Different Epithelial Loci.

Previous studies have suggested a role for selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac®) in the treatment of dizziness and inner ear vestibular dysfunction. The potential mechanism of action within the vestibular system remains unclear; however, fluoxetine has been reported to block certain types of K+ channel in other systems. Here, we investigated the direct actions of fluoxetine on membrane currents in presynaptic hair cells and postsynaptic calyx afferents of the gerbil peripheral vestibular system using whole cell patch clamp recordings in crista slices. We explored differences in K+ currents in peripheral zone (PZ) and central zone (CZ) calyces of the crista and their response to fluoxetine application. Outward K+ currents in PZ calyces showed greater inactivation at depolarized membrane potentials compared to CZ calyces. The application of 100 µM fluoxetine notably reduced K+ currents in calyx terminals within both zones of the crista, and the remaining currents exhibited distinct traits. In PZ cells, fluoxetine inhibited a non-inactivating K+ current and revealed a rapidly activating and inactivating K+ current, which was sensitive to blocking by 4-aminopyridine. This was in contrast to CZ calyces, where low-voltage-activated and non-inactivating K+ currents persisted following application of 100 µM fluoxetine. Additionally, marked inhibition of transient inward Na+ currents by fluoxetine was observed in calyces from both crista zones. Different concentrations of fluoxetine were tested, and the EC50 values were found to be 40 µM and 32 µM for K+ and Na+ currents, respectively. In contrast, 100 µM fluoxetine had no impact on voltage-dependent K+ currents in mechanosensory type I and type II vestibular hair cells. In summary, micromolar concentrations of fluoxetine are expected to strongly reduce both Na+ and K+ conductance in afferent neurons of the peripheral vestibular system in vivo. This would lead to inhibition of action potential firing in vestibular sensory neurons and has therapeutic implications for disorders of balance.

A randomized controlled add-on trial of fluoxetine and cognitive behavioral therapy for help-seeking men with a sexual interest in children: presentation of the PARACHUTES trial protocol and initial feasibility data.

Background: Sexual Interest in Children (SIC) is a major risk factor for sexual offending, yet clinical trials are sparse. The present protocol outlines a randomized controlled trial (RCT) that aims to investigate the effectiveness of fluoxetine and Cognitive Behavioral Therapy (CBT) in help-seeking men with SIC. Methods: Adult men contacting the Swedish telephone helpline PrevenTell are screened for inclusion and invited to further assessment on site. One hundred and eleven men with SIC (defined as DSM-5 pedophilic disorder or hebephilia) will be randomized (1:1:1 ratio) to receive one of three interventions for 14 weeks: (1) an internet-administered psychoeducational program (iPP), (2) iPP and the addition of fluoxetine 20-40 mg or (3) iPP and the addition of internet-administered CBT (iCBT). Exclusion criteria include severe psychiatric illness, contraindicating treatment and an elevated risk of committing hands-on sexual offences. Symptom intensity is assessed at baseline, pre-treatment, every other week for 12 weeks, and post treatment. The primary outcome measure is the Sexual Interest in Children: Current Assessment Scale (SIC: CAS) that quantifies sexual behaviors associated with SIC as well as perceived distress and impairment. Secondary outcomes include measures of dynamic risk-factors for committing sexual offences. Results: The data collected during the initial 20 months of recruitment were analyzed to predict the required number of individuals to be screened and estimate the probable length of the data collection phase. As of March 2022 to November 2023, 146 men have called PrevenTell and disclosed a sexual interest in minors. Following pre-screening, 110 men were excluded from participation in the trial. Current SSRI therapy was the primary reason for exclusion (n = 24; 22%), followed by an elevated risk of committing hands-on sexual offences (n = 14; 13%). Among the 31 men who underwent the screening procedure on site, 26 were allocated to either iPP, iPP+fluoxetine, or iPP+iCBT. The recruitment rate indicates that the trial will be concluded within the pre-estimated timeframe. Discussion: This is the first RCT of treatment with SSRI and iCBT in a population of help-seeking men with SIC. The significance of this trial and its methodological strengths and limitations are discussed.

Serum Metabolites as Potential Markers and Predictors of Depression-like Behavior and Effective Fluoxetine Treatment in Chronically Socially Isolated Rats.

Metabolic perturbation has been associated with depression. An untargeted metabolomics approach using liquid chromatography-high resolution mass spectrometry was employed to detect and measure the rat serum metabolic changes following chronic social isolation (CSIS), an animal model of depression, and effective antidepressant fluoxetine (Flx) treatment. Univariate and multivariate statistics were used for metabolic data analysis and differentially expressed metabolites (DEMs) determination. Potential markers and predictive metabolites of CSIS-induced depressive-like behavior and Flx efficacy in CSIS were evaluated by the receiver operating characteristic (ROC) curve, and machine learning (ML) algorithms, such as support vector machine with linear kernel (SVM-LK) and random forest (RF). Upregulated choline following CSIS may represent a potential marker of depressive-like behavior. Succinate, stachydrine, guanidinoacetate, kynurenic acid, and 7-methylguanine were revealed as potential markers of effective Flx treatment in CSIS rats. RF yielded better accuracy than SVM-LK (98.50% vs. 85.70%, respectively) in predicting Flx efficacy in CSIS vs. CSIS, however, it performed almost identically in classifying CSIS vs. control (75.83% and 75%, respectively). Obtained DEMs combined with ROC curve and ML algorithms provide a research strategy for assessing potential markers or predictive metabolites for the designation or classification of stress-induced depressive phenotype and mode of drug action.

Changes in chemical characteristics and toxicity of fluoxetine and humic acid during chlorination.

The coexistence of emerging pollutants and dissolved organic matter in wastewater complicates the transformation and generation of disinfection byproducts (DBPs) during chlorination treatment, which is essential for effective water quality evaluation and chlorination optimization. This study used fluoxetine (FLX) and humic acid (HA) as representative substances to analyze changes in their chemical characteristics and zebrafish embryonic developmental toxicity under different chlorination conditions. The analysis of the fluorescence characteristics and Fourier transform ion cyclotron resonance mass spectrometry indicated that chlorination treatment increased the aromatic compound content of the HA solution. FLX addition further increased the presence of aromatic ring structures and oxidized molecules, resulting in the formation of numerous Cl-DBPs with highly unsaturated and phenolic structures. Moreover, different responses in zebrafish embryo development and behavior were found with FLX, HA, and FLX + HA exposures. Cardiotoxicity was linked to changes in the concentration of cTn-I protein and expression of various genes. Prolonged chlorination conditions showed higher toxicities. Correlation analysis found a weak relation between chemical indicators and toxicity data, indicating that both analysis methods need to be considered when analyzing the impact of the chlorination. Further, a combination of chemical analyses and toxicity tests revealed that the FLX + HA solution with chlorination conditions of 3 mg/L for 30 min had lower chemical and toxic effects in this experiment. This study provides valuable scientific insights for the safe discharge of chlorinated water containing FLX and dissolved organic matter, as well as guidance for optimizing chlorination parameters in wastewater treatment.

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

[Antidepressants in psychiatric practice]. / Antidepressanty v psikhiatricheskoi praktike.

The choice of antidepressants for depression or neurotic disorder is analyzed in the article. Drugs of the group of selective serotonin reuptake inhibitors are used for various mental disorders more often than other antidepressants according to clinical recommendations. Drugs of other groups (selective serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, tetracyclic antidepressants, monoamine oxidase inhibitors) are used when the effectiveness of selective serotonin reuptake inhibitors is insufficient or the severity of the mental disorder is significant. The duration of therapy, if well tolerated, can range from several months to many years. Antidepressants from Canonpharma Production are successfully used in clinical practice: Sertraline Canon, Fluoxetine Canon, Escitalopram Canon, Duloxetine Canon, Mirtazapine Canon, Agomelatine Canon. These drugs have different mechanisms of action. They are used for various depression and other mental disorders. All antidepressants from Canonpharma Production have been tested for bioequivalence to the original drugs. This fact increases confidence in these medicines. Some features of the use of these antidepressants based on clinical recommendations and personal experience are discussed in the article.

Effect of depression and the antidepressant fluoxetine on osseointegration-A pre-clinical in vivo experimental study.

OBJECTIVE: The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing. METHODS: Forty-eight 6- to 8-week-old SPF Sprague-Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation. RESULTS: After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone-implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group. CONCLUSIONS: Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic-pituitary-adrenal axis and inflammation in the body.

Fluoxetine Rescues Excessive Myelin Formation and Psychological Behaviors in a Murine PTSD Model.

Posttraumatic stress disorder (PTSD) is a complex mental disorder notable for traumatic experience memory. Although current first-line treatments are linked with clinically important symptom reduction, a large proportion of patients retained to experience considerable residual symptoms, indicating pathogenic mechanism should be illustrated further. Recent studies reported that newly formed myelin could shape neural circuit function and be implicated in fear memory preservation. However, its role in PTSD remains to be elucidated. In this study, we adopted a restraint stress-induced PTSD mouse model and found that PTSD-related neuropsychiatric symptoms were accompanied by increased myelination in the posterior parietal cortex and hippocampus. Fluoxetine, but not risperidone or sertraline, has a more profound rescue effect on neuropsychological behaviors and myelin abnormalities. Further mechanistic experiments revealed that fluoxetine could directly interfere with oligodendroglial differentiation by upregulating Wnt signaling. Our data demonstrated the correlation between PTSD and abnormal myelination, suggesting that the oligodendroglial lineage could be a target for PTSD treatment.

Pharmaceutical Pollution Alters the Structure of Freshwater Communities and Hinders Their Recovery from a Fish Predator.

Freshwater ecosystems are under threat from rising pharmaceutical pollution. While such pollutants are known to elicit biological effects on organisms, we have limited knowledge on how these effects might cascade through food-webs, disrupt ecological processes, and shape freshwater communities. In this study, we used a mesocosm experiment to explore how the community impacts of a top-order predator, the eastern mosquitofish (Gambusia holbrooki), are mediated by exposure to environmentally relevant low (measured concentration: ∼10 ng/L) and high concentrations (∼110 ng/L) of the pervasive pharmaceutical pollutant fluoxetine. We found no evidence that exposure to fluoxetine altered the consumptive effects of mosquitofish on zooplankton. However, once mosquitofish were removed from the mesocosms, zooplankton abundance recovered to a greater extent in control mesocosms compared to both low and high fluoxetine-exposed mesocosms. By the end of the experiment, this resulted in fundamental differences in community structure between the control and fluoxetine-treated mesocosms. Specifically, the control mesocosms were characterized by higher zooplankton abundances and lower algal biomass, whereas mesocosms exposed to either low or high concentrations of fluoxetine had lower zooplankton abundances and higher algal biomass. Our results suggest that fluoxetine, even at very low concentrations, can alter aquatic communities and hinder their recovery from disturbances.

Clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride on mild-to-moderate depression.

BACKGROUND: Depression is a common, chronic, and recurrent mood disorder that has become a worldwide health hazard. Fluoxetine hydrochloride, a common treatment method, can inhibit 5-hydroxytryptamine (5-HT) recycling in the presynaptic membrane; however, the efficacy of a single drug is inadequate. At present, mild-to-moderate depression can be treated with acupuncture of ghost caves, but the clinical curative effect of combined therapy with fluoxetine hydrochloride has not been sufficiently reported. AIM: To evaluate the clinical effect of acupuncture at ghost points combined with fluoxetine hydrochloride in the treatment of mild-to-moderate depression. METHODS: This retrospective study included 160 patients with mild-to-moderate depression who were admitted to Shanghai Hospital of Integrated Traditional Chinese and Western Medicine, Affiliated to Shanghai University of Traditional Chinese Medicine, between January 2022 and June 2023. Patients were separated into a single-agent group (fluoxetine hydrochloride treatment, n = 80) and a coalition group (fluoxetine hydrochloride treatment combined with acupuncture at ghost points, n = 80). Pre-treatment symptoms were recorded, and the clinical curative effect and adverse reactions [Asberg Antidepressant Side Effects Scale (SERS)] were assessed. Depression before and after treatment [Hamilton Depression Scale (HAMD)-24], neurotransmitter levels [5-HT, norepinephrine (NE), dopamine (DA)], oxidative stress indicators [superoxide dismutase (SOD), malondialdehyde (MDA)], and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were compared. RESULTS: The total efficacy rate was 97.50% in the coalition group and 86.25% in the single-agent group (P < 0.05). After 2, 4, 6, and 8 wk of treatment, the HAMD, self-rating depression scale, and SERS scores of the coalition and single-agent groups decreased compared with pre-treatment, and the decrease was more significant in the coalition group (P < 0.05). After 8 wk of treatment, the levels of NE, DA, 5-HT, and SOD in the coalition and single-agent groups increased, while the levels of MDA decreased; the increases and decrease in the coalition group were more significant (P < 0.05). The PSQI scores of the coalition and single-agent groups decreased, and the decrease was more significant in the coalition group (P < 0.05). CONCLUSION: Acupuncture at ghost points combined with paroxetine tablets can safely improve depressive symptoms and sleep disorders, regulate neurotransmitter levels, and reduce stress responses in patients with mild-to-moderate depression.

Initiation of fluoxetine in a pediatric patient with Mucopolysaccharidosis IIIA: Early observations.

Fluoxetine has been identified as a potential treatment for mucopolysaccharidosis IIIA (MPS IIIA), a debilitating and progressive lysosomal storage disorder for which no treatments are approved. In the MPS IIIA mouse model, fluoxetine decreases the accumulation of glycosaminoglycans and aggregated autophagic substrates, reducing inflammation, and slowing cognitive deterioration. 1 We treated a single patient, 6 years old, under off-label prescription of fluoxetine, a selective serotonin reuptake inhibitor (SSRI). The primary endpoint was safety. Secondary exploratory assessments included urine quantitative heparan sulfate. Fluoxetine was well-tolerated in this patient and the patient continued treatment following the 12-month monitoring period. The patient experienced an increase in daytime somnolence which resolved with rescheduling fluoxetine administration to bedtime. Quantitative heparan sulfate levels remained elevated during treatment. Parents reported improved sleep latency time and less nighttime waking. These findings support general tolerability and further study of fluoxetine as a potential therapy for MPS IIIA.

Effects of selective serotonin reuptake inhibitors on endocrine system (Review).

Selective serotonin reuptake inhibitors (SSRIs) are typically prescribed for treating major depressive disorder (MDD) due to their high efficacy. These drugs function by inhibiting the reuptake of serotonin [also termed 5-hydroxytryptamine (5-HT)], which raises the levels of 5-HT in the synaptic cleft, leading to prolonged activation of postsynaptic 5-HT receptors. Despite the therapeutic benefits of SSRIs, this mechanism of action also disturbs the neuroendocrine response. Hypothalamic-pituitary-adrenal (HPA) axis activity is strongly linked to both MDD and the response to antidepressants, owing to the intricate interplay within the serotonergic system, which regulates feeding, water intake, sexual drive, reproduction and circadian rhythms. The aim of the present review was to provide up-to-date evidence for the proposed effects of SSRIs, such as fluoxetine, citalopram, escitalopram, paroxetine, sertraline and fluvoxamine, on the endocrine system. For this purpose, the literature related to the effects of SSRIs on the endocrine system was searched using the PubMed database. According to the available literature, SSRIs may have an adverse effect on glucose metabolism, sexual function and fertility by dysregulating the function of the HPA axis, pancreas and gonads. Therefore, considering that SSRIs are often prescribed for extended periods, it is crucial to monitor the patient closely with particular attention to the function of the endocrine system.