Current Neuropharmacology - Current Issue

Limited research has delved into the comprehensive impact of monotherapy on weight and glycolipid metabolism in schizophrenia (SCZ) patients. Our study aims to longitudinally investigate the multidimensional effects of olanzapine (OLA) monotherapy on weight and glycolipid metabolism in first-episode and antipsychotic-naïve (FEAN) SCZ patients.

A total of 74 FEAN-SCZ patients were recruited, as well as 58 sex- and age-matched healthy controls. Eligible patients underwent a 4-week OLA treatment regimen, with weight assessments conducted at baseline and week 4. Moreover, lipid profiles and fasting plasma glucose (FPG) were measured at baseline and week 4. Insulin, leptin (LEP), and adiponectin (APN) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits.

At baseline, FEAN-SCZ patients showed elevated levels of insulin, low-density lipoprotein (LDL), impaired insulin sensitivity, and reduced levels of APN compared to the healthy controls. Following 4-week OLA treatment, patients showed an increase in body mass index (BMI) of 0.96 kg/m². Additionally, FPG, quantitative insulin sensitivity check index (QUICKI), HOMA-insulin sensitivity index (HOMA-ISI), and fasting plasma glucose to insulin ratio (G/I) displayed significant decreases, while insulin, HOMA-IR, and LEP levels showed significant increases. Stepwise regression analysis revealed that baseline FPG independently predicted the change in BMI after 4 weeks of OLA treatment.

FEAN-SCZ patients exhibited pre-existing alterations in glucose homeostasis. After 4 weeks of OLA treatment, SCZ patients experienced significant weight gain, deteriorating insulin resistance, and increased LEP levels. In addition, baseline FPG emerged as a predictor of BMI changes after 4 weeks of OLA treatment.

Today more and more people search the web for health-related information, risking to come across misinformation and biased content that may affect their treatment decisions. Cannabidiol (CBD) is among the products for which beneficial effects have been claimed, often at the expense of the risks; further keeping in mind unreliable information reported on products themselves.

This study evaluated the quality of information retrieved by Google on the potential effects of CBD on weight management, also comparing Italian and English contents, hypothesizing generally low quality and language-driven differences in offered information.

Queries regarding cannabidiol and obesity-related terms were entered into Google, ranking the first 50 webpages from both merged Italian and English results for analysis.

Of the outputs, 37 Italian and 27 English websites addressed the topic and were not related to medical literature. As expected, a substantial proportion of information was of low quality, with English sites performing better (29.6%) than Italian ones (54%, p = 0.052) in terms of “JAMA benchmarks” for trustworthiness of information. Also, while most English sites were “Health portals” (40.7%) with neutral stance toward CBD (74.1%), Italian ones were predominantly “commercial” (78.4%, p = 0.001) and promoting CBD use (89.2%, p < 0.001).

Findings suggest the need for better online information, especially in non-English-speaking countries, as scarce and unequal information can lead people to make poor health choices, with potentially harmful consequences.

The incidence of Major Depressive Disorder (MDD) is high among adolescent females, and MDD is often accompanied by suicide attempts (SAs), which have a serious negative impact on health. However, changes in lipids, thyroid hormone, and brain metabolism among female adolescents with MDD and the relationships between these three markers and MDD with SA have yet to be elucidated.

This study enrolled 71 MDD patients with SA (MDD+SA), 66 MDD patients without SA (MDD-SA), and 47 healthy controls (HCs). We analysed the lipid and thyroid hormone levels and magnetic resonance spectroscopy results of the subjects.

Low levels of social support, high levels of life stress, and high levels of suicidal ideation (SI) were risk factors for SA. In MDD patients, 1) thyroid stimulating hormone was positively correlated with triglyceride (TG) and N-acetyl aspartic acid (NAA)/creatinine in the prefrontal cortex (PFC) and negatively correlated with high-density lipoprotein and the choline/creatinine in the thalamus; 2) free thyroxine was negatively correlated with the choline/creatinine in the thalamus; 3) total cholesterol, TG, low-density lipoprotein, and choline/NAA in the PFC were positively correlated with the severity of SI and suicide risk; and 4) NAA/creatinine in the thalamus was negatively correlated with the severity of SI and suicide risk.

In female adolescents with MDD, there are significant synergistic changes in lipids, thyroid hormones, and brain metabolism-related factors, and the changes in these indicators may be related to the pathological mechanism of SA.

The treatment of Burning Mouth Syndrome (BMS) represents a challenge in tailoring appropriate medication for individual patients. The augmentation of pregabalin to conventional treatment has shown promising outcomes in relieving pain and improving the quality of life in chronic pain conditions. This study aimed to compare the efficacy of vortioxetine with other antidepressants (SSRIs/SNRIs) in combination with pregabalin in a cohort of unresponsive BMS patients and to predict treatment response by using clinical data.

A 52-week randomized, open-label, comparative clinical study was conducted, enrolling 203 BMS patients previously treated with one antidepressant for 12 weeks and non-responders to the treatment (clinical trial registration: NCT06025474). The study sample included two groups: Group A (136) received vortioxetine, while Group B (67) received SSRIs/SNRIs. Pregabalin (75 mg/day) was added to both groups, with a potential dosage increase to 150 mg/day for inadequate responders after 12 weeks. Treatment response was assessed with VAS and SF-MPQ, HAM-A, and HAM-D scores at 12, 24, 36, and 52 weeks. Stepwise logistic regression analysis was used to predict treatment response.

A total of 84 (61.8%) BMS patients in Group A and 39 (58.2%) in Group B showed treatment response. Group A reported a faster onset of action compared to Group B (44.8% versus 22.4% at time 1; p:0.002**) and lower adverse event rates (8.8% versus 20.8%; p:0.001).

The addition of pregabalin to vortioxetine may be considered a potential treatment option for BMS. Further research is required to corroborate these findings and optimize personalized treatment approaches for BMS patients.

ClinicalTrials.gov (NCT06025474).

The abuse of veterinary drugs has emerged as a concerning trend, with global fatalities on the rise. Our understanding of this phenomenon remains limited. This study aims to identify the veterinary drugs being misused, the reasons behind their misuse, and how they are obtained.

Utilising PubMed, Scopus, and Web of Science databases, along with related grey literature, we applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) framework for data collection. Screening and cross-referencing yielded 66 relevant articles, encompassing case reports, surveys, reports, and systemic literature reviews. The analysis identified 28 distinct veterinary drugs being misused in humans, primarily falling into categories, e.g., α-2- and β-2-adrenergic receptor agonists, GABAergic receptor modulators, opioid receptor agonists, non-steroidal anti-inflammatory drugs (NSAIDs), and N-methyl-D-aspartate (NMDA) receptor antagonists. These drugs were used for various purposes, including recreational use, weight loss, bodybuilding, pain relief, and self-medication for stress-related symptoms.

Routes of administration predominantly included parenteral, oral, and inhalation methods. Veterinary workers/assistants and individuals connected to animals were identified as contributors to the misuse of these medications. Motivations for their utilisation ranged from affordability and accessibility to the ease of obtaining multiple prescriptions from various veterinary sources, often in conjunction with other illicit substances. Dependence and addiction were common outcomes of the misuse of veterinary medicines by humans.

Overall, this systematic review underscores the increasing popularity of veterinary prescription drug misuse despite being under-reported with limited available data. Healthcare professionals are urged to remain vigilant to potential overdose events involving these medications.

Catamenial epilepsy, which is defined as a periodicity of seizure exacerbation occurring during the menstrual cycle, has been reported in up to 70% of epileptic women. These seizures are often non-responsive to medication and our understanding of the relation between menstrual cycle and seizure generation (i.e. ictogenesis) remains limited.

Here, we employed the in vitro 4-aminopyridine model of epileptiform synchronization, to analyze the effects induced by optogenetic activation of parvalbumin (PV)-positive interneurons at 8 Hz during estrous and non-estrous phases in female PV-ChR2 mice.

We found that: (i) optogenetic stimulation of PV-positive interneurons induced an initial interictal spike followed by field oscillations occurring more often in estrous (59%) than in non-estrous slices (17%); (ii) these oscillations showed significantly higher power in estrous compared to non-estrous slices (p < 0.001); (iii) significantly higher rates of interictal spikes and ictal discharges were identified in both estrous and non-estrous slices during optogenetic stimulation of PV-positive interneurons compared to periods of no stimulation (p < 0.05); and (iv) ictal events appeared to occur more frequently during optogenetic stimulation in estrous compared to non-estrous slices.

Our findings show that optogenetic activation of PV-interneurons leads to more powerful network oscillations and more frequent ictal discharges in estrous than in non-estrous slices. We conclude that during the rodent estrous cycle, PV-interneuron hyperexcitability may play a role in epileptiform synchronization and thus in catamenial seizures.

The study demonstrates that pharmacological blockade of type 3 metabotropic glutamate (mGlu3) receptors at the time of tumor induction significantly reduces the incidence of brain gliomas in rats. The overall survival of patients with high-grade brain gliomas is 14-20 months after current multimodal therapy, including surgery, radiotherapy, and adjuvant chemotherapy.

To demonstrate in this experimental model that pharmacological blockade of group II metabotropic glutamate receptors reduces the incidence of brain tumors induced by prenatal exposure to N- ethyl-N-nitrosourea (ENU) in rats.

Dams received a single injection of ENU (40 mg/kg, e.v.) at day 20 of pregnancy, combined with 5 daily injections of either saline or the mGlu2/3 receptor antagonist, LY341495 (10 mg/kg) (from day 15 to day 21 of pregnancy). Assessment of brain tumors in the offspring at 5 months of age showed the presence of mixed gliomas (astrocytomas/oligodendrogliomas) in 70% of the ENU + saline group of rats and only in 30% of the ENU + LY341495 group.

Tumors in both groups of rats showed a moderate/high expression of the astrocyte marker, GFAP, and the oligodendrocyte marker, OLIG-2, and a low expression of the proliferation marker, Ki-67. However, tumors of the ENU + LY341495 group showed a reduced density of Iba-1⁺ cells, suggesting a lower extent of neuroinflammation in the tumor microenvironment. These findings strengthen the hypothesis that mGlu3 receptors are candidate drug targets for the treatment of malignant gliomas.