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Objective: Major depressive disorder (MDD) is predicted to be one of the biggest disease burden in the future. The antidepressant activity of gemfibrozil has been recently considered. In this study, we assessed the effectiveness of gemfibrozil as a sertraline adjunct in treating patients with MDD. Method : In this study, 46 patients with MDD based on the DSM-V criteria with a minimum score of 22 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were divided into two groups. One group was treated with 300 mg of gemfibrozil daily and the other group treated with placebo. Each group was treated simultaneously with 100 mg of sertraline daily for 8 weeks. The trial was randomized and double-blind. To assess the response to treatment, patients were evaluated at baseline and then at weeks 2, 4 and 8 using the HAM-D score. Results: The study was completed by 45 patients up to the final stages and follow-up visits. Repeated measure ANOVA with a Greenhouse-Geisser correction showed a significant difference for time×treatment interaction on within-subjects HAM-D scores [p-value= 0.026]. A notable difference was seen in time [p-value < 0.001]. The test of between-subject effects also represented a remarkable consequence of treatment on HAM-D scores at weeks 2, 4, and 8 [p-value = 0.07]. Using Kaplan-Meier estimate curves, time to remission periods were notable different between the 2 trial groups [Log-Rank p-value = 0.003]. Conclusion: Gemfibrozil is an effective adjunctive treatment in MDD and can be used to reduce depression symptoms.

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OBJECTIVE: In this study, we aimed to evaluate the executive profile of juvenile myoclonic epilepsy (JME) patients using the Frontal Assessment Battery (FAB) as a bedside screening tool and investigate its association with seizure proximity, family history of epilepsy, and polytherapy/monotherapy with antiepileptic drugs (AEDs). BACKGROUND: JME patients have deficits in various aspects of executive functions. FAB has proved to be a useful tool for evaluating executive functions in clinical settings. METHODS: Thirty-one JME patients and 110 healthy controls (HCs) were enrolled in this study. The participants were assessed using six subsets of FAB, including conceptualization, mental flexibility, motor programming, sensitivity to interference, inhibitory control, and environmental autonomy. RESULTS: Compared to HCs, JME patients showed lower scores in conceptualization, mental flexibility, programming, sensitivity to interference, and total FAB. The number of AEDs (polytherapy versus monotherapy) and duration of time since the last seizure had no significant effect on FAB scores in JME patients. We found significant associations between disease duration and conceptualization, mental flexibility, inhibitory control, and total FAB score only in JME patients with recent seizure. Finally, receiver operating characteristic (ROC) analysis showed area under the curve (AUC) of 0.971 (95% confidence interval (CI): 0.947-0.994) for FAB total score, 0.933 for conceptualization (95% CI: 0.973-894), and 0.836 for mental flexibility (95% CI: 0.921-751). CONCLUSIONS: In summary, JME patients had deficits in different aspects of executive functions. FAB is a useful clinical tool for evaluation of executive functions in JME patients.

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Levodopa remains to be the mainstay for treatment of Parkinson disease (PD). Long-term levodopa treatment bears a risk for developing levodopa-induced dyskinesia (LID). LID significantly overshadows patients' quality of life and therapeutic efficacy of levodopa. Pre- and post-synaptic changes in dopamine secretion and signaling, along with altered glutamate receptor expression and glutamatergic signaling in striatal neurons, and the resulting disinhibition-like changes in the corticostriatal circuitry, lead to aberrant activity of motor cortex and formation of LID. Research has highlighted the role of group I metabotropic glutamate receptors especially the metabotropic glutamate receptor 5 (mGlu5) in formation of LID through potentiating of ionotropic glutamate NMDA receptors and dopamine D1/D5 receptors in direct pathway. Accordingly, MTEP and MPEP were the first mGlu5 receptor antagonists which were shown to attenuate LID in animal models through suppression of downstream signaling cascades involving mitogen-activated protein kinase (MAPK) and FosB/delta FosB activation, as well as modulation of prodynorphinegic, preproenkephalinergic, and GABA-ergic neurotransmission systems. Beneficial effects of other mGlu5 receptor antagonists such as AFQ056/mavoglurant and ADX48621/dipraglurant in amelioration of LID has been shown not only in animal models but also in clinical trials. Considering the presence of mGlu receptor dysregulation in rapid eye movement (REM) sleep behavior disorder and depression, which are prodromal signs of PD, along with the neuroprotective effects of mGlu receptor antagonists, and their cognitive benefits, potential effectiveness of mGlu receptor antagonists in early prevention of PD remains to be investigated.

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Background: Parkinson's disease (PD) is characterized by proteinopathies and these proteinopathies seem to interact synergistically and lead to protein aggregations and changes in protein cerebrospinal fluid (CSF) levels. In this study, we aimed to explore the longitudinal changes of CSF a lpha-synuclein (α-syn), total tau (t-tau), phosphorylated tau (p-tau), and beta-amyloid (Aß1-42) and their relationships with each other and with baseline clinical entities like REM sleep behavior disorder (RBD), cognitive impairment, motor symptoms, and olfaction dysfunction. Method: One hundred and twelve non-demented PD patients and 110 controls were recruited from Parkinson's Progression Markers Initiative (PPMI).We used a linear mixed model within groups to assess longitudinal protein changes over 6 and 12 months and a random regression coefficient within the linear mixed model to investigate the correlation between proteins and their baseline clinical characteristics. Results: P-tau was lower in PDs only at baseline, but during a year, p-tau increased more rapidly in PDs than controls. Aß1-42 was not significantly different between groups at any separate timepoint; however, when assessed longitudinally, Aß1-42 showed significant changes in both groups. Conversely, t-tau and α-syn differed significantly between groups, but their longitudinal changes were not significant in either of the groups. Moreover, all proteins' baseline levels, except p-tau, could determine estimated longitudinal tau changes. Baseline RBDSQ scores but not UPDRS III, MoCA, or UPSIT scores were predictive of longitudinal increase in α-syn levels. Conclusion: Longitudinal changes in levels of CSF proteins are related to each other and could help researchers further understand PD pathology. In addition, RBD seems to be a potential prognostic factor for PD progression. However, in order to reach a consensus, longer follow-up times are required.