Uncovering the Roles of MicroRNAs in Major Depressive Disorder: From Candidate Diagnostic Biomarkers to Treatment Response Indicators

Major depressive disorder (MDD) is a recurrent debilitating illness that represents a major health burden due to its increasing worldwide prevalence, unclear pathological mechanism, nonresponsive treatment, and lack of reliable and specific diagnostic biomarkers. Recently, microRNA species (miRs) have gained particular interest because they have the ability to post-transcriptionally regulate gene expression by modulating mRNA stability and translation in a cohesive fashion. By regulating entire genetic circuitries, miRs have been shown to have dysregulated expression levels in blood samples from MDD patients, when compared to healthy subjects. In addition, antidepressant treatment (AD) also appears to alter the expression pattern of several miRs. Therefore, we critically and systematically reviewed herein the studies assessing the potential biomarker role of several candidate miRs for MDD, as well as treatment response monitoring indicators, in order to enrich the current knowledge and facilitate possible diagnostic biomarker development for MDD, which could aid in reducing both patients’ burden and open novel avenues toward a better understanding of MDD neurobiology

Comparative Spectrographic Analysis of the Newborns’ Cry in the Presence of Tight Intrapartum Nuchal Cord vs. Normal Using the Neonat App. Preliminary Results

Background and objectives: The objective of this study was to contribute to the evaluation of the newborn (NB) cry as a means of communication and diagnosis. Materials and Methods: The study implied the recording of the spontaneous cry of 101 NBs with no intrapartum events (control sample), and of 72 NBs with nuchal cord (study sample) from the “Bega” University Clinic of Obstetrics–Gynecology and Neonatology of Timisoara, Romania. The sound analysis was based upon: Imagistic highlighting methods, descriptive statistics, and data mining techniques. Results: The differences between the cry of NBs with no intrapartum events and that of NBs affected by nuchal cord are statistically significant regarding the volume unit meter (VUM) (p = 0.0021) and the peak point meter (PPM) (p = 0.041). Conclusions: While clinically there are no differences between the two groups, the cry recorded from the study group (nuchal cord group) shows distinctive characteristics compared to the cry recorded from the control group (eventless intrapartum NBs group)

Untargeted Plasma Metabolomic Profiling in Patients with Major Depressive Disorder Using Ultra-High Performance Liquid Chromatography Coupled with Mass Spectrometry

Major depressive disorder (MDD) is a neuropsychiatric illness with an increasing incidence and a shortfall of efficient diagnostic tools. Interview-based diagnostic tools and clinical examination often lead to misdiagnosis and inefficient systematic treatment selection. Diagnostic and treatment monitoring biomarkers are warranted for MDD. Thus, the emerging field of metabolomics is a promising tool capable of portraying the metabolic repertoire of biomolecules from biological samples in a minimally invasive fashion. Herein, we report an untargeted metabolomic profiling performed in plasma samples of 11 MDD patients, at baseline (MDD1) and at 12 weeks following antidepressant therapy with escitalopram (MDD2), and in 11 healthy controls (C), using ultra-high performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry (UHPLC-QTOF-(ESI+)-MS). We found two putative metabolites ((phosphatidylserine PS (16:0/16:1) and phosphatidic acid PA (18:1/18:0)) as having statistically significant increased levels in plasma samples of MDD1 patients compared to healthy subjects. ROC analysis revealed an AUC value of 0.876 for PS (16:0/16:1), suggesting a potential diagnostic biomarker role. In addition, PS (18:3/20:4) was significantly decreased in MDD2 group compared to MDD1, with AUC value of 0.785

ATTRIBUTIONAL STYLE AND REACTION TO FRUSTRATION IN DELUSIONAL DISORDERS

REZUMAT Scopul: Stilul atribuţional şi reacţiile la frustrare joacă un rol important atât în depresie cât şi în paranoia. Aceste aspecte reprezintă elemente caracteristice cogniţiei sociale. Ultimele studii în acest sens (există studii doar pe stilul de atribuire) au demonstrat deficite semnificative ale stilului atribuţional, deficite ce se reflectă apoi în mecanismul de producere şi menţinere a simptomatologiei delirante precum şi în funcţionarea socială a deliranţilor. Obiectivul acestei lucrâri a fost de a studia stilul de atribuire şi reacţiile la frustrare în cadrul deliranţilor persistenţi cu şi fără depresie asociată, în scopul unei mai bune înţelegeri a cogniţei sociale a acestora. Instrumente şi metodă: Un grup de 40 de subiecţi, diagnosticaţi după ICD 10 cu tulburare delirantă şi având o perioadă de evoluţie de 8 ani au fost împărţiţi în doua loturi : a) cu depresie şi b) fără depresie. Toate cazurile fac parte din Proiectul Timişoara de Studiu al Tipologiei Psihozelor Endogene ce monitorizează psihozele funcţionale cu debut de după 1985. Pentru fiecare subiect au fost aplicate în perioada de remisie BPRS (Brief Psychiatric Rating Scale), ASQ (Attributional Style Questionnaire) şi Rosenzweig frustration test. Rezultate: Deliranţii depresivi fac atribuiri stabile pentru ambele tipuri de evenimente, însă pentru cele negative atribuirea este predominant externă, iar pentru evenimentele pozitive, atribuirea este internă. În cazul reacţiilor de frustrare aceştia reacţionează mai frecvent extrapunitiv şi de tipul persistenţei necesităţii. Deliranţii simpli pentru evenimentele de viaţă negative fac atribuiri externe şi particulare, iar pentru cele pozitive interne şi stabile. În cazul situaţiilor frustrante, aceştia dau frecvent răspunsuri fără pedeapsă şi de tipul persistenţei necesităţii. Concluzii: În ciuda coloraturii depresive, deliranţii depresivi fac atribuiri externe pentru evenimentele negative, iar, spre deosebire de cei fără coloratură depresivă, aceştia reacţionează extrapunitiv în situaţiile frustrante. Cuvinte cheie: atribuire, reacţie la frustrare, delir, depresie ABSTRACT Background: The attribution style and the reactions to frustration play an important role both in depression and paranoia. These aspects are characteristic elements of social cognition. The latest studies done in this area (there are studies only related to attribution) proved significant deficiencies to the attribution style, that later reflect in the mechanism of production and manifestation of delusional symptomatology and also in the social functionality of the delusional. The objective of this paper is to study the attribution style and the reactions to frustration in the persistent delusional patients with and without an associated depression, in order to better understand their social cognition. Material and methods: Forty patients diagnosed with ICD 10 delusional disorder with a period of evolution of 8 years, were grouped into 2 subgroups: a) patients with depression and b) patients without depression. They are all part of the Case Register of Timisoara Psychiatric Clinic (CRPTC), which monitors the functional psychoses since 1985. ASQ (Attribution Style Questionnaire) and Rosenzweig frustration test was applied for each patient in the period of remission BPRS (Brief Psychiatric Rating Scale). Results: Depressive delusional patients make stable attributions for both type of events, but for the negative ones, the attribution is prevalently external and for the positive events the attribution is internal. Common delusional patients make external and particular attributions for negative life events, while for the positive events the attributions are internal and stable. Concerning the response to frustrating situations, persistent delusional psychosis patients with depression give answers which are prevailing extra punitive, whereas those without depression give prevailing need-persistence answers. There are significant similarities between the two groups concerning the type of persisting necessity. Conclusions: Among the persistent delusional psychosis patients, those with depressive features demonstrate an aggression directed mostly towards the exterior in frustrating situations, while associating less the negative events to their own personality, compared to the pure persistent delusional patients

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders

Effectiveness of Psychostimulant and Non-Psychostimulant Drug Therapy in the Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperkinetic Disorder (ADHD) is a neurobiological behavioral disorder of the child, adolescent, and adult characterized by problems of concentration, hyperactivity, and impulsivity caused by an imbalance of chemical neurotransmitters in the brain—dopamine and noradrenaline. ADHD first-line drugs are divided in psychostimulant, as Methylphenidate and Amphetamines and non-psychostimulant medications-Atomoxetine (the only representative non-psychostimulant medication approved in our country in children and adolescents). The purpose of our research was to assess the clinical evolution of patients with ADHD based on the drug treatment that is administered: psychostimulant or non-psychostimulant. Both psychostimulant—Methylphenidate, and non-psychostimulant therapy—Atomoxetine, proved to significantly improve the symptoms of attention deficit hyperkinetic disorder. There was a significant reduction in the severity of ADHD symptoms at six months and at one year from the start of treatment in the case of the psychostimulant group, whereas in the non-psychostimulant group, the significant reduction in severity of symptomatology occurs only at six months after the start of treatment. We can conclude that both types of drugs are effective in reducing the severity of symptoms and in improving the clinical condition of patients with ADHD, but the comparative analysis of the two groups demonstrated that significantly better results are obtained with psychostimulant treatment

Proniosomal Gel for Topical Delivery of Rutin: Preparation, Physicochemical Characterization and In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis Tissue and 2D Cells

Rutin (Rut) is a natural flavonol, well-known for its broad-spectrum of therapeutic effects, including antioxidant and antitumoral activities; still, it has a reduced clinical outcome due to its limited solubility in aqueous solutions. To overcome this drawback, this study proposes a novel formulation for rutin as a proniosomal gel for cutaneous applications. The gel was prepared by coacervation phase-separation method and complies with the standard requirements in terms of particle size (140.5 ± 2.56 nm), zeta potential (−27.33 ± 0.09 mV), encapsulation capacity (> 50%), pH (7.002 ± 0.18) and rheological properties. The results showed high biocompatibility of the gel on the 3D reconstructed human epidermis model characterized by increased viability of the cells and a lack of irritant and phototoxic potential. The evaluations on 2D cells confirm the preferential cytotoxic effect of Rut on melanoma cells (IC50 value = 8.601 µM, nuclear fragmentation) compared to normal keratinocytes. Our data suggest that the proniosomal gel is a promising drug carrier for Rut in the management and prevention of skin disorders