Effects of electroconvulsive therapy on cortical thickness in depression: a systematic review.

OBJECTIVE: Electroconvulsive therapy (ECT) is one of the most studied and validated available treatments for severe or treatment-resistant depression. However, little is known about the neural mechanisms underlying ECT. This systematic review aims to critically review all structural magnetic resonance imaging studies investigating longitudinal cortical thickness (CT) changes after ECT in patients with unipolar or bipolar depression. METHODS: We performed a search on PubMed, Medline, and Embase to identify all available studies published before April 20, 2023. A total of 10 studies were included. RESULTS: The investigations showed widespread increases in CT after ECT in depressed patients, involving mainly the temporal, insular, and frontal regions. In five studies, CT increases in a non-overlapping set of brain areas correlated with the clinical efficacy of ECT. The small sample size, heterogeneity in terms of populations, comorbidities, and ECT protocols, and the lack of a control group in some investigations limit the generalisability of the results. CONCLUSIONS: Our findings support the idea that ECT can increase CT in patients with unipolar and bipolar depression. It remains unclear whether these changes are related to the clinical response. Future larger studies with longer follow-up are warranted to thoroughly address the potential role of CT as a biomarker of clinical response after ECT.

Understanding the Influence of Target Acquisition on Survival, Integration, and Phenotypic Maturation of Dopamine Neurons within Stem Cell-Derived Neural Grafts in a Parkinson's Disease Model.

Midbrain dopaminergic (DA) neurons include many subtypes characterized by their location, connectivity and function. Surprisingly, mechanisms underpinning the specification of A9 neurons [responsible for motor function, including within ventral midbrain (VM) grafts for treating Parkinson's disease (PD)] over adjacent A10, remains largely speculated. We assessed the impact of synaptic targeting on survival, integration, and phenotype acquisition of dopaminergic neurons within VM grafts generated from fetal tissue or human pluripotent stem cells (PSCs). VM progenitors were grafted into female mice with 6OHDA-lesions of host midbrain dopamine neurons, with some animals also receiving intrastriatal quinolinic acid (QA) injections to ablate medium spiny neurons (MSN), the A9 neuron primary target. While loss of MSNs variably affected graft survival, it significantly reduced striatal yet increased cortical innervation. Consequently, grafts showed reduced A9 and increased A10 specification, with more DA neurons failing to mature into either subtype. These findings highlight the importance of target acquisition on DA subtype specification during development and repair.SIGNIFICANCE STATEMENT Parish and colleagues highlight, in a rodent model of Parkinson's disease (PD), the importance of synaptic target acquisition in the survival, integration and phenotypic specification of grafted dopamine neurons derived from fetal tissue and human stem cells. Ablation of host striatal neurons resulted in reduced dopamine neuron survival within grafts, re-routing of dopamine fibers from striatal to alternate cortical targets and a consequential reduced specification of A9 dopamine neurons (the subpopulation critical for restoration of motor function) and increase in A10 DA neurons.

DNase Treatment Prevents Cerebrospinal Fluid Block in Early Experimental Pneumococcal Meningitis.

OBJECTIVE: Streptococcus pneumoniae is the most common cause of bacterial meningitis, a disease that, despite treatment with antibiotics, still is associated with high mortality and morbidity worldwide. Diffuse brain swelling is a leading cause of morbidity in S pneumoniae meningitis. We hypothesized that neutrophil extracellular traps (NETs) disrupt cerebrospinal fluid (CSF) transport by the glymphatic system and contribute to edema formation in S pneumoniae meningitis. METHODS: We used DNase I treatment to disrupt NETs and then assessed glymphatic function by cisterna magna injections of CSF tracers in a rat model of S pneumoniae meningitis. RESULTS: Our analysis showed that CSF influx into the brain parenchyma, as well as CSF drainage to the cervical lymph nodes, was significantly reduced in the rat model of S pneumoniae meningitis. Degrading NETs by DNase treatment restored glymphatic transport and eliminated the increase in brain weight in the rats. In contrast, first-line antibiotic treatment had no such effect on restoring fluid dynamics. INTERPRETATION: This study suggests that CSF accumulation is responsible for cerebral edema formation and identifies the glymphatic system and NETs as possible new treatment targets in S pneumoniae meningitis. ANN NEUROL 2021;90:653-669.

Complete Implant Wrapping with Porcine-Derived Acellular Dermal Matrix for the Treatment of Capsular Contracture in Breast Reconstruction: A Case-Control Study.

BACKGROUND: Capsular contracture (CC) represents one of the most common complications in breast reconstruction surgery, impairing final result and patients' well-being. The role of acellular dermal matrixes (ADM) has been widely described for the treatment and prevention of contracture. The aim of the study was to evaluate the efficacy and safety of complete implant coverage with porcine-derived ADM in preventing CC limiting complications. In addition, patients' reported outcomes were evaluated in order to define the role of ADM in improving sexual, physical and psychosocial well-being and satisfaction. METHODS: 42 patients who underwent surgical treatment of 46 contracted reconstructed breasts from May 2018th to May 2019th were collected in the two groups (ADM group vs. Control group). RESULTS: The ADM group showed lower rate of CC recurrence and a higher rate of implant losses and minor complications. A significant difference was observed in red breast syndrome (27.3% in the ADM group vs. absent in control the group) and skin ulceration rates (18.2% in the ADM group vs. 4.18% in the control group). As for patients' perceived outcomes, the ADM group showed a statistically significant higher postoperative Satisfaction of Breast Scale score compared to the control group. In addition, a significant difference was observed in the improvement of Physical Well-Being of the Chest Scale and the Satisfaction of Breast Scale after surgery, in favor to the ADM group. CONCLUSION: Complete implant coverage with ADM may reduce the risk of CC recurrence in breast reconstruction. An accurate patient selection allows minimizing complications improving patient well-being and satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Cyberball task in people after obesity surgery: preliminary evaluation of cognitive effects of social inclusion and exclusion with a laboratory task.

BACKGROUND: Social cognition and temperamental and interpretative styles could play a role in the outcome of bariatric surgery. This study aims to assess preliminary evidence about how obesity surgery patients evaluate social inclusion and exclusion through a ball-tossing game called Cyberball, looking at the influence of early maladaptive schemas. METHODS: Thirty-four patients with a history of obesity surgery interventions and 44 controls were recruited for this study. A psychological evaluation was performed before and after the Cyberball task with self-report questionnaires. RESULTS: In the ostracism condition, significant differences were seen across all the patients' fundamental psychological needs with less perceived ostracization (p = 0.001) even if they recognized less interaction via fewer ball tosses than controls. Moreover, the ostracism paradigm resulted in patients experiencing a higher urge to binge (p = 0.010) and a higher urge to restrain (p = 0.012) than controls. Looking at differences due to the Cyberball paradigm applied, clear differences emerged only between controls subgroups at the specific self-report scales applied, corroborating the reduced perception of the exclusion. As evidenced by the schema domains, the study found a connection between the impaired limits-schema domain and the drive to binge. CONCLUSION: The results show that obesity surgery patients reported different effects of the Cyberball task than controls. Different possible interpretations are discussed, and future directions for studies are exposed, both for the evaluation of social interactions effects and in the assessment of the role of specific cognitive schemas. LEVEL OF EVIDENCE: Level III: evidence obtained from well-designed cohort or case-control analytic studies.

Olfactory and Gustatory Function before and after Laparoscopic Sleeve Gastrectomy.

Background and Objectives: Bariatric surgery is the gold standard for the treatment of morbid obesity, and current evidence suggests that patients undergoing surgery can show changes in their sense of taste and smell. However, no definitive conclusions can be drawn given the heterogeneity of the studies and the contrasting results reported in the literature. Materials and Methods: We enrolled 18 obese patients undergoing laparoscopic sleeve gastrectomy (LSG) and 15 obese controls. At baseline (T0) and 6 months after enrollment/surgery (T1), both groups underwent Sniffin' Sticks and whole mouth test. Post-operative qualitative taste variations were also analyzed and SNOT-22, VAS for taste and smell, and MMSE were administered. Results: An improvement in the olfactory threshold was observed in the treatment group (p = 0.03) at 6 months. At multivariate analysis, the olfactory threshold differences observed correlated with MMSE (p = 0.03) and T0 gustatory identification (p = 0.01). No changes in sense of taste were observed between the two groups at 6 months, even though nine subjects in the treatment group reported a worsening of taste. This negatively correlated with age (p < 0.001), but a positive marginal correlation was observed with the olfactory threshold difference between T0 and T1 (p = 0.06). Conclusions: Olfaction can improve after LSG, and this seems to be the consequence of an improved olfactory threshold. Although we did not observe any change in gustatory identification, food's pleasantness worsened after bariatric surgery.

Psychological and Psychiatric Traits in Post-bariatric Patients Asking for Body-Contouring Surgery.

BACKGROUNDS: Obese patients, mainly females, feel uncomfortable and unsatisfied with their physical appearance; they have a wrong perception of their image and consequently diminish their self-esteem, sometimes showing difficulties in functional areas such as work, relationship, social activity. Beside health concerns, improving their appearance and body image are often common motives for weight loss in obese individuals and after weight loss about 30% of bariatric surgery patients undergo plastic surgical correction of excessive skin. The authors investigated psychological and psychiatric traits in post-bariatric patients undergoing body-contouring surgery to underline the strong correlation between psychiatry and obesity and avoid unsatisfactory results in post-bariatric patients. METHODS: The Mini International Neuropsychiatric Interview, Beck Depression Inventory II, Yale-Brown Obsessive Compulsive Scale modified for Body Dysmorphic Disorder Tridimensional Personality Questionnaire, Body Uneasiness Test, Barratt Impulsiveness Scale 11, and Binge Eating Scale were performed in 36 post-bariatric patients looking for plastic surgery and 21 controls, similar for clinical features, not seeking shape remodelling. RESULTS: Much different psychiatric pathology characterizes cases, including current body dysmorphic disorder and previous major depression and anxiety disorders, impulsivity, binging and body uneasiness are other common traits. CONCLUSIONS: In post-obesity rehabilitation, a strong collaboration between the plastic surgeon and psychiatrist is recommended to reduce the number of non-compliant patients. Preoperative psychological assessment of the body-contouring patient should be a central part of the initial plastic surgery consultation, as it should be for all plastic surgery patients. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Exploring weight bias and negative self-evaluation in patients with mood disorders: insights from the BodyTalk Project.

Background: Negative body image and adverse body self-evaluation represent key psychological constructs within the realm of weight bias (WB), potentially intertwined with the negative self-evaluation characteristic of depressive symptomatology. Although WB encapsulates an implicit form of self-critical assessment, its exploration among people with mood disorders (MD) has been under-investigated. Our primary goal is to comprehensively assess both explicit and implicit WB, seeking to reveal specific dimensions that could interconnect with the symptoms of MDs. Methods: A cohort comprising 25 MD patients and 35 demographically matched healthy peers (with 83% female representation) participated in a series of tasks designed to evaluate the congruence between various computer-generated body representations and a spectrum of descriptive adjectives. Our analysis delved into multiple facets of body image evaluation, scrutinizing the associations between different body sizes and emotionally charged adjectives (e.g., active, apple-shaped, attractive). Results: No discernible differences emerged concerning body dissatisfaction or the correspondence of different body sizes with varying adjectives. Interestingly, MD patients exhibited a markedly higher tendency to overestimate their body weight (p = 0.011). Explicit WB did not show significant variance between the two groups, but MD participants demonstrated a notable implicit WB within a specific weight rating task for BMI between 18.5 and 25 kg/m2 (p = 0.012). Conclusions: Despite the striking similarities in the assessment of participants' body weight, our investigation revealed an implicit WB among individuals grappling with MD. This bias potentially assumes a role in fostering self-directed negative evaluations, shedding light on a previously unexplored facet of the interplay between WB and mood disorders.

The state of brain activity modulates cerebrospinal fluid transport.

Earlier studies based on 2-photon imaging have shown that glymphatic cerebrospinal fluid (CSF) transport is regulated by the sleep-wake cycle. To examine this association, we used 3DISCO whole-body tissue clearing to map CSF tracer distribution in awake, sleeping and ketamine-xylazine anesthetized mice. The results of our analysis showed that CSF tracers entered the brain to a significantly larger extent in natural sleep or ketamine-xylazine anesthesia than in wakefulness. Furthermore, awake mice showed preferential transport of CSF tracers in the rostro-caudal direction towards the cervical and spinal cord lymphatic vessels, and hence to venous circulation and excretion by the kidneys. The study extends the current literature by showing that CSF dynamics on the whole-body scale is controlled by the state of brain activity.

Prevalence and Risk Factors for QTc Prolongation in Acute Psychiatric Hospitalization.

Objective: Prolongation of corrected QT (QTc) interval increases the risk of severe ventricular arrhythmias, in particular torsades de pointes. Patients with severe mental illness (SMI) represent a vulnerable population. This study aimed to measure the prevalence of QTc prolongation in inpatients with SMI and to identify risk factors for QTc prolongation.Methods: Demographic, clinical, anthropometric, laboratory, and electrocardiographic information was extracted from the electronic records of a cohort of patients hospitalized in a psychiatry inpatient unit between July 1, 2017, and July 22, 2019. The primary outcome was the estimation of prevalence of QTc prolongation. The secondary outcome was the identification of risk factors for QTc prolongation.Results: A total of 597 admissions were included. Only 1.4% had a QTc > 500 msec, while 11.6% had a QTc > 460 msec. The proportion of women with a QTc > 470 msec was 3.6% and men with a QTc > 450 msec was 7.3%. Several risk factors were individually associated with QTc prolongation. In the multivariate model explaining almost one-third of QTc variance, female sex (P = .04), older age (P = .011), heart rate (P < .001), systolic blood pressure (P = .042), potassium (P = .012), hemoglobin (P = .006), number of antipsychotics (P = .026), and treatment with clotiapine (P = .012) and clozapine (P = .003) were associated with QTc length. Several factors beyond pharmacologic treatment identify subjects at risk for QTc prolongation, and polypharmacotherapy does not seem to increase the risk of QTc prolongation.Conclusions: QTc prolongation was rare in this cohort of SMI inpatients. Most of the risk factors involved in QTc prolongation are unchangeable elements or linked to general medical conditions, and only a few are modifiable factors, including psychotropic treatment.

Self-Oriented Empathy and Personality Organisation Level: Insights from a Psychiatric Sample.

Objective: Empathy functioning is among the criteria to delineate psychiatric diagnosis. However, the self-oriented empathy dimension is almost neglected in the existing literature. On the basis of previous fragmented contributions, we hypothesised that an individual's level of personality organisation is explained by this facet of empathy more than the other components of empathy, both transversally and independently from the specific psychiatric diagnosis. Method: Fifty-nine psychiatric inpatients were evaluated with clinical interviews inspired by the Structured Clinical Interview for DSM-5, completed the Symptom Checklist-90-Revised, and Interpersonal Reactivity Index (IRI). A panel of experts established each patient's psychiatric diagnosis and the level of personality organisation according to DSM-5 and PDM-2. Thirty-two patients were considered functioning at a psychotic level, 27 at a borderline level, and none at a neurotic level. Multinomial models were compared with the corrected AIC to determine if self-oriented empathy, among all IRI subscales, was the best-fitting model for explaining the levels of personality organisation. A further analogue series of models was used to investigate the best IRI subscale to explain each patient's psychiatric diagnosis. Results: The first series of models revealed self-oriented empathy (IRI personal distress subscale) as the best empathic dimension to explain levels of personality organisation. The second series revealed that none of the four IRI subscales explained psychiatric diagnoses. Conclusions: The consistency of our findings with evolutionary concepts pertaining to both traditional psychodynamic models and contemporary models of psychopathology, such as the p factor theory, was illustrated. Despite the many limitations of our consecutive sampling jeopardising the findings' generalisability, the insight of self-oriented empathy as the best predictor of the level of personality organisation, irrespective of psychiatric diagnosis, has several implications from both research and clinical/diagnostic perspectives.

Retrospective analysis of the predictive factors associated with good surgical outcome in brachioplasty in massive weight loss patients.

BACKGROUND: Upper arm lift is a widespread body contouring procedure, but no globally accepted guidelines exist in selecting patients and, due to comorbidity and heterogeneity of them, it is difficult to identify predictive factors of good surgical outcome. The authors review the team's experience of 56 brachioplasty performed in massive weighs loss patients. METHODS: Data of 56 consecutive arm lifts were reviewed for preoperative, perioperative and postoperative variables and outcomes (complications, scarring, wound healing, revision surgery, need for blood transfusion, satisfaction, etc.). Surgical technique and postoperative care are described. A statistical analysis was performed to identify relationship between possible predictive factors and outcomes. Furthermore, an evaluation of different employed wound management devices was conducted. RESULTS: Follow-up ranged from 6 to 36 months (mean 20.1 months). Outcomes summary is reported (overall complication rate 50%, poor scarring rate 25%, delayed wound healing rate 26.8%, revision surgery rate 37.5%, need for blood transfusion rate 8.9%, satisfaction rate 71.4%) and statistical investigation evidenced the role of prior plastic surgery BMI and the associated change in BMI before and after weight loss, just prior brachioplasty, and the modality of weight loss. CONCLUSION: The authors' technique resulted in positive outcomes overall, considering the difficulty in dealing with the problems of MWL patients. Based on our results, we aim to suggest to perform brachioplasty in patient with the lower achievable BMI (preferably <30kg/m2) to reduce the negative effect of unmodifiable factors as diabetes, modality of weight loss, a wide ΔBMI, and other well-known negative predictive factors.

On the Implementation of Computerized Adaptive Observations for Psychological Assessment.

The use of observational tools in psychological assessment has decreased in recent years, mainly due to its personnel and time costs, and researchers have not explored methodological innovations like adaptive algorithms in observational assessment. In the present study, we introduce the behavior-driven observation procedure to develop, test, and implement observational adaptive instruments. In Study 1, we use a preexisting observational checklist to evaluate nonverbal behaviors related to psychotic symptoms and to specify the adaptive algorithm's model. We fit the model to observational data collected from 114 participants. The results support the model's goodness of fit. In Study 2, we use the estimated model parameters to calibrate the adaptive procedure and test the algorithm for accuracy and efficiency in adaptively reconstructing 58 nonadaptively collected response patterns. The results show the algorithm's good accuracy and efficiency, with a 40% average reduction in the number of administered items. In Study 3, we used real raters to test the adaptive checklist built with behavior-driven observation. The results indicate adequate intrarater agreement and good consistency of the observed response patterns. In conclusion, the results support the possibility of using behavior-driven observation to create accurate and affordable (in terms of resources) observational assessment tools.

Body Image Disturbances and Weight Bias After Obesity Surgery: Semantic and Visual Evaluation in a Controlled Study, Findings from the BodyTalk Project.

PURPOSE: Body image has a significant impact on the outcome of obesity surgery. This study aims to perform a semantic evaluation of body shapes in obesity surgery patients and a group of controls. MATERIALS AND METHODS: Thirty-four obesity surgery (OS) subjects, stable after weight loss (average 48.03 ± 18.60 kg), and 35 overweight/obese controls (MC), were enrolled in this study. Body dissatisfaction, self-esteem, and body perception were evaluated with self-reported tests, and semantic evaluation of body shapes was performed with three specific tasks constructed with realistic human body stimuli. RESULTS: The OS showed a more positive body image compared to HC (p < 0.001), higher levels of depression (p < 0.019), and lower self-esteem (p < 0.000). OS patients and HC showed no difference in weight bias, but OS used a higher BMI than HC in the visualization of positive adjectives (p = 0.011). Both groups showed a mental underestimation of their body shapes. CONCLUSION: OS patients are more psychologically burdened and have more difficulties in judging their bodies than overweight/obese peers. Their mental body representations seem not to be linked to their own BMI. Our findings provide helpful insight for the design of specific interventions in body image in obese and overweight people, as well as in OS.

Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design.

Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients' treatment. Anyway, some drugs possess antioxidant capacity themselves and this aspect is discussed in this review, focusing on antipsychotics and antidepressants. In the context of a collection of clinical observations, in vitro and in vivo results are critically reported, often highlighting controversial aspects. Finally, a new challenge is discussed, i.e., the possibility of assessing in silico the antioxidant potential of these drugs, exploiting computational chemistry methodologies and machine learning. Despite the physiological environment being incredibly complex and the detection of meaningful oxidative stress biomarkers being all but an easy task, a rigorous and systematic analysis of the structural and reactivity properties of antioxidant drugs seems to be a promising route to better interpret therapeutic outcomes and provide elements for the rational design of novel drugs.

A functional observational battery for evaluation of neurological outcomes in a rat model of acute bacterial meningitis.

BACKGROUND: Acute bacterial meningitis is a disease with a high mortality and a high incidence of neurological sequelae in survivors. There is an acute need to develop new adjuvant therapies. To ensure that new therapies evaluated in animal models are translatable to humans, studies must evaluate clinically relevant and patient-important outcomes, including neurological symptoms and sequelae. METHODS: We developed and tested a functional observational battery to quantify the severity of a variety of relevant neurological and clinical symptoms in a rat model of bacterial meningitis. The functional observational battery included symptoms relating to general clinical signs, gait and posture abnormalities, involuntary motor movements, focal neurological signs, and neuromotor abnormalities which were scored according to severity and summed to obtain a combined clinical and neurological score. To test the functional observational battery, adult Sprague-Dawley rats were infected by intracisternal injection of a clinical isolate of Streptococcus pneumoniae. Rats were evaluated for 6 days following the infection. RESULTS: Pneumococcal meningitis was not lethal in this model; however, it induced severe neurological symptoms. Most common symptoms were hearing loss (75% of infected vs 0% of control rats; p = 0.0003), involuntary motor movements (75% of infected vs 0% of control rats; p = 0.0003), and gait and posture abnormality (67% of infected vs 0% of control rats; p = 0.0013). Infected rats had a higher combined score when determined by the functional observational battery than control rats at all time points (24 h 12.7 ± 4.0 vs 4.0 ± 2.0; 48 h 17.3 ± 7.1 vs 3.4 ± 1.8; 6 days 17.8 ± 7.4 vs 1.7 ± 2.4; p < 0.0001 for all). CONCLUSIONS: The functional observational battery described here detects clinically relevant neurological sequelae of bacterial meningitis and could be a useful tool when testing new therapeutics in rat models of meningitis.

Effects of novel antidepressant drugs on mesenchymal stem cell physiology.

It is known that users of psychotropic drugs often have weight gain, adverse effects on bone mineral density and osteoporosis, but the molecular basis for these side effects is poorly understood. The aim of this study is to evaluate the effects in vitro of duloxetine (a serotonin and norepinephrine reuptake inhibitor) and fluoxetine (a selective serotonin reuptake inhibitor) on the physiology of human adult stem cells. Adipose-derived stem cells (ADSCs) were isolated and characterized investigating phenotype morphology, expression and frequency of surface markers. Then, a non-toxic concentration of duloxetine and fluoxetine was selected to treat cells during adipogenic and osteogenic differentiation. Stemness properties and the differentiation potential of drug-treated cells were investigated by the quantification of adipogenic and osteogenic markers gene expression and histological staining. The collected data showed that the administration of a daily non-toxic dose of duloxetine and fluoxetine has not directly influenced ADSCs proliferation and their stemness properties. The treatment with duloxetine or fluoxetine did not lead to morphological alterations during adipogenic or osteogenic commitment. However, treatments with the antidepressant showed a slight difference in adipogenic gene expression timing. Furthermore, duloxetine treatment caused an advance in gene expression of early and late osteogenic markers. Fluoxetine instead caused an increase in expression of osteogenic genes compared to untreated cells. In contrast, in pre-differentiated cells, the daily treatment with duloxetine or fluoxetine did not alter the expression profile of adipogenic and osteogenic differentiation. In conclusion, a non-toxic concentration of duloxetine and fluoxetine does not alter the stemness properties of ADSCs and does not prevent the commitment of pre-differentiated ADSCs in adipocytes or osteocyte. Probably, the weight gain and osteoporotic effects associated with the use of psychotropic drugs could be closely related to the direct action of serotonin.

Psychiatric Disorders and Oxidative Injury: Antioxidant Effects of Zolpidem Therapy disclosed In Silico.

Zolpidem (N,N-Dimethyl-2-[6-methyl-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]acetamide) is a well-known drug for the treatment of sleeping disorders. Recent literature reports on positive effects of zolpidem therapy on improving renal damage after cisplatin and on reducing akinesia without sleep induction. This has been ascribed to the antioxidant and neuroprotective capacity of this molecule, and tentatively explained according to a generic structural similarity between zolpidem and melatonin. In this work, we investigate in silico the antioxidant potential of zolpidem as scavenger of five ROSs, acting via hydrogen atom transfer (HAT) mechanism; computational methodologies based on density functional theory are employed. For completeness, the analysis is extended to six metabolites. Thermodynamic and kinetic results disclose that indeed zolpidem is an efficient radical scavenger, similarly to melatonin and Trolox, supporting the biomedical evidence that the antioxidant potential of zolpidem therapy may have a beneficial effect against oxidative injury, which is emerging as an important etiopathogenesis in numerous severe diseases, including psychiatric disorders.

Cisterna Magna Injection in Rats to Study Glymphatic Function.

The recently discovered glymphatic system, which supports brain-wide clearance of metabolic waste, has become the subject of intense research within the past few years. Its nomenclature arose due to its functionally analogous nature to the lymphatic system in combination with glial cells that are part of its anatomical boundaries. The influx of cerebrospinal fluid (CSF) from perivascular spaces into the brain interstitium acts to clear intraparenchymal solutes. CSF is produced by the choroid plexus and flows from the ventricles to the subarachnoid space via the cisterna magna, and as such the injection of tracer molecules into any one of these spaces could be used for studying CSF movement through the glymphatic system. Of these options, the cisterna magna is most favorable as it offers a route of entry that does not involve craniotomy. Herein we describe the cisterna magna (CM) injection procedure carried out in rats, essential for studying glymphatic influx and efflux dynamics.

Neutrophil extracellular traps in the central nervous system hinder bacterial clearance during pneumococcal meningitis.

Neutrophils are crucial mediators of host defense that are recruited to the central nervous system (CNS) in large numbers during acute bacterial meningitis caused by Streptococcus pneumoniae. Neutrophils release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures composed of decondensed DNA and neutrophil-derived antimicrobial proteins. Here we show NETs in the cerebrospinal fluid (CSF) of patients with pneumococcal meningitis, and their absence in other forms of meningitis with neutrophil influx into the CSF caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the CSF. Disrupting NETs using DNase I significantly reduces bacterial load, demonstrating that NETs contribute to pneumococcal meningitis pathogenesis in vivo. We conclude that NETs in the CNS reduce bacterial clearance and degrading NETs using DNase I may have significant therapeutic implications.