Mexican Psychiatric Trainees' Attitudes Towards People with Mental Illness: A Qualitative Study.

Despite their training, psychiatrists have been found to have negative attitudes towards people with mental illness, including the patients they treat. Similarly, studies focused on service users have identified psychiatrists as a source of stigma. Even though negative attitudes in psychiatrists have been identified in different countries and settings, in Mexico the attitudes of these professionals have never been assessed. Because of this, we invited psychiatric trainees from a hospital in Mexico to participate in individual interviews to describe their opinions regarding mental health-related stigma, to evaluate their attitudes towards people with mental illness and to identify factors that could be influencing their attitudes. Interviews were audio recorded, transcribed and analysed using thematic analysis. A total of 29 trainees participated in the study. The results suggested that trainees recognised psychiatrists can have negative attitudes towards people with mental illness, such as poor empathy, judgement and labelling, and mainly towards patients considered difficult and with borderline personality disorder. Participants recognised these attitudes can influence their relationship with patients, and considered it is necessary to develop interventions to improve their own attitudes and reduce mental health stigma. From this study we concluded Mexican psychiatrists are not free from stigma towards people with mental illness. However, Mexican psychiatric trainees are interested in improving their attitudes and reactions towards their patients.

Mental Health Service Users' Perceptions of Stigma, From the General Population and From Mental Health Professionals in Mexico: A Qualitative Study.

Negative attitudes towards people with mental health disorders have been widely studied and identified in the general population, and even within health care professionals. Moreover, studies focused on service users have also identified mental health professionals, including psychiatrists, as a source of stigma. However, in Mexico and Latin America few studies have been conducted addressing this issue. To explore mental health service users' perceptions of stigma by members of the general population and by psychiatrists in Mexico, service users at a psychiatric hospital in Mexico were invited to participate in either focus groups or individual interviews, which were audio recorded, transcribed and analysed using thematic analysis. A total of 47 service users participated in this study. The results suggested that participants were not only aware of the possible consequences of mental health related stigma, but they have also experienced stigmatisation for having a mental illness. Participants also considered psychiatrists can hold negative attitudes towards people with mental illness, something that can represent a barrier for them to have optimal quality of care. Therefore, participants agreed that these attitudes should be addressed to improve the care they received from these professionals. This study suggests that, like members of the general population, psychiatrists are also considered as a source of stigma by people with mental illness in Mexico. These findings not only add to previous work conducted in Mexico and other countries, they also confirm the importance of addressing negative attitudes in this group of health professionals.

Emotional facial expressions during REM sleep dreams.

Although motor activity is actively inhibited during rapid eye movement (REM) sleep, specific activations of the facial mimetic musculature have been observed during this stage, which may be associated with greater emotional dream mentation. Nevertheless, no specific biomarker of emotional valence or arousal related to dream content has been identified to date. In order to explore the electromyographic (EMG) activity (voltage, number, density and duration) of the corrugator and zygomaticus major muscles during REM sleep and its association with emotional dream mentation, this study performed a series of experimental awakenings after observing EMG facial activations during REM sleep. The study was performed with 12 healthy female participants using an 8-hr nighttime sleep recording. Emotional tone was evaluated by five blinded judges and final valence and intensity scores were obtained. Emotions were mentioned in 80.4% of dream reports. The voltage, number, density and duration of facial muscle contractions were greater for the corrugator muscle than for the zygomaticus muscle, whereas high positive emotions predicted the number (R2 0.601, p = 0.0001) and voltage (R2 0.332, p = 0.005) of the zygomaticus. Our findings suggest that zygomaticus events were predictive of the experience of positive affect during REM sleep in healthy women.

Clinical and behavioral profile of young inhalant users.

INTRODUCTION: Currently, misuse inhalants is increasing: addictive potential has been demonstrated in several studies. Until now there was no quantifiable clinical evidence of behavioral characteristics inhalant users. Main objective was to evaluate craving, impulsivity, frontalized behaviors and recognition of emotions in young inhalant users. METHOD: Eleven male, aged 15-22 years (17.73±2.14), schooling 3-12 years (8.18±2.56) were evaluated. RESULTS: Evaluation showed that inhalant users exhibit signs of craving, high ranges of impulsivity, frontal behavioral deficits and difficulties detection of emotional expressions. CONCLUSIONS: In inhalants addiction, symptoms of craving and behavioral alterations are exhibited, time use increases frontal behaviors.

Evidence of validity of an inhalant-craving questionnaire.

Inhalants are substances widely used as recreational drugs: their addictive potential has been demonstrated by many studies. There is no reported measurable evidence of craving in inhalant users. The main goal of this study was to design and obtain evidence of validity of the score of a questionnaire for the evaluation of inhalant craving (ICQ) in a Mexican population sample. The ICQ is a type of visual analog scale with ten items. Face validity was evaluated by a group of experts in the addiction field. Reviewers considered the completeness, semantics, and sentence structure to guarantee a conceptual representation of the items. The final ICQ was applied to a sample of 520 Mexican high school students, 46% women and 54% men, between 12-19 years of age (M=15.18; SD=1.48), from 7th to 12th grades. The internal consistency of the ICQ showed a Cronbach's Alpha of 0.947. The 10 items were grouped into one single factor, with a factor loading above 0.74 for each of them. ROC analysis breakpoint was located at 18.5 mm with a sensitivity of 0.855 and specificity of 0.753. Thirty-three per cent (n= 172) of the student population evaluated reported the use of inhalants at some point in their lifetimes, with an average of misuse beginning at 13.6 years of age. The ICQ showed adequate psychometric properties, suggesting that the instrument may be considered a useful tool for screening for craving in young inhalant users.

Los inhalables son sustancias ampliamente utilizadas como drogas recreativas: su potencial adictivo ha sido demostrado por numerosos estudios. No hay reportada evidencia medible del craving en usuarios de inhalables. El objetivo principal de este trabajo fue diseñar y obtener las evidencias de validez de las puntuaciones en un cuestionario para la evaluación del craving a sustancias inhalables (ICQ) en una muestra de población mexicana. El ICQ es un tipo de escala análoga visual de diez ítems. La validación de apariencia fue evaluada por un grupo de expertos en el campo de las adicciones. Los revisores consideraron la integridad, la semántica y la estructura de los enunciados, para garantizar una representación conceptual de los ítems. La versión final del ICQ fue aplicada a una muestra de 520 estudiantes mexicanos, 46% mujeres y 54% hombres, con edad comprendidas entre 12-19 años (M=15.18; SD=1.48), con años de escolaridad entre 7-12 años. La consistencia interna del ICQ mostró un Alfa de Cronbach de 0.947. Los 10 ítems se agruparon en un solo factor, con una carga factorial por encima de 0.74 para cada uno de ellos. El análisis ROC mostró que el punto de corte se localizó a 18.5 mm con una sensibilidad de 0.855 y especificidad de 0.753. El 33% (n=172) de la población de estudiantes evaluados reportó el uso de inhalables en algún momento de su vida, con un promedio de edad de inicio de 13.6 años. El ICQ mostró propiedades psicométricas adecuadas, lo que sugiere que el instrumento puede ser una herramienta útil para el tamizaje de craving en jóvenes usuarios de inhalables.

Human olfactory neural progenitor cells reveal differences in IL-6, IL-8, thrombospondin-1, and MCP-1 in major depression disorder and borderline personality disorder.

Background: Discovering biological markers is essential for understanding and treating mental disorders. Despite the limitations of current non-invasive methods, neural progenitor cells from the olfactory epithelium (hNPCs-OE) have been emphasized as potential biomarker sources. This study measured soluble factors in these cells in Major Depressive Disorder (MDD), Borderline Personality Disorder (BPD), and healthy controls (HC). Methods: We assessed thirty-five participants divided into MDD (n=14), BPD (n=14), and HC (n=7). MDD was assessed using the Hamilton Depression Rating Scale. BPD was evaluated using the DSM-5 criteria and the Structured Clinical Interview for Personality Disorders. We isolated hNPCs-OE, collected intracellular proteins and conditioned medium, and quantified markers and soluble factors, including Interleukin-6, interleukin-8, and others. Analysis was conducted using one-way ANOVA or Kruskal-Wallis test and linear regression. Results: We found that hNPCs-OE of MDD and BPD decreased Sox2 and laminin receptor-67 kDa levels. MASH-1 decreased in BPD, while tubulin beta-III decreased in MDD compared to controls and BPD. Also, we found significant differences in IL-6, IL-8, MCP-1, and thrombospondin-1 levels between controls and MDD, or BPD, but not between MDD and BPD. Conclusions: Altered protein markers are evident in the nhNPCs-OE in MDD and BPD patients. These cells also secrete higher concentrations of inflammatory cytokines than HC cells. The results suggest the potential utility of hNPCs-OE as an in vitro model for researching biological protein markers in psychiatric disorders. However, more extensive validation studies are needed to confirm their effectiveness and specificity in neuropsychiatric disorders.

Repetitive transcranial magnetic stimulation and fluoxetine reverse depressive-like behavior but with differential effects on Olig2-positive cells in chronically stressed mice.

Depression is a mood disorder coursing with several behavioral, cellular, and neurochemical alterations. The negative impact of chronic stress may precipitate this neuropsychiatric disorder. Interestingly, downregulation of oligodendrocyte-related genes, abnormal myelin structure, and reduced numbers and density of oligodendrocytes in the limbic system have been identified in patients diagnosed with depression, but also in rodents exposed to chronic mild stress (CMS). Several reports have emphasized the importance of pharmacological or stimulation-related strategies in influencing oligodendrocytes in the hippocampal neurogenic niche. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as an intervention to revert depression. Here, we hypothesized that 5 Hz (Hz) of rTMS or Fluoxetine (Flx) would revert depressive-like behaviors by influencing oligodendrocytes and revert neurogenic alterations caused by CMS in female Swiss Webster mice. Our results showed that 5 Hz rTMS or Flx revert depressive-like behavior. Only rTMS influenced oligodendrocytes by increasing the number of Olig2-positive cells in the hilus of the dentate gyrus and the prefrontal cortex. However, both strategies exerted effects on some events of the hippocampal neurogenic processes, such as cell proliferation (Ki67-positive cells), survival (CldU-positive cells), and intermediate stages (doublecortin-positive cells) along the dorsal-ventral axis of this region. Interestingly, the combination of rTMS-Flx exerted antidepressant-like effects, but the increased number of Olig2-positive cells observed in mice treated only with rTMS was canceled. However, rTMS-Flx exerted a synergistic effect by increasing the number of Ki67-positive cells. It also increased the number of CldU- and doublecortin-positive cells in the dentate gyrus. Our results demonstrate that 5 Hz rTMS has beneficial effects, as it reverted depressive-like behavior by increasing the number of Olig2-positive cells and reverting the decrement in hippocampal neurogenesis in CMS-exposed mice. Nevertheless, the effects of rTMS on other glial cells require further investigation.

5 Hz of repetitive transcranial magnetic stimulation improves cognition and induces modifications in hippocampal neurogenesis in adult female Swiss Webster mice.

Adult hippocampal neurogenesis is regulated by several stimuli to promote the creation of a reserve that may facilitate coping with environmental challenges. In this regard, repetitive transcranial magnetic stimulation (rTMS), a neuromodulation therapy, came to our attention because in clinical studies it reverts behavioral and cognitive alterations related to changes in brain plasticity. Some preclinical studies emphasize the need to understand the underlying mechanism of rTMS to induce behavioral modifications. In this study, we investigated the effects of rTMS on cognition, neurogenic-associated modifications, and neuronal activation in the hippocampus of female Swiss Webster mice. We applied 5 Hz of rTMS twice a day for 14 days. Three days later, mice were exposed to the behavioral battery. Then, brains were collected and immunostained for Ki67-positive cells, doublecortin-positive (DCX+)-cells, calbindin, c-Fos and FosB/Delta-FosB in the dentate gyrus. Also, we analyzed mossy fibers and CA3 with calbindin immunostaining. Mice exposed to rTMS exhibited cognitive improvement, an increased number of proliferative cells, DCX cells, DCX cells with complex dendrite morphology, c-Fos and immunoreactivity of FosB/Delta-FosB in the granular cell layer. The volume of the granular cell layer, mossy fibers and CA3 in rTMS mice also increased. Interestingly, cognitive improvement correlated with DCX cells with complex dendrite morphology. Also, those DCX cells and calbindin immunoreactivity correlated with c-Fos in the granular cell layer. Our results suggest that 5 Hz of rTMS applied twice a day modify cell proliferation, doublecortin cells, mossy fibers and enhance cognitive behavior in healthy female Swiss Webster mice.

Evaluation of an anti-stigma intervention for Mexican psychiatric trainees.

BACKGROUND: There is research evidence regarding the presence of stigmatising attitudes in psychiatrists towards people with mental illness, but a lack of studies and interventions focused on this issue in low and middle-income countries. AIMS: To assess the feasibility of implementing an anti-stigma intervention for Mexican psychiatric trainees, and its potential effects. METHODS: This study comprised a pre-post design with outcome measures compared between baseline and 3-month follow-up. Quantitative outcome measures were used to evaluate the potential effects of the intervention, whilst the process evaluation required the collection and analysis of both quantitative and qualitative data. RESULTS: Twenty-nine trainees (25% of those invited) participated in the intervention, of whom 18 also participated in the follow-up assessment. Outcome measures showed the intervention had moderately large effects on reducing stereotypes and the influence of other co-workers on trainees' own attitudes. The main mechanisms of impact identified were recognition of negative attitudes in oneself and colleagues, self-reflection about the impact of stigma, one's own negative attitudes and recognition of one's ability to make change. Participants accepted and were satisfied with the intervention, which many considered should be part of their routine training. However, trainees' work overload and lack of support from the host organisation were identified as barriers to implement the intervention. CONCLUSIONS: A brief anti-stigma intervention for Mexican psychiatric trainees is feasible, potentially effective, well accepted and was considered necessary by participants. This study also suggests mechanisms of impact and mediators should be considered for developing further interventions, contributing to reducing the damaging effects that mental health-related stigma has on people's lives.

The Mexican magnetic resonance imaging dataset of patients with cocaine use disorder: SUDMEX CONN.

Cocaine use disorder (CUD) is a substance use disorder (SUD) characterized by compulsion to seek, use and abuse of cocaine, with severe health and economic consequences for the patients, their families and society. Due to the lack of successful treatments and high relapse rate, more research is needed to understand this and other SUD. Here, we present the SUDMEX CONN dataset, a Mexican open dataset of 74 CUD patients (9 female) and matched 64 healthy controls (6 female) that includes demographic, cognitive, clinical, and magnetic resonance imaging (MRI) data. MRI data includes: 1) structural (T1-weighted), 2) multishell high-angular resolution diffusion-weighted (DWI-HARDI) and 3) functional (resting state fMRI) sequences. The repository contains unprocessed MRI data available in brain imaging data structure (BIDS) format with corresponding metadata available at the OpenNeuro data sharing platform. Researchers can pursue brain variability between these groups or use a single group for a larger population sample.

Clinical and Functional Connectivity Outcomes of 5-Hz Repetitive Transcranial Magnetic Stimulation as an Add-on Treatment in Cocaine Use Disorder: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Cocaine use disorder (CUD) is a global condition lacking effective treatment. Repetitive transcranial magnetic stimulation (rTMS) may reduce craving and frequency of cocaine use, but little is known about its efficacy and neural effects. We sought to elucidate short- and long-term clinical benefits of 5-Hz rTMS as an add-on to standard treatment in patients with CUD and discern underlying functional connectivity effects using magnetic resonance imaging. METHODS: A total of 44 patients with CUD were randomly assigned to complete the 2-week double-blind randomized controlled trial (acute phase) (sham [n = 20, 2 female] and active [n = 24, 4 female]), in which they received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (PFC). Subsequently, 20 patients with CUD continued to an open-label maintenance phase for 6 months (two weekly sessions for up to 6 mo). RESULTS: rTMS plus standard treatment for 2 weeks significantly reduced craving (baseline: 3.9 ± 3.6; 2 weeks: 1.5 ± 2.4, p = .013, d = 0.77) and impulsivity (baseline: 64.8 ± 16.8; 2 weeks: 53.1 ± 17.4, p = .011, d = 0.79) in the active group. We also found increased functional connectivity between the left dorsolateral PFC and ventromedial PFC and between the ventromedial PFC and right angular gyrus. Clinical and functional connectivity effects were maintained for 3 months, but they dissipated by 6 months. We did not observe reduction in positive results for cocaine in urine; however, self-reported frequency and grams consumed for 6 months were reduced. CONCLUSIONS: With this randomized controlled trial, we show that 5-Hz rTMS has potential promise as an adjunctive treatment for CUD and merits further research.

Mental health problems among healthcare workers involved with the COVID-19 outbreak.

OBJECTIVE: The mental health problems and perceived needs of healthcare workers involved with coronavirus disease (COVID-19) may vary due to individual and contextual characteristics. The objective of this study was to evaluate healthcare workers' mental health problems during the common COVID-19 exposure scenario in Mexico, comparing those on the frontline with other healthcare workers according to gender and profession, determining the main risk factors for the most frequent mental health problems. METHODS: A cross-sectional online study was conducted with a non-probabilistic sample of 5,938 Mexican healthcare workers who completed brief screening measures of mental health problems and ad hoc questions about sociodemographic professional characteristics, conditions related to increased risk of COVID-19 infection, life stressors during the COVID-19 emergency, and perceived need to cope with COVID-19. RESULTS: The identified mental health problems were insomnia, depression, and posttraumatic stress disorder (PTSD), all of which were more frequent in frontline healthcare workers (52.1, 37.7, and 37.5%, respectively) and women (47.1, 33.0 %, and 16.3%, respectively). A lack of rest time was the main risk factor for insomnia (OR = 3.1, 95%CI 2.6-3.7, p ≤ 0.0001). Mourning the death of friends or loved ones due to COVID-19 was the main risk factor for depression (OR = 2.2, 95%CI 1.8-2.7, p ≤ 0.0001), and personal COVID-19 status was the main risk factor for PTSD (OR = 2.2, 95%CI 1.7-2.9, p ≤ 0.0001). CONCLUSION: The most frequent mental health problems during the common exposure scenario for COVID-19 in Mexico included the short-term psychological consequences of intense adversity. A comprehensive strategy for preventing mental health problems should focus on individuals with cumulative vulnerability and specific risk factors.

EEG sources in a group of patients with major depressive disorders.

EEG sources were assessed in a group of patients with major moderate-severe depressive disorder (MDD) as classified by trained clinicians according to DSM-IV criteria. Frequency Domain Variable Resolution Electromagnetic Tomography (FD-VARETA) was used to calculate EEG sources. The Z-values indicated that EEG sources were abnormal (increase in current density) in all patients, with most demonstrating abnormal EEG sources in both hemispheres but with maximal inverse solution located primarily in the right. Twenty-nine patients had a predominant topography of the abnormal EEG maximal inverse solution in the frontal lobes. The remaining seven patients had a bilateral abnormal increase in current density in the superior parietal lobe. The EEG maximal abnormal inverse solution frequency was observed in both hemispheres such that the increases in current density were prevalent in alpha and theta bands. The results suggest that any of the two hemispheres could be affected by MDD, but abnormal EEG sources can be found more frequently in the right one, with the maximal abnormal inverse solution at the alpha and theta bands in frontal and parietal cortices.

Effects of Childhood Maltreatment on Social Cognition and Brain Functional Connectivity in Borderline Personality Disorder Patients.

Borderline personality disorder (BPD) is a chronic condition characterized by high levels of impulsivity, affective instability, and difficulty to establish and manage interpersonal relationships. However, little is known about its etiology and neurobiological substrates. In our study, we wanted to investigate the influence of child abuse in the psychopathology of BPD by means of social cognitive paradigms [the Movie for the Assessment of Social Cognition (MASC) and the reading the mind in the eyes test (RMET)], and resting state functional magnetic resonance imaging (rs-fMRI). For this, we recruited 33 participants, 18 BPD patients, and 15 controls. High levels of self-reported childhood maltreatment were reported by BPD patients. For the sexual abuse subdimension, there were no differences between the BPD and the control groups, but there was a negative correlation between MASC scores and total childhood maltreatment levels, as well as between physical abuse, physical negligence, and MASC. Both groups showed that the higher the level of childhood maltreatment, the lower the performance on the MASC social cognitive test. Further, in the BPD group, there was hypoconnectivity between the structures responsible for emotion regulation and social cognitive responses that have been described as part of the frontolimbic circuitry (i.e., amygdala). Differential levels of connectivity, associated with different types and levels of abuse were also observed.

Identifying cognitive deficits in cocaine dependence using standard tests and machine learning.

There is a growing need to address the variability in detecting cognitive deficits with standard tests in cocaine dependence (CD). The aim of the current study was to identify cognitive deficits by means of Machine Learning (ML) algorithms: Generalized Linear Model (Glm), Random forest (Rf) and Elastic Net (GlmNet), to allow more effective categorization of CD and Non-dependent controls (NDC and to address common methodological problems. For our validation, we used two independent datasets, the first consisted of 87 participants (53 CD and 34 NDC) and the second of 40 participants (20 CD and 20 NDC). All participants were evaluated with neuropsychological tests that included 40 variables assessing cognitive domains. Using results from the cognitive evaluation, the three ML algorithms were trained in the first dataset and tested on the second to classify participants into CD and NDC. While the three algorithms had a receiver operating curve (ROC) performance over 50%, the GlmNet was superior in both the training (ROC = 0.71) and testing datasets (ROC = 0.85) compared to Rf and Glm. Furthermore, GlmNet was capable of identifying the eight main predictors of group assignment (CD or NCD) from all the cognitive domains assessed. Specific variables from each cognitive test resulted in robust predictors for accurate classification of new cases, such as those from cognitive flexibility and inhibition domains. These findings provide evidence of the effectiveness of ML as an approach to highlight relevant sections of standard cognitive tests in CD, and for the identification of generalizable cognitive markers.

Borderline Personality Disorder With Cocaine Dependence: Impulsivity, Emotional Dysregulation and Amygdala Functional Connectivity.

Background: Borderline personality disorder is present in 19% of cocaine dependence cases; however, this dual pathology is poorly understood. We wished to characterize the dual pathology and find its functional connectivity correlates to better understand it. Methods: We recruited 69 participants divided into 4 groups: dual pathology (n = 20), cocaine dependence without borderline personality disorder (n = 19), borderline personality without cocaine dependence (n = 10) and healthy controls (n = 20). We used self-reported instruments to measure impulsivity and emotional dysregulation. We acquired resting state fMRI and performed seed-based analyses of the functional connectivity of bilateral amygdala. Results: Borderline personality disorder and cocaine dependence as factors had opposing effects in impulsivity and emotional dysregulation, as well as on functional connectivity between left amygdala and medial prefrontal cortex. On the other hand, in the functional connectivity between right amygdala and left insula, the effect of having both disorders was instead additive, reducing functional connectivity strength. The significant functional connectivity clusters were correlated with impulsivity and emotional dysregulation. Conclusions: In this study, we found that clinical scores of dual pathology patients were closer to those of borderline personality disorder without cocaine dependence than to those of cocaine dependence without borderline personality disorder, while amygdala-medial prefrontal cortex functional connectivity patterns in dual pathology patients were closer to healthy controls than expected.

Glucose and cholesterol stabilization in patients with type 2 diabetes mellitus with depressive and anxiety symptoms by problem-solving therapy in primary care centers in Mexico City.

Aim The aim of this study was to determine if the problem-solving therapy (PST) helps control metabolic variables in patients with type 2 diabetes mellitus (T2DM) who show depressive and anxiety symptoms. BACKGROUND: T2DM is a chronic-degenerative multifactorial disease. It is considered one of the main public health problems in the world, and it represents an important social and economic burden. It is frequently associated with major depression and anxiety disorders, which are related with high glycated hemoglobin (HbA1c) concentrations and poor metabolic control. METHOD: We initially included 123 patients diagnosed with T2DM from five primary care centers (PCC) in Mexico City. HbA1c, central glucose, and lipid profile were measured in each patient. In addition, the Kessler psychological distress scale (K-10), the Beck Depression Inventory, and the Beck Anxiety Inventory were applied at the beginning and, to those who continued, at the end of the PST, as well as four months later. Findings In total, 36 patients completed the PST and the follow-up. There was a significant decrease in depressive and anxiety symptoms (P<0.001), as well as in total cholesterol (P=0.002), HbA1c (P=0.05), and low-density lipoprotein (LDL) (P=0.022). The PST helps reduce depressive and anxiety symptoms and may help stabilize glucose and cholesterol up to four months. Further studies on this area are recommended. If our findings are confirmed, the PST could help improve the quality of life of thousands of individuals with psychiatric-metabolic co-morbidity who only visit PCC.

Clinical improvement in patients with borderline personality disorder after treatment with repetitive transcranial magnetic stimulation: preliminary results.

OBJECTIVE: Current treatment of borderline personality disorder (BPD) consists of psychotherapy and pharmacological interventions. However, the use of repetitive transcranial magnetic stimulation (rTMS) could be beneficial to improve some BPD symptoms. The objective of this study was to evaluate clinical improvement in patients with BPD after application of rTMS over the right or left dorsolateral prefrontal cortex (DLPFC). METHOD: Twenty-nine patients with BPD from the National Institute of Psychiatry, Mexico, were randomized in two groups to receive 15 sessions of rTMS applied over the right (1 Hz, n=15) or left (5 Hz, n=14) DLPFC. Improvement was measured by the Clinical Global Impression Scale for BPD (CGI-BPD), Borderline Evaluation of Severity Over Time (BEST), Beck Depression Inventory (BDI), Hamilton Anxiety Rating Scale (HAM-A), and Barratt Impulsiveness Scale (BIS). RESULTS: Intragroup comparison showed significant (p < 0.05) reductions in every psychopathologic domain of the CGI-BPD and in the total scores of all scales in both groups. CONCLUSIONS: Both protocols produced global improvement in severity and symptoms of BPD, particularly in impulsiveness, affective instability, and anger. Further studies are warranted to explore the therapeutic effect of rTMS in BPD. CLINICAL TRIAL REGISTRATION: NCT02273674

Human neural stem/progenitor cells derived from the olfactory epithelium express the TrkB receptor and migrate in response to BDNF.

Neurogenesis constitutively occurs in the olfactory epithelium of mammals, including humans. The fact that new neurons in the adult olfactory epithelium derive from resident neural stem/progenitor cells suggests a potential use for these cells in studies of neural diseases, as well as in neuronal cell replacement therapies. In this regard, some studies have proposed that the human olfactory epithelium is a source of neural stem/progenitor cells for autologous transplantation. Although these potential applications are interesting, it is important to understand the cell biology and/or whether human neural stem/progenitor cells in the olfactory epithelium sense external signals, such as brain-derived neurotrophic factor (BDNF), that is also found in other pro-neurogenic microenvironments. BDNF plays a key role in several biological processes, including cell migration. Thus, we characterized human neural stem/progenitor cells derived from the olfactory epithelium (hNS/PCs-OE) and studied their in vitro migratory response to BDNF. In the present study, we determined that hNS/PCs-OE express the protein markers Nestin, Sox2, Ki67 and ßIII-tubulin. Moreover, the doubling time of hNS/PCs-OE was approximately 38h. Additionally, we found that hNS/PCs-OE express the BDNF receptor TrkB, and pharmacological approaches showed that the BDNF-induced (40ng/ml) migration of differentiated hNS/PCs-OE was affected by the compound K252a, which prevents TrkB activation. This observation was accompanied by changes in the number of vinculin adhesion contacts. Our results suggest that hNS/PCs-OE exhibit a migratory response to BDNF, accompanied by the turnover of adhesion contacts.

Vascular endothelial growth factor influences migration and focal adhesions, but not proliferation or viability, of human neural stem/progenitor cells derived from olfactory epithelium.

In humans, new neurons are continuously added in the olfactory epithelium even in the adulthood. The resident neural stem/progenitor cells (hNS/PCs-OE) in the olfactory epithelium are influenced by several growth factors and neurotrophins. Among these modulators the vascular endothelial growth factor (VEGF) has attracted attention due its implicated in cell proliferation, survival and migration of other type of neural/stem progenitor cells. Interestingly, VEGFr2 receptor expression in olfactory epithelium has been described in amphibians but not in humans. Here we show that VEGFr is expressed in the hNS/PCs-OE. We also investigated the effect of VEGF on the hNS/PCs-OE proliferation, viability and migration in vitro. Additionally, pharmacological approaches showed that VEGF (0.5 ng/ml)-stimulated migration of hNS/PCs-OE was blocked with the compound DMH4, which prevents the activation of VEGFr2. Similar effects were found with the inhibitors for Rac (EHT1864) and p38MAPK (SB203850) proteins, respectively. These observations occurred with changes in focal adhesion contacts. However, no effects of VEGF on proliferation or viability were found in hNS/PCs-OE. Our results suggest that hNS/PCs-OE respond to VEGF involving VEGFr2, Rac and p38MAPK.