Ultrahypofractionation in postoperative radiotherapy for breast cancer: A single-institution retrospective cohort series.

BACKGROUND: The 'FAST-forward', study published in April 2020, demonstrated the effectiveness of an extremely hypofractionated radiotherapy schedule, delivering the total radiation dose in five sessions over the course of 1 week. We share our department's experience regarding patients treated with this regimen in real-world clinical settings, detailing outcomes related to short-term toxicity and efficacy. METHODS: A descriptive observational study was conducted on 160 patients diagnosed with breast cancer. Between July 2020 and December 2021, patients underwent conservative surgery followed by a regimen of 26 Gy administered in five daily fractions. RESULTS: The median age was 64 years (range: 43-83), with 82 patients (51.3%) treated for left-sided breast cancer, 77 patients (48.1%) for right-sided breast cancer, and 1 instance (0.6%) of bilateral breast cancer. Of these, 66 patients had pT1c (41.3%), 70.6% were infiltrative ductal carcinomas, and 11.3% were ductal carcinoma in situ. Most tumours exhibited intermediate grade (41.9%), were hormone receptor positive (81.3%), had low Ki-67 (Ki-67 < 20%; 51.9%) and were Her 2 negative (85%). The majority of surgical margins were negative (99.4%). Among the patients, 72.5% received hormonotherapy, and 23.8% received chemotherapy. Additionally, 26 patients (16.3%) received an additional tumour boost following whole breast irradiation (WHBI) of 10 Gy administered in five sessions of 2 Gy over a week. The median planning target volume (PTV) was 899 cm3 (range: 110-2509 cm3). Early toxicity was primarily grade I radiodermatitis, affecting 117 patients (73.1%). During a median follow-up of 15 months (range: 3.9-28.77), only one patient experienced a local relapse, which required mastectomy. CONCLUSIONS: The implementation of this highly hypofractionated regimen in early-stage breast cancer appears feasible and demonstrates minimal early toxicity. However, a more extended follow-up duration would be required to evaluate long-term toxicity and efficacy accurately.

Influence of the microbiome on radiotherapy-induced oral mucositis and its management: A comprehensive review.

Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting more than 65% of patients. Oral microbiota significantly changes during cancer therapy and appears to be involved on its pathophysiology. This review aims to present a comprehensive update of new etiopathogenic factors and treatments that may decrease the incidence of mucositis, mainly modifications of dietary interventions to modify microbiome. Despite advances in recent years, its management is mainly symptomatic opioid-based with variable results on different substances analyzed for its prevention. Immunonutrition seems to play a significant role, particularly the supplementation of compounds such as fatty acids, polyphenols or selected probiotics have shown to promote commensal bacteria diversity and reduced incidence of ulcerative mucositis. Modification of the microbiome is a promising preventive treatment for mucositis although its evidence is still scarce. Large studies are needed to demonstrate the efficacy of interventions on microbiome and its clinical impact on radiation-induced mucositis.

Maintaining Factors of Anorexia Nervosa Addressed from a Psychotherapeutic Group for Parents: Supplementary Report of a Patient's Therapeutic Success.

(1) Background: Anorexia nervosa is an eating disorder (ED) where up to 30% of individuals remain unresponsive to treatments, whether they partially respond, or do respond and later relapse. It has been broadly reported how presenting maladaptive family functioning and communication style contributes to treatment drop-out, poor treatment compliance, and poor long-term outcomes. We studied the mother and father of a patient with AN, binge-purge subtype (according to DSM-IV TR) who achieved remission after her parents but not her attended an intervention through a psychotherapy group for parents (PGP). (2) Methods: We previously reported this patient's case report, and now, through an Interpretative Phenomenological Analysis (IPA) approach, we aimed to explore the understanding and meanings ascribed by the mother and father to their experience at the PGP and to their daughter's clinical and functional improvement. (3) Results: We identified two main stages along the process: one related to the presence of maintaining factors of their daughter's disorder, and the other related to the emergence of a reflective function and to the implementation of behavioral, emotional and cognitive changes. (4) Conclusions: The interview revealed both parents' experience at the PGP promoted a change process, where they were able to modify their previous style of communication and functioning, and to identify them as a contributors to maintain their daughter's disorder. Reflective function (RF) emerged in the mother and father throughout the psychotherapeutic process. Both parents also revealed some elements that were intergenerationally transmitted, that affected three generations and contributed to maintaining the ED. We observed the multilevel open-group structure of the PGP, enhancing the mother's and father's change process.

Parent-Focused Psychotherapy for the Preventive Management of Chronicity in Anorexia Nervosa: A Case Series.

BACKGROUND: Anorexia nervosa (AN) is a complex eating disorder where involvement of family plays a central role in first line treatment in adolescents, but which is not so for adults where poor response to treatment is frequent. Given the reluctance of some patients to receive treatment, we set out to explore the hypothesis that certain family dynamics may be involved in the maintenance of the disorder. METHODS: We aimed to understand what is underlying in the cases of patients who present clinical improvement with their parents, but not the ones who received a parent-focused psychotherapeutic intervention. We conducted a mixed methods study. On the one hand we performed a case series of 14 patients who dropped out of treatment while their parents actively attended the intervention, and on the other hand, we followed the evolution of the parents of those patients reluctant to continue treatment, through non-participant observation. RESULTS: We present preliminary evidence where we found the parent-focused psychotherapeutic intervention was able to elicit a reflective function of the parents. We also observed that the intervention modified certain family dynamics that could be related to maintaining factors of the disorder. In patients, we found that in parallel to the assistance of their parents to psychotherapeutic treatment, and even when they were receiving no intervention, they showed significant clinical improvement of symptomatology and global functioning; we observed 9 of 14 of them who voluntarily decided to return to pharmacological treatment. CONCLUSIONS: This parent-focused intervention elicited changes in reflective functioning of participant parents; the intervention produced favorable changes in family dynamics, which we believe is probably related to improvement of global functioning, symptomatology, and insight of patients.

Oligometastatic non-small cell lung cancer: Current management.

BACKGROUND: In the past decade, major developments have improved the survival of patients with oligometastatic non-small cell lung cancer (NSCLC). About 20% - 50% of patients with NSCLC present with oligometastases at diagnosis. For this group of patients, it seems that an increase in survival would justify aggressive local therapies. The development of minimally invasive surgery and advanced radiotherapy techniques like stereotactic body radiation therapy (SBRT) makes local control possible for selected patients with metastatic NSCLC. The advantage of SBRT over surgery is that it is a non-invasive technique, with minimum side effects, and is more suitable for fragile and elderly patients, non-candidates for surgery, or patients who refuse surgery. AIM: The purpose of this review is to summarize the latest scientific evidence on the management of oligometastatic NSCLC, focusing on the role of radiotherapy. RELEVANCE FOR PATIENTS: The initial treatment recommended for patients with oligometastatic NSCLC is systemic therapy. Patients should be considered for radical treatment to both the primary tumor and oligometastases. Aggressive local therapy comprises surgery and/or definitive radiotherapy such as SRS or SBRT, and may be preceded or followed by systemic treatment. Recent clinical evidence from Phase II trials reports benefits in terms of PFS in patients with good performance status and long disease-free periods, with good response to systemic therapy, especially in EGFR wild-type tumors. Phase I and II trials have shown that radiotherapy combined with immunotherapy can improve tumor response rate and possibly overall survival. The recommendation is also to include OM patients in ongoing clinical trials.

Group family psychotherapy during relapse. Case report of a novel intervention for severe and enduring anorexia nervosa / Psicoterapia familiar grupal durante la recaída. Caso clínico de una intervención novedosa para la anorexia nerviosa grave y duradera

Abstract Background Anorexia nervosa is a complex and highly variable disorder. Preventing patients from becoming resistant to treatments is fundamental since an important percentage develops a severe and enduring disorder; and because relapse is highly associated with psychiatric comorbidity, poor prognosis, and serious medical consequences due to malnutrition. Contemporary treatments for anorexia nervosa support the benefits of involving the family in treatment, and although the gold standard of family psychotherapy offers an excellent option for anorexia nervosa, that intervention is aimed at early stages, and therapeutic options for later stages of the disorder are reduced and not clearly established. Objective Expose the therapeutic effect of the protocol for severe and enduring cases of anorexia nervosa at relapse, used at the Clinic of Eating Behavior of the National Institute of Psychiatry, Ramón de la Fuente Muñiz, whose theoretical foundation is systemic therapy. Method To develop this case report, we carried out an in-depth review of the clinical records, and of the clinic attendance records of the case presented here. CARE clinical case report guidelines format were used. Results The case shows how a young woman, diagnosed with anorexia nervosa with clinical signs of severe and enduring anorexia nervosa (SE-AN), was able to achieve symptomatic remission after her parents, but not her, were administered the protocol for SE-AN. Discussion and conclusion Here we present an emblematic case showing the importance of getting the parents involved in the treatment of anorexia nervosa.

Resumen Antecedentes La anorexia nervosa es un trastorno complejo y muy variable. Evitar que los pacientes se vuelvan resistentes a los tratamientos es fundamental, pues un porcentaje importante desarrolla un trastorno grave y duradero; adicionalmente, la recaída está muy asociada con una alta comorbilidad psiquiátrica, un mal pronóstico y graves consecuencias médicas debido a la desnutrición. El tratamiento actual de la anorexia nervosa respalda los beneficios de involucrar a la familia en el tratamiento, y, aunque el estándar de oro en psicoterapia familiar ofrece una excelente opción para la anorexia nervosa, dicha intervención está orientada a etapas tempranas y las opciones para las etapas tardías del trastorno son reducidas, además de no estar claramente establecidas. Objetivo Exponer el efecto terapéutico del protocolo para casos graves y duraderos de anorexia nervosa en recaída, de la Clínica de Trastornos de la Conducta Alimentaria (CTA) del Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, cuya base teórica es la terapia sistémica. Método Para integrar este caso, realizamos una revisión a fondo del expediente clínico y de los registros asistenciales del caso que aquí presentamos. Se utilizó el formato de reporte de caso de las guías CARE. Resultados El caso muestra cómo una joven, con signos clínicos de anorexia nervosa grave y duradera (AN-GD), pudo lograr remisión sintomatológica después de que sus padres, pero no ella, recibieran tratamiento con el protocolo para AN-GD. Discusión y conclusión Aquí presentamos un caso emblemático que muestra la importancia de involucrar a los padres en el tratamiento de la anorexia nervosa.

Importance of dose in palliative treatment for incurable head and neck cancer with radiotherapy.

PURPOSE: To identify predictors of palliation for head and neck cancer treated with the "Hypo Trial" hypofractionated radiation therapy regimen in a clinical setting. DESIGN/METHOD: We retrospectively assessed 106 consecutive patients with incurable cancer, treated between January 2008 and December 2018. Regimen used was 30-36Gy in 5-6 biweekly fractions of 6Gy. RESULTS: The prescription dose was 30Gy in 57 (53.8%) patients and 36Gy in 49 (46.2%) patients. 89.6% patients completed the prescribed treatment. With a median follow-up of 6.92 months, 79.2% of the patients experienced clinical palliation. Palliation was correlated with the radiation therapy dose (P = 0.05). Median overall and progression-free survival (OS, PFS) were 7 and 4.63 months, respectively. Achieving palliation was associated to OS (P = 0.01). CONCLUSIONS: This short palliative hypofractionated scheme resulted in a high rate of palliation, with excellent compliance and acceptable toxicity. Our results show that radiation dose is a predictive factor for palliation.

Evaluation of blood mercury and serum selenium levels in the pregnant population of the Community of Madrid, Spain.

BACKGROUND: The main exposure route to methylmercury (MeHg) is from eating fish and shellfish containing this compound. Since 2004, women of childbearing age in Spain have been urged not to eat some species (eg, tuna, shark, and swordfish), instead choosing low-MeHg seafood as part of a healthy diet. OBJECTIVE: To describe maternal total blood mercury (THg) and serum selenium (Se) in a cohort of pregnant women living in Spain as it relates to fish intake during the three trimesters and to assess whether or not Spanish women of childbearing age follow the recommendations listed in fish advisories and choose fish species with lower mercury levels. METHODS: We studied 141 female volunteers of childbearing age (16-45 years), interviewing all participants about their overall eating habits and seafood intake. Hg and Se levels were tested using cold-vapor atomic absorption spectrometry (CVAAS) and electrothermal atomic absorption spectrometry (ETAAS), respectively. RESULTS: Average THg levels in pregnant women were 2.89 µg/L (standard deviation [SD], 2.75 µg/L, geometric mean [GM], 2.19 µg/L), and THg GM was positively associated with fish intake. Mean Se levels in pregnant women were 73.06 µg/L (SD, 13.38 µg/L), and Se levels were found to increase with tuna intake. In 16 (12%) pregnant women, THg was higher than the level recommended by the U.S. Environmental Protection Agency (EPA) (6.4 µg/L). A positive association was also found between THg and serum Se. CONCLUSION: Women of childbearing age in Spain had higher THg levels than women in other Western studies. Our study observed that 12% of women had THg levels above the safety limit set by the EPA (6.4 µg/L), and 31% had levels above the relevant benchmark level of 3.5 µg/L suggested by various researchers.

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.

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

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.

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.

Should pathological gambling and obesity be considered addictive disorders? A factor analytic study in a nationally representative sample.

OBJECTIVE: Pathological gambling (PG) is now aligned with substance use disorders in the DSM-5 as the first officially recognized behavioral addiction. There is growing interest in examining obesity as an addictive disorder as well. The goal of this study was to investigate whether epidemiological data provide support for the consideration of PG and obesity as addictive disorders. METHOD: Factor analysis of data from a large, nationally representative sample of US adults (N=43,093), using nicotine dependence, alcohol dependence, drug dependence, PG and obesity as indicators. It was hypothesized that nicotine dependence, alcohol dependence and drug use dependence would load on a single factor. It was further hypothesized that if PG and obesity were addictive disorders, they would load on the same factor as substance use disorders, whereas failure to load on the addictive factor would not support their conceptualization as addictive disorders. RESULTS: A model with one factor including nicotine dependence, alcohol dependence, drug dependence and PG, but not obesity, provided a very good fit to the data, as indicated by CFI=0.99, TLI=0.99 and RMSEA=0.01 and loadings of all indicators >0.4. CONCLUSION: Data from this study support the inclusion of PG in a latent factor with substance use disorders but do not lend support to the consideration of obesity, as defined by BMI, as an addictive disorder. Future research should investigate whether certain subtypes of obesity are best conceptualized as addictive disorders and the shared biological and environmental factors that account for the common and specific features of addictive disorders.

Análisis de fuentes del EEG en pacientes tratados con estimulación magnética transcraneal a 5 Hz como tratamiento antidepresivo / Electroencephalographic source analysis in patients receiving 5-Hz transcranial magnetic stimulation as antidepressant treatment

Transcranial Magnetic Stimulation (rTMS) is a technique that allows noninvasive electrical stimulation of the cortex with few side effects. An antidepressant effect has been proposed when rTMS is delivered over prefrontal dorsolateral cortex (DLPFC) ≥5Hz. Quantitative EEG studies have shown increases in alpha and theta power bands as well as frontal interhemispheric asymmetries in most recordings from depressed patients. rTMS over left DLPFC at 5Hz involve a safer and more tolerable procedure, and its neurophysiological correlates has not been explored using EEG source analysis. The aim of this research was to study changes in EEG sources using VARTERA method in a group of patients with major depressive disorder (MDD) treated with 5Hz rTMS over left DLPFC as single or combined treatment with escitalopram. Methods 18 patients with DSM-IV MDD diagnosis without treatment for the current episode were included. Subjects were randomly assigned to one of two groups: A) rTMS+escitalopram 10mg, n=9; B) rTMS+placebo, n=9. Subjects received 15 sessions of rTMS on a daily basis. In order to compare changes in EEG sources two recordings were obtained, prior and after treatment. HDRS, BDI and HARD were used for clinical assessments. Results All patients of group A and eight patients of group B showed response to treatment (considered as a reduction of 50% in HDRS score). An increase in absolute power at 9.37Hz and 10.17Hz in temporal and postcentral gyrus on the left hemisphere was found in group B. Absolute power in those frequencies was decreased in the same regions for group A. In addition, an increased power in beta band frequencies was observed in both hemispheres for group A. Conclusion Increases in alpha band could be the hallmark of the 5Hz rTMS, but it could be reduced by escitalopram. Besides, increases observed in beta band for group A could be related to escitalopram effect.

La estimulación magnética transcraneal repetitiva (EMTr) es una técnica que permite estimular eléctricamente la corteza cerebral de manera no invasiva y con pocos efectos secundarios. Se ha propuesto que la EMTr aplicada sobre la corteza prefrontal dorsolateral (CPFDL) izquierda con frecuencias ≥5Hz tiene efectos antidepresivos. Se ha encontrado que en el electroencefalograma cuantitativo (QEEG por sus siglas en inglés) la mayoría de pacientes deprimidos presentan incrementos en las bandas theta y alfa, así como asimetrías interhemisféricas en la actividad alfa en regiones anteriores. La EMTr sobre la CPFDL izquierda a 5Hz ofrece ventajas considerables en seguridad y tolerabilidad; sin embargo, sus correlatos neurofisiológicos no han sido explorados por el análisis de fuentes del EEG. Objetivo Estudiar los cambios en las fuentes del EEG según el método VARETA en un grupo de pacientes con trastorno depresivo mayor que recibieron EMTr a 5Hz sobre la corteza prefrontal dorsolateral izquierda como tratamiento único o en combinación con escitalopram. Material y métodos Se estudiaron 18 pacientes con diagnóstico de trastorno depresivo mayor de acuerdo con los criterios del DSM-IV sin tratamiento para el episodio en curso. Los sujetos habían sido aleatoriamente asignados a uno de los siguientes grupos de tratamiento: A) EMTr+escitalopram 10mg, n=9; B) EMTr+placebo, n=9. Se aplicó EMTr, a 5Hz en una sesión diaria durante 15 días. Se obtuvieron dos registros electroencefalográficos, uno basal y otro final, con el fin de comparar los cambios en las fuentes de actividad eléctrica cerebral, pretratamiento y post-tratamiento. Se realizaron evaluaciones clinimétricas con las escalas de Hamilton para Depresión y Ansiedad y el Inventario de Depresión de Beck. Resultados Todos los pacientes en el grupo A y ocho pacientes en el grupo B respondieron al tratamiento, con una reducción de 50% o más en la escala HDRS. En el análisis de fuentes se encontró un efecto en el grupo B caracterizado por incremento en la PA de 9.37 a 10.17Hz, en regiones temporales y giro poscentral izquierdos, mismo que se encontró disminuido en el grupo A, Además se encontró un incremento en fracuencias correspondientes a la banda beta en regiones frontales de ambos hemisferios en el grupo A. Conclusiones Podría considerarse que el incremento en la banda alfa es característico de la EMTr a 5Hz, mismo que se ve reducido por efecto del escitalopram. Por otro lado, se observó que el grupo A mostró incrementos en fuentes correspondientes a la banda beta como posible efecto relacionado del fármaco antidepresivo.

Clinical and electrophysiological effect of right and left repetitive transcranial magnetic stimulation in patients with major depressive disorder / Efecto clínico y electrofisiológico de la estimulación magnética transcraneal repetitiva derecha e izquierda en pacientes con transtorno depresivo mayor

Major Depressive Disorder (MDD) is a common psychiatric disorder that represents one of the main public health problems worldwide. It has been projected that for 2020 it will be the second cause of disability-adjusted life years just below ischemic heart disease. Quantitative electroencephalogram provides the opportunity to study cortical oscillatory activity across the different frequency bands. It constitutes an accessible tool to explore the clinical and neurophysiologic correlates underlying psychiatric disorders as well as the effect of diverse therapeutic options and the performance through cognitive tasks. Repetitive transcranial magnetic stimulation is a technique that allows the stimulation of the cerebral cortex noninvasively, relatively painlessly and with fairly few side effects. The vast majority of rTMS studies target left dorsolateral prefrontal cortex (DLPFC) based on imaging studies showing that left prefrontal cortex dysfunction is pathophysiologically linked to depression. However, there is some evidence implicating right PFC in the pathophysiology of depression. Comparison of antidepressant efficacy of diverse stimulation frequencies is relevant since a main concern around rTMS is its potential to induce seizures; hence we consider that frequency of stimulation is an important aspect to be studied. For this study we aimed to elucidate the clinical efficacy of rTMS comparing two groups of depressed patients stimulated over DLPFC, one over the left (at 5 Hz) and other over the right (at 1 Hz). We also meant to know if there were clinical and electroencephalographic differential long-term after-effects between those groups of treatment. We included twenty right-handed patients with a DSM-IVR diagnosis of MDD. They were assigned into two groups of treatment. Group 1 received 5Hz rTMS over the left DLPFC. Group 2 received 1Hz rTMS over the right DLPFC. We obtained two EEG measurements in order to analyze Z score of broad-band spectral parameters and cross-spectral. No statistical differences among groups were found in response to treatment after weekly comparisons of clinimetric scores and significant differences between baseline and final assessment by HDRS, MADRS, BDI and HARS. The major rTMS effect on EEG was observed in the group that received 1 Hz over the right DLPFC and no significant effects were observed for the group that received 5 Hz over the left DLPFC. Our results propose that administration of 15 sessions on either left (5 Hz) or right (1 Hz) rTMS over DLPFC is sufficient to reach response to treatment, assessed by HDRS, MADRS, BDI and HARS in subjects with MDD. Moreover, in both cases rTMS was able to induce an equivalent antidepressant effect. The major effect of rTMS on EEG was observed in the right 1 Hz rTMS group where changes were elicited mainly over frontal, central and temporal regions on alpha and particularly beta frequency bands. In a lesser extent for left 5 Hz rTMS group the main effect was observed on anterior regions for beta and particularly alpha frequency bands. We believe it is pertinent to continue exploring the therapeutic potential of lower stimulation frequencies, for what further research including larger samples is still necessary to confirm these trends.

El trastorno depresivo mayor es una entidad psiquiátrica que representa uno de los principales problemas de salud pública a nivel mundial. Se ha proyectado que para el año 2020 será la segunda causa de discapacidad únicamente por debajo de la cardiopatía isquémica. La utilización del electroencefalograma cuantitativo ofrece la oportunidad de estudiar la actividad oscilatoria cortical a través de las diferentes bandas de frecuencias. Éste constituye una herramienta para explorar las características clínicas y neurofisiológicas que subyacen a los trastornos psiquiátricos, así como un instrumento para evaluar el efecto de diversas opciones terapéuticas y el desempeño de los sujetos durante la realización de tareas cognitivas. La estimulación magnética transcraneal repetitiva (EMTr) es una técnica que permite la estimulación de la corteza cerebral de manera no invasiva, relativamente sin dolor y con pocos efectos secundarios. Con base en los estudios de neuroimagen que vinculan la fisiopatología de la depresión con disfunción en la corteza prefrontal dorsolateral (CPFDL), la mayoría de las investigaciones se han enfocado en estimular dicha corteza en el hemisferio izquierdo. No obstante, existen pruebas que implican a la corteza prefrontal derecha con la fisiopatología de la depresión. La relevancia de comparar la eficacia antidepresiva de diversas frecuencias radica en el hecho de que un tema de interés particular alrededor de la EMTr es su potencial para inducir convulsiones, por ello consideramos que la exploración de las diversas frecuencias de estimulación con efecto terapéutico constituye un aspecto importante de estudio. Para este trabajo nos propusimos determinar la eficacia antidepresiva de la EMTr comparando dos grupos de pacientes que fueron estimulados en la CPFDL derecha a 1 Hz o en la izquierda a 5 Hz. También buscamos dilucidar si existen diferencias clínicas y electroencefalográficas a largo plazo entre grupos de tratamiento. Para este estudio se incluyeron 20 pacientes con diagnóstico de trastorno depresivo mayor de acuerdo con los criterios del DSM-I V. Los sujetos fueron asignados aleatoriamente a uno de dos grupos de tratamiento. Un grupo recibió EMTr sobre la CPFDL izquierda a 5Hz; el otro recibió estimulación a 1 Hz sobre la corteza contralateral. Se obtuvieron dos registros electroencefalográficos, uno basal y otro final, con el fin de comparar las medidas espectrales de banda ancha y estrecha, pretratamiento y postratamiento. Se realizaron evaluaciones clinimétricas con las escalas de Hamilton para Depresión y Ansiedad, la escala de Depresión de Montgomery-Asberg y el Inventario de Beck. No encontramos diferencias significativas al comparar la respuesta a la EMTr entre ambos grupos. Los pacientes de ambos grupos presentaron respuesta a tratamiento (disminución de ≥50% de la sintomatología depresiva) medida por clinimetría. El efecto más importante de la EMTr sobre el EEG se observó en el grupo de estimulación derecha a 1 Hz donde encontramos disminución postratamiento en los valores Z de banda estrecha alfa y beta, principalmente en regiones fronto-centro-temporales. Aunque en menor proporción, en el grupo de estimulación izquierda a 5 Hz encontramos incrementos significativos post EMTr, predominantemente en las bandas beta y alfa sobre todo en regiones anteriores. No se encontraron resultados significativos en el análisis de banda ancha. Nuestros resultados sugieren que la administración de 15 sesiones de EMTr ya sea sobre la CPFDL derecha (1 Hz) o izquierda (5 Hz) es capaz de lograr respuesta antidepresiva. Nuestros hallazgos electrofisiológicos sugieren que uno de los efectos a largo plazo de la EMTr es la reorganización de los circuitos neuronales implicados en la depresión.

Premorbid adjustment in schizophrenia and schizoaffective disorder.

There is evidence that premorbid adjustment can differentiate schizophrenia from schizoaffective disorder. We recruited 41 patients with schizophrenia and 24 patients with schizoaffective disorder without substance abuse 6 months before the assessment. Diagnoses were based on the Structured Clinical Interview for DSM-IV. Psychotic symptoms were rated with the Positive and Negative Syndrome Scale, the Calgary Depression Scale was used to assess depressive symptoms, and the Global Assessment of Functioning Scale was used to rate global psychosocial functioning. Premorbid adjustment was evaluated with the Premorbid Adjustment Scale. Patients with schizophrenia showed worse premorbid adjustment compared with the patients with schizoaffective disorder. The areas of "peer relationships" and "scholastic performance" showed deficits in schizophrenia. Significant associations were found between premorbid adjustment life periods and symptom severity in both groups. Differences found between groups may be related to an earlier illness onset in the schizophrenic group. Premorbid adjustment may be a useful clinical feature to differentiate schizoaffective disorder from schizophrenia.

The P50 auditory evoked potential in violent and non-violent patients with schizophrenia.

BACKGROUND: Emotionally driven violence is facilitated by increased arousal. It may be a consequence of an information-processing deficit and the cognitive attributions for the stimuli given by the subject. The aim of this study was to compare the P50 evoked potential responses of violent patients with schizophrenia with non-violent patients with schizophrenia and healthy controls. METHOD: Patients were classified into violent and non-violent in accordance to the Overt Aggression Scale. P50 auditory evoked potentials of 32 unmedicated patients with schizophrenia (violent=14, non-violent=18) and 17 healthy controls were recorded during five runs of 30 click pairs. RESULTS: Healthy controls exhibited a lower S2/S1 ratio when compared to violent (p<0.001) and non-violent (p=0.04) patients. Using a cutoff point of 0.50 for S2/S1 ratio to define abnormal gating a significant proportion of violent patients did not show P50 suppression (71.4%) in comparison to non-violent patients (38.9%) and healthy controls (23.5%) (p=0.02). CONCLUSIONS: Violent behavior in patients with schizophrenia could be associated with a disturbed information sensory gating. Violence in patients with schizophrenia may be facilitated by an increased arousal which may in turn be the result of an information-processing deficit.

Association between violent behavior and psychotic relapse in schizophrenia: once more through the revolving door? / Asociación de la conducta violenta y la recída psicótica en la esquizofrenia: ¿una vez más a través de la puerta revolvente?

Summary: The potential for violence in a number of persons with mental illnesses stimulates public fear and prevents general acceptance of persons with psychiatric disabilities. Schizophrenia has been the diagnosis most often associated with violence as it has been taken as a paradigm of insanity, incompetence and dangerousness. Clinicians' efforts to prevent violence through conventional external patient treatment are impede by several situational variables and patients become trapped in a costly cycle of repeated institutional admissions (revolving door phenomenon) in the most restrictive settings, going through involuntary in-patient treatment. The major hypothesis proposed in this review is that violence in schizophrenia can become a part of a self-perpetuating cycle, in which the combination of non-adherence to treatment and an inadequate management of illness from families and caregivers leads to violent behavior and deteriorated social relationships, finally resulting in institutional recidivism. As some of the initial symptoms of the illness, such as irritability and agitation may not be detected by the patient and his/her family, these symptoms eventually can easily escalate into open hostility, and the accompanying behavior is frequently violent. Disturbed moods secondary to psychotic symptoms, such as fear and anger apparently can also activate violent psychotic action. Accordingly, the path from the characteristics of the illness to violence leads to them through psychotic symptoms and lack of insight, and results in symptom-consistent violence. When psychotic symptoms and violent behavior cannot be managed by caregivers, patients are brought to the attention of psychiatric services and frequently admitted to patient service. During admission for a psychotic episode, there are more violent incidents than later on in the disease. As patients respond to medication and hospital environment, violent incidents and psychotic symptoms decrease in frequency and severity. After hospital discharge, patients may assume greater autonomy and control over several aspects of their daily lives. Nevertheless, this process may be hampered by familial reactions to the burden of living with a family member with schizophrenia. This burden can also be exacerbated because many patients have a history of violent behavior and families may experience negative attitudes towards them. In line with this, there is evidence of significant differences between the professionals' perception about symptoms and illness, and that of the patient and his/her family. Sometimes, these different conceptions may reflect a lack of awareness regarding illness and treatment that may lead to discontinue medication. Medication suspension can lead to an eventual relapse which most obvious sign is the emergence of positive psychotic symptoms. Nevertheless if a patient has a past history of violent behavior, it is very likely that these behaviors will appear during relapse and it may be necessary to consider hospitalization. Although treatment with antipsychotics may be useful when violence is secondary to psychotic symptoms, violence might be indirectly reduced through clinical programs aimed at increasing insight into illness and treatment. A psychoeducational strategy may improve antipsychotic treatment compliance by helping the patients to work through their ambivalence regarding antipsychotic medication. For families, a psychoeducation strategy can lead to a change in attitudes toward the disorder, as well as to promote problem-solving skills for violence. The model presented here suggests that violence in schizophrenia is conditioned by several factors such as psychotic symptoms, medication non-compliance and lack of social support. The prevention of violent behavior in schizophrenia should include attention to other areas, such as the quality of the social environment surrounding the patient. For the "revolving door" patients, violence may be a key factor that complicates treatment. Health professionals have the responsibility to work in partnership with patients and their families for the prevention of violence.

Resumen: La esquizofrenia ha sido el principal diagnóstico psiquiátrico asociado con la violencia. La prevención de la violencia a través del tratamiento ambulatorio se ha visto obstaculizada por diversas variables situacionales y muchos pacientes llegan a verse inmersos en un ciclo de continuas admisiones hospitalarias (fenómeno de la puerta revolvente). La hipótesis central de la presente revisión es que la violencia en la esquizofrenia puede formar parte de un ciclo recurrente de hospitalizaciones psiquiátricas, en el que, combinados la falta de adhesión al tratamiento y el manejo inadecuado de la enfermedad por parte de los familiares, dan por resultado la manifestación del comportamiento violento. Diversas investigaciones han mostrado que tanto los síntomas psicóticos, como las alteraciones del ánimo secundarias a su presencia y la falta de una conciencia de enfermedad, son las principales características de la esquizofrenia, asociadas con la manifestación de la violencia en dicho padecimiento. Cuando los familiares no pueden manejar los síntomas psicóticos y el comportamiento violento del paciente, se busca la atención en un servicio especializado de psiquiatría, y con frecuencia, el paciente tiene que ser hospitalizado. La manifestación de conductas violentas ha sido considerada como una de las principales causas de hospitalización psiquiátrica. Diversas investigaciones han documentado que los actos violentos se presentan con mayor frecuencia durante la admisión hospitalaria por un episodio psicótico que en otros momentos durante el curso del padecimiento. Asimismo, la hospitalización psiquiátrica pos sí misma reduce la frecuencia e intensidad de la violencia, debido probablemente al tratamiento con antipsicóticos y al entorno restrictivo de las instalaciones. Tras la alta hospitalaria, los pacientes viven un proceso de transición mediante el cual van asumiendo mayor autonomía y control sobre diversos aspectos de su vida cotidiana. Sin embargo, este proceso se puede ver obstaculizado por las reacciones familiares secundarias al desgaste físico y emocional de vivir con un familiar con esquizofrenia. Asimismo, este desgaste puede verse exacerbado debido al antecedente de violencia en muchos de estos pacientes. Se ha descrito que la percepción que tienen los pacientes y sus familiares con respecto a los síntomas de la enfermedad difiere significativamente de la de los especialistas de la salud mental. A veces, estas diferencias se asocian con falta de discernimiento y conciencia sobre la enfermedad y con la necesidad de tratamiento médico, lo que a su vez puede llevar a la suspensión del mismo. La suspensión del tratamiento farmacológico induce a una eventual recaída cuyos signos más evidentes son los síntomas psicóticos. No obstante, si un paciente tiene antecedentes de comportamiento violento, es muy probable que este comportamiento surja durante la recaída y que sea necesario considerar nuevamente la hospitalización. En estos pacientes, en quienes la violencia tiene un importante papel en las hospitalizaciones recurrentes, es necesario considerar el establecimiento de programas clínicos, que incluyan la psicoeducación, dirigidos a incrementar la conciencia del paciente y de los familiares, sobre la enfermedad y la necesidad del tratamiento farmacológico. El modelo presentado en esta revisión sugiere que la violencia en la esquizofrenia es una condición generada por diversos factores tales como los síntomas psicóticos, la falta de adherencia al tratamiento y el inadecuado apoyo social. La prevención de la conducta violenta en la esquizofrenia no sólo debe fundamentarse en el uso de antipsicóticos, ya que existen otras áreas en las que intervienen las características propias del individuo y su entorno social. Los profesionales de la salud mental tienen la responsabilidad de trabajar en conjunto con los pacientes y sus familiares para prevenir la manifestación de conductas violentas. Es necesario realizar futuros estudios dirigidos a evaluar la forma en la que los servicios de salud mental pueden ser más efectivos en la reducción y prevención de la violencia en la esquizofrenia.

[Impact of the duration of untreated psychosis among patients with a first episode: a one year follow-up study]. / Impacto de la duración de la psicosis no tratada en pacientes con primer episodio psicótico. Estudio de seguimiento a un año.

BACKGROUND: The delay on the onset of specific treatment has several prognostic implications for psychotic patients. Duration of untreated psychosis (DUP) has been considered a prognostic variable. A longer DUP has been associated with a poor clinical outcome. OBJECTIVE: To determine the DUP in a sample of first-episode psychotic patients and its relationship with recovery and relapse on a one-year follow-up study. MATERIAL AND METHODS: A sample of 66 first-episode psychotic patients was recruited and divided according to their diagnoses in affective and non-affective psychoses. Diagnoses were obtained with SCAN and DUP was registered for each patient. A clinical assessment for psychotic and affective symptoms was performed using standardized instruments. RESULTS: All patient studied showed clinical improvement during follow-up. Patients with a longer DUP showed poorer psychosocial adjustment and lower recovery indexes. Treatment suspension was the main variable associated with relapse. CONCLUSIONS: DUP is an important prognostic variable. Early detection programs are required to decrease the period between illness onset, diagnosis and treatment in first-episode psychotic patients.

Impacto de la duración de la psicosis no tratada en pacientes con primer episodio psicótico: estudio de seguimiento a un año / Impact of the duration of untreated psychosis among patients with a first episode: a one year follow-up study

Antecedentes: El retraso en la atención especializada conlleva a implicaciones pronósticas en los pacientes con trastornos psicóticos. La duración de la Psicosis No Tratada (DPNT) es un parámetro importante con valor pronóstico. Una DPNT larga se asocia con un peor pronóstico clínico. Objetivo: Determinar la DPNT en un grupo de pacientes con primer episodio psicótico y determinar su influencia en los índices de recuperación y recaída a un año de seguimiento. Material y métodos: Se incluyeron 66 pacientes en su primer episodio psicótico que agrupados en psicosis afectivas y no afectivas. El diagnóstico se efectuó con el SCAN. Se registró la DPNT y se evaluó la severidad de los síntomas psicóticos y afectivos con instrumentos validados en nuestro medio. Resultados: Se observó mejoría sindromática global en los grupos diagnósticos. Los pacientes con DPNT larga presentaron menor ajuste psicosocial global y menor índice de recuperación. La suspensión del tratamiento fue el principal predictor de las recaídas. Conclusiones: la DPNT es un importante factor asociado al pronóstico. El modelo de los estudios de detección temprana permite reducir el tiempo que tarda en tratarse la psicosis, e identificar oportunamente a los pacientes que han tenido el primer episodio psicótico.

BACKGROUND: The delay on the onset of specific treatment has several prognostic implications for psychotic patients. Duration of untreated psychosis (DUP) has been considered a prognostic variable. A longer DUP has been associated with a poor clinical outcome. OBJECTIVE: To determine the DUP in a sample of first-episode psychotic patients and its relationship with recovery and relapse on a one-year follow-up study. MATERIAL AND METHODS: A sample of 66 first-episode psychotic patients was recruited and divided according to their diagnoses in affective and non-affective psychoses. Diagnoses were obtained with SCAN and DUP was registered for each patient. A clinical assessment for psychotic and affective symptoms was performed using standardized instruments. RESULTS: All patient studied showed clinical improvement during follow-up. Patients with a longer DUP showed poorer psychosocial adjustment and lower recovery indexes. Treatment suspension was the main variable associated with relapse. CONCLUSIONS: DUP is an important prognostic variable. Early detection programs are required to decrease the period between illness onset, diagnosis and treatment in first-episode psychotic patients.