Neuropsicología del TDAH y su relación con el nivel de cortisol salival y factores psicofisiológicos cerebrales

Introducción: El trastorno por déficit de atención e hiperactividad (TDAH) se caracteriza por inatención clínicamente significativa acompañada de hiperactividad e impulsividad. Su perfil neuropsicológico muestra alteración de los procesos atencionales y ejecutivos, íntimamente relacionados con la sintomatología del trastorno. El estudio de factores biológicos asociados al funcionamiento cognitivo podría contribuir a explicar las dificultades neuropsicológicas del TDAH y su correlato comportamental. Objetivos: Estudiar la posible asociación entre los niveles de cortisol libre y factores psicofisiológicos cerebrales con el rendimiento neuropsicológico en el TDAH. Métodos: En el contexto de evaluaciones neuropsicológicas amplias de pacientes con TDAH y controles, se analizaron los resultados de la prueba AULA (evaluación neuropsicológica del TDAH con realidad virtual), se determinaron niveles de cortisol salival en intervalos de media hora y se realizó electroencefalografía cuantitativa para el cálculo del ratio theta-beta (TBR) y de la frecuencia del pico alfa (APF). Se calcularon promedios y se comprobaron posibles diferencias intergrupales. Resultados: El grupo TDAH (N=27, edad 11,2±3,3 con 74% hombres) reveló diferencias significativas respecto al grupo control (N=25, edad 9,6±2,4 con 76% hombres), mostrando menores niveles de cortisol salival, disminución de TBR y APF, menor atención sostenida y mayor número de omisiones, comisiones y actividad motora. Conclusiones: Los resultados sugieren que el bajo rendimiento atencional, pobre control de impulsos y elevada actividad motora del grupo TDAH podría estar relacionada con hipoactivación cortical generalizada y una menor actividad del eje hipotálamo-hipofisario-adrenal. Estos hallazgos podrían contribuir a profundizar en el conocimiento de los aspectos psicobiológicos del TDAH.2022-2

Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment

The effect of HF-rTMS over the left DLPFC on stress regulation as measured by cortisol and heart rate variability

The prefrontal cortex, and especially the Dorsolateral Prefrontal Cortex (DLPFC), plays an inhibitory role in the regulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis under stressful situations. Moreover, recent evidence suggests that a sustained DLPFC activation is associated with adaptive stress regulation in anticipation of a stressful event, leading to a reduced stress-induced amygdala response, and facilitating the confrontation with the stressor. However, studies using experimental manipulation of the activity of the DLPFC before a stressor are scarce, and more research is needed to understand the specific role of this brain area in the stress-induced physiological response. This pre-registered study investigated the effect on stress regulation of a single excitatory high frequency (versus sham) repetitive transcranial magnetic stimulation (HF-rTMS) session over the left DLPFC applied before the Trier Social Stress Test in 75 healthy young women (M = 21.05, SD = 2.60). Heart rate variability (HRV) and salivary cortisol were assessed throughout the experimental protocol. The active HFrTMS and the sham group showed a similar cognitive appraisal of the stress task. No differences in HRV were observed during both the anticipation and the actual confrontation with the stress task and therefore, our results did not reflect DLPFC-related adaptive anticipatory adjustments. Importantly, participants in the active HF-rTMS group showed a lower cortisol response to stress. The effect of left prefrontal HF-rTMS on the stress system provides further critical experimental evidence for the inhibitory role played by the DLPFC in the regulation of the HPA axis

Constitutive hippocampal cholesterol loss underlies poor cognition in old rodents

Cognitive decline is one of the many characteristics of aging. Reduced long-term potentiation (LTP) and long-term depression (LTD) are thought to be responsible for this decline, although the precise mechanisms underlying LTP and LTD dampening in the old remain unclear. We previously showed that aging is accompanied by the loss of cholesterol from the hippocampus, which leads to PI3K/Akt phosphorylation. Given that Akt de-phosphorylation is required for glutamate receptor internalization and LTD, we hypothesized that the decrease in cholesterol in neuronal membranes may contribute to the deficits in LTD typical of aging. Here, we show that cholesterol loss triggers p-Akt accumulation, which in turn perturbs the normal cellular and molecular responses induced by LTD, such as impaired AMPA receptor internalization and its reduced lateral diffusion. Electrophysiology recordings in brain slices of old mice and in anesthetized elderly rats demonstrate that the reduced hippocampal LTD associated with age can be rescued by cholesterol perfusion. Accordingly, cholesterol replenishment in aging animals improves hippocampal-dependent learning and memory in the water maze test.publishedVersionFil: Martín, Mauricio Gerardo. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Martín, Mauricio Gerardo. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Martín, Mauricio Gerardo. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Ahmed, Tariq. Katholieke Universiteit Leuven. Faculty of Psychology and Educational Sciences. Laboratory of Biological Psychology; Bélgica.Fil: Korovaichuk, Alejandra. Consejo Superior de Investigaciones Científicas. Instituto Cajal. Departamento de Neurobiología Funcional y de Sistemas; España.Fil: Venero, César. Universidad Nacional de Educación a Distancia. Facultad de Psicología. Departamento de Psicobiología; España.Fil: Menchón, Silvia Adriana. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Menchón, Silvia Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Física Enrique Gaviola; Argentina.Fil: Menchón, Silvia Adriana. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; Argentina.Fil: Salas, Isabel. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Salas, Isabel. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Salas, Isabel. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Munck, Sebastian. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Fil: Herreras, Oscar. Consejo Superior de Investigaciones Científicas. Instituto Cajal. Departamento de Neurobiología Funcional y de Sistemas; España.Fil: Balschun, Detlef. Katholieke Universiteit Leuven. Faculty of Psychology and Educational Sciences. Laboratory of Biological Psychology; Bélgica.Fil: Dotti, Carlos Gerardo. Consejo Superior de Investigaciones Científicas. Centro de Biología Molecular Severo Ochoa; España.Fil: Dotti, Carlos Gerardo. Universidad Autónoma de Madrid. Centro de Biología Molecular Severo Ochoa; España.Fil: Dotti, Carlos Gerardo. Katholieke Universiteit Leuven. Center for Human Genetics. VIB Center for the Biology of Disease; Bélgica.Biofísic

Differential Susceptibility to the Impact of the COVID-19 Pandemic on Working Memory, Empathy, and Perceived Stress: The Role of Cortisol and Resilience

There are important individual differences in adaptation and reactivity to stressful challenges. Being subjected to strict social confinement is a distressful psychological experience leading to reduced emotional well-being, but it is not known how it can affect the cognitive and empathic tendencies of different individuals. Cortisol, a key glucocorticoid in humans, is a strong modulator of brain function, behavior, and cognition, and the diurnal cortisol rhythm has been postulated to interact with environmental stressors to predict stress adaptation. The present study investigates in 45 young adults (21.09 years old, SD = 6.42) whether pre-pandemic diurnal cortisol indices, overall diurnal cortisol secretion (AUCg) and cortisol awakening response (CAR) can predict individuals’ differential susceptibility to the impact of strict social confinement during the Coronavirus Disease 2019 (COVID-19) pandemic on working memory, empathy, and perceived stress. We observed that, following long-term home confinement, there was an increase in subjects’ perceived stress and cognitive empathy scores, as well as an improvement in visuospatial working memory. Moreover, during confinement, resilient coping moderated the relationship between perceived stress scores and pre-pandemic AUCg and CAR. In addition, in mediation models, we observed a direct effect of AUCg and an indirect effect of both CAR and AUCg, on change in perceived self-efficacy. These effects were parallelly mediated by the increase in working memory span and cognitive empathy. In summary, our findings reveal the role of the diurnal pattern of cortisol in predicting the emotional impact of the COVID-19 pandemic, highlighting a potential biomarker for the identification of at-risk groups following public health crises

Effectiveness of the rifaximin for the treatment of irritable bowel syndrome

OBJETIVO. Determinar la eficacia y seguridad de la rifaximina en un grupo de pacientes con el diagnóstico de síndrome del intestino irritable (SII). MATERIAL Y MÉTODOS. Se realizó un estudio observacional, prospectivo, longitudinal, multicéntrico y descriptivo, entre marzo 2015 y enero 2016. La población de estudio fueron los adultos mayores de 18 años que acudían a consulta ambulatoria de médicos gastroenterólogos. Los pacientes cumplían los criterios de inclusión de Roma III como criterio diagnóstico de SII y subtipos. RESULTADOS. Se encuestó a 221 pacientes, de los cuales 24 no completaron la visita de seguimiento. Asimismo, 14 fichas de recolección de datos no fueron llenadas adecuadamente. Así, ingresaron al estudio 183 pacientes, 138 de sexo femenino (75,4 %). Según los criterios de Roma III, 114 pacientes (62,3 %) tuvieron el diagnóstico de SII-D, 45 (24,59 %) SII-E y 24 (13,1 %) SII-M. La remisión de la distensión abdominal al finalizar el tratamiento se produjo en 89,2 % (n = 91), 95,4 % (n = 21) y 66,6 % (n = 30) para los grupos de SII-D, SII-E y SII-M, respectivamente, tendencia que se mantuvo al finalizar el seguimiento. La remisión del dolor abdominal al finalizar el tratamiento se produjo en 84,0 % (n = 84), 95,2 % (n = 20) y 91,1 % (n =41), para los grupos de SII-D, SII-E y SII-M, respectivamente, tendencia que también se mantuvo al finalizar el seguimiento. De los 183 pacientes, se logró la remisión global de todos los síntomas tanto al término del tratamiento como del seguimiento en 94,5 % (n = 173) y 96,1 % (n =176), respectivamente. Trece (7 %) de los 183 pacientes reportaron eventos adversos, ninguno de ellos fue serio. CONCLUSIONES. El tratamiento con rifaximina resultó ser altamente eficaz y seguro en la remisión de la distensión abdominal y dolor abdominal en los tres subtipos clásicos del SII, así como en la mejoría global de todos los síntomas tanto al final del tratamiento como luego del seguimiento promedio de dos semanas.OBJECTIVE. To determine the efficacy and safety of rifamixin in a group of patients with diagnosis of irritable bowel syndrome. MATERIAL AND METHODS. It was carried out an observational, prospective, longitudinal, multicenter and descriptive study between March 2015 and January 2016. The study population were 18 yr-old or older attending to gastroenterologists‘ outpatient clinics. Patients met the inclusion criteria of Rome III as criterion diagnosis of IBS and subtypes. RESULTS. Two hundred twenty one patients were surveyed, of which 24 have not completed the follow-up visit and 14 sheets of data collection were not filled properly. Thus, the study contained 183 patients, of which 138 (75,4 %) were female. According to the Rome III criteria, 114 patients (62,3 %) had the diagnosis of IBS-D, 45 (24,59 %) IBS-C and 24 (13,1 %) SII-M. Remission of the bloating by each subtype at the end of the treatment occurred in 89,2 % (n = 91), 95,4 % (n =21) and 66,6 % (n = 30) for groups of IBS-D, IBS-IBS-M, respectively, and it was a trend that remained at the end of the track. Remission of the abdominal pain at the end of the treatment by each subtype occurred in: 84,0 % (n = 84), 95,2 % (n =20) and 91,1 % (n = 41) for groups of IBS-D, IBS-IBS-M, respectively, a trend that also remained at the end of the follow-up. Global remission of all symptoms at the end of the treatment and the follow-up was achieved in 94,5 % (n = 173) and 96,1 % (n = 176), respectively. Thirteen (7 %) of 183 patients reported adverse events, none of them was serious. CONCLUSIONS. Treatment with rifamixin turned out to be highly effective and safe in remission of abdominal pain and bloating in the three classical subtypes of IBS, as well as a global improvement all symptoms at the end of the treatment and after an average follow-up of two weeks.&nbsp

Upregulation of polysialylated neural cell adhesion molecule in the dorsal hippocampus after contextual fear conditioning is involved in long-term memory formation

The role of the hippocampus in pavlovian fear conditioning is controversial. Although lesion and pharmacological inactivation studies have suggested a key role for the dorsal hippocampus in contextual fear conditioning, the involvement of the ventral part is still uncertain. Likewise, the debate is open with regard to the putative implication of each hippocampal subdivision in fear conditioning to a discrete conditioned stimulus. We explored the potential existence of dissociations occurring in the dorsal versus ventral hippocampus at the cellular level while dealing with either contextual or cued fear conditioning and focused in a molecular "signature" linked to structural plasticity, the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). We found an upregulation of PSA-NCAM expression in the dorsal (but not ventral) dentate gyrus at 24 h after contextual (but not tone) fear conditioning. Specific removal of PSA through microinfusion of the enzyme endoneuraminidase-N in the dorsal (but not ventral) hippocampus reduced freezing responses to the conditioned context. Therefore, we present evidence for a specific role of PSA-NCAM in the dorsal hippocampus in the plasticity processes occurring during consolidation of the context representation after "standard" contextual fear conditioning. Interestingly, we also found that exposing animals just to the context induced an activation of PSA-NCAM in both dorsal and ventral dentate gyrus. Altogether, these findings highlighting the distinctive occurrence of these neuroplastic processes in the dorsal hippocampus during the standard contextual fear-conditioning task enlighten the ongoing debate about the involvement of these hippocampal subdivisions in pavlovian fear conditionin

Sex-related differences in the associations between diurnal cortisol pattern and social and emotional loneliness in older adults

IntroductionLoneliness is a distressful feeling that can affect mental and physical health, particularly among older adults. Cortisol, the primary hormone of the Hypothalamic-Pituitary-Adrenal axis (HPA-axis), may act as a biological transducer through which loneliness affects health. While most previous studies have evaluated the association between loneliness, as a unidimensional construct, and diurnal cortisol pattern, no research has examined this relationship discriminating between social and emotional loneliness in older adults. As sex differences in the negative mental health outcomes of loneliness have been reported, we also investigated whether diurnal cortisol indices and loneliness associations occur in a sex-specific manner.MethodsWe analyzed the diurnal cortisol- pattern in 142 community-dwelling, non-depressed, Caucasian older adults (55,6% female) aged 60-90. Social and emotional (family and romantic) loneliness scores were assessed using the Spanish version of the Social and Emotional Loneliness Scale for Adults (SELSA). Five salivary cortisol samples were used to capture key features of the diurnal cortisol pattern, including: awakening and bedtime cortisol levels, awakening response (CAR), post-awakening cortisol output (post-awakening cortisol [i.e., the area under the curve with reference to the ground: AUCG]), total diurnal cortisol release (AUCG), and diurnal cortisol slope (DCS).ResultsAfter controlling for sociodemographic variables, the hierarchical linear multiple regression analyses revealed that in male older adults, higher scores on social and family loneliness were associated with elevated awakening cortisol levels, total diurnal cortisol output, and a steeper diurnal cortisol slope (DCS). However, these associations were not observed in female older adults. In addition, feelings of romantic loneliness were positively associated with bedtime cortisol levels and AUCG in older males. Multilevel growth curve modeling showed that experiencing more social and emotional loneliness predicted higher diurnal cortisol output throughout the day in older male adults.DiscussionThe presence of sex differences in the relationship between cortisol indices and loneliness among older adults holds particular significance for diagnostic and screening procedures. Combining loneliness scales as screening tools with diurnal cortisol measures has the potential to be an effective and cost-efficient approach in identifying higher-risk individuals at early stages

PTEN Activity Defines an Axis for Plasticity at Cortico-Amygdala Synapses and Influences Social Behavior

Phosphatase and tensin homolog on chromosome 10 (PTEN) is a tumor suppressor and autism-associated gene that exerts an important influence over neuronal structure and function during development. In addition, it participates in synaptic plasticity processes in adulthood. As an attempt to assess synaptic and developmental mechanisms by which PTEN can modulate cognitive function, we studied the consequences of 2 different genetic manipulations in mice: presence of additional genomic copies of the Pten gene (Ptentg) and knock-in of a truncated Pten gene lacking its PDZ motif (Pten-ΔPDZ), which is required for interaction with synaptic proteins. Ptentg mice exhibit substantial microcephaly, structural hypoconnectivity, enhanced synaptic depression at cortico-amygdala synapses, reduced anxiety, and intensified social interactions. In contrast, Pten-ΔPDZ mice have a much more restricted phenotype, with normal synaptic connectivity, but impaired synaptic depression at cortico-amygdala synapses and virtually abolished social interactions. These results suggest that synaptic actions of PTEN in the amygdala contribute to specific behavioral traits, such as sociability. Also, PTEN appears to function as a bidirectional rheostat in the amygdala: reduction in PTEN activity at synapses is associated with less sociability, whereas enhanced PTEN activity accompanies hypersocial behavior.Spanish Ministry of Economy and Competitiveness (SAF2016-78071-R and SAF2015-62540-ERC to S.K.; PCIN-2016-095 and SAF2017-86983-R to J.A.E.; BFU201563769-R to R.L.; SAF2014-58598-JIN and RYC-2016-20414 to M.N.); Basque Ministry of Health (RIS3 and ELKARTEK to S.K.); University of the BasqueCountry (EHUrOPE14/03 to S.K.); Junta de Comunidades de Castilla–La Mancha (PPII2014-005-P to R.L.); Spanish Ministry of Economy and Competitiveness (BES-2011-043464 to C.S.-P.)

Agudizaciones endodóncicas: incidencia y su relación con el diagnóstico pre-operatorio

Objetivo. Determinar la incidencia de agudizaciones endodóncicas como un porcentaje del total de tratamientos de conductos radiculares realizados durante un periodo de julio a diciembre del 2011 en la Clínica Estomatológica de la Facultad de Odontología de la Universidad de San Martín de Porres-Filial Norte y correlacionarlo con el diagnostico pre-operatorio. Materiales y métodos. Fueron evaluados clínicamente 187 tratamientos de conductos radiculares. Fueron registrados las exacerbaciones agudas de una enfermedad pulpar asintomática después de la iniciación y hasta 48 horas después de la obturación de los conductos radiculares.Resultados. Las agudizaciones se dieron en 9 casos (4,8 %). En este estudio los casos que presentaron agudizaciones, 7 de ellos con diagnóstico pre-operatorio de pulpitis irreversibles (4,4 %) y 2 con diagnóstico pre-operatorio de necrosis pulpar (6,8 %).Conclusiones. Existe una baja incidencia de agudizaciones endodóncicas en tratamientos de con