Autonomic and brain morphological predictors of stress resilience

Stressful life events are an important cause of psychopathology. Humans exposed to aversive or stressful experiences show considerable inter-individual heterogeneity in their responses. However, the majority does not develop stress-related psychiatric disorders. The dynamic processes encompassing positive and functional adaptation in the face of significant adversity have been broadly defined as resilience. Traditionally, the assessment of resilience has been confined to self-report measures, both within the general community and putative high-risk populations. Although this approach has value, it is highly susceptible to subjective bias and may not capture the dynamic nature of resilience, as underlying construct. Recognizing the obvious benefits of more objective measures of resilience, research in the field has just started investigating the predictive value of several potential biological markers. This review provides an overview of theoretical views and empirical evidence suggesting that individual differences in heart rate variability (HRV), a surrogate index of resting cardiac vagal outflow, may underlie different levels of resilience toward the development of stress-related psychiatric disorders. Following this line of thought, recent studies describing associations between regional brain morphometric characteristics and resting state vagally-mediated HRV are summarized. Existing studies suggest that the structural morphology of the anterior cingulated cortex (ACC), particularly its cortical thickness, is implicated in the expression of individual differences in HRV. These findings are discussed in light of emerging structural neuroimaging research, linking morphological characteristics of the ACC to psychological traits ascribed to a high-resilient profile and abnormal structural integrity of the ACC to the psychophysiological expression of stress-related mental health consequences. We conclude that a multidisciplinary approach integrating brain structural imaging with HRV monitoring could offer novel perspectives about brain-body pathways in resilience and adaptation to psychological stres

Deontological morality can be experimentally enhanced by increasing disgust. A transcranial direct current stimulation study

Previous studies empirically support the existence of a distinctive association between deontological (but not altruistic) guilt and both disgust and obsessive-compulsive (OC) symptoms. Given that the neural substrate underlying deontological guilt comprises brain regions strictly implicated in the emotion of disgust (i.e. the insula), the present study aimed to test the hypothesis that indirect stimulation of the insula via transcranial direct current stimulation (tDCS) would enhance disgust and morality in the deontological domain. A randomized, sham-controlled, within-subject design was used. Thirty-seven healthy individuals (25 women) underwent 15-min anodal and sham tDCS over T3 in two different days, while their heart rate (HR) was recorded to derive measures of parasympathetic nervous system activity (HR variability; HRV). After the first 10-min of sham or active tDCS stimulation, participants were asked to 1) complete a series of 6-item words that could be completed with either a disgust-related word (cleaning/dirtiness) or neutral alternatives; 2) rate how much a series of vignettes, each depicting a behavior that violated a specific moral foundation, were morally wrong. Levels of trait anxiety, depression, disgust sensitivity, scrupulosity, and altruism as well as pre- and post- stimulation momentary emotional states were assessed. Compared to the sham condition, after active stimulation of T3 a) HRV significantly increased and participants b) completed more words in terms of cleaning/dirtiness and c) reported greater subjective levels of disgust, all suggesting the elicitation of the emotion of disgust. Although the results are only marginally significant, they point to the absence of difference between the two experimental conditions for moral vignettes in the altruistic domain (i.e., animal care, emotional and physical human care), but not in the deontological domain (i.e., authority, fairness, liberty, and sacrality), where vignettes were judged as more morally wrong in the active compared to the sham condition. Moreover, scores on the OCI-R correlated with how much vignettes were evaluated as morally wrong in the deontological domain only. Results preliminarily support the association between disgust and morality in the deontological domain, with important implications for OC disorder (OCD). Future studies should explore the possibility of decreasing both disgust and morality in patients with OCD by the use of non-invasive brain stimulation techniques

Mutaciones somáticas raras en un paciente con retinoblastoma unilateral

Retinoblastoma (RB) is the most common primary intraocular malignancy in children. Somatic inactivation of both alleles of the RB1 tumor suppressor gene in a developing retina is a crucial event in the initiation of tumorigenesis in most cases of isolated unilateral retinoblastoma. We analyzed the DNA from tumor tissue and peripheral blood of a unilateral retinoblastoma patient to determine the RB1 mutation status and to provide an accurate genetic counseling. A comprehensive approach, based on our previous experience, was used to identify the causative RB1 mutations. Screening for RB1 mutations was performed by PCR direct sequencing, multiplex ligation-dependent probe amplification (MLPA) and Real Time-PCR analyses. Three different mutations were identified in the tumor DNA, which were absent in blood DNA. The somatic origin of these mutations was vital to rule out the heritable condition in this patient.El retinoblastoma (RB) es el cáncer ocular más común de la niñez. La inactivación somática de ambos alelos del gen supresor de tumores RB1 en la retina en desarrollo es un evento crucial en la iniciación de la tumorigénesis en la mayoría de los casos de retinoblastoma unilateral. Nosotros analizamos el ADN de tumor y de sangre periférica de un paciente con retinoblastoma unilateral para identificar las mutaciones y así proveer un asesoramiento genético a la familia. Para ello utilizamos un protocolo basado en nuestra previa experiencia para identificar todas las mutaciones en el gen RB1 que causaron el RB. El rastreo de mutaciones se realizó por medio de los siguientes análisis: PCR-secuenciación, amplificación multiplex de sondas ligadas (MLPA) y PCR-Tiempo Real. Se encontraron tres mutaciones diferentes en el ADN del tumor, las cuales estaban ausentes en el ADN de la sangre. El origen somático de estas mutaciones es importante para indicar que la enfermedad no es hereditaria.Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Association between attention and heart rate fluctuations in pathological worriers

Recent data suggests that several psychopathological conditions are associated with alterations in the variability of behavioral and physiological responses. Pathological worry, defined as the cognitive representation of a potential threat, has been associated with reduced variability of heart beat oscillations (i.e., decreased heart rate variability; HRV) and lapses of attention indexed by reaction times (RTs). Clinical populations with attention deficit show RTs oscillation around 0.05 and 0.01 Hz when performing a sustained attention task. We tested the hypothesis that people who are prone to worry do it in a predictable oscillating pattern revealed through recurrent lapses in attention and concomitant oscillating HRV. Sixty healthy young adults (50% women) were recruited: 30 exceeded the clinical cut-off on the Penn State Worry Questionnaire (PSWQ; High-Worry, HW); the remaining 30 constituted the Low-Worry (LW) group. After a diagnostic assessment, participants performed two 15-min sustained attention tasks, interspersed by a standardized worry-induction procedure. RTs, HRV and moods were assessed. The analyses of the frequency spectrum showed that the HW group presents a significant higher and constant peak of RTs oscillation around 0.01 Hz (period 100 s) after the induction of worry, in comparison with their baseline and with the LW group that was not responsive to the induction procedure. Physiologically, the induction significantly reduced high-frequency HRV and such reduction was associated with levels of self-reported worry. Results are coherent with the oscillatory nature of the default mode network (DMN) and further confirm an association between cognitive rigidity and autonomic nervous system inflexibility

Reducing the meta-emotional problem decreases physiological fear response during exposure in phobics

Anxiety disorders may not only be characterized by specific symptomatology (e.g., tachycardia) in response to the fearful stimulus (primary problem or first-level emotion) but also by the tendency to negatively evaluate oneself for having those symptoms (secondary problem or negative meta-emotion). An exploratory study was conducted driven by the hypothesis that reducing the secondary or meta-emotional problem would also diminish the fear response to the phobic stimulus. Thirty-three phobic participants were exposed to the phobic target before and after undergoing a psychotherapeutic intervention addressed to reduce the meta-emotional problem or a control condition. The electrocardiogram was continuously recorded to derive heart rate (HR) and heart rate variability (HRV) and affect ratings were obtained. Addressing the meta-emotional problem had the effect of reducing the physiological but not the subjective symptoms of anxiety after phobic exposure. Preliminary findings support the role of the metaemotional problem in the maintenance of response to the fearful stimulus (primary problem)

Hemodynamic profiles of functional and dysfunctional forms of repetitive thinking

Background: The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. Purpose: To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Methods: Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Results: Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Conclusions: Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease

Compassion is not a benzo: distinctive associations of heart rate variability with its empathic and action components

Recent studies have linked compassion with higher vagally mediated heart rate variability (vmHRV), a measure of parasympathetic activity, and meta-analytic evidence confirmed significant and positive associations. Compassion, however, is not to be confused with soothing positive emotions: in order to engage in actions aimed to alleviate (self or others) suffering, the pain should resonate, and empathic sensitivity should be experienced first. The present study examined the association between vmHRV and the empathic sensitivity and action components of trait and state compassion. To do so, several dispositional questionnaires were administered and two videos inducing empathic sensitivity (video 1) and compassionate actions (video 2) were shown, while the ECG was continuously recorded, and momentary affect was assessed. Results showed that (i) scores on subscales assessing the empathic component of trait compassion were inversely related to resting vmHRV; (ii) vmHRV decreased after video 1 but significantly increased after video 2. As to momentary affect, video 1 was accompanied with an increase in sadness and a decrease in positive affect, whereas video 2 was characterized by an increase in anger, a parallel decrease in sadness, and an increase (although non-significant) in positive affect. Overall, present findings support the notion that it is simplistic to link compassion with higher vmHRV. Compassion encompasses increased sensitivity to emotional pain, which is naturally associated with lower vmHRV, and action to alleviate others' suffering, which is ultimately associated with increased vmHRV. The importance of adopting a nuanced perspective on the complex physiological regulation that underlies compassionate responding to suffering is discussed

Mutations in the RB1 Gene in Argentine Retinoblastoma Patients and Uncommon Clinical Presentations

Background: Retinoblastoma, the most common ocular cancer of childhood, is caused by inactivation of the RB1 tumor suppressor gene in the developing retina. It may occur as unilateral, bilateral or rarely as multicentric retinoblastoma, including pineal or suprasellar tumors. Being the retinoblastoma a hereditary cancer, identification of the causative mutation is important for risk prediction in the family members. An early detection of tumor is critical for survival and eye preservation. Screening for RB1 mutations is important for early tumor detection, critical for survival and eye preservation. Purpose: To identify causative RB1 mutations in retinoblastoma patients with different clinical presentations, some of them with a rare multicentric retinoblastoma or with a second non ocular malignancy, as well as the rare association with down syndrome. A comprehensive approach was used to identify the mutations and to detect children with a hereditary condition. Methods: A cohort of 20 patients with unilateral, bilateral and multicentric retinoblastoma was studied. Blood and tumor DNA was analyzed by sequencing, segregation of polymorphisms and MLPA analyses. Some of the rare mutations were validated by cloning or by Real-Time PCR. Results: Six germline and seven somatic mutations were identified; they include nonsense, frameshift, splice mutations and gross rearrangements, four of them novel. Three out of four nonsense/ frameshift germline mutations were associated with severe phenotype: bilateral and multicentric retinoblastomas. The at-riskhaplotype was identified in a familial case including one patient with osteosarcoma; it was useful for detection of mutation carriers. Conclusions: This study allowed us to identify causative RB1 mutations, including several novels. Some patients showed uncommon clinical presentations of retinoblastoma. These data are significant for genetic counseling. Our results support the relevance of carrying out complete genetic screening for RB1 mutations in both constitutional and tumor tissues.Fil: Ottaviani, Daniela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Parma, Diana Lidia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Ferrer, Marcela Maria. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Florencia Giliberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Luce, Leonela Natalia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; ArgentinaFil: Alonso, Cristina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Servicio de Hemato-Oncología; ArgentinaFil: Szijan, Irena. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Genética y Biología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Association between cognitive impairment and criteria for frailty syndrome among older adults

OBJECTIVE: The association between cognitive impairment and physical frailty has been studied in older adults. The criteria degree of frailty may be keys to associated cognitive impairment. To analyze the association between cognitive impairment and the criteria for frailty. METHODS: We cross-sectionally examined data from 667 older adults (≥60 years of age) from a study entitled 'Variables associated to cognition in elderly caregivers' involving patients in an urban and rural primary healthcare center. We defined cognitive impairment based on different groups of scores on the Mini Mental State Examination, and defined frailty and prefrailty using the criteria by the Cardiovascular Health Study. We performed multinomial regression models to analyze the association between levels of frailty and cognitive impairment. RESULTS: Similar proportions of women (54.8%) and men (45.2%) participated in the study (mean age: 71 years old). We found cognitive impairment, prefrailty and frailty in 34, 54, and 24% of the participants, respectively. Concomitant cognitive impairment and frailty was found in 13% of them. The chances of cognitive impairment increased up to 330% (Odds Ratio [OR]: 4.3; 95% confidence interval [95%CI] 2.4‒7.7; p<0.001) among frail individuals, and 70% (OR: 1.7; 95%CI 1.0‒2.8; p=0.033) among prefrail individuals compared to robust/non-frail individuals. After controlling for age, education, place of residence and functional dependence, slowness and fatigue criteria were significantly associated with cognitive impairment. CONCLUSION: Older adults with frailty have a greater likelihood of concomitant cognitive impairment than prefrail and robust older adults. The prevalence of cognitive impairment and frailty is consistent with data reported in literature. The present findings contribute to the investigation of cognitive frailty