The role of telomeres and telomerase in the clinical effect and mechanism of action of psychopharmacological interventions

Originally studied in relation to aging and cancer research, telomeres and telomerase are now also investigated in relation to psychiatric disorders and treatments. Based on findings emerging from clinical and preclinical data, we hypothesize that the telomere–telomerase system represents a novel element mediating the mechanism of action of certain psychopharmacological interventions. In this symposium I’ll present the preliminary evidence on the complex translational relationships between specific psychiatric medications (i.e. antidepressants, lithium and antipsychotics), the telomere–telomerase system and clinical outcomes. The modulation of intracellular Wnt/b-catenin or PI3 K/Akt signaling pathways, the interaction with BDNF and 5-HT, and the antioxidant properties could represent possible mechanisms by which the different types of psychiatric medications could modulate telomere length and telomerase activity. The potential of the telomere–telomerase system in promoting cellular survival and/or function in the brain and in the periphery could, in turn, represent a neurobiological substrate through which these molecules can mediate the therapeutic effect of such interventions. Further, in the present symposium I’ll show data from our research team on telomere length and telomerase activity in leukocytes predicting clinical response to serotonin–specific reuptake inhibitors (SSRIs) in subjects with major depressive disorder

Condotte compulsive in paziente con sindrome di Aicardi. agenesia del corpo calloso

The corpus callosum, which is the largest white matter structure in the brain of all placental mammals, connects the left and right cerebral hemispheres. An alteration in its morphology, hypoconnectivity or hyperconnectivity is a common marker of various neuropsychiatric pathologies. One of these is Aicardi syndrome, which is characterized by a triad of callosal agenesis, infantile spasms and chorioretinal lacunae. Patients affected by Aicardi syndrome frequently display other malformations together with congenital defects of the eyes, ribs and vertebrae. Based on the current clinical knowledge, this syndrome is now recognized as a complex neurodevelopmental disorder that includes neurological and constitutional symptoms. However, literature data have not yet defined the presence of a particular set of symptoms in psychiatric patients with this condition. The present case is the first report in which an on-going compulsive behaviour focused on the insistence to order objects has been observed in Aicardi syndrom

A phenotype of resiliency? cross-sectional psychobiological differences between caregivers who are vulnerable vs. resilient to depression, and controls

Introduction: Being a caregiver of chronically ill children is a source of chronic-psychological stress affecting general physical and mental health. However, there is tremendous variance among caregivers: some may develop stress-related depression, whereas others are more “resilient”. The objective of the study was to phenotypically differentiate on psychobiology caregivers who developed depressive symptoms (“vulnerable”) vs. those who did not (“resilient”) from each other and from age-matched controls. Methods: Forty-five mothers of chronically-ill children and 18 controls have been examined. Caregivers were divided via a median split of Center for Epidemiological Studies Depression Scale scores in “resilient” (RCs) and “vulnerable” (VCs). We assessed cognitive, affective, metabolic, neuroendocrine and oxidative markers at rest and in response to a laboratory social stressor. ANCOVAs and Bonferroni post-hoc tests were used to examine between-group differences. Results: Although RCs compared to VCs had similar levels of objective parenting-related burden (P = 0.51), they had lower subjective distress (P < 0.01) and higher levels of positive affect (P = 0.04). Although RCs compared to controls had higher levels of objective parenting-related burden (P = 0.04), they had greater cortisol suppression post-dexamethasone (P = 0.05), lower F2-isoprostanes/vitamin E ratio (P < 0.01) and lower fasting insulin levels (P = 0.06). Discussion: Our results suggest that caregivers with higher resiliency demonstrate more salutary stress-related functioning in comparison with less resilient caregivers and, more surprisingly, non-caregiver controls. These findings might be interpreted in the spirit of Nietzsche's quote “What does not kill me, makes me stronger” and of the idea that successfully overcoming adversity may be more psychobiologically beneficial than not having been exposed to any adversity

Trait mindfulness at baseline predicts increases in telomerase activity over time

Introduction Preliminary investigations of cross-sectional samples have linked trait mindfulness with measures related to the hypothalamic–pituitary–adrenal (HPA)-mediated stress response and to the inflammatory system, suggesting that this is one potential pathway linking mindfulness based interventions and health. However, no previous studies explored the association between the trait mindfulness construct and markers of cellular ageing. Methods In the current study we examined in a sample of healthy mothers (n = 92) of a child with Autism Spectrum Disorder (i.e. women showing high levels of chronic psychological stress) the prospective associations between a multidimensional scale of trait mindfulness, the Five Facet Mindfulness Questionnaire (FFMQ), and telomerase activity (TA), a marker of cellular ageing and telomere homeostasis. Participants’ trait mindfulness and TA were assessed at baseline as well as 9 and 18 month follow-up. Results Analysis showed that higher levels of baseline mindfulness on FFMQ observation and describe subscales were related to increase in TA from baseline to 9 month (r = 0.27, P = 0.03 and r = 0.24, P = .04, respectively). Additionally, the FFMQ Describe subscale was related to increase in TA from baseline to 18 month (r = .30, P = .02). Results are reported following covariate adjustment of age, BMI, ethnicity, and education. Discussion Our results showed that higher levels of baseline mindfulness are associated with higher increases in TA after 9 months and 18 months, with increased TA reportedly being associated with decreased oxidative damage, increased telomere length and overall more functional cellular physiology. These findings support a role of mindfulness-related interventions to increase general and mental health

A Model-Driven Approach for the Formal Verification of Storm-Based Streaming Applications

Data-intensive applications (DIAs) based on so-called Big Data technologies are nowadays a common solution adopted by IT companies to face their growing computational needs. The need for highly reliable applications able to handle huge amounts of data and the availability of infrastructures for distributed computing rapidly led industries to develop frameworks for streaming and big-data processing, like Apache Storm and Spark. The definition of methodologies and principles for good software design is, therefore, fundamental to support the development of DIAs. This paper presents an approach for non-functional analysis of DIAs through D-VerT, a tool for the architectural assessment of Storm applications. The verification is based on a translation of Storm topologies into the CLTLoc metric temporal logic. It allows the designer of a Storm application to check for the existence of components that cannot process their workload in a timely manner, typically due to an incorrect design of the topology

Capgras-like syndrome in a patient with an acute urinary tract infection.

Delusional misidentification syndromes are a group of delusional phenomena in which patients misidentify familiar persons, objects, or themselves, believing that they have been replaced or transformed. In 25%-40% of cases, misidentification syndromes have been reported in association with organic illness. We report an acute episode of Capgras-like delusion lasting 8 days, focused on the idea that people were robots with human bodies, in association with an acute urinary infection. To our knowledge, this is the first case report associating urinary tract infection with Capgras-like syndrome. Awareness of the prevalence of delusional misidentification syndromes associated with acute medical illness should promote diligence on the part of clinicians in recognizing this disorder

Maturation stages of glauconites: A combined electron microprobe, Raman, and thermogravimetric study

Glauconite mineral is one of the most sensitive indicators of low sedimentation rate in the marine environment. The time of residence of glauconites at the sea bottom before burial is reflected by their so-called maturity that is differentiated based on their K2O content. The present work aims to investigate the evolution of glauconites during the transition toward the highly evolved level. Complementary electron microprobe, Raman, and Thermogravimetric analysis were performed on glauconitic grains from the Belluno basin (N Italy) with different K2O content in order to verify whether the level of glauconites evolution affects the results of these surveys

Capture and printing of fixed stromal cell membranes for bioactive display on PDMS surfaces

Polydimethylsiloxane (PDMS) has emerged as an extremely useful polymer for various biological applications. The conjugation of PDMS with bioactive molecules to create functional surfaces is feasible, yet limited to single molecule display with imprecise localization of the molecules on PDMS. Here we report a robust technique that can transfer and print the membrane surface of glutaraldehyde-fixed stromal cells intact to a PDMS substrate using an intermediate polyvinylalcohol (PVA) film as a transporter system. The cell-PVA film capturing the entirety of surface molecules can be peeled off and subsequently printed onto PDMS while maintaining the spatial display of the original cell surface molecules. Proof-of-concept studies are described using human bone marrow stromal cell membranes, including the demonstration of bioactivity of transferred membranes to capture and adhere hematopoietic cells. The presented process is applicable to virtually any adherent cell and can broaden the functional display of biomolecules on PDMS for biotechnology applications

Equilibria determination of elastic articulated duoskelion beams in 2D via a Riks-type algorithm

The overall behavior of an articulated beam structure constituted by elements arranged according to a specific chirality is studied. The structure as a whole, due to its slenderness and geometry, is called duoskelion beam. The name duoskelion is a neologism which is inspired by the Greek word δύοσκέλιον (two-legged). A discrete model for shearable beams, formulated recently, is exploited to investigate its mechanics. A purposely designed numerical scheme, adapting the Riks rationale, is used to calculate large displacement and deformation equilibria of duoskelion beams. Aimed at computing the current step correction, the Riks arc-length method is modified and made more efficient by applying a specific orthogonality condition, defined via the stiffness matrix, to an adapted extrapolation step. The robustness of the resulting scheme and its capability to follow equilibrium branches allows, in principle, for the exploration of the whole set of local energy minima in the introduced space of configurations, by using suitably modulated perturbative external loads. The developed numerical tool can be used to understand the mechanics of duoskelion beams. It is proved that there exists a stable principal equilibrium branch in which only compression is observed for any compression load. Additional stable equilibrium branches are found in compression such that the clamped–clamped compressed beam assumes a characteristic S shape which, upon reaching a critical load, is significantly amplified. A mechanically relevant stable equilibrium is also found in extension, being observed the S-shaped configuration experimentally found in Misra et al. (2020)

P300 component in euthymic patients with bipolar disorder type I, bipolar disorder type II and healthy controls: a preliminary event-related potential study

The aim of the present study was to investigate P300 event-related potential components in euthymic bipolar disorder type I (BDI) and bipolar disorder type II (BDII) patients and matched controls. A total of 10 BDI patients, 10 BDII patients and 10 healthy individuals were enrolled in the study. Event-related potential data were collected according to a standard auditory 'oddball' paradigm. A significant groups effect in both the peak amplitude (P<0.001) and the mean amplitude (P<0.001) was observed; post-hoc comparisons showed that the peak and mean amplitudes of BDI and BDII patients were significantly lower than the peak and mean amplitudes of the healthy controls. The neurophysiological patterns found in the present study might at least partially reflect the presence of a mild selective cognitive impairment in euthymic BDI and BDII patients. From a clinical point of view, these evidences support the potential role of cognitive interventions in the treatment of BD