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Brain-Derived Neurotrophic Factor (BDNF) and IL-1beta in Pediatric and Adolescent' Depressive Disorders: a look towards precision psychiatry
Full text linkIntroduction. Depression is one of the main and most debilitating mood disorders, as for personal functioning and social costs (Masi and Brovedani, 2011). It is estimated that depression affects more than 15% of the population lifetime (Kessler et al., 2003), with percentages in pediatric age that reach about 1-2% in prepuberal age and 4-6% in adolescence (Kessler et al., 2001). Although the early-onset depression usually tends to improve over time and resolve in a part of the cases, the functional impact of the disease is more difficult to recover, with consequences that tend to take a chronic trend and finally predispose to a high rate of recurrence of disease, a high risk of psychopathology in the future, as well as increase risk of suicide attempts and completed suicides (Masi and Brovedani, 2011). Studies on neuroanatomy, post-mortem brain observations and in vivo neuroimaging suggest that the impairment of neuroplasticity in specific neuronal networks may be involved in the pathogenesis of mood disorders (Biggio, 2011). In particular, recent studies have emphasized the role of the neurotrophic factor called Brain Derived Neurotrophic Factor (BDNF) whose depletion is associated with a reduction in neurogenesis and in the volume of important brain areas including the hippocampus, the prefrontal cortex and the amygdala (Biggio, 2011). Other researches found reduced BDNF concentrations in the blood of depressed patients, which increased after undergoing treatment with psychopharmacological therapy (Brunoni et al., 2008; Sen et al., 2008; Bocchio-Chiavetto et al., 2010; Molendijk et al. al., 2014). Scientific studies also found that the neuroinflammation process could contribute to the origin of some psychiatric conditions, especially depression (Dantzer et al. 2008; Miller et al. 2009; Kim et al. 2014; Rosenblat et al. 2014). Depressed patients often present an increase levels of proinflammatory cytokines (like IL-1beta) in blood and cerebrospinal fluid (Miller et al, 2009; Kim et al. 2014), so many authors have hypothesized their role as early clinical biomarker of pathology.
Objective. The aim of the present study is to measure plasma levels of BDNF and IL-1beta in subjects affected by depression in the developmental age compared to healthy peers. Secondary aims are: a) the evaluation in the depressed subjects of the trend of plasma levels before and after psychopharmacological treatment (at 3, 6 and 12 months); b) the analysis of the relationship between plasma levels of BDNF and IL-1beta and clinical psychopatological features of depression. The last objective is to verify the usefulness of BDNF and IL-1beta dosages as peripheral biomarkers of disease or of unresponsiveness to treatment, finally to improve diagnostic characterization of depressed patients and to target the treatment in pediatric age.
Methods. Thirteen subjects aged 11-17,9 years, diagnosed with depressive disorder (according to DSM-IV-TR; APA, 2002), as well as matched healthy subjects (n =12), were evaluated by trained raters and provided blood for BDNF and IL-1beta measurements.
The diagnostic evaluation was conducted through free talks and the administration of a panel of structured (YSR-CBCL, CDI, MASC, CGI, C-GAS, SadPerson) and projective tests. The same panel was adminstrated to healthy subjects to explore subthereshold dimensions. Depressed subjects were treated with pharmacological therapy (Selective Serotonin Reuptake Inhibitors, mood stabilizers, SGAs) and psychotherapy.
The plasma levels of BDNF and IL-1beta were measured according to definite timing (basal T0, before the start of therapy / psychotherapy, after 6 and 12 months). For depressed patients, an additional measure after 3 months of therapy was performed.
Analysis of BDNF and IL-1beta levels were performed using specific ELISA kits (BDNF Emax ImmunoAssay System, Promega, Madison, U.S.A and Antigenix America, Huntington Station, NY, USA)
Results. The depressed subjects, compared to the healthy peers, differ in a statistically significant way for a constant familiarity for psychiatric pathology, in particular in the maternal line, a history of events experienced as traumatic, a constant presence of conflicts within the family, scholastic and relational problems, sleep disorders and alcohol/drugs use. Compared to heathy subjects at intake, plasma BDNF concentrations are lower, while IL-1beta are higher in depressed patients, even if they do not reach a statistical significance. Regarding psychodiagnostic assessment, comparing test scores between depressed and non-depressed subjects at T0, there are significant differences in CBCL, YSR, C-GAS, CGI-S, CDI (p <0.05) and SadPerson (p <0.001) scores. No significant differences were found between the gropus in the MASC scores. Statistically significant correlations were found between BDNF levels at T0 of depressed subjects and problems of attention (r=-.695, p=.026) and school skills (r= .878, p= .004). At T6, BDNF inversely correlates to affective disorders (r=-.975, p=.005) reported at YSR T12. In depressed group, considering the presence of suicidal attempts, there are statistical significative differences for anxious-depressed (Z=-2.158, p=.031) and anxiety problems (Z=-2.669, p=.008) at YSR. The same analysis performed considering the personal history of trauma, highlighted statistical significative differences for rule break (Z=-2.384, p=.017) and conduct disorders (Z=-2.037, p=.042).
Conclusions. Depressed pediatric patients present lower levels of BDNF and higher levels of IL-1beta compared to healthy peers at the moment of diagnosis, although without a statistical significant difference. At intake BDNF appears to correlate to academic competences, while after 6 months of therapy higher BDNF levels orient to a better prognosis as for depression symptomatology. The evolution from suicidal ideation to SA appear to be linked to the perception of limited social support (reduced resilience) in adolescents with reduced levels of BDNF.
Depressed children with a history of trauma present more externalizing symptoms, while the dimension of anxiety appears to be somehow protective from suicidal attempts.
The study supports the bio-psycho-social model of DD, highlighting the importance of a balance between neurogenesis, neuroinflammation and cerebral plasticity in the delicate period of developmental age. BDNF seems to be a symptoms or disease biomarker more than a severity index, so the integration of different instruments of evaluations, both clinical and biological (multimodal methods), as well as the integration of different voices (multi-informant approach) seems to represent the “best practice” for pediatric clinical assessment of mental health in line with precision psychiatry.
Further studies are needed to explore the role of BDNF and cytokines in the response of pediatric population to SSRIs, to identify biomarkers for predicting early treatment response, to produce new drug targets, to find preventive strategies and individually target therapy
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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