14 research outputs found
Specificity profile of venlafaxine and sertraline in major depression: metaregression of double-blind, randomized clinical trials.
No full textDespite the well-known efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of major depressive disorder, there is a lack of indications for each drug in different groups of patients. The aim of this study is to investigate the possible role of clinical sociodemographic factors as moderators of clinical response to venlafaxine (SNRI) and sertraline (SSRI). Research was performed on Medline and EMBASE for randomized control trials in English focused on sertraline and venlafaxine in the treatment of major depressive disorder and 59 studies were included. Clinical efficacy of each treatment was assessed on the basis of Hamilton Depressive Rating Scale and Montgomery-Asberg Depression Rating Scale. A metaregression analysis was performed to evaluate the role of clinical and sociodemographic factors as moderators of outcome, calculating the effect of each variable with the random-effects method. Gender, ethnicity and duration of depressive episode could have a role in prediction of clinical response to both antidepressants. Venlafaxine seems to have better effects in females and in Caucasian patients. Sertraline seems to be more efficacious in the treatment of females. Both drugs were more efficacious in patients who suffered a shorter episode of illness. Our results could represent an interesting point of view in the perspective of choosing the most suitable therapy based on clinical and social features for each patient. Metaregression is a retrospective analysis, based on the cumulative results of previous studies, so the lack of original data could represent the main limitation in this report and in the interpretation of the results obtained
De Novo Pathogenic Variant in FBRSL1, Non OMIM Gene Paralogue AUTS2, Causes a Novel Recognizable Syndromic Manifestation with Intellectual Disability; An Additional Patient and Review of the Literature
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De Novo Pathogenic Variant in FBRSL1, Non OMIM Gene Paralogue AUTS2, Causes a Novel Recognizable Syndromic Manifestation with Intellectual Disability; An Additional Patient and Review of the Literature
by Nenad Bukvic 1,2,*ORCID,Marta De Rinaldis 3,Massimiliano Chetta 4ORCID,Antonio Trabacca 5ORCID,Maria Teresa Bassi 6ORCID,René Massimiliano Marsano 7ORCID,Lenka Holoubkova 8,Maria Rivieccio 4,Maria Oro 4,Nicoletta Resta 1,2ORCID,Jennifer Kerkhof 9ORCID,Bekim Sadikovic 9,10 andLuigi Viggiano 7
1
Medical Genetic, Department of Precision and Regenerative Medicine and Ionian Area (DiMePRe-J), University of Bari Aldo Moro, 70124 Bari, Italy
2
Medical Genetics Section, University Hospital Consortium Corporation Polyclinics of Bari, 70124 Bari, Italy
3
Unit for Severe Disabilities in Developmental Age and Young Adults, Associazione “La Nostra Famiglia”—IRCCS “E. Medea”, Scientific Hospital for Neurorehabilitation, Piazza A. Di Summa, 72100 Brindisi, Italy
4
Medical Genetics Laboratory, A.O.R.N. Cardarelli, Building Y, 80127 Naples, Italy
5
Scientific Direction, Scientific Institute IRCCS Eugenio Medea, Via D. L. Monza 20, Bosisio Parini, 23842 Lecco, Italy
6
Laboratory of Molecular Biology, Scientific Institute IRCCS Eugenio Medea, Via D. L. Monza 20, Bosisio Parini, 23842 Lecco, Italy
7
Department of Biosciences, Biotechnology and Environment, University of Bari Aldo Moro, 70125 Bari, Italy
8
ReStart—Professional Practice of Occupational Therapy, Via di Vittorio, 76125 Trani, Italy
9
Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON N6A 3K7, Canada
10
Department of Pathology and Laboratory Medicine, Western University, London, ON N6A 3K7, Canada
*
Author to whom correspondence should be addressed.
Genes 2024, 15(7), 826; https://doi.org/10.3390/genes15070826
Submission received: 20 May 2024 / Revised: 13 June 2024 / Accepted: 19 June 2024 / Published: 22 June 2024
(This article belongs to the Special Issue Molecular Basis and Genetics of Intellectual Disability)
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Abstract
FBRSL1, together with FBRS and AUTS2 (Activator of Transcription and Developmental Regulator; OMIM 607270), constitutes a tripartite AUTS2 gene family. AUTS2 and FBRSL1 are evolutionarily more closely related to each other than to FBRS (Fibrosin 1; OMIM 608601). Despite its paralogous relation to AUTS2, FBRSL1’s precise role remains unclear, though it likely shares functions in neurogenesis and transcriptional regulation. Herein, we report the clinical presentation with therapeutic approaches and the molecular etiology of a patient harboring a de novo truncating variant (c.371dupC) in FBRSL1, leading to a premature stop codon (p.Cys125Leufs*7). Our study extends previous knowledge by highlighting potential interactions and implications of this variant, alongside maternal and paternal duplications, for the patient’s phenotype. Using sequence conservation data and in silico analysis of the truncated protein, we generated a predicted domain structure. Furthermore, our in silico analysis was extended by taking into account SNP array results. The extension of in silico analysis was performed due to the possibility that the coexistence of FBRSL1 truncating variant contemporary with maternal and paternal duplication could be a modifier of proband’s phenotype and/or influence the novel syndrome clinical characteristics. FBRSL1 protein may be involved in neurodevelopment due to its homology with AUTS2, together with distinctive neuronal expression profiles, and thus should be considered as a potential modulation of clinical characteristics in a novel syndrome. Finally, considering that FBRSL1 is apparently involved in neurogenesis and in transcriptional regulatory networks that orchestrate gene expression, together with the observation that different genetic syndromes are associated with distinct genomic DNA methylation patterns, the specific episignature has been explored
Effects of SORL1 gene on Alzheimer's disease. Focus on gender, neuropsychiatric symptoms and pro-inflammatory cytokines
No full textIt was suggested that the gene encoding for sorLa, (SORL1) may affect Alzheimer's disease (LOAD) through a female-specific mechanism. The aims of this study were to confirm the role of gender in modulating the association between SORL1 and LOAD and to ascertain the influence of SORL1 on cognitive impairment, neuropsychiatric symptoms (BPSD) and secretion of pro-inflammatory cytokines. Ninety six outpatients with LOAD and 120 unrelated controls were genotyped for APOE and three SNPs at the 5' end of SORL1(intron 6): SNP 8 (rs668387); SNP 9 (rs68902); SNP 10 (rs641120). Clinical evaluation was made with the MMSE, Neuropsychiatric Inventory (NPI) and Cornell Scale for Depression in Dementia (CDDS). ELISPOT assays were used to measure pro-inflammatory cytokine (TNF-alpha; IL-6; IL-1beta; IFN-gamma) production in peripheral blood mononuclear cell (PBMC) supernatant from AD patients. SORL1 SNPs were not associated with LOAD in overall sample. Instead the G-alleles at SNPs 9 (p=0.015) and 10 (p=0.015) and the CGG haplotype (p=0.02) were associated with LOAD in the women subgroup. The TAA haplotype was marginally protective in AD patients being associated with lower BPSD scores (p=0.01). The same haplotype was also associated with higher IL-1beta (p=0.01) production. These genetic effects were not modified by APOE4 allele and controlled for illness duration and treatment. In conclusion, SORL1 does not appear to be a major risk factor for LOAD. Its contribution could be underestimated in our small sample. Sex-specific factors could modulate the association between SORL1 and AD. The influence of SORL1 variants on production of inflammatory cytokines warrants further investigation. © 2013 Bentham Science Publishers
Nine differentially expressed genes from a post mortem study and their association with suicidal status in a sample of suicide completers, attempters and controls
No full textSeveral lines of evidence indicate that suicidal behaviour is partly heritable, with multiple genes implicated in its aetiology. We focused on nine genes (S100A13, EFEMP1, PCDHB5, PDGFRB, CDCA7L, SCN2B, PTPRR, MLC1 and ZFP36) which we previously detected as differentially expressed in the cortex of suicide victims compared to controls. We investigated 84 variants within these genes in 495 suicidal subjects (299 completers and 196 attempters) and 1513 controls (109 post-mortem and 1404 healthy). We evaluated associations with: 1) suicidal phenotype; 2) possible endophenotypes for suicidal behaviour. Overall positive results did not survive the correction threshold. However, we found a nominally different distribution of EFEMP1 genotypes, alleles and haplotypes between suicidal subjects and controls, results that were partially replicated when we separately considered the subgroup of suicide completers and post-mortem controls. A weaker association emerged also for PTPRR. Both EFEMP1 and PTPRR genes were also related to possible endophenotypes for suicidal behaviour such as anger, depression-anxiety and fatigue. Because of the large number of analyses performed and the low significance values further replication are mandatory. Nevertheless, neurotrophic gene variants, in particular EFEMP1 and PTPRR, may have a role in the pathogenesis of suicidal behaviour
La guerra del Cenepa: veintiséis años después. Una aproximación al estado actual de las investigaciones sobre el último conflicto armado del siglo XX entre Perú y Ecuador
No full textA veintiséis años de la guerra del Cenepa existen pocas investigaciones sobre el tema en
Perú. Entre el 26 de enero y el 28 de febrero de 1995 tuvo lugar este enfrentamiento
militar. Este trabajo de investigación para el bachillerato está basado en métodos
cualitativos de información documental. A través de un balance historiográfico, se busca
presentar un estado de la cuestión sobre la situación actual de las investigaciones
académicas y periodísticas en Perú y en Ecuador. Cada autor consultado es útil para
comprender el desarrollo de esta guerra. La consulta de fuentes muestra que, a pesar del
tiempo transcurrido, todavía quedan temas pendientes que necesitan ser profundizados.Twenty-six years after the Cenepa war there is little research on the subject in Peru.
Between January 26
th, 1995, and February 28
th, 1995, this military confrontation took
place. This research work for the baccalaureate is based on qualitative methods of
documentary information. Through a historiographic balance, the aim is to present a state
of the art on the current situation of academic and journalistic research in Peru and
Ecuador. Each author consulted is useful to understand the development of this war. The
consultation of sources shows that, despite the time that has elapsed, there are still
pending issues that need to be deepened
La guerra del Cenepa: veintiséis años después. Una aproximación al estado actual de las investigaciones sobre el último conflicto armado del siglo XX entre Perú y Ecuador
No full textA veintiséis años de la guerra del Cenepa existen pocas investigaciones sobre el tema en
Perú. Entre el 26 de enero y el 28 de febrero de 1995 tuvo lugar este enfrentamiento
militar. Este trabajo de investigación para el bachillerato está basado en métodos
cualitativos de información documental. A través de un balance historiográfico, se busca
presentar un estado de la cuestión sobre la situación actual de las investigaciones
académicas y periodísticas en Perú y en Ecuador. Cada autor consultado es útil para
comprender el desarrollo de esta guerra. La consulta de fuentes muestra que, a pesar del
tiempo transcurrido, todavía quedan temas pendientes que necesitan ser profundizados.Twenty-six years after the Cenepa war there is little research on the subject in Peru.
Between January 26
th, 1995, and February 28
th, 1995, this military confrontation took
place. This research work for the baccalaureate is based on qualitative methods of
documentary information. Through a historiographic balance, the aim is to present a state
of the art on the current situation of academic and journalistic research in Peru and
Ecuador. Each author consulted is useful to understand the development of this war. The
consultation of sources shows that, despite the time that has elapsed, there are still
pending issues that need to be deepened
PPP3CC gene: A putative modulator of antidepressant response through the B-cell receptor signaling pathway
No full textAntidepressant pharmacogenetics represents a stimulating, but often discouraging field. The present study proposes a combination of several methodologies across three independent samples. Genes belonging to monoamine, neuroplasticity, circadian rhythm and transcription factor pathways were investigated in two samples (n=369 and 88) with diagnosis of major depression who were treated with antidepressants. Phenotypes were response, remission and treatment-resistant depression. Logistic regression including appropriate covariates was performed. Genes associated with outcomes were investigated in the STAR∗D (Sequenced Treatment Alternatives to Relieve Depression) genome-wide study (n=1861). Top genes were further studied through a pathway analysis. In both original samples, markers associated with outcomes were concentrated in the PPP3CC gene. Other interesting findings were particularly in the HTR2A gene in one original sample and the STAR∗D. The B-cell receptor signaling pathway proved to be the putative mediator of PPP3CC's effect on antidepressant response (P=0.03). Among innovative candidates, PPP3CC, involved in the regulation of immune system and synaptic plasticity, seems promising for further investigation.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Temperament and character inventory in bipolar disorder versus healthy controls and modulatory effects of 3 key functional gene variants
No full textBACKGROUND: Bipolar disorder (BD) has been associated with temperamental and personality traits, although the relationship is still to be fully elucidated. Several studies investigated the genetic basis of temperament and character, identifying catechol-O-methyltransferase (COMT), brain derived neurotrophic factor (BDNF), and serotonin transporter (5-HTT) gene variants as strong candidates. METHODS: In the GECO-BIP study, 125 BD patients and 173 HC were recruited. Subjects underwent to a detailed assessment and the temperament and character inventory 125 items (TCI) was administrated. Three functional genetic variants within key candidate genes (COMT rs4680, BDNF rs6265, and the serotonin-transporter-linked polymorphic region (5-HTTLPR)) were genotyped. Univariate and multivariate analyses were performed. RESULTS: Compared to HC, BD patients showed higher scores in novelty seeking (NS; p = 0.001), harm avoidance (HA; p < 0.001), and self transcendence (St; p < 0.001), and lower scores in self directness (p < 0.001) and cooperativeness (p < 0.001) TCI dimensions. Concerning the genetic analyses, COMT rs4680 was associated with NS in the total sample (p = 0.007) and in the male subsample (p = 0.022). When performing the analysis in the HC and BD samples, the association was confirmed only in HC (p = 0.012), and in the HC male subgroup in particular (p = 0.004). BDNF rs6265 was associated with St in the BD group (p = 0.017). CONCLUSION: COMT rs4680 may modulate NS in males in the general population. This effect was not detected in BD patients, probably because BD alters the neurobiological basis of some TCI dimensions. BDNF rs6265 seems to modulate St TCI dimension only in BD patients, possibly modulating the previously reported association between rs6265 and BD treatment response. Further studies are needed to confirm our findings
