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    Women with polycystic ovary syndrome (PCOS): Likelihood of cooccurring neuropsychiatric conditions and the dual hit hypothesis
    (Elsevier BV, 2025-04)
    Juan Pablo Del Río
    ;
    Alexandros Tsompanidis
    ;
    Pablo A. Gaspar
    ;
    Alejandro Maturana-Hurtado
    ;
    Gonzalo M. Rojas-Costa
    Scopus© Citations 7  6
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    Inbreeding and Gallbladder Cancer Risk: Homozygosity Associations Adjusted for Indigenous American Ancestry, BMI, and Genetic Risk of Gallstone Disease
    (MDPI AG, 2024-12-17)
    Francisco Ceballos
    ;
    Felix Boekstegers
    ;
    Dominique Scherer
    ;
    Carol Barahona Ponce
    ;
    Katherine Marcelain
    <jats:p>Latin Americans have a rich genetic make-up that translates into heterogeneous fractions of the autosomal genome in runs of homozygosity (FROH) and heterogeneous types and proportions of indigenous American ancestry. While autozygosity has been linked to several human diseases, very little is known about the relationship between inbreeding, genetic ancestry, and cancer risk in Latin Americans. Chile has one of the highest incidences of gallbladder cancer (GBC) in the world, and we investigated the association between inbreeding, GBC, gallstone disease (GSD), and body mass index (BMI) in 4029 genetically admixed Chileans. We calculated individual FROH above 1.5 Mb and weighted polygenic risk scores for GSD, and applied multiple logistic regression to assess the association between homozygosity and GBC risk. We found that homozygosity was due to a heterogeneous mixture of genetic drift and consanguinity in the study population. Although we found no association between homozygosity and overall GBC risk, we detected interactions of FROH with sex, age, and genetic risk of GSD that affected GBC risk. Specifically, the increase in GBC risk per 1% FROH was 19% in men (p-value = 0.002), 30% in those under 60 years of age (p-value = 0.001), and 12% in those with a genetic risk of GSD above the median (p-value = 0.01). The present study highlighted the complex interplay between inbreeding, genetic ancestry, and genetic risk of GSD in the development of GBC. The applied methodology and our findings underscored the importance of considering the population-specific genetic architecture, along with sex- and age-specific effects, when investigating the genetic basis of complex traits in Latin Americans.</jats:p>
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    Documentary Analysis of Hypericum perforatum (St. John’s Wort) and Its Effect on Depressive Disorders
    (MDPI AG, 2024-12-03)
    María Carolina Otero
    ;
    CERIC GARRIDO, FRANCISCO JOSE  
    ;
    Sebastián Miranda-Rojas
    ;
    Carolina Carreño
    ;
    Rachelly Escares
    <jats:p>Hypericum perforatum, also known as St. John’s Wort, pericon, or yellow grass, is known for its antidepressant potential. It could represent a natural alternative to current pharmacological antidepressant treatments, which have a high incidence of side effects in patients and therefore lead to early dropouts. Through a bibliographic revision of clinical trials and information collected from scientific articles during the first period of 2020, we aimed to evaluate whether its administration could be beneficial in the treatment of mild-to-moderate depression, with fewer side effects compared to synthetic drugs. Among the main components, hypericin and hyperforin have been related to the observed antidepressant activity; therefore, their possible mechanism of action was reviewed and highlighted. Furthermore, patients receiving Hypericum extracts were less likely to withdraw from studies because of adverse effects compared to those receiving older standard antidepressants. This review aims to provide suggestions for an alternative treatment of mild-to-moderate depression disorder under the supervision of a medical doctor, since, although it appears to be a potentially efficient treatment with a low presence of adverse effects in comparison to synthetic antidepressants, it might also interact with other medications and lead to therapeutic failures if misused for self-medication.</jats:p>
      3Scopus© Citations 19
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    Scopus© Citations 6  5
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    The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release
    (2024)
    Yorley Duarte
    ;
    Daisy Quintana-Donoso
    ;
    Rodrigo Moraga-Amaro
    ;
    Ivanka Dinamarca
    ;
    Yordan Lemunao
    <jats:p>The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.</jats:p>
    Scopus© Citations 5  8
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    Síndrome de Ovario Poliquístico y Salud Mental en Adolescentes
    (2024)
    María Rosario Matte
    ;
    Juan Pablo Del Rio
    ;
    Olga Fernández
    ;
    Nicolás Crisosto King
    <jats:p>El Síndrome de Ovario Poliquístico (SOP) es el desorden endocrino-metabólico más frecuente en las adolescentes. Se asocia a complicaciones metabólicas, cardiovasculares y reproductivas. Hallazgos recientes sugieren también una asociación con patología psiquiátrica, tanto en las pacientes afectadas como en su descendencia. En la presente actualización, se realizó una síntesis de la literatura reciente relativa a la salud mental en mujeres y adolescentes con SOP. Se realizó una búsqueda sistematizada en PubMed, Epistemonikos y Scielo de los artículos publicados en los últimos 5 años. Se confirmó que existe un aumento significativo del riesgo de presentar trastornos por ansiedad, depresión, trastornos alimenticios, trastorno obsesivo compulsivo, trastorno afectivo bipolar y psicosis en mujeres con SOP. Además, presentan riesgo de trastornos del neurodesarrollo, tales como trastorno del espectro autista y trastorno por déficit atencional e hiperactividad, tanto en ellas como en su descendencia. La hiperinsulinemia y el hiperandrogenismo podrían explicar parte de estas asociaciones, afectando la maduración del sistema nervioso central, especialmente durante la vida intrauterina y la adolescencia. El distrés derivado de las características fenotípicas físicas de la enfermedad también podría impactar la salud mental de las pacientes. Aún no se cuenta con suficientes estudios que expliquen el origen de esta correlación, ni tampoco con ensayos clínicos que aborden la salud mental de forma específica en estas pacientes. La evidencia actual sugiere la necesidad de evaluar activamente la salud mental de estas pacientes y coordinar a los distintos equipos de salud que intervengan en el manejo de la patología.</jats:p>
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      5
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    Sense of direction in vestibular disorders
    (2024)
    Alexander I.G. Moore
    ;
    John F. Golding
    ;
    Anastasia Alenova
    ;
    CASTRO ABARCA, PATRICIA BERNARDITA  
    ;
    Adolfo M. Bronstein
    <jats:p>BACKGROUND: Our sense of direction (SOD) ability relies on the sensory integration of both visual information and self-motion cues from the proprioceptive and vestibular systems. Here, we assess how dysfunction of the vestibular system impacts perceived SOD in varying vestibular disorders, and secondly, we explore the effects of dizziness, migraine and psychological symptoms on SOD ability in patient and control groups. METHODS: 87 patients with vestibular disorder and 69 control subjects were assessed with validated symptom and SOD questionnaires (Santa Barbara Sense of Direction scale and the Object Perspective test). RESULTS: While patients with vestibular disorders performed significantly worse than controls at the group level, only central and functional disorders (vestibular migraine and persistent postural perceptual dizziness), not peripheral disorders (benign-paroxysmal positional vertigo, bilateral vestibular failure and Meniere’s disease) showed significant differences compared to controls on the level of individual vestibular groups. Additionally, orientational abilities associated strongly with spatial anxiety and showed clear separation from general dizziness and psychological factors in both patient and control groups. CONCLUSIONS: SOD appears to be less affected by peripheral vestibular dysfunction than by functional and/or central diagnoses, indicating that higher level disruptions to central vestibular processing networks may impact SOD more than reductions in sensory peripheral inputs. Additionally, spatial anxiety is highly associated with orientational abilities in both patients and control subjects.</jats:p>
    Scopus© Citations 2  2
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    Six-month post-intensive care outcomes during high and low bed occupancy due to the COVID-19 pandemic: A multicenter prospective cohort study
    (2023)
    CASTRO AVILA, ANA CRISTINA  
    ;
    Catalina Merino-Osorio
    ;
    GONZALEZ SEGUEL, FELIPE ANDRES  
    ;
    CAMUS MOLINA, AGUSTIN  
    ;
    Felipe Muñoz-Muñoz
    <jats:sec id="sec001"> <jats:title>Introduction</jats:title> <jats:p>The COVID-19 pandemic can be seen as a natural experiment to test how bed occupancy affects post-intensive care unit (ICU) patient’s functional outcomes. To compare by bed occupancy the frequency of mental, physical, and cognitive impairments in patients admitted to ICU during the COVID-19 pandemic.</jats:p> </jats:sec> <jats:sec id="sec002"> <jats:title>Methods</jats:title> <jats:p>Prospective cohort of adults mechanically ventilated &gt;48 hours in 19 ICUs from seven Chilean public and private hospitals. Ninety percent of nationwide beds occupied was the cut-off for low versus high bed occupancy. At ICU discharge, 3- and 6-month follow-up, we assessed disability using the World Health Organization Disability Assessment Schedule 2.0. Quality of life, mental, physical, and cognitive outcomes were also evaluated following the core outcome set for acute respiratory failure.</jats:p> </jats:sec> <jats:sec id="sec003"> <jats:title>Results</jats:title> <jats:p>We enrolled 252 participants, 103 (41%) during low and 149 (59%) during high bed occupancy. Patients treated during high occupancy were younger (P<jats:sub>50</jats:sub> [P<jats:sub>25</jats:sub>-P<jats:sub>75</jats:sub>]: 55 [44–63] vs 61 [51–71]; p&lt;0.001), more likely to be admitted due to COVID-19 (126 [85%] vs 65 [63%]; p&lt;0.001), and have higher education qualification (94 [63%] vs 48 [47%]; p = 0.03). No differences were found in the frequency of at least one mental, physical or cognitive impairment by bed occupancy at ICU discharge (low vs high: 93% vs 91%; p = 0.6), 3-month (74% vs 63%; p = 0.2) and 6-month (57% vs 57%; p = 0.9) follow-up.</jats:p> </jats:sec> <jats:sec id="sec004"> <jats:title>Conclusions</jats:title> <jats:p>There were no differences in post-ICU outcomes between high and low bed occupancy. Most patients (&gt;90%) had at least one mental, physical or cognitive impairment at ICU discharge, which remained high at 6-month follow-up (57%).</jats:p> </jats:sec> <jats:sec id="sec005"> <jats:title>Clinical trial registration</jats:title> <jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/ct2/show/NCT04979897" xlink:type="simple">NCT04979897</jats:ext-link> (clinicaltrials.gov).</jats:p> </jats:sec>
      3Scopus© Citations 3