A Study of Candidate Genes in Depression and Disturbed Sleep

Depression is a complex psychiatric disorder that comprises a variety of symptoms. In addition to depressed mood state, depression has symptoms of disturbed sleep such as early morning awakenings and fatigue. Poor sleep has been demonstrated to be one of the modifiable risk factors in the onset of depression. However, the mechanisms remain largely unknown. In the present study, depressive patients from the Finnish population-based samples were grouped according to the presence or absence of disturbed sleep. The genetic background of depression was hypothesized to be different between the groups. The regulation of sleep, and of mood, was assumed to partly share a common genetic background. The aim of this thesis was to identify genetic variants associated with depression and disturbed sleep in order to gain a better understanding of this hypothesis in the population-based Finnish samples. First, the association between genetic markers from 14 functionally-relevant candidate genes was assessed. These genes were related to serotonergic and glutamatergic neurotransmission, to neural plasticity, and to the hypothalamic-pituitary-adrenal axis (HPA-axis) with depression, depression with early morning awakenings, and depression with fatigue in a sample from the population-based Health 2000 survey. Overall, 1654 individuals were studied (384 depressed patients and 1270 population-matched controls). The data suggested that allelic variants from a gene coding for a key regulatory protein of the serotonergic neurotransmission system, TPH2, is associated with depression accompanied by fatigue in females. An association between a numbers of genes related to glutamatergic neurotransmission and neural plasticity, such as GAD1, GRIA3, and BDNF with depression accompanied by fatigue in females. A significant association between CREB1, a neural plasticity related gene, and depression in men, was also identified. Of the genes related to the HPA-axis, an association was found between CRHR1 and depression accompanied by early morning awakenings in females. The hypothesis was then expanded to encompass 18 genes from the circadian system in the same study subjects (N=1654) from the Health 2000 cohort. In this study, a significant association of two distinctive allelic variants of TIMELESS was associated with depression accompanied by fatigue (Permutation-based corrected empirical P=0.0056), to seasonal mood fluctuation (Pointwise P=0.016) in females, and with depression accompanied by early morning awakenings (Permutation-based corrected empirical P=0.0374) in males. In an independent set of 1512 control individuals (Genmets (D-) sample) from the complete Health 2000 cohort, the same variant was also associated with seasonal mood fluctuation (Pointwise P=0.036) in females, and with early morning awakenings (Pointwise P=0.038) or fatigue (Pointwise P=0.0016) in healthy males. Finally, the shared genetic background for sleep and mood in healthy individuals (N=3147) drawn from the population-based Health 2000 and FINRISK study 2007 survey was examined. In this study, for association analyses with sleep duration, 23 variants from 12 candidate genes were selected that had shown association (P less than 0.05) with depression and disturbed sleep in studies I and II. A significant association of a GRIA3 variation with sleep duration in females (Permutation-based corrected empirical P=0.00001) was identified. The frequency of the allele which associated with depression was highest among females who slept for 8 hours or less in all age groups younger than 70 years. However, no prominent associations were found among males, suggesting a sex-specific effect for the X-chromosomal GRIA3 gene. In conclusion, these results support the involvement of genes related to serotonergic (TPH2) or glutamatergic neurotransmission (GAD1, GRIA3), to neural plasticity (CREB1), to the HPA-axis (CRHR1), and the circadian system (TIMELESS), in the genetic aetiology of depression and disturbed sleep. The results obtained in this thesis support the hypothesis that the different phenotypes of depression and disturbed sleep would also be genetically distinct. Depression is heterogeneous and its genetic background may be partly different in women and men. This study also shows that the regulation of sleep and of mood may have a common genetic background.Depressio on merkittävä psykiatrinen sairaus, johon kuuluu masentuneen mielialan lisäksi joukko muita oireita kuten unen häiriintymiseen liittyvät aamuyön heräilyt tai väsymys. Useat epidemiologiset tutkimukset osoittavat, että heikko uni on yksi merkittävimmistä depression riskitekijöistä. Jaottelimme tutkimuksessamme potilaat sen mukaan, ilmenikö heillä unen häiriöihin liittyviä oireita. Hypoteesinamme oli, että geneettinen depressioalttius olisi ainakin osin erilainen riippuen siitä, ilmeneekö potilaalla häiriintyneeseen uneen liittyviä oireita. Toinen tutkimushypoteesimme oli, että unen ja mielialan geneettisessä säätelyssä on ainakin osin yhteneväisiä mekanismeja. Selvitimme aluksi toiminnallisten, serotoniini- tai glutamiinihermovälitykseen, plastisuuteen ja stressinsäätelyyn liityvien ehdokasgeenien assosiaatiota (i) depressioon, (ii) depressioon ja aamuyön heräilyyn ja (iii) depressioon ja väsymykseen väestöpohjaisessa Terveys 2000-aineistossa. Tuloksemme osoittivat että osa geeneistä, kuten serotoniinin tuottoa aivoissa säätelevä TPH2, liittyy depressioon naisilla silloin kun oireena on myös väsymystä. Lisäksi havaitsimme naisilla useiden eri glutamiinivälitykseen sekä plastisuuteen liittyvien geenien assosiaation depressioon ja väsymykseen ja stressinsäätelyjärjestelmän CRHR1-geenin assosiaation depressioon ja aamuyön heräämisiin. Miehillä totesimme depression merkittävän assosiaation CREB1 geeniin. Laajensimme tutkimuksemme vuorokausirytmiä sääteleviin ns. kellogeeneihin. Havaitsimme kahden eri TIMELESS-geenimuodon assosioituvan depressioon ja väsymykseen sekä depressioon ja aamuyön heräämiseen miehillä. Samat riskivariantit asioituivat myös terveillä naisilla mielialan vuodenaikaiseen vaihteluun ja miehillä aamuyön heräilyihin. Tutkimme myös depression ja mielialan geneettistä taustaa selvittämällä aiemmin tunnistamiemme riskivarianttien vaikutusta unen pituuteen terveillä, Terveys 2000 ja Finriski 2007 aineistoista poimituilla yksilöillä. Tunnistimme glutamiinireseptoria koodaavan GRIA3-geenin variaation assosiaation unen pituuteen. Sama alleeli, joka assosioitui naisilla depressioon, assosioitui terveillä naisilla lyhyeen yöuneen. Tuloksemme osoittavat, kuinka serotoniini- (TPH2) ja glutamiinihermovälitykseen (GAD1, GRIA3), plastisuuteen (CREB1), HPA-akselin toimintaan (CRHR1) tai sirkadiaaniseen systeemiin (TIMELESS) liittyvillä geeneillä on tehtävä depression ja häiriintyneen unen etiologiassa. Tuloksemme viittaavat siihen, että depression etiologia olisi ainakin osittain erilainen riippuen potilaan oirekuvasta etenkin unen häiriön suhteen. Tuloksemme osoittavat myös depression heterogeenisyyden ja sen, että sairauden geneettinen etiologia on ainakin osittain erilainen naisilla ja miehillä. Lisäksi löydöksemme antavat viitettä siitä, että unen ja mielialan geneettinen säätely sisältävät päällekkäisiä, mm. glutamiinihermovälitykseen liittyviä mekanismeja. Jatkotutkimuksia tarvitaan, jotta voisimme ymmärtää näitä mekanismeja paremmin

Microsatellite markers for the yam bean <em>Pachyrhizus</em> (Fabaceae)

Premise of the study: Microsatellite loci were developed for the understudied root crop yam bean (Pachyrhizus spp.) to investigate intraspecific diversity and interspecific relationships within the genus Pachyrhizus. Methods and Results: Seventeen nuclear simple sequence repeat (SSR) markers with perfect di- and trinucleotide repeats were developed from 454 pyrosequencing of SSR-enriched genomic libraries. Loci were characterized in P. ahipa and wild and cultivated populations of four closely related species. All loci successfully cross-amplified and showed high levels of polymorphism, with number of alleles ranging from three to 12 and expected heterozygosity ranging from 0.095 to 0.831 across the genus. Conclusions: By enabling rapid assessment of genetic diversity in three native neotropical crops, P. ahipa, P. erosus, and P. tuberosus, and two wild relatives, P. ferrugineus and P. panamensis, these markers will allow exploration of the genetic diversity and evolutionary history of the genus Pachyrhizus

Inclusión en la universidad italiana: el caso de la Universidad de Roma “Foro Italico”

Through a historical-legislative itinerary, the initiatives to create the National University Conference of Delegates for Disability in Italian universities are highlighted. This is a body that deals with the various practices and problems of university students with disabilities and specific learning disabilities. The experience of the Università di Roma "Foro Italico" is presented as an example for its specific characteristics to combine Physical Activity and Sport Sciences with inclusiveness. This has been made possible by numerous initiatives and organisational and pedagogical changes to create an inclusive educational context that favours all students, without overlooking individual specificities, through collaboration and agreement with the university community.A través de un itinerario histórico-legislativo se evidencian las iniciativas para crear en las universidades italianas la CNUDD (Conferencia Nacional Universitaria de Delegados para la Discapacidad). Organismo que se confronta con las distintas praxis y con los problemas de los estudiantes universitarios con discapacidad y con TEA (trastornos específicos de aprendizaje). La experiencia de la Università di Roma “Foro Italico” se presenta como ejemplo por sus características específicas para conjugar las Ciencias de la Actividad Fisica y del Deporte con la inclusividad. Esto ha sido posible gracias a numerosas iniciativas y a transformaciones organizativas y pedagógico-didácticas para crear un contexto educativo inclusivo que favorezca a todos los estudiantes, sin pasar por alto las especificidades individuales, a través de la colaboración y el acuerdo con la comunidad universitaria

Polygenic Risk Score of SERPINA6/SERPINA1 Associates with Diurnal and Stress-Induced HPA Axis Activity in Children

Purpose: Corticosteroid-binding globulin (CBG) transports glucocorticoids in blood. Variation in genes SERPINA6 encoding for CBG, SERPINA2 and SERPINAI (serpin family A member 6, 2, and 1) have been shown to influence morning plasma cortisol and CBG in adults. However, association of this genetic variation with diurnal and stress-induced salivary cortisol remain unknown. This study aims to investigate the effect of genetic variation in SERPINA6/2/1 loci on diurnal and stress-induced salivary cortisol in children. Methods: We studied 186, 8-year-old children with genome-wide genotyping. We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229) derived from the CORNET meta-analyses. Salivary cortisol was measured across one day and in response to the Trier Social Stress Test for Children (TSST-C). Results: Mixed models, adjusted for covariates, showed that the PRS x sampling time interactions associated with diurnal (P <0.001) and stress-induced (P = 0.009) salivary cortisol. In the high PRS group (dichotomized at median) the diurnal salivary cortisol pattern decreased less from awakening to bedtime than in the low PRS group (standardized estimates of sampling time -0.64 vs. -0.73, P <0.0001 for both estimates). In response to stress, salivary cortisol increased in the high PRS group while it remained unchanged in the low PRS group (standardized estimates of sampling time 0.12, P = 0.015 vs. -0.06, P = 0.16). These results were mainly driven by minor alleles of rs7161521 (SERPINA6) and rs4900229 (SERPINAI). Conclusions: Genetic variation in SERPINA6/2/1loci may underpin higher hypothalamic-pituitary-adrenocortical axis activity in children.Peer reviewe

Geology of the northern sector of the Cura Mallín Basin in the Lagunas de Epulaufquen, Neuquén

Las secuencias aflorantes en la vertiente oriental de los Andes alrededor de la zona limítrofe argentino-chilena entre los 36º40´-50´S, 71º-71º10´O responden a dos génesis bien diferenciadas. Por un lado, las secuencias inferiores se han acumulado en una cuenca de intraarco extensional donde las unidades de synrift correspondientes al Miembro Lumabia de la Formación Cura Mallín son cubiertas por secuencias asociadas con el enfriamiento termal del Miembro Arroyo Pincheira de la Formación Cura Mallín. Por otra parte, las secuencias superiores denominadas Formación Cajón Negro representan un arco volcánico que se superpuso a la cuenca invertida de intraarco anteriormente descripta. En esta zona pueden distinguirse tres fases de deformación compresiva: las dos primeras corresponden a deformación de piel fina (Mioceno medio -pre 17 Ma- y tardío, respectivamente) mientras que la última es de piel gruesa asociada a la inversión tectónica de la cuenca de intraarco de Cura Mallín (Mioceno superior). Estudios geoquímicos sugieren que la mayor variación en el acortamiento cortical fue alcanzado en el tiempo transcurrido entre la depositación del Miembro Arroyo Pincheira y la Formación Cajón Negro/Trapa Trapa. Sin embargo, esta última fase compresiva ha producido gran parte de la estructura visible en la vertiente oriental de los Andes entre los 36º40´-50´S.The exposed sequences in the eastern Andes around the Argentinian-Chilean boundary between 36º40´-50´S, 71º-71º10´O are associated with two contrasting genesis. On one hand, the lowest sequences have been accumulated in an extensional intra-arc basin, where synrift units from the Lumabia Member of the Cura Mallín Basin are overlied by sequences associated with thermal cooling of the Arroyo Pincheira Member. On the other hand, the upper sequences of the Cajón Negro Formation represent a volcanic arc that were superimposed to a previously inverted intraarc basin. There are three compressive phases in the area. The two first are associated to thin-skinned deformation (Early and Middle Miocene), while the last one to thick-skinned deformation related to the tectonic inversion of the Cura Mallín intraarc basin (Late Miocene). Geochemical studies suggest that a major change in crustal thickening was reached between Arroyo Pincheira Member and Cajón Negro Formation. This last phase of contraction produced most of the Andean structures at the eastern slope of the high Andes around 36º40´-50´S.Fil: Utge, Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Folguera Telichevsky, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Litvak, Vanesa Dafne. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; ArgentinaFil: Ramos, Victor Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Estudios Andinos "Don Pablo Groeber". Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Estudios Andinos "Don Pablo Groeber"; Argentin

Seismic geomorphology of the last lacustrine transgression of the Pozo D-129 Formation in the Fold Belt region, Golfo San Jorge Basin

La cuenca del Golfo San Jorge cuenta con más de 100 años de historia de producción de hidrocarburos. La Formación Pozo D-129, principal roca generadora de la cuenca, es una unidad de origen lacustre con gran participación piroclástica, que cubre grandes extensiones en el subsuelo; sus espesores aumentan hacia el centro de la cuenca alcanzando los 1500 metros. En el ámbito de la faja plegada de San Bernardo, en la provincia de Santa Cruz, se analizó la información de más de 200 pozos y se reconocieron tres secciones principales en la Formación Pozo D-129, basadas en variaciones litológicas y geoquímicas. En la sección superior de la unidad un intervalo compuesto íntegramente por arcilitas negras ricas en materia orgánica representa la última y más extendida transgresión lacustre de esta unidad, que se denomina informalmente “cuello pelítico”. El análisis y caracterización de este intervalo constituye el objetivo del presente trabajo. Mediante técnicas de visualización 3D y la confección de mapas de facies sísmicas, se reconocieron geoformas asociadas al último evento transgresivo lacustre. Se evidencia una marcada variación de su espesor asociado a su depositación en depocentros aislados. La caracterización depositacional del “cuello pelítico” en este área permite ampliar el conocimiento del modelo paleoambiental existente de la unidad.The Golfo San Jorge Basin records a hydrocarbon production history of more than 100 years. The Pozo D-129 Formation, which is the main source rock of the basin, is a lacustrine unit with high pyroclastic participation that spreads over a wide extension within the subsurface of the basin; its thickness increases toward the central area of the basin, reaching up to 1500 meters. In the San Bernardo Fold Belt of Santa Cruz province, more than 200 wells were analyzed and three main sections in the Pozo D-129 Formation were recognized, based on lithological and geochemical variations. In the uppermost section of the unit an stratigraphic interval characterized by black shales rich in organic matter is interpreted as the last and most extended lacustrine transgression of this unit, informally named “cuello pelítico”. The analysis and characterization of this interval becomes the main objective of the present study. 3D seismic visualization and seismic facies identification allowed the recognition of the main geomorphologic patterns associated with the last lacustrine transgressive event. A strong thickness variation could be recognized mainly related to the distribution within isolated depocentres. The depositional characterization of the “cuello pelítico” in the area improves the knowledge of the current paleoenvironmental model of the unit.Facultad de Ciencias Astronómicas y Geofísica

Seismic geomorphology of the last lacustrine transgression of the Pozo D-129 Formation in the Fold Belt region, Golfo San Jorge Basin

La cuenca del Golfo San Jorge cuenta con más de 100 años de historia de producción de hidrocarburos. La Formación Pozo D-129, principal roca generadora de la cuenca, es una unidad de origen lacustre con gran participación piroclástica, que cubre grandes extensiones en el subsuelo; sus espesores aumentan hacia el centro de la cuenca alcanzando los 1500 metros. En el ámbito de la faja plegada de San Bernardo, en la provincia de Santa Cruz, se analizó la información de más de 200 pozos y se reconocieron tres secciones principales en la Formación Pozo D-129, basadas en variaciones litológicas y geoquímicas. En la sección superior de la unidad un intervalo compuesto íntegramente por arcilitas negras ricas en materia orgánica representa la última y más extendida transgresión lacustre de esta unidad, que se denomina informalmente “cuello pelítico”. El análisis y caracterización de este intervalo constituye el objetivo del presente trabajo. Mediante técnicas de visualización 3D y la confección de mapas de facies sísmicas, se reconocieron geoformas asociadas al último evento transgresivo lacustre. Se evidencia una marcada variación de su espesor asociado a su depositación en depocentros aislados. La caracterización depositacional del “cuello pelítico” en este área permite ampliar el conocimiento del modelo paleoambiental existente de la unidad.The Golfo San Jorge Basin records a hydrocarbon production history of more than 100 years. The Pozo D-129 Formation, which is the main source rock of the basin, is a lacustrine unit with high pyroclastic participation that spreads over a wide extension within the subsurface of the basin; its thickness increases toward the central area of the basin, reaching up to 1500 meters. In the San Bernardo Fold Belt of Santa Cruz province, more than 200 wells were analyzed and three main sections in the Pozo D-129 Formation were recognized, based on lithological and geochemical variations. In the uppermost section of the unit an stratigraphic interval characterized by black shales rich in organic matter is interpreted as the last and most extended lacustrine transgression of this unit, informally named “cuello pelítico”. The analysis and characterization of this interval becomes the main objective of the present study. 3D seismic visualization and seismic facies identification allowed the recognition of the main geomorphologic patterns associated with the last lacustrine transgressive event. A strong thickness variation could be recognized mainly related to the distribution within isolated depocentres. The depositional characterization of the “cuello pelítico” in the area improves the knowledge of the current paleoenvironmental model of the unit.Facultad de Ciencias Astronómicas y Geofísica

Оцінка якості життя у вікових першовагітних та вагітних з великим інтергенетичним інтервалом

Проведено изучение показателей качества жизни у 120 возрастных первобеременных и 240 беременных с большим интергенетическим интервалом с использованием опросника SF-36 Health Status Survey, разработанного The Health Institute, New England Medical Center, Boston, USA. Исследование показало, что пациентки обеих групп имеют низкие показатели качества жизни. При сравнении большинство изучаемых параметров оценки качества жизни в обследованных группах не отличались, однако у пациенток с большим интергенетическим интервалом – достоверно выше оценка социальной роли и энергетичности. Оценка качества жизни у возрастных первобеременных и беременных с большим интергенетическим интервалом является важным сегментом наблюдения во время беременности, который оценивает перспективы развития беременности в психологическом, физическом и социальном аспектах.A study of the life quality of 120 over-age primigravidas and of 240 women with a large intergenetic interval has been carried out using the questionnaire SF-36 Health Status Survey developed by The Health Institute, New England Medical Center, Boston, USA. This research has shown that the patients in the both groups have a low quality of life. The major part of the life quality parameters were the same in the both groups, however, in patients with a large interval between births the values of the social role and the energy level were significantly higher. The life quality of over-age primigravidas and pregnant women with a large interval between successive births is an important sector of observation during pregnancy, which allows assessing the prospects of pregnancy in the psychological, physical, and social aspects

Sleep Disorders and Genes

Versão preprintThe sleep-wake cycle is a neurobiological phenomenon that shows intervals of activity alternating with restfulness that appears with a periodicity approximating the 24h day-night cycle. The sleep-wake cycle is under the control of diverse neuroanatomical and neurochemical systems, including monoaminergic, cholinergic, adenosinergic among many other systems. In addition, neuroanatomical centers linked to sleep promotion, such as hypothalamus, project to the cerebral cortex, subcortical relays and brainstem. In addition, the sleep-wake cycle has been associated to aberrant features known as sleep disorders. Here, we will discuss the role of specific gene expression on sleep disturbances. Given the expansion of the knowledge in the sleep-wake cycle area, it is indeed ambitious to describe all the genetics involved in the sleep modulation. However, in this chapter we reviewed the current understanding of the sleep disorders and gene expression.info:eu-repo/semantics/publishedVersio

Systematic Analysis of Circadian Genes in a Population-Based Sample Reveals Association of TIMELESS with Depression and Sleep Disturbance

Peer reviewe