Diferencias biopsicosociales en el trastorno por consumo de sustancias entre el hombre y la mujer y consideraciones sobre su abordaje terapéutico

Introducción. Con la finalidad de investigar las diferencias vinculadas al sexo en el abuso de drogas, intentar com-prender los fundamentos biológicos y psicosociales subyacentes, y analizar la pertinencia de diseñar intervenciones diferenciales, se ha realizado un rastreo de la información científica publicada, especialmente en humanos, pero en algunos casos también en animales. Objetivos. Partiendo de las diferencias anatómicas y neuroquímicas del cerebro, de las diferentes destrezas y de la posible importancia de los factores evolutivos, se revisan las diferencias biopsicosociales, ligadas al sexo, en relación al abuso de sustancias, así como el sesgo en las enfermedades neuropsiquiátricas, en bastantes casos concurrentes. Se revisa asimismo el papel de las hormonas sexuales y el peso de los roles de género en la adicción. Además, se analizan las características diferenciales del tratamiento de las conductas adictivas según el sexo. Desarrollo y conclusiones. Los resultados señalan peculiaridades específicas en el proceso de la adicción según el sexo, causadas por las diferencias biológicas del cerebro y las diferentes hormonas sexuales circulantes. Estas dife-rencias se manifiestan tanto en los efectos de las drogas en el circuito de recompensa como en su metabolismo, y en el grado de severidad de las diferentes fases del proceso adictivo: adquisición, escalada de consumo, abstinencia y recaída. También se perciben diferencias significativas en las enfermedades neuropsiquiátricas asociadas. Todo ello está modulado por las particularidades de género impuestas socialmente. Finalmente, se valora la necesidad de abordajes terapéuticos específicos en función del sexo, que cobran aún más importancia ante la presencia de problemas psicológicos o psiquiátricos concomitantes.Introduction. A search of scientific papers has been carried out in order to investigate sexual differences in drug abuse, and to underlying biological and psychosocial explanatory causes of these differences. Goals. Based on the anatomical and neurochemical differences of the male and female brain, the difference in skills and the possible importance of evolutionary factors, the reasons for the differential characteristics of addictions in men and women, as well as the sexual bias in the concurrent neuropsychiatric disorders are reviewed. The impor-tance of sex hormones in these differences is also reviewed, as well as the influence of psychosocial conditioning factors associated with gender in addiction. Finally, the main features that differentiate the treatment of drug abuse in men and women are reviewed. Development and conclusions. The results obtained indicate that there is a close link between the differential bio-logical characteristics of the male and female brain and sex hormones, which explain the specific characteristics of drug abuse according to sex. These differences exist both in the reward circuit, in metabolism and in the different phases of the addictive process: acquisition, escalation of consumption, abstinence and relapse, as well as in the associated neuropsychiatric disorders, all them modulated by psychosocial gender particularities. Finally, the need for separate sex treatments, especially indicated in the presence of coexisting psychological or psychiatric disorders, is assessed

Estimation of phylogeographic patterns and divergence times of populations of small mammals from the Iberian Peninsula using genomic data

[eng] Phylogenetic and phylogeographic methods allow studying the evolutionary relationships between populations and species, patterns of genetic structure, and historical events that have modelled the current distribution of biodiversity. Molecular markers are a fundamental complement of morphological data to accomplish these studies. The divergence time between species and populations is among the most useful parameters to place evolutionary events in the proper historical context as well as to assess population differentiation, evolutionary units and taxonomic categories, but it is difficult to estimate. The emergence of coalescent theory indicated that different genes can reflect different histories and that the coalescence of genes might have occurred much before the actual divergence between populations or species, a phenomenon that is crucial to know divergence times and evidences the importance of multilocus analysis. The Iberian Peninsula played a major role in shaping the distribution of present biodiversity as it harbored different Pleistocene refugia that were the source of recolonizations of other European areas and created internal diversity within this peninsula. In this thesis, two Eurosiberian species, Neomys fodiens and Arvicola scherman, both of which have received little attention despite their biogeographical interest, have been used to advance in this framework of study. To obtain samples of both species, an important effort to optimize laboratory protocols and bioinformatic analysis was made to enable the work with minimally invasive samples. In chapter 1, a subspecies of the Eurasian water shrew, Neomys fodiens niethammeri, which is found in a narrow strip of the northern Iberian Peninsula, was studied. This subspecies presents an abrupt increase in skull size when compared to the rest of the Eurasian population, which has led to the suggestion that it is actually a different species. Skulls obtained from owl pellets collected over the last 50 years allowed us to perform a morphometric analysis in addition to an extensive multilocus analysis based on short intron fragments successfully amplified from these degraded samples. Interestingly, no genetic divergence was detected using either mitochondrial or nuclear data. Additionally, an allele frequency analysis revealed no significant genetic differentiation. The absence of genetic divergence and differentiation revealed here indicated that the large form of N. fodiens does not correspond to a different species and instead represents an extreme case of size increase, of possible adaptive value, which deserves further investigation. In chapter 2, the divergence time between two Iberian populations of the Montane water vole (Arvicola scherman) was estimated using double-digest restriction site-associated DNA (ddRAD) obtained through next-generation sequencing (NGS), including skulls from barn owl pellets among the samples, and applying an isolation-with-migration (IM) analysis. The Cantabrian and Pyrenean populations of A. scherman are geographically isolated and have subtle morphological differences between them. Thousands of single nucleotide polymorphisms (SNPs) derived from the ddRAD were used to study their genetic structure. In addition, a bioinformatic pipeline was developed to find orthologues of the ddRAD loci in other rodents and estimate specific mutation rates using a fossil calibration point (the mouse-rat split). By this means, 85 loci were calibrated. The IMa3 software was then used together with the specific mutation rates of the calibrated loci in order to estimate divergence times and other demographic parameters (population sizes and migration rates). The length of the markers used (145 base pairs) was small compared to other loci generally used with IM models, so the inclusion of only the calibrated loci did not provide enough information. However, it was demonstrated that using a set of 300 ddRAD loci, including the 85 with estimated mutation rates, resulted in good mixing and convergence of the model. The results of the analysis allowed concluding that the two Iberian populations of A. scherman diverged 39 thousand years (Kyr) ago with a 95% highest posterior density interval of 21 – 62 Kyr. A small amount of migration was detected between both populations. Based on this split time and the genetic structure found, it is suggested that the two populations have been present in isolated Iberian refugia at least since the last glaciation and are not the product of a recent colonization of the norther Iberian strip. The methodology developed here based on ddRAD data and coalescent theory allows estimating recent divergence times with high accuracy and comparing the results between different taxa. This can be of great help to understand the generation of diversity in a relatively small geographical area such as the Iberian Peninsula and determine whether the populations have differentiated for enough time to deserve separate taxonomic or conservation status

ddRAD data

Original reads for each sample in FASTQ format

Data from: A pipeline for metabarcoding and diet analysis from fecal samples developed for a small semi-aquatic mammal

Metabarcoding allows the genetic analysis of pooled samples of various sources. It is becoming popular in the study of animal diet, especially because it allows the analysis of the composition of feces without the need of handling animals. In this work, we studied the diet of the Pyrenean desman (Galemys pyrenaicus), a small semi-aquatic mammal endemic to the Iberian Peninsula and the Pyrenees, by sequencing COI minibarcodes from feces using next-generation sequencing techniques. For the identification of assembled sequences, we employed a tree-based identification method that used a reference tree of sequences of freshwater organisms. The comparison of freshly collected fecal samples and older samples showed that fresh samples produced significantly more sequencing reads. They also rendered more operational taxonomical units (OTUs), but not significantly. Our analyses of 41 samples identified 224 OTUs corresponding to species of the reference tree. Ephemeroptera, Diptera excl. Chironomidae, and Chironomidae were the most highly represented groups in terms of reads as well as samples. Other groups of freshwater organisms detected were Plecoptera, Trichoptera, Neuropteroida, Coleoptera, Crustacea, and Annelida. Our results are largely in line with previous morphological and genetic studies on the diet of the Pyrenean desman, but allowed the identification of a higher diversity of OTUs in each sample. Additionally, the bioinformatic pipeline we developed for deep sequencing of fecal samples will enable the quantitative analysis of the diet of this and other species, which can be highly useful to determine their ecological requirements

A pipeline for metabarcoding and diet analysis from fecal samples developed for a small semi-aquatic mammal.

Metabarcoding allows the genetic analysis of pooled samples of various sources. It is becoming popular in the study of animal diet, especially because it allows the analysis of the composition of feces without the need of handling animals. In this work, we studied the diet of the Pyrenean desman (Galemys pyrenaicus), a small semi-aquatic mammal endemic to the Iberian Peninsula and the Pyrenees, by sequencing COI minibarcodes from feces using next-generation sequencing techniques. For the identification of assembled sequences, we employed a tree-based identification method that used a reference tree of sequences of freshwater organisms. The comparison of freshly collected fecal samples and older samples showed that fresh samples produced significantly more sequencing reads. They also rendered more operational taxonomical units (OTUs), but not significantly. Our analyses of 41 samples identified 224 OTUs corresponding to species of the reference tree. Ephemeroptera, Diptera excl. Chironomidae, and Chironomidae were the most highly represented groups in terms of reads as well as samples. Other groups of freshwater organisms detected were Plecoptera, Trichoptera, Neuropteroida, Coleoptera, Crustacea, and Annelida. Our results are largely in line with previous morphological and genetic studies on the diet of the Pyrenean desman, but allowed the identification of a higher diversity of OTUs in each sample. Additionally, the bioinformatic pipeline we developed for deep sequencing of fecal samples will enable the quantitative analysis of the diet of this and other species, which can be highly useful to determine their ecological requirements

Divergence time estimation using ddRAD data and an isolation-with-migration model applied to water vole populations of Arvicola [Dataset]

Quality-filtered reads for each sample in FASTQ format. ddRAD_reads.zip Rodent alignments used for calibration in NEXUS format. BEAST_alignments.zipMolecular dating methods of population splits are crucial in evolutionary biology, but they present important difficulties due to the complexity of the genealogical relationships of genes and past migrations between populations. Using the double digest restriction-site associated DNA (ddRAD) technique and an isolation-with-migration (IM) model, we studied the evolutionary history of water vole populations of the genus Arvicola, a group of complex evolution with fossorial and semi-aquatic ecotypes. To do this, we first estimated mutation rates of ddRAD loci using a phylogenetic approach. An IM model was then used to estimate split times and other relevant demographic parameters. A set of 300 ddRAD loci that included 85 calibrated loci resulted in good mixing and model convergence. The results showed that the two populations of A. scherman present in the Iberian Peninsula split 34 thousand years ago, during the last glaciation. In addition, the much greater divergence from its sister species, A. amphibius, may help to clarify the controversial taxonomy of the genus. We conclude that this approach, based on ddRAD data and an IM model, is highly useful for analyzing the origin of populations and species.MCIN/AEI/10.13039/501100011033, Award: CGL2014-53968-P MCIN/AEI/10.13039/501100011033, Award: CGL2017-84799-P National Science Foundation, Award: 1625061 US Army Research Laboratory, Award: W911NF-16-2-0189Peer reviewe

Divergence time estimation using ddRAD data and an isolation-with-migration model applied to water vole populations of Arvicola

Molecular dating methods of population splits are crucial in evolutionary biology, but they present important difficulties due to the complexity of the genealogical relationships of genes and past migrations between populations. Using the double digest restriction-site associated DNA (ddRAD) technique and an isolation-with-migration (IM) model, we studied the evolutionary history of water vole populations of the genus Arvicola, a group of complex evolution with fossorial and semi-aquatic ecotypes. To do this, we first estimated mutation rates of ddRAD loci using a phylogenetic approach. An IM model was then used to estimate split times and other relevant demographic parameters. A set of 300 ddRAD loci that included 85 calibrated loci resulted in good mixing and model convergence. The results showed that the two populations of A. scherman present in the Iberian Peninsula split 34 thousand years ago, during the last glaciation. In addition, the much greater divergence from its sister species, A. amphibius, may help to clarify the controversial taxonomy of the genus. We conclude that this approach, based on ddRAD data and an IM model, is highly useful for analyzing the origin of populations and species.J.C. was financially supported by research projects CGL2014-53968-P and CGL2017-84799-P of MCIN/AEI/10.13039/501100011033, Spain, and "ERDF A way of making Europe", European Union. Temple University’s HPC resources of J.H. were supported by the National Science Foundation grant 1625061 and by the US Army Research Laboratory contract W911NF-16-2-0189. A.B.P was supported by research contract BES-2015-074119 of MCIN/AEI/10.13039/501100011033, Spain, and "ERDF A way of making Europe", European Union.Peer reviewe

Evaluating the use of non‐invasive hair sampling and ddRAD to characterize populations of endangered species: Application to a peripheral population of the European mink

Abstract The application of next‐generation sequencing (NGS) to non‐invasive samples is one of the most promising methods in conservation genomics, but these types of samples present significant challenges for NGS. The European mink (Mustela lutreola) is critically endangered throughout its range. However, important aspects such as census size and inbreeding remain still unknown in many populations, so it is crucial to develop new methods to monitor this species. In this work, we placed hair tubes along riverbanks in a border area of the Iberian population, which allowed the genetic identification of 76 European mink hair samples. We then applied a reduced representation genomic sequencing (ddRAD) technique to a subset of these samples to test whether we could extract sufficient genomic information from them. We show that several problems with the DNA, including contamination, fragmentation, oxidation, and possibly sample mixing, affected the samples. Using various bioinformatic techniques to reduce these problems, we were able to unambiguously genotype 19 hair samples belonging to six individuals. This small number of individuals showed that the demographic status of the species in this peripheral population is worse than expected. The data obtained also allowed us to perform preliminary analyses of relatedness and inbreeding. Although further improvements in sampling and analysis are needed, the application of the ddRAD technique to non‐invasively obtained hairs represents a significant advance in the genomic study of endangered species

Size increase without genetic divergence in the Eurasian water shrew Neomys fodiens

When a population shows a marked morphological change, it is important to know whether that population is genetically distinct; if it is not, the novel trait could correspond to an adaptation that might be of great ecological interest. Here, we studied a subspecies of water shrew, Neomys fodiens niethammeri, which is found in a narrow strip of the northern Iberian Peninsula. This subspecies presents an abrupt increase in skull size when compared to the rest of the Eurasian population, which has led to the suggestion that it is actually a different species. Skulls obtained from owl pellets collected over the last 50 years allowed us to perform a morphometric analysis in addition to an extensive multilocus analysis based on short intron fragments successfully amplified from these degraded samples. Interestingly, no genetic divergence was detected using either mitochondrial or nuclear data. Additionally, an allele frequency analysis revealed no significant genetic differentiation. The absence of genetic divergence and differentiation revealed here indicate that the large form of N. fodiens does not correspond to a different species and instead represents an extreme case of size increase, of possible adaptive value, which deserves further investigation.This work was financially supported by research projects CGL2014-53968-P and CGL2017-84799-P of the “Plan Nacional I + D + I del Ministerio de Ciencia, Innovación y Universidades (Spain)”, cofinanced with FEDER funds (AEI/FEDER, UE), to J.C. Support was also provided by grant 2017-SGR-991 of the “Generalitat de Catalunya”. A.B.P. was supported by research contract BES-2015-074119 of the “Ministerio de Ciencia, Innovación y Universidades”, cofinanced with FEDER funds