Polygenic risk has an impact on the structural plasticity of hippocampal subfields during aerobic exercise combined with cognitive remediation in multi-episode schizophrenia

Preliminary studies suggest that, besides improving cognition, aerobic exercise might increase hippocampal volume in schizophrenia patients;however, results are not consistent. Individual mechanisms of volume changes are unknown but might be connected to the load of risk genes. Genome-wide association studies have uncovered the polygenic architecture of schizophrenia. The secondary analysis presented here aimed to determine the modulatory role of schizophrenia polygenic risk scores (PRSs) on volume changes in the total hippocampus and cornu ammonis (CA) 1, CA2/3, CA4/dentate gyrus (DG) and subiculum over time. We studied 20 multi-episode schizophrenia patients and 23 healthy controls who performed aerobic exercise (endurance training) combined with cognitive remediation for 3 months and 21 multi-episode schizophrenia patients allocated to a control intervention (table soccer) combined with cognitive remediation. Magnetic resonance imaging-based assessments were performed at baseline and after 3 months with FreeSurfer. No effects of PRSs were found on total hippocampal volume change. Subfield analyses showed that the volume changes between baseline and 3 months in the left CA4/DG were significantly influenced by PRSs in schizophrenia patients performing aerobic exercise. A larger genetic risk burden was associated with a less pronounced volume increase or a decrease in volume over the course of the exercise intervention. Results of exploratory enrichment analyses reinforced the notion of genetic risk factors modulating biological processes tightly related to synaptic ion channel activity, calcium signaling, glutamate signaling and regulation of cell morphogenesis. We hypothesize that a high polygenic risk may negatively influence neuroplasticity in CA4/DG during aerobic exercise in schizophrenia

Patterns in Nuclear and Mitochondrial DNA Reveal Historical and Recent Isolation in the Black-Tailed Godwit (Limosa limosa)

On the basis of morphological differences, three subspecies of Black-tailed Godwit (Limosa limosa) have been recognized (L. l. limosa, L. l. islandica and L. l. melanuroides). In previous studies mitochondrial DNA (mtDNA) sequence data showed minimal genetic divergence between the three subspecies and an absence of sub-structuring within L. l. limosa. Here, population genetic structure and phylogeographic patterns have been analyzed using COI, HVR1 and HVR2 mtDNA sequence data as well as 12 microsatellite loci (nuDNA). The nuDNA data suggest genetic differentiation between L. l. limosa from Sweden and The Netherlands, between L. l. limosa and L. l. islandica, but not between L. l. limosa and L. l. melanuroides. However, the mtDNA data were not consistent with the nuDNA pattern. mtDNA did support a split between L. l. melanuroides and L. l. limosa/L. l. islandica and also demonstrated two L. l. limosa haplotype clusters that were not geographically isolated. This genetic structure can be explained by a scenario of isolation of L. l. melanuroides from L. l. limosa in Beringia during the Last Glacial Maximum. During the Pleistocene separation of L. l. islandica from L. l. limosa occurred, followed by colonization of Iceland by the L. l. islandica during the Holocene. Within L. l. limosa founder events, followed by population expansion, took place during the Holocene also. According to the patterns observed in both markers together and their geographic separation, we propose that the three traditional subspecies indeed represent three separate genetic units.

Identifying endophenotypes for depression in Generation Scotland: a Scottish family health study

Depression is the most common psychiatric disorder and the leading cause of disability worldwide. Despite evidence for a genetic component, the genetic aetiology of this disorder remains elusive. To date, only one association study has identified and replicated risk loci for depression. This thesis focuses on aiding genetic discovery by revisiting the depressed phenotype and developing a quantitative trait, using data from Generation Scotland: The Scottish Family Health Study. These analyses aim to test whether this derived quantitative trait has improved statistical power to identify genetic risk variants for depression, relative to the binary classification of case/control. Measures of genetic covariation were used to evaluate and rank ten measures of mood, personality and cognitive ability as endophenotypes for depression. The highest ranking traits were subjected to principal component analysis, and the first principal component used as a quantitative measure of depression. This composite trait was compared to the binary classification of depression in terms of ability to identify risk loci in a genome-wide association study, and phenotypic variance explained by polygenic profile scores for psychiatric disorders. I also compared the composite trait to the univariate traits in terms of their ability to fulfill the endophenotype criteria as described by Gottesman and Gould, namely: being heritable, genetically and phenotypically correlated with depression, state independent, co-segregating with illness in families, and observed at a higher rate in unaffected relatives than in unrelated controls. Four out of ten traits fulfilled most endophenotype criteria, however, only two traits - neuroticism and the general health questionnaire (a measure of current psychological distress) - consistently ranked highest across all analyses. As such, three composite traits were derived incorporating two, three, or four traits. Association analyses of binary depression, univariate traits and composite traits yielded no genome-wide significant results, with most traits performing equivalently. However, composite traits were more heritable and more highly correlated with depression than their constituent traits, suggesting that analyzing these traits in combination was capturing more of the heritable component of depression. Polygenic scores for psychiatric disorders explained more trait variance for the composite traits than the univariate traits, and depression itself. Overall, whilst the composite traits generally obtained more significant results, they did not identify any further insight into the genetic aetiology of depression. This work therefore provides support for the urgent need to redefine the depressed phenotype based on objective and quantitative measures. This is essential for risk stratification, better diagnoses, novel target identification and improved treatment

Contrasting genetic structuring between colonies of the world\u27s smallest penguin, Eudyptula minor (Aves: Spheniscidae)

The Little Penguin, Eudyptula minor, is a seabird that nests in colonies throughout New Zealand and southern Australia. Individuals from different colonies in southeast Australia differ significantly in morphology and ecology, suggesting that some genetic structuring may exist among colonies. In contrast, the marking of individuals with flipper bands has revealed some, albeit infrequent, movement between colonies. To determine the extent of genetic structuring, we tested the null hypothesis of substantial gene flow within southeast Australia by examining patterns of genetic variation across seven colonies separated by up to 1,500 km. Phylogeographic structuring was absent for mitochondrial control region sequences (2&ndash;3 individuals per colony). Microsatellite allele frequencies at five loci and mitochondrial haplotype frequencies (50 individuals per colony) were also homogenous among the majority of colonies sampled, although two colonies at the western periphery of the sampling range were distinct from those to the east. The genetic homogeneity among the majority of colonies can be explained by low but consistent contemporary gene flow among them, or a recent founder event in Bass Strait following the last marine transgression. The genetic break towards the western end of the sampling distribution appears best explained by differences in sea surface temperature and, consequentially breeding phenology, the latter hindering genetically effective migration. <br /