Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.

While clozapine is the most effective antipsychotic drug, its use is limited due to hematological adverse effects involving the reduction of granulocyte counts with potential life-threatening agranulocytosis. It is not yet possible to predict or prevent the risk of agranulocytosis, and the mechanisms are unknown but likely related to clozapine metabolism. Genome-wide association studies (GWASs) of clozapine metabolism and clozapine-induced agranulocytosis have identified few genetic loci.

Comparative analysis of intraoperative thermal and optical imaging for identification of the human primary sensory cortex.

Significance: The precise identification and preservation of functional brain areas during neurosurgery are crucial for optimizing surgical outcomes and minimizing postoperative deficits. Intraoperative imaging plays a vital role in this context, offering insights that guide surgeons in protecting critical cortical regions.

Aim: We aim to evaluate and compare the efficacy of intraoperative thermal imaging (ITI) and intraoperative optical imaging (IOI) in detecting the primary somatosensory cortex, providing a detailed assessment of their potential integration into surgical practice.

Genome-wide meta-analyses of non-response to antidepressants identify novel loci and potential drugs.

Antidepressants exhibit a considerable variation in efficacy, and increasing evidence suggests that individual genetics contribute to antidepressant treatment response. Here, we combined data on antidepressant non-response measured using rating scales for depressive symptoms, questionnaires of treatment effect, and data from electronic health records, to increase statistical power to detect genomic loci associated with non-response to antidepressants in a total sample of 135,471 individuals prescribed antidepressants (25,255 non-responders and 110,216 responders). We performed genome-wide association meta-analyses, genetic correlation analyses, leave-one-out polygenic prediction, and bioinformatics analyses for genetically informed drug prioritization.

Synaptic modulation of glutamate in striatum of the YAC128 mouse model of Huntington disease.

Background: Altered balance between striatal direct and indirect pathways contributes to early motor, cognitive and psychiatric symptoms in Huntington disease (HD). While degeneration of striatal D2-type dopamine receptor (D2)-expressing indirect pathway medium spiny neurons (iMSNs) occurs prior to that of D1-type dopamine receptor (D1)-expressing direct pathway neurons, altered corticostriatal synaptic function precedes degeneration. D2-mediated signaling on iMSNs reduces their excitability and promotes endocannabinoid (eCB) synthesis, suppressing glutamate release from cortical afferents.

Evolutionary potential and constraints in an aposematic species: Genetic correlations between warning coloration and fitness components in wood tiger moths.

Variability in warning signals is common but remains puzzling since deviations from the most common form should result in a higher number of predator attacks. One explanation may lie in constraints due to genetic correlations between warning colour and other traits under selection. To explore the relationship between variation in warning colour and different life-history traits, we used an extensive data set comprising 64,741 individuals from a Finnish and an Estonian population of the wood tiger moths, Arctia plantaginis, that have been maintained in captivity over 25 generations.