Biology subjects

Valstad, M.

Publications and source records attributed to Valstad, M..

5 recordsLinked to original sources

bioRxiv2026

LT-FGRS: a unifying R-package for the estimation of family-based genetic liabilities at population-scale

Estimates of per-individual genetic liability from large-scale family data are routinely used in biomedical research to describe genetic etiology of traits and disorders, boost the power of gene-mapping studies, and improve risk predictions. Here we present LT-FGRS, an R package for handling population-scale pedigrees and implementing multiple state-of-the-field methods for estimating genetic liability from such data. Benchmarking in population-scale Nordic registry data demonstrates that LT-FGRS reproduces estimates from existing implementations at manageable computational cost. LT-FGRS unifies previous parallel implementations into a single framework, lowering barriers for methodological comparison and applied use. Availability and ImplementationLT-FGRS is available as an R-package on CRAN. (https://CRAN.R-project.org/package=LTFGRS) Contactemp@au.dk; morten.dybdahl.krebs@regionh.dk Supplementary informationhttps://emilmip.github.io/LTFGRS

genetics↗

bioRxiv2023

Genetic mechanisms for impaired synaptic plasticity in schizophrenia revealed by computational modelling

Schizophrenia phenotypes are suggestive of impaired cortical plasticity in the disease, but the mechanisms of these deficits are unknown. Genomic association studies have implicated a large number of genes that regulate neuromodulation and plasticity, indicating that the plasticity deficits have a genetic origin. Here, we used biochemically detailed computational modelling of post-synaptic plasticity to investigate how schizophrenia-associated genes regulate long-term potentiation (LTP) and depression (LTD). We combined our model with data from post-mortem mRNA expression studies (CommonMind gene-expression datasets) to assess the consequences of altered expression of plasticity-regulating genes for the amplitude of LTP and LTD. Our results show that the expression alterations observed post mortem, especially those in anterior cingulate cortex, lead to impaired PKA-pathway-mediated LTP in synapses containing GluR1 receptors. We validated these findings using a genotyped EEG dataset where polygenic risk scores for synaptic and ion channel-encoding genes as well as modulation of visual evoked potentials (VEP) were determined for 286 healthy controls. Our results provide a possible genetic mechanism for plasticity impairments in schizophrenia, which can lead to improved understanding and, ultimately, treatment of the disorder.

neuroscience↗

bioRxiv2020

Evidence for reduced long-term potentiation-like visual cortical plasticity in schizophrenia and bipolar disorder

BackgroundSeveral lines of research suggest that impairments in long-term potentiation (LTP)-like synaptic plasticity might be a key pathophysiological mechanism in schizophrenia (SZ) and bipolar disorder type I (BDI) and II (BDII). Using modulations of visually evoked potentials (VEP) of the electroencephalogram, impaired LTP-like visual cortical plasticity has been implicated in patients with BDII, while there has been conflicting evidence in SZ, a lack of research in BDI, and mixed results regarding associations with symptom severity, mood states, and medication. MethodsWe measured the VEP of patients with SZ spectrum disorders (n=31), BDI (n=34), BDII (n=33), and other BD spectrum disorders (n=2), and age-matched healthy control participants (n=200) before and after prolonged visual stimulation. ResultsCompared to healthy controls, modulation of VEP component N1b, but not C1 or P1, was impaired both in patients within the SZ spectrum ({chi}2=35.1, p=3.1x10-9) and BD spectrum ({chi}2=7.0, p=8.2x10-3), including BDI ({chi}2=6.4, p=0.012), but not BDII ({chi}2=2.2, p=0.14). N1b modulation was also more severely impaired in SZ spectrum than BD spectrum patients ({chi}2=14.2, p=1.7x10-4). The reduction in N1b modulation was related to PANSS total scores ({chi}2=10.8, p=1.0x10-3), and nominally to number of psychotic episodes ({chi}2=4.9, p=0.027). Conclusions. These results suggest that LTP-like plasticity is impaired in SZ and BDI, but not BDII, and related to psychotic symptom severity. Adding to previous genetic, pharmacological, and anatomical evidence, these results implicate aberrant synaptic plasticity as a mechanism underlying SZ and BD.

neuroscience↗

bioRxiv2020

Experience-dependent modulation of the visual evoked potential: testing effect sizes, retention over time, and associations with age in 415 healthy individuals

Experience-dependent modulation of the visual evoked potential (VEP) is a promising proxy measure of synaptic plasticity in the cerebral cortex. However, existing studies are limited by small to moderate sample sizes as well as by considerable variability in how VEP modulation is quantified. In the present study, we used a large sample (n = 415) of healthy volunteers to compare different quantifications of VEP modulation with regards to effect sizes and retention of the modulation effect over time. We observed significant modulation for VEP components C1 (Cohens d = 0.53), P1 (d = 0.66), N1 (d = -0.27), N1b (d = -0.66), but not P2 (p = 0.1), and in one time-frequency cluster (~30 Hz and ~70 ms post-stimulus; d = -0.48), 2-4 minutes after 2 Hz prolonged visual stimulation. For components N1 (d = -0.21) and N1b (d = -0.38), as well for the time-frequency cluster (d = -0.33), this effect was retained after 54-56 minutes. Moderate to high correlations ({rho} = [0.39, 0.69]) between modulation at different postintervention blocks revealed a relatively high temporal stability in the modulation effect for each VEP component. However, different VEP components also showed markedly different temporal retention patterns. Finally, P1 modulation correlated positively with age (t = 5.26), and was larger for female participants (t = 3.91), with no effects of either age or sex on N1 and N1b potentiation. These results provide strong support for VEP modulation, and especially N1b modulation, as a robust measure of synaptic plasticity, but underscore the need to differentiate between components, and to control for demographic confounders.

neuroscience↗

bioRxiv2016

The correlation between central and peripheral oxytocin concentrations: a systematic review and meta-analysis

There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate central concentrations in psychiatric research. This methodological approach has obvious appeal given the invasiveness of cerebrospinal fluid collection. However, the validity of this approach and potential moderators of the association between central and peripheral levels are unclear. Thus, we conducted a pre-registered systematic search and meta-analysis of correlations between central and peripheral oxytocin concentrations. A search of databases yielded 17 eligible studies for effect size synthesis and moderator analysis, resulting in a total sample size of 516 participants and subjects. Overall, a positive association between central and peripheral oxytocin concentrations was revealed [r=0.29, 95% CI (0.15, 0.42), p<0.0001], along with a moderate-to-high level of heterogeneity across effect sizes [Q=88.14, p<0.0001], and no evidence of publication bias (p=0.45). This association was significantly moderated by experimental context [Qb(4), p=0.0016]. The strongest association was observed after intranasal oxytocin administration (r=0.67, p<.0001), a correlation that was significantly greater (p=.0002) than the equivalent association under baseline conditions (r=0.08, p=.31). These results support the use of peripheral levels of oxytocin as a marker of central levels, but only after exogenous oxytocin administration. Despite the popularity of using peripheral OT levels to approximate central levels during baseline conditions, this approach is not supported by the present results.

physiology↗