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Ahs, F.

Publications and source records attributed to Ahs, F..

7 recordsLinked to original sources

Fast and Slow Gene Expression Changes in Blood Following Acute Social Stress

Social stress is a risk factor for psychiatric disorders and also influences immune function. While it is known that acute social stress impacts the number of immune cells in circulation, the temporal dynamics of stress induced immune-related transcriptional changes in human blood remain unclear. To investigate changes in gene expression, we exposed 26 adults to the Trier Social Stress Test (TSST), and collected blood at baseline, as well as 5, 30, 60 and 90 min after stress. Whole-blood gene expression was profiled using a 5 targeted RNA-sequencing method (STRT). Differential expression was analyzed using linear and cubic models. We observed a total of 54 differentially expressed genes following stress. Fast responses, with a transient peak immediately following stress, were enriched for cytotoxic T cell, NK cell and dendritic cell functions (e.g., GZMB, GNLY, CCL4 and GZMA) and paralleled lymphocyte count changes. In contrast, gradual, linear responses without any evident peak were enriched for neutrophil related genes (e.g., FPR2, PLAUR, CXCR2, AQP9, and QPCT) and did not mirror neutrophil counts, indicating cell intrinsic transcriptional changes. From pathway and transcription factor enrichment analyses, IL-12 family mediated signaling is inferred as a central mechanism linking stress to immune gene regulation. Our results show that acute psychosocial stress induces both fast and slower changes in gene expression in different immune cell populations. The involvement of the IL-12-STAT4 axis and genes such as PLAUR and FPR2 suggests molecular mechanisms through which stress-related immune activation may contribute to vulnerability for anxiety and depressive disorders.

genetics↗

Genetic Influences on Neural Responses in Placebo Analgesia Circuitry

Placebo analgesia is a well-established medical phenomenon with overlapping neural representations between humans and rodents, but the genetic contribution to this conserved neural circuitry remains unknown. Using functional brain imaging in 305 monozygotic and dizygotic twins, we quantified the heritability of neural activation in placebo analgesia brain circuity during evoked pain, including the rostral anterior cingulate cortex, brainstem and cerebellum, using the ACE model. Neural responses showed significant heritability, with additive genetics accounting for 21 to 49% of the variance (A = 0.21-0.49), indicating that genetics have a moderate effect on pain-evoked brain activity within the placebo analgesia circuitry. For the first time, our findings reveal a heritable component of the neural network supporting placebo analgesia. By linking genetic variations to neural responses in placebo analgesia circuitry, this study bridges human and preclinical research and opens new ways for improving clinical trial methodology and tailoring pain therapies to individual genetic profiles.

neuroscience↗

Gray Matter Differentiation Between Two Subordinate Personality Traits of Extraversion: Enthusiasm and Assertiveness

Enthusiasm and assertiveness are two subordinate personality traits of extraversion. These traits reflect different aspects of extroversion and have distinct implications on mental health. Whereas enthusiasm predicts satisfaction in life and positive relationships, assertiveness predicts psychological distress and reduced social support. The neural basis of these subordinate traits is not well understood. To investigate brain regions where enthusiasm and assertiveness have diverging relationship with morphology, enthusiasm and assertiveness were regressed to gray matter volume (GMV) across the whole brain in a sample of 301 healthy individuals. A significant interaction was found between enthusiasm and assertiveness in the left angular gyrus (t(296) = 4.18, family wise error corrected, FWE p = .001 (cluster-level); Cluster size = 880 voxels). Larger GMV in this area was associated with more enthusiasm and less assertiveness. Our study emphasizes the value of separating extraversion into its subordinate traits when investigating associations to neuroanatomy.

neuroscience↗

Whole Brain Correlates of Individual Differences in Skin Conductance Responses during Human Fear Conditioning

Understanding the neural basis for individual differences in the conditioned skin conductance response (SCR) may inform on autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in conditioned SCR and neural activity throughout the whole brain by using data from a large functional magnetic resonance imaging study (N = 285). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe and midbrain. A ROI analysis replicated a correlation between amygdala activity and conditioned SCR, but amygdala contribution to SCR was modest compared with other regions. We suggest that implicated neural regions belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

neuroscience↗

Dopamine facilitates fear memory formation in the human amygdala

Learning which environmental cues that predict danger is crucial for survival and accomplished through Pavlovian fear conditioning. In humans and rodents alike, fear conditioning is amygdala-dependent and rests on similar neurocircuitry. Rodent studies have implicated a causative role for dopamine in the amygdala during fear memory formation, but the role of dopamine in aversive learning in humans is unclear. Here, we show dopamine release in the amygdala and striatum during fear learning in humans. Using simultaneous positron emission tomography and functional magnetic resonance imaging, we demonstrate that the amount of dopamine release is linked to strength of conditioned fear responses and linearly coupled to learning-induced memory trace activity in the amygdala. Thus, like in rodents, formation of amygdala-dependent fear memories in humans seems to be facilitated by endogenous dopamine release, supporting an evolutionary conserved neurochemical mechanism for aversive memory formation.

neuroscience↗

Genetic influences on brain activation and large-scale functional connectivity during nociceptive processing: a twin study

Nociceptive processing in the human brain is a signal that enables harm avoidance, with large interindividual variance. The relative contributions of genes and environment to the neural structures that support nociception have not been studied in twins previously. Here, we employed a classic twin-design to determine brain structures influenced by additive genetics. We found genetic influences on nociceptive processing in the midcingulate cortex, bilateral posterior insulae and thalamus. In addition to brain activations, we found genetic contributions to large-scale functional connectivity during nociceptive processing. We conclude that additive genetics influence specific aspects of nociceptive processing, which improves our understanding of human nociceptive processing.

neuroscience↗

GABA quantification in human anterior cingulate cortex

{gamma}-Aminobutyric acid (GABA) is a primary inhibitory neurotransmitter in the human brain. It has been shown that altered GABA concentration plays an important role in a variety of psychiatric and neurological disorders. The main purpose of this study was to propose a combination of PRESS and MEGA-PRESS acquisitions for absolute GABA quantification and to compare GABA estimations obtained using total choline (tCho), total creatine (tCr), and total N-acetyl aspartate (tNAA) as the internal concentration references with water referenced quantification. The second aim was to demonstrate the fitting approach of MEGA-PRESS spectra with QuasarX algorithm using a basis set of GABA, glutamate, glutamine, and NAA in vitro spectra. Thirteen volunteers were scanned with the MEGA-PRESS sequence at 3T. Interleaved water referencing was used for quantification, B0 drift correction and to update the carrier frequency of RF pulses in real time. Reference metabolite concentrations were acquired using a PRESS sequence with short TE (30 ms) and long TR (5000 ms). Absolute concentration were corrected for cerebrospinal fluid, gray and white matter water fractions and relaxation effects. Water referenced GABA estimations were significantly higher compared to the values obtained by metabolite references. We conclude that QuasarX algorithm together with the basis set of in vitro spectra improves reliability of GABA+ fitting. The proposed GABA quantification method with PRESS and MEGA-PRESS acquisitions enables the utilization of tCho, tCr, and tNAA as internal concentration references. The use of different concentration references have a good potential to improve the reliability of GABA estimation.

neuroscience↗