Mid Sweden University

Background: White blood cells or leukocytes, which have a variety of immunological functions, have been shown to migrate in and out of the blood stream in response to different types of stressors (Davis et al., 2008). Hence, leukocyte profiling can be used to measure stress related immune activation. In the present study we employed a psychosocial stress task to assess whether emotional arousal cause leukocyte migration. Methods: We used the Trier Social Stress Test (TSST) to induce psychosocial stress. Emotional arousal was assessed with ECG, self-report measures, and blood sampling. Results: We found an increase in heart rate from baseline throughout the TSST (p < .001) and increased blood cortisol levels directly and 30 minutes after the TSST compared to baseline (p < .001). We found an increase in total Leukocyte count after the stress task (p < .001) with a return to baseline at 30, 60 and 90 minutes after (p < .001). Conclusion: The results of our study indicate that psychosocial stress triggers a physiological response manifesting as increased heart rate, cortisol levels, and leukocyte count. Our findings suggest that emotional arousal might be a key factor in inducing an immune response under stressful conditions. It is important to note that the leukocyte count returned to baseline levels within 30 minutes following the stress task, suggesting a transient and adaptive response of the immune system to social stress. Our findings support the idea that the body's physiological and immune responses to stress are interconnected and influenced by emotional states.

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience-dependent adjustments of interpersonal distance.

Nociceptive processing in the human brain is complex and involves several brain structures and varies across individuals. Determining the structures that contribute to interindividual differences in nociceptive processing is likely to improve our understanding of why some individuals feel more pain than others. Here, we found specific parts of the cerebral response to nociception that are under genetic influence by employing a classic twin-design. We found genetic influences on nociceptive processing in the midcingulate cortex and bilateral posterior insula. In addition to brain activations, we found genetic contributions to large-scale functional connectivity (FC) during nociceptive processing. We conclude that additive genetics influence specific brain regions involved in nociceptive processing. The genetic influence on FC during nociceptive processing is not limited to core nociceptive brain regions, such as the dorsal posterior insula and somatosensory areas, but also involves cognitive and affective brain circuitry. These findings improve our understanding of human pain perception and increases chances to find new treatments for clinical pain.

Fear conditioning is an evolutionarily conserved type of learning serving as a model for the acquisition of situationally induced anxiety. Brain function supporting fear conditioning may be genetically influenced, which in part could explain genetic susceptibility for anxiety following stress exposure. Using a classical twin design and functional magnetic resonance imaging, we evaluated genetic influences (h²) on brain activity and standard autonomic measures during fear conditioning. We found an additive genetic influence on mean brain activation (h² = 0.34) and autonomic responses (h² = 0.24) during fear learning. The experiment also allowed estimation of the genetic influence on brain activation during safety learning (h² = 0.55). The mean safety, but not fear, related brain activation was genetically correlated with autonomic responses. We conclude that fear and safety learning processes, both involved in anxiety development, are moderately genetically influenced as expressed both in the brain and the body.

Background

Polygenic scores (PGSs) harness the potential to provide an overall measure of individuals’ genetic liability to develop a disease (Torkamani et al., 2018), though much research is still needed. The aim of the present study was to predict prescription of pharmacological treatment of anxiety or depression from PGSs.

Methods

The target sample comprised two cohorts of genotyped Swedish twins (n = 11037). Cases were defined as individuals prescribed pharmacological treatment of depression (n = 1129) or anxiety (n = 1446). We constructed 6 PGSs based on GWAS on MDD diagnosis, Anxiety, Schizophrenia, Neuroticism scores, the GAD-7 scale, and the PHQ-9. Data were analyzed by logistic regression models with change in pseudo-R2 (above the baseline model with sex, age, cohort, and 20 ancestral PCs) following the inclusion of PGSs to predict the risk of anxiety or depression medication. All results corrected for multiple comparisons.

Results

Predictive performance was estimated to ΔR2depression = 0.028; ΔR2anxiety = 0.025 when all PGSs were included in the same model, with PGS for MDD being the single best predictor for both anxiety and depression. Individuals in the top 10% of the PGS distribution had greater odds of drug prescription (ORdepression = 1.82; CI95% = 1.53—2.17; ORanxiety = 1.65; CI95% = 1.40—1.95), while the bottom 10% had decreased risk (ORanxiety = 0.56; CI95% = 0.45—0.70; ORdepression = 0.58; CI95% = 0.45—0.74) compared to the remaining 90% of the distribution.

Conclusions

PGSs can predict drug prescription for anxiety and depression in an independent sample.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of 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 SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). 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 additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR 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.

Recent genome-wide association studies (GWAS) have identified several common variants associated with depression (Howard et al. 2019; Levey et al. 2021) and anxiety disorders (Levey et al. 2020; Meier et al. 2019; Purves et al. 2020), and these findings have been harnessed to develop polygenic scores (PGS) in order to provide an overall measure of individuals’ genetic liability to develop a disease (Torkamani et al. 2018). Research on the utility of PGSs as predictors of risk for disease is gaining traction, with studies on somatic illness showing that disease risk increases sharply in the right tail of the PGS distribution (Khera et al. 2018). Thus, PGS stratification could be of clinical relevance if it provides an opportunity to target those in need of preventive interventions with increased precision. The current potential of PGS stratification for depression and anxiety disorders remains an open question. In the current study, we applied 36 predefined PGSs from the polygenic index repository (Becker et al. 2021) on a target sample of 11,210 genotyped twins. Cases were defined as those with prescribed medication, where the prescription explicitly stated that a drug was ordinated for indication of depression or anxiety, respectively. Drugs included antidepressants (SSRI and SNRI), Benzodiazepines, Antihistamines, Buspirone, and Betablockers.