Mapping vocal interactions in space and time differentiates signal broadcast versus signal exchange in meerkat groups.

Animal vocal communication research traditionally focuses on acoustic and contextual features of calls, yet substantial information is also contained in response selectivity and timing during vocalization events. By examining the spatiotemporal structure of vocal interactions, we can distinguish between 'broadcast' and 'exchange' signalling modes, with the former potentially serving to transmit signallers' general state and the latter reflecting more interactive signalling behaviour. Here, we tracked the movements and vocalizations of wild meerkat (Suricata suricatta) groups simultaneously using collars to explore this distinction. We found evidence that close calls (used for maintaining group cohesion) are given as signal exchanges. They are typically given in temporally structured call-response sequences and are also strongly affected by the social environment, with individuals calling more when they have more neighbours and juveniles responding more to adults than the reverse. In contrast, short note calls appear mainly in sequences produced by single individuals and show little dependence on social surroundings, suggesting a broadcast signalling mode. Despite these differences, both call categories show similar clustering in space and time at a group level. Our results highlight how the fine-scale structure of vocal interactions can give important insights into the usage and function of signals in social groups. This article is part of the theme issue 'The power of sound: unravelling how acoustic communication shapes group dynamics.'

Association between Maternal Perinatal Stress and Depression on Infant DNA Methylation in the First Year of Life.

Maternal stress and depression during pregnancy and the first year of the infant's life affect a large percentage of mothers. Maternal stress and depression have been associated with adverse fetal and childhood outcomes as well as differential child DNA methylation (DNAm). However, the biological mechanisms connecting maternal stress and depression to poor health outcomes in children are still largely unknown. Here we aim to determine whether prenatal stress and depression are associated with changes in cord blood mononuclear cell DNAm (CBMC-DNAm) in newborns (n = 119) and whether postnatal stress and depression are associated with changes in peripheral blood mononuclear cell DNAm (PBMC-DNAm) in children of 12 months of age (n = 113) from the Canadian Healthy Infant Longitudinal Development (CHILD) cohort. Stress was measured using the 10-item Perceived Stress Scale (PSS) and depression was measured using the Center for Epidemiologic Studies Depression Questionnaire (CESD). Both stress and depression were measured at 18 weeks and 36 weeks of pregnancy and six months and 12 months postpartum. We conducted epigenome-wide association studies (EWAS) using robust linear regression followed by a sensitivity analysis in which we bias-adjusted for inflation and unmeasured confounding using the bacon and cate methods. To investigate the cumulative effect of maternal stress and depression, we created composite prenatal and postnatal adversity scores. We identified a significant association between prenatal stress and differential CBMC-DNAm at 8 CpG sites and between prenatal depression and differential CBMC-DNAm at 2 CpG sites. Additionally, we identified a significant association between postnatal stress and differential PBMC-DNAm at 8 CpG sites and between postnatal depression and differential PBMC-DNAm at 11 CpG sites. Using our composite scores, we further identified 2 CpG sites significantly associated with prenatal adversity and 7 CpG sites significantly associated with postnatal adversity. Several of the associated genes, including PLAGL1, HYMAI, BRD2, and ERC2 have been implicated in adverse fetal outcomes and neuropsychiatric disorders. This suggested that differential DNAm may play a role in the relationship between maternal mental health and child health.

A practical guide for generating unsupervised, spectrogram-based latent space representations of animal vocalizations.

BACKGROUND: The manual detection, analysis and classification of animal vocalizations in acoustic recordings is laborious and requires expert knowledge. Hence, there is a need for objective, generalizable methods that detect underlying patterns in these data, categorize sounds into distinct groups and quantify similarities between them. Among all computational methods that have been proposed to accomplish this, neighbourhood-based dimensionality reduction of spectrograms to produce a latent space representation of calls stands out for its conceptual simplicity and effectiveness. Goal of the study/what was done: Using a dataset of manually annotated meerkat Suricata suricatta vocalizations, we demonstrate how this method can be used to obtain meaningful latent space representations that reflect the established taxonomy of call types. We analyse strengths and weaknesses of the proposed approach, give recommendations for its usage and show application examples, such as the classification of ambiguous calls and the detection of mislabelled calls. What this means: All analyses are accompanied by example code to help researchers realize the potential of this method for the study of animal vocalizations.

Investigation of MORC1 DNA methylation as biomarker of early life stress and depressive symptoms.

Early life stress (ELS) is associated with an increased risk of depression and this association may be mediated by epigenetic mechanisms. A previous epigenome-wide DNA methylation (DNAm) study investigating human newborns and two animal models of ELS suggested that the epigenetic regulator MORC1 is differentially methylated following ELS. The ELS-induced DNAm alterations were long-lasting in the animal models. However, whether this finding is also transferable to humans experiencing ELS in childhood was not investigated. Further, MORC1 may provide a link between ELS and adult depression, as MORC1 DNAm and genetic variants were found to be associated with depressive symptoms in humans. In the present study, we investigated the validity of MORC1 DNAm as a biomarker of ELS in humans and its role in linking ELS to depression later in life by studying childhood maltreatment. We analyzed whole blood MORC1 DNAm in an adult cohort (N = 151) that was characterized for both the presence of depressive symptoms and childhood maltreatment. Further, we investigated the association between MORC1 DNAm, depressive symptoms and childhood maltreatment in two additional cohorts (N = 299, N = 310). Overall, our data do not indicate an association of MORC1 DNAm with childhood maltreatment. An association of MORC1 DNAm with depressive symptoms was present in all cohorts, but was inconsistent in the specific CpG sites associated and the direction of effect (Tuebingen cohort: standardized ß = 0.16, unstandardized ß = 0.01, 95% CI [-0.0004, -0.0179], p = 0.061, PReDICT cohort: standardized ß = -0.12, unstandardized ß = -0.01, 95% CI [-0.0258, -0.0003], p = 0.045), Grady cohort: standardized ß = 0.16, unstandardized ß = 0.008, 95% CI [0.0019, 0.0143], p = 0.01). Our study thus suggests that peripheral MORC1 DNAm cannot serve as biomarker of childhood maltreatment in adults, but does provide further indication for the association of MORC1 DNAm with depressive symptoms.

Differential COMT DNA methylation in patients with Borderline Personality Disorder: Genotype matters.

Differential DNA methylation in peripheral tissues has been associated with Borderline Personality Disorder (BPD). Alterations have been found in several genes, among them the Catechol-O-methyltransferase (COMT) gene. COMT is a known neuropsychiatric candidate gene, which contains a genotype variant (Val108/158Met) that affects protein function and has been found associated with several psychiatric disorders. In addition, this variant also affects COMT DNA methylation. However, in previous epigenetic studies, the DNA methylation results have not always been controlled for genotype, even though overrepresentation of the Met allele has been frequently reported in cohorts of BPD patients. Therefore, in the present study, we investigated whether alteration of COMT DNA methylation in BPD patients is indeed associated with mental health status or merely influenced by a differential distribution of the COMT genotype between BPD patients and healthy control individuals. We found significant group differences, as well as a strong effect of genotype on COMT DNA methylation. While the direction of effect was different compared to a previous study, our study supports the finding of altered COMT DNA methylation in patients with BPD and reinforces the need to include genotype information in future DNA methylation studies of COMT.

CACNA1C risk variant affects microstructural connectivity of the amygdala.

Deficits in perception of emotional prosody have been described in patients with affective disorders at behavioral and neural level. In the current study, we use an imaging genetics approach to examine the impact of CACNA1C, one of the most promising genetic risk factors for psychiatric disorders, on prosody processing on a behavioral, functional and microstructural level. Using functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) we examined key areas involved in prosody processing, i.e. the amygdala and voice areas, in a healthy population. We found stronger activation to emotional than neutral prosody in the voice areas and the amygdala, but CACNA1C rs1006737 genotype had no influence on fMRI activity. However, significant microstructural differences (i.e. mean diffusivity) between CACNA1C rs1006737 risk allele carriers and non carriers were found in the amygdala, but not the voice areas. These modifications in brain architecture associated with CACNA1C might reflect a neurobiological marker predisposing to affective disorders and concomitant alterations in emotion perception.

Disrupted prefrontal functional connectivity during post-stress adaption in high ruminators.

Rumination is a perseverative thinking style that is associated with adverse mental and physical health. Stressful situations have been considered as a trigger for this kind of thinking. Until today, there are mixed findings with respect to the relations of functional connectivity (FC) and rumination. The study at hand aimed to investigate, in how far high and low ruminators would show elevated levels of state rumination after a stress induction and if these changes would show corresponding changes in FC in the cognitive control network (CCN) and dorsal attention network (DAN). 23 high and 22 low trait ruminators underwent resting-state measurements before and after a stress induction with the Trier Social Stress Test (TSST). Changes in rsFC through the TSST were measured with functional near-infrared spectroscopy within and between regions of the CCN. Stress successfully induced state rumination in both groups but stronger in the high trait ruminators. High trait ruminators showed elevated FC within the CCN at baseline, but attenuated increase in FC following the TSST. Increases in FC correlated negatively with state rumination. A lack of FC reactivity within the CCN in high ruminators might reflect reduced network integration between brain regions necessary for emotion regulation and cognitive control.

Increased BDNF methylation in saliva, but not blood, of patients with borderline personality disorder.

BACKGROUND: The importance of epigenetic alterations in psychiatric disorders is increasingly acknowledged and the use of DNA methylation patterns as markers of disease is a topic of ongoing investigation. Recent studies suggest that patients suffering from Borderline Personality Disorder (BPD) display differential DNA methylation of various genes relevant for neuropsychiatric conditions. For example, several studies report differential methylation in the promoter region of the brain-derived neurotrophic factor gene (BDNF) in blood. However, little is known about BDNF methylation in other tissues. RESULTS: In the present study, we analyzed DNA methylation of the BDNF IV promoter in saliva and blood of 41 BPD patients and 41 matched healthy controls and found significant hypermethylation in the BPD patient's saliva, but not blood. Further, we report that BDNF methylation in saliva of BPD patients significantly decreased after a 12-week psychotherapeutic intervention. CONCLUSIONS: Providing a direct comparison of BDNF methylation in blood and saliva of the same individuals, our results demonstrate the importance of choice of tissue for the study of DNA methylation. In addition, they indicate a better suitability of saliva for the study of differential BDNF methylation in BPD patients. Further, our data appear to indicate a reversal of disease-specific alterations in BDNF methylation in response to psychotherapy, though further experiments are necessary to validate these results and determine the specificity of the effect.

Stress-related dysfunction of the right inferior frontal cortex in high ruminators: An fNIRS study.

Repetitive thinking styles such as rumination are considered to be a key factor in the development and maintenance of mental disorders. Different situational triggers (e.g., social stressors) have been shown to elicit rumination in subjects exhibiting such habitual thinking styles. At the same time, the process of rumination influences the adaption to stressful situations. The study at hand aims to investigate the effect of trait rumination on neuronal activation patterns during the Trier Social Stress Test (TSST) as well as the physiological and affective adaptation to this high-stress situation. Methods: A sample of 23 high and 22 low ruminators underwent the TSST and two control conditions while their cortical hemodynamic reactions were measured with functional near-infrared spectroscopy (fNIRS). Additional behavioral, physiological and endocrinological measures of the stress response were assessed. Results: Subjects showed a linear increase from non-stressful control conditions to the TSST in cortical activity of the cognitive control network (CCN) and dorsal attention network (DAN), comprising the bilateral dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus (IFG) and superior parietal cortex/somatosensory association cortex (SAC). During stress, high ruminators showed attenuated cortical activity in the right IFG, whereby deficits in IFG activation mediated group differences in post-stress state rumination and negative affect. Conclusions: Aberrant activation of the CCN and DAN during social stress likely reflects deficits in inhibition and attention with corresponding negative emotional and cognitive consequences. The results shed light on possible neuronal underpinnings by which high trait rumination may act as a risk factor for the development of clinical syndromes.

Impaired PARP activity in response to the ß-adrenergic receptor agonist isoproterenol.

Psychological stress has been associated with DNA damage, thus increasing the risk of numerous diseases including cancer. Here, we investigate the effect of acute and chronic stress on poly(ADP-ribose) polymerase-1 (PARP-1), a sensor of DNA damage and DNA repair initiator. In order to mimic the chronic release of epinephrine, human peripheral blood mononuclear cells (PBMCs) were treated repeatedly with the sympathomimetic drug isoproterenol. We found significant induction of DNA strand breaks that remained unrepaired 24 h after ex vivo incubation. Isoproterenol-induced DNA strand breaks could be partially prevented by pre-treatment with the ß-adrenergic receptor antagonist propranolol. Furthermore, the level of PARP-1 protein and PARP activity decreased and the levels of the PARP substrate nicotinamide adenine dinucleotide (NAD+) and of adenosine triphosphate (ATP), necessary to replenish NAD+ pools, were lowered by isoproterenol treatment. In conclusion our data provide novel insights into the mechanisms of isoproterenol-induced genotoxicity linking ß-adrenergic stimulation and PARP-1.

Bayesian informed evidence against modulation of androstadienone-effects by genotypic receptor variants and participant sex: A study assessing Stroop interference control, mood and olfaction.

The androgen derivative androstadienone (AND) is present in human sweat and may act as human chemosignal. Though effects of AND have been reported with respect to emotional and cognitive processes, results have been highly inconsistent. For this reason, it is likely that AND-action is dependent on modulatory factors. Here we wanted to specifically investigate the impact of genotypic variations of the AND-receptor OR7D4, as well as the influence of participant sex and concomitant hormonal fluctuations on AND-action during emotional interference processing, olfactory performance and mood assessments. To this end 80 healthy individuals (women taking oral contraceptives; naturally cycling women measured during the luteal phase and men) were tested twice on two consecutive days (AND vs. placebo exposure) with an emotional Stroop task. Also, olfactory performance and mood was assessed. Participants provided saliva samples to measure testosterone, progesterone and estradiol and a blood sample to assess genotypic variations of the AND-receptor OR7D4. We found a small task-dependent reduction of overall error rates under AND but no modulation of effects by genetic variation or group (female OC, female NC, male) with respect to olfactory performance and mood. Additional analyses with help of Bayesian statistics gave strong evidence in favor of specific null hypotheses suggesting that the action of AND was not modulated by either genotypic variations or sex of participants with respect to interference control (bias indices), olfactory self-reports and mood parameters. Additional effects of AND in connection with hormonal fluctuations are reported.

Cortical hemodynamic changes during the Trier Social Stress Test: An fNIRS study.

The study of the stress response has been of great interest in the last decades due to its relationship to physical and mental health. Along with the technological progress in the neurosciences, different methods of stress induction have been developed for the special requirements regarding the acquisition of neuroimaging data. However, these paradigms often differ from ecologically valid stress inductions such as the Trier Social Stress Test (TSST) in substantial ways. In the study at hand, we used the rather robust optical imaging method of functional Near-infrared Spectroscopy (fNIRS) to assess brain activation during the TSST and two non-stressful control conditions. Additionally, we measured other stress parameters including the cortisol response and subjective stress ratings. As expected we found significant increases in subjective and physiological stress measures during the TSST in comparison to the baseline and control conditions. We found higher activation in parts of the cognitive control network (CCN) and dorsal attention network (DAN) - comprising the dorsolateral prefrontal cortex, the inferior frontal gyrus and superior parietal cortex - during the performance of the TSST in comparison to the control conditions. Further, calculation errors during the TSST as well as subjective and physiological stress parameters correlated significantly with the activation in the CCN. Our study confirms the validity of previous neuroimaging data obtained from adapted stress procedures by providing cortical activation data during a classical stress induction paradigm (i.e., the TSST) for the first time.

Differential effects of subchronic phencyclidine on anxiety in the light-enhanced startle-, light/dark exploration- and open field tests.

Subchronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP) is a valuable approach to model the symptomatology of schizophrenia, a multi-facetted psychiatric disorder, in rodents. We addressed the question whether subchronic PCP (scPCP) treatment (5 mg/kg bidaily for 7 days) would affect anxiety in rats, since contradictory findings have been reported so far. Anxiety-like behaviour was assessed using the light-enhanced startle paradigm (LES), a method which measures the effect of the natural aversion to light on the startle reflex and does not depend on motivated behaviour or exploratory drive. For comparison, anxiety-like behaviour was measured in the light-dark exploration test (LDT) and in an open field environment (OFT). The scPCP-treatment did not affect baseline startle reactivity or light-enhanced startle, suggesting normal anxiety levels in treated animals. Further, normal anxiety-like behaviour was also found in the OFT. In the LDT, scPCP treated rats displayed shorter latencies to enter the lit compartment and shuttled more between the dark and lit compartments, behaviours indicative of decreased anxiety and/or increased exploratory activity. Our findings therefore suggest that the effects of scPCP-treatment on anxiety-like behaviour are task-dependent and recommend the additional use of tests independent from exploratory drive or other motivated behaviours, such as the LES paradigm.