Julian Koenig

Background: Emotion dysregulation is common across psychiatric disorders, but the biological mechanisms underlying emotional vulnerability remain poorly understood. Cardiac vagal regulation and interoception, the perception of bodily signals, may jointly contribute to emotion regulation. We examined whether their interaction is associated with emotion dysregulation and psychopathology in adolescents receiving psychiatric inpatient treatment. Methods: We studied 279 adolescent psychiatric inpatients. Cardiac vagal regulation was assessed using heart rate variability and interoceptive accuracy using a measure of bodily signal perception. Structural equation modeling tested associations between cardiac vagal regulation, interoceptive accuracy, emotion dysregulation, depressive symptoms, and personality dysfunction, including sex-specific pathways and interactions. Results: Here we show that associations between autonomic regulation, interoception, and psychopathology differ by sex. In male adolescents, lower cardiac vagal regulation is associated with greater emotion dysregulation, which is associated with higher depressive symptoms and greater personality dysfunction. These associations depend on interoceptive accuracy and are most evident at low to intermediate levels of bodily signal perception. Comparable pathways are absent in female adolescents. Conclusions: These findings indicate that interactions between cardiac regulation and bodily signal perception contribute to emotional vulnerability in a sex-dependent manner. Altered body–brain communication may contribute to divergent developmental pathways of psychopathology. Integrating sex-specific autonomic and interoceptive processes may improve models of emotion regulation and psychiatric risk during adolescence. Plain Language Summary: Difficulties in regulating emotions are common across mental health conditions, but the biological factors underlying vulnerability remain poorly understood. This study investigated whether heart activity and the ability to perceive bodily signals are linked to emotional and mental health problems during adolescence. We examined 279 adolescents receiving psychiatric inpatient treatment and assessed their heart activity, perception of bodily signals, emotion regulation, and psychological symptoms. In male adolescents, lower vagal regulation of the heart was linked to greater emotion dysregulation, which was associated with more depressive symptoms and personality dysfunction. These relationships were strongest among those with lower to moderate accuracy in perceiving bodily signals and were not observed in females. The findings suggest that heart–brain communication may contribute to emotional and psychological vulnerability during adolescence, with potential implications for sex-specific prevention and treatment.

Non-suicidal self-injury (NSSI) in adolescents has previously been linked to alterations in the endocannabinoid system. While increasing evidence supports endocannabinoid levels as potential biomarker in psychiatric care, little is known about their longitudinal trajectories over the course of treatment or in predicting clinical symptoms. This is the first study to investigate endocannabinoids in a longitudinal cohort of patients with NSSI, exploring associations with the development of symptoms over time. Plasma endocannabinoids and NSSI, using the German version of the Self-Injurious Thoughts and Behaviors Interview (SITBI-G), were assessed in n = 47 female adolescents with NSSI at both baseline and after one year of treatment (follow-up). Associations between endocannabinoid levels and clinical symptoms over time were analyzed. Anandamide (AEA) significantly decreased from baseline to follow-up while 2-arachidonoylglycerol (2-AG) increased after one year. While lower AEA levels have previously been reported in adolescents with NSSI, this longitudinal study found that AEA decreased over one year despite an overall improvement in NSSI symptoms. The overall pattern suggests that changes in circulating endocannabinoids do not closely correspond to symptom improvement. These findings indicate that circulating endocannabinoid levels change over time in adolescents with NSSI, but their complex and partly inconsistent associations with clinical symptoms limit their clinical utility as biomarkers.

Introduction: Vagally mediated heart rate variability (vmHRV) reflects parasympathetic cardiac control and serves as a peripheral marker of brain-body interaction. While studies in adults link higher vmHRV to greater cortical thickness regions related autonomic regulatory, little is known about its association with longitudinal cortical maturation during puberty, a period of pronounced cortical thinning. Methods: This longitudinal study examined whether individual differences in cortical thinning trajectories are associated with vmHRV in two independent cohorts of children and adolescents. Structural MRI were acquired in an accelerated longitudinal design over three time points, each one year apart in two cohorts (n = 44; ages 9 and 12 at baseline). Cortical thickness was estimated using FreeSurfer, and annualized regional thinning slopes were derived for 62 cortical regions. vmHRV was measured one year later at follow-up. Elastic net regression with stability selection identified robust predictors, which were entered into linear models separately for each cohort. Results: Across both cohorts, vmHRV was associated with distributed patterns of cortical thinning. Consistent associations emerged in medial and posterior midline regions, including the precuneus, isthmus of the cingulate cortex, and medial prefrontal and orbitofrontal areas. Associations showed heterogeneous directions across regions, contrasting with uniform adult findings. Discussion: vmHRV may be linked to network-level cortical maturation during adolescence, particularly within default mode and fronto-limbic systems. Findings extend adult work by demonstrating that brain-autonomic coupling emerges during development and is characterized by regionally differentiated trajectories of cortical thinning.

Background: The maturation of the autonomic nervous system (ANS) has been suggested to play a crucial role in the development of emotion regulation and later psychosocial functioning. However, longitudinal evidence linking early autonomic development to long-term outcomes remains limited. This longitudinal study investigated the interplay between birth-related factors, early autonomic activity, and psychosocial outcomes across development. Methods: The sample comprised 101 participants followed from two weeks to 14 years of age, with heart rate (HR) and vagally ediated heart rate variability (vmHRV) assessed at 2 weeks, 6 weeks, 3 months, 14 months, and 14 years. Linear models were used to examine associations between birth-related factors and early HR and vmHRV, as well as whether HR and vmHRV trajectories during the first 14 months predicted psychosocial outcomes at 5 and 14 years. Results: Multiple birth-related factors significantly predicted HR and vmHRV at two weeks after birth. Moreover, flatter age-related increases in vmHRV and weaker decreases in HR during infancy predicted higher maternally reported psychosocial difficulties at 14 years in males only, with no such effects at 5 years or in females. Conclusions: These findings underscore the importance of early autonomic maturation in shaping later psychosocial functioning, with effects on adolescent outcomes observed in males only. Early ANS trajectories may represent meaningful predictors of neurodevelopmental outcomes, highlighting their potential relevance for early identification of later psychosocial risk in a sex-specific manner.

Risk taking has often been proposed to depend on homeostatic systems. However, empirical evidence remains inconsistent, and the underlying mechanisms remain debated. Changes in risky decision-making, which are associated with homeostatic alterations, may be affected by underlying ghrelin signaling, a peptide hormone that also interacts with dopaminergic functions. The deacylated form of ghrelin has recently received increased attention. Across two studies, we examined whether experimental interventions known to alter desacyl-ghrelin levels influence risky choice in healthy male participants. In study 1, participants underwent a brief fasting period (N =37; N =26 for fMRI analyses), whereas in study 2, participants experienced one night of total sleep deprivation (N =40; N =36 for fMRI analyses). Risky decision making was assessed using a standard choice paradigm, and behaviour was analysed using computational modelling. Across both studies, we found no credible effects of the experimental manipulations on the proportion of risky choices. Computational modelling indicated that the standard prospect theory (which describes how participants may overestimate small probabilities and underestimate large ones), without accounting for choice repetition, best described the observed behaviour. However, model parameters were not systematically influenced by the experimental manipulations, and changes in desacyl-ghrelin levels were not robustly associated with decision parameters. Functional MRI analyses revealed no effects of state manipulation on neural representations of subjective value or choice in a priori defined regions of interest, including the ventromedial prefrontal cortex, ventral striatum, posterior cingulate cortex, anterior cingulate cortex, and anterior insula. Overall, these findings suggest that state-dependent influences on risky decision making, and their modulation by desacyl-ghrelin, may be weaker than previously thought.

Human social interaction emerges through coordinated behavior, emotion, and physiology. Biobehavioral synchrony supports stress regulation, attachment, and socio-emotional development, yet its manifestation in psychologically healthy mother-infant dyads remains poorly understood. In particular, little is known about how behavioral and physiological modalities interact and how synchrony varies across contexts. To address this, 94 mother-infant dyads with 3-4-months-old infants participated in the Face-to-Face Still-Face paradigm while cardiac activity was recorded simultaneously in mothers and infants. Physiological synchrony was quantified using cross-correlations of heart rhythm and heart rate variability (HRV) time series, averaged in 10-second windows. We coded behavioral synchrony and assessed bonding via maternal self-report. Behavioral synchrony was higher during play but declined after the stressor, while physiological synchrony was primarily evident during play and lagged 10 s, with maternal responses following infant signals. Low behavioral synchrony corresponded to stronger negative physiological synchrony, indicating that physiological co-regulation persisted despite behavioral misalignment. Supporting theories of early co-regulation, higher behavioral synchrony was linked to fewer bonding difficulties. These findings suggest that low-risk mothers show coordinated physiological fluctuations with their infants, highlighting maternal responsiveness as a key co-regulatory mechanism, providing a framework to identify atypical parent-infant dynamics and guiding parenting interventions that support child development.

Structured Importance: Thymic involution in humans has traditionally been conceptualized as a linear, age-associated process. Animal studies suggest transient hormone-dependent fluctuations in thymus size during reproductive transitions, including across the estrous cycle, but translational evidence in humans remains limited. Objective: To determine whether thymus size changes across the menstrual cycle in healthy women and whether these changes are associated with fluctuations in estradiol and progesterone levels. Design: Observational repeated-measures study using quantitative computed tomography (qCT). Data were collected as part of an imaging study examining menstrual cycle–related physiological variation. Participants underwent assessments during menses and the early luteal phase within the same menstrual cycle. Mixed-effects models with robust variance estimation evaluated associations between cycle phase, hormonal contraception, reproductive hormone levels, and thymus size. Thymus segmentation was independently conducted by 2 blinded raters. Setting: Single-center university-based imaging study conducted at the University of Iowa. Participants: Thirty-one non-smoking women with regular menstrual cycles were included, of whom n = 16 used oral hormonal birth control and n = 15 did not use hormonal contraception. Exclusion criteria included pregnancy, breastfeeding, postmenopausal status, diabetes, body mass index greater than 30 kg/m ² , hysterectomy, or use of long-term noncyclic hormonal contraception. Participants tracked menstrual cycles using temperature monitoring and ovulation kits before completing visits during menses and the early luteal phase. All participants provided informed consent before study participation. Main Outcomes and Measures: Primary outcome was thymus size measured in mm ³ using ultra-low-dose qCT imaging. Secondary outcomes included serum estradiol and progesterone levels. Results: Estradiol levels increased from menses to the early luteal phase independent of hormonal contraceptive status. Progesterone levels were significantly lower among women using hormonal birth control. Thymus size differed significantly by hormonal contraceptive group, with larger thymus volumes observed among women not using hormonal birth control. Among women not using hormonal contraception, 66.7% demonstrated thymic involution from menses to the early luteal phase, compared with 37.5% of women using hormonal contraception. Estradiol and progesterone significantly interacted in predicting thymus size. Conclusions and Relevance: These findings provide first-in-human evidence suggesting that thymus involution demonstrates short-term dynamics across the menstrual cycle and may be influenced by reproductive hormones and hormonal contraception. Key Points: Question: Does thymus size change dynamically across the human menstrual cycle in association with fluctuations in reproductive hormones and hormonal contraception use? Findings: In this repeated-measures quantitative computed tomography study of n = 31 healthy women, thymus size demonstrated within-person variation across the menstrual cycle. Greater thymic involution was associated with larger increases in estradiol, whereas increases in thymus size were associated with larger increases in progesterone; thymus size also differed significantly by hormonal contraceptive status. Meaning: These findings suggest that thymic involution in humans may demonstrate short-term hormone-dependent dynamics beyond age-related atrophy, with potential implications for sex differences in immune regulation and inflammatory disease.