[under construction]

Neurovisceral Regulatory Systems

We study endogenous stress-response systems and associated neural circuitry. We focus on methods to observe and interfere with the action of the Autonomic Nervous System (ANS) and Hypothalamic-Pituitary-Adrenal Axis (HPA-axis). Building on existing work on ANS (e.g., Koenig 2020, Sigrist et al. 2021) and HPA-Axis (e.g., Schär et al. 2022) functioning in children and adolescents with psychiatric disorders and childhood trauma, we recently shifted 

The Autonomic Nervous System and Cholinergic-Antiinflammatory Pathway





Applied Methods:

  • Multimodal psychophysiological investigations in- and outside of the MR-scanner, recording hear rate and associated measures (e.g., left ventricular ejection time), respiratory frequency, skin conductance responses, beat-to-beat blood pressure etc.
  • Analyses of inflammatory markers from blood (e.g., Kindler et al. 2022) and saliva (e.g., Koenig et al. 2021)
  • Structural and functional neuroimaging of the central autonomic network (e.g., Min et al. 2023, Thome et al. 2017) and specific structures (e.g., locus coeruleus neuroimaging)

Selected Empirical Paper:

  • Min J, Koenig J, Nashiro K, Joo Yoo H, Cho C, Thayer JF, Mather M. Sex Differences in Neural Correlates of Emotion Regulation in Relation to Resting Heart Rate Variability. Brain Topography, 2023 36(5):698-709; DOI: 10.1007/s10548-023-00974-9 [PubMed]
  • Koenig J, Westlund Schreiner M, Klimes-Dougan B, Ubani B, Mueller B, Kaess M, Cullen KR. Brain Structural Thickness and Resting State Autonomic Function in Adolescents with Major Depression. Social Cognitive and Affective Neuroscience (SCAN) 2018; 13(7):741-753, DOI: 10.1093/scan/nsy046; [PubMED]
  • Thome J, Densmore M, Frewen PA, McKinnon M, Théberge J, Nicholson A, Koenig J, Thayer JF, Lanius RA. Desynchronization of Autonomic Response and Central Autonomic Network Connectivity in Posttraumatic Stress Disorder. Human Brain Mapping 2017; 38(1):27-4 DOI: 10.1002/hbm.23340; 4.96 Impact Factor  [PubMED]

Systematic Reviews/Meta-Analysis:

  • Koenig J. Neurovisceral Regulatory Circuits of Affective Resilience in Youth - Principal Outline of a Dynamic Model of Neurovisceral Integration in Development. Psychophysiology 2020, 57(5):e13568; DOI: 10.1111/psyp.13568; 3,378 Impact Factor [PubMED]
  • Sigrist C, Mürner-Lavanchy I, Peschel SKV, Schmidt SJ, Kaess M, Koenig J. Early Life Maltreatment and Resting-State Heart Rate Variability: A Systematic Review and Meta-Analysis. Neuroscience and Biobehavioural Reviews, 2021, 120:307-334, DOI: 10.1016/j.neubiorev.2020.10.026; 8.330 Impact Factor [PubMed]
  • Williams DP, Koenig J, Carnevali L, Sgoifo A, Jarczok MN, Sternberg EM, Thayer JF. Heart Rate Variability and Inflammation: A Meta-Analysis of Human Studies. Brain, Behavior, and Immunity 2019, S0889-1591(18)30466-5, DOI: 10.1016/j.bbi.2019.03.0096.306 Impact Factor [PubMED]
  • Koenig J, Kemp AH, Beauchaine TP, Thayer JF. Kaess M. Depression and Resting State Heart Rate Variability in Children and Adolescents – A Systematic Review and Meta-Analysis. Clinical Psychology Review 2016; 46: 136-150; DOI: 10.1016/j.cpr.2016.04.013; 7.18 Impact Factor [PubMED]
  • Peschel SKV, Feeling NR, Vögele C, Kaess M, Thayer JF, Koenig J. A Systematic Review on Heart Rate Variability in Bulimia Nervosa. Neuroscience & Biobehavioral Reviews 2016; 30;63:78-97 DOI: 10.1016/j.neubiorev.2016.01.012; 8.80 Impact Factor [PubMED]
  • Clamor A, Lincoln TM, Thayer JF, Koenig J. Resting Vagal Activity in Schizophrenia: A Meta-Analysis of Heart Rate Variability as a Potential Endophenotype. British Journal of Psychiatry 2016; 208(1):9-16; DOI: 10.1192/bjp.bp.114.160762; 7.99 Impact Factor [PubMED]



The Endocannabinoid System and Hypothalamic-Pituitary-Adrenal Axis 

Background: The endocannabinoid system is a neuromodulatory system and well known to interact with the Hypothalamic-Pituitary-Adrenal Axis (HPA-axis). Key molecular target of the endocannabinoid receptor is the CB1-receptor, that is targeted by two main endogenous ligands, the endocannabinoids N-arachidonyl ethanolamine (anandamide, AEA) and 2-archidonyl glycerol (2-AG). AEA and 2-AG are synthesized on demand in post-synaptic neurons and subsequently released in the synaptic cleft where they target the CB1-receptor. Activation of CB1-receptors result in a robust suppression of neurotransmitter release, resulting in both excitatory and inhibitory transmission as CB1 receptors are expressed on a variety of synapses like glutamatergic, GAGAergic, serotonergic, noradrenergic and dopaminergic terminals. Endocannabinoid signaling has a “gatekeeping” function on the HPA-axis. During acute stress - due to increased FAAH activity - AEA rapidly decreases to enable enhanced HPA-axis signaling, likely mediated by corticotropin-releasing hormone (CRH) dependent mechanisms. This model is supported by findings on higher corticosterone levels after AEA depletion, an increases in anxiety-like behaviour as well as a deficit in extinction of aversive memory. Following chronic corticosterone exposure FAAH activity increases resulting in reduction of AEA levels. The vast majority of  findings stem from animal research. Two hydrolytic enzymes, fatty acid amide hydrolase (FAAH) for AEA and monoacylglycerol lipase (MAGL) for 2-AG, have been identified to degrade the corresponding lipid endocannabinoids. We translate existing murine models studying the endocannabinoid system to children and adolescents with psychiatric disorers, in the hope to identify novel therapeutic targets for pharmacological intervention.

Applied Methods:

Selected Empirical Paper:

  • Koenig J, Lischke A, Bardtke K, Heinze AL, Kröller F, Pahnke R, Kaess M. Altered Psychobiological Reactivity but No Impairment of Emotion Recognition Following Stress in Adolescents with Nonsuicidal Self-injury. European Archives of Psychiatry and Clinical Neuroscience, 2023: 273(3): 379-395; DOI: 10.1007/s00406-022-01496-4 [PubMed]
  • Koenig J, Rinnewitz L, Warth M, Hillecke TK, Brunner R, Resch F, Kaess M. Psychobiological Response to Pain in Female Adolescents with Non-Suicidal Self-Injury. Journal of Psychiatry and Neuroscience 2017; 42(1):160074; DOI: 10.1503/jpn.160074; [PubMED]

Systematic Reviews/Meta-Analysis on the Topic:

  • Schär S, Mürner-Lavanchy I, Schmidt SJ, Koenig J Kaess M. Child maltreatment and hypothalamic-pituitary-adrenal axis functioning: A systematic review and meta-analysis. Frontiers in Neuroendocrinology, 2022: 66:100987; DOI: 10.1016/j.yfrne.2022.100987 [PubMed]
  • Flach E, Koenig J, van der Venner, P, Parzer P, Resch F, Kaess M. Hypothalamic-Pituitary-Thyroid Axis Function in Female Adolescent Nonsuicidal Self-Injury, and its Association with Comorbid Borderline Personality Disorder and Depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2021; 111: 110345, DOI: 10.1016/j.pnpbp.2021.110345 [PubMed]
  • Drews E, Fertuck E, Koenig J, Kaess M, Arntz A. Hypothalamic-Pituitary-Adrenal Axis Functioning in Borderline Personality Disorder: A Meta-Analysis. Neuroscience & Beiobehavioral Review 2019; 96:316-334, DOI: 10.1016/j.neubiorev.2018.11.008 [PubMED]


last update 2023 10 08

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