Coleykelley3287

Close translational collaboration between fundamental academic and discovery research will lead to badly needed breakthroughs in the search for new anxiolytics.Oxytocin, a neuropeptide synthesized by the hypothalamus, plays a central role in human social behavior, social cognition, anxiety, mood, stress modulation, and fear learning and extinction. The relationships between oxytocin and psychiatric disorders including depression, anxiety, schizophrenia, and autism spectrum disorder have been extensively studied. In this chapter, we focus on the current knowledge about oxytocin and anxiety disorder. We discuss the anxiolytic effects of oxytocin in preclinical and clinical findings, possible related neurobehavioral mechanisms (social cognition, fear learning, and extinction), related neurotransmitter and neuroendocrine systems (hypothalamus-pituitary-adrenal axis, serotoninergic, and GABAergic systems), and studies regarding plasma levels of oxytocin, genetic and epigenetic findings, and effects of intranasal oxytocin in DSM-5 anxiety disorder (primarily social anxiety disorder and separation anxiety disorder) patients.Several environmental risk factors such as early adverse childhood experiences, stress, and stressful life events are associated with anxiety disorders. Current approaches such as epigenetics and gene-environment interactions were used to identify candidate biomarkers for anxiety disorders to assess determinants of disease. In this chapter, in relation to gene-environment interactions, a variety of association studies regarding anxiety disorders were surveyed. We then showed supporting results from recent association studies such as human studies and animal models in terms of the epigenetic contribution to disease susceptibility to anxiety disorders. At last, future directions and limitations are highlighted. With the advances in multi-omics technologies, innovative ideas regarding disease prevention and drug responsiveness in anxiety disorders require further research in epigenetics and gene-environment interactions.Anxiety disorders include a variety of different disorders including panic disorder (PD), social anxiety disorder (SAD), generalized anxiety disorder (GAD), and phobias. We here focus our review on GAD, SAD, and PD and put a specific emphasis on resting state networks and the coupling between the brain and the heart as all anxiety disorders exhibit abnormal perception of their own heartbeat in some way or the other. Resting state functional connectivity (rsFC) studies demonstrate abnormalities in default-mode network (DMN) in all anxiety disorders, e.g., mostly decreases in rsFC of DMN. In contrast, resting state fMRI shows increased rsFC in salience network (SN) (SAD, GAD) and/or somato-motor/sensory network (SMN) (PD). Since rsFC is coherence- or phase-based operating in the infraslow frequency domain (0.01-0.1 Hz), these data suggest spatiotemporal hypo- or hyper-synchronization in DMN and SMN/SN, respectively. These abnormalities in the neural network's spatiotemporal synchronization may, in turn, impact phase-based temporal synchronization of neural and cardiac activities resulting in decreased (DMN) or increased (SMN/SN) neuro-cardiac coupling in anxiety disorders. That, in turn, may be related to the various psychopathological symptoms like unstable sense of self (as based on unstable DMN showing spatiotemporal hypo-synchronization), increased emotions and specifically anxiety (as related to increased SN showing spatiotemporal hyper-synchronization), and increased bodily awareness (mediated by increased SMN with spatiotemporal hyper-synchronization) in anxiety disorders. Taken together, we here suggest altered spatiotemporal synchronization of neural and cardiac activity within the brain's resting state to underlie various psychopathological symptoms in anxiety disorders. Such spatiotemporal basis of psychopathological symptoms is well compatible with the recently suggested "Spatiotemporal Psychopathology."Anxiety disorders are characterized by excessive fear and anxiety and related behavioral disturbances. Because diffusion tensor imaging is sensitive to detect subtle pathology of the brain, it has been used to characterize differences in white matter microstructure for a broad spectrum of psychiatric disorders. The neurobiological underpinnings of a trait anxiety seem to be associated with the uncinate fasciculus, a major pathway between the amygdala and orbitofrontal cortex. Apparent WM micro-alterations in patients with panic disorder are present in diverse and widespread regions, although alterations vary in terms of clinical symptom severity and comorbidities. Social anxiety disorder is associated with structural dysconnectivity in a fronto-limbic network consistent with reduced fractional anisotropy values in uncinate fasciculus and inferior longitudinal fasciculus. The pathogenesis of obsessive-compulsive disorder may include abnormal findings in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions of forceps major and cingulum bundle. Studies of white matter status in anxiety revealed overlapping patterns of front-cortical and fronto-limbic changes with uncinate fasciculus and cingulum alterations a frequent component.Electrocortical network dynamics are integral to brain function. Linear and nonlinear connectivity applications enrich neurophysiological investigations into anxiety disorders. Discrete EEG-based connectivity networks are unfolding with some homogeneity for anxiety disorder subtypes. Attenuated delta/theta/beta connectivity networks, pertaining to anterior-posterior nodes, characterize panic disorder. Nonlinear measures suggest reduced connectivity of ACC as an executive neuro-regulator in germane "fear circuitry networks" might be more central than considered. TP-1454 Enhanced network complexity and theta network efficiency at rest define generalized anxiety disorder, with similar tonic hyperexcitability apparent in social anxiety disorder further extending to task-related/state functioning. Dysregulated alpha connectivity and integration of mPFC-ACC/mPFC-PCC relays implicated with attentional flexibility and choice execution/congruence neurocircuitry are observed in trait anxiety. Conversely, state anxiety appears to recruit converging delta and beta connectivity networks as panic, suggesting trait and state anxiety are modulated by discrete neurobiological mechanisms.