Shared genetic risk between eating disorder- and substance-use-related phenotypes:Evidence from genome-wide association studies

First published: 16 February 202

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Short-Term Plasticity in the Auditory System

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Integration of somatosensory and motor-related information in the auditory system

An ability to integrate information provided by different sensory modalities is a fundamental feature of neurons in many brain areas. Because visual and auditory inputs often originate from the same external object, which may be located some distance away from the observer, the synthesis of these cues can improve localization accuracy and speed up behavioral responses. By contrast, multisensory interactions occurring close to the body typically involve a combination of tactile stimuli with other sensory modalities. Moreover, most activities involving active touch generate sound, indicating that stimuli in these modalities are frequently experienced together. In this review, we examine the basis for determining sound-source distance and the contribution of auditory inputs to the neural encoding of space around the body. We then consider the perceptual consequences of combining auditory and tactile inputs in humans and discuss recent evidence from animal studies demonstrating how cortical and subcortical areas work together to mediate communication between these senses. This research has shown that somatosensory inputs interface with and modulate sound processing at multiple levels of the auditory pathway, from the cochlear nucleus in the brainstem to the cortex. Circuits involving inputs from the primary somatosensory cortex to the auditory midbrain have been identified that mediate suppressive effects of whisker stimulation on auditory thalamocortical processing, providing a possible basis for prioritizing the processing of tactile cues from nearby objects. Close links also exist between audition and movement, and auditory responses are typically suppressed by locomotion and other actions. These movement-related signals are thought to cancel out self-generated sounds, but they may also affect auditory responses via the associated somatosensory stimulation or as a result of changes in brain state. Together, these studies highlight the importance of considering both multisensory context and movement-related activity in order to understand how the auditory cortex operates during natural behaviors, paving the way for future work to investigate auditory-somatosensory interactions in more ecological situations

Binaural sensitivity changes between cortical on and off responses

Neurons exhibiting on and off responses with different frequency tuning have previously been described in the primary auditory cortex (A1) of anesthetized and awake animals, but it is unknown whether other tuning properties, including sensitivity to binaural localization cues, also differ between on and off responses. We measured the sensitivity of A1 neurons in anesthetized ferrets to 1) interaural level differences (ILDs), using unmodulated broadband noise with varying ILDs and average binaural levels, and 2) interaural time delays (ITDs), using sinusoidally amplitude-modulated broadband noise with varying envelope ITDs. We also assessed fine-structure ITD sensitivity and frequency tuning, using pure-tone stimuli. Neurons most commonly responded to stimulus onset only, but purely off responses and on-off responses were also recorded. Of the units exhibiting significant binaural sensitivity nearly one-quarter showed binaural sensitivity in both on and off responses, but in almost all (∼97%) of these units the binaural tuning of the on responses differed significantly from that seen in the off responses. Moreover, averaged, normalized ILD and ITD tuning curves calculated from all units showing significant sensitivity to binaural cues indicated that on and off responses displayed different sensitivity patterns across the population. A principal component analysis of ITD response functions suggested a continuous cortical distribution of binaural sensitivity, rather than discrete response classes. Rather than reflecting a release from inhibition without any functional significance, we propose that binaural off responses may be important to cortical encoding of sound-source location

Adaptation to Stimulus Statistics in the Perception and Neural Representation of Auditory Space

Sensory systems are known to adapt their coding strategies to the statistics of their environment, but little is still known about the perceptual implications of such adjustments. We investigated how auditory spatial processing adapts to stimulus statistics by presenting human listeners and anesthetized ferrets with noise sequences in which interaural level differences (ILD) rapidly fluctuated according to a Gaussian distribution. The mean of the distribution biased the perceived laterality of a subsequent stimulus, whereas the distribution's variance changed the listeners' spatial sensitivity. The responses of neurons in the inferior colliculus changed in line with these perceptual phenomena. Their ILD preference adjusted to match the stimulus distribution mean, resulting in large shifts in rate-ILD functions, while their gain adapted to the stimulus variance, producing pronounced changes in neural sensitivity. Our findings suggest that processing of auditory space is geared toward emphasizing relative spatial differences rather than the accurate representation of absolute position