Steady-state responses to concurrent melodies: source distribution, top-down, and bottom-up attention.

Humans can direct attentional resources to a single sound occurring simultaneously among others to extract the most behaviourally relevant information present. To investigate this cognitive phenomenon in a precise manner, we used frequency-tagging to separate neural auditory steady-state responses (ASSRs) that can be traced back to each auditory stimulus, from the neural mix elicited by multiple simultaneous sounds. Using a mixture of 2 frequency-tagged melody streams, we instructed participants to selectively attend to one stream or the other while following the development of the pitch contour. Bottom-up attention towards either stream was also manipulated with salient changes in pitch. Distributed source analyses of magnetoencephalography measurements showed that the effect of ASSR enhancement from top-down driven attention was strongest at the left frontal cortex, while that of bottom-up driven attention was dominant at the right temporal cortex. Furthermore, the degree of ASSR suppression from simultaneous stimuli varied across cortical lobes and hemisphere. The ASSR source distribution changes from temporal-dominance during single-stream perception, to proportionally more activity in the frontal and centro-parietal cortical regions when listening to simultaneous streams. These findings are a step forward to studying cognition in more complex and naturalistic soundscapes using frequency-tagging.

Investigating the Relationship Between Childhood Music Practice and Pitch-Naming Ability in Professional Musicians and a Population-Based Twin Sample.

The relationship between pitch-naming ability and childhood onset of music training is well established and thought to reflect both genetic predisposition and music training during a critical period. However, the importance of the amount of practice during this period has not been investigated. In a population sample of twins (N = 1447, 39% male, 367 complete twin pairs) and a sample of 290 professional musicians (51% male), we investigated the role of genes, age of onset of playing music and accumulated childhood practice on pitch-naming ability. A significant correlation between pitch-naming scores for monozygotic (r = .27, p < .001) but not dizygotic twin pairs (r = -.04, p = .63) supported the role of genetic factors. In professional musicians, the amount of practice accumulated between ages 6 and 11 predicted pitch-naming accuracy (p = .025). In twins, age of onset was no longer a significant predictor once practice was considered. Combined, these findings are in line with the notion that pitch-naming ability is associated with both genetic factors and amount of early practice, rather than just age of onset per se. This may reflect a dose-response relation between practice and pitch-naming ability in genetically predisposed individuals. Alternatively, children who excel at pitch-naming may have an increased tendency to practice.

Auditory steady-state responses during and after a stimulus: Cortical sources, and the influence of attention and musicality.

The auditory steady-state response (ASSR) is an oscillatory brain response generated by periodic auditory stimuli and originates mainly from the temporal auditory cortices. Recent data show that while the auditory cortices are indeed strongly activated by the stimulus when it is present (ON ASSR), the anatomical distribution of ASSR sources involves also parietal and frontal cortices, indicating that the ASSR is a more complex phenomenon than previously believed. Furthermore, while the ASSR typically continues to oscillate even after the stimulus has stopped (OFF ASSR), very little is known about the characteristics of the OFF ASSR and how it compares to the ON ASSR. Here, we assessed whether the OFF and ON ASSR powers are modulated by the stimulus properties (i.e. volume and pitch), selective attention, as well as individual musical sophistication. We also investigated the cortical source distribution of the OFF ASSR using a melody tracking task, in which attention was directed between uniquely amplitude-modulated melody streams that differed in pitch. The ON and OFF ASSRs were recorded with magnetoencephalography (MEG) on a group of participants varying from low to high degree of musical sophistication. Our results show that the OFF ASSR is different from the ON ASSR in nearly every aspect. While the ON ASSR was modulated by the stimulus properties and selective attention, the OFF ASSR was not influenced by any of these factors. Furthermore, while the ON ASSR was generated primarily from temporal sources, the OFF ASSR originated mainly from the frontal cortex. These findings challenge the notion that the OFF ASSR is merely a continuation of the ON ASSR. Rather, they suggest that the OFF ASSR is an internally-driven signal that develops from an initial sensory processing state (ON ASSR), with both types of ASSRs clearly differing in cortical representation and character. Furthermore, our results show that the ON ASSR power was enhanced by selective attention at cortical sources within each of the bilateral frontal, temporal, parietal and insular lobes. Finally, the ON ASSR proved sensitive to musicality, demonstrating positive correlations between musical sophistication and ASSR power, as well as with the degree of attentional ASSR modulation at the left and right parietal cortices. Taken together, these results show new aspects of the ASSR response, and demonstrate its usefulness as an effective tool for analysing how selective attention interacts with individual abilities in music perception.

Why Is an Early Start of Training Related to Musical Skills in Adulthood? A Genetically Informative Study.

Experts in domains such as music or sports often start training early. It has been suggested that this may reflect a sensitive period in childhood for skill acquisition. However, it could be that familial factors (e.g., genetics) contribute to the association. Here, we examined the effect of age of onset of musical training on musical aptitude and achievement in professional musicians (n = 310) and twins (n = 7,786). In line with previous literature, results showed that an earlier age of onset was associated with higher aptitude and achievement in both samples. After we adjusted for lifetime practice hours, age of onset was associated only with aptitude (p < .001; achievement: p > .14). Twin analyses showed that the association with aptitude was fully explained by familial factors. Thus, these findings provide little support for a sensitive period for music but highlight that familiar factors play an important role for associations between age of onset of training and skills in adulthood.

Action-Perception Coupling and Near Transfer: Listening to Melodies after Piano Practice Triggers Sequence-Specific Representations in the Auditory-Motor Network.

Understanding how perception and action are coupled in the brain has important implications for training, rehabilitation, and brain-machine interfaces. Ideomotor theory postulates that willed actions are represented through previously experienced effects and initiated by the anticipation of those effects. Previous research has accordingly found that sensory events, if previously associated with action outcomes, can induce activity in motor regions. However, it remains unclear whether the motor-related activity induced during perception of more naturalistic sequences of actions actually represents "sequence-specific" information. In the present study, nonmusicians were firstly trained to play two melodies on the piano; secondly, they performed an fMRI experiment while listening to these melodies as well as novel, untrained melodies; thirdly, multivariate pattern analysis was used to test if voxel-wise patterns of brain activity could identify trained, but not novel melodies. The results importantly show that after associative learning, a series of sensory events can trigger sequence-specific representations in both sensory and motor networks. Interestingly, also novel melodies could be classified in multiple regions, including default mode regions. A control experiment confirmed these outcomes to be training-dependent. We discuss how action-perception coupling may enable spontaneous near transfer and action simulation during action observation.

Attentional modulation of the auditory steady-state response across the cortex.

Selective auditory attention allows us to focus on relevant sounds within noisy or complex auditory environments, and is essential for the processing of speech and music. The auditory steady-state response (ASSR) has been proposed as a neural measure for tracking selective auditory attention, even within continuous and complex soundscapes. However, the current literature is inconsistent on how the ASSR is influenced by selective attention, with findings based primarily on attention being directed to either ear rather than to sound content. In this experiment, a mixture of melody streams was presented to both ears identically (diotically) as we examined if selective auditory attention to sound content influences the ASSR. Using magnetoencephalography (MEG), we assessed the stream-specific ASSRs from three frequency-tagged melody streams when attention was directed between each melody stream, based on their respective pitch and timing. Our main results showed that selective attention enhances the ASSR power of an attended melody stream by 14% at a general sensor level. This ability to readily capture attentional changes in a stimuli-precise manner makes the ASSR a useful tool for studying selective auditory attention, especially in complex auditory environments. As a secondary aim, we explored the distribution of cortical ASSR sources and their respective attentional modulation using a distributed source model of the ASSR activity. Notably, we uncovered the existence of ASSR attentional modulation outside the temporal cortices. Across-subject averages of the attentional enhancement over the cortical surface suggest that frontal regions show up to ~80% enhancement, while temporal and parietal cortices were enhanced by 20-25%. Importantly, this work advocates a novel 'beyond the temporal cortex' perspective on ASSR modulation and also serves as a template for future studies to precisely pin-point which cortical sites are more susceptible to ASSR attentional modulation.

Structural covariability hubs in old age.

Studies have shown that inter-individual differences in grey matter, as measured by voxel-based morphometry, are coordinated between voxels. This has been done by studying covariance maps based on a limited number of seed regions. Here, we used GPU-based (Graphics Processing Unit) accelerated computing to calculate, for the first time, the aggregated map of the total structural topographical organisation in the brain on voxel level in a large sample of 960 healthy individuals in the age range 68-83 years. This map describes for each voxel the number of significant correlations with all other grey matter voxels in the brain. Voxels that correlate significantly with many other voxels are called hubs. A majority of these hubs were found in the basal ganglia, the thalamus, the brainstem, and the cerebellum; subcortical regions that have been preserved through vertebrate evolution, interact with large portions of the neocortex and play fundamental roles for the control of a wide range of behaviours. No significant difference in the level of covariability could be found with increasing age or between men and women in these hubs.

Same Genes, Different Brains: Neuroanatomical Differences Between Monozygotic Twins Discordant for Musical Training.

Numerous cross-sectional and observational longitudinal studies show associations between expertise and regional brain anatomy. However, since these designs confound training with genetic predisposition, the causal role of training remains unclear. Here, we use a discordant monozygotic (identical) twin design to study expertise-dependent effects on neuroanatomy using musical training as model behavior, while essentially controlling for genetic factors and shared environment of upbringing. From a larger cohort of monozygotic twins, we were able to recruit 18 individuals (9 pairs) that were highly discordant for piano practice. We used structural and diffusion magnetic resonance imaging to analyze the auditory-motor network and within-pair differences in cortical thickness, cerebellar regional volumes and white-matter microstructure/fractional anisotropy. The analyses revealed that the musically active twins had greater cortical thickness in the auditory-motor network of the left hemisphere and more developed white matter microstructure in relevant tracts in both hemispheres and the corpus callosum. Furthermore, the volume of gray matter in the left cerebellar region of interest comprising lobules I-IV + V, was greater in the playing group. These findings provide the first clear support for that a significant portion of the differences in brain anatomy between experts and nonexperts depend on causal effects of training.

Executive control and working memory are involved in sub-second repetitive motor timing.

The nature of the relationship between timing and cognition remains poorly understood. Cognitive control is known to be involved in discrete timing tasks involving durations above 1 s, but has not yet been demonstrated for repetitive motor timing below 1 s. We examined the latter in two continuation tapping experiments, by varying the cognitive load in a concurrent task. In Experiment 1, participants repeated a fixed three finger sequence (low executive load) or a pseudorandom sequence (high load) with either 524-, 733-, 1024- or 1431-ms inter-onset intervals (IOIs). High load increased timing variability for 524 and 733-ms IOIs but not for the longer IOIs. Experiment 2 attempted to replicate this finding for a concurrent memory task. Participants retained three letters (low working memory load) or seven letters (high load) while producing intervals (524- and 733-ms IOIs) with a drum stick. High load increased timing variability for both IOIs. Taken together, the experiments demonstrate that cognitive control processes influence sub-second repetitive motor timing.

Addressing a Paradox: Dual Strategies for Creative Performance in Introspective and Extrospective Networks.

Neuroimaging studies of internally generated behaviors have shown seemingly paradoxical results regarding the dorsolateral prefrontal cortex (DLPFC), which has been found to activate, not activate or even deactivate relative to control conditions. On the one hand, the DLPFC has been argued to exert top-down control over generative thought by inhibiting habitual responses; on the other hand, a deactivation and concomitant decrease in monitoring and focused attention has been suggested to facilitate spontaneous associations and novel insights. Here, we demonstrate that prefrontal engagement in creative cognition depends dramatically on experimental conditions, that is, the goal of the task. We instructed professional pianists to perform improvisations on a piano keyboard during fMRI and play, either with a certain emotional content (happy/fearful), or using certain keys (tonal/atonal pitch-sets). We found lower activity in primarily the right DLPFC, dorsal premotor cortex and inferior parietal cortex during emotional conditions compared with pitch-set conditions. Furthermore, the DLPFC was functionally connected to the default mode network during emotional conditions and to the premotor network during pitch-set conditions. The results thus support the notion of two broad cognitive strategies for creative problem solving, relying on extrospective and introspective neural circuits, respectively.

Investigating cognitive transfer within the framework of music practice: genetic pleiotropy rather than causality.

The idea of far transfer effects in the cognitive sciences has received much attention in recent years. One domain where far transfer effects have frequently been reported is music education, with the prevailing idea that music practice entails an increase in cognitive ability (IQ). While cross-sectional studies consistently find significant associations between music practice and IQ, randomized controlled trials, however, report mixed results. An alternative to the hypothesis of cognitive transfer effects is that some underlying factors, such as shared genes, influence practice behaviour and IQ causing associations on the phenotypic level. Here we explored the hypothesis of far transfer within the framework of music practice. A co-twin control design combined with classical twin-modelling based on a sample of more than 10,500 twins was used to explore causal associations between music practice and IQ as well as underlying genetic and environmental influences. As expected, phenotypic associations were moderate (r = 0.11 and r = 0.10 for males and females, respectively). However, the relationship disappeared when controlling for genetic and shared environmental influences using the co-twin control method, indicating that a highly practiced twin did not have higher IQ than the untrained co-twin. In line with that finding, the relationship between practice and IQ was mostly due to shared genetic influences. Findings strongly suggest that associations between music practice and IQ in the general population are non-causal in nature. The implications of the present findings for research on plasticity, modularity, and transfer are discussed.

On the Relationship Between Domain-Specific Creative Achievement and Sexual Orientation in Swedish Twins.

Despite the commonly held belief that homosexual males and females are more creative compared to heterosexuals, empirical studies on homosexuality and its relationship to creativity have been sparse, often with questionable methodology and very small sample sizes, reporting mixed findings. No study till date has explored the associations described above in a large population-based and genetically informative sample. Here, we examined such potential associations between sexual orientation and creative achievement in several different domains (music, writing, dance, visual arts, science, invention, and theater) using a large cohort of 4494 Swedish twins (of which 7.5 % were not exclusively heterosexual). Data were analyzed for the sexes separately as well as pooled. Results showed significant associations between sexual orientation and two of the creative domains-theater and writing-with non-heterosexuals being more creative in these domains. In all other domains, no significant differences were found between the non-heterosexual and heterosexual groups. Findings from co-twin control analyses suggested that the significant associations may not be causal in nature (i.e., homosexual orientation leads to higher creativity) but due to shared liability. However, we lacked power to differentiate between shared genetic and shared environmental influences. Results and potential implications are discussed critically.

Individual Differences in Personality Masculinity-Femininity: Examining the Effects of Genes, Environment, and Prenatal Hormone Transfer.

Males and females score differently on some personality traits, but the underlying etiology of these differences is not well understood. This study examined genetic, environmental, and prenatal hormonal influences on individual differences in personality masculinity-femininity (M-F). We used Big-Five personality inventory data of 9,520 Swedish twins (aged 27 to 54) to create a bipolar M-F personality scale. Using biometrical twin modeling, we estimated the influence of genetic and environmental factors on individual differences in a M-F personality score. Furthermore, we tested whether prenatal hormone transfer may influence individuals' M-F scores by comparing the scores of twins with a same-sex versus those with an opposite-sex co-twin. On average, males scored 1.09 standard deviations higher than females on the created M-F scale. Around a third of the variation in M-F personality score was attributable to genetic factors, while family environmental factors had no influence. Males and females from opposite-sex pairs scored significantly more masculine (both approximately 0.1 SD) than those from same-sex pairs. In conclusion, genetic influences explain part of the individual differences in personality M-F, and hormone transfer from the male to the female twin during pregnancy may increase the level of masculinization in females. Additional well-powered studies are needed to clarify this association and determine the underlying mechanisms in both sexes.

Self-reported psychological demands, skill discretion and decision authority at work: A twin study.

OBJECTIVES: To examine the contribution of genetic factors to self-reported psychological demands (PD), skill discretion (SD) and decision authority (DA) and the possible importance of such influence on the association between these work variables and depressive symptoms. METHODS: 11,543 participants aged 27-54 in the Swedish Twin Registry participated in a web survey. First of all, in multiple regressions, phenotypic associations between each one of the three work environment variables and depressive symptoms were analysed. Secondly, by means of classical twin analysis, the genetic contribution to PD, SD and DA was assessed. After this, cross-twin cross-trait correlations were computed between PD, SD and DA, on the one hand, and depressive symptom score, on the other hand. RESULTS: The genetic contribution to self-reported PD, DS and DA ranged from 18% for decision authority to 30% for skill discretion. Cross-twin cross-trait correlations were very weak (r values < .1) and non-significant for dizygotic twins, and we lacked power to analyse the genetic architecture of the phenotypic associations using bivariate twin modelling. However, substantial genetic contribution to these associations seems unlikely. CONCLUSIONS GENETIC CONTRIBUTIONS TO THE SELF-REPORTED WORK ENVIRONMENT SCORES WERE 18-30%.

Connecting to create: expertise in musical improvisation is associated with increased functional connectivity between premotor and prefrontal areas.

Musicians have been used extensively to study neural correlates of long-term practice, but no studies have investigated the specific effects of training musical creativity. Here, we used human functional MRI to measure brain activity during improvisation in a sample of 39 professional pianists with varying backgrounds in classical and jazz piano playing. We found total hours of improvisation experience to be negatively associated with activity in frontoparietal executive cortical areas. In contrast, improvisation training was positively associated with functional connectivity of the bilateral dorsolateral prefrontal cortices, dorsal premotor cortices, and presupplementary areas. The effects were significant when controlling for hours of classical piano practice and age. These results indicate that even neural mechanisms involved in creative behaviors, which require a flexible online generation of novel and meaningful output, can be automated by training. Second, improvisational musical training can influence functional brain properties at a network level. We show that the greater functional connectivity seen in experienced improvisers may reflect a more efficient exchange of information within associative networks of importance for musical creativity.

Practice does not make perfect: no causal effect of music practice on music ability.

The relative importance of nature and nurture for various forms of expertise has been intensely debated. Music proficiency is viewed as a general model for expertise, and associations between deliberate practice and music proficiency have been interpreted as supporting the prevailing idea that long-term deliberate practice inevitably results in increased music ability. Here, we examined the associations (rs = .18-.36) between music practice and music ability (rhythm, melody, and pitch discrimination) in 10,500 Swedish twins. We found that music practice was substantially heritable (40%-70%). Associations between music practice and music ability were predominantly genetic, and, contrary to the causal hypothesis, nonshared environmental influences did not contribute. There was no difference in ability within monozygotic twin pairs differing in their amount of practice, so that when genetic predisposition was controlled for, more practice was no longer associated with better music skills. These findings suggest that music practice may not causally influence music ability and that genetic variation among individuals affects both ability and inclination to practice.

Gene-environment interaction in expertise acquisition: Practice effects on musical expertise vary by polygenic scores for cognitive performance.

Expert performance is associated with practice, partly because of causal effects of practice on skill (i.e., learning). However, the practice-expertise association is also influenced by a complex interplay between genes and environment including partly overlapping genetic influences. The importance of cognitive ability in the practice-expertise association is less well understood. Therefore, we first examined whether genetic predisposition for cognitive performance, operationalized as a polygenic score, is associated with music practice and expertise. Next, we tested whether there is evidence for gene × environment interaction, i.e., whether effects of practice on expertise differ depending on an individual's genetic predisposition for cognitive performance. Polygenic scores for cognitive performance (PGScp) and multi-trait cognitive performances, including educational attainment and mathematical performances (PGScps) were calculated for approximately 3800 genotyped Swedish individuals with information available on their cumulative amount of music practice, musical achievement, and musical auditory discrimination. We found that higher PGScp and PGScps were associated with higher levels of achievement, musical auditory discrimination, and more practice, although the association with practice weakened when controlling for education. Music practice was linked to both expertise outcomes, and the effect sizes of these associations varied depending on an individual's PGScp and PGScps (with the exception of PGScp for musical auditory discrimination). These results suggest genetic pleiotropy between cognitive performance and musical expertise. Additionally, they reveal the presence of G × E interaction in skill acquisition, as effects of practice on musical expertise are stronger for individuals with a higher genetic predisposition for cognitive performance.

Can flow proneness be protective against mental and cardiovascular health problems? A genetically informed prospective cohort study.

Flow is a phenomenon where one experiences optimal challenge, marked by an intense, effortless, and rewarding concentration on a task. Past research shows that flow proneness is associated with good mental and cardiovascular health. However, this research has been primarily cross-sectional, based on self-report data, and has not controlled for potential confounding effects of neuroticism. In a large, longitudinal twin sample (N = 9361), we used nationwide patient registry data to test whether flow proneness predicted registry-based diagnoses of depression, anxiety, schizophrenia, bipolar disorder, stress-related disorders, or cardiovascular diseases. We used survival analyses taking time to diagnosis into account to test if (a) there is a relationship between flow proneness and health diagnoses over time, (b) neuroticism confounds this relationship, and (c) the relationship remains present within discordant monozygotic twin pairs (N = 952), thereby controlling for genetic and shared environmental confounding. Individuals with higher flow proneness had a decreased risk of receiving diagnoses for depression (16%; CI [14%, 18%]), anxiety (16%; CI [13%, 18%]), schizophrenia (15%; CI [4%, 25%]), bipolar (12%; CI [6%, 18%]), stress-related (9%; CI [9%, 12%]), and cardiovascular disorders (4%; CI [1%, 8%]). When controlling for neuroticism, higher flow proneness still decreased the risk of depression (6%; CI [3%, 9%]) and anxiety diagnoses (5%; CI [1%, 8%]). Monozygotic twins who experienced more flow than their co-twin had a lower risk for depression (16%; CI [5%, 26%]) and anxiety (13%; CI [1%, 24%]), though only the association with depression remained significant when also controlling for neuroticism (13%; CI [1%, 24%]). Findings are in line with a causal protective role of flow experiences on depression and potentially anxiety and highlight that neuroticism and familial factors are notable confounding factors in observed associations between flow proneness and health outcomes.

Testing the Deliberate Practice Theory: Does Practice Reduce the Heritability of Musical Expertise?

The deliberate practice (DP) theory claims that expertise essentially reflects the accumulated amount of deliberate practice, and that with sufficient practice, genetic influences on expertise will be bypassed. Thus, a core prediction of the DP theory is that genetic effects on performance decrease as a function of practice. Here, we test this prediction using music as a model domain. Musical expertise (measured with a musical auditory discrimination test) and lifetime practice hours were determined in 6471 twins including 1302 complete twin pairs. We fitted a bivariate Cholesky decomposition with practice hours as a moderator to determine to what extent genetic and environmental influences on musical expertise are influenced by practice hours. On average, 50% of individual differences in musical expertise were due to genetic influences, whereas shared environmental and residual influences each explained about 25%. Importantly, music practice significantly moderated these estimates. Variation in musical expertise decreased with more practice hours due to decreased shared environmental and residual variance. In contrast, the overall genetic component was unaffected by the number of practice hours. Consequently, the relative genetic contribution (heritability) increased with more practice hours. These findings are in contrast with predictions from the DP theory and suggest that genetic predisposition remains important for musical expertise even after prolonged practice.

Adolescent Psychedelic Use and Psychotic or Manic Symptoms.

Importance: While psychedelic-assisted therapy has shown promise in the treatment of certain psychiatric disorders, little is known about the potential risk of psychotic or manic symptoms following naturalistic psychedelic use, especially among adolescents. Objective: To investigate associations between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents using a genetically informative design. Design, Setting, and Participants: This study included a large sample of adolescent twins (assessed at age 15, 18, and 24 years) born between July 1992 and December 2005 from the Swedish Twin Registry and cross-sectionally evaluated the associations between past psychedelic use and psychotic or manic symptoms at age 15 years. Individuals were included if they answered questions related to past use of psychedelics. Data were analyzed from October 2022 to November 2023. Main Outcomes and Measures: Primary outcome measures were self-reported psychotic and manic symptoms at age 15 years. Lifetime use of psychedelics and other drugs was also assessed at the same time point. Results: Among the 16 255 participants included in the analyses, 8889 were female and 7366 were male. Among them, 541 participants reported past use of psychedelics, most of whom (535 of 541 [99%]) also reported past use of other drugs (ie, cannabis, stimulants, sedatives, opioids, inhalants, or performance enhancers). When adjusting for substance-specific and substance-aggregated drug use, psychedelic use was associated with reduced psychotic symptoms in both linear regression analyses (ß, -0.79; 95% CI, -1.18 to -0.41 and ß, -0.39; 95% CI, -0.50 to -0.27, respectively) and co-twin control analyses (ß, -0.89; 95% CI, -1.61 to -0.16 and ß, -0.24; 95% CI, -0.48 to -0.01, respectively). In relation to manic symptoms, likewise adjusting for substance-specific and substance-aggregated drug use, statistically significant interactions were found between psychedelic use and genetic vulnerability to schizophrenia (ß, 0.17; 95% CI, 0.01 to 0.32 and ß, 0.17; 95% CI, 0.02 to 0.32, respectively) or bipolar I disorder (ß, 0.20; 95% CI, 0.04 to 0.36 and ß, 0.17; 95% CI, 0.01 to 0.33, respectively). Conclusions and Relevance: The findings in this study suggest that, after adjusting for other drug use, naturalistic use of psychedelic may be associated with lower rates of psychotic symptoms among adolescents. At the same time, the association between psychedelic use and manic symptoms seems to be associated with genetic vulnerability to schizophrenia or bipolar I disorder. These findings should be considered in light of the study's limitations and should therefore be interpreted with caution.