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.

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.

Notes from Beethoven's genome.

Rapid advances over the last decade in DNA sequencing and statistical genetics enable us to investigate the genomic makeup of individuals throughout history. In a recent notable study, Begg et al.1 used Ludwig van Beethoven's hair strands for genome sequencing and explored genetic predispositions for some of his documented medical issues. Given that it was arguably Beethoven's skills as a musician and composer that made him an iconic figure in Western culture, we here extend the approach and apply it to musicality. We use this as an example to illustrate the broader challenges of individual-level genetic predictions.

How being perceived to be an artist boosts feelings of attraction in others.

Music production is a universal phenomenon reaching far back into our past. Given its ubiquity, evolution theorists have postulated adaptive functions for music, such as strengthening in-group cohesion, intimidating enemies, or promoting child bonding. Here, we focus on a longstanding Darwinian hypothesis, suggesting that music production evolved as a vehicle to display an individual's biological fitness in courtship competition, thus rendering musicality a sexually selected trait. We also extend this idea to visual artists. In our design, we employed different versions of naturalistic portraits that manipulated the presence or absence of visual cues suggesting that the person was an artist or a non-artist (e.g., farmer, teacher, physician). Participants rated each portrayed person's appeal on multiple scales, including attractiveness, interestingness, sympathy, and trustworthiness. Difference scores between portrait versions revealed the impact of the artistic/non-artistic visual cues. We thus tested Darwin's hypothesis on both a within-subject and within-stimulus level. In addition to this implicit approach, we collected explicit ratings on the appeal of artists versus non-artists. The results demonstrate divergent findings for both types of data, with only the explicit statements corroborating Darwin's hypothesis. We discuss this divergence in detail, along with the particular role of interestingness revealed by the implicit data.

Music and Genetics.

The first part of this review provides a brief historical background of behavior genetic research and how twin and genotype data can be utilized to study genetic influences on individual differences in human behavior. We then review the field of music genetics, from its emergence to large scale twin studies and the recent, first molecular genetic studies of music-related traits. In the second part of the review, we discuss the wider utility of twin and genotype data beyond estimating heritability and gene-finding. We present four examples of music studies that utilized genetically informative samples to analyze causality and gene-environmental interplay for music skills. Overall, research in the field of music genetics has gained much momentum over the last decade and its findings highlight the importance of studying both environmental and genetic factors and particularly their interplay, paving the way for exciting and fruitful times to come.

A comprehensive investigation into the genetic relationship between music engagement and mental health.

While music engagement is often regarded as beneficial for mental health, some studies report higher risk for depression and anxiety among musicians. This study investigates whether shared underlying genetic influences (genetic pleiotropy) or gene-environment interaction could be at play in the music-mental health association using measured genotypes. In 5,648 Swedish twins with information on music and sport engagement, creative achievements, self-reported mental health and psychiatric diagnoses based on nationwide patient registries, we derived polygenic scores for major depression, bipolar disorder, schizophrenia, neuroticism, sensitivity to environmental stress, depressive symptoms and general musicality. In line with phenotypic associations, individuals with higher polygenic scores for major depression and bipolar disorder were more likely to play music, practice more music and reach higher levels of general artistic achievements, while a higher genetic propensity for general musicality was marginally associated with a higher risk for a depression diagnosis. Importantly, polygenic scores for major depression and bipolar remained associated with music engagement when excluding individuals who experienced psychiatric symptoms, just as a genetic propensity for general musicality predicted a depression diagnosis regardless of whether and how much individuals played music. In addition, we found no evidence for gene-environment interaction: the phenotypic association between music engagement and mental health outcomes did not differ for individuals with different genetic vulnerability for mental health problems. Altogether, our findings suggest that mental health problems observed in musically active individuals are partly explained by a pre-existing genetic risk for depression and bipolar disorder and likely reflect horizontal pleiotropy (when one gene influences multiple traits), rather than causal influences of mental health on music engagement, or vice versa (referred to as vertical pleiotropy).

Exploring the genetics of rhythmic perception and musical engagement in the Vanderbilt Online Musicality Study.

Uncovering the genetic underpinnings of musical ability and engagement is a foundational step for exploring their wide-ranging associations with cognition, health, and neurodevelopment. Prior studies have focused on using twin and family designs, demonstrating moderate heritability of musical phenotypes. The current study used genome-wide complex trait analysis and polygenic score (PGS) approaches utilizing genotype data to examine genetic influences on two musicality traits (rhythmic perception and music engagement) in N = 1792 unrelated adults in the Vanderbilt Online Musicality Study. Meta-analyzed heritability estimates (including a replication sample of Swedish individuals) were 31% for rhythmic perception and 12% for self-reported music engagement. A PGS derived from a recent study on beat synchronization ability predicted both rhythmic perception (ß = 0.11) and music engagement (ß = 0.19) in our sample, suggesting that genetic influences underlying self-reported beat synchronization ability also influence individuals' rhythmic discrimination aptitude and the degree to which they engage in music. Cross-trait analyses revealed a modest contribution of PGSs from several nonmusical traits (from the cognitive, personality, and circadian chronotype domains) to individual differences in musicality (ß = -0.06 to 0.07). This work sheds light on the complex relationship between the genetic architecture of musical rhythm processing, beat synchronization, music engagement, and other nonmusical traits.

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.

Music and verbal ability - a twin study of genetic and environmental associations.

Musical aptitude and music training are associated with language-related cognitive outcomes, even when controlling for general intelligence. However, genetic and environmental influences on these associations have not been studied, and it remains unclear whether music training can causally increase verbal ability. In a sample of 1,336 male twins, we tested the associations between verbal ability measured at time of conscription at age 18 and two music related variables: overall musical aptitude and total amount of music training before the age of 18. We estimated the amount of specific genetic and environmental influences on the association between verbal ability and musical aptitude, over and above the factors shared with general intelligence, using classical twin modelling. Further, we tested whether music training could causally influence verbal ability using a co-twin-control analysis. Musical aptitude and music training were significantly associated with verbal ability. Controlling for general intelligence only slightly attenuated the correlations. The partial association between musical aptitude and verbal ability, corrected for general intelligence, was mostly explained by shared genetic factors (50%) and non-shared environmental influences (35%). The co-twin-control-analysis gave no support for causal effects of early music training on verbal ability at age 18. Overall, our findings in a sizeable population sample converge with known associations between the music and language domains, while results from twin modelling suggested that this reflected a shared underlying aetiology rather than causal transfer.

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.

Using a polygenic score in a family design to understand genetic influences on musicality.

To further our understanding of the genetics of musicality, we explored associations between a polygenic score for self-reported beat synchronization ability (PGSrhythm) and objectively measured rhythm discrimination, as well as other validated music skills and music-related traits. Using family data, we were able to further explore potential pathways of direct genetic, indirect genetic (through passive gene-environment correlation) and confounding effects (such as population structure and assortative mating). In 5648 Swedish twins, we found PGSrhythm to predict not only rhythm discrimination, but also melody and pitch discrimination (betas between 0.11 and 0.16, p < 0.001), as well as other music-related outcomes (p < 0.05). In contrast, PGSrhythm was not associated with control phenotypes not directly related to music. Associations did not deteriorate within families (N = 243), implying that indirect genetic or confounding effects did not inflate PGSrhythm effects. A correlation (r = 0.05, p < 0.001) between musical enrichment of the family childhood environment and individuals' PGSrhythm, suggests gene-environment correlation. We conclude that the PGSrhythm captures individuals' general genetic musical propensity, affecting musical behavior more likely direct than through indirect or confounding effects.

Genome-wide association study of musical beat synchronization demonstrates high polygenicity.

Moving in synchrony to the beat is a fundamental component of musicality. Here we conducted a genome-wide association study to identify common genetic variants associated with beat synchronization in 606,825 individuals. Beat synchronization exhibited a highly polygenic architecture, with 69 loci reaching genome-wide significance (P < 5 × 10-8) and single-nucleotide-polymorphism-based heritability (on the liability scale) of 13%-16%. Heritability was enriched for genes expressed in brain tissues and for fetal and adult brain-specific gene regulatory elements, underscoring the role of central-nervous-system-expressed genes linked to the genetic basis of the trait. We performed validations of the self-report phenotype (through separate experiments) and of the genome-wide association study (polygenic scores for beat synchronization were associated with patients algorithmically classified as musicians in medical records of a separate biobank). Genetic correlations with breathing function, motor function, processing speed and chronotype suggest shared genetic architecture with beat synchronization and provide avenues for new phenotypic and genetic explorations.

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.

The effects of playing music on mental health outcomes.

The association between active musical engagement (as leisure activity or professionally) and mental health is still unclear, with earlier studies reporting contrasting findings. Here we tested whether musical engagement predicts (1) a diagnosis of depression, anxiety, schizophrenia, bipolar or stress-related disorders based on nationwide patient registers or (2) self-reported depressive, burnout and schizotypal symptoms in 10,776 Swedish twins. Information was available on the years individuals played an instrument, including their start and stop date if applicable, and their level of achievement. Survival analyses were used to test the effect of musical engagement on the incidence of psychiatric disorders. Regression analyses were applied for self-reported psychiatric symptoms. Additionally, we conducted co-twin control analyses to further explore the association while controlling for genetic and shared environmental confounding. Results showed that overall individuals playing a musical instrument (independent of their musical achievement) may have a somewhat increased risk for mental health problems, though only significant for self-reported mental health measures. When controlling for familial liability associations diminished, suggesting that the association is likely not due to a causal negative effect of playing music, but rather to shared underlying environmental or genetic factors influencing both musicianship and mental health problems.

Gene-environment interaction in expertise: The importance of childhood environment for musical achievement.

Both genes and the environment are important for individual differences in expertise, but little is known about gene-environment interactions underlying domain-specific achievement. Here we explored this issue in a large Swedish twin cohort (N = 6,610), using moderator modeling with musical expertise as a model domain. Specifically, we tested whether musical enrichment of the childhood environment moderates adult musical achievement, as well as the magnitude of genetic and nongenetic influences on individual differences in achievement. Musical achievement was measured using the Creative Achievement Questionnaire and enrichment of the childhood environment was indexed with a principal component derived from the number of music records in the family home, number of individuals in the family environment playing an instrument, frequency of concert visits, and music education before the age of 12. As expected, we found a positive association between childhood musical enrichment and musical achievement in adulthood. Interestingly, however, the total variance in musical achievement as well as the relative importance of genetic influences increased with a higher level of musical enrichment. Estimates of genetic and environmental influences as well as the magnitude of the environmental moderation differed for men and women. These findings suggest that, in line with recent multifactorial models of expert performance, a musically enriched childhood environment amplifies individual differences, an effect which is largely driven by an increase in the importance of genetic factors. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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.

Talking about childhood music: A twin study.

To what extent do childhood experiences of music practice influence thinking about music later in life? In this contribution, 27-54-year-old monozygotic twins discordant with regard to piano playing in life were interviewed about music experiences during childhood and adult years. Recordings of heart rate variability were performed continuously during the interviews which were done separately with playing and nonplaying cotwins. Random factors had determined whether the twin chose to play or not. The rationale behind using monozygotic twins was that this offered a possibility to account totally for genetic influence. The physiological recordings in general showed small intrapair differences. However, during the initial discussion about how the difference arose in piano practice during childhood, the nonplaying twin used more time and showed evidence of a stronger sympathetic activation than the cotwin. These findings are discussed against the background of music's importance in childhood.