SMURF: soft-segmentation for single-cell reconstruction and topological analysis of spatial transcriptomic data.

Substance use – especially alcohol and cannabis use – is very common [, ]. Most individuals initiate use during adolescence, with substance use peaking during young adulthood, after which most people moderate use without formal intervention []. Historically, this process of “maturing out” has often been proposed to be primarily guided by brain development, with increased behavioral control resulting in an increased ability to moderate use []. However, any theory relying primarily on brain development as an explanation of substance use trajectories ignores a crucial component: the social component of substance use. Over the last 2 decades, more studies have attempted to evaluate the role of social influence in substance use trajectories [], and more recent theories of substance use have attempted to integrate neurocognitive with social factors in explaining initiation, escalation, and reduction of substance use []. The social plasticity hypothesis proposes that social attunement – the extent to which one adapts to and harmonizes with the social environment – and its interaction with brain developmental plays an important role in substance use trajectories []. Most adolescents start experimenting with substances in social settings; the social value of substance use, and alcohol use specifically, is generally high among peer groups in this age range. During mid to late adolescence, we usually see high social attunement to the peer group (e.g., risk-taking behavior in the presence of peers). Together with brain processes supporting high learning flexibility and suboptimal behavioral control, which are characteristic for this age group, social attunement can result in the escalation of substance use, especially when the peer environment encourages substance use [, ]. While transitioning to adulthood, the social value of substance use generally decreases – for example, reflected by a change in drinking norms [] – while behavioral control improves []. During this period, social attunement to the environment – first partially responsible for increases in substance use – can facilitate de-escalation of use. For example, one would expect social attunement to be positively associated with alcohol use during adolescence where the social value of alcohol is high, while this association would become more negative with increasing age and social devaluation of alcohol use []. Similar mechanisms are to be expected regarding other substances with a large social component during adolescence, such as cannabis. To be able to explore these theories, we developed the 11-item, 2-subscale Dutch Social Attunement Questionnaire (SAQ; []). The 5-item Cognition subscale assesses the extent to which people think about their behavior and how others perceive that behavior. The 6-item Behavior subscale assesses the extent to which people change their behavior to harmonize with the social environment. Our results using the Dutch SAQ are initial but have been largely in line with the stated hypotheses. We consistently showed that social attunement is negatively associated with age [, , ]. Full-scale SAQ scores have also been positively associated with some implicit social attunement outcomes (i.e., the increase in willingness to drink when peers indicate higher willingness to drink in ambiguous drinking situations) [] and play a mediating role in the association between age and alcohol use []. Furthermore, social attunement appeared to be differentially associated with prospective alcohol use, AUD symptomology, and fMRI social alcohol cue reactivity in adolescent and adult male drinkers []; the association between social attunement and alcohol use outcomes was positive during mid-adolescence, but these associations were negative during adulthood. Hence, social attunement might be a risk or protective factor for alcohol use depending on the developmental period. Although the SAQ might overlap with other questionnaires evaluating different aspects of social influence, previous results show a substantial diversion from social conformity []. Furthermore, the SAQ distinguishes itself by the positively phrased items, limited number of items, and the lack of specific examples in the questions (e.g., party settings, social influence on buying something), potentially enabling broader generalizability over settings (i.e., not restricted to substance use) and age ranges.