Music's context-dependent influence on oxytocin, social bonding, and emotion regulation: a systematic review

Abstract

Objective:

This systematic review aims to explore how individual and group musical activities influence social bonding and emotion regulation through the oxytocinergic system.

Methods:

Following the PRISMA 2020 guidelines, a systematic search of PubMed, Embase, Scopus, Web of Science Core Collection, and PsycInfo was conducted to identify studies up to October 2024, supplemented by a manual search. One reviewer screened studies, extracted data, and assessed the study quality. Framework synthesis and narrative synthesis were conducted to integrate findings.

Results:

A total of 1,865 records were identified. After reviewing the full-text papers, 20 studies (seven randomized controlled trials and 13 quasi-experiments) were included, which involved 877 participants across healthy and clinical populations. The reviewed interventions included singing, playing instruments, listening to music, and music therapy. Most studies reported improvements in psychosocial outcomes, such as reduced anxiety and depression or enhanced social cognition, but they do not always align with peripheral oxytocin (OXT) changes. However, certain psychosocial outcomes or contexts revealed relatively consistent patterns in OXT responses, suggesting the presence of context-dependent modulation. Short-term interventions often reported detectable peripheral OXT changes, which only partially reflected the temporary activity of magnocellular OXT neurons in the hypothalamus. No significant changes in baseline peripheral OXT levels were observed after long-term interventions.

Conclusion:

Music-induced OXT responses are context-dependent. The bidirectional modulation of OXT supports social bonding and emotion regulation in musical contexts. Clinicians and music therapists should carefully consider therapeutic goals, individual differences, and environmental factors when designing music therapy.

1 Introduction

There is growing interest in music therapy, which has shown promise in promoting mental health and wellbeing (Bernatzky et al., 2011; Bhandarkar et al., 2024). Recent studies have begun to explore the underlying neural mechanisms of music's effects, with a particular focus on oxytocin (OXT), a crucial neuropeptide for social bonding and emotion regulation (Olff et al., 2013).

OXT is synthesized by the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus and released into the central nervous system (CNS) and endocrine system to exert its effects (Meyer-Lindenberg et al., 2011). In the endocrine system, OXT is secreted by the posterior pituitary into the bloodstream to support reproductive processes like uterine contraction and lactation (Grewen et al., 2010; Maud et al., 2018). In the CNS, OXT is released from dendritic or axonal terminals to specific brain regions to modulate neurotransmitter release, synaptic plasticity, and neural network activity (Chini et al., 2017; Jurek and Neumann, 2018). For example, OXT promotes the release of γ-aminobutyric acid (GABA), which reduces neuronal excitability and produces anxiolytic effects (Sobota et al., 2015; Yuki, 2023). OXT engages in intracellular signaling to regulate gene expression (Jurek and Neumann, 2018; Uvnas-Moberg, 2024) and synaptic plasticity in the amygdala (Gur et al., 2014), hippocampus (Lin and Hsu, 2018), and prefrontal cortex (Ninan, 2011) to support long-term adaptations in emotional responses and social behaviors (Marlin and Froemke, 2017). OXT can suppress the expression of corticotropin-releasing hormone (CRH) and reduce downstream cortisol secretion to moderate stress responses (Bowling, 2023; Harvey, 2020; Jurek and Neumann, 2018).

OXT also plays a role in social cognition (Harvey, 2020). It enhances an individual's ability to recognize, process, and respond to social cues. Notably, these effects are influenced by contextual factors (e.g., safe or threatening environments), and individual factors, including sex, hormonal status, gene variations, attachment style, history of childhood trauma, and the presence of psychiatric disorders, influence the OXTergic system responsiveness (Olff et al., 2013). These findings suggest that the role of OXT is to enhance sensitivity to environmental changes for appropriate behavioral selection (Steinman et al., 2019).

It is unclear how music modulates the OXTergic system to influence emotion regulation and social bonding. Although empirical studies have suggested that music can lead to peripheral OXT changes, the findings are inconsistent. Some studies reported OXT increases after musical activities (Grape et al., 2003; Nilsson, 2009), while others observed no significant change (Palumbo et al., 2022) or even decreases (Eerola et al., 2021; Fancourt et al., 2016; Schladt et al., 2017). The discrepancies may arise from differences in participant characteristics, types of music-based intervention, study designs, OXT measurements, and contextual factors (Engel et al., 2019; MacLean et al., 2019; Tabak et al., 2023). Besides, most studies have been conducted in laboratory or clinical settings with limited ecological validity, which raises questions about whether music-induced OXT changes observed under controlled conditions can be generalized to real-life contexts, especially collective musical rituals.

To address the gaps, this systematic review synthesizes current evidence on how music modulates the OXTergic system in humans. By considering the contextual factors, population characteristics, and intervention features, the review refines the theoretical model of music-induced OXT response to offer guidance to optimize music-based interventions for populations with social impairments. For a rapidly developing field, it will provide a reliable foundation for future research and clinical applications.

The objective of the current review is to explore how individual and group musical activities influence mental health through the OXTergic system in terms of social bonding and emotion regulation. We will address the following questions:

• (1) How do OXT levels change in different populations in music-based interventions?

• (2) Which characteristics of music-based interventions can be associated with significant changes in OXT levels and psychosocial outcomes?

• (3) What are the strengths and limitations of OXT measurements in music-based interventions?

2 Methods

2.1 Search strategy

The systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. Literature searches were conducted on November 23, 2024, in five databases: PubMed, Embase, Scopus, Web of Science Core Collection, and PsycInfo. Search terms combined keywords related to music, ritual, OXT, emotion regulation, and social bonding. A detailed search strategy is presented in the Supplementary material S1.

2.2 Eligibility criteria

Studies were included if they met the following criteria: (1) original, peer-reviewed, full-text articles published in English up to October 2024; (2) study designs were randomized controlled trials (RCTs), quasi-experimental designs, or observational studies; (3) populations including healthy individuals, clinical populations, or both; (4) interventions involving music therapy or musical activities (e.g., music listening, singing, or playing instruments) delivered individually or in groups; and (5) outcomes reporting OXT measurements along with at least one psychosocial, clinical, or subjective outcome. Exclusion criteria included: (1) non-human studies; (2) reviews or editorials without original data; (3) studies focusing solely on pharmacotherapy (unless compared to music-based interventions); (4) conference abstracts or book chapters; and (5) non-peer-reviewed papers. There were no restrictions regarding participant age, sample size, geographical location, or comparator.

2.3 Study selection

All identified records were imported into reference management software, and duplicates were removed. Titles and abstracts were screened independently by the first author. Full texts of potentially relevant articles were then assessed for eligibility. Uncertainties were resolved through discussion with the second author.

2.4 Quality assessment

The quality of included studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for RCTs and for quasi-experimental studies. The tools evaluate the validity of study design, methodology, statistical conclusions, and risk of bias (Barker et al., 2024, 2023). The quality assessment was conducted by the first author and verified by the second author.

2.5 Data extraction, analysis, and synthesis

From the full texts of selected articles and their supplementary material, one reviewer extracted the data, including study characteristics, participant characteristics, intervention details, outcome measures, results, and statistical analyses.

Quantitative OXT changes were transformed into qualitative categories: increase, decrease, or no significant change. Psychosocial outcomes were grouped into broader domains: anxiety, depression, empathy, social bonding, trust, stress and relaxation, as well as emotion and mood. Contextual descriptions were extracted and categorized into four dimensions: (1) nature of the activity (e.g., passive listening, active music-making, or music therapy); (2) stress signals (e.g., levels of physical or mental stress); (3) social cues (e.g., presence of others); and (4) familiarity (e.g., familiarity with the music, participants, or environments).

The reviewer conducted a framework synthesis and a narrative synthesis. The framework synthesis was based on the model proposed by Bowling (2023), following a five-stage process (Brunton et al., 2020): familiarization, framework selection, indexing, charting, and mapping/interpretation. The narrative synthesis was used to summarize patterns within and across studies, explore relationships, and assess the robustness of findings in terms of methodological quality (Impellizzeri and Bizzini, 2012). Finally, a convergent design (Hong et al., 2017) was used to integrate quantitative and qualitative data.

3 Results

3.1 Study selection and study characteristics

A PRISMA flow diagram is presented in Figure 1, showing study identification and inclusion of eligible studies. A total of 1,865 records were identified, of which 1,860 were from electronic databases, and five were from other sources. After removing duplicates, 902 records were screened based on titles and abstracts. Thirty-one full-text articles were assessed for eligibility, and 11 studies were excluded (five duplicates, two conference abstracts, two with wrong outcomes, and two without OXT data). Finally, 20 studies (seven RCTs and 13 quasi-experiments) were included in the systematic review.

Figure 1

Table 1 summarizes the characteristics of the included studies, which were published between 2003 and 2023 across 11 countries. The majority of the studies were conducted in Europe (n = 12, 60%), followed by North America (n = 5, 25%), and Asia (n = 3, 15%). All studies comprised 877 participants. Sample sizes ranged from 4 to 193 participants (median = 25.5).

The reviewed music-based interventions encompassed singing, playing instruments, listening to music, and music therapy. Most studies used pieces of classical music as materials. Only two studies adopted quasi-ritualistic music-based interventions grounded in culture: one study from Japan used group taiko drumming (Yuhi et al., 2017), and one study from Indonesia examined a school-based intervention program combining Indonesian traditional music (Maramis et al., 2021).

One reviewer used the JBI critical appraisal tools to assess study quality. Among the studies, 17 were rated as low risk of bias, two as moderate risk, and one as high risk. Tables 2, 3 present the detailed results of the quality assessment. No studies were excluded based on quality alone.

3.2 Population characteristics and OXT responses

The included studies encompassed diverse populations, with a primary focus on healthy adults. Other studies examined clinical populations, including cancer patients and their carers Fancourt et al., (2016), pregnant women Wulff et al., (2021), preterm infants Filippa et al., (2021) and their mothers Filippa et al., (2023), individuals with Williams syndrome Dai et al., (2012), post-surgical patients (Nilsson, 2009), post-stroke patients (Palumbo et al., 2022), children with autism spectrum disorder (ASD; Corbett et al., 2011), and maltreated children (Yuhi et al., 2017). Two studies (Grape et al., 2003; Kreutz, 2014) recruited mixed samples that varied in age, sex, health status, and singing experiences, as detailed in Table 1.

Participant ages ranged from 34.8 gestational weeks (preterm infants) to 72.8 years (healthy older adults). Most studies had a predominance of female participants. Baseline peripheral OXT levels showed notable differences between populations. In typical control individuals, the patterns of plasma OXT response to music demonstrated low inter-individual variability (Dai et al., 2012), although they had different baseline OXT levels. By contrast, patients with Williams syndrome exhibited higher baseline plasma OXT levels and greater variability in response to music Dai et al., (2012). In pregnant and postpartum mothers (Filippa et al., 2023; Wulff et al., 2021), baseline peripheral OXT levels were low, with small yet statistically significant changes after musical activities. The patterns of OXT response to music were not influenced by sex (Bowling et al., 2022; Filippa et al., 2021). Other covariates the phase of the menstrual cycle, the use of hormonal contraception, and the musical sophistication index did not change the patterns (Eerola et al., 2021).

Tables 4, 5 summarize the peripheral OXT changes induced by music across populations and contexts (also see Supplementary material S2). These results revealed the context-dependence of OXT responses to music. After group singing, OXT levels decreased in healthy young adults Bowling et al., (2022); Keeler et al., (2015); Schladt et al., (2017) but increased in healthy older adults Good and Russo, (2022). OXT reductions were observed in cancer patients and their carers after choral singing Fancourt et al., (2016). For preterm infants Filippa et al., (2021) and their mothers Filippa et al., (2023), as well as pregnant women Wulff et al., (2021), maternal singing to infants or fetuses increased their OXT levels. Listening to slow-tempo music generally triggered OXT release in several populations, including healthy males Ooishi et al., (2017), pregnant women with trait anxiety Wulff et al., (2021), and post-surgical patients Nilsson, (2009). Interestingly, listening to sad music led to significant OXT decreases in healthy females with high empathy but not in healthy females with low empathy Eerola et al., (2021). However, in children with ASD Corbett et al., (2011) and post-stroke patients Palumbo et al., (2022), no significant changes in peripheral OXT levels were observed after long-term group music therapy.

3.3 Psychosocial outcomes and OXT changes

Across the included studies, associations between psychosocial outcomes and peripheral OXT changes varied by population, context, and measurement time point. Table 6 summarizes the relationships between psychosocial outcomes, OXT changes, and context characteristics.

Long-term intervention programs did not lead to significant changes in peripheral OXT levels, despite the improvements in psychosocial outcomes. For instance, after participating in interactive improvised group music-making therapy for 6 weeks, post-stroke patients showed improvements in depression and motor functions without significant OXT changes Palumbo et al., (2022). Similarly, a 3-month structured musical theater therapy improved the ASD children's skills of theory of mind and memory for faces, but no significant plasma OXT changes were observed Corbett et al., (2011).

Short-term music-based interventions, such as a single session of singing, often resulted in improvements in anxiety, though not always accompanied by changes in peripheral OXT levels. Maternal singing led to anxiety reduction and OXT increases in mothers of preterm infants Filippa et al., (2023), whereas in other contexts (e.g., healthy adults engaging in choir singing), anxiety reductions occurred accompanied by OXT decreases Schladt et al., (2017). Additionally, unpleasant music stimuli under stress conditions both increased anxiety and plasma OXT levels in healthy males Jezova et al., (2013).

Empathy-related outcomes unveiled noteworthy patterns. For high-empathy healthy females, listening to unfamiliar sad instrumental music elicited stronger self-reported emotional responses, accompanied by significant decreases in plasma OXT levels. In contrast, low-empathy healthy females reported smaller emotional improvements but showed modest OXT increases Eerola et al., (2021).

In an RCT, Riedl et al. (2017) examined whether music listening in a trust game influenced the trust behavior and perceived trustworthiness. During the trust game, no significant changes in OXT levels were observed in the participants in the music conditions, but they tended to show greater trust behavior and rated faces and nicknames as more trustworthy compared to those in the no-music conditions, although the trends did not reach statistical significance.

All studies on choral singing reported that participants had experienced social bonding, and OXT levels declined in most cases Bowling et al., (2022); Fancourt et al., (2016); Keeler et al., (2015), except in improvised choral singing, where OXT levels increased Keeler et al., (2015).

Last, participants frequently reported subjective improvements in relaxation and mood scales after musical activities across studies. However, these changes were not always accompanied by increases in peripheral OXT levels Bowling et al., (2022); Eerola et al., (2021); Fancourt et al., (2016); Good and Russo, (2022); Grape et al., (2003); Kreutz, (2014); Maramis et al., (2021); Nilsson, (2009); Wulff et al., (2021).

Overall, improvements in psychosocial outcomes do not correspond with changes in peripheral OXT levels, and consistent OXT response patterns were observed only for specific psychosocial outcomes.

3.4 Effects of contextual factors on patterns of OXT responses and psychosocial outcomes

3.4.1 Patterns of OXT responses

Analyses of OXT responses across studies consistently revealed interaction effects, which indicated that patterns of OXT change were context-dependent (see Table 7). Kreutz (2014) demonstrated a significant time × condition interaction for salivary OXT responses (F(1,21) = 7.988, p < 0.05). The dependence on activity was further supported by several studies: Filippa et al. (2021) reported a significant time × condition interaction (χ²(2) = 6.99, p = 0.03), as did Good and Russo (2022) (z = −2.142, p = 0.032). Schladt et al. (2017) observed a significant time × context interaction (F(4) = 7.27, p < 0.001), and Bowling et al. (2022) found a significant time × vocal mode interaction (χ²(1) = 5.7, p = 0.018). Evidence for OXT's sensitivity to stress signals was provided by Ooishi et al. (2017), who observed a significant time × tempo interaction (F(1,22) = 13.44, p = 0.0014). However, Bowling et al. (2022) found no significant time × social context interaction (p = 0.230) or time × vocal mode × social context interaction (p = 0.190), indicating that OXT responses were not significantly influenced by the explicitly manipulated social setting in their study.

3.4.2 Patterns of psychosocial outcomes

Psychosocial outcomes exhibited varying degrees of context-dependence (see Table 7). Kreutz (2014) found a significant time × condition interaction for positive feelings (F(1,20) = 9.655, p < 0.01). Schladt et al. (2017) observed significant time × context interactions for excitement (F(1) = 6.51, p = 0.015) and happiness (F(1) = 5.27, p = 0.028), but not for worry or sadness. Jezova et al. (2013) examined the effects of pleasant vs. unpleasant music and found a significant time × condition interaction for state anxiety (F(1, 26) = 5.10, p < 0.05). In Bowling et al. (2022), the social bonding measure (IOS scale) showed a significant time × vocal mode interaction (χ²(1) = 7.06, p = 0.008). In contrast, the subjective emotion measure (PANAS) in the same study exhibited a significant three-way interaction among time, vocal mode, and social context (χ²(1) = 10.54, p = 0.001). The findings indicate that changes in psychosocial outcomes, particularly positive affect measures, were significantly influenced by activity and social cues.

3.5 The characteristics of OXT measurements

All the included studies used peripheral OXT measurements as biomarkers, and they varied in collection protocols, sample types, and quantification methods, as summarized in Table 8. Twelve studies provided details on the time of sample collection. Of these, nine studies scheduled collection during the afternoon or evening hours to avoid interference from the cortisol awakening response (CAR). The remaining studies adopted different protocols: one study collected samples across many time points throughout the day (morning, afternoon, and evening), and another between 9:00 and 13:00. Notably, Maramis et al. (2021) was the sole study that conducted sample collection during the CAR period in the early morning.

In short-term interventions, samples were often collected immediately before and after a single session to measure acute OXT changes. Six studies collected samples at three or more time points (Dai et al., 2012; Eerola et al., 2021; Jezova et al., 2013; Nilsson, 2009; Riedl et al., 2017; Schladt et al., 2017), whereas the others relied on pre-test and post-test measurements. Long-term interventions assessed baseline OXT levels before and after the entire program, which lasted from several weeks to months. However, long-term interventions generally showed no significant changes in baseline OXT levels.

Sample types included plasma (n = 5), serum (n = 4), and saliva (n = 11). Generally, plasma and serum samples showed higher OXT concentrations (ranging from tens to hundreds of pg/ml) compared to saliva samples (approximately 0–20 pg/ml). In terms of quantification methods, 12 studies used enzyme immunoassay (EIA), of which four applied sample extraction procedures prior to EIA. Five studies used radioimmunoassay (RIA), one study used electrochemiluminescence assay, and two used fluorescence immunoassay. Studies that omitted sample extraction before EIA tended to report higher OXT concentrations (Dai et al., 2012; Grape et al., 2003; Keeler et al., 2015; Maramis et al., 2021; Palumbo et al., 2022; Yuhi et al., 2017) than those that included extraction steps (Bowling et al., 2022; Eerola et al., 2021; Nilsson, 2009; Ooishi et al., 2017).

Therefore, methodological differences in OXT measurements may contribute to inconsistencies in OXT levels reported across studies.

4 Discussion

4.1 The bidirectional modulation of OXT

4.1.1 Context-dependence of OXT responses

High-quality studies have shown that music can lead to both increases and decreases in peripheral OXT levels. Overall, clinical condition appears to be the most influential factor in modulating OXT release. For instance, individuals with Williams syndrome exhibit exaggerated OXT release in response to their favorite positive music, suggesting dysregulation of the OXTergic system (Dai et al., 2012). In pregnant and postpartum mothers, the OXTergic system is highly active yet peripheral OXT levels tend to be low (Filippa et al., 2023; Wulff et al., 2021), since pregnancy inhibits OXT secretion but enhances OXT receptor (OXTR) expression and enzymatic degradation (Uvnas-Moberg, 2024).

Context-dependence can explain the variability in OXT responses across studies. Under basal conditions, central and peripheral OXT levels show no significant correlation (Kagerbauer et al., 2013; Valstad et al., 2017), since peripheral OXT reflects only the activity of magnocellular OXT neurons projecting to the posterior pituitary but central release involves both magnocellular and parvocellular OXT neurons (Bowling, 2023). However, during acute stress or strong physiological or social stimulation, coordinated OXT release in the CNS and periphery may occur and produce higher correlations between central and peripheral OXT levels (Martin et al., 2018; Valstad et al., 2017). As illustrated in Figure 2, music can induce such release by shaping the context, which is comprised of several elements, including the type of activity, stress signals, social cues, and familiarity with the music or social setting. The auditory signals travel through the classical pathway to the auditory cortex, while contextual inputs, including all sensory inputs, stress signals, and social cues, go through the non-classical pathway to the limbic system and the hypothalamus. The inputs are integrated in the hypothalamus, which may trigger coordinated or independent release of OXT in the CNS and periphery, and activate or deactivate the hypothalamic-pituitary-adrenal (HPA) axis.

Figure 2

Nevertheless, the dimensions that constitute the context differ in their importance. Our contextual analysis (Tables 6, 7) indicates that activity and stress signals have combined effects on OXT responses, with qualitative analysis showing that activity is the primary driver, while stress signals may reverse these effects under certain conditions. Social cues and familiarity showed limited predictive power. Statistical evidence also supports the patterns. Schladt et al. (2017) found a significant time × context interaction, showing that OXT changes over time depend on contexts, consistent with other studies (Filippa et al., 2021; Good and Russo, 2022; Kreutz, 2014). Bowling et al. (2022) distinguished two contextual factors, vocal mode and social context, and identified vocal mode (corresponding to activity type) as the key factor that influences OXT response patterns, with social context showing no significant effect. Ooishi et al. (2017) confirmed OXT's responsiveness to stress signals, as evidenced by a significant time × tempo interaction effect in a music-listening task that manipulated arousal or stress levels via tempo.

As for the weak effect of the social context, we attribute this to potential issues in the current experimental paradigm. Just as HPA axis activation requires high-stress conditions, OXT modulation may need sufficiently demanding social cues. Keeler et al. (2015) observed the influence of social cues through improvised group singing, which involved trust, synchrony, and real-time interaction. Instead, the structured singing tasks in Schladt et al. (2017) and Bowling et al. (2022) required participants to focus on vocal performance with limited spontaneous social interactions and should have been insufficient to reveal the effects of social cues. As a result, the context-dependence of OXT responses to music is specifically attributed to its reliance on two factors, namely the activity type and the stress signals, based on the statistical findings.

4.1.2 Functional adaptation of OXT to musical contexts

OXT exhibits temporally and spatially specific release patterns, and peripheral release can occur independently of or in parallel with central release (Jurek and Neumann, 2018). In the circulation, OXT follows a pulsatile release pattern, and pulse characteristics are strongly linked with baseline socio-emotional functioning. Mean OXT pulse height and pulse mass were negatively correlated with avoidant attachment and positively correlated with perceived social support (Baskaran et al., 2017). It suggested that temporal dynamics of peripheral OXT release carry crucial psychosocial information.

In the CNS, spatial specificity of OXT release allows for nuanced modulation. OXT activates OXTRs, which are coupled with Gq or Gi/o proteins, resulting in diverse downstream effects (Jurek and Neumann, 2018). For example, OXT release directly activates dopaminergic neurons and indirectly inhibits them via local GABAergic interneurons, but the relative magnitudes of the two mechanisms differ in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc; Xiao et al., 2017). OXT functions as a allosteric modulator of μ opioid receptor (MOR), and enhances the MOR signaling without altering receptor affinity (Meguro et al., 2018). In the striatum, OXTR activation on astrocytes inhibits glutamate release (Amato et al., 2022), and D2R-OXTR heterocomplexes facilitate dopaminergic signaling (Hernandez-Mondragon et al., 2023; Pérez de la Mora et al., 2016). The differential modulation of OXT supports its excitatory and inhibitory effects, which depend on cell type, receptor coupling, and local neurotransmitter interactions.

Thus, OXT increases or decreases play different roles in reward processing, social cognition, and social behaviors:

• (1) Reward processing: the ventral striatum is central in reward processing. The nucleus accumbens (NAcc) is responsible for recognizing the salience and valence of stimuli (Cooper and Knutson, 2008). The left NAcc recognizes pleasure, while the right NAcc responds to all noteworthy stimuli whether they are positive or negative. When OXT increases, it may promote dopaminergic signaling (Xiao et al., 2017) and enhance the output of the striatum.

• (2) Empathy network: the ventromedial prefrontal cortex (vmPFC), a core area of the empathy network (Taruffi et al., 2021), normally receives inhibitory OXT projections. Increased OXT reduces activity in vmPFC, accelerates the response to social cues, reduces recall accuracy, and blurs the boundaries between self and others (Zhao et al., 2016). Decreased OXT might enhance the local activity of the empathy network and right striatum, strengthen emotional responses, and promote deeper emotional engagement with music, though direct evidence for this pattern in musical contexts remains to be established.

• (3) Social behavior: in both approach and avoidance behaviors, increased OXT reduces right striatum activity, potentially suppressing excessive emotional interference and promoting appropriate behavioral selection. Although OXT may weaken overall motivation, it improves the accuracy of approach to positive stimuli (Yao et al., 2018). This effect may reflect a compensatory mechanism in which motivation control shifts toward the left striatum when the right striatal activity is reduced.

The bidirectional modulation of OXT suggests that the OXTergic system adapts flexibly to musical context. Happy music primarily activates the left NAcc (Trost et al., 2012), and OXT release may facilitate dopaminergic signaling (Dai et al., 2012). Sad music selectively activates the right NAcc over the left (Trost et al., 2012), and is often accompanied by peripheral OXT decreases, especially in females with high trait empathy (Eerola et al., 2021).

Furthermore, there is a bidirectional relationship between the OXTergic system and the HPA axis (Bowling, 2023; Harvey, 2020; Jurek and Neumann, 2018). Under acute stress conditions, three temporal patterns may occur:

• (1) Concurrent release of OXT and adrenocorticotropic hormone (ACTH)/cortisol (Keeler et al., 2015);

• (2) An initial OXT increase that attenuates HPA activation (Jezova et al., 2013; Keeler et al., 2015);

• (3) HPA activation that selectively inhibits OXT release from the PVN (Jezova et al., 2013; Keeler et al., 2015).

Engaging in low-exertion social activities under low-stress conditions is conducive to OXT release since OXT is primarily involved in physiological relaxation rather than psychological relaxation (Ooishi et al., 2017). Slow-tempo music is more likely to induce OXT release without inhibition by the HPA axis (Ooishi et al., 2017; Wulff et al., 2021), as it is usually perceived as more pleasant and relaxing (Ooishi et al., 2017). In contrast, fast-tempo music or singing may initially activate the HPA axis due to increased arousal or stress, which can temporarily suppress OXT release, even though the HPA responses may decrease by the end of the intervention (Bowling et al., 2022; Fancourt et al., 2016; Good and Russo, 2022; Grape et al., 2003; Jezova et al., 2013; Keeler et al., 2015; Ooishi et al., 2017; Schladt et al., 2017). Additionally, prolonged singing sessions (e.g., over an hour) may lead to fatigue and limit other social interactions (Fancourt et al., 2016). If the reward from music is insufficient to counteract the earlier inhibition, OXT levels may remain unchanged or even decrease, as observed in studies where the participants sang touching sublime religious songs (Bowling et al., 2022; Schladt et al., 2017).

In summary, the findings challenge the assumption that higher OXT levels are beneficial. Instead, both increases and decreases in OXT levels may support adaptive emotional and social functions. Importantly, the context-dependence of music and OXT emphasizes the need to consider baseline physiological and psychological states, intervention types, and environmental factors.

4.2 Peripheral OXT and subjective outcomes

Discrepancies between peripheral OXT levels and psychosocial outcomes have led to ongoing debate about the relationship between central and peripheral OXT activity. While context-dependence may account for the variability and direction of peripheral OXT responses, subjective outcomes exhibit different context-dependence.

Evidence from Bowling et al. (2022) implied the dissociation. The patterns of OXT responses were mainly determined by vocal mode (time × vocal mode interaction) rather than social cues. IOS scale also showed a significant time × vocal mode interaction, which suggested that social bonding might be associated with the physiological processes behind vocal synchrony. However, PANAS showed a significant three-way interaction (time × vocal mode × social context), indicating that the changes of affective experiences were dependent on both the activity and social cues. In addition, there were no significant correlations between the pre-post change of OXT and self-reported emotion, mood or stress scores (Fancourt et al., 2016; Ooishi et al., 2017). Thus, different outcome measures are sensitive to different contextual factors. OXT responses should be regarded as intrinsic physiological adaptations to musical activities. Since OXT secretory dynamics (e.g., pulse characteristics) are more likely to reflect subjective socio-emotional functioning than a single measurement or pre-post change (Baskaran et al., 2017), pre-post changes of OXT often fail to predict subjective outcomes, which are heavily influenced by placebo effects, expectations, and the infeasibility of blinding in music-based interventions. As a result, perceived benefits may reflect cognitive and cultural interpretations of musical meaning.

Behavioral changes following musical activities are likely mediated by central mechanisms not fully captured by peripheral OXT measurements (Martins et al., 2020). For example, social cognition and reward processing can be mediated by OXT and OXTR, while social communication relies more on arginine-vasopressin (AVP) and its receptor (V1aR; Song and Albers, 2018). Since OXT and AVP share structural similarities and can activate each other's receptors, this phenomenon, “cross-talk” (Song and Albers, 2018), is likely to participate in shaping social behaviors in musical contexts. Therefore, peripheral OXT levels have limited predictive value for subjective outcomes. When interpreting outcomes regarding social cognition, social reward, or social behavior, we recommend considering the OXT-AVP systems that mediate the adaptive responses to social stimuli.

4.3 Clinical implications

The bidirectional modulation of OXT suggests that therapeutic strategies need to move beyond merely increasing OXT levels, as OXT enhances the salience of both positive and negative social cues, encouraging social approach in safe contexts but inducing avoidance in aversive environments (Steinman et al., 2019). From a translational medicine perspective, the context-dependence of OXT responses implies that existing music-based interventions could be refined by considering the activity type and stress signals involved.

For social anxiety disorder (SAD) patients, social cues belong to intense stress signals since they usually interpret social cues negatively and lack motivation for positive social interaction. Based on our contextual analysis, at the initial stage, treatment should begin with a safe setting using neutral, calming, or peaceful music, with limited social interactions. It is advisable that the musical emotions not completely simulate anxiety to avoid overwhelming negative feelings in patients. Social engagement can be gradually introduced only after basic trust is established and the emotional state is stabilized. We recommend structured group singing in a small choir (Keeler et al., 2015) for SAD patients, as it provides appropriately limited social cues which is sufficient for therapeutic effects but not overwhelming.

Some typical characteristics of ASD, such as deficits in imitation, emotional empathy, and attributing intentions to others, reflect the mirror system dysfunction (Cattaneo and Rizzolatti, 2009). For ASD children, rhythmic musical activities could mobilize the mirror systems, improve self-control, and help process acoustic prosody for conversational quality (Wynn et al., 2022). Because rhythmic music involves precise timing prediction and synchronization, patients need to pay more attention to social cues. Patients who are sensitive to OXT will benefit from improvement in social information processing. Thus, group drumming (Yuhi et al., 2017) and musical theater therapy (Corbett et al., 2011) are recommended for individuals with ASD. The therapy design requires setting up lessons of different levels and breaking them down into manageable parts to learn. Rhythm complexity needs to increase gradually, from simple, accessible patterns to more complex synchronization tasks, to avoid frustrations for beginners.

Understanding the mechanisms through which music influences emotion regulation and social bonding benefits the design of music therapy, as it enables a better understanding of which strategies are more effective in mobilizing the neural networks to achieve therapeutic goals.

4.4 Strengths and limitations of the included study

Several included studies demonstrated methodological rigor that strengthens confidence in their findings. The RCTs provided stronger evidence for causal relationships between music-based interventions and OXT changes. Some studies accounted for biological and environmental confounders, used validated OXT assays with extraction procedures (Gan et al., 2023), and employed real-world settings that enhanced ecological validity. An advantage was the predominant use of saliva samples. Unlike plasma OXT, which fluctuates rapidly due to its 7-min half-life (Shafer et al., 2025) and pulsatile release pattern (Baskaran et al., 2017), salivary OXT can provide more stable measurements since it has a longer half-life (Quintana et al., 2018).

However, the studies exhibit several limitations that necessitate discussion. A primary concern is the reliance on pre-post measurements of peripheral OXT, which may not reflect central OXT activity (Kagerbauer et al., 2013; Valstad et al., 2017) or be correlated with attachment style, perceived social support, and emotional awareness (Baskaran et al., 2017). Timing issues were also evident in some studies. Specifically, OXT's dramatic fluctuations within CAR period could potentially mask intervention effects. Comparability across studies was hindered by inconsistencies in sampling methods and quantification techniques (Lefevre et al., 2017), as well as insufficient reporting of musical and contextual details. Moreover, common issues like small sample sizes and the lack of negative controls reduced the internal validity. While fasting and exercise restrictions did not have significant influence on OXT levels (Engel et al., 2019), other behavioral confounders, such as hospital anxiety or sexual activity prior to sampling, still need to be considered (Jurek and Neumann, 2018).

4.5 Strengths and limitations of the current study

This review addressed the research questions through comprehensive search strategies, predefined eligibility criteria, and structured syntheses that integrated heterogeneous findings. Our contextual analysis provides a key insight by identifying four distinct contextual dimensions and their different contribution on OXT modulation.

However, there were several limitations in the review. First, it was mainly conducted by one reviewer, which may introduce selection bias, and restrictions to English publications could have excluded relevant studies. None of the included studies examined OXTR gene polymorphisms, which associate with social behavior variability in clinical populations (Harrison et al., 2015) and may influence individual responses to music. Additionally, no studies directly investigated receptor interactions such as functional complexes of OXTR with dopamine, serotonin, and opioid receptors. Only Fancourt et al. (2016) reported correlated declines of OXT and beta-endorphin after choral singing. Thus, the interpretation scope of the review is limited.

5 Conclusion

The context-dependence of OXT responses to music has significant implications for clinical practice and research. Evidence supports a bidirectional relationship in which music induces subtle emotional responses, which are further modulated by OXT. The effectiveness of music-based interventions may not rely on the direction of OXT change but on the adaptive modulation of OXT. For clinical applications, music-based interventions should be carefully tailored to specific populations and contexts. Larger sample sizes, standardized outcome measures, and well-controlled experimental designs are needed in the future. Given the limitations of peripheral OXT measurements, we suggest that future studies explore central OXT signaling or receptor interactions. Integrating genetic studies and peptide assessments, the use of OXTR agonists or antagonists, combined with neuroimaging techniques such as functional magnetic resonance imaging (fMRI), may provide deeper insights into how music modulates brain activity through the OXTergic system.

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