Bipolar Disorder (BD) is a severe and chronic psychiatric condition characterized by recurrent episodes of mania, hypomania, depression, and mixed states, affecting approximately 1 % of the global population (Rowland and Marwaha, 2018). These mood fluctuations significantly impair daily functioning and quality of life, contributing to high rates of disability, mortality, and suicide risk (Nierenberg et al., 2023; Oliva et al., 2023). Among the core features of BD, Emotion Dysregulation (ED) has emerged as a fundamental mechanism influencing both the onset and the course of the disorder (De Prisco et al., 2023).

ED encompasses a range of definitions, terms, and manifestations, reflecting the heterogeneity with which the construct is understood and applied. At its core, however, it is commonly described as involving rapid oscillations of intense emotional states and a diminished capacity to regulate these fluctuations or their behavioral outcomes (Brancati et al., 2023). Hence, ED represents a multidimensional and transdiagnostic construct, referring to a patterns of emotional experience and expression that interfere with the ability to engage in goal-directed behavior (Thompson, 2019). In particular, ED includes difficulties in controlling impulsive behaviors or modulating emotional responses to negative emotions (Gratz and Roemer, 2004), abrupt or excessively slow changes in emotions, and a slower return to an emotional baseline (Carpenter and Trull, 2013). In individuals with BD, ED is also associated with atypical attentional allocation to emotional stimuli (García-Blanco et al., 2015; Henry, 2012).

From a neurobiological perspective, ED in BD arises from multi-level abnormalities in both fronto-limbic circuits and large-scale brain networks, which play a crucial role in emotional regulation (Bi et al., 2022). At the core level, disruptions in the fronto-limbic circuit—where a hyperactive amygdala is insufficiently regulated by the ventromedial prefrontal cortex (vmPFC) and the anterior cingulate cortex (ACC)—lead to heightened emotional reactivity and poor affective modulation. (Lawrence et al., 2004; Radaelli et al., 2015; Strakowski et al., 2012; Townsend et al., 2013; Wessa and Linke, 2009). At higher levels, dysregulations in large-scale brain networks further impair emotional control. Specifically, hyperactivity in the Default Mode Network (DMN) and Salience Network (SN), combined with reduced activity in the Central Executive Network (CEN), results in severe deficits in cognitive control over emotional responses, contributing to mood liability (Ellard et al., 2018; Goya-Maldonado et al., 2016; Zarp Petersen et al., 2022; Zovetti et al., 2020).

From a clinical standpoint, ED exacerbates manic and depressive symptom severity, and overall illness burden (De Prisco et al., 2023). During manic episodes, ED contributes to heightened emotional reactivity, impulsivity, and increased sensitivity to reward, likely driven by amygdala hyperactivity and reduced prefrontal inhibitory control (Mesbah et al., 2023; Phillips and Swartz, 2014). On the other hand, during depressive episodes, ED is characterized by blunted affect, rumination, and impaired emotional modulation, associated with hypoactive limbic responses and DMN hyperactivity (Rey et al., 2021). In mixed states, ED results in heightened emotional distress and rapid mood fluctuations, reflecting simultaneous hyperactivity in emotional processing-related brain networks, weakness in cognitive control (M'Bailara et al., 2012), and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (Fitzgerald et al., 2018). Even in euthymia, persistent fronto-limbic dysconnectivity suggests a trait-like vulnerability, predisposing individuals to future mood episodes (Bi et al., 2022). Understanding the underlying mechanisms of ED in BD is therefore crucial for predicting clinical outcomes and developing tailored interventions.

In mental health, an emerging field of investigation is represented by interoception, which refers to the organism's ability to perceive, interpret and regulate internal signals of the body, both from a conscious (e.g. hunger, thirst, heartbeat, muscle tension, visceral pain) and an unconscious level (e.g. variations in neurotransmitters, hormones, receptors) (Chen et al., 2021). This process occurs through the interplay between brain networks anchored to specific areas (insula, anterior cingulate cortex, vagus nerve), physiological signals of the body (e.g. receptor stretching, cellular turnover), and experience in the world (Chen et al., 2021; Khalsa et al., 2018).

According to the Embodied-Predictive Interoception Coding (EPIC) model, through these mechanisms, the organism is able to predict internal and external requests in a Bayesian way and generate appropriate behavioral responses (Barrett and Simmons, 2015). Alterations at this level are implicated in the pathophysiology of a wide range of psychiatric disorders, including anxiety, mood disorders, schizophrenia, and addiction (Bonaz et al., 2021). In this sense, emotions do not arise in isolation from the body, nor are they reducible to cognitive interpretation alone. Rather, they emerge from the integration of distributed interoceptive signals – cardiac, respiratory, and visceral – into unified experiential states (Critchley and Garfinkel, 2017). When interoception is dysregulated – whether through amplification, attenuation, or loss of signals integration – the resulting perturbations can manifest as affective instability, heightened stress reactivity, and impaired adaptive behavior (Khalsa et al., 2018).

Building on these insights, ED and interoceptive impairments could be conceptualized as elements of a broader transdiagnostic domain spanning several psychiatric conditions.

Bipolar Disorder offers a persistent, internally driven form of affective instability, likely reflecting a trait-like neurobiological vulnerability (De Prisco et al., 2023; Durdurak et al., 2025). This trait orientation contrasts with the more context-dependent forms of emotion dysregulation observed in other conditions (Carpenter and Trull, 2013; Shaw et al., 2014).

For instance, Borderline Personality Disorder (BPD), Attention-Deficit/Hyperactivity Disorder (ADHD), and atypical depression have all been associated with both emotion dysregulation and interoceptive dysfunction (Carpenter and Trull, 2013; Flasbeck et al., 2020; Hu et al., 2023; M. Bruton et al., 2025; Shaw et al., 2014), though likely with differing profiles and mechanisms.

In BPD and ADHD, emotion dysregulation tends to manifest as a rapid, reactive response to external stimuli and is closely linked to interpersonal instability or attentional dyscontrol (Martel, 2009; Sebastian et al., 2013; Shaw et al., 2014). In atypical depression, ED seems related to rejection sensitivity and somatic amplification (Silverstein et al., 2006).

Thus, this study adopts a real-world approach by focusing on Bipolar II Disorder inpatients hospitalized for depressive episodes, the most common reason for admission in our clinical setting, drawing on both the high availability of this patient group and the specific opportunities that BD offers for investigating the potential mediating role of interoceptive sensibility in emotion dysregulation.