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OBM Neurobiology

(ISSN 2573-4407)

OBM Neurobiology is an international peer-reviewed Open Access journal published quarterly online by LIDSEN Publishing Inc. By design, the scope of OBM Neurobiology is broad, so as to reflect the multidisciplinary nature of the field of Neurobiology that interfaces biology with the fundamental and clinical neurosciences. As such, OBM Neurobiology embraces rigorous multidisciplinary investigations into the form and function of neurons and glia that make up the nervous system, either individually or in ensemble, in health or disease. OBM Neurobiology welcomes original contributions that employ a combination of molecular, cellular, systems and behavioral approaches to report novel neuroanatomical, neuropharmacological, neurophysiological and neurobehavioral findings related to the following aspects of the nervous system: Signal Transduction and Neurotransmission; Neural Circuits and Systems Neurobiology; Nervous System Development and Aging; Neurobiology of Nervous System Diseases (e.g., Developmental Brain Disorders; Neurodegenerative Disorders).

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Open Access Review

Biochemical Foundations of Emotion Regulation: Implications for Pharmacological and Psychological Interventions-A Narrative Review

Marina M Gerges 1, Vladimir Kosonogov 2,*

  1. Institute for Cognitive Neuroscience, HSE University, Moscow, Russia

  2. Affective Psychophysiology Laboratory, Institute of Health Psychology, HSE University, Saint Petersburg, Russia

* Correspondence: Vladimir Kosonogov

Academic Editor: Bart Ellenbroek

Received: May 02, 2025 | Accepted: November 02, 2025 | Published: November 19, 2025

OBM Neurobiology 2025, Volume 9, Issue 4, doi:10.21926/obm.neurobiol.2504310

Recommended citation: Gerges MM, Kosonogov V. Biochemical Foundations of Emotion Regulation: Implications for Pharmacological and Psychological Interventions-A Narrative Review. OBM Neurobiology 2025; 9(4): 310; doi:10.21926/obm.neurobiol.2504310.

© 2025 by the authors. This is an open access article distributed under the conditions of the Creative Commons by Attribution License, which permits unrestricted use, distribution, and reproduction in any medium or format, provided the original work is correctly cited.

Abstract

Emotion regulation (ER) involves processes by which individuals modulate the intensity, duration, and expression of emotional responses, and its dysregulation is associated with a broad spectrum of psychological disorders. While traditionally conceptualized within psychological frameworks, ER is increasingly recognized as biologically grounded, involving intricate interactions between neurochemical, hormonal, and metabolic systems. This narrative review aims to synthesize current evidence on biochemical substrates of ER, with a specific focus on integrating findings across neurotransmitters (serotonin, dopamine, GABA, glutamate), classical regulatory hormones (cortisol, oxytocin), and metabolic hormones (leptin, ghrelin, insulin). We critically examine how these systems interact with both adaptive and maladaptive ER strategies, and how they are modulated by pharmacological treatments (e.g., antidepressants, mood stabilizers) and substances (e.g., alcohol, illicit drugs). A particular contribution of this review lies in its emphasis on metabolic hormones. This domain remains underrepresented in mainstream ER models despite emerging relevance in stress reactivity and emotion-linked behavior. Although evidence suggests compelling associations, much of the existing research remains correlational, and further longitudinal studies are warranted. Although structured to capture key developments, the narrative design may not encompass every relevant study, and variations in methodologies across research contexts suggest that comparisons should be interpreted with caution. Nevertheless, this work identifies conceptual gaps and outlines practical implications, including the potential to tailor interventions based on individual neurochemical and behavioral profiles.

Keywords

Emotion regulation; cognitive reappraisal; expressive suppression; biochemistry; neurotransmitters; hormones; mental health; pharmacological interventions

1. Introduction

Numerous works in both biology and psychology address the concept of emotion. While there is no universally accepted definition, an emotion can generally be described as a strong, brief affective response to an event, accompanied by specific physiological changes [1]. Emotional processing begins with a trigger that elicits arousal, culminating in a mental and behavioral reaction. This process takes place between the initial stimulus that evokes an emotion and the subsequent physiological and behavioral responses. It involves a series of interconnected activities, steps, and tasks necessary to modify information each time the process occurs, ideally leading to a more adaptive outcome [2].

The ability to control these emotional responses is known as emotion regulation (ER), which governs both the internal experience and external expression of emotion [1,2]. ER includes a range of strategies that individuals use to manage emotional responses in daily life. For example, cognitive reappraisal involves changing one's interpretation of a situation to reduce its emotional impact [3], while expressive suppression involves inhibiting emotional expression without altering the underlying emotional state [3]. Other strategies include mindfulness (nonjudgmental awareness of emotions) [4], distraction (shifting attention away from distressing stimuli) [5], and rumination (repetitive focus on negative feelings, typically maladaptive) [6]. Healthy regulation enables individuals to flexibly apply these strategies, while persistent reliance on maladaptive strategies can lead to adverse outcomes. While the psychological dimensions of ER have been extensively studied, its biological underpinnings remain comparatively underexplored. Neurotransmitters such as serotonin, dopamine, GABA, and glutamate shape emotional processing by modulating affective neural circuits [7,8]. Hormones like cortisol and oxytocin also play additional roles in modulating stress and social attachment [9,10]. However, there is growing recognition that a more integrated perspective is needed, combining these neurotransmitters with metabolic hormones such as leptin, ghrelin, and insulin to fully understand emotion regulation, particularly through their involvement in appetite, stress, and mood [11,12]. Despite the availability of domain-specific reviews, few studies have comprehensively integrated these biochemical systems into a unified framework for understanding ER [7,8,10]. Moreover, emerging intersections between ER and metabolic signaling remain underrepresented in the literature, even as these pathways show increasing clinical relevance in conditions such as eating disorders, obesity, and chronic stress-related illness.

This review aims to bridge this gap by synthesizing the current evidence on how neurotransmitters, hormones, and metabolic systems interact to regulate emotions. By contextualizing classical emotional regulators (e.g., serotonin, cortisol) alongside less-explored metabolic agents, this review provides a broader, more clinically actionable perspective on emotional dysregulation. A distinctive contribution of this work is its attention to metabolic hormones, which are often overlooked despite their relevance to emotional and behavioral health. By bringing together biochemical, psychological, and pharmacological perspectives, this review aims to support more comprehensive and personalized approaches to emotion regulation, with implications for mental health research and clinical practice. To support this synthesis, relevant peer-reviewed studies published from 2000 to 2024 were identified through a narrative review of databases including PubMed, PsycINFO, and Scopus, with the emphasis on original human research and meta-analyses examining biochemical correlates of emotion regulation.

2. Neurotransmitters and Hormones Involved in Emotional Regulation

2.1 Serotonin

Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter critical in emotion regulation. Serotonergic neurons originating in the nucleus raphe project extensively to emotion-processing areas such as the prefrontal cortex, amygdala, and hippocampus [13]. Serotonin helps maintain emotional balance by influencing various aspects of emotional processing. It modulates synaptic activity across affective circuits, particularly by regulating input from subcortical structures (like the amygdala) to prefrontal regions responsible for cognitive control. Dysfunctions in the serotonergic system can lead to mood disorders such as depression and anxiety. This reinforces its important role in emotional homeostasis [14].

Altering serotonin levels pharmacologically impacts how emotions are processed, influences attention to emotional stimuli, affects emotional memory, and can modify decision-making and attitudes. In healthy individuals, increased serotonin activity enhances attention to and recognition of positive emotions [15]. Lower serotonin activity reduces recognition of positive emotional cues and leads to a greater focus on negative stimuli. Genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) significantly affects reactivity to emotional stimuli, influencing the use of strategies. S-allele carriers show greater limbic activity and tend to rely more on suppression, while L-allele carriers more commonly use reappraisal [16,17]. These differences are supported by neuroendocrine evidence showing that S-carriers exhibit stronger cortisol responses under stress and altered prefrontal recruitment during emotional regulation tasks [16].

From a genetic perspective, one study examined how the 5-HTTLPR genotype influences cognitive reappraisal during emotion regulation tasks. S-allele carriers showed a reduced posterior insula activation during passive perception. Still, they increased prefrontal and anterior insula activation during the cognitive reappraisal, suggesting heightened emotional reactivity and modulation capacity in these individuals. The 5-HTTLPR polymorphism influences emotion regulation under stress, with S-allele carriers relying more on expressive suppression, which mediates the link between stress and depressive symptoms. In contrast, L-allele carriers more frequently use adaptive strategies, such as cognitive reappraisal, to buffer the effects of stress on mental health [17,18].

Tryptophan, an essential amino acid found in dietary proteins, is a precursor to serotonin. Studies on acute tryptophan depletion (ATD), which lowers central serotonin levels, have yielded inconsistent findings regarding emotion regulation. While some studies show increased negative emotional reactivity under ATD, others report no impact on cognitive reappraisal [19,20,21]. These conflicting results underscore the context-dependent role of serotonin and the difficulty of drawing causal inferences from correlational paradigms. For instance, one study observed that ATD amplified feelings of guilt and shame in social scenarios [21]. ATD has been associated with a heightened negative emotional bias, characterized by enhanced memory for negative distractors compared to neutral ones, along with increased neural activation in response to negative distractors in brain regions such as the left orbital-inferior frontal gyrus, dorsomedial prefrontal cortex, and bilateral angular gyri [22]. This suggests that serotonin may selectively influence specific emotional responses. Conversely, another study found no significant effect of tryptophan depletion on emotional reappraisal, a crucial mechanism in emotional processing [23]. These conflicting findings indicate that ATD may not capture the full complexity of serotonin's role in emotion regulation.

A study hypothesized that serotonin plays a role in emotion regulation during virtual violence, predicting that SSRIs would modulate hemodynamic responses in relevant brain networks. Their findings revealed that short-term inhibition of 5-HT reuptake through SSRI administration reduced activity in the prefrontal cortex during violent scenarios. This effect was contingent on the balance between inhibitory and excitatory 5-HT receptors, supporting the ecological validity of the 5-HT model of aggressive behavior. These early functional changes in the emotion regulation network may contribute to the treatment effects of SSRIs [24].

Similarly, research found that treatment with SSRIs or cognitive behavioural therapy (CBT) improved emotion regulation strategies such as reappraisal and suppression in patients with internalizing disorders like anxiety and depression [25]. Interestingly, while both SSRIs and CBT were effective, SSRIs appeared to have a specific influence on reducing repetitive negative thinking, suggesting a nuanced interaction between pharmacological and therapeutic approaches.

Moreover, paroxetine increased activation in the dorsolateral prefrontal cortex and supplementary motor area during emotion regulation in veterans with PTSD. Those with the least pre-treatment involvement of prefrontal brain regions showed the most significant symptom reduction following SSRI treatment. Further, SSRIs, such as escitalopram, have been shown to selectively reduce emotional responses of fear and disgust, with effects localized in emotion-specific neural circuits [26,27]. Neuroimaging studies support a role for serotonin in emotion control by showing that lower serotonin transporter availability in the dorsal raphe nucleus is associated with greater amygdala activation and increased amygdala-prefrontal connectivity during negative emotions [28].

These findings reinforce the importance of the serotonergic system in shaping emotion regulation circuits through both tonic and phasic neuromodulation. Moreover, pharmacogenetic findings indicate that 5-HTTLPR genotype may modulate SSRI response, with S-allele carriers showing differential treatment outcomes in disorders such as ADHD and depression [29]. This highlights the importance of personalized approaches when targeting serotonin pathways for emotional dysregulation.

2.2 Dopamine

Because of its effects on motivation, reward processing, and behavioral adaptability, dopamine, a monoamine neuromodulator, is also essential for emotional regulation.

Research by Wu et al. [30] highlights dopamine's role in cognitive reappraisal, showing that dopaminergic reward circuits—including the amygdala, midbrain, and nucleus accumbens—are activated during creative reappraisal. These findings suggest that dopamine-driven pathways facilitate motivational and memory-related processes underlying effective cognitive reappraisal strategies. Similarly, Siep et al. [31] found that emotional upregulation increases activity in key mesocorticolimbic regions, such as the VTA and the ventral striatum. At the same time, suppression, compared to cognitive reappraisal, more effectively reduces activity in these areas. This supports the idea that distinct emotion regulation strategies selectively engage dopamine-mediated pathways in different ways.

Dysfunction in dopamine signaling can manifest in various emotional regulation disorders. In depression and anhedonia, reduced dopamine transmission in the mesolimbic pathway contributes to an inability to experience pleasure and disrupts standard reward processing, affecting both motivation and emotional response [32]. Addiction represents another significant pathological state where dopamine dysfunction plays a central role. Excessive dopamine release during substance use creates powerful emotional associations, while disrupted reward processing leads to profound emotional dysregulation [33]. Anxiety and stress disorders also show links to dopamine dysfunction, where altered signaling affects stress response and emotional resilience.

For example, a study by Woudstra et al. found that depressed individuals with lower approach motivation—which reflects reduced dopaminergic activity—showed decreased dorsolateral prefrontal cortex activation during reappraisal tasks, highlighting the role of dopamine in motivational engagement during emotion regulation [29]. Disruption of prefrontal dopamine circuits can significantly impair emotional coping strategies and stress management capabilities [34]. Both hypo- and hyperdopaminergic activity can disrupt the regulation of emotional responses, highlighting the need for a balanced dopaminergic system in adaptive emotional functioning.

2.3 Gamma-Aminobutyric Acid (GABA) and Glutamate

Gamma-aminobutyric acid (GABA) and glutamate are the primary inhibitory and excitatory neurotransmitters in the brain, respectively, both of which are important for emotion regulation. GABA is essential for maintaining excitation-inhibition balance in emotion circuits, particularly within the amygdala [35,36]. In the basolateral amygdala, GABAergic interneurons regulate glutamatergic principal neurons, and disruption of this control contributes to anxiety and hyperexcitability [37]. Neuroimaging studies also show that higher GABA in the dorsomedial prefrontal cortex is associated with reduced anterior cingulate cortex (ACC) activity during negative affect, suggesting inhibitory modulation of emotional responses [38]. Excessive GABA activity, however, may produce over-inhibition of cognitive control, as reported in young females with heightened anxiety [39]. Together, these findings highlight region- and population-specific effects of GABA in emotion regulation. Glutamate provides the principal excitatory drive in emotion circuits. In adults, higher glutamate levels in the ACC are positively associated with regulatory capacity [40]. Pre-task glutamate concentration in the dorsomedial prefrontal cortex predicts greater ACC responses to anger, underscoring its role in facilitating emotional processing [40]. Moreover, mindfulness training has been shown to increase glutamate metabolism in the ACC and posterior cingulate cortex, supporting improved regulation and cognitive flexibility [41].

Also, evidence suggests that glutamate-emotion links may differ across age: while glutamate supports regulation in adults, adolescents show opposite associations [42,43]. Moreover, recent neuroimaging work shows that up-regulation of negative emotions through distancing engages the right cerebellum, and that this cerebellar activity is positively correlated with medial prefrontal cortex GABA concentration—indicating that GABAergic modulation may support cerebellar involvement in emotion regulation via cognitive reappraisal strategies [44]. These findings indicate developmental differences in glutamatergic involvement in emotion regulation. In sum, GABA provides inhibitory control and glutamate excitatory drive; their dynamic balance is essential for adaptive emotional regulation, and disruptions in either system can contribute to mood and anxiety disorders.

2.4 Cortisol and the Hypothalamus-Pituitary-Adrenal (HPA) Axis in Emotion Regulation

The hypothalamus-pituitary-adrenal (HPA) axis is the central component of the neuroendocrine system, regulating stress responses, metabolism, immune function, and emotional processing [45]. Cortisol, the primary glucocorticoid in humans, is a key effector hormone of this axis. Its role in emotion regulation, however, is complex and context-dependent. Rather than exerting uniformly beneficial or detrimental effects, cortisol dynamically interacts with other neuromodulators, particularly noradrenaline. It influences emotion-related brain regions, such as the prefrontal cortex (PFC), hippocampus, and amygdala [46].

Experimental evidence indicates that cortisol can both impair and facilitate cognitive regulation of emotions, depending on timing, intensity of stress, and task demands. During acute stress, glucocorticoid elevations may transiently disrupt top-down control by the PFC, impairing the flexible use of recently acquired regulatory strategies, particularly in fear-conditioning paradigms [46,47,48,49,50].

Evidence from functional magnetic resonance imaging (fMRI) suggests that cortisol may enhance regulatory processes in specific contexts. In a study by Jentsch et al. [46], cortisol administration 90 minutes before exposure to neutral and negative images enhanced regulatory activation in the ventrolateral PFC during distraction and reduced amygdala reactivity during cognitive reappraisal. Similarly, Langer et al. [47] demonstrated that cortisol promoted downregulation of highly intense negative affect across both 30- and 90-minute intervals, with improved valence ratings and reduced arousal; these effects appear to be highly time-sensitive. These time-dependent effects align with dual-action models of glucocorticoid function, whereby rapid non-genomic effects differ from slower genomic actions [47].

In another randomized, double-blind neuroimaging study, Pan et al. [48] observed time-dependent effects of cortisol on emotional responses—while rapid cortisol enhanced amygdala and dorsolateral PFC activity, longer-term effects reduced activation in these regions, thereby improving the regulation of negative emotions. A recent work by Langer et al. [49] further supported this notion, proposing the PRESSURE model, which posits that cortisol's involvement in emotion regulation depends on the balance between the HPA axis and the sympathetic nervous system, as well as on context, individual differences, and regulation strategies. This integrative perspective helps explain the variability in cortisol facilitative effects across studies. Such findings highlighted that cortisol's role in emotion regulation is not unidirectional but evolves across temporal phases: initial disruption may give way to later facilitation, supporting recovery and adaptation to stressors. Nevertheless, these conclusions must be interpreted cautiously. Most evidence derives from short-term pharmacological manipulations in healthy samples, limiting generalizability to chronic stress conditions, clinical populations, or real-world contexts. Individual differences in stress reactivity and prior learning history may further modulate outcomes. Thus, while converging studies suggest that cortisol contributes to both impairments and enhancements in cognitive emotion regulation, its precise role remains dependent on timing, context, and person-specific factors.

2.5 Oxytocin

Oxytocin (OT), a nonapeptide hormone synthesized predominantly in the hypothalamus, emerges as an essential neuromodulator within emotion regulation circuits. Operating in concert with arginine vasopressin (AVP), oxytocin is distributed in key brain regions involved in emotional processing and regulation—including the amygdala, hypothalamus, hippocampus, nucleus accumbens, insula, and striatum—where its effects are mediated via oxytocin receptors [51].

In the context of emotion regulation, oxytocin influences neural mechanisms that support adaptive emotional responses. Meta-analytic investigations suggest that intranasal oxytocin (IN OT) administration enhances the activity within prefrontal regions associated with emotion regulation while strengthening amygdala-prefrontal connectivity [52]. Such connectivity has been interpreted as facilitating top-down control, particularly in regulating fear- and anxiety-related emotions, although results remain heterogeneous. Research indicates that individuals with lower emotion regulation abilities may particularly benefit from oxytocin's effects; for example, individuals with reduced emotional reactivity and awareness who received intranasal oxytocin showed improvements relative to placebo, though replication is needed [53].

The role of oxytocin in emotion regulation becomes particularly evident in its modulation of the stress response. Its regulatory properties include potential attenuation of cortisol secretion and modulation of sympathetic activity during emotional challenges [54]. In individuals diagnosed with emotion regulation difficulties, such as those with PTSD, oxytocin administration has been associated with increased connectivity between regulation circuits, which may support cognitive control. However, findings are inconsistent [55]. Furthermore, research has shown that early-life stress and emotion-suppression tendencies correlate with altered oxytocin function, suggesting that early experiences may influence emotion regulation through oxytocin-mediated pathways [56].

Oxytocin's role in neural pathways governing emotional learning and adaptation remains under investigation. Some evidence points to more substantial effects in individuals with baseline difficulties. Still, these results should be interpreted cautiously, given methodological variability (dose, timing, route of administration) and limited ecological validity [57]. Overall, oxytocin appears to modulate emotion regulation processes, but its effects are not uniform across contexts or individuals. Current evidence is preliminary, and more rigorous, ecologically valid studies are needed before firm therapeutic claims can be made.

2.6 Leptin and Ghrelin

Leptin and ghrelin are essential metabolic hormones with well-established roles in appetite and energy balance. Leptin, an adipokine secreted by adipose tissue, signals satiety and energy sufficiency, thereby contributing to long-term appetite regulation [58]. In contrast, ghrelin, a peptide hormone produced by gastrointestinal cells, stimulates hunger and short-term food intake [59,60].

Nevertheless, studies suggest that social and psychological stressors can modulate these hormones in ways that overlap with emotional processes. For example, loneliness and social isolation have been associated with higher post-meal ghrelin levels in leaner women, potentially driving compensatory eating in response to social disconnection [61]. Similarly, marital conflict and perceived low social status—both interpersonal stressors—have been associated with altered ghrelin responses, whereas leptin appears to show more modest buffering effects during acute stress [62,63,64,65,66,67]. More recent research underscores the importance of distinguishing hunger-related affect from emotion regulation per se. In bariatric surgery candidates, emotion dysregulation was found to mediate the association between pathological eating styles and psychopathological traits, highlighting the interplay between metabolic signals, ER deficits, and maladaptive eating [68]. Dysregulation of ghrelin and leptin pathways has also been implicated in anorexia nervosa and binge eating, with altered hormone profiles linked to impaired stress responses and emotional instability [69,70]. In summary, leptin and ghrelin should not be regarded as direct regulators of emotion but as metabolic signals that interact with stress, social context, and individual vulnerability. This distinction clarifies their role in shaping emotional eating and maladaptive regulation strategies rather than cognitive ER processes themselves [71,72].

2.7 Apelin

Apelin, a peptide hormone secreted by adipose tissue and a ligand for the G-protein-coupled receptor APJ, is involved in multiple physiological processes, including the stress response, energy metabolism, and cardiovascular regulation. Preclinical studies suggest a role of apelin in modulating hypothalamic-pituitary-adrenal activity and reducing depressive-like behaviors [73,74]. However, evidence from human studies remains scarce. For example, a recent study in children reported that higher salivary apelin concentrations were positively associated with serotonin levels, and both markers were linked to better emotion regulation skills after adjusting for age and gender [75,76,77]. At present, apelin should be considered a candidate modulator of emotional functioning rather than a confirmed regulator of emotion regulation.

2.8 Insulin and HbA1c

Insulin, a critical hormone produced by the pancreas, is essential for glucose metabolism but also crosses the blood-brain barrier, influencing reward, mood, and cognition [78,79,80,81,82,83]. Dysregulated insulin signaling has been linked to depression and cognitive impairments [78,82,83].

Clinical evidence suggests that insulin dysregulation undermines emotion regulation. Beam et al. [81] showed that adolescents with type 1 diabetes, who restricted insulin, reported greater difficulties in ER and higher HbA1c levels. Brouwer et al. [82] also observed that insulin resistance was associated with irritability and depressive symptoms in individuals with type 2 diabetes. These findings support the idea that insulin dysregulation may indirectly impair ER via effects on cognition, mood, and stress reactivity. Reviews also highlight reciprocal feedback loops between poor glycemic control, executive dysfunction, and emotional dysregulation [83]. Intervention studies also suggest that improving ER may benefit metabolic outcomes. Coccaro et al. [84] found that higher ER and emotional intelligence were associated with lower HbA1c levels in adults with type 2 diabetes, proposing that ER-focused interventions could reduce metabolic and psychological burden. Taken together, evidence indicates that insulin and HbA1c are not merely metabolic markers but exert direct influences on emotional and cognitive processes. Insulin dysregulation affects neural circuits involved in mood and self-regulation, while poor glycemic control (HbA1c) amplifies stress and emotional difficulties, creating a bidirectional feedback loop. Addressing emotion regulation in this context may therefore yield dual benefits, improving both psychological resilience and metabolic stability [85].

2.9 Integrative Perspectives: Interactions Between Neurotransmitters and Metabolic Hormones in Emotion Regulation

While the preceding sections have reviewed individual biochemical systems, emerging evidence suggests that neurotransmitters and metabolic hormones interact through multiple pathways to shape emotion regulation capacity. Understanding these interactions is critical for developing a unified framework of ER biochemistry.

Serotonin and insulin interact bidirectionally, influencing both metabolic and emotional processes. Insulin crosses the blood-brain barrier and modulates serotonergic neurotransmission in emotion-processing regions [79]. This reciprocal relationship may explain why insulin dysregulation in diabetes is frequently accompanied by mood disturbances and emotional dysregulation [82,83], while serotonergic dysfunction can contribute to metabolic syndrome. Similarly, leptin interacts with dopaminergic reward circuits, modulating reward sensitivity and motivational states [70]. Under conditions of leptin resistance—common in obesity—this modulatory capacity is impaired, potentially contributing to altered reward processing and emotion-driven eating behaviors.

Ghrelin also interfaces with stress-responsive systems. During acute stress, ghrelin levels increase and interact with cortisol to influence both appetite and emotional reactivity [71,72]. This relationship suggests that hunger-related hormonal fluctuations may modulate stress vulnerability and the efficacy of emotion regulation strategies, particularly in individuals with disrupted eating patterns or metabolic conditions [66].

Collectively, these interactions suggest that emotion regulation capacity emerges from the dynamic interplay between neurochemical, neuroendocrine, and metabolic signaling networks rather than from isolated systems. This integrated perspective has important implications: interventions targeting one system (e.g., SSRIs for serotonin) may have downstream effects on metabolic hormones, while metabolic interventions (e.g., glycemic control, weight management) may influence neurotransmitter function and ER capacity [83,84]. Future research should explicitly examine these cross-system interactions to develop more comprehensive models of ER biochemistry.

3. Effects of Emotional Regulation on Biochemical Markers

3.1 Cortisol Levels

3.1.1 Meditation and Mindfulness

Emotional regulation strategies, particularly mindfulness and meditation practices, have demonstrated effectiveness in reducing cortisol levels by modulating the HPA axis and enhancing connectivity between the ACC and medial prefrontal cortex (mPFC), regions critical for emotion regulation and self-control. For instance, brief mindfulness interventions—such as a 4-day mindfulness meditation program [85] and a 48-hour Integrated Amrita Meditation [86]—significantly reduced cortisol levels. These findings suggest that even short-term meditation practices can reduce the physiological stress response and promote emotional balance, although causal mechanisms remain incompletely established. The link between emotional regulation and cortisol recovery has also been established; for example, a study found that individuals employing adaptive emotion regulation strategies exhibited better cortisol recovery following exposure to a stressor [10], and another showed that adaptive emotion regulation predicts greater recovery of salivary cortisol, indicating improved HPA axis regulation and resilience to stress [11]. A broader neuroendocrine perspective was provided by Wu et al. [30], who reviewed evidence demonstrating that mindfulness meditation improves emotion processing and regulation by enhancing HPA axis function. Integrative body-mind training (IBMT), a form of mindfulness meditation, was highlighted for its ability to reduce both the amount and duration of cortisol release in response to stressful challenges, while also enhancing connectivity and activity in the ACC and medial prefrontal cortex (mPFC)—brain regions critical for emotion regulation and self-control. In addition to stress reduction, mindfulness-based practices have shown promise in addiction prevention and treatment, with IBMT reducing stress-related cortisol while enhancing ACC/mPFC activity, which is associated with better emotion regulation in both healthy and addicted individuals [30]. Limitations include reliance on short-term interventions and correlational data; more longitudinal and mechanistic studies are needed to confirm causality.

3.1.2 Exercise

Regular physical activity increases endorphins, improves prefrontal cortex function, and supports attentional control and emotion regulation. These mechanisms explain its effects on cortisol regulation [31,87,88]. The impact of physical activity on cortisol regulation is particularly notable. For instance, research demonstrated that a single 15-minute aerobic exercise session significantly reduced salivary free cortisol levels in depressed patients, coinciding with improvements in subjective depressive symptoms [89].

Moreover, physical activity is closely linked to HPA axis regulation; regular exercise has been identified as a mechanism for improving stress-coping abilities [90]. Notably, Caplin et al. [91] observed a dose-response relationship between higher-intensity exercise. They accelerated recovery following a psychosocial stressor in healthy young adults, with findings emphasizing a dose-response relationship between exercise intensity and cortisol regulation.

3.1.3 Sleep

Sleep plays a vital role in regulating cortisol levels and maintaining emotional balance, forming a bidirectional relationship with emotion regulation. High-quality sleep is fundamental to emotional stability and psychological well-being, with research consistently documenting strong associations between sleep quality and difficulties in emotion regulation [92,93].

Adequate sleep supports emotional stability by influencing key aspects of emotion recognition and response; for example, sleep deprivation impairs brain regions such as the amygdala and prefrontal cortex—critical for processing emotional information—thereby reducing the accuracy of emotion recognition [94]. Furthermore, poor sleep quality exacerbates negative emotional responses, increasing susceptibility to symptoms of anxiety and depression [95]. The effects of insufficient sleep are particularly pronounced in adolescents, who are more prone to emotional volatility and impulsive behavior when sleep-deprived [96]. These findings underscore the importance of sleep quality for effective emotion regulation across different age groups. Sleep also impacts mechanisms underpinning emotion regulation—such as attentional control, cognitive appraisal, and modulation of emotional responses—and poor sleep quality may compromise these processes, reducing the ability to engage in adaptive emotion regulation [97].

Conversely, difficulties in emotion regulation can disrupt sleep; inadequate handling of emotional triggers or daily stressors often leads to heightened pre-sleep arousal, resulting in longer sleep onset latency and reduced rapid eye movement sleep duration [98].

Neurobiological studies further elucidate the link between sleep and emotion regulation by showing that sleep deprivation reduces activity in regions such as the intraparietal sulcus and superior parietal lobule while simultaneously increasing cortisol levels—the body's primary stress hormone [98,99]. These hormonal changes further affect the HPA axis, contributing to dysregulated cortisol secretion [100]. Interestingly, while prolonged poor sleep quality is associated with elevated cortisol levels, one night of acute sleep deprivation has been shown to decrease circulating cortisol levels while increasing inflammatory markers such as CRP and IL-6 [101]. This complex interplay between sleep, immune function, and endocrine signaling underscores the intricate connections between sleep, cortisol regulation, and emotion [102,103,104]. Finally, a study by Demichelis et al. [105] reported that lower sleep quality was associated with higher perceived stress, and this link was statistically mediated by poorer emotion regulation capacity. In turn, reduced emotion regulation was also linked to greater levels of aggression, suggesting that emotion regulation may be a key pathway connecting insufficient sleep with both stress and aggressive behavior. These findings emphasize the importance of sleep in maintaining emotional stability and highlight its role in mitigating stress-related dysregulation. In summary, sleep serves as a critical foundation for emotion regulation, influencing both cortisol levels and key neurobiological mechanisms. The reciprocal relationship between sleep quality and emotion regulation underscores the need for interventions targeting both domains to enhance emotional well-being and resilience to stress.

3.2 Inflammatory Markers

Inflammation, a multifaceted biological response, involves a complex interplay of molecules. Among the primary biomarkers frequently analyzed are interleukin-6 (IL-6) and C-reactive protein (CRP). IL-6 is a pro-inflammatory cytokine that prompts the liver to produce CRP, which is easily measurable in the bloodstream. These markers are widely used in behavioral research to assess low-grade inflammation due to their relevance to numerous physiological and psychological conditions [10,106,107]. However, while their utility as broad indicators is well-established, their specificity is limited, and findings across studies often diverge depending on context, population, and methodological design.

Psychosocial interventions—including cognitive-behavioral therapy (CBT) and mindfulness meditation—have been shown to modulate inflammatory responses, suggesting potential therapeutic benefits. Evidence highlights a bidirectional feedback loop in which negative emotions exacerbate inflammation, while inflammation worsens emotional well-being. Experimental studies have shown that induced inflammation can amplify emotional reactivity, and chronic inflammatory conditions (e.g., depression) can predict future increases in inflammation [108,109]. Still, the directionality of causality remains debated, with some longitudinal studies supporting reciprocal effects and others suggesting stronger unidirectional pathways.

Emotion regulation strategies and their associations with inflammation have been widely studied. For instance, while some work reports strong links between regulatory difficulties and higher CRP, others fail to replicate these findings, highlighting the need for standardized measurement approaches [110]. Stress-related emotional responses also contribute to inflammation; for example, negative emotions following a Trier Social Stress Test have been linked to higher levels of IL-6, IL-1β, and tumor necrosis factor-α (TNF-α) [111].

Expressive suppression—a less adaptive emotion regulation strategy—has frequently been associated with heightened inflammatory markers such as CRP and fibrinogen. This association has been observed in trauma-exposed veterans, bereaved spouses, and individuals with Type D personality traits [112,113,114,115]. On the other hand, adaptive strategies like cognitive reappraisal have been linked to lower levels of inflammation. Longitudinal research has shown that cognitive reappraisal correlates with reduced IL-6 levels, though its effects on CRP remain less consistent [116]. In healthy adults, cognitive reappraisal tends to minimize IL-6 and CRP, while habitual use of expressive suppression is linked to higher TNF-α and interferon-γ (IFN-γ) levels [117,118]. These inconsistencies suggest that inflammatory outcomes may vary depending on context (e.g., acute vs. chronic stress), population (clinical vs. community samples), and the biomarker chosen, underscoring the limitations of relying solely on correlational designs.

Adding to this body of knowledge, a recent systematic review by Moriarity et al. [117] examined how emotion regulation traits relate to inflammation. An analysis of 38 out of 2,816 identified studies revealed that 74% supported the idea that poor emotion regulation is linked to higher inflammation. In contrast, effective emotion regulation is associated with reduced inflammatory activity [118]. This review highlighted that the most consistent results were related to positive coping, social support seeking, or broadly defined emotion regulation/dysregulation constructs. Moreover, studies employing stress reactivity paradigms, vulnerability-stress frameworks, or longitudinal designs offered the most reliable evidence, reinforcing the importance of methodological rigor in understanding these associations [119].

Similarly, an investigation by Ospina et al. examined inflammation and emotion regulation strategies using data from the MIDUS II study [118]. They found that higher levels of expressive suppression were associated with lower levels of anti-inflammatory markers (e.g., IL-10) and of TNF-α and intercellular adhesion molecule-1 (ICAM-1), with TNF-α emerging as a significant predictor of expressive suppression. Interestingly, no significant associations were observed between cognitive reappraisal and inflammatory markers, emphasizing the differential roles these strategies play in modulating immune function [118,119].

Collectively, these findings underscore the importance of considering both adaptive and maladaptive emotion regulation strategies in psycho-immunological research. The evidence supports the notion that enhancing emotion regulation skills through psychosocial interventions could help mitigate inflammatory processes and improve both psychological and physical health Outcomes.

3.2.1 Metabolic Hormones and Inflammation

The relationship between metabolic hormones and inflammatory markers in the context of emotion regulation is an emerging area of interest. Leptin, beyond its role in appetite regulation, functions as a pro-inflammatory adipokine, and elevated leptin levels have been associated with increased CRP and IL-6 in metabolic disorders [120]. Conversely, ghrelin exhibits anti-inflammatory properties. Recent evidence demonstrates that ghrelin downregulates pro-inflammatory cytokines and may protect against inflammation-related pathology [121]. Additionally, research indicates that leptin and ghrelin dysregulation contribute to eating disorders characterized by emotional dysregulation, with ghrelin's role extending beyond appetite to influence stress responses and mood stability [122]. However, how these metabolic-inflammatory interactions influence emotion regulation capacity remains largely unexplored. It is plausible that individuals with metabolic dysregulation (e.g., obesity, insulin resistance) may experience heightened inflammatory responses during emotional stress, thereby compromising ER effectiveness. Additionally, emotion regulation strategies that reduce cortisol may also modulate metabolic hormone secretion, potentially creating indirect anti-inflammatory effects. Longitudinal studies examining concurrent changes in metabolic hormones, inflammatory markers, and ER outcomes are needed to test these hypotheses. Such research would inform whether metabolic interventions (e.g., weight loss, exercise, dietary modification) could enhance ER capacity, at least in part through inflammatory pathways.

4. Effects of Medications on Emotional Regulation

4.1 Positive Impact of Medications

4.1.1 Antidepressants (SSRIs, MAOIs)

Pharmacological treatments can facilitate improvements in emotional regulation, though effects are often modest and context-dependent. Antidepressant medications (ADMs), including selective serotonin reuptake inhibitors (SSRIs) and monoamine oxidase inhibitors (MAOIs), modulate emotion-generative brain systems to alleviate symptoms and enhance emotion regulatory capacity [123]. SSRIs have shown notable impacts on emotional processing mechanisms. In a longitudinal study by McRae et al. [124], participants undergoing an 8-week antidepressant treatment demonstrated significant improvements in emotion regulation. The research revealed decreased reliance on emotional suppression and increased utilization of cognitive reappraisal strategies; these changes correlated positively with treatment outcomes, independent of baseline depressive symptoms. Neuroimaging studies further substantiate these findings. MacNamara et al. [125] conducted a 12-week clinical trial with veterans diagnosed with PTSD, investigating the neurological effects of paroxetine. The study observed increased activation in the left dorsolateral prefrontal cortex (dlPFC) and supplementary motor area (SMA) during reappraisal tasks. Notably, participants with initial lower activation in the right ventrolateral prefrontal cortex (vlPFC) and the inferior frontal gyrus (IFG) experienced the most tremendous treatment-related gains.

Monoamine oxidase inhibitors (MAOIs) provide an alternative pharmacological approach to emotion regulation. By inhibiting monoamine oxidase enzymes, these medications increase the availability of neurotransmitters (including serotonin, dopamine, and norepinephrine) [126].

Research has demonstrated their efficacy in treating atypical depression characterized by emotional reactivity and mood dysregulation. MAOIs have the potential to enhance prefrontal activity and reduce hyperresponsivity in emotion-processing brain regions, such as the amygdala [127]. SSRIs and MAOIs demonstrate distinct yet complementary mechanisms in improving emotion regulation. While SSRIs promote adaptive emotional strategies and normalize prefrontal activity, MAOIs enhance neurotransmitter availability and modulate emotional responses. However, both SSRIs and MAOIs are limited by side effects (e.g., sexual dysfunction, weight gain, dietary restrictions for MAOIs), high discontinuation rates, and variability in patient response. Long-term efficacy remains debated, with relapse common once treatment is discontinued. Thus, while pharmacological interventions can support emotion regulation, their benefits must be weighed against safety, adherence, and sustainability challenges.

4.1.2 Anxiolytics (Benzodiazepines and Neurosteroids)

Anxiolytics, particularly benzodiazepines, reduce anxiety and promote emotional stability by enhancing gamma-aminobutyric acid (GABA) activity. Benzodiazepines bind to GABA-A receptors, increasing GABAergic inhibitory signalling, which calms hyperactive neural circuits implicated in anxiety and emotional dysregulation [128]. These medications help regulate emotional responses by reducing activity in overactive brain regions such as the amygdala, thereby facilitating improved cognitive control over emotional states [129]. Research suggests that perceived control over stressors and anxiolytic effects share overlapping neural mechanisms with emotion regulation. Salomons et al. [130] investigated the relationship between perceived control, anxiety reduction, and functional connectivity in brain regions associated with emotion regulation; their findings revealed that reduced state anxiety was linked to increased functional connectivity between the amygdala, nucleus accumbens, and the ventrolateral/ventromedial prefrontal cortex (PFC). These regions are critical for the cognitive regulation of negative emotions through reappraisal, suggesting that perceived control over stress may reduce anxiety by engaging the general emotion regulation network that overlaps with circuits involved in emotion reappraisal.

Another class of anxiolytics, neurosteroids like dehydroepiandrosterone (DHEA), has also shown promise in modulating emotional stability. DHEA exhibits anxiolytic, antidepressant, and antiglucocorticoid properties and is released endogenously in response to stress. Exogenous administration of DHEA impacts emotion neurocircuitry, including the amygdala, hippocampus, insula, and anterior cingulate cortex [131]. Neuroimaging studies indicate that DHEA enhances activity in the anterior cingulate cortex and connectivity between the amygdala and hippocampus—regions essential for emotion regulation and episodic memory. In experimental settings, DHEA administration has been associated with reduced negative affect and enhanced regulatory processes in key brain regions. For example, Sripada et al. [132] demonstrated that DHEA reduces activity in areas associated with the generation of negative emotions (e.g., the amygdala) while enhancing activity in regions linked to emotion regulation (e.g., the ACC). While benzodiazepines and DHEA can dampen acute distress, both classes have limitations. Benzodiazepines are associated with sedation, dependency risk, and cognitive impairment, which restrict their long-term use. Evidence for DHEA is still preliminary, with small samples and limited replication. This suggests that anxiolytics may provide short-term relief but require careful clinical management and are not sufficient as standalone solutions for chronic emotion dysregulation.

4.1.3 Mood Stabilizers (Lithium, Antipsychotics)

Mood stabilizers, such as lithium and antipsychotics, play a central role in the management of bipolar disorder (BD), in which emotion regulation difficulties are a core challenge. Lithium is a pharmacological intervention for acute mania in both adults and youth with bipolar disorder [133,134]. Similarly, quetiapine—a mixed dopamine-serotonin receptor antagonist—has demonstrated efficacy in managing manic episodes in pediatric and adult BD populations [135].

Evidence from neuroimaging studies suggests that disruption of the fronto-limbic network underlies ER impairments in BD. Structurally, abnormalities such as increased amygdala volumes [136,137], grey matter reductions in cortical regions like the anterior cingulate cortex [137,138,139,140,141,142,143,144,145,146], and disrupted white matter integrity in prefrontal areas (dlPFC, vlPFC, mPFC) as well as the left parietal cortex [141] have been widely reported. These structural disruptions correlate with functional deficits in BD, particularly in the use of cognitive reappraisal—a key ER strategy.

Recent studies examining the role of lithium suggest its ability to stabilize mood is linked to its effect on neural circuits implicated in emotional regulation. Lithium modulates reappraisal processes by targeting the fronto-parietal and limbic networks, as well as superior and medial temporal regions [142]. In particular, lithium enhances the neural activity of areas involved in cognitive and emotional processing (frontal, temporal, parietal, and occipital regions), accompanied by lower self-reported negative affect during exposure to negative stimuli. Lithium demonstrates robust effects but poses critical clinical challenges, including a narrow therapeutic range, potential nephrotoxicity, and adherence difficulties due to monitoring requirements. Quetiapine, in contrast, induces faster improvements in emotion-related brain circuits, particularly in the limbic and striatal regions [143]. However, it is also associated with side effects such as sedation, metabolic changes, and weight gain, which can reduce compliance. Although variability in study designs and sample populations complicates direct comparisons, the cumulative evidence suggests that lithium normalizes the activity and connectivity of emotion regulation networks in BD patients. These effects occur across different tasks and paradigms, underscoring lithium's robust influence on brain circuits involved in ER [144]. Quetiapine, in contrast to lithium, induces a faster and broader normalization of brain function, particularly in the limbic and striatal regions—structures critical for emotional processing and regulation. Lei et al. [145] demonstrated that quetiapine effectively reduces pre-treatment functional alterations in emotion-related brain circuits, suggesting its superior capacity to restore balance in neural systems implicated in ER rapidly. Mood stabilizers appear to normalize dysfunctional neural circuits underlying ER in BD, though adherence issues, side-effect profiles, and variability across patient populations moderate their benefits. Ongoing research is needed to clarify how these agents can be optimized within multimodal treatment strategies.

4.2 Negative Impact of Substances

4.2.1 Alcohol

Understanding the relationship between emotions and alcohol use is a fundamental theoretical issue [146]. Alcohol consumption is frequently linked to attempts at regulating affective states, yet its effects are diffuse, context-dependent, and often maladaptive over time. Rather than a simple strategy of mood modification, alcohol use reflects a dynamic interplay between acute reward-related effects, long-term emotional dysregulation, and underlying vulnerabilities. Neuroimaging studies in individuals with alcohol use disorder (AUD) have revealed that the neural circuits involved in regulating craving overlap significantly with those regulating emotions more broadly [7,147]. Craving has been linked to specific emotion regulation deficits, particularly those involving response modulation [2,3]. This reciprocal relationship suggests that emotion regulation deficits not only increase craving but are themselves exacerbated by repeated alcohol exposure, creating a self-reinforcing cycle of dysregulation and dependence [148]. Emotion dysregulation appears to be a hallmark of alcohol addiction. Studies have shown that individuals with AUD exhibit significantly higher levels of emotion dysregulation across various dimensions compared to healthy controls, as well as impaired interoceptive abilities—specifically, lower interoceptive accuracy and higher interoceptive sensibility [149].

Interoceptive accuracy (the ability to accurately perceive internal physiological states) is associated with better emotion regulation in AUD, particularly the capacity to accept emotional distress or negative emotions [150]. In contrast, higher interoceptive sensibility (the subjective perception of internal states) has been linked to difficulties in regulating behavior under emotional distress, highlighting the complex relationship between interoception and emotion regulation in AUD.

Importantly, research underscores the strong association between emotion regulation difficulties and both problematic alcohol use and its negative consequences [151,152]. However, alcohol is not merely a "self-medication" tool; genetic predispositions (e.g., polymorphisms in GABAergic and dopaminergic genes), social drinking norms, and stress-related environments interact with ER deficits to shape vulnerability to AUD. Metacognitive beliefs about alcohol use further elucidate its role in emotion regulation. While positive metacognitions (e.g., "alcohol helps me reduce anxiety") may encourage initiation, negative metacognitions (e.g., "I cannot control my drinking") maintain dependence. These beliefs operate within broader cognitive-attentional syndromes, where repetitive negative thinking and attentional biases amplify emotional vulnerability [153,154,155,156,157].

This dynamic is particularly evident in the metacognitive model of problem drinking, which posits that alcohol use becomes a maladaptive control strategy due to the activation of a cognitive-attentional syndrome encompassing repetitive negative thinking, attentional biases, and poor self-regulation [156,157]. In comparison, abstinence has been associated with a shift toward more adaptive emotion regulation strategies; inefficient regulation during active drinking reinforces craving and maintains alcohol dependence [149]. Most studies rely on cross-sectional or self-report designs, limiting causal inference, while genetic and social moderators remain underexplored.

4.2.2 Illicit Drugs (e.g., Cocaine, Amphetamines)

Emotion dysregulation is a prominent feature in individuals with substance use disorders (SUDs), often manifesting as heightened negative emotionality and impaired emotional regulation compared to those without SUDs [158]. Theoretical models, such as the resource model of self-control [159], help explain how ER deficits diminish the ability to inhibit maladaptive behaviors, particularly under emotional stress. Yet, contemporary research also emphasizes neurobiological and genetic vulnerabilities that interact with these deficits. In drug use, the imbalance between effortful regulation and immediate reinforcement biases attention toward drug-related cues, reinforcing substance-seeking. This mechanism is particularly salient in stimulants, where dopaminergic pathways amplify both craving and negative affect sensitivity [160]. Neurobiologically, dysregulation of the dopamine system is central to SUDs. Altered dopaminergic signaling in the mesolimbic pathway affects reward sensitivity, motivation, and the capacity to regulate emotions adaptively [161,162,163,164,165,166,167,168,169,170,171,172,173]. Heightened dopamine reactivity to drug-related cues can exacerbate craving and impair inhibitory control, linking emotional dysregulation directly to substance-seeking behaviors.

Empirical evidence highlights the association between emotion regulation deficits and substance use. Studies demonstrate that individuals with drug use disorders exhibit greater impairments in emotion regulation than those without these disorders [13]. Cross-sectional studies further corroborate the link, revealing that greater emotion regulation deficits are associated with increased substance use severity [159,168]. Clinical interventions targeting emotion regulation have shown promising results in reducing substance use; For instance, ER-focused cognitive-behavioral interventions predict reductions in both alcohol and illicit drug use, while therapies such as dialectical behavior therapy and metacognitive therapy directly address maladaptive ER processes (e.g., suppression, rumination) with measurable improvements [149,153,159]. Meta-analytic findings support these Conclusions. Weiss et al. [161] conducted a comprehensive review of 95 studies involving 156025 participants and found a modest relationship between emotion regulation and substance use (r = 0.19). Significantly, this association varies by strategy: maladaptive ER (suppression, avoidance) predicts higher use, whereas adaptive ER (reappraisal, problem-solving) is protective. Similarly, emotion dysregulation plays a significant role in opioid use. Casseli et al. [168] found that among individuals undergoing methadone maintenance treatment, emotion regulation difficulties, particularly the nonacceptance of emotional responses, were strongly predictive of coping motives for drug use, suggesting that impaired emotion regulation drives maladaptive coping strategies that perpetuate substance dependence. In SUDs, ER difficulties not only predict relapse but also co-occur with aggression, impulsivity, and comorbid psychiatric symptoms [163,164,165,166,167,168]. These patterns highlight the necessity of multi-level interventions that consider neurobiological sensitivity, genetic predispositions, and the broader social environment shaping substance use trajectories.

Approaches such as Metacognitive Therapy have shown promise in addressing repetitive negative thinking and maladaptive metacognitive beliefs central to emotion dysregulation in SUDs [163]. Techniques such as restructuring metacognitive beliefs, Socratic questioning, behavioral experiments, and attention training may interrupt maladaptive thought patterns, thereby reducing emotional dysregulation and the likelihood of substance use [164]. These findings collectively emphasize the crucial role of dopamine-mediated emotional dysregulation in the etiology of SUDs and the potential for targeted emotion regulation interventions to mitigate substance dependence by fostering greater emotional resilience and reducing reliance on substances for coping [165]. Nonetheless, much of the evidence derives from correlational studies; that is, genetic moderators, cultural influences, and longitudinal causal pathways are still insufficiently studied.

5. Conclusion

Emotion regulation is deeply rooted in a complex interplay of biochemical processes. This review has synthesized evidence demonstrating that neurotransmitters (serotonin, dopamine, GABA, glutamate), classical regulatory hormones (cortisol, oxytocin), and metabolic hormones (leptin, ghrelin, insulin, apelin) collectively shape how emotions are processed, expressed, and managed. A key contribution of this review is to highlight that these systems do not operate independently but rather interact dynamically: serotonin modulates insulin signaling, leptin influences dopaminergic reward circuits, and metabolic state affects the excitatory-inhibitory balance in emotion-processing networks.

Dysfunctions in these interconnected pathways—often triggered by chronic stress, maladaptive coping mechanisms, or substance use—can lead to cascading effects including elevated cortisol, increased inflammation, neurotransmitter imbalances, and metabolic dysregulation. Pharmacological interventions (antidepressants, mood stabilizers, anxiolytics) restore biochemical balance primarily through neurotransmitter modulation, but may also exert indirect effects on metabolic hormones that warrant further investigation. Conversely, substances like alcohol and illicit drugs disrupt these pathways across multiple levels, impairing emotional control through dopaminergic, serotonergic, and potentially metabolic mechanisms.

A distinctive contribution of this review is its emphasis on metabolic hormones—particularly leptin, ghrelin, and insulin—which remain underrepresented in mainstream ER models despite their relevance to stress reactivity, reward processing, and emotion-linked behavior. The evidence reviewed suggests that metabolic health and emotion regulation capacity are bidirectionally linked: metabolic dysfunction impairs ER through effects on cognition, mood, and neural circuits, while poor ER contributes to maladaptive eating and metabolic dysregulation. However, significant gaps remain. Metabolic hormones have been minimally studied in the context of emotion regulation interventions (meditation, exercise, sleep), inflammatory responses to ER strategies, or pharmacological treatments for mood disorders. These gaps represent important directions for future research.

Future studies should adopt integrative approaches that examine cross-system interactions rather than isolated biochemical markers. Key priorities include: (1) elucidating mechanisms linking metabolic hormones with neurotransmitter function and ER capacity; (2) investigating whether metabolic interventions (glycemic control, weight management, nutritional support) enhance ER outcomes; (3) examining how pharmacological and psychological treatments simultaneously affect neurotransmitter, hormonal, and metabolic profiles; (4) exploring individual differences (genetic, developmental, environmental) that moderate these relationships; and (5) assessing emerging therapies (e.g., psychedelics, neurostimulation) that may modulate emotional biochemistry through novel pathways.

Understanding the biochemical foundations of emotion regulation has significant clinical implications. Disruptions in leptin and ghrelin signaling contribute to eating disorders; dopamine and serotonin dysfunction underlie addictive behaviors; and insulin dysregulation compounds emotional instability in diabetes. By integrating pharmacological treatments with evidence-based psychological strategies (mindfulness, cognitive-behavioral therapy) and lifestyle interventions (exercise, sleep optimization, dietary modification), clinicians can develop more comprehensive, personalized approaches. This multi-level perspective—recognizing that ER emerges from the dynamic interplay of neurochemical, neuroendocrine, and metabolic systems—offers a framework for improving mental health outcomes across a range of conditions characterized by emotional dysregulation.

Abbreviations

Acknowledgments

The study is an output of Basic Research Program at HSE University.

Author Contributions

Marina Gerges: Conceptualization, Writing – Original Draft. Vladimir Kosongov: Review & Editing.

Competing Interests

We declare no conflict of interest.

AI-Assisted Technologies Statement

The author utilized ChatGPT, an AI language model, to assist with grammar and spelling checks during the manuscript preparation process. The author remains fully responsible for the content and integrity of the manuscript, including any sections where AI assistance was employed.

References

  1. Ochsner KN, Gross JJ. The cognitive control of emotion. Trends Cogn Sci. 2005; 9: 242-249. [CrossRef] [Google scholar]
  2. Gross JJ. The emerging field of emotion regulation: An integrative review. Rev Gen Psychol. 1998; 2: 271-299. [CrossRef] [Google scholar]
  3. Gross JJ, John OP. Individual differences in two emotion regulation processes: Implications for affect, relationships, and well-being. J Pers Soc Psychol. 2003; 85: 348-362. [CrossRef] [Google scholar]
  4. Kabat-Zinn J. Mindfulness-based interventions in context: Past, present, and future. Clin Psychol. 2003; 10: 144-156. [CrossRef] [Google scholar]
  5. Sheppes G, Gross JJ. Is timing everything? Temporal considerations in emotion regulation. Pers Soc Psychol Rev. 2011; 15: 319-331. [CrossRef] [Google scholar]
  6. Nolen-Hoeksema S. Responses to depression and their effects on the duration of depressive episodes. J Abnorm Psychol. 1991; 100: 569-582. [CrossRef] [Google scholar]
  7. Seo D, Lacadie CM, Tuit K, Hong KI, Constable RT, Sinha R. Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. JAMA Psychiatry. 2013; 70: 727-739. [CrossRef] [Google scholar]
  8. Kober H, Kross EF, Mischel W, Hart CL, Ochsner KN. Regulation of craving by cognitive strategies in cigarette smokers. Drug Alcohol Depend. 2010; 106: 52-55. [CrossRef] [Google scholar]
  9. Holsboer F. The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology. 2000; 23: 477-501. [CrossRef] [Google scholar]
  10. Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep. 2011; 13: 467-475. [CrossRef] [Google scholar]
  11. Krkovic K, Krink S, Lincoln TM. Emotion regulation as a moderator of the interplay between self-reported and physiological stress and paranoia. Eur Psychiatry. 2018; 49: 43-49. [CrossRef] [Google scholar]
  12. Hensler JG. Serotonergic modulation of the limbic system. Neurosci Biobehav Rev. 2006; 30: 203-214. [CrossRef] [Google scholar]
  13. Fox HC, Hong K, Sinha R. Difficulties in emotion regulation and impulse in recently abstinent alcoholics compared with social drinkers. Addict Behav. 2008; 33: 388-394. [CrossRef] [Google scholar]
  14. Hornung JP. The human raphe nuclei and the serotonergic system. J Chem Neuroanat. 2003; 26: 331-343. [CrossRef] [Google scholar]
  15. Berger M, Gray JA, Roth BL. The expanded biology of serotonin. Annu Rev Med. 2009; 60: 355-366. [CrossRef] [Google scholar]
  16. Rogers RD. The roles of dopamine and serotonin in decision making: Evidence from pharmacological experiments in humans. Neuropsychopharmacology. 2011; 36: 114-132. [CrossRef] [Google scholar]
  17. Plieger T, Melchers M, Vetterlein A, Görtz J, Kuhn S, Ruppel M, et al. The serotonin transporter polymorphism (5-HTTLPR) and coping strategies influence successful emotion regulation in an acute stress situation: Physiological evidence. Int J Psychophysiol. 2017; 114: 31-37. [CrossRef] [Google scholar]
  18. Firk C, Siep N, Markus CR. Serotonin transporter genotype modulates cognitive reappraisal of negative emotions: A functional magnetic resonance imaging study. Soc Cogn Affect Neurosci. 2013; 8: 247-258. [CrossRef] [Google scholar]
  19. Jenkins TA, Nguyen JC, Polglaze KE, Bertrand PP. Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis. Nutrients. 2016; 8: 56. [CrossRef] [Google scholar]
  20. Kanen JW, Arntz FE, Yellowlees R, Cardinal RN, Price A, Christmas DM, et al. Serotonin depletion amplifies distinct human social emotions as a function of individual differences in personality. Transl Psychiatry. 2021; 11: 81. [CrossRef] [Google scholar]
  21. Wang L, Mullette-Gillman OD, Gadde KM, Kuhn CM, McCarthy G, Huettel SA. The effect of acute tryptophan depletion on emotional distraction and subsequent memory. Soc Cogn Affect Neurosci. 2009; 4: 357-368. [CrossRef] [Google scholar]
  22. Bîlc MI, Iacob A, Szekely-Copîndean RD, Kiss B, Ștefan MG, Mureșan RC, et al. Serotonin and emotion regulation: The impact of tryptophan depletion on emotional experience, neural and autonomic activity. Cogn Affect Behav Neurosci. 2023; 23: 1414-1427. [CrossRef] [Google scholar]
  23. Sghendo L, Mifsud J. Understanding the molecular pharmacology of the serotonergic system: Using fluoxetine as a model. J Pharm Pharmacol. 2012; 64: 317-325. [CrossRef] [Google scholar]
  24. Feurer C, Francis J, Ajilore O, Craske MG, Phan KL, Klumpp H. Emotion regulation and repetitive negative thinking before and after CBT and SSRI treatment of internalizing psychopathologies. Cognit Ther Res. 2021; 45: 1064-1076. [CrossRef] [Google scholar]
  25. Sklivanioti Greenfield M, Wang Y, Msghina M. Behavioral, cortical and autonomic effects of single-dose escitalopram on the induction and regulation of fear and disgust: Comparison with single-session psychological emotion regulation with reappraisal. Front Psychiatry. 2023; 13: 988893. [CrossRef] [Google scholar]
  26. Luo SX, Huang EJ. Dopaminergic neurons and brain reward pathways: From neurogenesis to circuit assembly. Am J Pathol. 2016; 186: 478-488. [CrossRef] [Google scholar]
  27. Kosten TR, George TP. The neurobiology of opioid dependence: Implications for treatment. Sci Pract Perspect. 2002; 1: 13-20. [CrossRef] [Google scholar]
  28. Kemmis LK, Wanigaratne S, Ehntholt KA. Emotional processing in individuals with substance use disorder and posttraumatic stress disorder. Int J Ment Health Addict. 2017; 15: 900-918. [CrossRef] [Google scholar]
  29. Wang X, Zhou X, Dai Q, Ji B, Feng Z. The role of motivation in cognitive reappraisal for depressed patients. Front Hum Neurosci. 2017; 11: 516. [CrossRef] [Google scholar]
  30. Wu R, Liu LL, Zhu H, Su WJ, Cao ZY, Zhong SY, et al. Brief mindfulness meditation improves emotion processing. Front Neurosci. 2019; 13: 1074. [CrossRef] [Google scholar]
  31. Siep N, Roefs A, Roebroeck A, Havermans R, Bonte M, Jansen A. Fighting food temptations: The modulating effects of short-term cognitive reappraisal, suppression and up-regulation on mesocorticolimbic activity related to appetitive motivation. Neuroimage. 2012; 60: 213-220. [CrossRef] [Google scholar]
  32. Heshmati M, Russo SJ. Anhedonia and the brain reward circuitry in depression. Curr Behav Neurosci Rep. 2015; 2: 146-153. [CrossRef] [Google scholar]
  33. Volkow ND, Wise RA, Baler R. The dopamine motive system: Implications for drug and food addiction. Nat Rev Neurosci. 2017; 18: 741-752. [CrossRef] [Google scholar]
  34. Arnsten AF. Stress weakens prefrontal networks: Molecular insults to higher cognition. Nat Neurosci. 2015; 18: 1376-1385. [CrossRef] [Google scholar]
  35. Stefanits H, Milenkovic I, Mahr N, Pataraia E, Hainfellner JA, Kovacs GG, et al. GABAA receptor subunits in the human amygdala and hippocampus: Immunohistochemical distribution of 7 subunits. J Comp Neurol. 2018; 526: 324-348. [CrossRef] [Google scholar]
  36. Klausberger T, Somogyi P. Neuronal diversity and temporal dynamics: The unity of hippocampal circuit operations. Science. 2008; 321: 53-57. [CrossRef] [Google scholar]
  37. Prager EM, Bergstrom HC, Wynn GH, Braga MF. The basolateral amygdala γ‐aminobutyric acidergic system in health and disease. J Neurosci Res. 2016; 94: 548-567. [CrossRef] [Google scholar]
  38. Page CE, Coutellier L. Prefrontal excitatory/inhibitory balance in stress and emotional disorders: Evidence for over-inhibition. Neurosci Biobehav Rev. 2019; 105: 39-51. [CrossRef] [Google scholar]
  39. Johnstone N, Kadosh KC. Excitatory and inhibitory neurochemical markers of anxiety in young females. Dev Cogn Neurosci. 2024; 66: 101363. [CrossRef] [Google scholar]
  40. Widegren E, Frick MA, Hoppe JM, Weis J, Möller S, Fällmar D, et al. The influence of anterior cingulate GABA+ and glutamate on emotion regulation and reactivity in adolescents and adults. Dev Psychobiol. 2024; 66: e22492. [CrossRef] [Google scholar]
  41. Perica MI, Calabro FJ, Larsen B, Foran W, Yushmanov VE, Hetherington H, et al. Development of frontal GABA and glutamate supports excitation/inhibition balance from adolescence into adulthood. Prog Neurobiol. 2022; 219: 102370. [CrossRef] [Google scholar]
  42. Tang YY, Askari P, Choi C. Brief mindfulness training increased glutamate metabolism in the anterior cingulate cortex. NeuroReport. 2020; 31: 1142-1145. [CrossRef] [Google scholar]
  43. Oboshi Y, Iwabuchi T, Takata Y, Bunai T, Ouchi Y. Cerebellar contribution to emotion regulation and its association with medial frontal GABA level. Soc Cogn Affect Neurosci. 2025; 20: nsae091. [CrossRef] [Google scholar]
  44. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006; 8: 383-395. [CrossRef] [Google scholar]
  45. Tsumura H. The role of cortisol in cognitive emotion regulation failure. In: Brain, decision making and mental health. Cham: Springer; 2023. pp. 295-315. [CrossRef] [Google scholar]
  46. Jentsch VL, Merz CJ, Wolf OT. Restoring emotional stability: Cortisol effects on the neural network of cognitive emotion regulation. Behav Brain Res. 2019; 374: 111880. [CrossRef] [Google scholar]
  47. Langer K, Jentsch VL, Wolf OT. Cortisol promotes the cognitive regulation of high intensive emotions independent of timing. Eur J Neurosci. 2022; 55: 2684-2698. [CrossRef] [Google scholar]
  48. Pan DN, Jentsch VL, Langer K, Hagedorn B, Höffken O, Wolf OT, et al. What a difference timing makes: Cortisol effects on neural underpinnings of emotion regulation. Neurobiol Stress. 2023; 25: 100544. [CrossRef] [Google scholar]
  49. Langer K, Wolf OT, Merz CJ, Jentsch VL. The effects of stress hormones on cognitive emotion regulation: A systematic review and integrative model. Neurosci Biobehav Rev. 2025; 170: 106040. [CrossRef] [Google scholar]
  50. Yılmazer E. Hormonal underpinnings of emotional regulation: Bridging endocrinology and psychology. J Neurobehav Sci. 2024; 11: 60-75. [CrossRef] [Google scholar]
  51. Burbach JP, Young LJ, Russell J. Oxytocin: Synthesis, secretion, and reproductive functions. In: Knobil and Neill's physiology of reproduction. 3rd ed. Amsterdam, Netherlands: Elsevier; 2006. pp. 3055-3128. [CrossRef] [Google scholar]
  52. Ma Y, Shamay-Tsoory S, Han S, Zink CF. Oxytocin and social adaptation: Insights from neuroimaging studies of healthy and clinical populations. Trends Cogn Sci. 2016; 20: 133-145. [CrossRef] [Google scholar]
  53. Quirin M, Kuhl J, Düsing R. Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities. Psychoneuroendocrinology. 2011; 36: 898-904. [CrossRef] [Google scholar]
  54. Marsh N, Marsh AA, Lee MR, Hurlemann R. Oxytocin and the neurobiology of prosocial behavior. Neuroscientist. 2021; 27: 604-619. [CrossRef] [Google scholar]
  55. Koch SB, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M. Effects of intranasal oxytocin on distraction as emotion regulation strategy in patients with post-traumatic stress disorder. Eur Neuropsychopharmacol. 2019; 29: 266-277. [CrossRef] [Google scholar]
  56. Mohiyeddini C, Opacka-Juffry J, Gross JJ. Emotional suppression explains the link between early life stress and plasma oxytocin. Anxiety Stress Coping. 2014; 27: 466-475. [CrossRef] [Google scholar]
  57. Sippel LM, Allington CE, Pietrzak RH, Harpaz-Rotem I, Mayes LC, Olff M. Oxytocin and stress-related disorders: Neurobiological mechanisms and treatment opportunities. Chronic Stress. 2017; 1. doi: 10.1177/2470547016687996. [CrossRef] [Google scholar]
  58. Maffei Á, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, et al. Leptin levels in human and rodent: Measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med. 1995; 1: 1155-1161. [CrossRef] [Google scholar]
  59. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402: 656-660. [CrossRef] [Google scholar]
  60. Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D. Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time-and food-related cues. Am J Physiol Endocrinol Metab. 2004; 287: E297-E304. [CrossRef] [Google scholar]
  61. Jaremka LM, Belury MA, Andridge RR, Lindgren ME, Habash D, Malarkey WB, et al. Novel links between troubled marriages and appetite regulation: Marital distress, ghrelin, and diet quality. Clin Psychol Sci. 2016; 4: 363-375. [CrossRef] [Google scholar]
  62. Aguiar-Bloemer AC, Diez-Garcia RW. Influence of emotions evoked by life events on food choice. Eat Weight Disord. 2018; 23: 45-53. [CrossRef] [Google scholar]
  63. Jaremka LM, Lebed O, Sunami N. Threats to belonging, immune function, and eating behavior: An examination of sex and gender differences. Curr Psychiatry Rep. 2018; 20: 71. [CrossRef] [Google scholar]
  64. Sim AY, Lim EX, Leow MK, Cheon BK. Low subjective socioeconomic status stimulates orexigenic hormone ghrelin-A randomised trial. Psychoneuroendocrinology. 2018; 89: 103-112. [CrossRef] [Google scholar]
  65. Cardel MI, Johnson SL, Beck J, Dhurandhar E, Keita AD, Tomczik AC, et al. The effects of experimentally manipulated social status on acute eating behavior: A randomized, crossover pilot study. Physiol Behav. 2016; 162: 93-101. [CrossRef] [Google scholar]
  66. Cheon BK, Hong YY. Mere experience of low subjective socioeconomic status stimulates appetite and food intake. Proc Natl Acad Sci. 2017; 114: 72-77. [CrossRef] [Google scholar]
  67. Belloli A, Saccaro LF, Landi P, Spera M, Zappa MA, Dell'Osso B, et al. Emotion dysregulation links pathological eating styles and psychopathological traits in bariatric surgery candidates. Front Psychiatry. 2024; 15: 1369720. [CrossRef] [Google scholar]
  68. Lis M, Miłuch T, Majdowski M, Zawodny T. A link between ghrelin and major depressive disorder: A mini review. Front Psychiatry. 2024; 15: 1367523. [CrossRef] [Google scholar]
  69. Tolle V, du Montcel CT, Mattioni J, Schéle E, Viltart O, Dickson SL. To eat or not to eat: A role for ghrelin and LEAP2 in eating disorders? Neurosci Appl. 2024; 3: 104045. [CrossRef] [Google scholar]
  70. Brydon L, O'donnell K, Wright CE, Wawrzyniak AJ, Wardle J, Steptoe A. Circulating leptin and stress‐induced cardiovascular activity in humans. Obesity. 2008; 16: 2642-2647. [CrossRef] [Google scholar]
  71. Raspopow K, Abizaid A, Matheson K, Anisman H. Psychosocial stressor effects on cortisol and ghrelin in emotional and non-emotional eaters: Influence of anger and shame. Horm Behav. 2010; 58: 677-684. [CrossRef] [Google scholar]
  72. Geliebter A, Carnell S, Gluck ME. Cortisol and ghrelin concentrations following a cold pressor stress test in overweight individuals with and without night eating. Int J Obes. 2013; 37: 1104-1108. [CrossRef] [Google scholar]
  73. Tian SW, Xu F, Gui SJ. Apelin-13 reverses memory impairment and depression-like behavior in chronic social defeat stressed rats. Peptides. 2018; 108: 1-6. [CrossRef] [Google scholar]
  74. Zhang X, Gu Y, Ma Y, Wu J, Chen Y, Tao K, et al. The Apelin/APJ system modulates seizure activity and endocytosis of the NMDA receptor GluN2B subunit. Neurochem Int. 2023; 167: 105545. [CrossRef] [Google scholar]
  75. Dai TT, Wang B, Xiao ZY, You Y, Tian SW. Apelin-13 upregulates BDNF against chronic stress-induced depression-like phenotypes by ameliorating HPA axis and hippocampal glucocorticoid receptor dysfunctions. Neuroscience. 2018; 390: 151-159. [CrossRef] [Google scholar]
  76. Shen P, Yue Q, Fu W, Tian SW, You Y. Apelin-13 ameliorates chronic water-immersion restraint stress-induced memory performance deficit through upregulation of BDNF in rats. Neurosci Lett. 2019; 696: 151-155. [CrossRef] [Google scholar]
  77. Kırbaş ZÖ, Bayraktar B, Odabaşı Aktaş E. Investigation of emotion regulation skills, salivary apelin, and serotonin levels in children in Türkiye: A cross-sectional study. Nord J Psychiatry. 2024; 78: 570-576. [CrossRef] [Google scholar]
  78. Keegan R, Naumovski N. Insulin resistance, glucose regulation, obesity, and mood. In: Handbook of Psychocardiology. Singapore: Springer; 2016. pp. 849-871. [CrossRef] [Google scholar]
  79. Martin H, Bullich S, Guiard BP, Fioramonti X. The impact of insulin on the serotonergic system and consequences on diabetes‐associated mood disorders. J Neuroendocrinol. 2021; 33: e12928. [CrossRef] [Google scholar]
  80. Önal ZE, Atasayan V, Gürbüz T, Hepkaya E, Nuhoğlu Ç. Association of glycosylated hemoglobin (HbA1c) levels with Iinsulin resistance in obese children. Afr Health Sci. 2014; 14: 533-538. [CrossRef] [Google scholar]
  81. Beam AB, Wiebe DJ, Berg CA. Insulin restriction, emotion dysregulation, and depressive symptoms in late adolescents with diabetes. J Pediatr Psychol. 2021; 46: 1110-1118. [CrossRef] [Google scholar]
  82. Brouwer A, van Raalte DH, Lamers F, Rutters F, Elders PJ, Van Someren EJ, et al. Insulin resistance as a marker for the immune-metabolic subtype of depression. J Affect Disord. 2021; 295: 1371-1376. [CrossRef] [Google scholar]
  83. Black S, Kraemer K, Shah A, Simpson G, Scogin F, Smith A. Diabetes, depression, and cognition: A recursive cycle of cognitive dysfunction and glycemic dysregulation. Curr Diab Rep. 2018; 18: 118. [CrossRef] [Google scholar]
  84. Coccaro EF, Drossos T, Phillipson L. HbA1c levels as a function of emotional regulation and emotional intelligence in patients with type 2 diabetes. Prim Care Diabetes. 2016; 10: 334-341. [CrossRef] [Google scholar]
  85. Coccaro EF, Drossos T, Kline D, Lazarus S, Joseph JJ, de Groot M. Diabetes distress, emotional regulation, HbA1c in people with diabetes and a controlled pilot study of an emotion-focused behavioral therapy intervention in adults with type 2 diabetes. Prim Care Diabetes. 2022; 16: 381-386. [CrossRef] [Google scholar]
  86. Turakitwanakan W, Mekseepralard C, Busarakumtragul P. Effects of mindfulness meditation on serum cortisol of medical students. J Med Assoc Thai. 2013; 96: S90-S95. [Google scholar]
  87. Mandolesi L, Polverino A, Montuori S, Foti F, Ferraioli G, Sorrentino P, et al. Effects of physical exercise on cognitive functioning and wellbeing: Biological and psychological benefits. Front Psychol. 2018; 9: 509. [CrossRef] [Google scholar]
  88. Daniela M, Catalina L, Ilie O, Paula M, Daniel-Andrei I, Ioana B. Effects of exercise training on the autonomic nervous system with a focus on anti-inflammatory and antioxidants effects. Antioxidants. 2022; 11: 350. [CrossRef] [Google scholar]
  89. Zhang Y, Fu R, Sun L, Gong Y, Tang D. How does exercise improve implicit emotion regulation ability: Preliminary evidence of mind-body exercise intervention combined with aerobic jogging and mindfulness-based yoga. Front Psychol. 2019; 10: 1888. [CrossRef] [Google scholar]
  90. Chen C, Nakagawa S, An Y, Ito K, Kitaichi Y, Kusumi I. The exercise-glucocorticoid paradox: How exercise is beneficial to cognition, mood, and the brain while increasing glucocorticoid levels. Front Neuroendocrinol. 2017; 44: 83-102. [CrossRef] [Google scholar]
  91. Caplin A, Chen FS, Beauchamp MR, Puterman E. The effects of exercise intensity on the cortisol response to a subsequent acute psychosocial stressor. Psychoneuroendocrinology. 2021; 131: 105336. [CrossRef] [Google scholar]
  92. Dahl RE, Lewin DS. Pathways to adolescent health sleep regulation and behavior. J Adolesc Health. 2002; 31: 175-184. [CrossRef] [Google scholar]
  93. Wang W, Zhu Y, Yu H, Wu C, Li T, Ji C, et al. The impact of sleep quality on emotion regulation difficulties in adolescents: A chained mediation model involving daytime dysfunction, social exclusion, and self-control. BMC Public Health. 2024; 24: 1862. [CrossRef] [Google scholar]
  94. Yoo SS, Gujar N, Hu P, Jolesz FA, Walker MP. The human emotional brain without sleep-a prefrontal amygdala disconnect. Curr Biol. 2007; 17: R877-R878. [CrossRef] [Google scholar]
  95. Baglioni C, Spiegelhalder K, Lombardo C, Riemann D. Sleep and emotions: A focus on insomnia. Sleep Med Rev. 2010; 14: 227-238. [CrossRef] [Google scholar]
  96. Baum KT, Desai A, Field J, Miller LE, Rausch J, Beebe DW. Sleep restriction worsens mood and emotion regulation in adolescents. J Child Psychol Psychiatry. 2014; 55: 180-190. [CrossRef] [Google scholar]
  97. Palmer CA, Alfano CA. Sleep and emotion regulation: An organizing, integrative review. Sleep Med Rev. 2017; 31: 6-16. [CrossRef] [Google scholar]
  98. Vandekerckhove M, Wang YL. Emotion, emotion regulation and sleep: An intimate relationship. AIMS Neurosci. 2017; 5: 1-17. [CrossRef] [Google scholar]
  99. Javaheripour N, Shahdipour N, Noori K, Zarei M, Camilleri JA, Laird AR, et al. Functional brain alterations in acute sleep deprivation: An activation likelihood estimation meta-analysis. Sleep Med Rev. 2019; 46: 64-73. [CrossRef] [Google scholar]
  100. Wright Jr KP, Drake AL, Frey DJ, Fleshner M, Desouza CA, Gronfier C, et al. Influence of sleep deprivation and circadian misalignment on cortisol, inflammatory markers, and cytokine balance. Brain Behav Immun. 2015; 47: 24-34. [CrossRef] [Google scholar]
  101. Bouillon-Minois JB, Trousselard M, Thivel D, Benson AC, Schmidt J, Moustafa F, et al. Leptin as a biomarker of stress: A systematic review and meta-analysis. Nutrients. 2021; 13: 3350. [CrossRef] [Google scholar]
  102. Bali A, Singh Jaggi A. An integrative review on role and mechanisms of ghrelin in stress, anxiety and depression. Curr Drug Targets. 2016; 17: 495-507. [CrossRef] [Google scholar]
  103. Omisade A, Buxton OM, Rusak B. Impact of acute sleep restriction on cortisol and leptin levels in young women. Physiol Behav. 2010; 99: 651-656. [CrossRef] [Google scholar]
  104. Thompson KI, Chau M, Lorenzetti MS, Hill LD, Fins AI, Tartar JL. Acute sleep deprivation disrupts emotion, cognition, inflammation, and cortisol in young healthy adults. Front Behav Neurosci. 2022; 16: 945661. [CrossRef] [Google scholar]
  105. Demichelis OP, Grainger SA, Burr L, Henry JD. Emotion regulation mediates the effects of sleep on stress and aggression. J Sleep Res. 2023; 32: e13787. [CrossRef] [Google scholar]
  106. Baumeister D, Akhtar R, Ciufolini S, Pariante CM, Mondelli V. Childhood trauma and adulthood inflammation: A meta-analysis of peripheral C-reactive protein, interleukin-6 and tumour necrosis factor-α. Mol Psychiatry. 2016; 21: 642-649. [CrossRef] [Google scholar]
  107. Fagundes CP, Way B. Early-life stress and adult inflammation. Curr Dir Psychol Sci. 2014; 23: 277-283. [CrossRef] [Google scholar]
  108. Dooley LN, Kuhlman KR, Robles TF, Eisenberger NI, Craske MG, Bower JE. The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. Neurosci Biobehav Rev. 2018; 94: 219-237. [CrossRef] [Google scholar]
  109. Moriarity DP, Kautz MM, Mac Giollabhui N, Klugman J, Coe CL, Ellman LM, et al. Bidirectional associations between inflammatory biomarkers and depressive symptoms in adolescents: Potential causal relationships. Clin Psychol Sci. 2020; 8: 690-703. [CrossRef] [Google scholar]
  110. Yang LL, Stiernborg M, Skott E, Söderström Å, Giacobini M, Lavebratt C. Proinflammatory mediators and their associations with medication and comorbid traits in children and adults with ADHD. Eur Neuropsychopharmacol. 2020; 41: 118-131. [CrossRef] [Google scholar]
  111. Newton TL, Fernandez-Botran R, Lyle KB, Szabo YZ, Miller JJ, Warnecke AJ. Salivary cytokine response in the aftermath of stress: An emotion regulation perspective. Emotion. 2017; 17: 1007-1020. [CrossRef] [Google scholar]
  112. Appleton AA, Buka SL, Loucks EB, Gilman SE, Kubzansky LD. Divergent associations of adaptive and maladaptive emotion regulation strategies with inflammation. Health Psychol. 2013; 32: 748-756. [CrossRef] [Google scholar]
  113. Khan NA, Lawyer G, McDonough S, Wang Q, Kassem NO, Kas-Petrus F, et al. Systemic biomarkers of inflammation, oxidative stress and tissue injury and repair among waterpipe, cigarette and dual tobacco smokers. Tob Control. 2020; 29: s102-s109. [CrossRef] [Google scholar]
  114. Lopez RB, Brown RL, Wu EL, Murdock KW, Denny BT, Heijnen C, et al. Emotion regulation and immune functioning during grief: Testing the role of expressive suppression and cognitive reappraisal in inflammation among recently bereaved spouses. Biopsychosoc Sci Med. 2020; 82: 2-9. [CrossRef] [Google scholar]
  115. Habra ME, Linden W, Anderson JC, Weinberg J. Type D personality is related to cardiovascular and neuroendocrine reactivity to acute stress. J Psychosom Res. 2003; 55: 235-245. [CrossRef] [Google scholar]
  116. Jones K, Kimble R, Baker K, Tew GA. Effects of structured exercise programmes on physiological and psychological outcomes in adults with inflammatory bowel disease (IBD): A systematic review and meta-analysis. PLoS One. 2022; 17: e0278480. [CrossRef] [Google scholar]
  117. Moriarity DP, Grehl MM, Walsh RF, Roos LG, Slavich GM, Alloy LB. A systematic review of associations between emotion regulation characteristics and inflammation. Neurosci Biobehav Rev. 2023; 150: 105162. [CrossRef] [Google scholar]
  118. Ospina LH, Beck-Felts K, Ifrah C, Lister A, Messer S, Russo SJ, et al. Inflammation and emotion regulation: Findings from the MIDUS II study. Brain Behav Immun Health. 2022; 26: 100536. [CrossRef] [Google scholar]
  119. Buhle JT, Silvers JA, Wager TD, Lopez R, Onyemekwu C, Kober H, et al. Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cereb Cortex. 2014; 24: 2981-2990. [CrossRef] [Google scholar]
  120. Mancuso P. The role of adipokines in chronic inflammation. Immunotargets Ther. 2016; 5: 47-56. [CrossRef] [Google scholar]
  121. Mingardi J, Meanti R, Paoli C, Cifani C, Torsello A, Popoli M, et al. Ghrelin, neuroinflammation, oxidative stress, and mood disorders: What are the connections? Curr Neuropharmacol. 2025; 23: 172-186. [CrossRef] [Google scholar]
  122. Mao Q, Wang J, Yang Z, Ding R, Lv S, Ji X. The pathologic roles and therapeutic implications of Ghrelin/GHSR system in mental disorders. Depress Anxiety. 2024; 2024: 5537319. [CrossRef] [Google scholar]
  123. Harmer CJ, Shelley NC, Cowen PJ, Goodwin GM. Increased positive versus negative affective perception and memory in healthy volunteers following selective serotonin and norepinephrine reuptake inhibition. Am J Psychiatry. 2004; 161: 1256-1263. [CrossRef] [Google scholar]
  124. McRae K, Rekshan W, Williams LM, Cooper N, Gross JJ. Effects of antidepressant medication on emotion regulation in depressed patients: An iSPOT-D report. J Affect Disord. 2014; 159: 127-132. [CrossRef] [Google scholar]
  125. MacNamara A, Rabinak CA, Kennedy AE, Fitzgerald DA, Liberzon I, Stein MB, et al. Emotion regulatory brain function and SSRI treatment in PTSD: Neural correlates and predictors of change. Neuropsychopharmacology. 2016; 41: 611-618. [CrossRef] [Google scholar]
  126. Shulman KI, Herrmann N, Walker SE. Current place of monoamine oxidase inhibitors in the treatment of depression. CNS Drugs. 2013; 27: 789-797. [CrossRef] [Google scholar]
  127. Fournier JC, DeRubeis RJ, Hollon SD, Dimidjian S, Amsterdam JD, Shelton RC, et al. Antidepressant drug effects and depression severity: A patient-level meta-analysis. JAMA. 2010; 303: 47-53. [CrossRef] [Google scholar]
  128. Rudolph U, Möhler H. GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr Opin Pharmacol. 2006; 6: 18-23. [CrossRef] [Google scholar]
  129. Millan MJ. The neurobiology and control of anxious states. Prog Neurobiol. 2003; 70: 83-244. [CrossRef] [Google scholar]
  130. Salomons TV, Nusslock R, Detloff A, Johnstone T, Davidson RJ. Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain. J Cogn Neurosci. 2015; 27: 222-233. [CrossRef] [Google scholar]
  131. Alhaj HA, Massey AE, McAllister-Williams RH. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: A double-blind, placebo-controlled study. Psychopharmacology. 2006; 188: 541-551. [CrossRef] [Google scholar]
  132. Sripada RK, Marx CE, King AP, Rajaram N, Garfinkel SN, Abelson JL, et al. DHEA enhances emotion regulation neurocircuits and modulates memory for emotional stimuli. Neuropsychopharmacology. 2013; 38: 1798-1807. [CrossRef] [Google scholar]
  133. Naert G, Maurice T, Tapia-Arancibia L, Givalois L. Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats. Psychoneuroendocrinology. 2007; 32: 1062-1078. [CrossRef] [Google scholar]
  134. Cyr M, Landry M, Di Paolo T. Modulation by estrogen-receptor directed drugs of 5-hydroxytryptamine-2A receptors in rat brain. Neuropsychopharmacology. 2000; 23: 69-78. [CrossRef] [Google scholar]
  135. Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D. Suicide risk in bipolar disorder during treatment with lithium and divalproex. JAMA. 2003; 290: 1467-1473. [CrossRef] [Google scholar]
  136. Machado‐Vieira R, Manji HK, Zarate Jr CA. The role of lithium in the treatment of bipolar disorder: Convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord. 2009; 11: 92-109. [CrossRef] [Google scholar]
  137. Weisler RH, Calabrese JR, Thase ME, Arvekvist R, Stening G, Paulsson B, et al. Efficacy of quetiapine monotherapy for the treatment of depressive episodes in bipolar I disorder: A post hoc analysis of combined results from 2 double-blind, randomized, placebo-controlled studies. J Clin Psychiatry. 2008; 69: 769-782. [CrossRef] [Google scholar]
  138. Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: Implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry. 2008; 13: 833-857. [CrossRef] [Google scholar]
  139. Townsend J, Altshuler LL. Emotion processing and regulation in bipolar disorder: A review. Bipolar Disord. 2012; 14: 326-339. [CrossRef] [Google scholar]
  140. Won E, Kim YK. An oldie but goodie: Lithium in the treatment of bipolar disorder through neuroprotective and neurotrophic mechanisms. Int J Mol Sci. 2017; 18: 2679. [CrossRef] [Google scholar]
  141. Chen L, Wang Y, Niu C, Zhong S, Hu H, Chen P, et al. Common and distinct abnormal frontal-limbic system structural and functional patterns in patients with major depression and bipolar disorder. Neuroimage Clin. 2018; 20: 42-50. [CrossRef] [Google scholar]
  142. Kato T. Current understanding of bipolar disorder: Toward integration of biological basis and treatment strategies. Psychiatry Clin Neurosci. 2019; 73: 526-540. [CrossRef] [Google scholar]
  143. Zhang S, Wang Y, Deng F, Zhong S, Chen L, Luo X, et al. Disruption of superficial white matter in the emotion regulation network in bipolar disorder. Neuroimage Clin. 2018; 20: 875-882. [CrossRef] [Google scholar]
  144. Artiach Hortelano P, Martens MA, Pringle A, Harmer CJ. Effect of lithium administration on brain activity under an emotion regulation paradigm in healthy participants: A functional magnetic resonance imaging study. Psychopharmacology. 2023; 240: 1719-1734. [CrossRef] [Google scholar]
  145. Lei D, Li W, Qin K, Ai Y, Tallman MJ, Patino LR, et al. Effects of short-term quetiapine and lithium therapy for acute manic or mixed episodes on the limbic system and emotion regulation circuitry in youth with bipolar disorder. Neuropsychopharmacology. 2023; 48: 615-622. [CrossRef] [Google scholar]
  146. Cooper ML, Kuntsche E, Levitt A, Barber LL, Wolf S. Motivational models of substance use: A review of theory and research on motives for using alcohol, marijuana, and tobacco. In: The Oxford handbook of substance use and substance use disorders. Oxford, UK: Oxford University Press; 2016. pp. 375-421. [CrossRef] [Google scholar]
  147. Seo D, Sinha R. Neuroplasticity and Predictors of alcohol recovery. Alcohol Res. 2015; 37: 143-152. [CrossRef] [Google scholar]
  148. Cavicchioli M, Movalli M, Vassena G, Ramella P, Prudenziati F, Maffei C. The therapeutic role of emotion regulation and coping strategies during a stand-alone DBT skills training program for alcohol use disorder and concurrent substance use disorders. Addict Behav. 2019; 98: 106035. [CrossRef] [Google scholar]
  149. Jakubczyk A, Trucco EM, Klimkiewicz A, Skrzeszewski J, Suszek H, Zaorska J, et al. Association between interoception and emotion regulation in individuals with alcohol use disorder. Front Psychiatry. 2020; 10: 1028. [CrossRef] [Google scholar]
  150. Ramey T, Regier PS. Cognitive impairment in substance use disorders. CNS Spectr. 2019; 24: 102-113. [CrossRef] [Google scholar]
  151. Tiffany ST. Cognitive concepts of craving. Alcohol Res Health. 1999; 23: 215-224. [Google scholar]
  152. Berking M, Wupperman P. Emotion regulation and mental health: Recent findings, current challenges, and future directions. Curr Opin Psychiatry. 2012; 25: 128-134. [CrossRef] [Google scholar]
  153. Dvorak RD, Sargent EM, Kilwein TM, Stevenson BL, Kuvaas NJ, Williams TJ. Alcohol use and alcohol-related consequences: Associations with emotion regulation difficulties. Am J Drug Alcohol Abuse. 2014; 40: 125-130. [CrossRef] [Google scholar]
  154. Wellman RJ, DiFranza JR, Pbert L, Fletcher KE, Flint A, Young MH, et al. A comparison of the psychometric properties of the hooked on nicotine checklist and the modified Fagerström tolerance questionnaire. Addict Behav. 2006; 31: 486-495. [CrossRef] [Google scholar]
  155. Spada MM, Wells A. Metacognitive beliefs about alcohol use: Development and validation of two self-report scales. Addict Behav. 2008; 33: 515-527. [CrossRef] [Google scholar]
  156. Spada MM, Wells A. Metacognitions about alcohol use in problem drinkers. Clin Psychol Psychother. 2006; 13: 138-143. [CrossRef] [Google scholar]
  157. Spada MM, Caselli G, Nikčević AV, Wells A. Metacognition in addictive behaviors. Addict Behav. 2015; 44: 9-15. [CrossRef] [Google scholar]
  158. Weiss NH, Kiefer R, Goncharenko S, Raudales AM, Forkus SR, Schick MR, Contractor AA. Emotion regulation and substance use: A meta-analysis. Drug Alcohol Depend. 2022; 230: 109131. [CrossRef] [Google scholar]
  159. Stellern J, Xiao KB, Grennell E, Sanches M, Gowin JL, Sloan ME. Emotion regulation in substance use disorders: A systematic review and meta-analysis. Addiction. 2023; 118: 30-47. [CrossRef] [Google scholar]
  160. Inzlicht M, Schmeichel BJ. What is ego depletion? Toward a mechanistic revision of the resource model of self-control. Perspect Psychol Sci. 2012; 7: 450-463. [CrossRef] [Google scholar]
  161. Weiss NH, Tull MT, Sullivan TP, Dixon-Gordon KL, Gratz KL. Posttraumatic stress disorder symptoms and risky behaviors among trauma-exposed inpatients with substance dependence: The influence of negative and positive urgency. Drug Alcohol Depend. 2015; 155: 147-153. [CrossRef] [Google scholar]
  162. Axelrod SR, Perepletchikova F, Holtzman K, Sinha R. Emotion regulation and substance use frequency in women with substance dependence and borderline personality disorder receiving dialectical behavior therapy. Am J Drug Alcohol Abuse. 2011; 37: 37-42. [CrossRef] [Google scholar]
  163. London ED, Simon SL, Berman SM, Mandelkern MA, Lichtman AM, Bramen J, et al. Mood disturbances and regional cerebral metabolic abnormalities inrecently abstinent methamphetamine abusers. Arch Gen Psychiatry. 2004; 61: 73-84. [CrossRef] [Google scholar]
  164. Newton TF, Kalechstein AD, Duran S, Vansluis N, Ling W. Methamphetamine abstinence syndrome: Preliminary findings. Am J Addict. 2004; 13: 248-255. [CrossRef] [Google scholar]
  165. Zweben JE, Cohen JB, Christian D, Galloway GP, Salinardi M, Parent D, et al. Psychiatric symptoms in methamphetamine users. Am J Addict. 2004; 13: 181-190. [CrossRef] [Google scholar]
  166. Donegan NH, Sanislow CA, Blumberg HP, Fulbright RK, Lacadie C, Skudlarski P, et al. Amygdala hyperreactivity in borderline personality disorder: Implications for emotional dysregulation. Biol Psychiatry. 2003; 54: 1284-1293. [CrossRef] [Google scholar]
  167. Moeller SJ, Okita K, Robertson CL, Ballard ME, Konova AB, Goldstein RZ, et al. Low striatal dopamine D2-type receptor availability is linked to simulated drug choice in methamphetamine users. Neuropsychopharmacology. 2018; 43: 751-760. [CrossRef] [Google scholar]
  168. Caselli G, Martino F, Spada MM, Wells A. Metacognitive therapy for alcohol use disorder: A systematic case series. Front Psychol. 2018; 9: 2619. [CrossRef] [Google scholar]
  169. Fisher P, Wells A. Metacognitive therapy: Distinctive features. Abingdon, England: Routledge; 2009. [CrossRef] [Google scholar]
  170. Lanzenberger R, Wadsak W, Şavlı MÖ, Mitterhauser M, Spindelegger C, Stein P, et al. Serotonin transporter availability in dorsal raphe nucleus predicts serotonin-1A receptor binding in striatum: A multitracer PET study with [carbonyl-11C] WAY and [11C] DASB. Neuroimage. 2008; 41: T156. [CrossRef] [Google scholar]
  171. Tan HX, Md Kamal A, Thurairajasingam S, Phipps ME. Addressing emotional dysregulation and potential pharmacogenetic implication of 5-HTTLPR genotype in attention deficit hyperactivity disorder. Complex Psychiatry. 2023; 9: 70-88. [CrossRef] [Google scholar]
  172. Volkow ND, Morales M. The brain on drugs: From reward to addiction. Cell. 2015; 162: 712-725. [CrossRef] [Google scholar]
  173. Koob GF, Volkow ND. Neurobiology of addiction: A neurocircuitry analysis. Lancet Psychiatry. 2016; 3: 760-773. [CrossRef] [Google scholar]
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