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Interoceptive pathways to understand and treat mental health conditions

2022; Elsevier BV; Volume: 26; Issue: 6 Linguagem: Inglês

10.1016/j.tics.2022.03.004

1879-307X

Camilla L. Nord, Sarah N. Garfinkel,

Health, psychology, and well-being

Patients with neuropsychiatric disorders associated with altered emotional or physical experiences show disruptions in interoception.Interoception may be an important target of both existing and novel mental health treatments.Antidepressants modulate aspects of interoception and specific psychological therapies target interoceptive processes, particularly breathing.Medications for certain physical health conditions are associated with better mental health.Interoceptive measures could be used to stratify patients for treatment selection. An increasing recognition that brain and body are dynamically coupled has enriched our scientific understanding of mental health conditions. Peripheral signals interact centrally to influence how we think and feel, generating our sense of the internal condition of the body, a process known as interoception. Disruptions to this interoceptive system may contribute to clinical conditions, including anxiety, depression, and psychosis. After reviewing the nature of interoceptive disturbances in mental health conditions, this review focuses on interoceptive pathways of existing and putative mental health treatments. Emerging clinical interventions may target novel peripheral treatment mechanisms. Future treatment development requires forward- and back-translation to uncover and target specific interoceptive processes in mental health to elucidate their efficacy relative to interventions targeting other factors. An increasing recognition that brain and body are dynamically coupled has enriched our scientific understanding of mental health conditions. Peripheral signals interact centrally to influence how we think and feel, generating our sense of the internal condition of the body, a process known as interoception. Disruptions to this interoceptive system may contribute to clinical conditions, including anxiety, depression, and psychosis. After reviewing the nature of interoceptive disturbances in mental health conditions, this review focuses on interoceptive pathways of existing and putative mental health treatments. Emerging clinical interventions may target novel peripheral treatment mechanisms. Future treatment development requires forward- and back-translation to uncover and target specific interoceptive processes in mental health to elucidate their efficacy relative to interventions targeting other factors. Over a century after the introduction of peripheral theories of emotion (see Glossary) [1.Lange C.G. James W. The Emotions. Williams and Wilkins Co., 1922Crossref Google Scholar], the notion that physiological signals influence emotion is widely accepted [2.Barrett L.F. Are emotions natural kinds?.Perspect. Psychol. Sci. 2006; 1: 28-58Crossref PubMed Scopus (929) Google Scholar,3.Lindquist K.A. Barrett L.F. A functional architecture of the human brain: emerging insights from the science of emotion.Trends Cogn. Sci. 2012; 16: 533-540Abstract Full Text Full Text PDF PubMed Scopus (237) Google Scholar]. New techniques that combine peripheral and central signals are driving a rapid increase in research detailing the complex and multifaceted ways in which bodily state can interact with brain to influence cognition and emotion [4.Azzalini D. et al.Visceral signals shape brain dynamics and cognition.Trends Cogn. Sci. 2019; 23: 488-509Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar]. Recent work shows the nature of this influence ranges from moment-to-moment mapping, such as discrete cardiac cycle effects on emotion [5.Garfinkel S.N. Critchley H.D. Threat and the body: how the heart supports fear processing.Trends Cogn. Sci. 2016; 20: 34-46Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar], to long-term emotional changes arising from chronic alterations, as in the immune system [6.Dantzer R. et al.From inflammation to sickness and depression: when the immune system subjugates the brain.Nat. Rev. Neurosci. 2008; 9: 46-56Crossref PubMed Scopus (4415) Google Scholar,7.Hodes G.E. et al.Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.Proc. Natl. Acad. Sci. 2014; 111: 16136-16141Crossref PubMed Scopus (0) Google Scholar]. The influence of the body on emotion can be ascribed to two pathways that include bottom–up afferent signalling and/or top–down processing of the body. The body-to-brain axis maps bodily signals onto emotions, generating a patterned relationship between particular bodily states and emotions via neural representations of internal bodily signals. Higher-order paths represent someone's awareness of their bodily signals – for instance, how accurately they sense and interpret bodily information – which likewise contributes to emotional experience. These paths can be also be influenced by higher-order processes that interact with interoceptive signals, for example, appraisals given to undifferentiated bodily arousal [2.Barrett L.F. Are emotions natural kinds?.Perspect. Psychol. Sci. 2006; 1: 28-58Crossref PubMed Scopus (929) Google Scholar,8.Scherer K.R. et al.Appraisal Processes in Emotion: Theory, Methods, Research. Oxford University Press, 2001Google Scholar] and strong beliefs about the body that might override veridical input [9.Koreki A. et al.Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures.Epilepsia. 2020; 61: 1156-1165Crossref PubMed Scopus (21) Google Scholar]. The role of the body in emotion may be particularly relevant for the treatment of mental health disorders, today the world's leading cause of disability [10.Friedrich M.J. Depression is the leading cause of disability around the world.JAMA. 2017; 317: 1517Google Scholar]. Recent efforts to characterise the nature of disrupted interoception in mental health conditions mirror these two pathways. In the first, direct changes in the body, including resultant neural modulation, might promote vulnerability to poor mental health. Alternatively or additionally, the sensing and perception of bodily signals might be upregulated or downregulated in mental health conditions, and may influence the experience of particular mental health symptoms. Traditionally, interoceptive correlates of mental health have been considered in the context of specific diagnoses. More recently, it has been suggested that they might instead represent 'transdiagnostic' mechanisms conferring a common vulnerability across multiple disorders [11.Nord C.L. et al.Disrupted dorsal mid-insula activation during interoception across psychiatric disorders.Am. J. Psychiatr. 2021; 178: 761-770Crossref PubMed Scopus (2) Google Scholar]. Similarly, a range of effective mental health treatments alter interoception via effects on bodily physiology or on the perception of bodily processes. Understanding the path from interoception to mental health might reveal peripheral routes that render particular current treatments effective, as well as pave the way for future interventions designed explicitly to target interoceptive processes in mental health disorders. Initial characterisation of interoception confined it to the visceral organs [12.Sherrington C. The Integrative Action of the Nervous System. CUP Archive, 1906Google Scholar], although more recent definitions tend to encompass a broad set of bodily signals and general feeling states relevant to homeostatic control, physiological needs, and organ integrity [13.Craig A.D. How do you feel? Interoception: the sense of the physiological condition of the body.Nat. Rev. Neurosci. 2002; 3: 655Crossref PubMed Google Scholar,14.Critchley H.D. Garfinkel S.N. Interoception and emotion.Curr. Opin. Psychol. 2017; 17: 7-14Crossref PubMed Scopus (207) Google Scholar]. For this review, we adopt a broader definition originating from a recent white paper on interoception in mental health: namely, 'the processing of internal bodily stimuli by the nervous system' [15.Khalsa S.S. et al.Interoception and mental health: a roadmap.Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2018; 3: 501-513Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar], which includes sensing, interpreting, and integrating signals originating from inside the body, 'providing a moment-by-moment mapping of the body's internal landscape across conscious and unconscious levels' [15.Khalsa S.S. et al.Interoception and mental health: a roadmap.Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2018; 3: 501-513Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar]. This is distinct from nervous system processing of signals originating from exteroceptive or proprioceptive information, and also does not describe physiological states per se, but rather the processing of internal physiological information. But what counts as an 'internal' stimulus? Some sources of internal information, such as signals originating from the heart, are widely accepted interoceptive mechanisms. Others, such as the influence of the immune system on the nervous system, are more controversial. This review references both accepted and more controversial sources of interoceptive information, but provides a table indicating how widely accepted each source of information is as 'interoceptive' (Figure 1). The body's drive for homeostasis means our mental response to a glass of water depends acutely on whether we are thirsty or not. Likewise, physiological signals throughout the body have profound effects on emotional experience. How might physiological responses alter emotion experience? Classical models of bodily inference suggest that autonomic nervous system (ANS) activation causes an undifferentiated arousal response which affects nonspecific emotion processing. In this framework, the ANS is mobilised in response to metabolic demands to anticipate particular behaviours, resulting in general emotional arousal [2.Barrett L.F. Are emotions natural kinds?.Perspect. Psychol. Sci. 2006; 1: 28-58Crossref PubMed Scopus (929) Google Scholar,16.Kreibig S.D. Autonomic nervous system activity in emotion: a review.Biol. Psychol. 2010; 84: 394-421Crossref PubMed Scopus (1572) Google Scholar]. Appraisal theories of emotion denote that there is no direct mapping of internal signals to precise emotional feeling states; instead, largely undifferentiated changes in bodily state are 'appraised' to shape emotional feelings. These appraisal processes guide which emotions are experienced, and the appraisals themselves can be influenced by a variety of factors including past memories, external context, dispositional style and cultural context [8.Scherer K.R. et al.Appraisal Processes in Emotion: Theory, Methods, Research. Oxford University Press, 2001Google Scholar]. The theory of constructed emotion [2.Barrett L.F. Are emotions natural kinds?.Perspect. Psychol. Sci. 2006; 1: 28-58Crossref PubMed Scopus (929) Google Scholar] posits that the brain constructs instances of emotion, in a context-specific manner, by 'imposing meaning' on noisy and ambiguous data from the body and the world. These theories crucially detail the complex interplay of factors that interact with interoceptive signals to guide emotional experience. While not negating the influence of extraneous factors such as memory, personality, and context on emotion, contemporary empirical findings are furthering our understanding of the ways that internal bodily signals themselves can change emotion. A subset of bodily signals are now thought to be associated with specific emotions or subsets of emotions. For example, perception of 'core' disgust stimuli (e.g., faeces) elicits a shift in the electrical activity of the stomach [18.Harrison N.A. et al.The embodiment of emotional feelings in the brain.J. Neurosci. 2010; 30: 12878-12884Crossref PubMed Scopus (182) Google Scholar,19.Shenhav A. Mendes W.B. Aiming for the stomach and hitting the heart: dissociable triggers and sources for disgust reactions.Emotion. 2014; 14: 301-309Crossref PubMed Scopus (43) Google Scholar], which can be targeted pharmacologically to reduce disgust avoidance [17.Nord C.L. et al.A causal role for gastric rhythm in human disgust avoidance.Curr. Biol. 2021; 31: 629-634Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar]; this electrical activity is distinct from physiological changes associated with other subcategories of disgust (e.g., bodily violence) [18.Harrison N.A. et al.The embodiment of emotional feelings in the brain.J. Neurosci. 2010; 30: 12878-12884Crossref PubMed Scopus (182) Google Scholar,19.Shenhav A. Mendes W.B. Aiming for the stomach and hitting the heart: dissociable triggers and sources for disgust reactions.Emotion. 2014; 14: 301-309Crossref PubMed Scopus (43) Google Scholar]. Classical models of bodily influence on emotional experience may have disregarded effects with relatively fast or slow temporal characteristics. Experiments on the consequences of different aspects of the cardiac cycle have demonstrated the role of baroreceptors in emotion intensity and detection. For example, fear stimuli presented concurrently with baroreceptor activation (i.e., at cardiac T wave, when the heart–brain channel is active) can facilitate the encoding of fear memories, indexed by elevated next-day fear recall [20.Garfinkel S.N. et al.Interoceptive cardiac signals selectively enhance fear memories.J. Exp. Psychol. Gen. 2021; 150: 1165Crossref PubMed Scopus (3) Google Scholar]. This has implications for the nature of body state (i.e., high arousal, when the heart is beating stronger and faster) and how it might heighten subsequent fear memories. The cardiac cycle is associated with patterns of respiration, as indexed by respiratory sinus arrhythmia. Respiratory phase (inspiration/expiration) also alters emotion processing. Nasal inspiration, but not expiration, improves reaction times to fearful (but not surprising) faces, potentially due to the influence of respiratory phase on limbic brain regions [21.Zelano C. et al.Nasal respiration entrains human limbic oscillations and modulates cognitive function.J. Neurosci. 2016; 36: 12448-12467Crossref PubMed Scopus (158) Google Scholar]. Respiratory entrainment of amygdalar local field potential activity predicted emotion identification performance in one patient with implanted intracranial electrodes [21.Zelano C. et al.Nasal respiration entrains human limbic oscillations and modulates cognitive function.J. Neurosci. 2016; 36: 12448-12467Crossref PubMed Scopus (158) Google Scholar]. Rate of breathing also alters valence processing: the autonomic state induced by slow breathing preferentially modulates positive affect, while the autonomic state induced by fast breathing preferentially modulates negative affect [22.Strigo I.A. Craig A.D. Interoception, homeostatic emotions and sympathovagal balance.Phil. Trans. R. Soc. B. Biol. Sci. 2016; 37120160010Crossref PubMed Scopus (117) Google Scholar]. Likewise, slow breathing reduces heat pain intensity and unpleasantness, ameliorating negative affect [23.Zautra A.J. et al.The effects of slow breathing on affective responses to pain stimuli: an experimental study.Pain. 2010; 149: 12-18Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. Slow breathing influences physiology via respiratory, cardiovascular, and autonomic mechanisms. Within the autonomic domain, parasympathetic mechanisms are thought to be the principle driver of affective change following slow breathing [23.Zautra A.J. et al.The effects of slow breathing on affective responses to pain stimuli: an experimental study.Pain. 2010; 149: 12-18Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. This is particularly relevant for clinical conditions thought to involve a relative deficit of parasympathetic activity and its downregulation of negative affect [23.Zautra A.J. et al.The effects of slow breathing on affective responses to pain stimuli: an experimental study.Pain. 2010; 149: 12-18Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. By contrast, slow breathing 'enhances' parasympathetic afferent activation via bronchiopulmonary vagal afferents, increasing parasympathetic tone, also reflected in increased heart rate variability [23.Zautra A.J. et al.The effects of slow breathing on affective responses to pain stimuli: an experimental study.Pain. 2010; 149: 12-18Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar,24.Berntson G.G. et al.Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications.Psychophysiology. 1993; 30: 183-196Crossref PubMed Scopus (648) Google Scholar]. Slower breathing may be a useful intervention to reduce pain, and potentially, regulate affect [23.Zautra A.J. et al.The effects of slow breathing on affective responses to pain stimuli: an experimental study.Pain. 2010; 149: 12-18Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. These mechanisms may underpin a number of therapeutic applications of breathing regulation for mental health (discussed later). At a much slower physiological timescale, the immune system can evoke motivational reorientation away from positive- and towards negative-valence information [25.Harrison N.A. et al.A neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards.Biol. Psychiatry. 2016; 80: 73-81Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar]. In rats, injection of potent immune system activators like endotoxin induce marked anhedonia and other depression-like symptoms, which can be attenuated or completely blocked by chronic antidepressant administration [26.Yirmiya R. Endotoxin produces a depressive-like episode in rats.Brain Res. 1996; 711: 163-174Crossref PubMed Scopus (469) Google Scholar]. In studies using typhoid vaccination as a model of immune system activation, mood deterioration correlates with enhanced activation in the subgenual anterior cingulate during emotional face processing, and related coactivation between the subgenual anterior cingulate cortex (sgACC) and other regions involved in affect processing [27.Harrison N.A. et al.Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity.Biol. Psychiatry. 2009; 66: 407-414Abstract Full Text Full Text PDF PubMed Scopus (505) Google Scholar]. This may be coupled with shifts in learning: typhoid injection also enhances behavioural punishment (versus reward) sensitivity [25.Harrison N.A. et al.A neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards.Biol. Psychiatry. 2016; 80: 73-81Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar]. This could represent an adaptive reallocation of resources during acute sickness, away from learning to perform reward-associated actions, towards learning to avoid potentially punitive actions. Motivational reorienting explains the ability of sickness to induce negative affect, as well as more severe mental health symptoms. Emotional experience is a complex interplay between internal and external factors. Non-interoceptive factors contribute substantially to emotional experience, including cultural context (see [28.Moors A. Theories of emotion causation: a review.Cognit. Emot. 2009; 23: 625-662Crossref Scopus (0) Google Scholar] for a broader review of theories of emotion). Cognitive mechanisms, such as memory, reward, and attention, are also known to impact mental health (reviewed elsewhere, e.g., [29.Roiser J.P. Sahakian B.J. Hot and cold cognition in depression.CNS spectrums. 2013; 18: 139-149Crossref PubMed Scopus (191) Google Scholar]), although these cognitive processes have the potential to also be shaped by dynamic changes in visceral physiology and interoceptive processes [4.Azzalini D. et al.Visceral signals shape brain dynamics and cognition.Trends Cogn. Sci. 2019; 23: 488-509Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar,30.Critchley H.D. Garfinkel S.N. The influence of physiological signals on cognition.Curr. Opin. Behav. Sci. 2018; 19: 13-18Crossref Scopus (14) Google Scholar]. Even identical, highly differentiated physiological signals might not induce precisely the same subjective phenomena in two people. Therefore, emotion experience is shaped not only by our physiological responses, but also by our individual capacity to sense bodily signals [31.Wiens S. et al.Heartbeat detection and the experience of emotions.Cognit. Emot. 2000; 14: 417-427Crossref Google Scholar]. Quantifying the sensing of internal bodily signals is key to understanding the role of the body in emotion processing. Perception of the body's internal state, a core aspect of interoception [14.Critchley H.D. Garfinkel S.N. Interoception and emotion.Curr. Opin. Psychol. 2017; 17: 7-14Crossref PubMed Scopus (207) Google Scholar], arises via a diverse set of physiological mechanisms. Anatomically, interoceptive signals are thought to ascend spinal laminar 1 spinothalamic tract via unmyelinated and lightly myelinated afferents [14.Critchley H.D. Garfinkel S.N. Interoception and emotion.Curr. Opin. Psychol. 2017; 17: 7-14Crossref PubMed Scopus (207) Google Scholar]. Interoception can be subdivided into particular sources of information, or channels (for instance, mechanoreceptor-derived signals ascending a particular afferent pathway), and measured by probing various different dimensions of interoception, for example, interoceptive accuracy or interoceptive insight (Box 1). Each of these channels and dimensions represent specific ways of quantifying individual differences in interoceptive experience [32.Suksasilp C. Garfinkel S.N. Towards a comprehensive assessment of interoception in a multi-dimensional framework.Biol. Psychol. 2022; 168108262Crossref PubMed Scopus (1) Google Scholar]. Individual differences may underlie important variation in emotional experience in the population.Box 1Dimensions of interoception and their clinical relevanceInteroception is delineated across different dimensions [14.Critchley H.D. Garfinkel S.N. Interoception and emotion.Curr. Opin. Psychol. 2017; 17: 7-14Crossref PubMed Scopus (207) Google Scholar,15.Khalsa S.S. et al.Interoception and mental health: a roadmap.Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2018; 3: 501-513Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar]. Interoceptive dimensions are differentially altered in mental health conditions, and by pharmacological, psychological, and behavioural interventions. Here, we provide illustrative examples of relevant conditions and treatments affecting interoceptive dimensions.Interoceptive attentionAnxiety and related conditions increase self-focus, a bias of attention towards internal cues, including on the body and interoceptive sensations [113.Mansell W. et al.Internal versus external attention in social anxiety: an investigation using a novel paradigm.Behav. Res. Ther. 2003; 41: 555-572Crossref PubMed Scopus (0) Google Scholar,114.Ewing D.L. et al.Sleep and the heart: interoceptive differences linked to poor experiential sleep quality in anxiety and depression.Biol. Psychol. 2017; 127: 163-172Crossref PubMed Scopus (0) Google Scholar]. Therapeutic strategies such a 'behavioural activation' increase engagement in external activities, which may induce attentional shifts away from the self.Interoceptive attributionAttribution of bodily signals varies across clinical conditions; for example, catastrophic interpretations of cardiovascular signals (such as a signalling a heart attack) are more common in panic disorder, while patients with somatoform disorders show reduced emotional awareness [115.Okur Güney Z.E. et al.Emotion regulation in patients with somatic symptom and related disorders: a systematic review.PLoS One. 2019; 14e0217277Crossref PubMed Scopus (21) Google Scholar], suggesting a potential disposition for physical interpretations. Interventions such as cognitive behavioural therapy (CBT) incorporate strategies to alter the nature of interoceptive attributions.Interoceptive insightInteroceptive insight (also termed interoceptive metacognition and interoceptive awareness [70.Garfinkel S.N. et al.Knowing your own heart: distinguishing interoceptive accuracy from interoceptive awareness.Biol. Psychol. 2015; 104: 65-74Crossref PubMed Scopus (576) Google Scholar]), operationalised as confidence–accuracy correspondence during tests to assess interoceptive accuracy, and/or the alignment of interoceptive beliefs with veridical bodily state, can be altered in clinical conditions such as FND [9.Koreki A. et al.Trait and state interoceptive abnormalities are associated with dissociation and seizure frequency in patients with functional seizures.Epilepsia. 2020; 61: 1156-1165Crossref PubMed Scopus (21) Google Scholar]. Preliminary evidence suggests SSRIs might enhance interoceptive insight [86.Livermore J.J. et al.A single oral dose of citalopram increases interoceptive insight in healthy volunteers.Psychopharmacology (Berl). 2022; (Published online March 24, 2022. http://doi.org/10.1007/s00213-022-06115-7)Crossref PubMed Scopus (0) Google Scholar]. Long-term meditation may align interoceptive self-report and accuracy [104.Khalsa S.S. et al.Interoceptive awareness in experienced meditators.Psychophysiology. 2008; 45: 671-677Crossref PubMed Scopus (158) Google Scholar].Interoceptive self-reportInteroception can be assessed with self-report measures, such as questionnaires. Conditions such as autism and anxiety are associated with a tendency to report being more 'aware' of bodily sensations [114.Ewing D.L. et al.Sleep and the heart: interoceptive differences linked to poor experiential sleep quality in anxiety and depression.Biol. Psychol. 2017; 127: 163-172Crossref PubMed Scopus (0) Google Scholar,116.Garfinkel S.N. et al.Discrepancies between dimensions of interoception in autism: implications for emotion and anxiety.Biol. Psychol. 2016; 114: 117-126Crossref PubMed Google Scholar].Interoceptive accuracyInteroceptive accuracy can be quantified in different bodily axes, including heartbeat detection tests and respiratory resistance tests. Conditions such as alexithymia [117.Shah P. et al.Alexithymia, not autism, is associated with impaired interoception.Cortex. 2016; 81: 215-220Crossref PubMed Scopus (41) Google Scholar] and schizophrenia [118.Ardizzi M. et al.Interoception and positive symptoms in schizophrenia.Front. Hum. Neurosci. 2016; 10: 379Crossref PubMed Scopus (26) Google Scholar] show impaired interoceptive accuracy. Enhancing interoceptive accuracy may aid capacity for autonomic regulation and anxiety reduction [106.Quadt L. et al.Interoceptive training to target anxiety in autistic adults (ADIE): a single-center, superiority randomized controlled trial.EClinicalMedicine. 2021; 39101042Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar].Preconscious impact of afferent signalsBodily state alters stimulus processing, at both slow (e.g., immune state) and rapid timescales (e.g., with each heartbeat). For example, cardiovascular signals can increase fear processing, an effect heightened in anxious individuals [20.Garfinkel S.N. et al.Interoceptive cardiac signals selectively enhance fear memories.J. Exp. Psychol. Gen. 2021; 150: 1165Crossref PubMed Scopus (3) Google Scholar]. Blood pressure medications (e.g., losartan) can enhance the extinction of fear memories [89.Marvar P.J. et al.Angiotensin type 1 receptor inhibition enhances the extinction of fear memory.Biol. Psychiatry. 2014; 75: 864-872Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar].Neural processing interoceptionNeural activation in key areas subserves interoception. Disruption of dorsal mid-insula activation during interoception is found across a range of mental health disorders [11.Nord C.L. et al.Disrupted dorsal mid-insula activation during interoception across psychiatric disorders.Am. J. Psychiatr. 2021; 178: 761-770Crossref PubMed Scopus (2) Google Scholar]. Pharmacological interventions, such as SSRIs, are associated with changes in insula activation during affective processing [84.Simmons A.N. et al.Subchronic SSRI administration reduces insula response during affective anticipation in healthy volunteers.Int. J. Neuropsychopharmacol. 2009; 12: 1009-1020Crossref PubMed Scopus (56) Google Scholar].Afferent signalAutonomic signatures are linked to emotional state. Afferent signals such as heartbeats increase in frequency/intensity during heightened anxiety states. Medication, such as beta-adrenoreceptor blockers, can dampen afferent signals, reducing anxiety [119.Tyrer P. Anxiolytics not acting at the benzodiazepine receptor: beta blockers.Prog. Neuro-Psychopharmacol. Biol. Psychiatry. 1992; 16: 17-26Crossref PubMed Scopus (0) Google Scholar]. Interoception is delineated across different dimensions [14.Critchley H.D. Garfinkel S.N. Interoception and emotion.Curr. Opin. Psychol. 2017; 17: 7-14Crossref PubMed Scopus (207) Google Scholar,15.Khalsa S.S. et al.Interoception and mental health: a roadmap.Biol. Psychiatry Cogn. Neurosci. Neuroimaging. 2018; 3: 501-513Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar]. Interoceptive dimensions are differentially altered in mental health conditions, and by pharmacological, psychological, and behavioural interventions. Here, we provide illustrative examples of relevant conditions and treatments affecting interoceptive dimensions. Interoceptive attention Anxiety and related conditions increase self-focus, a bias of attention towards internal cues, including on the body and interoceptive sensations [113.Mansell W. et al.Internal versus external attention in social anxiety: an investigation using a novel paradigm.Behav. Res. Ther. 2003; 41: 555-572Crossref PubMed Scopus (0)