Interoceptive dysfunction: toward an integrated framework for understanding somatic and affective disturbance in depression

Abstract

Depression is characterized by disturbed sleep and eating, a variety of other nonspecific somatic symptoms, and significant somatic comorbidities. Why there is such close association between cognitive and somatic dysfunction in depression is nonetheless poorly understood. An explosion of research in the area of interoception-the perception and interpretation of bodily signals-over the last decade nonetheless holds promise for illuminating what have until now been obscure links between the social, cognitive-affective, and somatic features of depression. This article reviews rapidly accumulating evidence that both somatic signaling and interoception are frequently altered in depression. This includes comparative studies showing vagus-mediated effects on depression-like behaviors in rodent models as well as studies in humans indicating both dysfunction in the neural substrates for interoception (e.g., vagus, insula, anterior cingulate cortex) and reduced sensitivity to bodily stimuli in depression. An integrative framework for organizing and interpreting this evidence is put forward which incorporates (a) multiple potential pathways to interoceptive dysfunction; (b) interaction with individual, gender, and cultural differences in interoception; and (c) a developmental psychobiological systems perspective, emphasizing likely differential susceptibility to somatic and interoceptive dysfunction across the lifespan. Combined with current theory and evidence, it is suggested that core symptoms of depression (e.g., anhedonia, social deficits) may be products of disturbed interoceptive-exteroceptive integration. More research is nonetheless needed to fully elucidate the relationship between mind, body, and social context in depression.

Figure 1

A depiction of the integration and bidirectional “penetrance” of interoception and exteroception. A number of cognitive processes (closed box) necessarily rely upon the integration of interoceptive and exteroceptive information. For example, the homeostatic condition of the body is imperative for judging whether or not to approach, avoid, or even attend to a given stimulus. Penetrance describes “spill over” or bleed-through from one perceptual system to another—from interoception to exteroception or vice versa. For example, alliesthesia occurs when bodily signals shift the valence or attractiveness of an exteroceptive stimulus (Cabanac, 1971), whereas contagion occurs when an exteroceptive stimulus overrides representation of bodily signals. Interoceptive dysfunction can thus potentially influence a large number of cognitive processes, particularly those typically involving alliesthesia and contagion (e.g., motivational behavior, social cognition).

Figure 2

A simplified illustration of the major connections and many feedback loops involved in interoception in humans and other primates; adapted with permission from Craig (2003a), with additional connections added based on the work of others (e.g., Mufson et al., 1981; Ray & Price, 1993). Red lines indicate pathways that are phylogenetically novel in primates. Larger grey arrows indicate the general flow of bodily information from the vagus and brain stem upward to the right anterior insula—the theoretical nexus of consciously accessible feelings of the body and “self” (see Craig, 2003a). A1 = brainstem area 1; ACC = anterior cingulate cortex; ANS = autonomic nervous system; MD = medial dorsal nucleus of the thalamus; NTS = nucleus of the solitary tract; OFC = orbitofrontal cortex; PAG = periaqueductal gray; PB = parabrachial nucleus; mPFC = medial prefrontal cortex; RVLM = rostral ventrolateral medulla; VMb = basal ventral medial nucleus of the thalamus; VMpo = posterior ventral medial nucleus of the thalamus; VMM = ventral medial medulla.

Figure 3

An illustration of the Northoff et al. (2011) model of interoception in depression. An imbalance between interoceptive and exteroceptive processing is central to this model. Neurally, this is manifest as simultaneous hyperactivity in cortical-midline structures (e.g., interoceptive regions such as insula and related regions involved in temporal perception, affect and reward, such as the pACC, vmPFC, and amygdala) and hypoactivity in “lateral ring” structures (e.g., dlPFC and sensorimotor cortices). A number of potential causes of such imbalance are noted by Northoff et al., including genetic, neurochemical, endocrine, immune, and social factors. A variety of downstream consequences of interoceptive-exteroceptive imbalance, which overlap with symptoms of depression, are shown. A number of other symptoms not shown, such as negative biases, negative mood, anhedonia, psychomotor retardation, decreased goal orientation and working memory, are noted by Northoff et al. (2011). These are nonetheless related by Northoff et al. to changes in functioning of specific brain regions/networks rather than specifically to interoceptive-exteroceptive imbalance.

Figure 4

A framework for understanding interoceptive dysfunction (ID) in depression. The topmost row indicates common proximal causes of ID (e.g., stroke, stress, pro-inflammatory cytokines, behavioral or contextual changes). The next row illustrates the three main pathways by which these are likely to give rise to ID: (a) modification to neural systems underlying interoception, or the interoceptive nervous system (INS); (b) loss of exteroceptive cues ordinarily used to disambiguate interoceptive signals; and (c) attentional changes. Arrows indicate known interactions and likely causal influences, although these are not exhaustively illustrated (e.g., inflammatory cytokines, stroke, etc., may also influence stress hormone levels and vice versa). As is indicated in brackets, all such pathways ultimately interact with individual, gender, and cultural differences in interoception in giving rise to ID. ID is moreover likely to give rise to errors in somatic interpretation or missed somatic signals, contributing to the somatic symptoms (e.g., disrupted sleep and eating) typical of depression (cf. Healy & Williams, 1988).

Figure 5

A schematic illustration of common interoceptive and regulatory challenges across the lifespan, from a female and Western-biased cultural perspective. The framework put forward here assumes that over the course of the lifespan major somatic changes and regulatory transitions (e.g., from childhood to adolescence) likely place unique strain on regulatory and interoceptive capacities alike. Such challenges are nonetheless likely to be highly culture-specific (e.g., menopause is not universally viewed negatively). For vulnerable individuals, ensuing ID and somatic dysregulation may, theoretically, contribute to the development of anxiety and/or depression.