Understanding depression beyond the “mind‐body” dichotomy

In both the ICD‐11 and the DSM‐5, the core symptoms of depression are reported to be depressed mood (e.g., feeling sad, down or hopeless) and markedly diminished interest or pleasure in activities. However, in the ICD‐10 diagnostic guidelines, a third core symptom was also identified: “fatigue or low energy”. In two regions of the world (Latin America and East Asia), “fatigue” is the most commonly experienced depressive symptom ¹ . In a third region (Southeast Asia), “issues with the heart” are the most commonly reported depressive symptoms, along with depressed mood ¹ . Do people in these regions just “somatize” what is primarily a “psychological” experience? Do “somatic” symptoms just represent a “mask”, as implied some decades ago by the concept of “masked depression” ² ?

An alternative view may be that the core of the depressive syndrome, at least in part of the cases of this heterogeneous condition, is neither only “psychic” nor only “somatic”, but consists of an actual “depression” of the individual's psychic/physical tone, energy, drive and/or response to rewarding stimuli (partially captured by the constructs of depressed mood, fatigue, and diminished interest or pleasure), along with an overwhelming feeling of psychic/physical pain (which has a complex and probably variable relationship to the cognitive component of the syndrome). The way these core phenomena are perceived, elaborated and verbalized by the affected person likely depends upon how that person generally functions and appraises her functioning (e.g., how rich and articulated her cognitive life is, or how much she is focused on her body and its functioning), upon the influence of the cultural environment in which she is immersed, and upon the pattern of predisposing and precipitating factors at work in that individual case.

Feelings involving the heart (“heavy heart”, “heart pain”; chest tightness, weakness or excessive tension; palpitations) do not appear in textbook descriptions of depression, but are more frequently experienced by depressed individuals than we use to believe ¹ . Ordinary people sometimes refer to depression as “broken heart”, and we tend to regard this as a metaphor. But, the acute “broken heart syndrome” – which has the same precipitating factors as depression and, similarly to the heart involvement in depression, is ascribed to a sympathetic overactivation – is now a recognized clinical entity ³ . An intrinsic cardiac nervous system (“a brain in the heart”) has been recently described ⁴ , including a multitude of nervous ganglions consisting not only of neurons receiving sympathetic and parasympathetic input, but also of intracardiac interneurons which act as processors of information. Indeed, the heart conveys to the brain more information than the brain sends to the heart, and ascending fibres in the vagus nerve are more numerous than descending ones. Could the above dynamics be an under‐recognized factor contributing to the frequent coexistence (“comorbidity”) and complex interaction between depression and heart disease?

That many patients with a diagnosis of depression do not respond adequately to two subsequent antidepressant medications (“treatment resistance”) is not surprising. Clinical trials of both medications and psychotherapies for depression have aimed during the past few decades to document the “equivalence” of any new experimental intervention to an already consolidated one, while “differences” in the profiles of action of those interventions have usually not been a focus of attention. Consequently, antidepressants and evidence‐based psychotherapies for depression are regarded by treatment guidelines as essentially all “equivalent” to each other. It is only recently that secondary analyses of large trial databases, conducted using innovative methodologies, have started to focus again on the “differences” between the various antidepressants, and between antidepressants and evidence‐based psychotherapies, with respect to their profiles of action ⁵ , ⁶ . On the other hand, it is not common in ordinary practice that a patient with a diagnosis of depression receives a detailed clinical characterization beyond that diagnosis, guiding the choice of treatment. It is therefore understandable that a person may receive two or more antidepressants that, although validated for depression tout court, are not among the most appropriate for her specific case, and consequently may not elicit an adequate response. Furthermore, medications do not work in a vacuum: a variety of “aspecific” factors (e.g., the therapeutic relationship, family dynamics, the socio‐cultural context) may affect the outcome of an intrinsically efficacious intervention. The concept of “pseudo‐resistance” does not adequately consider at the moment these factors (not to mention problems with the definition of what is an “adequate response” to an antidepressant, difficulties in ascertaining the adherence to the antidepressant regimens that have been used, and the basic incongruence of defining a case as “treatment‐resistant” when one group of therapies currently regarded as first‐line in the treatment of depression, i.e. psychotherapies, have not been tried).

In this issue of the journal, two papers and a Forum deal, respectively, with the lived experience of depression ⁷ , with its multiple “physical comorbidities” ⁸ , and (in a critical vein) with “treatment‐resistant depression” and its management ⁹ . I think these contributions should be welcome by the scientific community, by people with depression and their families, and by the public at large.

A “depression” of the individual's psychic/physical tone, energy, drive and/or response to rewarding stimuli may be the outcome of repeated and inescapable adverse events, but also of a disruption of circadian rhythms, a non‐psychiatric disease, or the use of certain medications. Or it may occur in the absence of any such evidence as far as the person is aware of, as often happens in bipolar disorder. Perhaps research should more actively focus on those core phenomena, building on the reports of experts by experience and exploring their biological correlates, without any prejudice about whether they are primarily or essentially psychic or physical in nature.

The effects of the various antidepressant medications could perhaps be explored – beyond current stereotypes – in the same light (are they psychophysical “tonics”?; do they have energizing or disinhibiting properties?; do they affect reward responsiveness?; do they impact psychic/physical pain?), through a more in‐depth and nuanced reconstruction of patients’ experiences of “response” to those agents, and a more targeted investigation of their biological correlates. The same may apply to the effects of other interventions, from physical exercise and behavioural activation to neurostimulation techniques. Neuroscientific explorations of depression should probably look at the autonomic as well as the central nervous system (and at their interactions with the cardiovascular and gastrointestinal systems in addition to the immune and endocrine ones). Finally (or first of all), some more psychopathological sophistication should perhaps be added to the current conceptualization and description of “depression”.