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Physiognomy of the melancholic temperament (drawing by Thomas Holloway made for Johann Kaspar Lavater's Essays on Physiognomy, c. 1789)

Melancholia or melancholy (Ancient Greek: μελαγχολία, romanized: melancholía; from μέλαινα χολή, mélaina cholḗ, 'black bile')[1][2] is a concept found throughout ancient, medieval, and premodern medicine in Europe that describes a condition characterized by markedly depressed mood, bodily complaints, and sometimes hallucinations and delusions.

Melancholy was regarded as one of the four temperaments matching the four humours.[3] Until the 18th century, doctors and other scholars classified melancholic conditions as such by their perceived common cause – an excess of a notional fluid known as "black bile", which was commonly linked to the spleen. Hippocrates and other ancient physicians described melancholia as a distinct disease with mental and physical symptoms, including persistent fears and despondencies, poor appetite, abulia, sleeplessness, irritability, and agitation.[4][5] Later, fixed delusions were added by Galen and other physicians to the list of symptoms.[6][7] In the Middle Ages, the understanding of melancholia shifted to a religious perspective,[8][9] with sadness seen as a vice and demonic possession, rather than somatic causes, as a potential cause of the disease.[10]

During the late 16th and early 17th centuries, a cultural and literary cult of melancholia emerged in England, linked to Neoplatonist and humanist Marsilio Ficino's transformation of melancholia from a sign of vice into a mark of genius. This fashionable melancholy became a prominent theme in literature, art, and music of the era.[citation needed]

Between the late 18th and late 19th centuries, melancholia was a common medical diagnosis.[11] In this period, the focus was on the abnormal beliefs associated with the disorder, rather than depression and affective symptoms.[7] In the 19th century, melancholia was considered to be rooted in subjective 'passions' that seemingly caused disordered mood (in contrast to modern biomedical explanations for mood disorders). In Victorian Britain, the notion of melancholia as a disease evolved as it became increasingly classifiable and diagnosable with a set list of symptoms that contributed to a biomedical model for the understanding mental disease.[12] However, in the 20th century, the focus again shifted, and the term became used essentially as a synonym for depression.[7] Indeed, modern concepts of depression as a mood disorder eventually arose from this historical context.[13] Today, the term "melancholia" and "melancholic" are still used in medical diagnostic classification, such as in ICD-11 and DSM-5, to specify certain features that may be present in major depression.[14][15]

Related terms used in historical medicine include lugubriousness (from Latin lugere, 'to mourn'),[16][17] moroseness (from Latin morosus, 'self-will or fastidious habit'),[17][18] wistfulness (from a blend of wishful and the obsolete English wistly, meaning 'intently'),[17][19] and saturnineness (from Latin Saturninus, 'of the planet Saturn').[20][21]

Early history

[edit]
Melencolia I by Albrecht Dürer, 1514
Frontispiece for the 1628 3rd edition of The Anatomy of Melancholy

The name "melancholia" comes from the old medical belief of the four humours: disease or ailment being caused by an imbalance in one or more of the four basic bodily liquids, or humours. Personality types were similarly determined by the dominant humor in a particular person. According to Hippocrates and subsequent tradition, melancholia was caused by an excess of black bile,[22] hence the name, which means "black bile", from Ancient Greek μέλας (melas), "dark, black",[23] and χολή (kholé), "bile";[24] a person whose constitution tended to have a preponderance of black bile had a melancholic disposition. In the complex elaboration of humorist theory, it was associated with the earth from the Four Elements, the season of autumn, the spleen as the originating organ and cold and dry as related qualities. In astrology it showed the influence of Saturn, hence the related adjective saturnine.[20][21]

Melancholia was described as a distinct disease with particular mental and physical symptoms in the 5th and 4th centuries BC. Hippocrates, in his Aphorisms, characterized all "fears and despondencies, if they last a long time" as being symptomatic of melancholia.[4] Other symptoms mentioned by Hippocrates include: poor appetite, abulia, sleeplessness, irritability, agitation.[5] The Hippocratic clinical description of melancholia shows significant overlaps with contemporary nosography of depressive syndromes (6 symptoms out of the 9 included in DSM [25] diagnostic criteria for a Major Depressive).[26]

In ancient Rome, Galen added "fixed delusions" to the set of symptoms listed by Hippocrates. Galen also believed that melancholia caused cancer.[6] Aretaeus of Cappadocia, in turn, believed that melancholia involved both a state of anguish, and a delusion.[7] In the 10th century Persian physician Al-Akhawayni Bokhari described melancholia as a chronic illness caused by the impact of black bile on the brain.[27] He described melancholia's initial clinical manifestations as "suffering from an unexplained fear, inability to answer questions or providing false answers, self-laughing and self-crying and speaking meaninglessly, yet with no fever."[28]

In Middle-Ages Europe, the humoral, somatic paradigm for understanding sustained sadness lost primacy in front of the prevailing religious perspective.[8][9] Sadness came to be a vice (λύπη in the Greek vice list by Evagrius Ponticus,[29] tristitia vel acidia in the 7 vice list by Pope Gregory I).[30] When a patient could not be cured of the disease it was thought that the melancholia was a result of demonic possession.[10][31]

In his study of French and Burgundian courtly culture, Johan Huizinga[32] noted that "at the close of the Middle Ages, a sombre melancholy weighs on people's souls." In chronicles, poems, sermons, even in legal documents, an immense sadness, a note of despair and a fashionable sense of suffering and deliquescence at the approaching end of times, suffuses court poets and chroniclers alike: Huizinga quotes instances in the ballads of Eustache Deschamps, "monotonous and gloomy variations of the same dismal theme", and in Georges Chastellain's prologue to his Burgundian chronicle,[33] and in the late 15th-century poetry of Jean Meschinot. Ideas of reflection and the workings of imagination are blended in the term merencolie, embodying for contemporaries "a tendency", observes Huizinga, "to identify all serious occupation of the mind with sadness".[34]

Painters were considered by Vasari and other writers to be especially prone to melancholy by the nature of their work, sometimes with good effects for their art in increased sensitivity and use of fantasy. Among those of his contemporaries so characterised by Vasari were Pontormo and Parmigianino, but he does not use the term of Michelangelo, who used it, perhaps not very seriously, of himself.[35] A famous allegorical engraving by Albrecht Dürer is entitled Melencolia I. This engraving has been interpreted as portraying melancholia as the state of waiting for inspiration to strike, and not necessarily as a depressive affliction. Amongst other allegorical symbols, the picture includes a magic square and a truncated rhombohedron.[36] The image in turn inspired a passage in The City of Dreadful Night by James Thomson (B.V.), and, a few years later, a sonnet by Edward Dowden.

The most extended treatment of melancholia comes from Robert Burton, whose The Anatomy of Melancholy (1621) treats the subject from both a literary and a medical perspective. His concept of melancholia includes all mental illness, which he divides into different types. Burton wrote in the 17th century that music and dance were critical in treating mental illness.[37]

But to leave all declamatory speeches in praise of divine music, I will confine myself to my proper subject: besides that excellent power it hath to expel many other diseases, it is a sovereign remedy against despair and melancholy, and will drive away the devil himself. Canus, a Rhodian fiddler, in Philostratus, when Apollonius was inquisitive to know what he could do with his pipe, told him, "That he would make a melancholy man merry, and him that was merry much merrier than before, a lover more enamoured, a religious man more devout." Ismenias the Theban, Chiron the centaur, is said to have cured this and many other diseases by music alone: as now they do those, saith Bodine, that are troubled with St. Vitus's Bedlam dance.[38][39][40]

In the Encyclopédie of Diderot and d'Alembert, the causes of melancholia are stated to be similar to those that cause Mania: "grief, pains of the spirit, passions, as well as all the love and sexual appetites that go unsatisfied."[41]

English cultural movement

[edit]
Ch. Boirau, The Spleen (Melancholy). Postcard, c. 1915.
The young John Donne, the very picture of fashionable melancholy in the Jacobean era
Melancholy, etching by Giovanni Benedetto Castiglione, 1640s

During the later 16th and early 17th centuries, a curious cultural and literary cult of melancholia arose in England. In an influential[42][43] 1964 essay in Apollo, art historian Roy Strong traced the origins of this fashionable melancholy to the thought of the popular Neoplatonist and humanist Marsilio Ficino (1433–1499), who replaced the medieval notion of melancholia with something new:

Ficino transformed what had hitherto been regarded as the most calamitous of all the humours into the mark of genius. Small wonder that eventually the attitudes of melancholy soon became an indispensable adjunct to all those with artistic or intellectual pretentions.[44]

The Anatomy of Melancholy (The Anatomy of Melancholy, What it is: With all the Kinds, Causes, Symptomes, Prognostickes, and Several Cures of it... Philosophically, Medicinally, Historically, Opened and Cut Up) by Burton, was first published in 1621 and remains a defining literary monument to the fashion. Another major English author who made extensive expression upon being of an melancholic disposition is Sir Thomas Browne in his Religio Medici (1643).

Night-Thoughts (The Complaint: or, Night-Thoughts on Life, Death, & Immortality), a long poem in blank verse by Edward Young was published in nine parts (or "nights") between 1742 and 1745, and hugely popular in several languages. It had a considerable influence on early Romantics in England, France and Germany. William Blake was commissioned to illustrate a later edition.

In the visual arts, this fashionable intellectual melancholy occurs frequently in portraiture of the era, with sitters posed in the form of "the lover, with his crossed arms and floppy hat over his eyes, and the scholar, sitting with his head resting on his hand"[44] – descriptions drawn from the frontispiece to the 1638 edition of Burton's Anatomy, which shows just such by-then stock characters. These portraits were often set out of doors where Nature provides "the most suitable background for spiritual contemplation"[45] or in a gloomy interior.

In music, the post-Elizabethan cult of melancholia is associated with John Dowland, whose motto was Semper Dowland, semper dolens ("Always Dowland, always mourning"). The melancholy man, known to contemporaries as a "malcontent", is epitomized by Shakespeare's Prince Hamlet, the "Melancholy Dane".

A similar phenomenon, though not under the same name, occurred during the German Sturm und Drang movement, with such works as The Sorrows of Young Werther by Goethe or in Romanticism with works such as Ode on Melancholy by John Keats or in Symbolism with works such as Isle of the Dead by Arnold Böcklin. In the 20th century, much of the counterculture of modernism was fueled by comparable alienation and a sense of purposelessness called "anomie"; earlier artistic preoccupation with death has gone under the rubric of memento mori. The medieval condition of acedia (acedie in English) and the Romantic Weltschmerz were similar concepts, most likely to affect the intellectual.[46]

Modern connotations

[edit]

Until the 18th century, writings on melancholia were mainly concerned with beliefs that were considered abnormal, rather than affective symptoms.[7]

Melancholia was a category that "the well-to-do, the sedentary, and the studious were even more liable to be placed in the eighteenth century than they had been in preceding centuries."[47][48]

In the 20th century, "melancholia" lost its attachment to abnormal beliefs, and in common usage became entirely a synonym for depression.[7] Sigmund Freud published a paper on Mourning and Melancholia in 1918.

In 1907, the German psychiatrist Emil Kraepelin influentially proposed the existence of a condition he called 'involutional melancholia', which he thought could help explain the more frequent occurrence of depression among elderly people.[49] He surmised that in the elderly "the processes of involution in the body are suited to engender mournful or anxious moodiness", though by 1913 he had returned to his earlier view (first expounded in 1899) that age-related depression could be understood in terms of manic-depressive illness.[49]

In 1996, Gordon Parker and Dusan Hadzi-Pavlovic described "melancholia" as a specific disorder of movement and mood.[50] They attached the term to the concept of "endogenous depression" (claimed to be caused by internal forces rather than environmental influences).[51]

In 2006, Michael Alan Taylor and Max Fink also defined melancholia as a systemic disorder that could be identified by depressive mood rating scales, verified by the presence of abnormal cortisol metabolism.[52] They considered it to be characterized by depressed mood, abnormal motor functions, and abnormal vegetative signs, and they described several forms, including retarded depression, psychotic depression and postpartum depression.[52]

Melancholic depression

[edit]
Melancholic depression
Meditation by Domenico Fetti 1618
SpecialtyPsychiatry
SymptomsLow mood, low self-esteem, fatigue, insomnia, anorexia, anhedonia, lack of mood reactivity
ComplicationsSelf harm, suicide
Usual onsetEarly adulthood
CausesGenetic, environmental, and psychological factors
Risk factorsFamily history, trauma
TreatmentCounseling, antidepressant medication, electroconvulsive therapy

For the purposes of medical diagnostic classification, the terms "melancholia" and "melancholic" are still in use (for example, in ICD-11 and DSM-5) to specify certain features that may be present in major depression, referred to as depression with melancholic features such as:[14][15][53]

  • severely depressed mood, wherein the person often feels despondent, forlorn, disconsolate, or empty
  • pervasive anhedonia – loss of interest or pleasure in most activities that are normally enjoyable
  • lack of emotional responsiveness (mood does not brighten, even briefly) to normally pleasurable stimuli (such as food or entertainment) or situations (such as warm, affectionate interactions with friends or family)
  • terminal insomnia – unwanted early morning awakening (two or more hours earlier than normal)
  • marked psychomotor retardation or agitation
  • marked loss of appetite or weight loss

A specifier essentially is a subcategory of a disease, explaining specific features or symptoms that are added to the main diagnosis.[54] According to the DSM-IV, the "melancholic features" specifier may be applied to the following only:

  1. Major depressive episode, single episode
  2. Major depressive episode, recurrent episode
  3. Bipolar I disorder, most recent episode depressed
  4. Bipolar II disorder, most recent episode depressed

It is important to note, however, that people who suffer from melancholic depression do not need to have melancholic features in every depressive episode.[55]

Signs and symptoms

[edit]

Melancholic depression requires at least one of the following symptoms during the last depressive episode:

  • Anhedonia (the inability to find pleasure in positive things)
  • Lack of mood reactivity (i.e. mood does not improve in response to positive/desired events; failure to feel better)

And at least three of the following:

  • Depressed mood that is subjectively different from grief or loss (marked by despair, gloominess, and "empty-mood")
  • Severe weight loss or loss of appetite
  • Psychomotor agitation or retardation (i.e. increased or decreased movement, speech, and cognitive function)
  • Early morning awakening (i.e. waking up at least 2 hours before the normal wake up time of the patient)
  • Guilt that is excessive
  • Worse depressed mood in the morning

Melancholic features apply to an episode of depression that occurs as part of either major depressive disorder, persistent depressive disorder (dysthymia), or bipolar disorder I or II.[15] They are more likely to occur in patients who suffer from depression with psychotic features.[53] People with melancholic depression also tend to have more physically visible symptoms such as slower movement or speech.[56]

Causes

[edit]

The causes of melancholic depressive disorder are believed to be mostly biological factors that can be hereditary. Biological origins of the condition include problems with the HPA axis and sleep structure of patients.[57] MRI studies have indicated that melancholic depressed patients have issues with the connections between different regions of the brain, specifically the insula and fronto-parietal cortex.[58] Some studies have found that there are biological marker differences between patients with melancholic depression and other subtypes of depression.[59]

The research regarding melancholic depression consistently finds that men are more likely to receive a melancholic depression diagnosis.[60]

Treatment

[edit]

Melancholic depression, due to some fundamental differences with standard clinical depression or other subtypes of depression, has specific types of treatments that work, and the success rates for different treatments can vary.[61][57] Treatment can involve antidepressants and empirically supported treatments such as cognitive behavioral therapy and interpersonal therapy for depression.[62]

Melancholic depression is often considered to be a biologically based and particularly severe form of depression. Therefore, the treatments for this specifier of depression are more biomedical and less psychosocial (which would include talk therapy and social support).[63] The general initial or "ideal" treatment for melancholic depression is antidepressant medication, and psychotherapy is added later on as support if at all.[55] The scientific support for medication as the best treatment is that patients with melancholic depression are less likely to improve with placebos, unlike other depression patients. This indicates the improvements observed after medication actually come from the biological basis of the condition and the treatment.[57] There are several types of antidepressants that can be prescribed including SSRIs, SNRIs, tricyclic antidepressants, and MAOIs; the antidepressants tend to vary on how they work and what specific chemical messengers in the brain they target.[56] SNRIs are generally more effective than SSRIs because they target more than one chemical messenger (serotonin and norepinephrine).[60]

Although psychotherapy treatments can be used such as talk therapy and cognitive behavioral therapy (CBT), they have shown to be less effective than medication.[57] In a randomized clinical trial, it was shown that CBT was less effective than medication in treating symptoms of melancholic depression after 12 weeks.[64]

Electroconvulsive therapy (ECT) was previously believed to be an effective treatment for melancholic depression.[65] ECT has been more commonly used for patients with melancholic depression due to the severity. In 2010, a study found that 60% of depression patients treated with ECT had melancholic symptoms.[55] However, studies since the 2000s have failed to demonstrate positive treatment results from ECT, although studies also indicate a more positive response to ECT in melancholic patients than other depressed patients.[57][66]

It has been observed in studies that patients with melancholic depression tend to recover less often than other types of depression.[60]

Frequency

[edit]

The prevalence of having the melancholic depression specifier among patients diagnosed with clinical depression is estimated to be about 25% to 30%.[55]

The incidence of melancholic depression has been found to increase when the temperature and/or sunlight are low.[67]

See also

[edit]

Citations

[edit]
  1. ^ Burton, Bk. I, p. 147
  2. ^ Bell M (2014). Melancholia: The Western Malady. United Kingdom: Cambridge University Press. p. 38. ISBN 978-1-107-06996-1. Archived from the original on 2022-08-28. Retrieved 2022-08-28.
  3. ^ "The Four Human Temperaments". www.thetransformedsoul.com. Archived from the original on 2022-07-07. Retrieved 2022-08-28.
  4. ^ a b Hippocrates, Aphorisms, Section 6.23
  5. ^ a b Epidemics, III, 16 cases, case II
  6. ^ a b Clarke, R. J.; Macrae, R. (1988). Coffee: Physiology. Springer Science & Business Media. ISBN 978-1-85166-186-2. Archived from the original on 2022-07-03. Retrieved 2022-08-28 – via Google Books.
  7. ^ a b c d e f Telles-Correia, Diogo; Marques, João Gama (3 February 2015). "Melancholia Before the Twentieth Century: Fear and Sorrow or Partial Insanity?". Frontiers in Psychology. 6: 81. doi:10.3389/fpsyg.2015.00081. PMC 4314947. PMID 25691879.
  8. ^ a b Azzone P. (2013) pp. 23ff.
  9. ^ a b Azzone P (2012) Sin of Sadness: Acedia vel Tristitia Between Sociocultural Conditioning and Psychological Dynamics of Negative Emotions. Journal of Psychology and Christianity, 31: 50–64.
  10. ^ a b "18th-Century Theories of Melancholy & Hypochondria". loki.stockton.edu. Archived from the original on 2021-01-25. Retrieved 2022-08-28.
  11. ^ Berrios G E (1988) Melancholia and Depression during the 19th Century. British Journal of Psychiatry 153: 289–304
  12. ^ Jansson, Asa (2021). From Melancholia to Depression: Disordered Mood in 19th Century Psychiatry. Springer Nature Switzerland AG. ISBN 978-3-030-54801-8.
  13. ^ Kendler KS (August 2020). "The Origin of Our Modern Concept of Depression-The History of Melancholia from 1780–1880: A Review" (PDF). JAMA Psychiatry. 77 (8): 863–868. doi:10.1001/jamapsychiatry.2019.4709. PMID 31995137. S2CID 210949394. Archived (PDF) from the original on 2022-08-12. Retrieved 2022-08-28.
  14. ^ a b World Health Organization, "6A80.3 Current depressive episode with melancholia", International Statistical Classification of Diseases and Related Health Problems, 11th rev. (September 2020).
  15. ^ a b c American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders (DSM-5®). United States: American Psychiatric Publishing. p. 185. ISBN 978-0-89042-557-2. Archived from the original on 2021-07-10. Retrieved 2022-08-28.
  16. ^ "Definition of Lugubrious". Merriam-Webster Dictionary. Retrieved 2022-12-07.
  17. ^ a b c Porter, Stanley C.; Malcolm, Matthew R., eds. (2013-04-25). Horizons in Hermeneutics: A Festschrift in Honor of Anthony C. Thiselton. William B. Eerdmans Publishing Company. p. 162. ISBN 978-0-8028-6927-2. Melancholia [is] also translated as "lugubriousness," "moroseness," or "wistfulness".
  18. ^ "Definition of Moroseness". Merriam-Webster Dictionary. Retrieved 2022-12-07.
  19. ^ "Definition of Wistfulness". Merriam-Webster Dictionary. Retrieved December 7, 2022.
  20. ^ a b "Definition of Saturnine". Merriam-Webster Dictionary. Retrieved December 7, 2022.
  21. ^ a b Wallace, Ian, ed. (2015). Voices from Exile: Essays in Memory of Hamish Ritchie. Brill. p. 213. ISBN 978-90-04-29639-8. [This is] what humour-based physiology of the renaissance and baroque periods described as saturnine melancholia.
  22. ^ Hippocrates, De aere aquis et locis, 10.103 Archived 2022-06-01 at the Wayback Machine, on Perseus Digital Library
  23. ^ μέλας Archived 2011-06-05 at the Wayback Machine, Henry George Liddell, Robert Scott, A Greek-English Lexicon, on Perseus Digital Library
  24. ^ χολή Archived 2022-07-08 at the Wayback Machine, Henry George Liddell, Robert Scott, A Greek–English Lexicon, on Perseus Digital Library
  25. ^ American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition. APA, Washington DC., pp. 160–161.
  26. ^ Azzone, Paolo (2013). Depression as a psychoanalytic problem. Lanham, Md: University Press of America. ISBN 978-0-7618-6041-9. OCLC 816563937.
  27. ^ Delfaridi, Behnam (2014). "Melancholia in Medieval Persian Literature: The View of Hidayat of Al-Akhawayni". World Journal of Psychiatry. 4 (2): 37–41. doi:10.5498/wjp.v4.i2.37. PMC 4087154. PMID 25019055.
  28. ^ Matini, Jalal (1965). Hedayat al-Motaallemin fi Tebb. University Press, Mashhad.
  29. ^ Guillamont A., Guillamont C. (Eds.) (1971) Évagre le Pontique. Traité pratique ou le moine, 2 VV.. Sources Chrétiennes 170–171, Les Éditions du Cerf, Paris
  30. ^ Gregorius Magnus. Moralia in Iob. In J.-P. Migne (Ed.) Patrologiae Latinae cursus completus (Vol. 75, col. 509D – Vol. 76, col. 782AG)
  31. ^ Farmer, Hugh. An essay on demoniacs of the New Testament 56 (1818)
  32. ^ Huizinga, "Pessimism and the ideal of the sublime life", The Waning of the Middle Ages, 1924:22ff.
  33. ^ "I, man of sadness, born in an eclipse of darkness, and thick fogs of lamentation".
  34. ^ Huizinga 1924:25.
  35. ^ Britton, Piers, "Mio malinchonico, o vero... mio pazzo": Michelangelo, Vasari, and the Problem of Artists' Melancholy in Sixteenth-Century Italy, The Sixteenth Century Journal, Vol. 34, No. 3 (Fall, 2003), pp. 653–675, doi:10.2307/20061528, Archived 2020-11-14 at the Wayback Machine
  36. ^ Weisstein, Eric W. "Dürer's Solid". mathworld.wolfram.com. Archived from the original on 2022-01-30. Retrieved 2022-08-28.
  37. ^ Cf. The Anatomy of Melancholy, subsection 3, on and after line 3480, "Music a Remedy":
  38. ^ "Gutenberg.org". Archived from the original on 2020-08-09. Retrieved 2022-08-28.
  39. ^ "Humanities are the Hormones: A Tarantella Comes to Newfoundland. What should we do about it?" Archived February 15, 2015, at the Wayback Machine by Dr. John Crellin, Munmed, newsletter of the Faculty of Medicine, Memorial University of Newfoundland, 1996.
  40. ^ Aung, Steven K.H.; Lee, Mathew H.M. (2004). "Music, Sounds, Medicine, and Meditation: An Integrative Approach to the Healing Arts". Alternative & Complementary Therapies. 10 (5): 266–270. doi:10.1089/act.2004.10.266.
  41. ^ Denis Diderot (2015). "Melancholia". The Encyclopedia of Diderot & d'Alembert Collaborative Translation Project. Archived from the original on 2 April 2015. Retrieved 1 April 2015.
  42. ^ Goldring, Elizabeth (2005). "'So lively a portraiture of his miseries': Melancholy, mourning and the Elizabethan malady". The British Art Journal. 6 (2): 12–22. ISSN 1467-2006. JSTOR 41614620.
  43. ^ Ribeiro, Aileen (2005). Fashion and Fiction: Dress in Art and Literature in Stuart England. New Haven CN; London: Yale University Press. p. 52. ISBN 978-0-300-10999-3.
  44. ^ a b Strong, Roy (1964). "The Elizabethan Malady: Melancholy in Elizabeth and Jacobean Portraiture". Apollo. LXXIX., reprinted in Strong, Roy (1969). The English Icon: Elizabethan and Jacobean Portraiture. London: Routledge & Kegan Paul.
  45. ^ Ribeiro, Aileen (2005). Fashion and Fiction: Dress in Art and Literature in Stuart England. New Haven, CN; London: Yale University Press. p. 54. ISBN 978-0-300-10999-3.
  46. ^ Perpinyà, Núria (2014). Ruins, Nostalgia and Ugliness. Five Romantic Perceptions of Middle Ages and a Spoon of Game of Thrones and Avant-Garde Oddity Archived 2016-03-13 at the Wayback Machine. Berlin: Logos Verlag
  47. ^ Wear, A (2001). The Oxford Companion to the Body. Oxford University Press. Archived from the original on 2021-10-15. Retrieved 2022-08-28.
  48. ^ Ordronaux, John (1871). Regimen sanitatis salernitanum. Code of health of the school of Salernum. Philadelphia, J.B. Lippincott & co.
  49. ^ a b Kendler KS, Engstrom EJ (2020). "Dreyfus and the shift of melancholia in Kraepelin's textbooks from an involutional to a manic-depressive illness". Journal of Affective Disorders. 270: 42–50. doi:10.1016/j.jad.2020.03.094. PMID 32275219. S2CID 215726731.
  50. ^ Parker, Gordon; Hadzi-Pavlovic, Dusan, eds. (1996). Melancholia: A Disorder of Movement and Mood: A Phenomenological and Neurobiological Review. Sydney: Cambridge University Press. doi:10.1017/CBO9780511759024. ISBN 978-0-521-47275-3. Archived from the original on 2022-01-20. Retrieved 2022-08-28.
  51. ^ Parker, Gordon (6 September 2015). "Back to Black: Why Melancholia Must Be Understood as Distinct from Depression". The Conversation. Archived from the original on 2022-03-30. Retrieved 2022-08-28.
  52. ^ a b Taylor, Michael Alan; Fink, Max (2006). Melancholia: The Diagnosis, Pathophysiology and Treatment of Depressive Illness. New York: Cambridge University Press. ISBN 978-0-521-84151-1. Archived from the original on 2022-05-03. Retrieved 2022-08-28.
  53. ^ a b American Psychiatric Association (2013-05-22). Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). American Psychiatric Association. doi:10.1176/appi.books.9780890425596. ISBN 978-0-89042-555-8.
  54. ^ "What's the DSM-5?". Psych Central. 2017-05-17. Retrieved 2023-03-28.
  55. ^ a b c d "The Darkest Mood: Major Depression With Melancholic Features | Psychology Today". www.psychologytoday.com. Retrieved 2023-03-28.
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Melancholia

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Melancholia is a historical medical and psychological term denoting a profound characterized by persistent , , despondency, guilt, loss of enjoyment, appetite suppression, and physical symptoms such as , often accompanied by delusions or abnormal beliefs. Originating in humoral theory, it was attributed to an excess of black bile (melaina chole), one of the four bodily humors believed to govern temperament and health. This concept, first systematically described by (c. 460–370 BCE) as an affective disturbance involving and sorrow, evolved through the works of (129–216 CE), who integrated anatomical explanations linking cerebral imbalances to melancholic symptoms. In the medieval and early modern periods, melancholia was further elaborated by physicians like Avicenna (Ibn Sina, 980–1037 CE), who viewed it within a holistic framework encompassing environmental, social, and physiological factors. By the 18th and 19th centuries, European psychiatry, influenced by figures such as Philippe Pinel, redefined melancholia as a form of partial insanity dominated by fixed delusions (e.g., themes of persecution or guilt), shifting emphasis from humoral causes to observable psychiatric symptoms. The 19th century marked its reconfiguration as a modern mood disorder, distinct from broader madness, with Emil Kraepelin's early 20th-century nosology reclassifying it under manic-depressive illness, paving the way for its integration into unipolar depression. The Diagnostic and Statistical Manual of Mental Disorders (DSM-III, 1980) formalized major depressive disorder, subsuming melancholia as a specifier for severe, endogenous depression with features like psychomotor retardation and anhedonia, though debates persist on reinstating it as a distinct entity. Beyond medicine, melancholia has profoundly shaped Western , , and as a cultural of profound , , and existential . Iconic representations include Albrecht Dürer's engraving (1514), which depicts a winged figure surrounded by symbols of unfulfilled creativity and intellectual paralysis, embodying the ideal of melancholy as both affliction and inspiration. Burton's encyclopedic (1621) cataloged its causes, symptoms, and cures, blending scholarly analysis with literary flair to influence subsequent explorations in and modernist . Freud's 1917 essay "" further psychologized it as pathological narcissism and unresolved loss, cementing its role in 20th-century cultural theory. Today, melancholia persists as a motif in , , and , symbolizing the tension between creative potential and emotional stasis, while informing contemporary understandings of depression as a leading global cause of .

Etymology and Historical Origins

Ancient Greek and Roman Concepts

The term melancholia originates from the Ancient Greek words melas (μέλας), meaning "black," and kholē (χολή), meaning "bile," literally denoting "black bile." This etymology reflects the humoral theory's central role in classical medicine, where an excess of this substance was believed to underlie various psychological and physiological disturbances. Hippocrates, around 400 BCE, first employed the term in the Corpus Hippocraticum, a collection of medical texts attributed to him and his followers, to characterize a condition marked by prolonged fear and despondency without evident cause. In Aphorisms VI.23, he describes it as follows: "If a fright or despondency lasts for a long time, it is a melancholic affection." The Hippocratic view attributed melancholia to an imbalance of the four humors—blood, phlegm, yellow bile, and black bile—with excess black bile, produced in the spleen or lower intestines, leading to symptoms such as aversion to food, persistent despondency, sleeplessness, and irritability. Black bile's cold and dry qualities were thought to pervade the body, particularly affecting the mind when it reached the brain, distinguishing melancholia as both a temperament and a potential illness. In the 4th century BCE, (or the pseudo-Aristotelian author) explored melancholia's dual nature in Problemata Physica XXX.1, positing a connection between black bile and exceptional intellectual and creative capacities. The text questions: "Why is it that all men who have become outstanding in , statesmanship, or the arts are melancholics, some to such an extent as to be reputed mad?" suggested that black bile, when properly tempered, fostered by stimulating warmth and acuity in the , evident among figures like philosophers and statesmen, though excess could tip into madness. This view elevated melancholia from mere to a marker of potential brilliance, influencing later philosophical interpretations. Roman physician (2nd century CE) further developed these ideas in works such as On the Affected Parts and On the Natural Faculties, integrating and expanding the Hippocratic humoral framework while emphasizing black bile's role in both healthy contemplation and pathological states. described black bile as a natural humor essential for but harmful when corrupted or excessive, leading to "deep thought" in yet profound , , and delusions in imbalance. He differentiated types of melancholia based on black bile's location and quality, such as hypochondriacal (affecting the ) or cerebral forms causing mental disturbances. In his case studies, documented patients with melancholic delusions, including one who believed himself made of and feared breaking, illustrating how atrabilious vapors could distort perception and produce fixed, irrational beliefs. These observations reinforced melancholia as a spectrum from to severe illness, treatable through diet, purgatives, and to restore humoral equilibrium.

Humoral Theory in Medieval and Renaissance Periods

In the medieval period, Islamic scholars preserved and expanded upon ancient humoral theories of melancholia, with Avicenna's (completed around 1025) providing a foundational description of the condition as arising from a cold and dry temperament due to excess black bile, which could manifest in obsessive thoughts, prolonged staring, and excessive rumination specific to the . This work integrated Aristotelian roots from classical , emphasizing melancholia's dual potential for intellectual depth or pathological distress. Avicenna's systematic influenced subsequent European medical texts by detailing melancholia's somatic and psychological symptoms, including transitions to states like anger or . European medieval scholarship adapted these ideas, as seen in the (circa 12th century), a compilation of texts on that described uterine disorders such as suffocation of the womb, which produced symptoms of fear and physical immobility, often tied to melancholic states in women. The recommended humoral balancing through purges and dietary adjustments to alleviate these conditions related to menstrual irregularities and postpartum states. This gendered interpretation reflected broader medieval concerns with humoral imbalances in female physiology, distinguishing women's melancholia from general cases. During the , humoral melancholia evolved toward associations with genius, exemplified by Marsilio Ficino's De Vita Libri Tres (1489), which advised scholars prone to melancholic tendencies—characterized by cold, dry dispositions—to manage them through tailored diets, herbal remedies, and astrological talismans to channel Saturnine influences into creative productivity. Ficino synthesized medical and philosophical views, arguing that moderated black bile fostered intellectual brilliance while unchecked excess led to despair, thus promoting proactive for artists and thinkers. This revival influenced cultural perceptions, portraying melancholia as a noble affliction rather than mere illness. Robert Burton's (1621) compiled these humoral traditions into an encyclopedic treatise, systematically exploring causes, symptoms, and cures of melancholic states through personal reflections, literary quotations, and medical authorities, while emphasizing black bile's role in diverse manifestations from lovesickness to scholarly despondency. Burton drew on and Ficino to illustrate how excess humors disrupted the soul's harmony, using anecdotes to humanize the condition's pervasive impact. His work bridged medieval and early modern thought, reinforcing melancholia's intellectual allure amid therapeutic advice. Renaissance iconography captured this transformed view, as in Albrecht Dürer's engraving Melencolia I (1514), which depicts a winged figure surrounded by symbols of —such as a , scales, and an hourglass—symbolizing the artist's tormented genius immobilized by creative frustration and humoral imbalance. The figure's melancholic pose, with tools unused and a distant suggesting unattainable inspiration, embodies the era's toward black bile as both burdensome and divine. This artwork, one of Dürer's master engravings, visually encapsulated the linkage of melancholia to profound artistic endeavor.

Cultural and Philosophical Dimensions

Melancholy as Creative Inspiration

In , Aristotle's Problemata (Book 30, Chapter 1) associated individuals of —due to an excess of —with exceptional intellectual abilities and , observing that many eminent philosophers, statesmen, and artists exhibited such traits, though prone to despondency. This idea laid a foundational link between melancholy and creative depth. Plato's concept of , as articulated in the Phaedrus, portrayed not as mere but as a essential for poets, prophets, and visionaries, enabling them to access truths beyond rational . This notion of inspired influenced later aesthetic views on inspiration, though distinct from humoral melancholy. During the , Neoplatonist revived and synthesized Aristotelian ideas on melancholy with Platonic inspiration and humoral theory, positing that an excess of black bile—traditionally linked to melancholy—could elevate the intellect to when balanced with celestial influences, as explored in his De vita libri tres (1489). This perspective transformed melancholy from a mere affliction into a privileged state fostering artistic and philosophical depth, influencing depictions of creative figures as saturnine visionaries. In 19th-century , this ideal persisted and deepened, with Johann Wolfgang von Goethe's Faust (Part I, 1808) embodying the restless, melancholic striving of the human spirit toward transcendent knowledge, where the protagonist's inner turmoil fuels profound intellectual and aesthetic pursuits. Similarly, John Keats's (1819) celebrates melancholy as inextricably bound to beauty and joy, urging embrace of its intensity to fully apprehend life's transience and profundity. These works reframed melancholy as an aesthetic force amplifying sensitivity to existence's ephemerality. Sigmund Freud's essay "" (1917) introduced a psychoanalytic distinction, identifying pathological melancholia as an internalized loss leading to ego degradation, yet hinting at its potential sublimation into creative ego-idealization, where unresolved toward lost objects energizes artistic production. Building on this, 20th-century existential thought, particularly Walter Benjamin's "Theses on the Philosophy of History" (1940), framed melancholia as a critical historical awareness amid modern alienation, where the "angel of history" gazes backward in sorrow at progress's ruins, fostering redemptive insight into human rupture. A cross-cultural parallel appears in the Japanese aesthetic of mono no aware, which evokes a gentle melancholy over the impermanence of all things, underscoring a universal sensitivity to transience that echoes European interpretations while emphasizing serene acceptance over anguished striving.

Depictions in English Literature and Art

In the Elizabethan era, melancholia emerged as a prominent motif in English drama, particularly in William Shakespeare's As You Like It (1599), where the character Jaques embodies a melancholic worldview through his famous "All the world's a stage" speech, portraying life as a series of inevitable declines marked by sorrow and philosophical detachment. Jaques's self-proclaimed melancholy reflects the period's fascination with humoral imbalances, positioning him as an observer who finds profundity in human transience and folly, contrasting with the play's comedic resolution. During the , like incorporated melancholy as a marker of spiritual depth and intellectual rigor, evident in his poem "A Valediction: Forbidding Mourning" (1611), which navigates themes of separation and enduring love through a lens of restrained sorrow that elevates emotional experience to metaphysical insight. Donne's work, influenced by scholarly traditions of melancholy, uses the condition not as mere affliction but as a conduit for exploring the soul's complexities, blending wit and contemplation in a way that underscores the era's intellectualized approach to inner turmoil. The 18th-century "Graveyard School" of poetry romanticized rural melancholy, with Thomas Gray's "Elegy Written in a Country Churchyard" (1751) exemplifying this through its meditative reflections on the lives of the obscure dead, evoking a gentle, contemplative sorrow tied to the inexorability of fate and the equality of mortality. Gray's elegy transforms personal melancholy into a universal meditation, using the churchyard setting to blend nostalgia with philosophical resignation, influencing the period's pre-Romantic sensibilities. In , melancholia manifested as chronic isolation and emotional stagnation, as seen in Charles Dickens's (1861), where represents a figure trapped in perpetual grief, her decaying bridal attire and reclusive existence symbolizing the destructive hold of betrayed expectations and unresolved sorrow. Havisham's portrayal critiques social constraints on women while illustrating melancholy's corrosive impact on personal relationships and self-perception. In visual arts, Sir Joshua Reynolds's late 18th-century portraits captured contemplative melancholy among the British aristocracy, often depicting sitters in poised, introspective poses that conveyed a refined emotional depth, as in his works evoking quiet reflection and subtle pathos. Reynolds drew on classical ideals to infuse aristocratic subjects with this aura, elevating portraiture to explore inner states amid the era's cultural emphasis on sensibility. Robert Burton's The Anatomy of Melancholy (1621) exerted a subtle influence on these literary depictions, providing a scholarly framework for articulating melancholic themes across centuries.

Evolution in Psychiatric Understanding

18th to Early 20th Century Classifications

In the , during the Enlightenment, melancholia began transitioning from its ancient humoral roots toward a more modern understanding as a nervous disorder influenced by lifestyle and environment. Scottish physician George Cheyne, in his influential 1733 treatise The English Malady, portrayed melancholia—often equated with disorders, , and hypochondriacal distempers—as a prevalent affliction among the British elite, attributing it to the excesses of urban, sedentary living, rich diets, and the pressures of civilized society. Cheyne argued that such conditions arose from deviations from "the Purity and Simplicity of uncorrupted Nature," particularly affecting the upper classes who indulged in luxurious habits, and he estimated that nearly one-third of England's nobility suffered from these nervous maladies. By the early 19th century, French alienist Étienne Esquirol advanced the classification of melancholia within his theory, outlined in his 1838 Des Maladies Mentales, viewing it as a form of partial characterized by focused delusions rather than total mental derangement. Esquirol differentiated into subtypes, including a "sad" variant akin to melancholia, where delusions centered on themes of guilt, , or , contrasting with broader or ; this framework sparked debates on whether melancholia represented a localized intellectual lesion or a more diffuse emotional disturbance. His ideas influenced asylum practices, emphasizing melancholia's potential curability through and isolation from delusional triggers. Throughout the , melancholia became a common in expanding asylum systems, particularly in Britain, where institutionalization trends reflected growing optimism about treating it as a recoverable form of . Under the Lunacy Acts, including the 1890 that broadened asylum access to include wealthier patients and mandated detailed reception orders, melancholia accounted for about 26% of admissions to facilities like Cornwall's St. Lawrence Hospital in the 1870s, with over half of cases (57.5%) resulting in recovery and discharge within a year through regimens of rest, routine, and mild interventions. By the end of the , British asylums housed over 100,000 patients, many diagnosed with melancholia, underscoring its recognition as a treatable amenable to environmental and therapeutic management rather than lifelong confinement. At the turn of the 20th century, German psychiatrist Emil Kraepelin solidified melancholia's place in psychiatric nosology through his 1899 sixth edition of Psychiatrie, classifying it as the depressive pole of manic-depressive illness—a cyclic disorder distinct from dementia praecox (schizophrenia)—marked by profound anhedonia, psychomotor retardation, and endogenous mood swings without external precipitants. Kraepelin's dichotomous model emphasized melancholia's recurrent, endogenous nature, differentiating it from reactive depressions and establishing it as a core affective psychosis with a guarded prognosis due to risks of suicide and chronicity. Early 20th-century psychoanalysis further reframed melancholia as a pathological response to loss, with Karl Abraham's 1911 paper "Notes on the Psycho-Analytical Investigation and Treatment of Manic-Depressive Insanity and Allied Conditions" positing it as an internalized incorporation of a lost , leading to self-reproach and , in contrast to the reality-testing of normal mourning. Drawing on case studies, Abraham highlighted pregenital, oral-sadistic fixations in melancholic patients, where the ego turns inward upon the ambivalently loved object, influencing Freud's later elaboration and shifting focus from biological to psychodynamic etiologies.

Mid-20th Century Shifts and Modern Temperament Models

In the mid-20th century, Adolf Meyer's psychobiological framework, which emphasized the interplay of biological, psychological, and social factors in mental disorders, significantly influenced the reconceptualization of melancholia as an endogenous form of depression during the 1950s and 1960s. This approach shifted focus from purely exogenous triggers to internal biological processes, positioning melancholia as a condition amenable to somatic interventions like (ECT), which gained prominence as an effective treatment for severe, endogenous depressive states unresponsive to other methods. Meyer's legacy, though he passed in 1950, permeated post-war psychiatry, promoting a holistic yet biologically grounded view that distinguished endogenous melancholia from reactive depressions. The evolution of diagnostic manuals further standardized these shifts. The DSM-I (1952) classified depressive conditions under "affective reactions," including depressive reactions as responses to internal or external stressors, without a distinct melancholic category but acknowledging psychotic depressive reactions as severe forms. By DSM-III (1980), melancholia was formalized as a subtype of major depressive disorder, defined by vegetative symptoms such as significant weight loss, early morning awakening, psychomotor agitation or retardation, and excessive guilt, emphasizing its endogenous nature and distinct from non-melancholic depressions. This subtype was retained in DSM-5 (2013) as a specifier for major depressive disorder, requiring at least three of six melancholic features (e.g., pervasive anhedonia, lack of mood reactivity) during the most severe episode, to guide targeted treatments like ECT or tricyclic antidepressants. Temperament models integrated melancholia into broader typologies. Hans Eysenck's 1947 dimensional theory identified two primary axes—neuroticism (emotional instability) and extraversion-introversion—placing melancholics in the high-, introversion quadrant, characterized by traits like persistence, rigidity, and heightened . In modern frameworks, such as the Big Five model, melancholic depression correlates strongly with elevated , interpreted as high , alongside low extraversion and , predicting vulnerability to severe, recurrent episodes independent of environmental stressors. Cultural psychiatry in the 1970s advanced these distinctions through critiques like Donald Klein's 1974 "Two Theories of Depression," which differentiated melancholic (endogenous, biologically driven, with profound and psychomotor changes) from neurotic (reactive, personality-linked, with anxiety and interpersonal sensitivity) depressions, challenging unified models and advocating for subtype-specific pharmacotherapies. The (2019) reflects this legacy by classifying melancholic features under current depressive episode (6A80.3), requiring pervasive , non-reactivity to positive stimuli, and marked psychomotor disturbances (retardation or agitation), alongside and appetite/weight loss, to highlight its distinct neurobiological profile. Recent as of 2025 continues to support melancholia as a distinct subtype of depression, with studies identifying unique genetic risk factors, neurobiological markers, and differential responses to treatments like or specific antidepressants, informing approaches.

Clinical Features of Melancholic Depression

Symptoms and Diagnostic Criteria

Melancholic depression, a subtype of , is characterized by a severe and pervasive form of depressed mood that lacks responsiveness to external positive stimuli, often accompanied by distinct psychomotor disturbances and physiological symptoms. Core symptoms include a profound loss of pleasure () in all or nearly all activities, a depressed mood that feels qualitatively different from normal —often described as empty, despairing, or exaggeratedly gloomy—and a lack of mood reactivity, where the mood does not improve in response to positive events. Additional hallmark features encompass early morning awakening with terminal , or retardation (such as slowed speech, movements, or thinking), significant due to decreased , and excessive or inappropriate guilt feelings that may border on delusional proportions. These symptoms must occur in the of a major depressive episode and represent a more endogenous form of depression, tracing roots to Kraepelin's of endogenous depression as a distinct psychotic-affective . In the , melancholic features serve as a specifier for or bipolar depression, requiring the presence of either (1) a complete loss of pleasure in all activities or (2) a lack of mood reactivity to usually pleasurable stimuli, plus at least three of the following: a distinct quality to the depressed mood as described above; with symptoms worse in the morning; early morning awakening at least two hours before the usual time; marked or agitation; significant anorexia or ; or excessive or inappropriate guilt. This specifier helps delineate a subtype with more uniform symptom clustering compared to non-melancholic depression, emphasizing biological over psychological precipitants. The criteria underscore the endogenous nature, with psychomotor changes observed in observable behaviors like reduced gestures or . The ICD-11 similarly recognizes melancholia as a qualifier for a current depressive episode (code 6A80.3), defined by pervasive anhedonia and lack of emotional reactivity, in addition to a current depressive episode, with at least three of: a distinct despondent quality to the mood; diurnal variation worse in the morning; early morning awakening; marked psychomotor retardation or agitation; significant weight loss; or excessive guilt. Profound psychomotor disturbances, diurnal mood worsening, and terminal insomnia stand out as particularly indicative hallmarks, aligning closely with DSM-5 but integrated within the broader depressive episode framework that requires at least five symptoms including core mood changes. These descriptors facilitate cross-cultural diagnostic consistency by focusing on observable and physiological signs. Differentially, melancholic depression features diurnal variation with symptoms peaking in the morning and improving slightly later, contrasting with where mood worsens in the evening alongside and increased appetite. In severe cases, melancholic depression shows a higher of mood-congruent delusions, such as nihilistic delusions involving themes of personal non-existence, bodily decay, or cosmic worthlessness, which are common in psychotic presentations of the subtype. Assessment of melancholic features often employs the Hamilton Depression Rating Scale (HAM-D), particularly its 6-item melancholia subscale (HAM-D6), which scores items related to depressed mood, guilt, work and interests (capturing ), psychomotor retardation, psychic anxiety, and somatic symptoms to quantify severity of core melancholic elements. This subscale demonstrates high reliability in detecting psychomotor disturbances and , aiding in tracking treatment response and subtype validation across clinical trials. Individuals with melancholic depression exhibit unique comorbidities, including an elevated risk—up to twice that of non-melancholic depression due to the severity of and guilt—and a stronger familial aggregation of mood disorders, with estimates indicating genetic loading for the subtype in family studies.

Etiology and Neurobiological Mechanisms

The of melancholic depression involves a complex interplay of genetic vulnerability, environmental stressors, and neurobiological alterations, distinguishing it from other depressive subtypes through heightened biological underpinnings. Twin studies have estimated the of , including melancholic features, at approximately 40-50%, with monozygotic twin concordance rates around 46% compared to 20% for dizygotic twins, indicating a substantial genetic component without significant shared environmental effects. Specific genetic markers, such as the homozygous long-long (LL) genotype of the gene promoter polymorphism (), have been associated with increased risk for melancholic depression, conferring an of 1.7 relative to other genotypes. Environmental factors, particularly early life adversity like childhood maltreatment, interact with genetic predispositions to elevate risk via epigenetic mechanisms that alter without changing DNA sequences. Models of gene-environment interactions, such as those involving polymorphisms and stressful events, demonstrate how can amplify genetic liability, leading to persistent HPA axis dysregulation in adulthood. Neuroendocrine dysregulation is a hallmark, characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels, particularly in melancholic patients. The dexamethasone suppression test (DST), developed in the early 1980s, reveals nonsuppression of cortisol in up to 50-60% of individuals with melancholia, validating HPA overactivity as a biomarker specific to this subtype compared to non-endogenous depressions. Brain imaging studies highlight structural and functional abnormalities, including reduced volume in the prefrontal cortex and hypermetabolism in the subgenual cingulate cortex among melancholic patients. Functional MRI and positron emission tomography findings localize decreased activity in the ventral prefrontal cortex, correlating with symptom severity and implicating limbic-prefrontal circuit disruptions. The monoamine hypothesis posits deficits in key neurotransmitters, with particular emphasis on norepinephrine in melancholic depression, where reduced brain norepinephrine release has been observed in treatment-naive patients, contributing to and . These noradrenergic impairments align with the subtype's clinical profile, as evidenced by poorer response to selective serotonin reuptake inhibitors (SSRIs) and superior outcomes with tricyclic antidepressants (TCAs), which enhance noradrenergic transmission more robustly.

Treatment Modalities

Treatment of melancholic depression prioritizes biological interventions due to its endogenous features and robust response to agents targeting monoaminergic and neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis dysregulation observed in affected patients. Pharmacotherapy remains the cornerstone, with tricyclic antidepressants (TCAs) like demonstrating superior efficacy over selective serotonin reuptake inhibitors (SSRIs) in achieving remission, particularly in severe cases characterized by melancholic features. Meta-analyses confirm that TCAs yield higher response rates in melancholic unipolar depression compared to SSRIs, which show comparable outcomes to serotonin-norepinephrine reuptake inhibitors (SNRIs) but inferior remission odds overall. SNRIs, such as , also exhibit advantages over SSRIs for melancholic subtypes, with the (APA) guidelines recommending them as first- or second-line options based on tolerability and prior response. For cases with atypical features overlapping melancholia, inhibitors (MAOIs) like are effective, outperforming tricyclics in meta-analyses of while requiring strict dietary monitoring to mitigate hypertensive risks. Electroconvulsive therapy (ECT) serves as a first-line treatment for severe, treatment-resistant melancholic depression, achieving remission rates of 70-90% in acute courses. The ECT Review Group established that bilateral electrode placement yields greater symptom reduction than unilateral, particularly in endogenous depressions, though unilateral offers fewer cognitive side effects when dosed appropriately. Adjunctive therapies enhance outcomes in resistant or recurrent cases. infusions provide rapid antidepressant effects in treatment-resistant melancholic depression, with post-2010 trials showing sustained symptom relief after repeated dosing, comparable to ECT in nonpsychotic patients. Lithium augmentation effectively prevents relapse in recurrent unipolar depression when added to antidepressants, reducing recurrence risk by up to 50% in controlled trials. Psychotherapeutic approaches like (CBT) demonstrate limited standalone efficacy in melancholic depression, with slower initial improvement and lower response rates compared to alone. CBT is most beneficial as an adjunct to antidepressants, aiding residual anxiety and cognitive processing without addressing core psychomotor features. Emerging options include (), which targets the with high-frequency pulses and received FDA approval in 2008 for major depression, including resistant forms with melancholic traits. Clinical trials support its role in non-invasive symptom reduction, with remission rates of 30-50% in outpatient settings.

Prevalence and Long-Term Outcomes

Melancholic depression, characterized as a subtype of major depressive disorder with specific features under DSM-5 criteria, accounts for approximately 25-30% of all cases of major depression globally. This prevalence is derived from clinical and epidemiological assessments, where pure melancholic presentations are less common than mixed forms, but the subtype remains a significant proportion of depressive episodes. In specialized settings, such as inpatient populations with major depressive disorder, the rate of melancholic features rises substantially, reaching up to 60% in some multicenter studies across Europe. Among older adults, melancholic depression appears more frequent due to its association with severe, endogenous forms, though exact figures vary; community-based estimates for major depression in this group range from 13% to 31%, with melancholic subtypes contributing disproportionately to treatment-resistant cases. Demographic patterns reveal a higher incidence of melancholic depression in females, aligning with the overall 2:1 female-to-male ratio observed in , particularly peaking in midlife (ages 40-49). This gender disparity equalizes with advancing age, as postmenopausal factors and somatic comorbidities influence presentation. The subtype is also elevated in individuals with , where melancholic features often mark depressive phases, potentially affecting up to 40% of such episodes based on diagnostic overlap and symptom profiles in cohorts. Long-term outcomes for melancholic depression are generally poorer than for non-melancholic forms, with reduced responsiveness to interventions (typically 10-20% response rate compared to 30% in broader depression trials) and heightened chronicity. Recurrence rates are elevated, with studies indicating around 50% of cases relapsing within two years, as evidenced in large-scale surveys like the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Compared to non-melancholic depression, melancholic patients spend a of 17% of follow-up time in depressive states or on antidepressants, underscoring a more persistent course. Additionally, recent studies as of 2025 indicate that melancholic depression is associated with an elevated risk of heart disease compared to other depressive subtypes. Key prognostic factors include age of onset, where early-onset melancholic depression (before age 60) correlates with slower treatment responses, greater residual symptoms, and increased illness burden over time. In contrast, patients responding to (ECT) exhibit improved long-term trajectories, with remission rates exceeding 80% in severe cases and better five-year outcomes (up to 80% sustained remission) relative to alone (around 50%). The societal impact of melancholic depression includes elevated healthcare utilization, driven by frequent hospitalizations, treatment resistance, and comorbid conditions, contributing to higher overall costs in mental health systems. Suicide risk is markedly increased, with attempt rates around 19% in melancholic cohorts—approximately 2-3 times higher than in non-melancholic depression—exacerbating mortality and resource demands.

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