From Black Bile to the Brain: Tracing Melancholia and Depression

By Evan Balmuth

In the framework of Mental Health Awareness Month, Evan Balmuth reports from the Max Planck Institute for Experimental Medicine in Göttingen on the history of depression, highlighting the contributions of key physicians and scientists since ancient times.

Depression, as part of the human condition, has been traced over 2.5 millennia, and has gone by many names; melancholia is one of its best-known appellations. Furthermore, the illness has been defined in various conditions. Indeed, nearly all cultures known to us through history have identified some mental state resembling depression, although it has not always been considered a disease. Many have interpreted the symptoms as sinners’ punishment; others have viewed them as honorable qualities of a prophet. Sorting through such conceptualizations of melancholia and depression, we can trace the progression from antiquity to our current understanding.

Drawing back thousands of years, the very word “melancholia” (transliterated from the ancient Greek µέλαινα χολή, literally “black bile”) has its roots in Hippocratic medicine. This term originates from humoral theory, the predominant medical ideology from antiquity through the 19th century. According to generations of humoral practitioners, beginning with the Greek physician Hippocrates around 400 BCE, an excess of black bile was implicated in the melancholic temperament and related to depressive symptoms. Contemporaneously, Plato noted that black bile lends itself to “infinite varieties” of emotional distress and disorder; Celsus, the esteemed Roman writer of De Medicina libri octo, stated 400 years later that depressive symptoms were caused by black bile; and Galen, a highly influential Greek physician of the second century CE, suggested a theory of unbalanced “non-natural” elements responsible for depressive symptoms in parallel to humoral theory. Treatments in antiquity for such an ailment were predominated by bloodletting, purging, and exercise.

Moving into the Medieval Period, humoral etiologies for melancholia spread throughout the ancient world. Alexander of Tralles, a sixth century Byzantine academic compiler, propagated notions of excessive black bile as a cause of melancholia; Avicenna, a Persian medical writer, perpetuated similar humoral beliefs in his Canon of Medicine around 1000; and Constantinus Africanus, a prolific Arabic-to-Latin translator, made such theories accessible to Latin audiences again with the translation of De Melancholia from Arabic in the 11th century. Varying religious notions of melancholia also began to propagate at this time with the rise of Christianity; predominantly, God and the Devil represented ultimate causes of mental disorder, while the Bible described prophetic traits associated with melancholia. Of note, treatments to this point had still not changed perceivably from antiquity, although religious interventions such as prayer and exorcism became more commonplace.

Influential physicians in the Renaissance Period, such as Timothie Bright in Britain and Felix Platter in Switzerland, insisted upon humoral etiologies while accommodating familiar notions of sin and the supernatural through the 16th century. It was not until the 17th century that humoral theories received their first major blows in favor of modernized physiological etiologies. One important contributor was Thomas Willis, a 17th century English physician who proposed theories of spleen malfunction, and even pathological brain morphology. Yet, despite this impressive shift toward modern physiology in explaining melancholia, Willis’ and most other physicians’ treatments remained grounded in humoral theory.

The 19th century brought perhaps the most significant theoretical progress toward today’s treatments and understanding of depression. One key figure was the French physician Philippe Pinel, who influentially criticized humoral treatments for melancholia in favor of the psychological, with a goal of “interrupting the chain of […] gloomy ideas.” Another was Benjamin Rush, an American founding father nicknamed the “Father of American Psychiatry,” who stated that “all the operations in the mind are the effects of motions previously excited in the brain …” Most importantly, Rush considered mental illnesses to fall under the same category as other physical illnesses, with a physiological cause. Nonetheless, limited by the slow progress of medicine still grounded in ancient theories, his treatments remained dominated by the traditional bloodletting and purging. Lastly, two English psychiatrists, Daniel Tuke and John Bucknill, emphasized neurological causes of depression and promoted novel psychological treatments – along with opium for acute cases ­– in their 1858 Manual of Psychological Medicine.

In the 20th century, definitions and treatments of depression finally began to resemble those accepted today. Emil Kraepelin, a German psychiatrist, conducted some of the first longitudinal studies of mental patients and enumerated different forms of melancholia while proposing underlying neuropathological bases; Sigmund Freud proposed explanations of melancholia in terms of sexual development and grieving, and his theories inspired psychoanalytic therapies that remain prominent today. Diagnostics became standardized through clinical texts, with a foundation in the American Psychiatric Association’s first Diagnostic and Statistical Manual of Mental Disorders (the DSM-I) published in 1952. This first edition described three types of depression – manic depressive reaction, psychotic depressive reaction, and involutional melancholia – while defining cardinal symptoms of each. Further editions of the DSM have been published since, appended with revisions and additional types of depression. Over the last century, biological perspectives of depression have also come to the forefront of our understanding with the development of novel imaging technologies such as the MRI. Structurally, brain regions including the prefrontal cortex and the limbic system were implicated in unbalanced neuronal activity; and molecularly, neurotransmitter theories propagated as inter-cellular signaling became the target of novel drugs. Lastly, in terms of depression treatment, three general categories blossomed: talk therapy, including the Freudian psychoanalytic therapy as well as cognitive-behavioral therapy, became standard; pharmaceuticals were developed, aiming to restore neurotransmitter balances; and alternative therapies, such as electroconvulsive therapy, have emerged continuously since the 1930s.

Today, we know more than ever before about depression and how to treat it. The DSM-V recognizes five main types of depression, each with sub-categories. Our understanding of its biological underpinnings is advancing rapidly, with developing technologies for imaging in humans and translational studies in animal models; moreover, genetic correlates of depression are being uncovered in ongoing studies. New classes of antidepressants are developed regularly with improving efficacies, alongside novel alternative treatments such as transcranial magnetic stimulation. Undoubtedly, we are living in a time of unprecedented innovation in psychiatric medicine and research.

In conclusion, two important lessons can be learned from the history of melancholia and depression. First, depression has persisted as a tangible, physical illness described in various cultures around the world since antiquity; and second, despite thousands of years of progress, we still know relatively little about its causes and mechanisms. Indeed, one third of patients do not respond to treatments even today. Though we appear to be on the right track, it is important not to overestimate our knowledge on the subject, and to remain precautionary regarding treatments that alter our sensitive neurochemistry. Nevertheless, significant progress has been made from the theories and treatments of antiquity, as our focus has shifted from black bile to the brain.

Author information

Evan Balmuth is a visiting Neuroscience Fellow in the Clinical Neuroscience Laboratory at the Max Planck Institute for Experimental Medicine in Göttingen. He can be contacted at .


  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders (5thed.). Arlington, VA: American Psychiatric Publishing, 2013.
  • CONVERGE Consortium. “Sparse whole-genome sequencing identifies two loci for major depressive disorder.” Nature vol. 523 (2015): 588-591.
  • Esquirol, Jean-Étienne D. Des Maladies Mentales. Paris: Libraire de l’Académie Royale de Médecine, 1838.
  • Jackson, Stanley W. Melancholia and Depression: From Hippocratic Times to Modern Times. Yale University Press, 1986.
  • Lloyd, G.E.R. “Nature of Man.” Hippocratic Writings. London: Penguin Books, 1983.
  • Mendels, Joseph. Concepts of Depression. New York: Wiley, 1970.
  • National Institute of Mental Health. “Depression.”, 2016.
  • Ricq, Emily. “Down, but not out: Developments in depression research.” Science in the News. Harvard University: The Graduate School of Arts and Sciences, 2015.
  • Toohey, Peter. "Acedia in Late Classical Antiquity." Illinois Classical Studies (1990): 339-352.
  • Teaser Image: Pablo Picasso, Melancholy Woman, 1902 Source: Detroit Institute of Arts. Painting – oil on canvas.

Other Interesting Articles

Go to Editor View