Conceptualizations of Major Depressive Disorder (Melancholia) Throughout History<br />Daniel Fishman<br />Fielding Graduat...
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History
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Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History

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A history of the evolution of Major Depressive Disorder as a diagnosis

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Conceptualizations Of Major Depressive Disorder (Melancholia) Throughout History

  1. 1. Conceptualizations of Major Depressive Disorder (Melancholia) Throughout History<br />Daniel Fishman<br />Fielding Graduate University<br />Conceptualizations of Major Depressive Disorder (Melancholia) Throughout History<br />Attempts to understand, qualify, discern etiologies and establish treatments for disorders both physical and mental originate in the distant past. Progress in our understanding has proceeded at varying rates throughout history. One of the first disorders to be recognized (albeit under a variety of names other than those in use today) is Major Depressive Disorder (MDD). Written accounts of a distinct collection of symptoms resembling MDD can be found in the writings of the ancient Greek philosopher Hippocrates (Akiskal & Akiskal, 2007); however, suggestive accounts can be found in even earlier sources such as papyri from ancient Egypt (Nasser, 1987) and the Old Testament (Ben-Noun, 2004; Davison, 2006; Huisman, 2007; Kapusta, 1977; Stein, 2010). This paper will examine the diagnosis, etiology, and treatment of MDD and its progenitor disorders throughout history. We will begin with literary descriptions found in Egyptian papyri circa 1550 BCE as well as the Old Testament. We will then trace the evolution and development of MDD through Greece, Rome, the Middle Ages, the Enlightenment and into modern day conceptualizations.<br />Pre-Classical Descriptions<br />Over the past 200 years or so many papyri from ancient Egypt have been discovered and translated. Most significant to psychology and psychiatry are those referred to as the Ebers and the Edwin Smith papyri authored circa 1550 BCE. Interestingly, the Edwin Smith papyrus contains the first anatomical account of the brain being enclosed in a membrane with patterned convulsions along its hemispheres (Nasser, 1987). The ancient Egyptians recognized that the brain played a role in consciousness and that disorders related to mind could arise without supernatural cause. However, they also subscribed to belief in supernatural causes and cures. They recognized many disorders, such as the Greek concept of Hysteria, Alcoholism, and one referred to simply as "Sadness.” Sadness is described in detail in the papyri as illustrated by the case of Satri Khamois: "He huddled up in his clothes and lay, not knowing where he was, his wife inserted her hand under his clothes and said 'no fever in your chest, it is the sadness of the heart" (Nasser, 1987, p. 421). Satri is even quoted describing his own illness in the papyri as, "I feel my limbs heavy, I no longer know my own body, my eyes decline, my ears harden, my voice is speechless. Should the Master Physician come to me? My heart is not revived by their medicine" (Nasser, 1987 p.421). These quotes do not present enough evidence of symptomatology to warrant the diagnosis of MDD by today's standards but the absence of proof is not proof of absence. The story of Satri calls to mind a clear picture of one who is indeed racked by a deep sense of sadness, perhaps full blown depression. As is often the case in ancient society the individual entrusted with the care of people suffering from sadness was often the sorcerer or high priest. Although there were various other aspects of treatment, it is interesting to note that one of the mainstays of treatment involved the afflicted "confessing" secrets to the sorcerer, an act akin to psychotherapy.<br /> Some of the earliest references to MDD-like symptoms can be found in Old Testament accounts. Importantly, these accounts can be examined as literary descriptions (with established authorship date ranges) outside of their religious context. Read in this light, they become ancient accounts of human behavior and society. As Ben-Noun (2004) and Davison (2006) elegantly describe, one of the earliest such accounts can be found in the writings attributed to King David, the second King of Israel thought to have lived between 1040 and 970 BCE. In Psalm 21 David writes, "My soul in distress" (Psalm 31. 8). In Psalm 13 he writes of "having agony in my heart daily" (Psalm 13. 3). In Psalms 41 and 25 respectively, he pleads "Heal my soul; because I sinned" (Psalm 41. 5), and "The troubles of my heart are widened; bring thou me out of my distress" (Psalm 25. 17). These are clearly the words of someone experiencing severe psychological distress, but are they indicating something that may be MDD? By continuing to read through the works attributed to David, one can find examples indicative of: a depressed mood - "a broken and depressed heart" (Psalm 51. 19); weight loss - "My knees are weak through fasting/and my flesh failed of fatness" (Psalm 109. 24); insomnia with profuse crying - "All the night make I my bed to swim/I water my couch with my tears" (Psalm 6. 7); psychomotor disturbances - "Fearfulness and trembling are come upon me" (Psalm 55. 6), "My heart is shivering within me" (Psalm 55. 5), and 'Like a deaf man I would not hear and like a mute I would not speak" (Psalm 38. 14); fatigue - "My strength failed because of mine iniquity" (Psalm 31. 11); feelings of worthlessness - "But I am a worm, and no man/a disgrace of men, and despised of the people" (Psalm 22. 7) and "I am forgotten as a dead man out of mine mind/I am like a lost tool" (Psalm 31. 13); and finally recurrent fear and thoughts of death - "has brought me into the dust of the earth to death" (Psalm 22. 16), "the terrible fears of death had fallen upon me" (Psalm 55. 5), "The sorrows of death compassed me" (Psalm 18. 5) and "The mines of death preceded me" (Psalm 18. 6). By our current standards feelings and thoughts such as those contained in the above passages would be highly suggestive of MDD. In King David's time there was no formal concept of mental illness. Looking back, however, the pictures drawn by King David’s own writings demonstrate a compelling argument for the diagnosis.<br /> Another example of biblical period depictions of MDD can be found in the Book of Job. The Book of Job is perhaps best described as a wisdom book. Written between 500 and 300 BCE, it is one of several compiled by the ancient sages of Israel and designed to present professionals a realistic description and approach to the problems of life (Kapusta & Frank, 1977). Although basing their final diagnosis on criteria not considered the standard today, Kapusta and Frank, painstakingly outline Job's symptoms and their correlation to established MDD symptomatology. Moreover, Kapusta and Frank point out that the authors of the Book of Job drew connections more than 2,000 years ago that modern thought has only just rediscovered such as the connection between somatic complaints and depression. Interestingly, beyond description of symptoms, the authors of the Book of Job offer insights into appropriate treatment modalities that closely resemble those in use today, some of which we enjoy believing we invented not more than 50 to 100 years ago! <br />Classical Period Descriptions<br />Although, as just shown, descriptions of depression can be found in earlier works, the earliest written record of a diagnostic entity close to MDD is Hippocrates description of melancholia. Depression as we use it today is a relatively new usage of the term. Historically, melancholia has been the more widely applied appellation. Under today’s nosology, as prescribed by the Diagnostic and Statistical Manual of Mental Disorders IV Text Revision (DSM-IVTR), melancholy is a subset of MDD; however, in many parts of the world MDD can still be seen referred to as melancholia (Akiskal & Akiskal, 2007; Davison, 2006; Sullivan, 2008; Zilboorg, 1967). The term melancholia is reflective of the etiological conceptualization of Hippocrates' time based on the philosophy of the four humors. Hippocrates believed that human moods, emotions and behaviors were caused by the interaction of four bodily fluids, or humors: blood, yellow bile, black bile and phlegm. The Roman physician Galen expanded on Hippocrates' work and asserted that an individual's personality is derived from a mixing of these fluids. The word "temperament" is in fact derived from the Latin "temperare" or "to mix" (Sullivan, 2008; Zilboorg, 1967). Within this conceptual framework pathology is thought to arise from imbalances in the humors. Melancholia is Greek for "black bile," its use is meant to reflect the perceived over abundance of black bile present in those afflicted with depression. Although we no longer subscribe to the four humors philosophy, the symptomatology Hippocrates ascribed to melancholia exquisitely reflects that observed in MDD today. As described by Akiskal and Akiskal (2007), Hippocrates wrote "A woman of Thasos… as a result of justified grief became morose, and although she did not take to her bed, she suffered from insomnia, loss of appetite … she complained of fears and talked much; she showed despondency and …talked at random and used foul language… many intense and continuous pains… she leapt up and could not be restrained…" (p.1). This woman today would likely receive a diagnosis of MDD.<br /> A further example of classical depictions of MDD can be found in descriptions of Marcus Tullius Cicero (106–43 BC), the great Roman orator. A 2007 study by Evans examining Cicero's letters to friends and family was able to discern symptoms of MDD written in Cicero's own hand. Evans utilized DSM-IV-TR criteria and extensive review of the corpus of Cicero's personal letters to establish a diagnosis. He outlines three episodes of depression, but focuses on the episode following the death of Tullia, Cicero's daughter. Cicero's love for Tullia is extreme to the point of possible narcissistic fascination. When she dies after giving birth in his home, Cicero falls into a deep depression. As with his earlier bouts, he chronicles and attempts to cope with his feelings in letters to friends. On one occasion, for example, he writes to his friend Atticus stating, "When I am alone all my conversation is with my books, but it is interrupted by fits of weeping, against which I struggle as best I can. But so far it is an unequal fight" (Evans, 2007 p.86). The complete body of Cicero's letters allowed Evans to establish that over a period of four months following Tullia's death Cicero experienced symptoms of depressed mood almost every day for most of the day, diminished interest in previously pleasurable activities, insomnia, excessive guilt, difficulty concentrating, recurrent thoughts of death, suicidal ideation, and irritability resulting in significant distress and functional impairment. This is a clear depiction of MDD. Although Cicero was not diagnosed at the time, friends and relatives did recognize that he was disturbed beyond normal grief. Notably, his friends connected this disturbance to Tullia's death and processes within Cicero himself, not to outside forces such as demons or devils (Evans, 2007). In so doing his friends expressed tacit acknowledgment of a diseased mental state within the individual. As will unfortunately be demonstrated shortly by its absence in the Middle Ages, even without a diagnosis, this acknowledgement is a significant step in establishing MDD as a mental illness. Furthermore, the presence of the same collection of symptoms that we identify today as MDD without the presence of any of our current theoretical models as support is valuable empirical evidence for the validity of the diagnosis.<br />Before moving on to Byzantium and the Middle Ages, a final note on classical period conceptualizations of MDD merits mention. It has often been said that the there is a thin line between genius and madness. For instance, today we often note that so many of our great thinkers and artists were also afflicted with troubling mental illness. Van Gogh likely suffered from a mood disorder, perhaps on the bipolar spectrum. More modern examples can be found in individuals such as River Phoenix, Michael Jackson, Brittney Spears, and many others. This connection between exceptional mental gifts and crippling illness was observed even in ancient times. The Aristotelian tradition, for instance, maintains that the condition of melancholy was often accompanied by a degree of brilliance that set the individual apart from the general population (Sullivan, 2008). Of course observed correlation cannot imply causation and one can as easily argue that truly intelligent people perceive the true horror of existence and therefore become depressed rather than assume that the biological and psychological underpinnings of depression can simultaneously subserve mechanisms of exceptional intelligence.<br /> Conceptualizations from the Middle Ages: Western Europe, Byzantium, and the Islamic World<br />Medieval Western Society<br />In the medieval period Rome split into the Western and Eastern Empires. The Western Roman Empire evolved into medieval Western Europe, while the Eastern Roman Empire morphed into the Byzantine Empire with its capitol in Constantinople, modern day Istanbul. Although there was trade and cultural exchange between the two geographical regions, in large part they developed their own cultures. On the whole the philosophy of the four humors held sway in the known world until the 16th and 17th centuries (Davison, 2006). However, with onset of the Middle Ages, something of a split in the history of mental illness can be seen. On one side there is the Western/European world and it's almost complete return to demonological or supernatural explanations of psychopathology. On the other is the Byzantine and Islamic world which, although developing demonological constructs, also preserved the knowledge of the classical period until their rediscoveries in the Renaissance and Enlightenment. <br /> Western Society in the Middle Ages receded into philosophies espousing supernatural origins of psychopathology. Individuals were routinely thought to be possessed and mass epidemics of mania became frequent at times (Millon, 2004). Additionally, lean times resulting from famine and pestilence resulted in wandering indigent populations that appeared haggard, distraught, and confused. Following an all too often displayed human tendency to distance ourselves from a perceived threat, such individuals were thought to be possessed or cursed by G-d. In this fashion such dysfunctional and frightening people could be distanced from the "healthy" self. Furthermore, by assigning supernatural causes such as demonic possession or curses from G-d, people obtained a sense of control over these frightening symptoms. After all, in order to be possessed by a demon an individual must have had a kernel of evil within him/her and if one is cursed by an ever-loving G-d one must have surely done something sinful or horrific to deserve it. Therefore, by living a "good" life people could relieve themselves of the worry of developing such symptoms. Unfortunately, this line of thought lead to witch hunts, burnings, inquisitions, and other harsh punishments of some of the weakest and most vulnerable among us. <br /> In respect to MDD, the Christian church led by figures such as Aurelius Augustine (perhaps the greatest and most widely held authority in medieval Europe) developed the concept of accidie (acedia). One of the famed seven deadly sins, the manifestations of acedia were similar in many respects to traditional views of melancholia. The primary symptomatic differences were an emphasis on sloth and apathy in acedia when compared to classical melancholia. Additionally, congruent with the prevailing etiological theory of the day, acedia was thought to be caused by demonic possession resulting from sin. As acedia derived from sin, the proffered curative measures suggested included confession or manual labor as penance. Unfortunately, when these failed to alleviate the symptoms individuals, especially women, were often burned as witches (Davison, 2006; Millon, 2004). <br />Despite the dominant oppressive philosophical climate of medieval Europe, there were still individuals who sought to explore classical works. Albert Magnus, in the 13th century, was the first European to undertake the daunting task of reviewing all of Aristotle's known works. Foreshadowing those who came after him, Magnus emphasized logical inquiry as a means to truth. Another philosopher and contemporary of Magnus, Roger Bacon, emphasized systematic observation and mathematical constructs to reach truth. Together Magnus and Bacon provided grounding for the two pillars that came to serve as the foundation for all scientific and philosophical exploration to follow, reasoned logical argumentation and careful empirical observation. A third, and equally essential individual to the progress of philosophical investigation, was Thomas Aquinas. Also of the 13th century, Aquinas helped to establish Scholasticism. In so doing Aquinas provided a path for the reconciliation of faith and reason. Unfortunately, this reconciliation would take centuries to reach the wide and disparate parts of society only finding fruition in the Renaissance (Millon, 2004).<br /> Byzantium<br />Medieval Byzantine physicians maintained a degree of rationality in their approaches and resisted somewhat the fall into supernatural explanations that became rampant in the medieval period. Byzantine physicians were fluent in Greek and Latin and made efforts to catalogue and maintain the knowledge from that period, including the conceptualizations of MDD. In the course of their studies they made note of an alleged supernatural phenomenon, Lycanthropy. True to their cause, they attempted a rational exploration of the subject and concluded that it may simply be an example of depression (Poulakou-Rebelakou, Tsiamis, Panteleakos & Ploumpidis, 2009).<br /> Lycanthropy, or the transmogrification of a human - in both form and manner - into a wolf, has been described since antiquity. It forms the basis of many a rich and engaging myth, for example, the Greek myth of Lycaon, king of Arcadia as related by Pausanias, Apollodorus, or Pliny. Somewhat surprisingly, even to this day some patients report the belief that they can take the form of a wolf or other animal. In classical descriptions of such cases a human acquires the physical characteristics of a wolf, roams the night, frequents cemeteries, and feasts on human flesh. Although ancient Greek and Roman medical texts describe this phenomenon they do not contain references to any actual diagnosed cases or treatment. The descriptions of the disorder, however, are preserved and well described by Byzantine physicians from various periods ranging from Oribasius in the fourth century CE to Joannes Actuarious in the fourteenth century CE. According to these descriptions Lycanthropy is characterized by pale, dry or wan appearance, hollow (sunken) eyes, lack of tears, poor eyesight, scratches or ulcerations on the lower limbs and of course, frequenting cemeteries all night long (Poulakou-Rebelakou et al., 2009). These symptoms are grossly non-specific and may be due to a variety of causes none of which involve supernatural transmogrification. What is of note, is that physicians from as early as the fourth century CE, citing the work of Hippocrates and Aristotle, maintain that this disorder is not supernatural but a manifestation of extreme melancholia. These authors go so far as to prescribe treatment methods used for melancholia to treat lycanthropy, and in all honesty, who doesn't feel better after a good bloodletting? Humor aside, it is not difficult to imagine such an individual and through our modern day lens attribute his appearance, demeanor, and behavior to something similar to extreme grief.<br />Medieval Islamic & Jewish Thought<br />Concurrent with the Byzantine physicians there were Muslim and Jewish physicians who sought to maintain and even progress classical thought. Rhazes (860-930) wrote extensively on medical and psychological subjects. While subscribing to the philosophy of the four humors, he advocated the construction of a rational and empirical approach to psychopathology. Additionally, Rhazes described social influences on the psychology of the individual as well as why individuals give themselves over to quick fix solutions absent sound supporting evidence. Perhaps most importantly, Rhazes advocated for mental illness as a separate category of disease, one that required special and more humane treatment. Also living in the late ninth and early tenth century, Unhammad (870 - 925) was one of the first to produce a classification of mental disorders and Ahmed ibn Sahi al-Balkhi (850-934), was the first to suggest that psychological pathology could produce physical symptoms ADDIN ZOTERO_ITEM {"citationID":"1p70dcdvs3","citationItems":[{"uri":["http://zotero.org/users/178241/items/UW5EMKQP"]}]} (Adamson & Taylor, 2005). Slightly later in the late tenth and early eleventh century, Avicenna wrote the most complete compendium of medical and psychological knowledge of the era. Similar to Ahmed ibn Sahi al-Balkhi, Avicenna also emphasized the connection between intense emotions and physiological states. Additionally, with a remarkable level of insight Avicenna suggested that the frontal areas of the brain mediated common sense and reasoning. This assertion is extraordinarily accurate given the technological level of his day. Echoing Aquinas and perhaps one of the most notable physicians of his day, Maimonides in the late twelfth century attempted to reconcile faith with science and further legitimize rational and humane approaches to pathology (Millon, 2004). <br /> The medieval period is also often referred to as the Dark Ages. The appellation was first employed and intended to convey the apparent paucity of documentation remaining from the era thereby causing it to be difficult to envision in hindsight (i.e. dark). Having moved into common use, the term has also taken on the connotation of a period of time reflexively hostile to philosophies that differed from established dogma. Thus, although many individuals sought to maintain ancient knowledge and emphasize empirical methodology, we have sad tales like that of Galileo and others who sought to further our knowledge only to be ostracized. This repressive orthodoxy remained in place for almost 1600 years, with thinkers and philosophers only finding relief within the Renaissance. Along with its new emphasis on the rediscovery of ancient knowledge, the Renaissance encouraged new thought and exploration. This exploration was pushed even farther with the Enlightenment’s emphasis on reason and thought. It is in these periods that we next find advancement in many fields including mental illness. <br />The Sixteenth through Nineteenth Centuries<br />The sixteenth and seventeenth centuries saw significant advances in understandings of mental illness, for example, Paracelsus (1493 - 1541) was one of the first to question both the supernatural dogma and humoral theories governing mental illness. With respect to MDD, Timothie Bright (1550- 1615) was the first to distinguish between melancholia with and without a cause, while Andre du Laurens (1560-1609) brought focus to melancholia associated with delusions especially those with nihilistic attributes. Potentially, one of the most significant works of the period was The Anatomy of Melancholy by Robert Burton. Offering both vivid and elegant descriptions, Burton's text became extremely popular. Although Burton ultimately subscribed to the humoral theory of melancholia, he expanded the theory to include possible behavioral and biological routes all of which culminated in a final common pathway of excess black bile. Burton's work was one of the final great works to offer the humoral theory. As the seventeenth century drew to a close the humoral theory was increasingly questioned. In its place individuals such as Thomas Willis, the famed anatomist, offered theories emphasizing chemical intoxications as etiologies (Davison, 2006).<br />The eighteenth century introduced hemodynamic etiologies of depressive states. Individuals such as Pitcairn, Boerhaave, and Richard Mead offered similar explanations invoking a thickening of blood with concomitant slowing of circulation within the brain. This sluggish circulation, in turn, reduced the flow of “an extremely subtile fluid of the nerves, commonly called animal spirits” (Davison, 2006 p. 116). The eighteenth century also saw the personal testaments of prominent individuals afflicted with melancholia such as Dr. Samuel Johnson (1709–1784) and William Cowper (1831–1800) (Davison, 2006).<br />By the early nineteenth century, the term melancholia began to lose favor. Theorists at the time thought the term was applied to broadly, encompassing both pathological and well states. Thus a push towards a new nosology began, resulting in a plethora of nomenclature for melancholia. The quantity of classification systems became so large as to almost lose utility. As a result there were some individuals, such as Griesinger, who returned to the unitary psychosis hypothesis. This hypothesis envisioned all forms of insanity as different stages of a single morbid process within the brain (Davison, 2006). Although appealing in its simplicity, the great variety of histories offered by patients, as well as the large variety of symptoms present in various types of mental illness, makes such an assertion difficult to support. However, as will be discussed in more detail shortly, it is important to note that the current diathesis-stress model with its concept of a spectrum ranging from normality to pathology does in some ways incorporate aspects of the unitary psychosis hypothesis.<br />The Twentieth Century<br />The twentieth century saw an explosion of scientific process and knowledge across almost all fields of study including mental illness. The advent of new methodologies and technologies allowed for investigations previously thought impossible. The empiric data derived from these investigations drove new theoretical work, which in turn drove new observational and experimental work. New conceptual frameworks were constructed alongside established theories that were, in turn, revised and expanded. For example, Emil Kraepelin, who began his work in the late nineteenth century, emphasized careful observation and longitudinal studies of mental illness thereby contributing immensely to our understanding. Kraepelin was able to differentiate between schizophrenia (then dementia praecox) and mood disorders. Additionally, he was perhaps the first to use the term “depressive states” in reference to types of melancholia. He also popularized the idea of exogenous versus endogenous types of depression ADDIN ZOTERO_ITEM {"citationID":"23s9sbfi4l","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/4DTBHTKS"]},{"label":"page","uri":["http://zotero.org/users/178241/items/736XMT4M"]},{"label":"page","uri":["http://zotero.org/users/178241/items/UWWXKEDE"]},{"label":"page","uri":["http://zotero.org/users/178241/items/EQDQ4JKQ"]}]} (Davison, 2006; Millon, 2004; Sullivan, 2008; Zilboorg, 1967). The variety of theoretical and methodological approaches that flowered in the twentieth century led to parallel developments of competing and complimentary theories. What follows is a brief description of some of the more impactful theories.<br />Psychoanalytic theories<br />Sigmund Freud (1856-1939) developed his theory of psychoanalysis in the early part of the twentieth century; as such, it was heavily influenced by the intellectual and scientific climate of the day. Freud wrote that he first sought a biological explanation of psychopathology but owing to the inadequate technology of the time he abandoned that avenue of research in favor of a more philosophical and psychological approach ADDIN ZOTERO_ITEM {"citationID":"damr2fnck","citationItems":[{"uri":["http://zotero.org/users/178241/items/NR3AUSTA"]}]} (Tallis, 2002). Studies of the unconscious conducted by the likes of Charcot and Janet were popular at the time. Freud drew upon this work and his clinical observations to formulate his theory of unconscious competing psychic forces. In Freud’s view these forces ultimately provided more influence on thought and behavior than conscious forces. Psychoanalysis’ classic triad of Id, Ego, and Superego is the ultimate encapsulation of this concept. The impulsive and instinctual id is forever in conflict with the demanding superego, thereby forcing the ego to eternally mediate between the demands of instinctual drives and the demands of the external world. Within this construct Freud envisioned depression as the product of the interaction among past events, unconscious desires and conflicting realities. A precipitating event, conceptualized as a loss of a loved object (person, concept, or otherwise) resulted in a psychic conflict. This conflict manifested as an unconscious sense of anger at the self, or anger turned inward, displayed grossly as MDD ADDIN ZOTERO_ITEM {"citationID":"15ctdladun","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/4DTBHTKS"]},{"label":"page","uri":["http://zotero.org/users/178241/items/GZX7CRJB"]},{"label":"page","uri":["http://zotero.org/users/178241/items/B2WGVX3M"]}]} (Davison, 2006; Freud, 1994; Shahar, 2006). More recently the psychodynamic view has evolved to emphasize the role of early life losses, self-esteem, difficulties in managing acute losses and interpersonal relationships ADDIN ZOTERO_ITEM {"citationID":"2inf8idsq0","citationItems":[{"uri":["http://zotero.org/users/178241/items/8PVUFAT2"]}]} (Krishnan, 2010).<br />Adolf Meyer (1866-1950) was a contemporary and colleague of Freud. In some respects he was the most renowned American psychiatrist of his time. Although, he began as a devotee of both Freud and Kraepelin, he eventually broke from both while managing to maintain various aspects of both. Perhaps one of his central contributions to psychology was his emphasis on detailed case histories & consideration of patient’s life circumstance. Meyer maintained that psychopathology was not inherent in the individual, and instead emphasized a psychobiological perspective of depression similar to that expressed today by the diathesis-stress model of illness. He suggested that mental illness was a reaction to current stress through the lens of past maladjustments ADDIN ZOTERO_ITEM {"citationID":"26hp5vsdsq","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/4DTBHTKS"]},{"label":"page","uri":["http://zotero.org/users/178241/items/736XMT4M"]}]} (Davison, 2006; Millon, 2004).<br />Behaviorism<br />In contrast to the many esoteric theories of the time, Behaviorism as developed by John D. Watson (1878-1958) and B.F. Skinner (1904-1990) restricted its scope of inquiry into the directly observable. An individual’s internal thoughts, feelings, and drives were viewed as forever beyond direct observation. Therefore, in an effort to ensure extreme validity, theories and experiments were confined to directly observable phenomena (i.e. behaviors). This theory arose in the context of the early twentieth century American Dream ethos and Ivan Petrovitch Pavlov’s famous experiments detailing classical conditioning (Millon, 2004). Watson rejected Pavlov’s physiological claims and asserted that behavioral learning was sufficient to account for all of Pavlov’s results as well as the complete development of an individual. In one of his more well-known pieces Watson stated: <br />Give me a dozen healthy infants, well-formed, and my own special world to bring them up in and I’ll guarantee to take any one at random and train him to become any type of specialist I might select - doctor, lawyer, artist, merchant chief and, yes, even beggerman and thief, regardless of his talents, penchants, tendencies, abilities, vocations, and race of his ancestors. (2010, p. 104)<br />In this quote Watson is making the remarkable assertion that any individual is capable of becoming anything given the right learning sequence, a stunning rejection of the inherent nature arguments that enjoyed widespread support in parts of Europe at that time. This transatlantic difference in political/social philosophy (Fascism v. Democratic equipotentiality) and associated transatlantic difference in psychological philosophy (Inherent Nature v. environmental interactions and learning) is an interesting demonstration of the reciprocal relationship between scientific theory and the social milieu that spawns it.<br />As a final modification to what is considered pure Behaviorism, Skinner famously adapted the theory to take into account his operant conditioning model as well as Pavlov’s classical conditioning (Millon, 2004). In practice, this did not alter Watson’s assertion as stated in the above quote, but simply provided an alternative method to execute the associated learning. Behaviorism, therefore, accounts for the development of MDD through a series of learned behaviors the individual has acquired via various reinforcement paradigms. Interestingly, while researching the development of depression through the lens of behaviorism, two researchers were astonished to find that some of the outcomes they were observing were not only inconsistent but contrary to behaviorism based predictions. These inconsistencies led to the development of a new behavioristic theory of depression based on an idea called learned helplessness. <br />In the 1980s, Martin Seligman (1942- ) and Steve Maier (circa 1942- ) were conducting experiments into depression with dogs. In the course of their experiments they came to realize that some of their outcomes ran contrary to the predictions of traditional behaviorism. Seligman and Maier created three cohorts of dogs. Dogs in Group 1 were simply harnessed and released. Dogs in groups 2 and 3 were paired together such that each pair consisted of one dog from each group. Each pair was then harnessed and while harnessed received electric shocks. Each dog in the harnessed pair had a lever to press, however, only the lever given to the Group 2 member of the pair would actually discontinue the shock. Dogs from Groups 1 and 2 faired as expected according to behavioral theory. Sadly, group 3 – the group with no control – simply laid down and whined. Group 3 dogs had learned that they could not do anything to escape. <br />Astonishingly, this learned helpless extended to subsequent trials when the Group 3 dogs actually could escape. In these trials each of the dogs from Groups 1, 2 and 3 were placed in a box wherein half the floor could be intermittently electrified. In order to escape a dog simply had to jump over a separating barrier to the other side of the box where the floor was not electrified. Groups 1 and 2 dogs did this, Group 3 dogs did not, opting to instead lie down and whimper again. The helplessness they had learned in the first trial extended to subsequent trials ADDIN ZOTERO_ITEM {"citationID":"2c60e2q1o8","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/EC6TFTUM"]},{"label":"page","uri":["http://zotero.org/users/178241/items/8PTPNIWT"]}]} (Abramson, Seligman, & Teasdale, 1978; Seligman, 1992). On the surface this appeared to be an eerily precise model of depression in humans. Seligman and Maier proposed that having learned some sort of helplessness in the past, an individual would become resigned to it and stop trying to improve their situation, thus becoming depressed. It is important to note here that learned helplessness as discussed so far, refers solely to the observed set of behaviors in the experiments discussed. Although one could easily extend this description to emotional and mental states, it is not necessary to do so for the proposed mechanism to be valid. Surprisingly, however, subsequent experiments with humans demonstrated a somewhat irregular pattern wherein some individuals responded to a given situation with learned helplessness while others did not. This highlighted an additional critical aspect of learned helplessness -- situational attribution -- as a mechanism for generating depression in humans ADDIN ZOTERO_ITEM {"citationID":"1mt6d6qfj","citationItems":[{"uri":["http://zotero.org/users/178241/items/EC6TFTUM"]}]} (Abramson et al., 1978).<br />Fritz Heider (1896-1988) proposed that attributions of causality are not necessarily determined by objective reality. Instead, claims Heider, attributions of causality are made based on an individual's belief as to the cause of events. In this way an individual's perceptions, not objective reality, are the measure of attributions. For example, when individuals receive false reports of success on a task they attribute that success to their own effort and abilities. Conversely, when they receive false reports of failure on a task they attribute this failure to inadequacies external to themselves (Millon, 2004). Although such situational attributions can clearly lead to an individual overestimating their own capabilities, significant disruptions of this attributional bias can have severe consequences. In fact, as Abramson et al. (1978) propose, maladaptive errors of attribution may be the cause of learned helplessness in humans in response to various situations. Furthermore, differences in the tendency and extent of an individual to commit such maladaptive attribution errors result in the observed differences in acquisition of learned helplessness between various individuals across situations. Thus a "normal" individual would more often than not attribute failure and success in such a manner as to maximize his/her perceived control over life, whereas an individual possessing a maladaptive attribution style would attribute failures and successes in a manner that minimizes his/her control over life, thereby generating a sense of learned helplessness in the face of failure. As predicted by Seligman (1992), this sense of learned helplessness can ultimately result in MDD.<br />Cognitive therapy<br />Cognitive therapy shares some similarities with the two major philosophies discussed thus far, psychoanalysis and behaviorism, as well as some marked differences. Cognitive therapists primarily concentrate on the content and process of cognition and its effects on perception. Cognitions may be conscious, that is within awareness, but they also may not be. The presence of a cognition outside of awareness is not quite the same as the traditional psychoanalytic sense of unconscious thoughts or drives. In this context, awareness can best be pictured as a cone of light illuminating the dark, similar to a lighthouse in the dark. Those cognitions that fall within the cone of light are present in awareness, while those that do not are simply outside of awareness. Similar to the ever rotating light of a lighthouse, one's awareness may shift from time to time thereby bringing cognitions into awareness of which one was previously unaware. In this way cognitions are never truly beyond reach. Additionally, a cognition currently outside of awareness may still exert a force on the individual. For instance, automatic thoughts are cognitions that readily and freely occur to individuals, they provide color, character, and commentary to perceptions and cognitions. These thoughts are more often than not outside of direct awareness. For example, if a student receives a B on a test he/she may be disappointed and feel that he/she failed, however, another student may be elated with such a grade ADDIN ZOTERO_ITEM {"citationID":"1rjhv5qu0","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/736XMT4M"]},{"label":"page","uri":["http://zotero.org/users/178241/items/726T85QJ"]}]} (Millon, 2004; Szentagotai, David, Lupu, & Cosman, 2008). Astoundingly, cognitions can also influence perception. Although this is a new and emerging field numerous studies have demonstrated a wide range of biases that may affect perception from prospective priming effects to real-time interpretation affects to retrospective recall and analytical biases ADDIN ZOTERO_ITEM {"citationID":"59p11v4jl","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/DDR6TX48"]},{"label":"page","uri":["http://zotero.org/users/178241/items/ZMD83C8Z"]},{"label":"page","uri":["http://zotero.org/users/178241/items/TZJB55VK"]}]} (Busey & Loftus, 2007; Harley, Carlsen, & Loftus, 2004; Kouider & Dehaene, 2007). Cognitive therapy asserts that individuals develop maladaptive cognitions; therefore, redress of these maladaptive cognitions can remove or alleviate pathology. Thus MDD, as with all other psychopathology, results from maladaptive cognitions and thoughtful reshaping of these cognitions will result in alleviation of symptoms ADDIN ZOTERO_ITEM {"citationID":"162l999ri1","citationItems":[{"uri":["http://zotero.org/users/178241/items/8PVUFAT2"]}]} (Krishnan, 2010).<br />All of the theories discussed above have provided valuable insights into the etiology and treatment of MDD, however arguably one of the most influential contributions to the study and treatment of MDD has been a result of the fusion of behaviorist and cognitivist approaches into cognitive-behavioral theory (CBT). CBT proposes that depression results from both negative automatic thoughts and maladaptive behavior and thought patterns. All of these factors are reinforced in several ways including traditional learning/conditioning mechanisms as well as a confirmatory reinforcement bias. The maladaptive behavior and thought patterns encompass behaviors, perception paradigms, and coping strategies that have been learned over time. While these may have been adaptive in the past, they are now maladaptive and potentially destructive to the individual. This etiologic conceptualization has led CBT to prescribe therapeutic interventions designed to address the negative automatic thoughts, maladaptive behaviors, and maladaptive coping strategies in the here and now. CBT does allow room for the redress of deeply rooted problems but only insofar as they are directly relevant to the problem at hand. Therapy is therefore designed to challenge negative automatic thoughts replacing them with neutral or positive ones while simultaneously helping individuals relearn coping strategies as well as ways of looking at and interacting with the world. Importantly, these strategies are designed to affect change in the present in order to improve the life of the individual rather than correct or heal deep rooted issues ADDIN ZOTERO_ITEM {"citationID":"1oat0j6mov","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/P4QT3KT8"]},{"label":"page","uri":["http://zotero.org/users/178241/items/TVID88ND"]},{"label":"page","uri":["http://zotero.org/users/178241/items/2N42FA6J"]},{"label":"page","uri":["http://zotero.org/users/178241/items/8KXHTWTP"]},{"label":"page","uri":["http://zotero.org/users/178241/items/4R3W9SCD"]},{"label":"page","uri":["http://zotero.org/users/178241/items/8PVUFAT2"]},{"label":"page","uri":["http://zotero.org/users/178241/items/A46S9HM7"]},{"label":"page","uri":["http://zotero.org/users/178241/items/2T5QAFXZ"]}]} (Barlow & Durand, 2008; Bonin, & Moreland, , 2008; Espinoza, & Unutzer, 2008; Katon & Christo, 2008; Katon & Ciechanowski, 2008; Krishnan, 2010; Krishnan, 2010; Moreland & Bonin, 2008).<br />Current theories<br />So far we have divided the story of MDD somewhat arbitrarily into chronological eras, when in actuality the divisions are not that stark. For instance, developments in the description and categorization of MDD have largely been evolutionary and not revolutionary occurring as a slow progression over time. As an alternative example, some trace the origins of cognitive therapy to the Stoics of ancient Greece and Rome, both Plato and Cicero advocated rational discussion as a means of alleviating depression ADDIN ZOTERO_ITEM {"citationID":"7bkuq46mj","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/QTE6SWV5"]},{"label":"page","uri":["http://zotero.org/users/178241/items/736XMT4M"]},{"label":"page","uri":["http://zotero.org/users/178241/items/HXTNUB4T"]}]} (Grim, 2009; Millon, 2004; Robinson, 1997). Additionally, although discoveries progress in a somewhat chronological order with some conceptualizations developing after others, in practice many different modes of therapy are utilized today. Moreover the utility of one theoretical orientation does not preclude the utility or validity of another. Often times the most effective therapy is the one that best fits the patient. Keeping these pluralities in mind, the current accepted conceptualizations and treatments of MDD incorporate aspects from several of the orientations already discussed as well as input from newer developments in physiology and neural networking theory.<br />Classification and Diagnosis<br />Although possessing significant limitations, arguably one of the most noteworthy advancements in current conceptualizations of MDD was the advent of the DSM and its current incarnation the DSM-IV-TR. For want of a better term, the canonization of the DSM provided a uniform set of signs and symptoms for the diagnosis and classification of disorders. It is true that categorical descriptions of entities that appear to exist in spectra as opposed to distinct categorical states can create difficulties. For example, oftentimes a set of signs and symptoms can be found as descriptors for multiple disorders making diagnosis difficult and calling the validity of diagnostic entities into question. Overall, however, the ability to accurately and somewhat uniformly diagnose greatly enhances our ability to treat. Additionally, uniformly established and recognized diagnostic entities facilitate the scientific investigation of phenomena throughout a large and dispersed global population. The upcoming publication of DSM-V offers the opportunity to modify diagnostic characteristics and, indeed, alternative criteria and nosology for mood disorders are being considered ADDIN ZOTERO_ITEM {"citationID":"2c8hl0g5li","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/4DTBHTKS"]},{"label":"page","uri":["http://zotero.org/users/178241/items/6DPV3Z32"]}]} (Davison, 2006; Fawcett, 2009). The final outcome surrounding these discussions will no doubt have wide ranging impact on the field.<br />Diathesis-Stress model<br />As mentioned earlier, perhaps one of the most widely held models of pathology today is the diathesis-stress model. This model can be seen as independent of theoretical orientation and conceptualizes disease on a spectrum with healthy states. An individual is born with a certain set of predispositions, through interactions with the environment these predispositions are shaped into adult personalities and thought patterns. To draw on an example already discussed, individual differences in the propensity for developing learned helplessness in a given situation may result from natural predispositions. Predispositions may arise as a result of genetics, other physiologic means or possibly from exposure teratogens in utero. Current research has identified several promising areas for study such as genetics, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis, neurocellular alterations, neurocircuits, anatomic changes, altered brain activity, sleep and circadian rhythms, biological correlates to early life adversity, and social environment.<br />Genetics. It is unlikely that genes or altered gene expression are directly responsible for MDD. As suggested by the diathesis-stress model, it is more likely that an individual possesses a genetic predisposition which is exacerbated by stress or life events resulting in depression. A meta-analysis examining the genetics of MDD aggregated the results of six twin studies involving more than 21,000 individuals. This meta-analysis found a monozygotic concordance rate of 37% ADDIN ZOTERO_ITEM {"citationID":"kp9a9s1el","citationItems":[{"uri":["http://zotero.org/users/178241/items/UFUD74A5"]}]} (Sullivan, Neale, & Kendler, 2000). A subsequent study of approximately 15,500 twin pairs found a monozygotic concordance rate of 38% ADDIN ZOTERO_ITEM {"citationID":"1e2mid82nb","citationItems":[{"uri":["http://zotero.org/users/178241/items/HDWD4R5M"]}]} (Kendler, Gatz, Gardner, & Pedersen, 2006). Interestingly, this subsequent study also found a stronger genetic role in depression for females when compared to males. Unfortunately, most studies employing alternative methodologies for assessing the genetic contribution to MDD, such as single nucleotide polymorphism analysis, analyses of single genes, genome-wide association studies, and studies examining the interaction between genes and environmental factors have failed to yield robust or replicable results. In contrast, several studies examining linkage to other disorders have found evidence suggesting a genetic link between MDD and bipolar disorder (Krishnan, 2010). <br />Neurobiology. Evidence from multiple studies in multiple modalities have demonstrated altered brain structure and function in MDD. However, due to the nature of such studies it is not clear whether the observed changes are etiologic or whether they are consequences of MDD. <br />neurotransmitters. MDD is known to involve the abnormal functioning of many neurotransmitters such as the monoamines (serotonin, norepinephrine, and dopamine), Gamma-aminobutyric acid (GABA), and glutamate. Initially, it was thought that MDD was the result of diminished neurotransmission of monoamines, specifically serotonin and norepinephrine. It is now known that these levels are rapidly restored with pharmacotherapy whereas clinical antidepressant effect takes 2 to 6 weeks to fully manifest. Thus, the picture now appears to be more complex, involving intracellular signaling cascades triggered by the monoamines in both the onset of depression and response to antidepressant medication ADDIN ZOTERO_ITEM {"citationID":"1kjrj17g2n","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/PQH7UXJD"]}]} (Nutt et al., 2006) as well as reciprocal regulatory roles similar to that of serotonin and Brain-Derived Neurotrophic Factor (BDNF) ADDIN ZOTERO_ITEM {"citationID":"2jcgqp1nv6","citationItems":[{"uri":["http://zotero.org/users/178241/items/VQE2CTK6"]}]} (Martinowich & Lu, 2008). <br />hypothalamic-pituitary-adrenal (HPA) axis. Overproduction of corticotrophin releasing hormone is thought to cause excessive activity of the HPA axis. Such prolonged or excessive release of glucocorticoids may result in inhibition of neurogenesis and hippocampal atrophy. Although observed hypercortisolemia in patients with MDD was the basis for using a dexamethasone suppression test to diagnose major depression, the test has poor sensitivity and only fair specificity. Thus, it is no longer in wide use. Interestingly, a meta-analysis found that although baseline test results prior to treatment had no prognostic value, evidence of posttreatment non-suppression of cortisol was significantly correlated with poor outcome (Krishnan, 2010).<br />neurocellular alterations. Significant alterations in cellular number, density, and size of both neurons and glial cells have been found in postmortem studies of patients known to have MDD. These alterations were localized within the prefrontal cortex, anterior cingulate gyrus, and amygdala (Krishnan, 2010). <br />neural networking. Similar to other neural circuit models, the neural circuit model of depression is founded on structural and functional imaging studies as well as postmortem studies. It is thought that the circuit that is impaired consists of bidirectional projections from the orbital medial prefrontal cortex, dorsolateral prefrontal cortex, and anterior cingulate including the subgenual cortex, to the amygdala, nucleus accumbens, and various brainstem nuclei. Such a circuit may affect endocrine, autonomic, and behavioral aspects of emotion. Moreover, monoamines such as serotonin are involved in the circuit. Exposure to stress can increase the activity of serotonergic neurons located in the brainstem (dorsal raphe nucleus) and regulate the prefrontal cortex, amygdala, as well as other parts of the circuit. Simultaneously, glutamatergic projections from the prefrontal cortex synapse onto GABAergic neurons in the brain stem, in turn, inhibit serotonergic neurons (Krishnan, 2010; Price & Drevets, 2010). <br />anatomic changes. Structural neuroimaging studies in patients with long-standing untreated MDD have, in general, shown increased ventricular-brain ratio, smaller frontal lobe volumes, and smaller hippocampal volume (Lampe, Hulshoff, Pol, Janssen, Schnack, Kahn & Heeren, 2003; Sheline, Gado, & Kraemer, 2003; Taylor, Macfall, Payne, McQuoid, Steffens, Provenzale et al., 2007). Specific areas involved include the entorhinal cortex, the orbitofrontal cortex, subgenual cortex, left and right hippocampus, and the striatum. Interestingly, recent evidence has demonstrated the reduced hippocampal volumes may precede the onset of depression in at least some patients (Chen, Hamilton & Gotlib, 2010; Rao, Chen, Bidesi, Shad, Thomas, & Hammen, 2010). <br />brain activity. Functional neuroimaging studies confirm the observations of structural imaging with respect to areas involved in MDD. Areas identified by functional neuroimaging consist of the frontal and temporal lobes, parts of the stratum, pallidum, and thalamus. Additionally, the anterior cingulate cortex and the subgenual prefrontal cortex likely play roles in mediating the observed frontostriatal dysfunction (Krishnan, 2010). Furthermore, with treatment of MDD, functional neuroimaging studies have demonstrated changes in regional cerebral metabolic activity. For example, one study that compared patients with refractory depression, patients with treatment-responsive depression, and normal controls found significant differences in cerebral profusion of the frontal cortex, hippocampus, and stratum (Lui et al., 2009). Another study examining post-treatment regional metabolic changes demonstrated differing patterns of change in metabolic activity depending upon whether the patient had received pharmacotherapy or psychotherapy (Goldapple et al., 2004).<br />sleep and circadian rhythms. Although the role and function of sleep is still not entirely understood, it is becoming increasingly apparent that sleep and its various stages play central roles in proper mental functioning. MDD is associated with changes in sleep architecture, mostly decreased REM latency and decreased slow-wave sleep. With treatment, remission, and recovery from depression these alterations in sleep are thought to be reversible (Krishnan, 2010). Sleep is intricately related to central circadian rhythms. Therefore, it is not surprising that individuals with MDD also experience disruptions in circadian rhythms. These may involve changes in body temperature, pressure, pulse, plasma cortisol, norepinephrine, and melatonin. Studies have demonstrated that abnormal circadian rhythm patterns can be restored to normal with antidepressant treatment. Moreover, the restoration of these patterns is a likely mechanism benefit of therapies such as light therapy (Johansson, et al., 2003; Souêtre, et al., 1989).<br />early life adversity. Psychiatry and psychology have long emphasized the importance of early life experiences in the development of future psychopathology. Several recent studies have suggested biological mechanisms that may account for the effect of early childhood trauma, such as by altering sensitivity to stress in response to negative stimuli (Green et al., 2010; Heim & Nemeroff, 2001). Some preclinical data has even suggested that stress may result in long-lived hyperactivity of corticotrophin-releasing factor cells in the hypothalamus. This in turn may lead to increased stress responses (Krishnan, 2010). In another example, several studies have revealed that patterns of neglect and abuse may be transmitted from mother to daughter through epigenetic mechanisms such as methylation of DNA (Fish et al., 2004; McGowan et al., 2009). Moreover one study demonstrated decreased levels of messenger RNA and increased methylation of a neuron specific glucocorticoid receptor promoter in the postmortem hippocampus of suicide victims with histories of child abuse as compared with either suicide victims with no history of child abuse or normal controls (McGowan et al., 2009).<br />Social factors. Social factors have long been known to play a role in the development of MDD. These factors include but are not limited to isolation, criticism from family members, and depression in one's friends and neighbors. Family members, for example, may facilitate the onset or persistence of depression through negative or critical comments and emotional over involvement (Davila, Bradbury, Cohan & Tochluk, 1997; Hayhurst, Cooper, Paykel, Vearnals & Ramana, 1997; Hooley & Teasdale, 1989). One particularly interesting study utilized a prospective analysis of 268 college males and found that poor sibling relationships, but not poor parental relationships, prior to the age of 20 predicted occurrence of MDD as well as the frequency of use of mood altering substances by age 50 (Waldinger, Vaillant & Orav, 2007). An additional study utilizing 12,067 participants from the Framingham Heart Study examined the role social networks play in the spread of depression. Individuals enrolled in the study were evaluated for depression three times over the course of 18 years. The participants identified the names of their spouses, siblings, neighbors, friends, and coworkers, many of whom also participated in the study. The study found that subjects were more likely to be depressed by a factor of:<br />93% if an individual they were directly connected to was depressed<br />43% if an individual at 2° of separation was depressed<br />37% is a person at 3° of separation was depressed<br />This effect disappeared entirely at 4° of separation. Furthermore, female friends were especially influential in the spread of depression from one individual to another (Rosenquist, Fowler & Christakis, 2010). With the rapid expansion of Internet-based social networking it is important to note that this study refers to social networking in the real world. However, Internet-based social networking has evolved to become a fully integrated part of everyday life for many members of the young adult, teenage, and adolescent populations. In fact, it has become so prevalent and integrated into everyday life that new laws and regulations are evolving around concepts such as online bullying. Therefore, it would be interesting to examine if Internet-based social networking could also display the same effects seen in the Framingham study. Finally, in relation to the disparity of lifetime prevalence expressed cross culturally, it is interesting to note that studies have supported significant strong influence of societal and cultural factors in the development and expression of symptoms as well as the willingness or ability to seek care (Kleinman, 2004; Krishnan, 2010).<br />Today’s Standard of Care and Associated Theoretical Orientations<br />In large part, today we measure the validity of a theory by the efficacy of its associated treatment interventions. With this standard in mind many of the various theories in use today have established validity with respect to MDD; however, the two most successful methods of treatment stem from psychoanalytic (interpersonal therapy [IPT]) and CBT. IPT is relatively non-directional and focuses on interpersonal relationships and deficits as they relate to the patient’s current symptoms. As discussed earlier, CBT focuses on correcting maladaptive thought patterns and behaviors in the here and now. Studies have demonstrated that for treatment of mild to moderate MDD combination treatment of psychotherapy with pharmacotherapy yields the best results. However, the particular modality of psychotherapy used appears to rely more on the affinity of the patient for a given modality, that is both IPT and CBT in combination with pharmacotherapy demonstrate overall equal efficacy. Although the majority of studies support IPT and CBT there are also studies supporting the use of more traditional psychodynamic or behavioral approaches ADDIN ZOTERO_ITEM {"citationID":"2m4oiliiu3","citationItems":[{"label":"page","uri":["http://zotero.org/users/178241/items/TVID88ND"]},{"label":"page","uri":["http://zotero.org/users/178241/items/RP3M7N7Z"]},{"label":"page","uri":["http://zotero.org/users/178241/items/8KXHTWTP"]}]} (Bonin & Moreland, 2008; Gaffford & Searight, 2008; Katon & Christo, 2008).<br />The focus of this paper has been a description of the historical evolution of conceptualizations of MDD from antiquity to current thought. We began with ancient literary depictions of depression and traced the evolution of thought through the classical period, medieval societies, the Renaissance and Enlightenment, through early twentieth century thought and onto to current conceptualizations. We currently have several etiologic explanations for MDD in use; psychoanalytic, CBT, and purely biological to name just a few. Significantly, although at times these orientations may be at odds, they should not be viewed as competing but complimentary views from alternative perspectives. If history is any indication we have yet to arrive at a final conceptualization of MDD. As our ideas continue to develop they will likely incorporate aspects from all of the current orientations to generate new and as yet unknown theoretical frameworks. All of the predisposing factors just described have demonstrated potential roles in a diathesis-stress model of MDD. Importantly, as stated earlier, this model is atheoretical. The putative roles for the predisposing factors described do not depend on any one theory, nor do they necessarily advocate for any particular theory over another. Furthermore, multiple treatment modalities have demonstrated efficacy with MDD. 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