Mood Disorders Introduction and Historical Review

Mood disorders introduction and historical review.

Topics covered:

  • Background
    • Depressive and manic states
  • History of mood disorders
    • Graeco-Roman origins: the clinical–empirical tradition
    • The Middle Ages
    • The nineteenth century turning point:
    • French clinical psychiatry
    • The turn of the twentieth century and the Kraepelinian synthesis
    • Freud and the psychoanalytic view of mood disorders
    • Karl Jaspers' General Psychopathology: the phenomenological tradition
    • Mid-twentieth century: Adolf Meyer and the evolution of American psychiatry
    • Mid-twentieth-century European developments: Bleuler's influence
    • The bipolar–unipolar distinction
    • The psychopharmacology revolution and the neo-Kraepelinian restoration
    • Contemporary neo-Kraepelinian nosology: DSM-III and DSM-IV Introduction to mood disorders
  • Introduction to mood disorders
    • Diagnostic subtypes of mood disorders in DSM-IV
    • The affective spectrum
    • Moving from ‘depression' to diagnosis
  • Conclusions
  • References


Mood disorders magnify human experiences to larger-than-life proportions. Among their symptoms are exaggerations of normal sadness and fatigue, joy and exuberance, sensuality and sexuality, irritability and rage, energy and creativity. In their diverse forms, mood disorders afflict a large number of people—the exact number depending on how the illnesses are defined and how accurately they are ascertained. First described thousands of years ago, found in widely diverse cultures, manic–depressive illness is the prototypic mood disorder. To those afflicted, it can be so painful that suicide seems the only means of escape; one of every five untreated manic–depressive individuals actually commits suicide (1).  

Depressive and manic states

What are depression and mania? Ideally, one would first describe ‘normal' or average mood. While this can be difficult, an operational definition might be that ‘normal' or average mood is the state of not feeling particularly euphoric or sad, except under the right circumstances. For example, if something good happens, one would feel happy for a while, and if something bad were to happen, one would feel sad or down for a while. Most people can relate to this definition. Superficially, depression and hypomania can be viewed as extremes of these normal fluctuations in mood. But clinical depression (or mania) are more than extremes of normal mood. They represent syndromes in which, in addition to mood, there are disturbances in thought, psychomotor state, behaviour, motivation, physiology, and psychosocial function.

Depressive states are sometimes easier to comprehend owing to similarities with non-pathological depression and mourning. Mood is bleak, pessimistic, and despairing. A deep sense of futility is often accompanied, if not preceded, by the belief that the ability to experience pleasures is permanently gone. There is a slowing or decrease in almost all aspects of emotion and behaviour: rate of thought and speech, energy, sexuality, and the ability to experience pleasure. Basic physical ‘neurovegetative' activities are affected, such as eating, sleeping, and grooming. Severity varies widely, ranging from mild physical and mental slowing to severe psychosis, with self-denigrating, profoundly negative delusions and hallucinations.

At the outset, manic states often start as hypomania, characterized typically by heightened mood, more and faster speech, quicker thought, brisker physical and mental activity levels, more energy with a corresponding decreased need for sleep, irritability, perceptual acuity, paranoia, heightened sexuality, and impulsivity. As it evolves, it can often progress to frank psychosis with prominent paranoia, grandiose delusions, and even a confused state of delirium, a profoundly disruptive state that generally leads to hospitalization. At the level of hypomania, these changes are generally moderate and tend not to result in serious problems for the person experiencing them. For roughly half of all bipolar patients, the ‘high' does not progress beyond hypomania. It is notable that mania can occur without any euphoric mood at all, and simply display an irritable and/or dysphoric quality. In fact, a very common presentation of mania is a ‘mixed' episode, where depressive mood predominates. These mixed states can be difficult to distinguish from pure agitated depression. Manic and depressive states underlie the nosology of mood disorders.

History of mood disorders

Graeco-Roman origins: the clinical–empirical tradition

The Hippocratic school performed an essential first service for scientific psychiatry: it argued that these were illnesses of the body, not of supernatural or magical spirits (see Goodwin and Jamison (1) and Alexander and Selesnick (2) for most of the review of ancient and medieval sources discussed below). The Hippocratics described melancholia as a condition ‘associated with “aversion to food, despondency, sleeplessness, irritability, restlessness”,' (3) and mania, as a state of high energy and euphoria.

Hippocrates also placed the aetiology of mood disorders in the brain:

Men ought to know that from the brain and from the brain only arrives our pleasures, joys, laughter and jests, as well as our sorrows, pains, griefs and tears...wherefore, I assert, the brain is the interpreter of consciousness.

This Hippocratic insight was buried for two millennia under the humoral theory, solidified in medicine by Galen (second century AD), which held that melancholia resulted from excessive black bile, and mania from excessive yellow bile. The heart, rather than the brain, also was long thought to be the organ of mood disorders.

In the first century BC, Greek physicians first suggested a connection between melancholia and mania. Regarding treatment, some, like Soranus and Asclepiades, explicitly advocated humane treatment of the mentally ill, while others, like Celsus, ‘believed that right treatment would frighten the patient out of mental illness'. Asclepiades famously pledged: ‘Curare tuto, celeriter, et jucunde': the cure should be safe, quick, and pleasant. Thus, ‘he prescribed bathing, exercise, massages and wine'. (2)

The clinical acumen of that era peaked with Aretaeus of Cappadocia: (4)

According to Aretaeus, the classical form of mania was the bipolar one: the patient who previously was gay, euphoric, and hyperactive suddenly ‘has a tendency to melancholy; he becomes, at the end of the attack, languid, sad, taciturn, he complaints that he is worried about his future,he feels ashamed'. When the depressive phase is over, such patients go back to being gay, they laugh, they joke, they sing, ‘they show off in public with crowned heads as if they were returning victorious from the games; sometimes they laugh and dance all day and all night'. In serious forms of mania, called furor, the patient ‘sometimes kills and slaughters the servants'; in less severe forms, he often exalts himself: ‘without being cultivated he says he is a philosopher...and the incompetent (say they are) good artisans...others yet are suspicious and they feel that they are being persecuted, for which reasons they are irascible.

The Middle Ages

The Greek clinical–empirical tradition survived in the early Middle Ages among Arab Muslims and European Christians, although it later succumbed to religious intolerance. In Europe, monk-physicians, like Cassiodorus (490–585), upheld humane treatment and emphasized the Hippocratic empirical tradition. By the twelfth century, that tradition had given way to a more theological–non-empirical bent. Thus, Roger Bacon, arguing that empirical observation was required for knowledge and that mental illnesses had natural aetiologies, suffered the censure of the church and the condemnation of his colleagues at Oxford University. From the fourteenth century onwards, the Inquisition silenced empiricism as heresy, by intimidating or even killing its advocates.

A similar tension played out in the Middle East. The Hippocratic tradition was exemplified by Rhazes (AD865–925), a Persian equivalent of Roger Bacon. Adamantly believing that observation was the best guarantor of truth, he ran a foul of the theological status quo, was denounced, and ended his life in penury. Avicenna ( AD 980–1037) took a more diplomatic approach and prospered as a moderate synthesizer of Greek, Roman, and religious traditions. His medical synthesis, the Canon of Medicine, engendered near-Galenic respect for centuries, transmitting the view regarding mood disorders that ‘undoubtedly the material which is the effective producer of mania is of the same nature as that which produces melancholia'.

The early Islamic tradition, like its Christian counterpart, was humane in its treatment of the mentally ill. The first asylumsfor the mentally ill, for instance, were built in the eighth century in Fez, Morocco, and in Baghdad. Others were soon added in Cairo and Damascus. As the Baghdad Caliphate became more dogmatic and antirationalistic, the Hippocratic tradition in medicine found refuge in the rival Andalucian Caliphate of Spain, where European and Islamic cultures mixed with fecundity. The first European hospital exclusively organized for the mentally ill was inaugurated in 1409 in the Spanish city of Valencia (for a review of this period, see Alexander and Selesnick (2) ).

Beginning in the sixteenth and seventeenth centuries, the Enlightenment gave impetus to medical progress in Europe. The eighteenth century witnessed a flowering of the revival of the clinical–empirical tradition in medicine, with advanced descriptions of mania and melancholia, such as the following by Richard Mead (1751) (quoted by Jackson (3) ):

Medical writers distinguish two kinds of Madness, and describe them both as a constant disorder of the mind without any considerable fever; but with this difference, that the one is attended with audaciousness and fury, the other with sadness and fear: and that they call mania, this melancholy. But these generally differ in degree only. For melancholy very frequently changes, sooner or later, into maniacal madness; and, when the fury is abated, the sadness generally returns heavier than before.

Eighteenth-century medical descriptions were disconnected from one another, however, and many were accompanied by hastily erected classification systems and aetiological speculations.

The nineteenth century turning point: French clinical psychiatry

In 1854, Jean Falret (5) described a circular disorder (la folie circulaire), which for the first time expressly defined an illness in which ‘this succession of mania and melancholia manifests itself with continuity and in a manner almost regular'. The same year, Baillarger (6) described essentially the same thing (la folie double forme), emphasizing that the manic and depressive episodes were not different attacks but rather different stages of the same attack. For the first time, manic–depressive illness was conceived as a single disease, clearly anticipating Kraepelin's later synthesis (see Goodwin and Jamison (1) ).

Although mild cases of mania had been described by Falret, Esquirol, and other observers, Mendel (7) was the first to define hypomania, a ‘form of mania which typically shows itself only in the mild stages, abortively, so to speak.' Around the same time, Kahlbaum (8) described circular disorders (cyclothymia) which were characterized by episodes of both depression and excitement but which did not end in dementia, as chronic mania or melancholia could. Despite these contributions, most clinical investigators continued to regard mania and melancholia as separate entities, chronic in nature, which follow a deteriorating course.

The turn of the twentieth century and the Kraepelinian synthesis

It was left to Emil Kraepelin (9) to segregate psychotic illnesses from each other and clearly draw a perimeter around manic–depressive illness.

As is well known, Kraepelin emphasized those aspects of manic–depressive illness that separated it most clearly from dementia praecox (schizophrenia): the periodic or episodic course, the more benign prognosis, and a family history of manic–depressive illness.

Kraepelin's nosology was the first disease model in psychiatry to be backed by extensive and carefully organized observations and descriptions. It did not exclude psychological and social factors, and, in fact, Kraepelin was one of the first to point out that psychological stresses could precipitate individual episodes. By adding ‘slight colourings of mood' which ‘pass over without sharp boundary into the domain of personal predisposition', Kraepelin also anticipated the later development of spectrum concepts.

While later investigations explored the boundaries between manic–depressive illness and dementia praecox, Kraepelin's revolutionary contribution was unrivalled in the history of affective disorders since Hippocrates. Kraepelin's synthesis is important not because it draws the ultimately ‘correct' picture of nature, but rather because it builds a solid and empirically anchored base for future knowledge. This was his major accomplishment.

Unfortunately, Kraepelin and his colleagues did not possess many effective medical treatments for the two conditions they so painstakingly identified. Drug treatments for manic–depressive illness were not available, and the cure of psychosis seemed almost impossible. When Julius von Wagner-Jaurregg, the chief of psychiatry at the University of Vienna, appeared to cure a psychotic patient with malarial blood injections, it was such a feat that he won the Nobel prize. It turned out that Wagner-Jaurregg's patients suffered from neurosyphilis, and his malarial treatment worked by producing intermittent fevers and a decline in the patients spirochete counts. Penicillin obviously later proved to be a more specific cure. No other psychiatrist has ever won a Nobel prize. (10)

Given these therapeutic difficulties, the Kraepelinian school was criticized for being practically unhelpful. Patients could spontaneously recover from manic–depressive episodes, but there were no treatments available. Dementia praecox, with its deteriorating course was an even greater stimulus to therapeutic nihilism. As Karl Jaspers put it, ‘we were therapeutically hopeless but kind'. (11) The psychoanalytic followers of Freud roundly criticized the Kraepelinians on this score. But history returned Kraepelin to favour, at least for now, as the psychopharmacology revolution demonstrated the therapeutic utility of the traditional nosology.

Freud and the psychoanalytic view of mood disorders 

For most of the twentieth century, however, the psychoanalytic ‘climate of opinion' prevailed. Freud's classic work on mood disorders, ‘Mourning and melancholia', (12) set the tone. It argues that melancholia is essentially analogous to the depressive feelings of normal experiences, like bereavement. To Freud, the depressive process in mourning arises from the tension between ambivalent feelings toward the dead parent, like love and aggression. Melancholia was conceived to involve similar ambivalent feelings. Freud's basic insight into the connection between mourning and melancholia was expanded by later psychoanalysts into the general theory that depression is related to feelings of hostility towards another person, often one's parents. These unacceptably hostile feelings turned inwards toward oneself, rather than outwards toward others, leading to depression.

Karl Jaspers' General Psychopathology: the phenomenological tradition

Contemporaneously with Kraepelin and Freud, Karl Jaspers wrote General Psychopathology, (13) which emphasized the importance of unbiased extensive clinical description of psychopathological states. Jaspers argued that such clinical data needed to be gathered neutrally, free of underlying theories, like Freud's, and free of specific diagnostic paradigms, like Kraepelin's. Jaspers' influence led to more careful description of mood syndromes, as exemplified in the highly influential textbook Fish's Clinical Psychopathology, (14) and Max Hamilton's Depression Rating Scale, still in common use today. Jaspers' theoretical work still continues to provide important insights into the conceptual bases of psychiatry.

Mid-twentieth century: Adolf Meyer and the evolution of American psychiatry

During the first half of the twentieth century, the views of Adolf Meyer (15) gradually assumed a dominant position in American psychiatry. Meyer believed that psychopathology emerged from interactions between an individual's biological and psychological characteristics and his or her social environment. While allowing for biological and genetic factors, the Meyerians understood them as part of an individual's vulnerability to specific psychological and social influences. This perspective was symbolized by the rubric ‘manic–depressive reaction' in the first official American Psychiatric Association diagnostic manual published in 1952 (DSM-I). Meyer's approach differs from the standard disease model, in which clinical phenomena in a given patient are understood (and, therefore, potentially predictable) in terms of a given disease with a specific natural history and pathophysiology. When the Meyerian focus, considerably influenced by psychoanalysis, turned to manic–depressive illness, the individual and his or her environment became the focus, at the expense of clinical descriptions of symptoms and the longitudinal course of the illness.

Mid-twentieth-century European developments: Bleuler's influence

In Europe, the psychosocial and psychoanalytic traditions continued to develop in relative isolation from the mainstream of psychiatry, which largely retained its medical or disease orientation.

Among the academic psychiatrists, Eugen Bleuler (16) departed from Kraepelin by conceptualizing the relationship between manic–depressive (affective) illness and dementia praecox (schizophrenia) as a continuum without a sharp line of demarcation. Patients were distributed all along this spectrum, and an individual patient could be at different points on the spectrum at different times. Bleuler believed that a patient's location on the spectrum depended on the number of schizophrenic features he or she demonstrated. In that sense, Bleuler considered mood symptoms to be non-specific.

In 1933, Kasanin (17) identified a case series of patients who demonstrated the manic–depressive syndrome, but also displayed psychotic symptoms outside of mood episodes. These conditions seemed to lie outside of Kraepelin's dichotomy, and led to the concept of schizoaffective disorder. Some clinicians continue to see these observations as major challenges to the entire Kraepelinian nosology. (18,19)

The bipolar–unipolar distinction

In 1957, Karl Leonhard (20) observed that, within the broad category of manic–depressive illness, some patients had histories of both depression and mania, whereas others had depressions only. He then noted that patients with a history of mania (whom he termed bipolar) had a higher incidence of mania in their families when compared with those with depressions only (whom he termed monopolar). In 1966, Jules Angst (21) and Carl Perris (22) independently provided systematic family history data to support Leonhard's distinction, a distinction validated by an independent criterion—family history. Later genetic studies of this distinction proved less consistent with Leonhard's model, suggesting that bipolar and unipolar disorders may lie along a spectrum, with bipolar illnessbeing more severe.  

Figure 1 displays the evolution of the bipolar–unipolar distinction from Kraepelin's original conceptualization of manic–depressive illness.  

The evolution of the bipolar-unipolar distinction

the evolution of the bipolar-unipolar distinction


Fig. 1The evolution of the bipolar–unipolar distinction from manic–depressive illness. D, major depression; d, subthreshold depression; M, mania; m, hypomania. (Adapted from Goodwin and Jamison. (1) )

The psychopharmacology revolution and the neo-Kraepelinian restoration

After Freud, the object relations theory school made important psychoanalytic contributions to understanding mood disorders. Donald Winnicott, (23) for instance, described the ‘depressive position' in infant development, when the infant is helpless and unable to master his or her surroundings. The infant, Winnicott taught, responds to the mother's inability to provide everything for him or her with a necessary phase of depressive mood and activity. Winnicott felt that some adult psychopathology related to a reversion to or inability to conquer that depressive phase of development. Unfortunately, some clinicians translated this hypothesis into the belief that all individuals, pathologically depressed or not, have a tendency to depressive symptoms, and thus depression was conceptualized as a broad spectrum of pathology that existed in everyone.

Unlike the tradition of Kraepelin, where individual psychiatric illnesses were conceived as categorically different based on distinct pathophysiological processes, the Freudian focus was on a psychodynamic theory of instinctual drives and defence mechanisms. This theory, while perhaps useful incertain neuroses, retarded the development of an empirical descriptive basis for psychological categories. Further, when psychodynamic theories were extended to psychoses, the diagnostic distinctions among disorders became even more confused. The all-encompassing nature of Freudian theory also seemed to lead to impractical conclusions. Everyone, whether ill or not, would seem to benefit from psychoanalysis, and there seemed to be no predetermined limit to how much time and expense was spent in the process. At the other extreme, even the most psychotic patients were felt by some to be treatable by psychoanalysis, and schizophrenia was considered to arise from severe psychosocial childhood trauma. These hypotheses, too long accepted as dogma, have been contradicted by empirical studies.

This ideology, especially when undisciplined, allowed an unbridled optimism: anything, from worried wellness to the most severe schizophrenia, was liable to cure. Freud himself may be exonerated (‘Moi, je ne suis pas Freudiste', he once said, dissociating himself from some of his more extreme disciples); he directly disavowed the utility of psychoanalysis for schizophrenia and never discussed its use in any systematic manner in manic–depressive illness. But some of his intellectual descendants, like Harry Stack Sullivan, (24) vigorously argued otherwise, perhaps a reflection of American pragmatism and ‘can-do' optimism. Unfortunately, this optimism was as uncritically accepted as Kraepelinian nihilism had been.

Contemporary neo-Kraepelinian nosology: DSM-III and DSM-IV

The current nosology, codified in DSM-III in 1980, is neo-Kraepelinian. The empirical evidence for it is based on classical validity studies, deriving from the pioneering work of Robins and Guze, (25) who laid out a groundwork for establishing the validity of a psychiatric diagnosis based on the four criteria of clinical phenomenology, genetics, course, and treatment response. This group of thinkers, centred at the Washington University in St Louis in the 1970s, swam against the tide of psychoanalytic orthodoxy, empirically tested competing nosologies, and developed diagnostic criteria which became the basis for the first empirically based psychiatric nosology. While some studies have failed to find evidence in support of DSM-III's nosology, most of the empirical evidence continues to support the basic structure of the neo-Kraepelinian nosology. (26,27 and 28)

Introduction to mood disorders

Given this historical background, we can briefly summarize current views regarding mood disorders.  

Diagnostic subtypes of mood disorders in DSM-IV

  1. Major depressive (unipolar) disorder is characterized by depressive episodes without any hypomanic or manic states: the patient is either depressed or average in mood, but experiences no mania.
  2. Bipolar disorder is characterized by manic or hypomanic states: the patient is either depressed, euthymic (normal in mood), or hypomanic/manic. Bipolar disorder differs from unipolar disorder by including manic states. No matter how many times a patient is depressed, only one manic/hypomanic episode is required to diagnose bipolar rather than unipolar disorder. Bipolar disorder is further characterized as type I or type II. Type I is diagnosed when at least one manic episode is identified. Usually recurrent depression also occurs, but in 5 to 10 per cent of cases there are no diagnosable major depressive episodes, although almost always there will be minor depressive episodes. Bipolar disorder type II requires the absence of even one manic episode, and instead the occurrence of at least one hypomanic episode and at least one major depressive episode. The critical difference between mania and hypomania, in current DSM-IV nosology, is that mania requires significant social and occupational dysfunction, while in hypomania significant social and occupational dysfunction needs to be excluded. Durational criteria are less strict for hypomania (a minimum of 4 days) than for mania (a minimum of 1 week).
  3. Dysthymia refers to clinically significant major depressive symptoms that are present for 2 years or more but do not reach the threshold (with respect to severity and/or number of symptoms) for major depression. Cyclothymiais a condition in which, like dysthymia, depressive symptoms do not reach the threshold for diagnosis of a major depressive episode, and hypomania is present. Cyclothymia and dysthymia may represent a predisposition to major mood disorders. Lastly, whereas cyclothymia and dysthymia involve some depressive states, ‘hyperthymia' is sometimes used to describe chronic mild hypomania (decreased need for sleep, expansive behaviour, marked extroversion, ‘the life and soul of the party'). Patients with dysthymia, cyclothymia, or hyperthymia may develop unipolar or bipolar disorder under certain circumstances, such as with antidepressant use (see below).

The affective spectrum

The variations of mood disorders can be conceived along one broad spectrum of affective illness, with bipolar disorder type I and a single major depressive episode at the extremes. Type II bipolar disorder and cyclothymia display less severe manic symptoms. The area between cyclothymia and recurrent unipolar depression is controversial, corresponding to the DSM-IV diagnosis of ‘bipolar disorder, not otherwise specified'. We would suggest that it should include mid-spectrum cases; these might include those who only experience hypomanic or manic episodes with antidepressant medications but not spontaneously, and those with recurrent unipolar major depressive episodes and a first-degree relative with type I bipolar disorder. Some would add those with hyperthymic personality at baseline (i.e. when not depressed) who also experience recurrent unipolar major depressive episodes. Recurrent, psychotic, and atypical unipolar depression may also be closer to the bipolar end of the spectrum, with similarities in underlying pathophysiology and treatment response. At the extreme of the bipolar end of the spectrum, schizoaffective disorder, bipolar type might be viewed as a more severe psychotic form of bipolar illness (for a review of the data underlying these views, see Goodwin and Jamison (1) ).

Moving from ‘depression' to diagnosis

A common misperception among some clinicians and patients is to think of ‘depression' as being equivalent to unipolar depression, which is then treated with antidepressants. There are a number of reasons for this phenomenon: the first is that patients often lack insight into their manic symptoms; not knowing that they are ill, they deny their manic symptoms to clinicians. Second, depressive symptoms tend to last longer than manic symptoms, sometimes are more frequent, and often are more psychically painful; thus, patients tend to seek assistance when depressed rather than when manic. Third, the many new antidepressants that have become available over the past 10 years have been extensively marketed to physicians at the same time that ‘depression awareness' programmes have educated the public about the availability of safe and effective treatments. Simultaneously, few new treatments for bipolar disorder have become available, and there has been scant professional and public education about bipolar illness. For example, the mainstay of bipolar treatment, lithium, is an inexpensive generic drug with minimal funds available for its promotion or for educational efforts.

As with the differential diagnostic process in any medical disease, the diagnosis of mood disorders should start with those disorders that must be ruled out first to those that remain afterwards. We believe that this process should begin by ruling out depression which is clearly due to another medical or psychiatric disorder, or substance abuse. Such ‘secondary depressions' usually involve a single major episode occurring in the absence of prior depressive symptoms or family history, and at a later age of onset than is typical for primary depression. The second rule-out diagnosis is bipolar disorder: first, bipolar I, then bipolar II, and next bipolar ‘not otherwise specified' should be sequentially ruled out before unipolar depression can be diagnosed. Unfortunately, many clinicians and patients jump from the recognition of a major depressive syndrome directly to a diagnosis of unipolar depression without the critical intermediateprocess of ruling out bipolar conditions. The relevance of this process lies in the underappreciated fact that antidepressants can worsen bipolar illness, either by causing acute mania or by acting as mood destabilizers, counteracting the effects of mood stabilizers, and leading to a long-term rapid-cycling course of illness. (29)


Mood disorders are composed of depressive and manic states that can be conceptualized as unipolar or bipolar conditions and/or along an affective spectrum. Clinical experience with mania and melancholia date to the Hippocratic school, were preserved and connected to humane treatmentof the mentally ill in the Middle Ages and Enlightenment, and were systematized in the nineteenth century, culminating in the Kraepelinian nosology. After a de-emphasis of the medical disease model during the psychoanalytic period of influence in the mid-twentieth century, the current nosology has returned to a neo-Kraepelinian structure that is better supported by empirical research. Meanwhile, this nosology has proven useful in targeting new medications produced in the ongoing psychopharmacology revolution.



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