Bipolar Disorder Master Guide

1. 1 Introduction to Bipolar Disorder (Manic-Depressive Illness)

Bipolar disorder (also known as manic depressive illness) is a severe mental disorder, primarily characterised by extreme mood swings and episodes of depression and hypomania/mania. It has a highly recurrent course and a strong hereditary basis. Despite effective pharmacological  and more recently psychosocial treatments, once expressed the illness is characterised by a chronic course that will involve numerous bipolar episodes and equally persistent disabling sub-syndromal symptomatology. Depending on the diagnostic threshold used, severe presentations of it make it a relatively rare condition with approximately 1% prevalence rate. Nevertheless, milder forms of the disorder have been estimated to be highly prevalent (6.4%).

1. 2 Historical Roots in Medicine and Ancient Times

Presentations of Bipolar disorder were described by the ancient Greeks. It was observed and described not only by physicians like Hippocrates and Aretaeus, but also by philosophers and poets. Angst and Marneros (2001) review the historical evolution of the concept of bipolar disorder from ancient to present times.

The first physician to actually observe and describe in detail the features of Bipolar disorder is (Aretaeus, 150 AD) of Cappadocia in his two books ‘On the Aetiology and Symptomatology of Chronic Diseases’ and ‘The Treatment of Chronic Diseases’. Although like Hippocrates he emphasised the biological bases of mental illness, he also pointed out the role of psychological factors especially for depression. He distinguished between a biologically caused depression (melancholia) and a “reactive depression”. Apart from the hypotheses he made regarding the cause of the disorder, he also made interesting observations regarding the interplay between melancholia and mania, which highlight the mixture of bipolar symptoms.

‘‘ . . . I think that melancholia is the beginning and a part of mania . . . The development of a mania is really a worsening of the disease (melan-cholia) rather than a change into another disease. . . In most of them (melancholics) the sadness became better after various lengths of time and changed into happiness; the patients then developed a mania’’. Aretaeus of Cappadocia (150 AD)

Aretaeus observations of the two primary phases of bipolar disorder emphasised their development over time and the complex interplay of bipolar symptomatology. The emphasis on the variability of bipolar symptomatology as the primary feature of the disorder has continued to appear through out the academic literature on bipolar disorder.

Plato, on the other hand, observed and highlighted the role of psychological factors in mania. In his book “Phaedrus” he distinguished between two kinds of mania; one characterised by mental strain that arises from a bodily cause of origin (what would nowadays be considered dysphoric mania), and a second divine or inspired mania with Apollo being the source of “inspiration” (euphoric mania). Plato made further distinctions between psychogenic manias, which he called “inspirations”. These were the “prophetic inspiration”, the “erotic inspiration” (sent by the god of love, Eros), and “protreptic inspiration” (sent by the muses) that makes men sing. Such observations further set the ground for investigating different causal factors of bipolar symptoms and also contemporary knowledge with regards to the factor structure of mania (Cassidy et al., 2001).

Contemporary medical accounts of bipolar disorder by physicians in the 18th century continued to describe the longitudinal associations between melancholia and mania but did not see this as one single condition. According to (Angst and Marneros, 2001) it was the French psychiatrist Jean-Pierre Falret (1854) who recognised bipolar disorder as an entity on its own by calling it “folie circulaire”, and describing it as an entity that is “characterized by a continuous cycle of depression, mania and free intervals of varying length”, Jean-Pierre Falret (1854).

Our 20th century descriptive and diagnostic understanding of Bipolar disorder is primarily the end product of the work of German psychiatry, in particular Emil Kraepelin who made the distinction between manic depressive illness and schizophrenia (Kraepelin, 1919).

Kraepelin made the distinction based on his careful prospective observation of the symptoms course and the prognosis of the two disorders. He considered schizophrenia as an illness with a deteriorating course, in contrast to bipolar disorder that was characterised by an episodic course and overall a better prognosis. Kraepelin was also one of the first modern physicians to advance the method of Bipolar Life-Charting as he kept detailed graphical records/charts of his patients’ illness course.

Nevertheless, the clinical significance of sub-syndromal symptoms in bipolar disorder was first put forward by a non-organic psychoanalytically trained psychiatrist, Karl Abraham. Even though Karl Abraham (1911, 1924) is often considered the father of the manic-defence hypothesis, which was a psychoanalytic insight/hypothesis proposing that mania is a defence against depression, he should also be credited for his early observations on the presence of sub-syndromal symptoms during “free intervals”, what we nowadays call inter-episode periods.

In his 1924 monograph, “Manic Depressive states and the pre-genital of the libido”, he wrote: “For we find that the patient who is liable to periodic fits of depression and exaltation is not really perfectly well during his “free interval”. If we merely question such patients rather closely we learn that during long intervals of this kind they pass through depressive or hypo-manic states of mind from time to time” (p.423, 1924) Predictably, as an early psychoanalyst trained to observe personality functioning he even gave some insight into the differences in the characters of bipolar patients during these “free interval” periods.

“But what is specially interesting to the analyst is the fact that in all cycloid illnesses the patient is found to have an abnormal character-formation during his “free interval”; and that this character-formation coincides in a quite unmistakable way with that of the obsessional neurotic” (p. 423, 1924)

Of course given the nature of his psychoanalytic work and the fact that he based most of his theories on six case studies, Abraham did not attempt to make any links between his observation on sub-syndromal symptoms or the “abnormal” character formation during well periods and the course of the disorder.

1.3 Bipolar Disorders: Contemporary Diagnostic Definitions and a Course-Based Typology

Current diagnostic formulations of mental disorders describe the primary symptoms of each mental disorder without making direct references to the cause of the “illnesses”. There have been several debates on this practice of categorising and “lumping” mental disorders in this respect, primarily from psychologists and psychiatrists who are taking a dimensional or experimental view of these conditions (Bentall, 2006).

Interestingly, the very same discipline of psychiatric researchers investigating the biological and genetic causes of psychiatric disorder who are largely responsible for our current “nosological” standardisation, are now trying to redefine mental disorders given that the original categories do not appear to provide specific enough “phenotypes” for genetic investigations (Duffy and Grof, 2001)

Nevertheless, current clinical and research practice as it is reflected in the World Health Organisation and the American Psychiatric Association in their diagnostic manuals (ICD-10 and DSM-IV) recognise four different episodes that characterise Bipolar Disorder: Mania, Depression, Hypomania, and Mixed episode (Mania + Depression).

In order to meet the criteria for being present, each episode is characterised by a key number of basic symptoms. Additional criteria that refer to the duration, functional impairment and causal factors (aetiology) are laid out in order for a researcher or a clinician to be able to accurately diagnose the presence of an episode or else a syndromal state of Bipolar disorder.

1.3.1 Diagnostic (DSM-IV) Criteria for Bipolar Episodes

The Diagnostic and Statistical Manual of Mental Disorders by the American Psychiatric Association (DSM-IV) defines four Bipolar episodes (Mania / Hypomania / Depression / Mixed) with the following symptoms / criteria for each episode: Criteria for a Manic/Hypomanic Episodes



Table 1.1: DSM-IV Criteria for a Manic / Hypomanic Episode


A. A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalisation is necessary)


B. During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree

1. Inflated self-esteem or grandiosity

2. Decreased need for sleep (e.g. feels rested after only three hours of sleep)

3. More talkative than usual or pressure to keep talking

4. Flight of ideas or subjective experience that thoughts are racing

5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)

6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation

7. Excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g. engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)

C. The symptoms do not meet criteria for a Mixed Episode

D. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalisation to prevent harm to self or other, or there are psychotic features

E. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g. hyperthyroidism)

Note: Manic-like episodes that are clearly caused by somatic antidepressant treatment (e.g., medication, electroconvulsive therapy, light therapy) should not count towards a diagnosis of Bipolar I disorder Criteria for a Hypomanic Episode

Here it is more interesting to note the similarities and differences between the hypomanic episode and the manic one, rather than to reproduce the criteria. To start with the similarities, both a hypomanic and a manic episode share the same key diagnostic symptoms (A: elevated-expansive-irritable mood and B: 3 or 4 manic symptoms out of 7 identified). Also, similarly to the manic episode, the causation of the hypomanic episode cannot be due to substance use or a general medical condition.

But what really differentiates the two episodes or states from each other, is the severity, duration, and from a psychological point of view the experience of each patient. The DSM-IV sets four days as the minimum duration for a hypomanic episode and states that the mood has to be “clearly different from the usual non-depressed mood”. But the two most important criteria (D and E) that refer to functional impairment essentially summarise the major difference between a hypomanic and a manic episode. The hypomanic episode is associated with an “unequivocal change in functioning that is uncharacteristic of the person when not symptomatic” (criterion C of hypomanic episode) and “the episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalisation, and there are no psychotic features” (criterion D).

The four-day duration for hypomania has been challenged clinically, and more recently empirically (Benazzi and Akiskal, 2006). More recent criteria proposed by Swiss researchers (“Zurich criteria”, Angst et al., 2003), discuss at least a two-day duration for hypomania. These criteria make the diagnosis of Bipolar disorder easier in cases with brief hypomanias, but also tend to inflate the diagnosis of Bipolar disorder, and the time spent in syndromal states and number of episodes, that are usually reported in prospective naturalist studies on Bipolar symptoms (Bauer, Grof et al. 2006).

Any diagnostic definitions that rely on duration and severity of symptom states, especially in a variable condition such as a Bipolar disorder, require continuous monitoring in order to be accurate, and make prospective designs with multiple measurements a necessity.

Two more episodes that are often present in Bipolar disorder are major depressive and mixed episodes. Their symptoms and diagnostic criteria are given below. According to the DSM-IV, the diagnostic criteria and symptoms of a major depressive episode are the same both in Bipolar and Unipolar disorders. Mixed episodes by definition can only be present in Bipolar disorder as they require the presence of both a depressive and a manic episode. Criteria for a Major Depressive Episode

Table 1.2: DSM-IV Criteria for a Major Depressive Episode

A. Five (or more) of the following symptoms have been present during the same two-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure

1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g. feels sad or empty) or observation made by others (e.g. appears tearful)

2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly ever day (as indicated by either subjective account or observation made by others)

3. Significant weight loss when not dieting or weight gain (e.g. a change of more than 5% of body weight in a month), or decrease or increase in the appetite nearly every day

4. Insomnia or hypersomnia nearly every day

5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)

6. Fatigue or loss of energy nearly every day

7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)

8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)

9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide

B. The symptoms do not meet criteria for a Mixed episode

C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning

D. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g. hypothyroidism)

E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than two months or are characterised by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation Criteria for a Mixed Episode

Table 1.3: DSM-IV Criteria for a Mixed Episode

A. The criteria are met both for a Manic Episode and for a Major depressive episode (except for duration) nearly every day during at least a 1-week period

B. The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalisation to prevent harm to self or others, or there are psychotic features

C. The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g. hyperthyroidism)

1.3.2 Diagnostic Sub-types of Bipolar Disorder: A Course Based Typology

Based on the above episodes, the DSM-IV identifies only two primary bipolar sub-types / diagnoses. Bipolar I disorder, which is also considered the classic presentation of Bipolar illness, and Bipolar II disorder, often mistakenly considered a less severe presentation of the disorder. The different episodes serve as building blocks for reaching either a bipolar I or a bipolar II diagnosis.


A. Bipolar I Disorder


A diagnosis of bipolar I disorder requires the presence of only one manic episode, which is not due to the presence of a general medical condition (or any other underlying “organic cause”) or substance use. The manic episode should also be outside the context of a Schizo-Affective or a Schizophrenic disorder.

Nevertheless, psychotic symptoms similar to the ones observed in schizophrenia are often present during manic episodes (Keck et al., 2003). Patients with bipolar I disorder will often have severe major depressive episodes as well. However, their presence is not required for a diagnosis of Bipolar I disorder. Although there have been reported cases of unipolar mania (Abrams, Taylor et al. 1979; Perugi, Akiskal et al. 1998) this presentation is unusual and its diagnostic stability is weak. Most such cases are reported to have a depressive episode at some point in their lifetime or if the onset is later in life an “organic cause” is usually suspected (Moorhead and Young, 2003)

B. Bipolar II Disorder


Bipolar II disorder is defined by the presence of at least one hypomanic episode and at least one major depressive episode. Patients with a bipolar II diagnosis will primarily suffer with major depressive episodes. As a result of this presentation and also because of having the difficulty in differentiating a hypomanic episode from a return to a normal “well” period, cases of BPII are often misdiagnosed for unipolar depression (Ghaemi et al., 2001). An increase in the recent recognition of this problem has fuelled the development of screening measures for hypomanic states (Angst et al., 2005). Nevertheless our understanding and measurement of hypomanic states is still rather limited.


C. Other Sub-Types and Diagnostic challenges


The DMS-IV also provides other diagnostic categories based purely on the course of the disorder. These are called course specifiers. There is the Rapid Cycling specifier, which requires the presence of four or more bipolar episodes (MDE, Manic/Hypomanic, Mixed) in the past year, and the seasonal specifier in which episodes tend to occur at particular times of the year independently of any psychosocial stressors.


Finally, a milder and more common presentation of Bipolar disorder is defined in cyclothymia. Cyclothymia is diagnosed for

people who experience hypomanic symptoms and depressive symptoms without meeting the diagnostic criteria for bipolar episodes for at least two years.


The above definitions determine what is known about the prevalence of the bipolar disorder in the community. Many of the proposed criteria particularly about the duration of Hypomanic episodes (four days is an ad-hoc time frame) have caused considerable debate among epidemiologists and diagnosticians (Benazzi, 2007a). Additional debates have arisen from DMS-IV’s requirement of the presence of A1 symptom criteria (elevated or irritable mood) in order to allow the evaluation of the presence of further symptoms. Researchers (Benazzi, 2007b) (Bauer et al., 1991) who have challenged this practice argue that in hypomanic or mixed states the primary symptom is an increase in activity levels accompanied either by a positive or negative mood rather than a simply elevated or irritable mood that the patient may deny or not consider pathological. These problems often lead to missed episodes or even misdiagnosis, usually one of unipolar disorder. They also highlight the need for frequent and structured symptom monitoring in bipolar disorder, both for research and treatment/outcome monitoring purposes, and during all phases of the disorder.

Again the above diagnostic problems primarily plague the bipolar II sub-type and bipolar-spectrum cases. The severity of manic episodes present in bipolar I disorder has made it difficult for anyone to challenge their presence or deny their existence. Unlike other disorders, the diagnosis of what is considered the primary or classic presentation of bipolar disorder (Bipolar I) is a relatively easy task. The only requirement set out by the current diagnostic manuals is the presence of one manic episode. The diagnostic picture is complicated when one is trying to diagnose the disorder in milder bipolar-spectrum cases where a manic episode by definition is absent. This diagnostic problem is primarily a result of the difficulty we have in measuring and diagnosing hypomanic episodes as well as the difficulty of patients in reporting such states (Ghaemi et al., 2004), and also monitoring sub-syndromal presentations of these symptoms. However, all these problems and the obvious reliance on the course of the symptoms to derive a correct diagnosis make vital the use of prospective symptom severity and diagnostic assessments for continuous monitoring.