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From a strict diagnostic point of view, our discussion of mood disorders could now be mostly complete. However, there is the growing recognition that many patients seen in clinical practice have a mood disorder not well described by the above categories. Formally, they would be called “not otherwise specified” or “NOS,” but this creates a huge single category for many patients that belies the richness and complexity of their symptoms. Increasingly, such patients are seen as belonging in general to the “bipolar spectrum” ( ), and in particular to one of several additionalFigure 6-10 descriptive categories that have been proposed by experts such as Hagop Akiskal (Figures 6-10 through ).6-20

Bipolar ¼ (0.25)

One mood disorder often considered to be “not quite bipolar” and sometimes called bipolar ¼ (or 0.25) designates an unstable form of unipolar depression that responds sometimes rapidly but in an unsustained manner to antidepressants, the latter sometimes called antidepressant “poop-out” (

). These patients have unstable mood but not a formal bipolar disorder, yet can benefitFigure 6-11 from mood-stabilizing treatments added to robust antidepressant treatments.

Bipolar ½ (0.5) and schizoaffective disorder

Another type of mood disorder is called different things by different experts, from bipolar ½ (or 0.5) to “schizobipolar disorder” to “schizoaffective disorder” ( ). For over a century, experts haveFigure 6-12 debated whether psychotic disorders are dichotomous from mood disorders ( ) or areFigure 6-13A part of a continuous disease spectrum from psychosis to mood ( ).Figure 6-13B

The dichotomous disease model is in the tradition of Kraepelin and proposes that schizophrenia is a chronic unremitting illness with poor outcome and decline in

Figure 6-10. . There is a huge variation in the presentation of patients with bipolar disorder.Bipolar spectrum Historically, bipolar disorder has been categorized as I, II, or not otherwise specified (NOS). It may be more useful, instead, to think of these patients as belonging to a bipolar spectrum and to identify subcategories of presentations, as has been done by Akiskal and other experts and as illustrated in the next several figures.

function whereas bipolar disorder is a cyclical illness with a better outcome and good restoration of function between episodes. However, there is great debate as to how to define the borders between these two illnesses. One notion is that cases with overlapping symptoms and intermediate disease courses can be seen as a third illness, schizoaffective disorder. Today, many define this border with the idea that “even a trace of schizophrenia is schizophrenia.” From this “schizophrenia-centered perspective,” many overlapping cases of psychotic mania and psychotic depression might be

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considered either to be forms of schizophrenia, or to be schizoaffective disorder as a form of schizophrenia with affective symptoms. A competing point of view within the dichotomous model is that “even a trace of mood disturbance is a mood disorder.” From this “mood-centered perspective,” many overlapping cases of psychotic mania and psychotic depression might be considered either to be forms of a mood/bipolar disorder or to be schizoaffective disorder as a form of mood/bipolar disorder with psychotic symptoms. Where patients have a mixture of mood symptoms and psychosis, it can obviously be very difficult to tell whether they have a psychotic disorder such as schizophrenia, a mood disorder such as bipolar disorder, or a third condition, schizoaffective disorder. Some even want to eliminate the diagnosis of schizoaffective disorder entirely.

Proponents of the dichotomous model point out that treatments for schizophrenia differ from those for bipolar disorder, since lithium is rarely helpful in schizophrenia, and anticonvulsant mood stabilizers have limited efficacy for psychotic symptoms in schizophrenia, and perhaps only as augmenting agents. Treatments for schizoaffective disorder can include both treatments for schizophrenia and treatments for bipolar disorder. The current debate within the dichotomous model is: If you have bipolar disorder, do you have a good outcome? – but if you have schizophrenia, do you have a poor outcome? – and what genetic and biological markers rather than clinical symptoms can distinguish one dichotomous entity from the other?

Figure 6-11. . Some patients may present only with depressive symptoms yet exhibit rapid butBipolar ¼ unsustained response to antidepressant treatment (sometimes called rapid “poop out”). Although such patients may have no spontaneous mood symptoms above normal, they potentially could benefit from mood-stabilizing treatment. This presentation may be termed bipolar ¼ (or bipolar 0.25).

The continuum disease model proposes that psychotic and mood disorders are both manifestations of one complex set of disorders that is expressed across a spectrum, at one end schizophrenia (plus schizophreniform disorder, brief psychotic disorder, delusional disorder, shared psychotic disorder, subsyndromal/ultra-high-risk psychosis prodrome, schizotypal, paranoid, schizoid, and even avoidant personality disorders), and at the other end bipolar/mood disorders (mania, depression, mixed states , melancholic depression, atypical depression, catatonic depression, postpartum depression, psychotic depression, seasonal affective disorder), with schizoaffective disorder in the middle, combining features of positive symptoms of psychosis with manic, hypomanic, or depressive episodes ( ).Figure 6-13B

Modern genomics suggests that the spectrum is not a single disease, but a complex of hundreds if not thousands of different diseases, with overlapping genetic, epigenetic, and biomarkers as well as overlapping clinical symptoms and functional outcomes. Proponents of the continuum model point out that treatments for schizophrenia overlap greatly now with those for bipolar disorder, since second-generation atypical antipsychotics are effective in the positive symptoms of schizophrenia and in psychotic mania and psychotic depression, and are also effective in nonpsychotic mania and in bipolar depression and unipolar depression. These same second-generation atypical

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antipsychotics are effective for the spectrum of symptoms in schizoaffective disorder. From the continuum disease perspective, failure to give mood-stabilizing medications may lead to suboptimal symptom relief in patients with psychosis, even those whose prominent or eye-catching psychotic symptoms mask or distract clinicians from seeing underlying and perhaps more subtle mood symptoms. In the continuum disease model, schizophrenia can be seen as the extreme end of a spectrum of severity of mood disorders and not a disease unrelated to a mood disorder. Schizophrenia can therefore share with schizoaffective disorder severe psychotic symptoms that obscure mood symptoms, a chronic course that eliminates cycling, resistance to antipsychotic treatments, and prominent

Figure 6-12. . Bipolar ½ (0.5) has been described as schizobipolar disorder, which combines positiveBipolar ½ symptoms of psychosis with manic, hypomanic, and depressive episodes.

Figure 6-13

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A. . Schizophrenia and bipolar disorderSchizophrenia and bipolar disorder: dichotomous disease model have been conceptualized both as dichotomous disorders and as belonging to a continuum. In the dichotomous disease model, schizophrenia consists of chronic, unremitting psychosis, with poor outcomes expected. Bipolar disorder consists of cyclical manic and other mood episodes and has better expected outcomes than schizophrenia. A third distinct disorder is schizoaffective disorder, characterized by psychosis and mania as well as other mood symptoms.

B. . Schizophrenia and bipolar disorder haveSchizophrenia and bipolar disorder: continuum disease model been conceptualized both as dichotomous disorders and as belonging to a continuum. In the continuum disease model, schizophrenia and mood disorders fall along a continuum in which psychosis, delusions, and paranoid avoidant behavior are on one extreme and depression and other mood symptoms are on the other extreme. Falling in the middle are psychotic depression and schizoaffective disorder.

negative symptoms, yet be just a severe form of the same illness. In the continuum disease model, schizoaffective disorder would be a milder form of the illness with less severe psychotic features and more severe mood features.

The debate rages on . . .

Bipolar I½ (1.5)

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Although patients with protracted or recurrent hypomania without depression are not formally diagnosed as bipolar II disorder, they are definitely part of the bipolar spectrum, and may benefit from mood stabilizers that have been studied mostly in bipolar I disorder ( ). Eventually, suchFigure 6-14 patients will often develop a major depressive episode and their diagnosis will then change to bipolar II disorder, but in the meantime they can be treated for hypomania while being vigilant to the future onset of a major depressive episode.

Bipolar II½ (2.5)

Bipolar II½ is the designation for cyclothymic patients who develop major depressive episodes ( ). Many patients with cyclothymia are just considered “moody” and do not consultFigure 6-15

professionals until experiencing full depressive episodes. It is important to recognize patients in this part of the bipolar spectrum, because treatment of their major depressive episodes with antidepressant monotherapy may actually cause increased mood cycling or even induction of a full manic episode, just as can happen in patients with bipolar I or II depressive episodes.

Bipolar III (3.0)

Patients who develop a manic or hypomanic episode on an antidepressant are sometimes called bipolar III ( ). According to formal diagnostic criteria, however, when an antidepressantFigure 6-16 causes mania or hypomania, the diagnosis is not bipolar disorder, but rather, “substance-induced mood disorder.” Many experts disagree with this designation and feel that patients who have a hypomanic or manic response to an antidepressant do so because they have a bipolar spectrum disorder, and can be more appropriately diagnosed as bipolar III disorder ( ) until theyFigure 6-16 experience a spontaneous manic or hypomanic episode while taking no drugs, at which point their diagnosis would be bipolar I or II, respectively. The bipolar III designation is helpful in the meantime, reminding clinicians that such patients are not good candidates for antidepressant monotherapy.

Bipolar III½ (3.5)

A variant of this bipolar III disorder has been called bipolar III½, to designate a type of bipolar disorder associated with substance abuse ( ).Figure 6-17

Figure 6-14. . A formal diagnosis of bipolar II disorder requires the occurrence of not only hypomanicBipolar I½ episodes but also depressive episodes. However, some patients may experience recurrent hypomania without having experienced a depressive episode – a presentation that may be termed bipolar I½. These patients may be at risk of eventually developing a depressive episode and are candidates for mood-stabilizing treatment, although no treatment is formally approved for this condition.

Although some of these patients can utilize substances of abuse to treat depressive episodes, others have previously experienced natural or drug-induced mania and take substances of abuse to induce

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mania. This combination of a bipolar disorder with substance abuse is a formula for chaos, and can often be the story of a patient prior to seeking treatment from a mental health professional.

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