TB1, TB2, TB3, 2,5, 3,5.
  A). Il était une fois la dépression (Henry EY), classée en dépressions unipolaires et dépressions bipolaires.  Dans son manuel de psychiatrie, Henry EY qui a été le leader de la psychiatrie française durant 40 ans décrivait la dépression bipolaire comme une dépression endogéne (d'origine biologique) dont les crises reviennent périodiquement et implacablement. Il la classait dans les psychoses.
    En contraste, la dépression réactionnelle, réaction normale et typique d'un deuil (deuil = tout événement extérieur grave), n'est pas récurrente et se termine normalement en 6 mois à 9 mois. Ce n'est pas une maladie, mais un mécanisme de réajustement de la personnalité. Les médicaments permettent de ramener la phase dépressive à un mois. C'est une névrose.
   Tout cela est clair, net et précis. Mais à la fin de cet exposé une phrase désabusée  indique qu'il y a tous les intermédiaires en pratique. La belle construction théorique se réduit à deux poteaux indicateurs dans un paysage chaotique.
  B). Classification DSM IV. Le DSM-IV (ou son équivalent OMS le CIM-10) a classé les troubles de l'humeur en trois grandes catégories, les troubles dépressifs, les troubles bipolaires et les autres troubles de l'humeur. Le mouvement qui a donné naissance au DSM4 était la préoccupation des psychiatres américains de parler avec un seul langage des affections psychiatriques. Il s'agissait de définir des symptômes objectivement, déterminés d'après des questionnaires, et de regrouper les symptômes en syndromes avant de faire le diagnostic d'un trouble psychiatrique. Ce mouvement a permis d'objectiver la psychiatrie et de faire des études statistiques.
  C). Une tendance de la fin des années 90 était de décrire des sous-catégories précises de diagnostic TB 3,4,5,6,7 puis 1,5 2,5 etc.. L'espoir était de trouver des traitements précis s'appliquant a ces sous-catégories. Cet espoir a été déçu.
    Une autre voie de recherche de recherche était de trouver des marqueurs biologiques de chaque type de trouble et de relier ces marqueurs aux études des neurotransmetteurs. Espoir encore une fois déçu.
    La troisième voie de recherche était la voie génétique : trouver les génes des troubles bipolaires, ce qui permettrait de classer les différentes malfonctions La recherche des génes n'a pas échoué, mais s'est égaré dans un océan de complexité : il n'y a pas un géne, mais 11 génes au moins impliqués, la causalité n'est pas directe mais c'est plutôt des facteurs de prédisposition, etc Voir les notes sur l' organisation biologique  et sur les facteurs génétiques Il n'y a pas lien direct entre le génotype et le phénotype mais un passage par des endophénotypes (par ex thyroidite auto-immune). La recherche génétique actuellement se focalise sur la recherche de sous-groupes distingués et l'élucidation des mécanismes fondamentaux en créant des souris knock-out ad-hoc, pour fournir un modèle animal du trouble bipolaire..

TROUBLES BIPOLAIRES

L'épisode dépressif majeur (EDM) ou plutôt que majeur, caractérisé, voit l'humeur être dépressive durant un intervalle de temps important.   La dysthymie est une humeur constamment dépressive, mais qui n'atteint pas une intensité négative importante.    La cyclothymie voit se succéder très rapidement de courtes périodes d'humeur positives (exaltation) et négative (dépression).    Le trouble bipolaire de type I (TBI) voit se succéder des périodes d'exaltation importante (manie) suivies de dépressions plus ou moins fortes et de période de calme (euthymie).    Dans le trouble bipolaire de type II (TBII) la période d'exaltation est peu marquée et socialement bénigne. On parle d'hypomanie. Par contre, la période dépressive est souvent profonde et prolongée.    On parle de cycles rapides quand il y a au moins quatre cycles exaltation-dépression par an.    Les états mixtes sont des états ou des symptômes dépressifs coexistent avec des symptômes d'exaltation. ( cf chronique de N.Ghaemi)

Voici ci-dessous la classification du DSM-IV TR. Les diagnostics sont posés lorsque des scores sont atteints aux questionnaires. Si le score reste en -dessous de la barre on parle de trouble bipolaire NOS  (non spécifiés).
 296.XX Trouble bipolaire I.
  296.x Episode maniaque isolé
  296.40 Episode le plus récent hypomaniaque
  296.4x Episode le plus récent maniaque
  296.5x Episode le plus récent dépressif
  296.6x Episode le plus récent mixte
  296.7  Episode le plus récent non spécifié
296.89 Trouble bipolaire II
  spécifier (épisode actuel ou le plus récent)  hypomaniaque/dépressif
 301.13 trouble cyclothymique
 296.80 trouble bipolaires non spécifié

AUTRES TROUBLES DE L'HUMEUR
   De nombreuses affactions médicales ont pour symptômes secondaires des troubles psychiatriques.
  296.83  Trouble de l'humeur due une affection médicale générale
  291.8 Trouble de l'humeur induit par l'alcool
  292.84 Trouble de l'humeur induit par d'autres substances
  296.90 Troubles de l'humeur non spécifié
Le DSM-IV comporte des listes de symptomes qui permettent de donner des notes permettant de classer un malade dans une ou plusieurs affections spécifiées..
 
   TB2,5, 3,5, ...

SPECTRE BIPOLAIRE
  AKISKAL .et PINTO, en réaction avec le recherche de sous-groupes, les TB 3.14157 , ont mis l'accent sur la continuité statistique entre les différentes formes de trouble bipolaire. Pour cela il ont inventé la notion de spectre bipolaire . N.Ghaemi dans sa chronique Le spectre bipolaire : une forme fruste  fait une analyse historique des limites des diagnostics des troubles de l'humeur.

BPI et BP II, continuité ou rupture

    Une premiére application de la notion de spectre bipolaite a été l'étude statistiques des TBI et TB2. Akiskal et col. analysent dans deux articles de 2003 la validité de la notion de spectre bipolaire sur un ensemble de patients. Il faut se poser la question de l'influence de l'instrument de mesure sur les réponses. Le niveau de dépression ou d'exaltation est déterminé par une questionnaire avec de très nombreuses questions. Il est normal que les réponses (les notes) se répartissent suivant une courbe de Gauss. Mais cela tient plus au questionnaire qu'à la pathologie. En pratique, TB1 et TB2 sont deux entités cliniques bien séparées.

DEPRESSIONS RECURRENTES ET TB II
  D'autres auteurs (en particulier l'école italienne autour de Benazzi) ont poursuivi dans cette voie "spectrale" et ont analysé la continuité ou discontinuité statistique avec les dépressions récurrentes et avec les dépressions unipolaires.

LA SYNTHESE DE ANGST

J.ANGST et A.GAMMA(Zurich) dans une synthése de 2002 (Clinical Approaches in Bipolar Disorders 2002; 1: 10-14) essaient de recadrer les études épidimiologiques recentes (EPIMAN et EPIDEP par exemple en France), avec la classification induite par les critéres du DSM-IV. Voici le tableau auxquels ils parviennent dans leur classification :

  

Les critéres du DSM-IV aboutissent à une prédominance écrasante du symptôme de dépression caractérisée (EDM) dans les troubles de l'humeur. Le ration entre la dépression unipolaire et les troubles bipolaires est de 10.8.  Or ce n'est pas ce que l'on constate dans les enquêtes cliniques ou l'on trouve de 25 à 50% des dépressions qui sont en réalités des dépressions bipolaires.

Le rééxamen des réponses aux questionnaires ervant de base au diagnostic dans le DSM-IV, en changeant les critéres de seuil de l'hypomanie  aboutit à une répartition en sous-groupes mieux en éféquation avec la clinique. Suivant le critére de seuil, pour une même prévalence, le rapport entre dépression et bipolarité varie de 3 (hard criterie) à 1(soft criteria).

   
Serretti A, Mandelli L, Lattuada E, Cusin C, Smeraldi E. Clinical and demographic features of mood disorder subtypes.
    Psychiatry Res. 2002 Nov 15;112(3):195-210.
Benazzi F. Clinical differences between bipolar II depression and unipolar major depressive disorder: lack of an effect of age.
    J Affect Disord. 2003 Jul;75(2):191-5.
Dorz S, Borgherini G, Conforti D, Scarso C, Magni G. Depression in inpatients: bipolar vs unipolar.
    Psychol Rep. 2003 Jun;92(3 Pt 1):1031-9.
Benazzi F. Bipolar II disorder and major depressive disorder: continuity or discontinuity?
    World J Biol Psychiatry. 2003 Oct;4(4):166-71.
Benazzi F. Bipolar II versus unipolar chronic depression: a 312-case study.
    Compr Psychiatry 1999 Nov-Dec;40(6):418-21

   Les résultats des analyses ont été en faveur d'une continuité du trouble bipolaire.

  CONSEQUENCES SUR LES TRAITEMENTS
    Si les troubles ont des affections distinctes (des boites séparées), à chaque boîte doit correspondre un ensemble de traitements. Si les troubles forment un continuum (le spectre bipolaire) le traitement doit varier aussi, de manière continue, en fonction des formes du troubles. L'enjeu diagnostique se double d'un enjeu thérapeutique.

  Les conséquences cliniques sont discutées dans le numéro de janvier 2006 du "Canadian Journal of Psychiatry". Un article de Scott Patten  "Does Almost Everybody Suffer From a Bipolar Disorder?".  Dans sa conclusion,il indique que les données épidémiologiques ne doivent pas sous-tendre les décisions thérapeutiques. Quand des décisions thérapeutiques sont nécessaires, seuls des essais cliniques randomisés peuvent apporter une évidence scientifique..

Les conséquences cliniques du large spectre, admises, sont minimes. Un traitement par thymorégulateur doit être réservé aux cas les plus graves.

 Une vision opposée est de souligner la mauvaise prise en charge des troubles bipolaires atténués (subthreshold) avec les graves conséquences pour les malades.  (5 mai 2007 Merikangas et col Arch Gen Psychiatry 2007; 64: 543–552)

---

Judd LL, Akiskal HS, Schettler PJ, Coryell W, Maser J, Rice JA, Solomon DA, Keller MB.
The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders?
J Affect Disord. 2003 Jan;73(1-2):19-32.
"BACKGROUND: The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. METHODS: The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. RESULTS: BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II patietns had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. LIMITATIONS: BP-I patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap in long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. CONCLUSIONS: The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems." [Abstract]

Judd LL, Schettler PJ, Akiskal HS, Maser J, Coryell W, Solomon D, Endicott J, Keller M.
Long-term symptomatic status of bipolar I vs. bipolar II disorders.
Int J Neuropsychopharmacol. 2003 Jun;6(2):127-137.
"Weekly affective symptom severity and polarity were compared in 135 bipolar I (BP I) and 71 bipolar II (BP II) patients during up to 20 yr of prospective symptomatic follow-up. The course of BP I and BP II was chronic; patients were symptomatic approximately half of all follow-up weeks (BP I 46.6% and BP II 55.8% of weeks). Most bipolar disorder research has concentrated on episodes of MDD and mania and yet minor and subsyndromal symptoms are three times more common during the long-term course. Weeks with depressive symptoms predominated over manichypomanic symptoms in both disorders (31) in BP I and BP II at 371 in a largely depressive course (depressive symptoms=59.1% of weeks vs. hypomanic=1.9% of weeks). BP I patients had more weeks of cyclingmixed polarity, hypomanic and subsyndromal hypomanic symptoms. Weekly symptom severity and polarity fluctuated frequently within the same bipolar patient, in which the longitudinal symptomatic expression of BP I and BP II is dimensional in nature involving all levels of affective symptom severity of mania and depression. Although BP I is more severe, BP II with its intensely chronic depressive features is not simply the lesser of the bipolar disorders; it is also a serious illness, more so than previously thought (for instance, as described in DSM-IV and ICP-10). It is likely that this conventional view is the reason why BP II patients were prescribed pharmacological treatments significantly less often when acutely symptomatic and during intervals between episodes. Taken together with previous research by us on the long-term structure of unipolar depression, we submit that the thrust of our work during the past decade supports classic notions of a broader affective disorder spectrum, bringing bipolarity and recurrent unipolarity closer together. However the genetic variation underlying such a putative spectrum remains to be clarified." [Abstract]

Serretti A, Mandelli L, Lattuada E, Cusin C, Smeraldi E.
Clinical and demographic features of mood disorder subtypes.
Psychiatry Res. 2002 Nov 15;112(3):195-210.
"The aim of this study was to investigate demographic, clinical and symptomatologic features of the following mood disorder subtypes: bipolar disorder I (BP-I); bipolar disorder II (BP-II); major depressive disorder, recurrent (MDR); and major depressive episode, single episode (MDSE). A total of 1832 patients with mood disorders (BP-I=863, BP-II=141, MDR=708, and MDSE=120) were included in our study. The patients were assessed using structured diagnostic interviews and the operational criteria for psychotic illness checklist (n=885), the Hamilton depression rating scale (n=167), and the social adjustment scale (n=305). The BP-I patients were younger; had more hospital admissions; presented a more severe form of symptomatology in terms of psychotic symptoms, disorganization, and atypical features; and showed less insight into their disorder than patients in the other groups. Compared with the major depressive subgroups, BP-I patients were more likely to have an earlier age at onset, an earlier first lifetime psychiatric treatment, and a greater number of illness episodes. BP-II patients had a higher suicide risk than both BP-I and MDSE patients. MDSE patients presented less severe symptomatology, lower age at observation, and a higher number of males. The retrospective approach and the selection constraints due to the inclusion criteria are the main limitations of the study. Our data support the view that BP-I disorder is quite different from the remaining mood disorders from a demographic and clinical perspective, with BP-II disorder having an intermediate position to MDR and MDSE, that is, as a less severe disorder. This finding may help in the search for the biological basis of mood disorders." [Abstract]

Benazzi F.
Clinical differences between bipolar II depression and unipolar major depressive disorder: lack of an effect of age.
J Affect Disord. 2003 Jul;75(2):191-5.
"BACKGROUND: Inconsistent clinical differences were reported in bipolar II versus unipolar depression. Age difference may be a confounding factor. Study aims were to describe the clinical and family history features of bipolar II versus unipolar depression, and to control for the possible confounding effect of age on clinical features. METHODS: Consecutive 126 unipolar and 187 bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. Variables studied were gender, age, age of onset, MDE recurrences, axis I comorbidity, MDE severity, psychotic, melancholic, and atypical features, depression chronicity, melancholic, atypical, and hypomanic symptoms, depressive mixed state-DMX3 (MDE+three or more concurrent hypomanic symptoms), and mood disorders family history. The effect of age on clinical differences was controlled by logistic regression (by adding age as an independent variable after each independent variable). RESULTS: Bipolar II had significantly lower age, lower age of onset, more recurrences, more atypical features, more DMX3, more family history of bipolar II and MDE. Almost all the clinical differences found significant in the first analysis resulted still significant when controlled for age. LIMITATIONS: Single interviewer, non-blind, cross-sectional assessment, bipolar II diagnosis based on history. CONCLUSIONS: Results confirmed previous findings, and showed that bipolar II-unipolar MDE clinical differences were not related to age." [Abstract]

Dorz S, Borgherini G, Conforti D, Scarso C, Magni G.
Depression in inpatients: bipolar vs unipolar.
Psychol Rep. 2003 Jun;92(3 Pt 1):1031-9.
"162 depressed inpatients were divided into three diagnostic groups to compare patterns of sociodemographic characteristics, psychopathology, and psychosocial: 35 had a single episode of major depression, 96 had recurrent major depression, and 31 had a bipolar disorder. Psychopathology and psychosocial functioning were measured by clinician-rated scales, Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, Clinical Global Impression, and self-rating scales, Symptom Checklist-90, Social Support Questionnaire, Social Adjustment Scale. The three groups were comparable on sociodemographic variables, with the exception of education. Univariate analyses showed a similar social impairment as measured by Social Support Questionnaire, Social Adjustment Scale, and no significant differences were recorded for the psychopathology when the total test scores (Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, Clinical Global Index, Symptom Checklist-90) were evaluated. Some differences emerged for single items in the Montgomery-Asberg Depression Rating Scale and Symptom Checklist-90. These findings suggest a substantial similarity among the three groups. Results are discussed in terms of the clinical similarities between unipolar and bipolar patients during a depressive episode as well as the limitations of cross-sectional study implies." [Abstract]

Benazzi F.
Bipolar II disorder and major depressive disorder: continuity or discontinuity?
World J Biol Psychiatry. 2003 Oct;4(4):166-71.
"AIM: To find if bipolar II disorder (BPII) and major depressive disorder (MDD) were distinct categories or overlapping syndromes. METHODS: 308 BPII and 236 MDD outpatients, presenting for major depressive episode (MDE) treatment, were interviewed with the Structured Clinical Interview for DSM-IV. History of mania and hypomania, and hypomanic symptoms present during MDE, were systematically investigated. Presence of zones of rarity between BPII and MDD depressive syndromes was assessed. Atypical and hypomanic symptoms were chosen because atypical features and depressive mixed state (ie, MDE plus more than 2 concurrent hypomanic symptoms, according to Akiskal and Benazzi 2003) were often reported to distinguish BPII from MDD depressive syndromes (more common in BPII). If BPII were a distinct category, distributions of these symptoms should show zones of rarity between BPII and MDD depressive syndromes. Histograms and Kernel density estimate were used to study distributions of these symptoms. RESULTS: BPII had significantly more atypical features and depressive mixed state than MDD. Histograms and Kernel density estimate curves of distributions of atypical and hypomanic symptoms in the entire sample did not show zones of rarity. CONCLUSIONS: Finding no zones of rarity supports a continuity between BPII and MDD (meaning partly overlapping disorders without clear boundaries)." [Abstract]

Benazzi F.
Bipolar II versus unipolar chronic depression: a 312-case study.
Compr Psychiatry 1999 Nov-Dec;40(6):418-21
"Differences between bipolar II depression and unipolar depression have been reported, such as a lower age at onset and more atypical features in bipolar II depression. The aim of the present study was to compare chronic/nonchronic bipolar II depression with chronic/nonchronic unipolar depression to determine whether the reported differences are present when chronicity is taken into account. Three hundred twelve outpatients in a bipolar II/unipolar major depressive episode were assessed with the Structured Clinical Interview for DSM-IV-Clinician Version (SCID-CV), the Montgomery and Asberg Depression Rating Scale (MADRS), and the Global Assessment of Functioning (GAF) Scale. No significant difference was found between chronic bipolar II and chronic unipolar depression (age at intake and onset, gender, duration of illness, recurrences, psychosis, atypical features, axis I comorbidity, and severity). A significantly lower age at onset and more atypical features were observed when comparing chronic/nonchronic bipolar II with nonchronic unipolar depression. These findings suggest that differences reported between bipolar II and unipolar depression are mainly due to nonchronic unipolar depression. Chronic unipolar depression may be a subtype intermediate between bipolar II depression and nonchronic unipolar depression." [Abstract]

The Bipolar Spectrum: A Valid Forme Fruste?

by S. Nassir Ghaemi, M.D.   http://www.mhsource.com/bipolar/insight0128gha.html

Closely related to the question of my previous column-whether or not bipolar disorder (BD) is misdiagnosed-is the issue of how to define bipolar disorder. For most of this century, American psychiatry's definition of manic-depressive illness has tended to be rather narrow (while those of schizophrenia and depression have been correspondingly broad). Over the last two decades, the diagnostic limits of schizophrenia have been narrowed greatly and those of affective disorders (including BD) broadened somewhat. This trend has led to increasing discussion of the concept of a "bipolar spectrum." Is this concept valid and useful?

Historically, the original conceptions underlying BD always reflected the controversy over whether to view the illness broadly or narrowly. (This history is best reviewed in Baldessarini [2000], and Goodwin and Jamison [1990]). In the mid- to late 19th century, leaders in French psychiatry identified mania and depression; they tended to diagnose manic-depressive conditions narrowly, with many subgroupings. In the late 19th and early 20th century, the German psychiatrist Emil Kraepelin first argued for a neat division of all psychotic syndromes into schizophrenia (narrowly conceived and limited to a small number of individuals in the population) and manic-depressive illness (broadly conceived and including what today we would call recurrent major depression). Kraepelin's work gained much influence for a few decades, but it was soon eclipsed by the rise of interest in Freud. Freud had little interest in diagnosis, and thus the controversy between Kraepelin's broad view and the earlier narrower French perspective ebbed. In the 1950s and 1960s, some European psychiatrists resuscitated the earlier French conceptions and made the distinction between bipolar (mania being present) and unipolar (mania not present) affective illnesses. Genetic and outcome research supported this model and led to its acceptance in American nosology with DSM-III in 1980. More recently, BD has been further divided into type I (mania present) and type II (hypomania present, a milder form of manic symptoms) in DSM-IV.

Thus, if one begins with Kraepelin's original broad concept of manic-depressive illness, mainstream psychiatry has moved to a more narrow description of BD (type I or II) and unipolar depression. For the last half century, this has meant that most clinicians have not diagnosed BD unless a patient was frankly, overtly and unequivocally manic (usually extremely agitated, psychotic and hospitalized). The tendency has been for everyone else to receive a diagnosis of unipolar depression or schizophrenia. This scenario is a source of some wonder. The textbooks say, and everyone claims to agree, that unipolar depression and schizophrenia are diagnoses of exclusion. One is supposed to rule out past mania before diagnosing unipolar depression in a nonpsychotic depressed individual; one is also supposed to rule out mania before diagnosing schizophrenia in a psychotic individual. Yet, in each case, since mania has only been diagnosed when extreme and severe, it is my opinion that the tendency is to underdiagnose BD. (See my previous columns for empirical studies that support this notion.)

The concept of the bipolar spectrum is, in many senses, a reversion to the original Kraepelinian perspective. Today, when referring to the bipolar spectrum, the clinician is first making the statement that mania is not necessary for the diagnosis of bipolar disorder. Hypomania would do, being defined as milder manic symptoms lasting a few days or more that are not associated with any significant social or occupational dysfunction. This last qualifier is extremely important. With hypomania, one has no difficulties; in fact, one is functioning more effectively in life. I believe that hypomania is the only diagnosis in DSM-IV that does not have, as one of its criteria, the presence of significant social or occupational dysfunction. This makes type II BD (hypomania and depression) unique-the defining diagnostic feature (hypomania) occurs when someone is feeling well. This, of course, often makes it difficult for individuals and clinicians to recognize. The problem with bipolar II disorder, consequently, is not hypomania, but the inevitable depressions that precede or follow it.

Bipolar II disorder is becoming more and more accepted as a valid diagnosis, although it remains a quite unreliable one, i.e., clinicians often do not agree on what to call hypomania and what to call normal mood. In my opinion, most clinicians are culturally biased to overdiagnose normality and underdiagnose hypomania.

The other part of the bipolar spectrum would be the category of NOS (not otherwise specified). (The evidence for the following discussion is best detailed in Akiskal [1996].) This could include individuals with a family history of type I BD and those who have hypomania only on antidepressants. Other potential "soft signs" of BD include atypical (increased sleep and appetite) and psychotic depressive episodes (both are more common in bipolar than unipolar depression); early age of onset of depressive illness; many brief recurrent depressive episodes (Kraepelin included them in his concept of manic-depressive illness); transient antidepressant response ("poop-out," meaning acute improvement but later relapse); and "hyperthymic" baseline personality when not depressed (a kind of chronic hypomania that is not brief and episodic but rather seems to be one's basic personality). A single soft sign is not diagnostic of the bipolar spectrum, but the more soft signs that exist, the increased likelihood that it is bipolar spectrum rather than unipolar depressive illness.

This broad bipolar spectrum view stems from observations regarding treatment response with lithium and antidepressants and, thus, has practical utility. Bipolar spectrum patients may be less likely to respond to antidepressants (thus representing part of that pool of people diagnosed with treatment-resistant depression) and may be more likely to respond to mood stabilizers (alone or along with antidepressants) (Akiskal, 1996).

If valid, the bipolar spectrum concept would have the advantage of redressing the imbalance in diagnostic perspectives and influencing clinicians to diagnose milder cases of mania and hypomania. An increase in diagnosis of the bipolar spectrum would also narrow down the diagnostic range of unipolar depression to more realistic and accurate levels. This is the perspective of individuals, myself included, who are attracted to the concept of the bipolar spectrum.

What can be said against the bipolar spectrum? First, there is little research to validate or invalidate it. To some extent, this is a circular problem: Since the field has generally ignored anything but classic bipolar I disorder, researchers and grant-giving agencies are often wary of giving money for research on a new and poorly documented concept such as the bipolar spectrum. I ran into this problem a few years ago when gabapentin (Neurontin), a new medication approved by the U.S. Food and Drug Administration for epilepsy, was to be studied for use in psychiatric conditions. I suggested that the drug be studied in type II bipolar depression along with, or perhaps instead of, type I BD. In my early clinical experience, I found limited efficacy for the medication in type I BD, but found suggested efficacy in type II bipolar illness. If gabapentin had mild to moderate mood-stabilizing effects, it might not work in type I BD, but it might have benefits in the milder parts of the bipolar spectrum (Ghaemi et al., 1998). This suggestion was not accepted on the grounds that the diagnosis of bipolar II disorder was unreliable (clinicians often disagree in defining hypomania), and that the diagnosis itself was too vague to be worth studying. Another factor may have been that the FDA has never recognized any bipolar diagnosis other than mania, and thus studying hypomania or the bipolar spectrum would not necessarily meet with any support on the part of federal regulators when seeking a treatment indication. Gabapentin went on to be ineffective in double-blind research on bipolar I disorder (Pande, 1999), and controlled research in the bipolar spectrum was never conducted.

The other major criticism made of the bipolar spectrum-in my opinion, the one with the most merit-is that the spectrum concept waters down the definition of bipolar disorder so much that it would impair biological research (Baldessarini, 2000). In general, for biological studies into the etiology and pathophysiology of a disease, it is necessary for the clinical definition of the condition to be as precise and homogeneous as possible. Since the spectrum concept is, by definition, broad and heterogeneous, it might impair the ability of biological studies to find the underlying problems leading to BD. This is a real concern.

One solution would be a "two-hat" answer. Wearing the researcher's hat, I would continue to focus on narrow, clearly defined bipolar I disorder. Wearing the clinician's hat, I would broaden my view to include the bipolar spectrum. Is this proposed solution inconsistent? Yes, but as Emerson long ago pointed out, consistency is not necessarily a component of truth. Whatever the biological etiology, the clinical manifestations of that etiology can vary immensely, especially as those manifestations might be influenced by varied environmental and other factors. This has long been recognized in medicine, where the concept of the forme fruste has long been invoked to describe mild, subtle forms of specific diseases.

Does bipolar disorder have a forme fruste? Probably. But we need to do more work on describing, defining and validating its characteristics.

Dr. Ghaemi is a research psychiatrist in the Psychopharmacology Program at Cambridge Hospital and an instructor in psychiatry at Harvard Medical School.

References

Akiskal HS (1996), The prevalent clinical spectrum of bipolar disorders: beyond DSM-IV. J Clin Psychopharmacol 16(2 suppl 1):4S-14S.

Baldessarini RJ (2000), A plea for the integrity of the bipolar disorder concept. Bipolar Disorders 2(1):3-7.

Ghaemi SN, Katzow JJ, Desai SP, Goodwin FK (1998), Gabapentin treatment of mood disorders: a preliminary study. J Clin Psychiatry 59(8):426-429.

Goodwin FK, Jamison KR (1990), Manic-Depressive Illness. New York: Oxford University Press.

Mixed States: Broad or Narrow?

by S. Nassir Ghaemi, M.D.   http://www.mhsource.com/bipolar/insight1001gha.html

I have previously discussed in this column several controversial questions related to bipolar disorder. I have expressed my opinion and presented some evidence that bipolar disorder is at times misdiagnosed, frequently as unipolar depression, and that antidepressants often are overused in the treatment of bipolar disorder. I have also suggested that a broad notion of the bipolar spectrum is likely to be clinically and scientifically accurate. Some of these views touch on the question of mixed states, which is the subject of this column.

Mixed episodes are currently defined by DSM-IV as the occurrence of a full manic episode and a full major depressive episode at the same time (with the exception that the duration of a mixed episode can be a minimum of one week, compared to two weeks for pure major depression). The inclusion of mixed episodes in DSM nosology is relatively new, and it appears that the criteria have been made deliberately narrow, perhaps to discourage overdiagnosis. Earlier definitions of mixed states were broader.

Like so much else related to bipolar disorder, the concept of mixed states dates back to Emil Kraepelin, who described two basic forms. (This subject has been reviewed well by Akiskal and colleagues [2000]). One type of mixed state was characterized predominantly by manic symptoms, with a few depressive symptoms also present. This has come to be called dysphoric mania. The other type was characterized predominantly by depressive symptoms, with a few manic symptoms also present. This has been referred to as agitated depression. For Kraepelin, and for those who would follow his approach to nosology in detail, both dysphoric mania and agitated depression would be considered mixed states of manic-depressive illness.

Part of the uncertainty concerning mixed states relates to the concept of the bipolar spectrum. Where should we draw the line on dysphoric mania, as opposed to pure mania? Where should we draw the line on agitated depression (viewed as a mixed state), as opposed to pure depression? How are we to decide?

As I have discussed previously in this column ("The Bipolar Spectrum: A Valid Forme Fruste?"), questions of diagnostic validity in psychiatry are difficult because of the lack of a gold standard. It is convention to base psychiatric diagnostic validity on five factors, and the more these factors converge and agree, the greater the likely validity of a diagnostic group. To recap, these factors are: 1) clinical signs and symptoms, 2) course, 3) family history/genetics, 4) biological markers, and 5) treatment response (Robins and Guze, 1970). Let us try to apply these diagnostic validators to different concepts of mixed states.

Beginning with dysphoric mania, how many depressive symptoms are needed to distinguish this state from pure mania: one, two, three? Since DSM-IV requires that full symptom criteria for major depression be met, the current nosology would answer that five depressive symptoms are needed. In one study, the presence of one depressive symptom (e.g., isolated depressed mood) predicted poor response to lithium and good response to an anticonvulsant, divalproex (Depakote) (Swann et al., 1997). This is one validator of diagnosis, since anticonvulsants generally are more effective in mixed states than lithium. However, treatment response is probably the weakest single validator of a diagnosis. This is because psychotropic medications are generally nonspecific--they are effective in multiple diagnoses, rather than being magic bullets for one diagnosis. Nonetheless, that observation should raise some doubt in one’s mind about an extremely narrow definition of mixed state. Other studies suggest that two or three depressive symptoms are associated with other features of mixed states, such as suicidality and poor outcome (Akiskal et al., 2000). In this same article, Akiskal et al. suggest that a broad definition of mixed states may be clinically useful.

One of the key confounding aspects of mixed states is the presence of depressive symptoms. Frequently clinicians and patients focus on the depressive symptoms and may fail to notice that manic symptoms are also present. In any depressed patient, it is important to rule out manic symptoms.

Antidepressant-induced manic symptoms sometimes seem to be of the mixed variety. Such mixed states may not be recognized as manic conditions, but rather be labeled “activation” or “agitation.” I often wonder whether some cases of antidepressant-related suicidality may not represent mixed states.

Obviously, the definition of mixed states is still not clear. It seems accepted that mixed states occur, but how frequently and where one draws the line between them and pure mood states are still subjects of some conjecture.

Dr. Ghaemi is director of the Bipolar Disorder Research Program at Cambridge Hospital and assistant professor of psychiatry at Harvard Medical School in Cambridge, Mass.

References

Akiskal HS, Bourgeois ML, Angst J et al. (2000), Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 59(suppl 1):S5-S30.

Robins E, Guze SB (1970), Establishment of diagnostic validity in psychiatric illness: its application to schizophrenia. Am J Psychiatry 126(7):983-987.

Swann AC, Bowden CL, Morris D et al. (1997), Depression during mania. Treatment response to lithium or divalproex. Arch Gen Psychiatry 54(1):37-42[see comment].


Pini S, de Queiroz V, Pagnin D, Pezawas L, Angst J, Cassano GB, Wittchen HU
Prevalence and burden of bipolar disorders in European countries.
Eur Neuropsychopharmacol. 2005 Aug;15(4):425-34.
A literature search, supplemented by an expert survey and selected reanalyses of existing data from epidemiological studies was performed to determine the prevalence and associated burden of bipolar I and II disorder in EU countries. Only studies using established diagnostic instruments based on DSM-III-R or DSM-IV, or ICD-10 criteria were considered. Fourteen studies from a total of 10 countries were identified. The majority of studies reported 12-month estimates of approximately 1% (range 0.5-1.1%), with little evidence of a gender difference. The cumulative lifetime incidence (two prospective-longitudinal studies) is slightly higher (1.5-2%); and when the wider range of bipolar spectrum disorders is considered estimates increased to approximately 6%. Few studies have reported separate estimates for bipolar I and II disorders. Age of first onset of bipolar disorder is most frequently reported in late adolescence and early adulthood. A high degree of concurrent and sequential comorbidity with other mental disorders and physical illnesses is common. Most studies suggest equally high or even higher levels of impairments and disabilities of bipolar disorders as compared to major depression and schizophrenia. Few data are available on treatment and health care utilization

Scott Patten
 "Does Almost Everybody Suffer From a Bipolar Disorder?"
"Canadian Journal of Psychiatry".  janvier 2006 (Can J Psychiatry 2006:51:6–8)
  Note :cet article vient après un article de Angst rappelant sa conception large du spectre bipolaire issue des données épidémiologiques.

The concept of a broad and inclusive bipolar spectrum disorders appear to be gaining momentum in the psychiatric literature, although cautionary comments have previously been made (for example, by Baldessarini; 1). The possibility that a large proportion of people diagnosed with depression actually have BD is an important clinical consideration and a natural corollary of this trend. I will not focus specifically on the unipolar-bipolar distinction, however, since the general trend toward broadening the diagnostic boundaries of BD raises similar issues for many other conditions (such as impulse control disorders and Axis II pathology). Rather, I will direct my comments toward the broad, ongoing debate about the bipolar spectrum concept. My intention is not to argue that existing diagnostic conventions are perfect or that a bipolar spectrum does not exist but to draw attention to certain issues that have not received adequate emphasis in the literature. These issues include setting appropriate diagnostic thresholds, the inevitable tension in psychiatry between empirically oriented and theory-driven concepts, and debate over the relative merits of categorical and dimensional measurement.
The arguments put forward in favour of a broad bipolar spectrum are protean. In 2000, Akiskal and colleagues provided a detailed review (2). Some of the more notable arguments are that hypomanic episodes may last less than the 4-day threshold specified in the DSM-IV, that certain subsets of subjects without a DSM-IV BD have a higher-than-expected proportion of relatives with BDs, that mixed states occur frequently and are underrecognized clinically, that patients with manic or hypomanic episodes induced by antidepressants often later manifest bipolar states, and that some subjects who do not meet DSM-IV criteria for a BD respond to mood stabilizers.
There is no formally accepted definition of what is meant by the term bipolar spectrum. The published works of various authors have adopted quite different emphases. To some authors, the idea of a spectrum implies a spectrum of symptom severity, resulting in the argument that a larger or milder set of bipolar symptoms should be accepted as fulfilling diagnostic criteria for hypomanic or mixed episodes. For some, the emphasis has been more deeply conceptual, typically targeting what is seen as an artificial distinction in the DSM-IV between unipolar and bipolar disorders. In this latter instance, the spectrum concept can be understood not simply as the broadening of a diagnostic category but as a more basic reappraisal, perhaps one that favours dimensional measurement.
The DSM-IV includes a kind of bipolar spectrum: BD I and BD II, as well as cyclothymic disorder. These are classified together with other mood disorders. Mixed states are treated much like manic states in the 6 DSM-IV coding categories for BD I. Further, the categories are fluid: a manic episode can move an afflicted individual from one category (such as major depressive disorder, recurrent) to another (such as BD I, most recent episode manic). However, the movement occurs as a result of signs and symptoms identified according to explicit diagnostic criteria. The classification operates within a fruitful empirical tradition established by the DSM-III, which attempts to be neutral with respect to etiologic theory. Some authors supporting the concept of a broad bipolar spectrum have emphasized that some patients diagnosed originally as suffering from unipolar depression later develop manic, hypomanic, or mixed episodes. Often, this observation is offered as if it provided self-evident confirmation of problems with the existing nosology—but it is rarely acknowledged that this is how the criteria are designed to work. The DSM-IV makes “no assumption that all individuals described as having the same disorder are alike in all important ways” (3, Introduction, p xxxi). Returning to a diagnostic approach that depends on theoretical assumptions about what bipolarity theoretically means (including assumptions about underlying pathophysiology) can jeopardize the advantages that an empirical approach offers. Similarly, modification of the diagnostic criteria for BD that results in the inclusion of people without actual evidence of the illness but whose clinical features suggest they may be at higher risk of developing it later (for example, by virtue of having a family history of BD or some other clinical feature that may be predictive of later development of a BD) would amount to backing away from the DSM-IV’s empirical stance and moving back toward the use of diagnostic definitions that are more subjective and more dependent on theoretical and etiologic beliefs.
Another set of issues revolves around the idea of a spectrum itself. The argument has been made that the bipolar spectrum spans a dimension ranging from acute psychopathology all the way to temperamental differences (2). These arguments challenge the utility of categorization in diagnostic practice, usually without offering much in the way of boundaries for the new entities being proposed. The most developed expression of this thrust is bipolarity scaling, several examples of which have appeared in the literature in recent years. The developers of these instruments have, however, typically presented the new scales as a means of augmenting, rather than replacing, categorical diagnoses.
Dimensional strategies have been recommended as an alternative to categorical diagnoses in almost every area of psychiatry. However, dimensional approaches have drawbacks. Dimensions tend to interface poorly with diagnostic practice and are more difficult to integrate, for example, with clinical practice guidelines. In the area of depression, dimensional symptom ratings are considered poor guides to clinical action, since a high score on a symptom rating scale may indicate a completely normal occurrence, such as bereavement, or a serious disorder. The same ambiguities are raised by dimensional evaluation of bipolarity, whether this uses explicit scaling or, more implicitly, the “soft bipolar spectrum” concept. A spectrum that does not differentiate clearly between, for example, differences in temperament and personality and overt psychopathology may not be useful in clinical practice.
Almost all measurable human characteristics distribute along spectrums. This is not de facto a critical flaw for diagnostic categorization. Blood pressure is an obvious example. In juxtaposition to the physical measurement of blood pressure, essential hypertension is a diagnostic construction that helps to bridge the gap between what can be evaluated in clinical practice and what should be done therapeutically. Nevertheless, like any diagnosis, the concept of essential hypertension is a construction that is vulnerable to rhetorical attack. It is even easier to argue that the diagnosis of essential hypertension should be replaced with a spectrum concept than it is to make the same case for bipolarity. Additional questions need to be answered, though. In the case of bipolarity, one question is of paramount importance: Can current treatment strategies for BD be generalized to the broader spectrum?
It has been asserted that epidemiologic studies, because of their reliance on “traditional” concepts of BD, have produced unrealistically low prevalence estimates for BD (2,4). The reality is that most studies attempting to apply DSM criteria by structured interview have found a very high prevalence of BD. Although instruments such as the DIS and the CIDI use existing diagnostic criteria, reappraisal studies have consistently found that clinicians conducting validation interviews believe that most of the bipolar syndromes identified are not clinically relevant (5,6). This same phenomenon probably accounts for the high prevalence of BD recently reported in Canada from the Canadian Community Health Survey: Mental Health and Well-Being, which used an interview based on the CIDI. The prevalence of BD I among people aged 25 to 64 years was 2.6% (7). These epidemiologic data suggest that manic and hypomanic symptoms blend to an appreciable extent with (what many psychiatrists would regard as being) normal experience, such that great caution must be used to constrain diagnostic definitions to what truly constitutes a disorder.
At this stage in the scientific development of psychiatry, diagnostic definitions and clinical guidelines should certainly remain somewhat fluid. However, changes should be driven by evidence, and the level of evidence must be appropriate to the question being addressed. In epidemiology, the evidence should derive from data showing enhanced performance (such as improved predictive validity) of reconstructed diagnostic categories or proposed dimensional alternatives. In the realm of therapeutics, randomized controlled clinical trials (including pragmatic trials) are the required standard of evidence. Some enthusiastic proponents of a broadened bipolar spectrum concept have seemed quick to assume that their arguments for redefinition, relabelling, and dimensional conceptualization have straightforward, self-evident therapeutic implications. This undercurrent is evident in frequent claims of vast underrecognition and undertreatment of BDs (2). These claims seem to imply that a large proportion of the population, including currently untreated people or people currently being treated with antidepressants, should be managed instead with mood stabilizers. However, basing treatment recommendations on theoretical, historical, and epidemiologic evidence exceeds the boundaries of what is now regarded as evidence-based practice.
When should diagnostic definitions be modified? Recently, it has been argued that the concept of clinical utility may provide an answer (8). Another consideration is scientific utility. If one conceptualizes an observable phenotype as being an indicator of some underlying etiologic disturbance, then definitions that are not specific for that disturbance will slow the rate of scientific progress by introducing bias toward the null, a dilution of observed effect known in epidemiology as nondifferential misclassification bias (9). Broadening diagnostic categories can be scientifically risky.
Proponents of the spectrum concept have raised interesting hypotheses that warrant continued evaluation in appropriately designed studies. Longitudinal studies, as pioneered and championed by Professor Angst, provide invaluable data that are capable of informing debate about many of the issues outlined above. Epidemiologic data, however, should not inform therapeutic decisions. When therapeutic decisions are involved, randomized controlled trials provide the required standard of evidence. Appropriate constraint in the bipolar spectrum literature will help to ensure continued progress.

                                                                            References

1. Baldessarini RJ. A plea for integrity of the bipolar disorder concept. Bipolar Disord 2000;2:3–7.

2. Akiskal HS, Bourgeois ML, Angst J, Post R, Möller HJ, Hirschfeld R. Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000;59(Suppl 1):S5–S30.

3. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. Text revision (DSM-IV-TR). Washington (DC): American Psychiatric Association; 2000.

4. Carta MG, Angst J. Epidemiological and clinical aspects of bipolar disorders: controversies or a common need to redefine the aims and methodological aspects of surveys. Clin Pract Epidemiol Ment Health 2005;1:4.

5. Kessler RC, Rubinow DR, Holmes C, Abelson JM, Zhao S. The epidemiology of DSM-III-R bipolar I disorder in a general population survey. Psychol Med 1997;27:1079–89.

6. Regeer EJ, ten Have M, Rosso ML, Hakkaart-van Roijen L, Vollebergh W, Nolen WA. Prevalence of bipolar disorder in the general population: a reappraisal study of the Netherlands Mental Health Survey and Incidence Study. Acta Psychiatr Scand 2004;110:374–82.

7. Wilkins K. Bipolar I disorder, social support and work. Health Rep 2004;15Suppl:21–30.

8. First MB, Pincus HA, Levine JB, Williams JB, Ustun B, Peele R. Clinical utility as a criterion for revising psychiatric diagnoses. Am J Psychiatry 2004;161:946–54.

9. Kleinbaum DG, Kupper LL, Morgenstern H. Information bias: epidemiologic research. New York (NY): Van Nostrand Reinhold; 1982. p 220–41.

Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication

Kathleen R. Merikangas, PhD; Hagop S. Akiskal, MD; Jules Angst, MD; Paul E. Greenberg, MA; Robert M. A. Hirschfeld, MD; Maria Petukhova, PhD; Ronald C. Kessler, PhD

Arch Gen Psychiatry. 2007;64:543-552. 5 mai 2007.

8 May 2007  Subthreshold bipolar disorder 'unrecognized and poorly treated

Medwire News: Subthreshold bipolar disorder is clinically significant, yet is often undetected in medical settings and inappropriately treated, results of a US survey indicate.

Kathleen Merikangas, from the National Institute of Mental Health in Bethesda, Maryland, and colleagues studied the prevalence, correlates, and treatment patterns of bipolar spectrum disorder. They say that clinicians increasingly see bipolar disorder as a spectrum of conditions that together are more common than bipolar I disorder.

Merikangas et alsurveyed a nationally representative sample of 9282 adults aged at least 18 years using the third version of the World Health Organization's Composite International Diagnostic Interview. Subthreshold bipolar disorder was defined as recurrent hypomania without a major depressive episode or with fewer symptoms than required for threshold hypomania.

For bipolar I disorder, the lifetime and 12-month prevalence estimates were 1.0% and 0.6%, respectively. This compares with 1.1% and 0.8%, respectively, for bipolar II disorder, while those for subthreshold bipolar disorder were 2.4% and 1.4%, respectively.

The average age of onset for symptoms was 18.2 years for bipolar I disorder, compared with 20.3 years for bipolar II disorder, and 22.2 years for bipolar II disorder. The persistence of each condition, defined as the ratio of the 12-month prevalence to the lifetime prevalence, was 63.3% for bipolar I disorder, versus 73.2% for B-II and 59.5% for subthreshold bipolar disorder.

Comorbid psychiatric conditions, such as anxiety disorder or substance use disorder, were identified in 95.8%–97.7% of patients with threshold bipolar disorder, compared with 88.4% of those with subthreshold disease.

While 89.2%–95.0% of patients with threshold bipolar disorder had a history of treatment, this compared with just 69.3% of those with a subthreshold disorder. Furthermore, the findings show that, over the previous 12 months, just 25.0% of patients with bipolar I disorder, 15.4% of those with bipolar II disorder, and 8.1% of those with subthreshold bipolar disorder were given appropriate medication.

The team says: "The present results reinforce the argument of other researchers that clinically significant subthreshold bipolar disorder is at least as common as threshold bipolar disorder. Although most individuals with bipolar disorder receive treatment owing to comorbid disorders, the lack of recognition of their underlying bipolarity leads to only a few receiving appropriate treatment."

The research is published in the Archives of General Psychiatry.
Source: Arch Gen Psychiatry 2007; 64: 543–552

ABSTRACT :
Context  There is growing recognition that bipolar disorder (BPD) has a spectrum of expression that is substantially more common than the 1% BP-I prevalence traditionally found in population surveys.

Objective  To estimate the prevalence, correlates, and treatment patterns of bipolar spectrum disorder in the US population.

Design  Direct interviews.

Setting  Households in the continental United States.

Participants  A nationally representative sample of 9282 English-speaking adults (aged 18 years).

Main Outcome Measures  Version 3.0 of the World Health Organization's Composite International Diagnostic Interview, a fully structured lay-administered diagnostic interview, was used to assess DSM-IV lifetime and 12-month Axis I disorders. Subthreshold BPD was defined as recurrent hypomania without a major depressive episode or with fewer symptoms than required for threshold hypomania. Indicators of clinical severity included age at onset, chronicity, symptom severity, role impairment, comorbidity, and treatment.

Results  Lifetime (and 12-month) prevalence estimates are 1.0% (0.6%) for BP-I, 1.1% (0.8%) for BP-II, and 2.4% (1.4%) for subthreshold BPD. Most respondents with threshold and subthreshold BPD had lifetime comorbidity with other Axis I disorders, particularly anxiety disorders. Clinical severity and role impairment are greater for threshold than for subthreshold BPD and for BP-II than for BP-I episodes of major depression, but subthreshold cases still have moderate to severe clinical severity and role impairment. Although most people with BPD receive lifetime professional treatment for emotional problems, use of antimanic medication is uncommon, especially in general medical settings.

Conclusions  This study presents the first prevalence estimates of the BPD spectrum in a probability sample of the United States. Subthreshold BPD is common, clinically significant, and underdetected in treatment settings. Inappropriate treatment of BPD is a serious problem in the US population. Explicit criteria are needed to define subthreshold BPD for future clinical and research purposes.

Author Affiliations: Intramural Research Program, Section on Developmental Genetic Epidemiology, National Institute of Mental Health, Bethesda, Md (Dr Merikangas); the International Mood Center, University of California San Diego and VA Psychiatry Service, San Diego (Dr Akiskal); Zurich University Psychiatric Hospital, Zurich, Switzerland (Dr Angst); Analysis Group, Boston, Mass (Mr Greenberg); Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston (Dr Hirschfeld); and Department of Health Care Policy, Harvard Medical School, Boston (Drs Petukhova and Kessler).