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    Akiskal (1996) - The Prevalent Clinical Spectrum of Bipolar Disorders, Beyond DSM-IV

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    cxrs.ore1602 045408000 Jour of Cites Pyehophaaeolgy ‘oppaght ©1006 by Waama & Wine Vol 16,802 The Prevalent Clinical Spectrum of Bipolar Disorders: Beyond DSM-IV HAGOP S, AKISKAL, MD International Mood Clinic, University of California at San Diego, La Jolla, California Based on the author's work and that of collabo- rators, as well as other contemporaneous research, this article reaffirms the existence of a broad bipo- lar spectrum between the extremes of psychotic manic-depressive illness and strictly defined unipo- lar depression. The alternation of mania and melan- cholia beginning in the juvenile years is one of the most classic descriptions in clinical medicine that has come to us from Greco-Roman times. French alienists in the middle of the nineteenth century and Kraepelin at the turn of that century formalized itinto manic-depressive psychosis. In the pre-DSM- Ulera during the 1960s and 1970s, North American Psychiatrists rarely diagnosed the psychotic forms of the disease; now, there is greater recognition that most excited psychoses with a biphasic course, including many with schizo-affeetive features, be- long to the bipolar spectrum. Current data also sup- port Kraepelin’s delineation of mixed states, which frequently take on psychotic proportions. However, full syndromal intertwining of depressive and manie states into dysphoric or mixed mania—as empha- sized in DSM-IV—is relatively uncommon; depres- sive symptoms in the midst of mania are more rep- resentative of mixed states. DSM-IV also does not formally recognize hypomanic symptomatology that intrudes into major depressive episodes and gives rise to agitated depressive and/or anxious, dys- phoric, restless depressions with flight of ideas. Many of these mixed depressive states arise within the setting of an attenuated bipolar spectrum characterized by major depressive episodes and soft signs of bipolarity. DSM-IV conventions are most explicit for the bipolar II subtype with major depressive and clear-cut spontaneous hypomanic episodes; temperamental cyclothymia and hyper- thymia receive insufficient recognition as potential factors that could lead to switching from depres- sion to bipolar I disorder and, in vulnerable sub- jects, to predominantly depressive cycling. In the ‘main, rapid-cycling and mixed states are distinct. Nonetheless, there exist ultrarapid-cycling forms where morose, labile moods with irritable, mixed features constitute patients’ habitual self and, for ‘that reason, are often mistaken for “borderline” 4s personality disorder. Clearly, more formal researe, needs to be conducted in this temperamental inter. face between more classic bipolar and unipolar dis. orders. The clinical stakes, however, are such that anarrow concept of bipolar disorder would deprive many patients with lifelong temperamental dysreg ulation and depressive episodes of the benefits of! mood-regulating agents. (J Clin Psychopharmacg 1996;16{supp! 1]:4S-148) ‘uch of the recent thrust of research on mood dsr ders and their treatment has been aimed at major |" depressive illness, and bipolar disorder has been rele tively neglected. This is in part atiributable to epidemic logic studies,*= which estimate the lifetime risk for de pression to be 10 to 17%, whereas the comparable risk o bipolar disorder is 0.4 to 1.7%, Even in psychiatrie pops, lations, the ratio of unipolar to bipolar illness is skew | in favor of the former, ranging from 10:1 to 4:12 It is now ‘well documented that before the publication of the Diag nostic and Statistical Manual of Mental Disorders, thitt edition, (DSM-IID, patients with severe psychotic mari | were often diagnosed as “schizophrenic.”! A related ani) ‘more current reason for the relative neglect of bipolar is that nonresponders to lithium have been considers! schizo-affective, characterologically disturbed, or othe | ‘ise atypical thereby obscuring the relationship oft condition to bipolar disorders. Emerging research findings are changing this narrov picture. Several overlapping subtypes of bipolar disor der with hypomanic rather than manic features ha | been deseribed.# Moreover, severe or more comples| evolutive forms ofthe illness, with extreme psychoti | mixed,” and rapid-cycling!' forms have receive! greater clinical recognition. Finally, several anticonv sant agents have been shown to be efficacious for bat the classic and “new” forms of bipolar illness." As a result of these developments, which have ca siderably broadened the boundaries of bipolar illnes our clinical approach to this disorder is undergoing examination. This broadening of bipolar boundaries* | in line with Kraepelin’s position, and has received " ‘povalent Clinical Spectrum of Bipolar Disorders jor support in the GoodwinJamison textbook on inanie-lepressive illness." In this broadened perspec- five, both bipolar and cyclic “unipolar” disorders are considered to belong to the same morbid process. In this article, I will highlight these and other historic and landmark contributions that support the existence of a broad bipolar spectrum. I will then selectively review contemporaneous research developments since I first delineated the broad terrain of the bipolar spectrum in 1983." will examine the extent to which these devel- opments are reflected in the fourth edition of the Diag- nostic and Statistical Manual of Mental Disorders, the ‘agnostic system in clinical use in the United States and in many parts of the world. Finally, I will provide suggestions that go beyond DSM-IV, to enhance clini- clans’ approach to the complex diagnostic problems of bipolar patients observed in contemporary practice, History of the Bipolar Spectrum Aretaeus of Cappadocia, often credited for having ‘ade the historic connection between mania and metan- :holiain the second century A.D., was apparently not the inst to make this observation. According to Jackson,” several followers of the Methodist and Herophilus schools of medical thought had pointed out this eonneo- onasearly as the first century B.C. However, ofthe clas- Sictexts that have come tous, the description of Aretaeus isthe most compelling.* Building on the rich tradition of| Greco-Roman medicine, Aretacus revealed an intimate understanding of both the milder and extreme psychotic manifestations of these affective states, their tempera- mental bases, seasonality, sudden switches, aswell asthe association of the manic form with male gender and jouth. IL is noteworthy, particularly from the standpoint afte broad bipolar thesis being presented in this article, zat Aretaeus described the different stages of mania. Ini ially the illness would present in a euphoric-grandiose ‘orm: “If mania is associated with joy, the patient. may augh, play, dance night and day, and go to the market crowned as if vietorin some contest of skill... "The ideas he patients have are infinite .. . believing} they are ex- 2ers in astronomay, philosophy, or poetry. Atamore severe stage of mania, malignant psychotic tansformation would occur: “The patient may become “xcitable, suspicious, and iritabe..... his hearing may Decome sharp. ... some get noises and buzzing in the cars... or may have visual hallucinations... bad dreams and his sexual desires may get uncontrollable ifaroused to anger, he may become wholly mad and “un unrestrainedly, roar aloud... Kill his keepers, and ay violent hands upon himsell.” ‘These brilliant insights into the origin and evotution af affective states were lost for nearly two millennia, J. CuN PsvcHOPRARNACOR, VOL HSNO 2, SUPL I, APRN. 19 58 until rediscovered by French alienists in the nineteenth century.” Esquirol and his disciples® excelled in the clinical de- scription of the various mental maladies and their course over time; they were also concerned with docu- menting factors that contributed to new episodes, led to their evolution into more malignant forms, or produced recovery. This paved the way for Baillarger's character- ization of La Folie @ Double Forme" and Falret's de- scription of La Folie Circulaire.® ‘These developments in turn foreshadowed Krae- ppelin's description of different affective states under the rubric of manic-depressive psychosis.¥ This rubric represented the concept of the disease as a continuum in that recurrent melancholia, mania, as well as sub- syndromal fluctuations of activity, mood, and cognition between affective episodes—-which Kraepelin termed affective temperaments—were postulated to be part of the same disease process. Episodes of either polarity periodically erupted from these temperamental sub- strates, giving rise to the cyclic course of the illness. Similar to the French authors, Kraepelin'? described variety of course patterns, including continuous and rapid-eycling forms. Furthermore, he described six types of mixed states that he characterized by various admixtures of depression and mania that occur simul- taneously. Kraepelin thus provided a fundamental ar- gument in favor of the concept of a unitary affective dis- order. Table I surumarizes the cardinal features of three types of mixed states commonly observed today. ‘The kraepelinian position dominated psychiatric thinking until the 1960s, when a demarcation was made between unipolar and bipolar mood disorders. The International Classification of Diseases-10 (ICD-10),”" based in part on the Diagnostic and Statistical Manual of Mental Disorders, revised third edition, (DSM-ILR), basically endorsed this classification, thereby providing international sanction to this dichotomy. These manu- als describe patients with major or unipolar depression as those without episodes of mania or hypomania, ‘whereas dysthymia refers to the subsyndromal, chronic counterpart of unipolar depression and cyclothymia to the subsyndromal, more intermittent counterpart of bipolar disorder. ‘TanLe 1, Common varieties of mixed states observed in clinica ractce today Type of Mixed State Mood Thinking Aativiy Depressive oF Dyophoric Rush ofideas Increased Agitated depression Mournfil Pressure of speech Increased Depression with Decreased fight of ileas “Based on Kracpelins schema. Depressed Accelerated 6S Cur PsvoHormaRuicoL, Vor 16No 2, SUPPL, APRIL 1006 DSMAILR disregarded familial-genetie findings pub- lished in the early 1980s, arguing for a continuum be- tween unipolar and bipolar disorders. It also glossed over my 1983 proposal that the unipolar-bipolar di- chotomy needed revision, that many cyclical depres- sions belonged to a broad bipolar spectrum." Indeed, current clinical observations reveal greater complexity and variability than envisioned by the assumption of two fundamental affective forms.™'*' Thus, there are patients with dysthymia who become hypomanic and even manic,® patients with eyclothymia who evolve into se- vere depressive episodes,” and patients with “unipolar” depression who develop hypomania and even mania.%® Classical French and German psychiatrists had already described many such transitional forms of mood disor: ders." In today’s clinical practice, these transformations occur so frequently that the universe of mood disorders ‘cannot beso sharply divided between unipolar and bipo- Jar, Full-blown bipolar disorder with mania and strict unipolar depression (without manic or hypomanic episodes) represent the extremes of a spectrum! re- current depressions with hypomania occupy a middle territory (Table 2). Unlike DSM, where recurrent de- pressions with hypomania were ingloriously dubbed “bipolar not otherwise specified,” DSM-IV has accorded them formal nosologic recognition as bipolar IL This is tacit recognition of their prevalence and clinical signifi cance—this spectrum of soft bipolar disorders repre- sents among the greatest diagnostic and therapeutic challenges in clinical practice today, ‘The bipolar IIrubric as originally used by Dunner and colleagues' refers to patients hospitalized with depres- sion who had no mania but who, upon expert question- ing, gave histories of milder excitements of hypomanic proportions. Extensive longitudinal clinical observa. tions in the United States® and Italy®®" have revealed more subtle forms of hypomania that occur as part of a cyclothymic temperament (lifelong alternation of hy- pomania and minidepressions) or that of a hyperthymic ‘temperament (permanent hypomanic adjustment). This expansion of the area of soft bipolarity creates a large terrain of bipolar spectrum disorders and limits that of strictly defined unipolar disorders (Table 2). ‘The challenge for DSM-III was to guide practitioners to accept the concept that most excited psychotic pa- tients with a biphasic course (even many with mood- incongruent features) were suffering from manic- depressive or bipolar I disorder. This point of view was vindicated in a post-DSM-II research report by Gershon. and colleagues who have shown that schizo-affective disorder concentrates in the families of individuals with bipolar disorder. Further, they reported that of all the bipolar subtypes, schizo-affective disorder is associated with the highest risk for familial mood disorders, Abiay | TaBLE 2. Spectrum of bipolar disorders compared with nipoae depressions with special attention to the soft bipolar spectains ube Deseripion Bipolar me manic episode Dipolar Recurrent depressions with typomania and/or eycotyne | disorder Bipolar Recurrent depressions witha, | Soft bipolar") {pseudo- _apontancons hypomania buy unipolar) often with hyperthymle temperament andor bipolar family history Unipolar No evidence for hypomani, depressions cyclothymic disorder, hyperthymic disorde, or bipolar fail history “Based on Alaska." DSMAIV has made official the concept of milder, less! than manic, bipolar disorder such as bipolar T (evi! many from being cassifed as having unipolar depres sion). Interestingly, this manual has retained the rubric} “Dipolar not otherwise specified” for bipolar condos} wth lesser clang than bipolar I this contin, wih ts basically undefined, in principle acknowledges the possibility that some patients with cyelic depression] Couldstilbe considered bipolar inthe absence of dear cut hypomania. In bret, the greater challenge for cin cians today is the recognition of less than hypomanie| bipolar patients. ‘The remainder of this article focuses primarily on! clinical issues inthis new bipolar spectrum tat go be yond the conservative eonstraints of DSM. Manic-Depressive Disorder, Bipolar Type | Mania is uncommonly recurrent without depressive} episodes. Patients with recurrent mania have extremely poor insight and judgment and typically do not comply with long-term treatment.*5* Their course often leads to some deterioration. More commonly mania is par of a biphasic disorder that includes depressive episodes ‘This altemation between excited and profoundly de Jected periods is one of the unmistakable course pat tems in all of medicine. The clinician should note that bipolar depression can present with stupor, pseudode ‘mentia, anergia, hypersomnolence, somatization, agi tion, insomnia, and rarely, with tragic suicide or mut- dersuicide sequence.” Mania has an even broadet behavioral repertoire of clinical presentations that it clude, among others, intrusive meddlesome behavior, civie disturbances and brawls, sexual misconduct, | nancial ruin, alcohol and stimulant abuse, isolated ant: | social acts, paranoid psychosis, explosive psychosis and even delirious psychosis."* valent Clinica Spectrum of BXpolar Disorders ‘The classic concept of manic psychosis that can seach extremely psychotic proportions has been reaf- med" Misdiagnosis as schizophrenia can occur be- cause ofa variety of pitfalls suramaized in Table 8. Per- taps the most important of these is failure to take the prot course into consideration, Bipolar disorder is a phasic illness with relative normaley (sometimes «ven superior functioning) in the episode-free intervals. ‘his, incidental, cross-sectional symptoms that: may inggest “bizarteness,” “looseness,” or “mood incongr. |fce” should not be deciding factors. With respect to the ist feature in Table 3, not infrequently a schneiderian- Iype symptom such as “thought broadcasting” may be ipart of the grandiose delusional process of mania and {hould not be considered mood incongruent simply be- |cause itis one of Schneider's “first-rank symptoms.” Indeed, the experience of mania can be so compelling hat it can give rise to many seemingly bizarre and in coherent statements that, upon expert phenomenologie scrutiny, are ascribable to mania. Another deficiency of ie DSMAV definition of mania is failure to give promi- jtence to “heightened perceptions” asa cardial feature jof the disease;* coupled with distractible attention and he rush of ideas so characteristic of severe mania this, heightened perceptual set can produce a variety of hal- \iicinatory and delusional experiences that an spill | ower into so-called mood incongruence. Finally, itis im- Jportant to note that treatment with mood regulators— sad even with classic neuroleptics—could nearly abot sh the manic acceleration and elevated mood with relatively minor change of the psychotic experiences, jtereby creating a diagnostic artifact of psychotic symptoms in the absence of affective symptoms. |_Teis now well documented that depressive mania or |Pemhoric mixed states are particulary prone to de- ‘elop into severe psychotic states.® Tn these patients, |tescribed in a classic article by Himmelhoch and cok kagues,” depressive elements intrude into a manic syn- tome, giving rise to an extremely agitated psychotic Picture characterized by dysphorically elevated moods, jvere insomnia, psychomotor agitation, racing ‘thoughts, suicidal ideation, grandiosity, hypersexuality, | tisz:3, Common pitfalls in the evaluation of bipolar disorder ‘eng to asdagnonis of schizophreise ¥elance on cross-sectional rather than longitudinal picture { beampleteinterepisotic recovery equated with schizophrenic Sefoee "uation of bizarreness with schizophrenic thought disorder ‘scribing of iitable and cantankerous mood to paranokd delusions taking of depressive anhedonia and depersoraization for ) pitopheni emotional bunting Agito ideas pereeived as lose associations "eary eight given to incidental sehnelderian symptoms {)“Suumarized from Akiska and Puzantian? 4 CuN PSYCHOPHARMACOL, VoL ISINO2, SUPPL, APRIL1996 7S persecutory delusions, auditory hallucinations, and confusion. DSM-IV emphasizes full syndromal depres- sion and mania as necessary for diagnosing the mixed ‘manic phases of bipolar disorder. In clinical reality, a few depressive symptoms falling short of the syndrome are sufficient for creating a mixed manic pictures! ‘Neuroleptics often complicate the diagnostic processin mixed states in that, when prescribed to reduce agita- tion or acceleration, they could produce affective blunt- ing and give the false impression of bleulerian sympto- matology along schizophrenic lines. Ina more general vein, the clinical distinction of bipo- lar psychosis from schizophrenia'® ® can be accom: plished by several of the following: (1) loaded three-gen- eration family history for mood disorder, that is, with numerous affected family members in consecutive gen- erations; (2) biphasic course; (3) absence of persistent in- coherence and poverty of content; (4) good affective con- tact; (5) dramatic response to mood regulators; and (6) ‘good quality remission. Bipolar Types I and IL In outpatient clinical practice, recurrent depressions associated with spontaneous hypomania are preva- lent The interepisodie temperament in many, but not all, of these bipolar II patientsis cyclothymic, thatis,in- termittent depressions alternating with hypomanias (Table 4).® Other patients with depression, when first observed clinically, appear “unipolar” but are actually prebipolar in that their hypomania is first evident upon pharmacologic challenge; many of these patients have family history of bipolar disorder or a premorbid hyper- thymic temperament, that is, a permanently elevated baseline of hypomanic adjustment (Table 5). These depressed patients are best described as having bipolar Ill disorder. Whereas clinical depression oceurs later in the life of these patients with hyperthymia,” those with cyclothymia develop major depression by midadoles- cence or early adulthood. ‘The Pisa Memphis collaborative study" has demon- strated that, from a familial standpoint, the foregoing soft bipolar conditions are indistinguishable from bipo- lar I disorder. However, given that no more than 15% of these soft bipolar conditions are positive for a family history of bipolar disorder, such history itself is not of great value in clinical diagnosis. It is the presence of Iong-term temperamental dysregulation such asc) clothymia and hyperthymia, constituting part of the ha- bitual or interepisodic condition of the patient, that is of the greatest utility in assigning a diagnosis of a soft bipolar spectrum. ‘Some patients with dysthymie symptoms, especially those with intermittent minidepressions meeting the 88 FOUN PerctiormaRstAcon, Vou 16%NO2, SuPPL 1, AP 1096 ‘TaBtr 4 Clinical expressions of cyelotymic temperament Biphasic dysregulation sine teenage or ealy adult years and characterized by abrupt endoreactive shi from one phase to the other, each phase lasting for afew days at atime, with infrequent cethytnia Behavioral manifestations ypersonnuia vorsus decreased need for sleep Inteoverted selfabsorption versus uninhibited people seeking ‘Tocinum versus talkative ‘Unexplained tearfulness versus buoyant joculaity Psychomotor inetia versus restless pursit of aeliles Subjective manifestations Lethargy and somatic dscomfort versus eutoria Dulling of senses versus keen perceptions Slow-vitted versus sharpened thinking ‘Shaky self-esteem altemating between low self-confidence and ‘overconfidence Pessimistic brooding versus optimism and carefree atitudes “Updated from Aliskal and associates = criteria for depressive temperament, can also be considered part of the soft bipolar spectrum, This con- clusion is based on the finding that nearly one of three dysthymic patients observed prospectively in mood clinics develops hypomania, a phenomenon that typi- cally follows pharmacotherapy with antidepressants. This phenomenon occurs in adults* as well as in dys. thymie children. When monitored prospectively, some affected children also progress to dysphoric mixed- manic episodes. Dysthymie children who switch to hy- pomania usually do so after a superimposed major de- pressive episode. This means that a proportion of “double depressives" (patients with dysthymia plus ma- Jor depression) belong to the soft bipolar spectrum. ‘The latter conclusion is buttressed by family history.® Acloser examination of the spectrum of affective con- ditions observed among family members of the affec- lively ill can shed further light on the foregoing consid- erations.*® Patients with unipolar major depression have few bipolar relatives, although the number is much higher than in the general population, Patients with bipolar disorder, however, have more depressive ‘Tanur ._Hyperthymic temperament ‘These attributes are not episode-bound and constitute part ofthe ‘habitual long-term functioning ofthe individual Cheerful and exuberant Amticulate and jocular Overoptimistic and carefree Overeontident, boast, and grandiose Extroverted and people seeking igh energy level, full of plans and improvident activities Versatile with broad interests Overinvolved and meddlesome Uninhbited and stimulus seeking ‘Habitual short sleper less than 6 hoursnight) Updated from Akiskal® Aisa than manic relatives.# These apparently “unipolar ry tives of patients with bipolar disorder actually consti “pseudounipolar depressive” patients “Expert question: {ng will often reveal cyclic depressions interspersed with spontaneous hypomania; hence, most of these patieny, ‘will meet DSMIV criteria for bipolar Il disorder. Indeed a study from Johns Hopkins® has shown that bipolar i disorder is the most common phenotype in bipolar pe. grees. Other family members of probands with bipoly disorder are best described as bipolar II depressive episodes arising from a permanently elevated hyper tiiymic baseline, without evidence for clear-cut hypo. manic episodes. Finally, many depressive relatives ofp, ‘dents with bipolar disorder switch to hypomania or ‘mania during prospective follow-up. One ofthe best pre dictors (90-100%) of bipolar switching includes hypomne nia that develops during antidepressant pharmacother. apy. Even among patients with milder neurotic depression,® nine of ten patients with treatment-erer gent hypomania proceeded into spontaneous hypoma nias during prospective observation of 3 to 4 years only five patients developed bipolarity without passing through a pharmacologically mobilized hypomania (sen sitivity of 64%), In a recent review of the literature on “arug.induced” elations, Sultzer and Cummaings® found that most patients had either a family history of bipolar disorder or current mood disorder. In the agaregate, the foregoing findings argue against the DSMIV conserva. tive convention that excludes pharmacologically occa sioned hypomania from the bipolar rubric. Other predictors of bipolar II switching,® likewise validated through prospective observations, include temperamental mood lability and high-energetic activ. ity. The traits constituting energetic activity basicaly reflect a hyperthymic adjustment. As for mood lability, it is actually one of the core characteristics of cy clothyinia. Patients with eyclothymia exhibit alternat- ing subsyndromal depressive and elated states for shot periods of time; this eyelic variability is in essence ae! flection of these patients’ high-mood lability. Interest ingly, among clinically identified eyelothymic patients, very few (@%) become manic;’ by contrast, an average! of 25% of such patients develop major depression—in essence they develop bipolar I disorder. | ‘The depressive episodes of bipolar I disordertendto! be hypersomnie and hyperphagic, although, in some it) stances, insomnia is observed because of mixed pet ods. Furthermore, patients with bipolar Il disorder have soft signs of bipolarity and, unlike patients with strict unipolar depressive disorder, are at risk for switching with tricyclic antidepressants (TCAs);" this! propensity for hypomania induction appears someshal less with the selective serotonin reuptake inhibitors” ‘The Muctuaing alteration of depresove and hypo 2revatent Clinical Spectrum of Bipolar Disorders nanic periods in bipolar Il patients typically gives rise ‘9 interpersonal crises, often mistaken for borderline sersonality disorder. The essential clinical character- stics of bipolar Il disorder are sunumarized in Table 6. Hypomania is distinguished from mania by minimal mpairment, if any, and by the fact that it is of shorter uration. Although ICD-10" and DSM-IV stipulate a du- ‘ation of at least 4 days, hypomania duration of 2 days sas been validated in a Memphis, Tennessee, study,” and a modal range of I to 3 days has been found in dutich® The diagnosis of hypomanic states by history requires observation by others who testify that these states are different from the patient's habitual self. This point, emphasized by DSM-IV, represents important ex- ternal validation for hypomania as a clinical construct. Nonetheless, inexperienced clinicians often raise the uestion of how to differentiate “normal” happiness from clinically significant. hypomania: hypomania is a recurrent or intermittent condition, whereas ordinary human happiness is not! Furthermore, hypomania of- tenrepresents a sudden switch from a retarded depres- sive episode, ora sudden (typically morning) shift, from aeuthiymic baseline, Both seem to arise from rapid eye rovernent sleep preceded by night or so of sleep re- duction.* Ultimately, the retrospective diagnosis of hy- pomania will depend on a clinician sophisticated in the long-term examination of bipolar II patients. Prevalence and Comorbidity ‘The prevalence of bipolar disorder has been esti- nated to range from 0.4 to 1.7%? The lower figures are tased on studies focusing on euphoric mania, and the tigher figures derive from studies reporting on bipolar and I disorder. Other studies in community and clinical settings that lave examined hypomanic, eyctothymic, and related conditions have reported much higher rates. We first re- farted cyelothymia in 1086 of a chronic outpatient pop: Yation in Memphis in 197.” This finding was met with ‘ereat deal of skepticism. The following year, however, Weissman and Myers published an article on moody. luals at a subsyndromal level, accounting for 69% ‘the New Haven, Connecticut community subsample ‘der study. Subsequently, a study of college students a te inajor depressions ‘Soesomnic and hyperphaste fesson and resteseness tabi and switching during depressive episodes | Sey ornypomanic episodes or helo eelthymia ‘Bective or flamboyant appearance = tevetoua lope from Aliskal and associates = J. C1s PsvewomtARMacol, VoL INO 2, SUPPL, APRIL 1996 8S. by Depue and coworkers’ in Buffalo, New York, showed that 6% of their sample were cyclothymic. In 1986, Eckbald and Chapman® reported that up to 6% of | subsample of college students in Madison, Wisconsin, ‘met criteria for repeated hypomania. In the same year, Casey and ‘Tyrer; in Nottingham, England, reported that 0% in the community were explosive moody peo- ple. In another clinical study,*! in an unselected mental health population, we found 5% of patients were cy- clothymic. Finally, two epidemiologic studies in the 1990s reported on rates of hypomania in special age co- horts: 456 of 28- to 30-year olds in the Zurich, Switzer- land, canton, and 3 to 5% in teenagers in Oregon.* ‘Thus, 3 to 6¥ of the general population, possibly world- wide, seem to exhibit temperamental instability along hypomanic or eyciothymic lines. If we were to add full blown, manic-depressive cases, we would arrive at an estimate of 5 to 7% for the entire spectrum of bipolar disorders. ‘These figures explain the high prevalence of ey- . | logic overlap suggests that the clinician can approach many, but certainly nota, borderiine patients from ty | perspective of ulrarapid-cycling affective pathology an | its treatment. may be that borderline personal ds order—at least a common subtype—represents.a unique { condition where rapid cycling and switching are so fast | that mint-mixed states with iitablehostile depresive feanaresrepresent the modalmental and behavioral state ofthe patient. These considerations are obviously con troversial and stem from elinieal premises that lémately aspire to bring emerging treatments for mood disorder to benefit those with recalcitrant personality disorders.° | My main point in presenting this unsettled boundary issue is to highlight that nosology, especially ay it pe. tains to the broad realm of affective disorders, is nt just a matter of nuance or administrative necessity for our profession, butit has profound implications on ho wwe teat the affectivelyillin tenarrow sense and nore ‘TaBLe 10. Overlap inthe pharmacotherapy and paychotherapstot | borderline personality disorder and rapic-eycing and mixed bipote disotders Treatment Hordeine Personality Rapid-Gycling and Modality Disorder Mixed Bipolar Disorder? Tea = SSRI + 2 MAOr +e + Neurolepties + + Lithium + + BZ or DYPX + +e Sleep deprivation ? ~ BCT + +e Insightoriented therapy + * Supportandedveation + + “Updated from Aldskal and ssociaies” indicates worsening; =, equivocal response; + to ++, lm creasing responsiveness; ?, uncertainty, TCA, tieyelic antidepre ‘sant; SSRI, selective serotonin reuptake inhibitor, MAOI, monoaine ‘oxidose inhibitor: CBZ, carbamazepine; DYPS, divalproex, BCT, lc ‘roconwulsvetherspy frrviet int Spc ptr orden broadly, those with the full spectrum of affective dys- regulation. Researchers and clinicians who favor the | sepetinan schema would fee more comfortable with } tke paradigm presented in this article. Obviously, much debate will take place in our profession before DSM-V appears. I believe that the broad range of affective dis- turbances observed among the family members of the affectively ill—which eventually should be buttressed by emerging molecular-genetic approaches—would play a deciding role in redefining our current concepts of the spectrum of bipolar disorders and mood disor- ders in general. The thrust of my thinking has been that temperamental dysregulation is highly germane to the fidamental disturbance of bipolar spectrum disor ders,* leading to the postulate that- many recurrent de- | pressions arising from such dysregulation are within the broadened bipolar realm, References 1. Robins LN, Regler DA, eds. Paychiate disorders in Ametica [New York Froe Press, 101 | 2 Kessler RC, McGonagle KA, Zhao 8, Nelson CB, Hughes M, Esh: | leman 8, Witichen HU, Kendler KS Lifetime and I2-month prove | lence of DSMEILR psychiatric disorders inthe United States Re- sults trom the National Comorbidity Survey. 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