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Early recognition of bipolar disorder
European Psychiatry 22 (2007) 92e98 http://france.elsevier.com/direct/EURPSY/
Early recognition of bipolar disorder ¨ zgu¨rdal a,c, Andreas Heinz a, Marta Hauser a, Andrea Pfennig b, Seza O Michael Bauer b, Georg Juckel a,c,* a
Early Recognition Center of Beginning Psychoses, Department of Psychiatry, Charite´, Campus Mitte, Berlin, Germany b Bipolar Research Group, Department of Psychiatry, Charite´, Campus Mitte, Berlin, Germany c Bochum Early Recognition and Therapy Center, Department of Psychiatry, Ruhr-University Bochum, Bochum, Germany Received 16 March 2006; received in revised form 3 August 2006; accepted 5 August 2006 Available online 4 December 2006
Abstract Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale. Ó 2006 Elsevier Masson SAS. All rights reserved. Keywords: Early recognition; Bipolar disorder; Risk factors; Early symptom scale; Early intervention
1. Introduction The early recognition of mental disorders is a burning issue in clinical research. This is particularly important for bipolar disorders as they are often diagnosed only years after the onset of the illness. Such late recognition of the illness has far-reaching consequences for patients suffering from bipolar disorder. Reports of prevalence rates for bipolar disorders vary, in part due to methodological limitations (e.g., use of different diagnostic instruments, untrained interviewers, etc.), and in part because of the diagnostic criteria applied. In the past, milder forms of bipolar disorder, which today are included in the ‘‘bipolar spectrum’’, were disregarded in the diagnostic
* Corresponding author. Westfalian Centre Bochum, Psychiatrye PsychotherapyePsychosomatic Medicine, Ruhr-University Bochum, Alexandrinenstrasse 1, 44791 Bochum, Germany. Tel.: þ49 0234 5077 201; fax: þ49 0234 5077 204. E-mail addresses: [email protected] (M. Hauser), andrea.pfennig@ ¨ zgu¨rdal), andreas. charite.de (A. Pfennig), [email protected] (S. O [email protected] (A. Heinz), [email protected] (M. Bauer), georg. [email protected] (G. Juckel). 0924-9338/$ - see front matter Ó 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2006.08.003
process. When one considers the whole bipolar spectrum, lifetime prevalence rates rise to 2.8% and even 6.5% [9] (cf. Table 1). For those affected, bipolar disorder has considerable effects on social and occupational functioning. For example, only few marriages survive more than three manic episodes. This destructive picture also includes a 40% higher rate of suicide attempts, 15% of which are lethal [25]. 2. Background for early recognition Bipolar disorders are often not diagnosed until years after the onset of the illness. Patients often already have a longstanding history of psychiatric illness because the correct differential diagnosis to schizophrenia, attention-deficit hyperkinetic disorder (ADHD) or borderline personality disorder is difficult to establish. Additionally, bipolar disorders are initially often diagnosed as unipolar depression because most patients seek out treatment or are hospitalized during the depressive episodes. Such misdiagnosis of the bipolar spectrum disorders can have negative effects on the course of treatment in that it can lead to more frequent occurrences of
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Table 1 Prevalence rates of bipolar disorder by diagnostic criteria (modified according to [6])
Narrow definitions of bipolar disorder
Broader definitions of bipolar disorder
Authors
Country
Lifetime prevalence (%)
Kessler et al., 1994 Regier et al., 1988 Weissmann et al., 1996 Levinsohn et al., 1995 Szadoczky et al., 1998 Angst et al., 1998
USA USA Cross national USA Hungary Switzerland
1.6 1.2 0.3e1.5 5.7 5.0 2.8
episodes (e.g., rapid cycling) with increased age. In addition, longer duration of the untreated illness leads to greater chronicity of the illness in that residual symptoms that were initially absent from healthy periods do persist and the patient does not experience a full remission in between episodes any more, which also leads to more social impairment. A misdiagnosis and, consequently, inadequate treatment can have a far-reaching negative impact on the subsequent course of the disease, particularly in cases of patients presenting with unipolar depression. Studies indicate that treatment with antidepressants in the presence of an undetected bipolar disorder can lead to an increased risk of suicide [10] and can, particularly in patients with a genetic risk for bipolar disorder, trigger manic symptoms [24] or strong mood swings [16]. These findings are especially significant given that studies show that 20e40% of adolescents experiencing a depressive episode will be diagnosed with bipolar disorder within the next five years. Similar numbers are presented by the American Academy of Child and Adolescent Psychiatry, which reflects the situation of approximately 1.1 million children and adolescents in the USA alone. Fig. 1 shows a graphic representation of the time lost between an initially mistaken diagnosis and a final correct diagnosis. In order to prevent these debilitating consequences for the patients, it is imperative that bipolar disorders are diagnosed correctly and treated as early as possible. One promising approach is the use of diagnostic instruments for early recognition of the illness and consequently provision of early interventions. Such instruments have been successfully used for schizophrenia disorders for several years now [18]. Research on the schizophrenic ‘‘Basic Symptoms’’ has produced a short version of the ‘‘Bonn Scale for Assessment of Basic Symptoms’’ (BSABS-P, Schultze-Lutter andKlosterko¨tter, Ko¨ln). It was shown to have satisfactory predictive power, a relatively low false-positive prediction rate and appears to be particularly useful in the early recognition of very early
Age
19,3
23,1
first depression
first visit of a doctor
28,4
28,8
first mania first treatment with AD
schizophrenic prodromes [17]. Research conducted in order to establish the definition for the prodromal phase of schizophrenia disorders in the DSM-III-R led to the development of critical criteria, which today are also used for the assessment of pre-psychotic prodromes [27]. This kind of specific early recognition is not yet within reach for bipolar illness. The goal for future research must be to establish specific early symptoms and criteria, which can be used for the definition and assessment of the bipolar prodrome. This paper presents first considerations and research approaches. 3. Integrating previous research on early recognition of bipolar disorders to an Early Symptoms Scale 3.1. At what age should early recognition begin? For anyone inquiring about the topic of early recognition, age of onset is one of the first questions posed. In retrospective studies patients reported that the first signs of bipolar disorder were usually noticed between the ages of 15 and 19 years (Table 2). If those persons who report that signs of their illness were observed even before this age, i.e. in childhood, are taken into account, then the number increases to 59%, which means that over half experience early signs of the illness before the age of 19. Considering these results, it seems that a diagnosis of bipolar disorder in adulthood, during which time the illness is generally diagnosed, is much too late, and thus the prospect of recognizing bipolar disorders in adolescence is very promising. Consequently, this also points to the need for collaboration with child psychiatrists. Nevertheless other findings indicate later onset of bipolar disorders outside the USA; for example, the results of the Stanley Foundation Bipolar Network find the age of 24 to be the mean age of onset in a naturalistic follow-up study among German Centers [14]. Furthermore, Amminger et al. [1] found
34,1
first treatment with Mood stabilizer
Fig. 1. Extended time axis of a late recognized bipolar disorder (adapted from [16]).
36,1
diagnosis: bipolar disorder
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Table 2 Age at first signs of bipolar illness (adapted from [19]) Age in years
%
Absolute number
Under 5 5 to 9 10 to 14 15 to 19 20 to 24 25 to 29 30 and older
5 12 14 28 15 9 10
25 59 71 140 77 47 81
that an early age of onset (before age 18) was the best predictor to distinguish between affective and non-affective psychosis with non-affective psychoses showing later onset. Thus, considerations towards an early recognition in fact should estimate juvenile adolescents as well, especially as long as we do not know much about the natural course of the bipolar prodrome. Nevertheless, clinicians especially outside the United States should also consider older adolescents as persons at risk for bipolar disorder with later onset. 3.2. Early symptoms of bipolar disorder According to the National Depressive and Manic-Depressive Association, depressive symptoms are with 47% the predominant early signs of bipolar illness (Fig. 2). This is consistent with other investigations (for a review see, e.g., [9]), which showed that the course of bipolar disorders usually begins with a depressive and not with a manic episode. However, depressive symptoms are also the most common 8% 8%
11% 47%
26%
Depression
Mania/Hyperactivity
Mood Swings
Anger/Irritability
Delusions/Paranoia
Fig. 2. Most common initial symptoms (adapted from [19]).
initial symptoms of many other psychiatric disorders, are therefore not specific to bipolar disorders, and consequently not a reliable indicator of bipolar illness. This presents a big problem for the assessment and early recognition of bipolar disorders, whose main characteristic is the disturbance of affect. Therefore, such symptoms naturally have to be taken into account when diagnosing bipolar disorders. The Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia (PACE), a center for the early recognition of psychoses, presents first indications as to the nature of the prodromal phase of bipolar disorders that do not come from retrospective studies on patients with bipolar disorder or from prospective following of offspring but from a prospective following of symptomatic patients within an Early Recognition Center. Thompson et al. [26] report on three patients (average age 21 years) who came to the Early Recognition Center seeking clarification of a psychotic prodrome, which within the course of the following year manifested as a bipolar disorder (I and II). These patients initially showed predominantly depressive and anxiety symptoms, eating disorders, and substance abuse as comorbid disorders, only one of them against the background of a family history of bipolar disorder. Two of these patients also presented with racing thoughts and mood swings. The presence of attenuated positive symptoms in all three cases, i.e. psychotic symptoms not severe enough to meet diagnostic criteria for schizophrenia, was considered by the authors to be attributable to a patient selection particular to the nature of the Early Recognition Center and does not necessarily represent a typical characteristic of a prodromal phase of bipolar disorder, in particular because it was initially indistinguishable from a schizophrenic prodrome. More findings from other prospective followings within Early Recognition Centers, namely from the Recognition And Prevention Program (RAP) at the Zucker Hillside Hospital, New York, also lead to indicators of the bipolar prodrome, which are to be investigated in an Early Recognition Scale (Correll et al. 2006, personal communication). Consequently, depressive mood appears to be a basic feature of the bipolar prodrome, which for purposes of early recognition should be a prerequisite symptom. To allow for a reliable prediction, additional criteria with high predictive power must be included. In the search for these additional criteria, just as is the case with attenuated positive symptoms accompanying the pre-psychotic schizophrenic prodrome, we might be able to find certain bipolar symptoms lurking subclinically just below the threshold of severity so that a diagnosis of bipolar disorder is not yet warranted. This would mean that alongside the sub-threshold depressive mood, sub-threshold (hypo-)manic symptoms would be present. Bipolar disorder risk studies singled out mood dysregulationd‘‘frequent ups and downs’’das the strongest known risk factor. An examination [4] of 591 individuals from the Zurich cohort study using logistic regression analyses showed that mood regulation has a greater influence as a risk factor for bipolar disorder than does family history of bipolar disorder or a personality exhibiting ‘‘emotional and vegetative lability’’. However, the same result was found for (unipolar) depressive
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disorders, which according to the authors might be explained by the presence of individuals in the study with not yet recognized bipolar disorders. In our own sample of >20 bipolar patients investigated up to now, nearly all of them did not report ¨ zgu¨rdal et al. 2006, ‘‘ups and downs’’ as initial symptoms (O unpublished). They rather experienced mood swings prior to the first manic episodes that followed the first manifestation of depression. Interestingly the patients described themselves mostly as ‘‘good humored’’ persons until they suffered a depressive mood for the first time, which lasted longer and was more intensive than they had known it from ‘‘normal sadness’’. An 11-year prospective study by Akiskal et al. [8] also found mood dysregulation as the most powerful predictor for the transition from a unipolar to a bipolar disorder and ‘‘energy activity’’ as well as ‘‘daydreaming’’ to be of additional predictive power [7]. 3.3. Difficulties in determining affective symptoms as specific risk factors for the bipolar prodrome It is imperative for further research of early recognition to define the exact temporal and qualitative properties of the ‘‘ups and downs’’, i.e. the nature of the dysregulation, for it is the best predictive characteristic of the bipolar prodrome known so far. Existing definitions of the typical ‘‘ups and downs’’ of bipolar disorder are inadequate. The study by Angst et al. [4] operationalized the concept with the general question ‘‘Would you say you were one of those people who have frequent ups and downs?’’. It is surprising that on this basis healthy controls reported to hardly ever have ‘‘ups and down’’ (3.8%); however, patients reported experiencing frequent rapid mood swings in the form of brief sub-diagnostic depressive episodes (46.6%), which made the control group easily distinguishable from the group with affective disorders. In addition, in the study by Akiskal et al. [8] the construct of emotional dysregulation was elicited as a factor using various personality questionnaires. Angst et al. suggest a ‘‘new bipolar spectrum’’ [2,3] which includes the ‘‘softer’’ criteria for hypomania, dysthymic episodes as well as recurring brief depressive episodes as indicators for the presence of a bipolar II disorder. However, it seems very difficult to distinguish between these syndromes, so that the prodrome of a bipolar disorder seems to be part of the extended spectrum of bipolar disorders. The question arises of
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how one can define the ‘‘up’’- phases of the ‘‘ups and downs’’ risk factor, considering that the definition of hypomania in the extended bipolar spectrum does not include any necessary minimal duration or social impairment. Furthermore it is difficult to distinguish between the mild-bipolar II disorder, as defined by the previous mentioned mild hypomania and brief recurrent dysthymic, disorder and the bipolar prodrome in terms of episode frequency. Besides the above mentioned syndromes, the prodrome of bipolar disorder must also be differentiated from cyclothymia. Cyclothymia is characterized by numerous depressive and hypomanic episodes over a two-year period, and if a bipolar prodrome, similar to the schizophrenic prodrome, occurs several years before the manifestation of the illness, it would almost be impossible to distinguish between cyclothymia and the bipolar prodrome in terms of the time criterion and a definition of episodes. Table 3 is an attempt to present the difficulties encountered in delineating the conceptualizations of symptoms of a bipolar prodrome, cyclothymia and bipolar II disorder according to the extended criteria. Another difficulty is the differential diagnosis between the bipolar prodrome and a cyclothymic temperament [7]. Following the assumption that affective disorders are on a continuum, and that a particular type of temperament could be the basis for the development of a affective disorder later in life, bipolar disorder could develop from a cyclothymic temperament, whereby a particular clinical picture does not necessarily have to correspond to the underlying temperament. Akiskal et al. [7], therefore, prefer to speak of temperament when dealing with subclinical forms of an affective illness. A cyclothymic temperament, for example, can be measured by the TEMPS-A Scale. Some of the items on the questionnaire come very close to a possible definition of the risk factor ‘‘frequent ups and downs’’ for a bipolar prodrome (Items 23, 24, 29, 30, 34, 38). However, if a cyclothymic temperament is the basis for later bipolar disorder, and if similar items are used to measure the best predictive risk factor, namely the ups and downs/emotional dysregulation, the question arises of what additional factors point to a transition into the manifestation of bipolar illness. This is particularly relevant, in particular considering that the prodromal phase, as well as the cyclothymic temperament, can remain stable for years. Recent studies have compared persons with a family risk for bipolar disorder with persons diagnosed with bipolar disorder, persons diagnosed with a unipolar depressive disorder as
Table 3 Symptom conceptualizations for bipolar prodrome, cyclothymia and extended bipolar II disorder
Symptomatology
Onset Duration
Potential bipolar Prodrome
Cyclothymia
Extended Definition of a Bipolar II Disorder
Depressive and anxious mood
Episodes of mild depression
Frequent ups and downs
Episodes of slightly elated mood
Dysthymic episodes or brief recurring depressive episodes Hypomania in the sense of a syndrome with no minimal duration requirement and no social consequences
Adolescence Several months or years
Frequent switches of these episodes Late adolescence or early adulthood At least 2 years
Possible at any age
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well as persons with cyclothymic temperament. The results showed differences among these patient groups, which can be evaluated in terms of risk, but provided no specific risk factors. A comparison with the above-mentioned TEMPS-A Temperament Scale between healthy individuals with a family history for bipolar illness, bipolar patients in remission and healthy controls showed that the values for cyclothymic temperament for healthy individuals with family risk were lower than the ones for bipolar patients in remission, but higher than the ones for individuals without family risk for bipolar disorder [20]. A similar investigation of cyclothymic temperament yielded a continuum between healthy individuals without any risk, healthy individuals with a family risk of an unspecified affective disorder and healthy individuals with a positive family history of bipolar disorder [13]. Meyer and Hautzinger [22] established a connection between high values on the Hypomanic Personality Scale and more frequent patient reports of manic and hypomanic episodes in the subsequent clinical interview. However, this connection did not pertain to other mental disorders, which the authors viewed as an indication for the validity of the scale for bipolar disorders. Yet another difficulty for the diagnosis of a bipolar prodrome comes from different symptomatology corresponding with the wide range of ages of onset. For example, childhood bipolar disorders are characterized by slightly different symptoms of manic and depressive episodes than the ones in adulthood; whereas the symptomatology of adolescent and adult bipolar disorders is quite similar. Manic episodes in children show a more frequent fluctuation of symptoms and often include mixed states. The euphoria often found in adults is missing in children, and is replaced by increased irritability. The depressive syndrome manifests itself more with vegetative symptoms such as headaches, abdominal pains and increased tiredness. Additionally childhood bipolar disorder is characterized by higher frequency of manic and depressive episodes than adult bipolar disorder. Moreover, in contrast to studies which showed that depressive episodes are the first to occur at the development of bipolar disorders, Faedda et al. [15] found depressive symptoms in pediatric bipolar disorder to be reported least often by parents as symptoms at onset. Parents rather reported dysphoric-mania or mixed states. Chang et al. [12] singled out mood dysregulation and disruptive behavior as characteristic for the risk of bipolar disorder in offspring. Thus symptomatic changes and developments over time can complicate the assessment and diagnosis of the bipolar prodrome considerably. Nevertheless, it has to be considered that pediatric bipolar disorder may be a different clinical and neurobiological entity than bipolar disorder in adulthood and accordingly the bipolar prodrome, so that the characteristics in children do not necessarily give information about the nature of the bipolar prodrome in adolescence. In addition to the number of psychiatric syndromes that may develop during adolescence and early adulthood and that constitute similar unspecific symptomatology as the bipolar syndrome (e.g., schizophrenia, unipolar depression, personality disorders,
neurotic maladaptations, etc.), it also has to be differentiated from ‘‘normal’’ pubertal or adolescent crises. 3.4. Further potential risk factors According to Angst et al. [4] a positive family history of mania was another independent, though weaker factor than the ‘‘ups and downs’’, contributing to the risk for bipolar disorder. It is known that children of one bipolar parent have a 15e30% increased risk for bipolar disorder. The risk increases to 50e75% for children whose parents both have bipolar disorder. Taking another approach, Angst et al. [5] conducted a prospective study in which they looked at specific characteristics of individuals who moved from a diagnosis of unipolar depression to bipolar disorder as opposed to those who did not. Male gender and early onset of the illness were the resulting risk factors for the transition into bipolar I disorder. For the transition to bipolar II disorder, being female, a later onset of the illness and a family history of mania were found to be the main risk factors. On the other hand Birmaher et al. [11] found children and adolescents with major depressive disorder to be at higher risk for the development of bipolar disorder in cases where they show psychotic features, psychomotor retardation, pharmacological induced hypomania or mania and/or family history for bipolar disorder. Meyer and Blechert [21] investigated differences in attention deficit of healthy controls, individuals with a risk for unipolar depressive disorder and individuals with a risk for bipolar disorder. The study produced an interesting group classification. The group at risk for a bipolar disorder consisted of individuals who showed values in the upper 10% on the Hypomanic Personality Scale but had no further risk factors such as a positive family history for bipolar disorder. There were no general differences in attention deficit between the group of individuals who were at risk for a depressive disorder and those at risk for a bipolar disorder, though lesser differences pointed to cognitive deficits in individuals with a possible risk for bipolar disorder. 4. Necessary steps toward an early diagnosis of bipolar disorders As the review demonstrates, more research has been done in recent years in order to find specific features of the bipolar prodrome, i.e. the risk for developing bipolar disorder. The next step, in an effort to systemize the existing results, is to develop an early recognition scale and to evaluate it in prospective case studies in early recognition centers as was done with the schizophrenia prodrome. The scale should encompass the following criteria, which should help identify a person who is at risk and who then should be followed, e.g., through a prospective study: Considering the results of a connection between the cyclothymic temperament and bipolar disorder, a cut-off score on the TEMPS-A Scale should be set which indicates an
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increased risk for bipolar illness. Preliminarily the cut-off score could be set according to the discriminating score for individuals with family history as found by Mendlowicz et al. [20]. This score may need to be changed if prospective studies yield a more precise score. An individual meeting this requirement should be expected to also exhibit: The frequent ‘‘ups and downs’’ are the most powerful known predictor to date. This predictor should be examined further and defined in more detail than has been the case thus far. It is possible that these ‘‘ups and downs’’ express subjectively perceived, acute changes in the form of more frequent or more severe mood swings. Alongside the ‘‘ups and downs’’, there should be identifiable current or past distinct depressive or anxious mood episodes. Even minor symptoms pointing toward a mania such as elated mood, irritability or racing thoughts should be probed for, though paying careful attention to the agespecific symptomatology. No minimal duration for and no consequences from the symptoms are necessary in order to qualify them. To raise the probability of an actual existing risk and to allow for a better differentiation to bipolar disorder in childhood, screening for a bipolar prodrome with an early recognition scale in case of suspicion should be conducted with individuals from the age of 15 on, keeping in mind that later onset might be equally typical for the bipolar prodrome and older individuals in equal potential risk for bipolar disorder. Family history should be most definitely explored and taken into account as an additional predictor.
A prospective follow-up of individuals presenting with such features can yield important insight into a more precise characterization of the risk for bipolar disorder and thus the bipolar prodrome. To better distinguish between a schizophrenic and a bipolar prodrome, it would also be beneficial to examine individuals at risk for bipolar disorder with the BSABS-P (Schultze-Lutter and Klosterko¨tter, Ko¨ln) and the SIPS (Structured Interview for Prodromal Symptoms) [23], i.e., to check for basic symptoms and attenuated psychotic symptoms. It is rather improbable that psychosocial factors can add to the differentiation. 5. Summary and future directions Current efforts at early recognition of bipolar disorder are of greatest clinical relevance, especially in terms of the course of the illness. It is an enormous challenge to research that is being addressed in increasing numbers of studies. Drawing on already available results, considerations for an early recognition scale were presented in this paper, with which individuals can be identified for risk of bipolar disorder better than has been possible to date. It was suggested to assess these individuals in the context of early recognition centers and follow them in order to receive detailed information about potential risk factors, so that this knowledge can be used in the
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development of early intervention strategies as well as prevention for bipolar disorders. References [1] Amminger GP, Leicester S, Yung AR, Phillips LJ, Berger GE, Francey SM. Early-onset of symptoms predicts conversion to non-affective psychosis in ultra-high risk individuals. Schizophr Res 2006;84:67e76. [2] Angst G, Gamma A, Benazzi F, Ajdacic V, Eich D, Ro¨ssler W. Research report: Towards a re-definition of subthreshold bipolarity: epidemiology and proposed criteria for bipolar-II, minor bipolar disorders and hypomania. J Affect Disord 2003;73:133e46. [3] Angst G, Gamma A, Benazzi F, Ajdacic V, Eich D, Ro¨ssler W. Diagnostic issues in bipolar disorder. Eur Neuropsychopharmacol 2003;13:43e50. [4] Angst G, Gamma A, Endrass J. Risk factors for the bipolar and depression spectra. Acta Psychiatr Scand 2003;108(Suppl. 418):15e9. [5] Angst G, Sellaro R, Stassen HH, Gamma A. Research report: Diagnostic conversion from depression to bipolar disorders: results of a long-term prospective study of hospital admissions. J Affect Disord 2005;84:149e57. [6] Akiskal HS, Bourgeois ML, Angst J, Post R, Mo¨ller HJ, Hirschfeld R. Reevaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders. J Affect Disord 2000;59:S5e30. [7] Akiskal HS, Brieger P, Mundt C, Angst J, Marneros A. Temperament und affektive Sto¨rungen. Die TEMPS-A-Skala als Konvergenz europa¨ischer und US-amerikanischer Konzepte. Nervenarzt 2002;3:262e71. [8] Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller M. Switching from ‘unipolar’ to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995;52(2):114e23. [9] Bauer M, Pfennig A. Epidemiology of bipolar disorders. Epilepsia 2005;46(Suppl. 4):8e13. [10] Berk M, Dodd S. Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression? Med Hypotheses 2005;65:39e43. [11] Birmaher B, Arbelaez C, Brent D. Course and outcome of child and adolescent major depressive disorder. Child Adolesc Psychiatr Clin North Am 2002;11(3):619e37. [12] Chang K, Steiner H, Dienes K, Adleman N, Ketter T. Bipolar offspring: A window into bipolar disorder evolution. Biol Psychiatry 2003;53(11):945e51. [13] Chiaroni P, Hantouche E-G, Gouvernet J, Azorin J-M, Akiskal HS. Research report: The cyclothymic temperament in healthy controls and familially at risk individuals for mood disorder: endophenotype for genetic studies? J Affect Disord 2005;85:135e45. [14] Dittman S, Biedermann NC, Grunze H, Hummel B, Scha¨rer LO, Kleindienst N. The Stanley Foundation Bipolar Network: Results of the naturalistic follow-up study after 2.5 years of follow-up in the German centres. Neuropsychobiology 2002;46(suppl. 1):2e9. [15] Faedda GL, Baldessarini RJ, Glovinsky IP, Austin NB. Pediatric bipolar disorder: phenomenology and course of illness. Bipolar Disord 2004;6:305e13. [16] Ghaemi SN, Hsu DJ, Soldani F, Goodwin FK. Antidepressants in bipolar disorder. The case for caution. Bipolar Disord 2003;5(6):421e33. [17] Klosterko¨tter J, Hellmich M, Steinmeyer EM, Schultze-Lutter F. Diagnosing schizophrenia in the initial prodromal phase. Arch Gen Psychiatry 2001;58:158e64. [18] Klosterko¨tter J, Ruhrmann S, Schultze-Lutter F, Salokangas RK, Linszen D, Birchwood M, et al. The European Prediction of Psychosis Study (EPOS): integrating early recognition and intervention in Europe. World Psychiatry 2005;4(3):161e7. [19] Lish JD, Dime-Meenan S, Whybrow PC, Price RA, Hirschfeld RM. The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. J Affect Disord 1994;31(4):281e94. [20] Mendlowicz MV, Girardin J-L, Kelsoe JR, Akiskal HS. Research report: A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A. J Affect Disord 2005;85:147e51.
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[21] Meyer TD, Blechert J. Research report: Are there attentional deficits in people putatively at risk for affective disorders? J Affect Disord 2005;84:63e72. [22] Meyer TD, Hautzinger M. Research report: Screening for bipolar disorder using the Hypomanic Personality Scale. J Affect Disord 2003;75:149e54. [23] Miller TJ, McGlashan TH, Woods SW, Stein K, Driesen N, Corcoran CM, et al. Symptom assessment in schizophrenic prodromal states. Psychiatr Q 1999;70:273e87. [24] Reichart CG, Nolen WA. Earlier onset of bipolar disorder in children by antidepressants or stimulants? An hypothesis. JAffect Disord 2004;78(1):81e4.
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Early recognition of bipolar disorder ¨ zgu¨rdal a,c, Andreas Heinz a, Marta Hauser a, Andrea Pfennig b, Seza O Michael Bauer b, Georg Juckel a,c,* a
Early Recognition Center of Beginning Psychoses, Department of Psychiatry, Charite´, Campus Mitte, Berlin, Germany b Bipolar Research Group, Department of Psychiatry, Charite´, Campus Mitte, Berlin, Germany c Bochum Early Recognition and Therapy Center, Department of Psychiatry, Ruhr-University Bochum, Bochum, Germany Received 16 March 2006; received in revised form 3 August 2006; accepted 5 August 2006 Available online 4 December 2006
Abstract Bipolar disorders are frequently not diagnosed until long after their onset, leaving patients with no or correspondingly inadequate treatment. The course of the disorder is all the more severe and the negative repercussions for those affected all the greater. Concerted research effort is therefore going into learning how to recognize bipolar disorders at an early stage. Drawing on current research results, this paper presents considerations for an integrative Early Symptom Scale with which persons at risk can be identified and timely intervention initiated. This will require prospective studies to determine the predictive power of the risk factors integrated into the scale. Ó 2006 Elsevier Masson SAS. All rights reserved. Keywords: Early recognition; Bipolar disorder; Risk factors; Early symptom scale; Early intervention
1. Introduction The early recognition of mental disorders is a burning issue in clinical research. This is particularly important for bipolar disorders as they are often diagnosed only years after the onset of the illness. Such late recognition of the illness has far-reaching consequences for patients suffering from bipolar disorder. Reports of prevalence rates for bipolar disorders vary, in part due to methodological limitations (e.g., use of different diagnostic instruments, untrained interviewers, etc.), and in part because of the diagnostic criteria applied. In the past, milder forms of bipolar disorder, which today are included in the ‘‘bipolar spectrum’’, were disregarded in the diagnostic
* Corresponding author. Westfalian Centre Bochum, Psychiatrye PsychotherapyePsychosomatic Medicine, Ruhr-University Bochum, Alexandrinenstrasse 1, 44791 Bochum, Germany. Tel.: þ49 0234 5077 201; fax: þ49 0234 5077 204. E-mail addresses: [email protected] (M. Hauser), andrea.pfennig@ ¨ zgu¨rdal), andreas. charite.de (A. Pfennig), [email protected] (S. O [email protected] (A. Heinz), [email protected] (M. Bauer), georg. [email protected] (G. Juckel). 0924-9338/$ - see front matter Ó 2006 Elsevier Masson SAS. All rights reserved. doi:10.1016/j.eurpsy.2006.08.003
process. When one considers the whole bipolar spectrum, lifetime prevalence rates rise to 2.8% and even 6.5% [9] (cf. Table 1). For those affected, bipolar disorder has considerable effects on social and occupational functioning. For example, only few marriages survive more than three manic episodes. This destructive picture also includes a 40% higher rate of suicide attempts, 15% of which are lethal [25]. 2. Background for early recognition Bipolar disorders are often not diagnosed until years after the onset of the illness. Patients often already have a longstanding history of psychiatric illness because the correct differential diagnosis to schizophrenia, attention-deficit hyperkinetic disorder (ADHD) or borderline personality disorder is difficult to establish. Additionally, bipolar disorders are initially often diagnosed as unipolar depression because most patients seek out treatment or are hospitalized during the depressive episodes. Such misdiagnosis of the bipolar spectrum disorders can have negative effects on the course of treatment in that it can lead to more frequent occurrences of
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Table 1 Prevalence rates of bipolar disorder by diagnostic criteria (modified according to [6])
Narrow definitions of bipolar disorder
Broader definitions of bipolar disorder
Authors
Country
Lifetime prevalence (%)
Kessler et al., 1994 Regier et al., 1988 Weissmann et al., 1996 Levinsohn et al., 1995 Szadoczky et al., 1998 Angst et al., 1998
USA USA Cross national USA Hungary Switzerland
1.6 1.2 0.3e1.5 5.7 5.0 2.8
episodes (e.g., rapid cycling) with increased age. In addition, longer duration of the untreated illness leads to greater chronicity of the illness in that residual symptoms that were initially absent from healthy periods do persist and the patient does not experience a full remission in between episodes any more, which also leads to more social impairment. A misdiagnosis and, consequently, inadequate treatment can have a far-reaching negative impact on the subsequent course of the disease, particularly in cases of patients presenting with unipolar depression. Studies indicate that treatment with antidepressants in the presence of an undetected bipolar disorder can lead to an increased risk of suicide [10] and can, particularly in patients with a genetic risk for bipolar disorder, trigger manic symptoms [24] or strong mood swings [16]. These findings are especially significant given that studies show that 20e40% of adolescents experiencing a depressive episode will be diagnosed with bipolar disorder within the next five years. Similar numbers are presented by the American Academy of Child and Adolescent Psychiatry, which reflects the situation of approximately 1.1 million children and adolescents in the USA alone. Fig. 1 shows a graphic representation of the time lost between an initially mistaken diagnosis and a final correct diagnosis. In order to prevent these debilitating consequences for the patients, it is imperative that bipolar disorders are diagnosed correctly and treated as early as possible. One promising approach is the use of diagnostic instruments for early recognition of the illness and consequently provision of early interventions. Such instruments have been successfully used for schizophrenia disorders for several years now [18]. Research on the schizophrenic ‘‘Basic Symptoms’’ has produced a short version of the ‘‘Bonn Scale for Assessment of Basic Symptoms’’ (BSABS-P, Schultze-Lutter andKlosterko¨tter, Ko¨ln). It was shown to have satisfactory predictive power, a relatively low false-positive prediction rate and appears to be particularly useful in the early recognition of very early
Age
19,3
23,1
first depression
first visit of a doctor
28,4
28,8
first mania first treatment with AD
schizophrenic prodromes [17]. Research conducted in order to establish the definition for the prodromal phase of schizophrenia disorders in the DSM-III-R led to the development of critical criteria, which today are also used for the assessment of pre-psychotic prodromes [27]. This kind of specific early recognition is not yet within reach for bipolar illness. The goal for future research must be to establish specific early symptoms and criteria, which can be used for the definition and assessment of the bipolar prodrome. This paper presents first considerations and research approaches. 3. Integrating previous research on early recognition of bipolar disorders to an Early Symptoms Scale 3.1. At what age should early recognition begin? For anyone inquiring about the topic of early recognition, age of onset is one of the first questions posed. In retrospective studies patients reported that the first signs of bipolar disorder were usually noticed between the ages of 15 and 19 years (Table 2). If those persons who report that signs of their illness were observed even before this age, i.e. in childhood, are taken into account, then the number increases to 59%, which means that over half experience early signs of the illness before the age of 19. Considering these results, it seems that a diagnosis of bipolar disorder in adulthood, during which time the illness is generally diagnosed, is much too late, and thus the prospect of recognizing bipolar disorders in adolescence is very promising. Consequently, this also points to the need for collaboration with child psychiatrists. Nevertheless other findings indicate later onset of bipolar disorders outside the USA; for example, the results of the Stanley Foundation Bipolar Network find the age of 24 to be the mean age of onset in a naturalistic follow-up study among German Centers [14]. Furthermore, Amminger et al. [1] found
34,1
first treatment with Mood stabilizer
Fig. 1. Extended time axis of a late recognized bipolar disorder (adapted from [16]).
36,1
diagnosis: bipolar disorder
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Table 2 Age at first signs of bipolar illness (adapted from [19]) Age in years
%
Absolute number
Under 5 5 to 9 10 to 14 15 to 19 20 to 24 25 to 29 30 and older
5 12 14 28 15 9 10
25 59 71 140 77 47 81
that an early age of onset (before age 18) was the best predictor to distinguish between affective and non-affective psychosis with non-affective psychoses showing later onset. Thus, considerations towards an early recognition in fact should estimate juvenile adolescents as well, especially as long as we do not know much about the natural course of the bipolar prodrome. Nevertheless, clinicians especially outside the United States should also consider older adolescents as persons at risk for bipolar disorder with later onset. 3.2. Early symptoms of bipolar disorder According to the National Depressive and Manic-Depressive Association, depressive symptoms are with 47% the predominant early signs of bipolar illness (Fig. 2). This is consistent with other investigations (for a review see, e.g., [9]), which showed that the course of bipolar disorders usually begins with a depressive and not with a manic episode. However, depressive symptoms are also the most common 8% 8%
11% 47%
26%
Depression
Mania/Hyperactivity
Mood Swings
Anger/Irritability
Delusions/Paranoia
Fig. 2. Most common initial symptoms (adapted from [19]).
initial symptoms of many other psychiatric disorders, are therefore not specific to bipolar disorders, and consequently not a reliable indicator of bipolar illness. This presents a big problem for the assessment and early recognition of bipolar disorders, whose main characteristic is the disturbance of affect. Therefore, such symptoms naturally have to be taken into account when diagnosing bipolar disorders. The Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia (PACE), a center for the early recognition of psychoses, presents first indications as to the nature of the prodromal phase of bipolar disorders that do not come from retrospective studies on patients with bipolar disorder or from prospective following of offspring but from a prospective following of symptomatic patients within an Early Recognition Center. Thompson et al. [26] report on three patients (average age 21 years) who came to the Early Recognition Center seeking clarification of a psychotic prodrome, which within the course of the following year manifested as a bipolar disorder (I and II). These patients initially showed predominantly depressive and anxiety symptoms, eating disorders, and substance abuse as comorbid disorders, only one of them against the background of a family history of bipolar disorder. Two of these patients also presented with racing thoughts and mood swings. The presence of attenuated positive symptoms in all three cases, i.e. psychotic symptoms not severe enough to meet diagnostic criteria for schizophrenia, was considered by the authors to be attributable to a patient selection particular to the nature of the Early Recognition Center and does not necessarily represent a typical characteristic of a prodromal phase of bipolar disorder, in particular because it was initially indistinguishable from a schizophrenic prodrome. More findings from other prospective followings within Early Recognition Centers, namely from the Recognition And Prevention Program (RAP) at the Zucker Hillside Hospital, New York, also lead to indicators of the bipolar prodrome, which are to be investigated in an Early Recognition Scale (Correll et al. 2006, personal communication). Consequently, depressive mood appears to be a basic feature of the bipolar prodrome, which for purposes of early recognition should be a prerequisite symptom. To allow for a reliable prediction, additional criteria with high predictive power must be included. In the search for these additional criteria, just as is the case with attenuated positive symptoms accompanying the pre-psychotic schizophrenic prodrome, we might be able to find certain bipolar symptoms lurking subclinically just below the threshold of severity so that a diagnosis of bipolar disorder is not yet warranted. This would mean that alongside the sub-threshold depressive mood, sub-threshold (hypo-)manic symptoms would be present. Bipolar disorder risk studies singled out mood dysregulationd‘‘frequent ups and downs’’das the strongest known risk factor. An examination [4] of 591 individuals from the Zurich cohort study using logistic regression analyses showed that mood regulation has a greater influence as a risk factor for bipolar disorder than does family history of bipolar disorder or a personality exhibiting ‘‘emotional and vegetative lability’’. However, the same result was found for (unipolar) depressive
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disorders, which according to the authors might be explained by the presence of individuals in the study with not yet recognized bipolar disorders. In our own sample of >20 bipolar patients investigated up to now, nearly all of them did not report ¨ zgu¨rdal et al. 2006, ‘‘ups and downs’’ as initial symptoms (O unpublished). They rather experienced mood swings prior to the first manic episodes that followed the first manifestation of depression. Interestingly the patients described themselves mostly as ‘‘good humored’’ persons until they suffered a depressive mood for the first time, which lasted longer and was more intensive than they had known it from ‘‘normal sadness’’. An 11-year prospective study by Akiskal et al. [8] also found mood dysregulation as the most powerful predictor for the transition from a unipolar to a bipolar disorder and ‘‘energy activity’’ as well as ‘‘daydreaming’’ to be of additional predictive power [7]. 3.3. Difficulties in determining affective symptoms as specific risk factors for the bipolar prodrome It is imperative for further research of early recognition to define the exact temporal and qualitative properties of the ‘‘ups and downs’’, i.e. the nature of the dysregulation, for it is the best predictive characteristic of the bipolar prodrome known so far. Existing definitions of the typical ‘‘ups and downs’’ of bipolar disorder are inadequate. The study by Angst et al. [4] operationalized the concept with the general question ‘‘Would you say you were one of those people who have frequent ups and downs?’’. It is surprising that on this basis healthy controls reported to hardly ever have ‘‘ups and down’’ (3.8%); however, patients reported experiencing frequent rapid mood swings in the form of brief sub-diagnostic depressive episodes (46.6%), which made the control group easily distinguishable from the group with affective disorders. In addition, in the study by Akiskal et al. [8] the construct of emotional dysregulation was elicited as a factor using various personality questionnaires. Angst et al. suggest a ‘‘new bipolar spectrum’’ [2,3] which includes the ‘‘softer’’ criteria for hypomania, dysthymic episodes as well as recurring brief depressive episodes as indicators for the presence of a bipolar II disorder. However, it seems very difficult to distinguish between these syndromes, so that the prodrome of a bipolar disorder seems to be part of the extended spectrum of bipolar disorders. The question arises of
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how one can define the ‘‘up’’- phases of the ‘‘ups and downs’’ risk factor, considering that the definition of hypomania in the extended bipolar spectrum does not include any necessary minimal duration or social impairment. Furthermore it is difficult to distinguish between the mild-bipolar II disorder, as defined by the previous mentioned mild hypomania and brief recurrent dysthymic, disorder and the bipolar prodrome in terms of episode frequency. Besides the above mentioned syndromes, the prodrome of bipolar disorder must also be differentiated from cyclothymia. Cyclothymia is characterized by numerous depressive and hypomanic episodes over a two-year period, and if a bipolar prodrome, similar to the schizophrenic prodrome, occurs several years before the manifestation of the illness, it would almost be impossible to distinguish between cyclothymia and the bipolar prodrome in terms of the time criterion and a definition of episodes. Table 3 is an attempt to present the difficulties encountered in delineating the conceptualizations of symptoms of a bipolar prodrome, cyclothymia and bipolar II disorder according to the extended criteria. Another difficulty is the differential diagnosis between the bipolar prodrome and a cyclothymic temperament [7]. Following the assumption that affective disorders are on a continuum, and that a particular type of temperament could be the basis for the development of a affective disorder later in life, bipolar disorder could develop from a cyclothymic temperament, whereby a particular clinical picture does not necessarily have to correspond to the underlying temperament. Akiskal et al. [7], therefore, prefer to speak of temperament when dealing with subclinical forms of an affective illness. A cyclothymic temperament, for example, can be measured by the TEMPS-A Scale. Some of the items on the questionnaire come very close to a possible definition of the risk factor ‘‘frequent ups and downs’’ for a bipolar prodrome (Items 23, 24, 29, 30, 34, 38). However, if a cyclothymic temperament is the basis for later bipolar disorder, and if similar items are used to measure the best predictive risk factor, namely the ups and downs/emotional dysregulation, the question arises of what additional factors point to a transition into the manifestation of bipolar illness. This is particularly relevant, in particular considering that the prodromal phase, as well as the cyclothymic temperament, can remain stable for years. Recent studies have compared persons with a family risk for bipolar disorder with persons diagnosed with bipolar disorder, persons diagnosed with a unipolar depressive disorder as
Table 3 Symptom conceptualizations for bipolar prodrome, cyclothymia and extended bipolar II disorder
Symptomatology
Onset Duration
Potential bipolar Prodrome
Cyclothymia
Extended Definition of a Bipolar II Disorder
Depressive and anxious mood
Episodes of mild depression
Frequent ups and downs
Episodes of slightly elated mood
Dysthymic episodes or brief recurring depressive episodes Hypomania in the sense of a syndrome with no minimal duration requirement and no social consequences
Adolescence Several months or years
Frequent switches of these episodes Late adolescence or early adulthood At least 2 years
Possible at any age
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well as persons with cyclothymic temperament. The results showed differences among these patient groups, which can be evaluated in terms of risk, but provided no specific risk factors. A comparison with the above-mentioned TEMPS-A Temperament Scale between healthy individuals with a family history for bipolar illness, bipolar patients in remission and healthy controls showed that the values for cyclothymic temperament for healthy individuals with family risk were lower than the ones for bipolar patients in remission, but higher than the ones for individuals without family risk for bipolar disorder [20]. A similar investigation of cyclothymic temperament yielded a continuum between healthy individuals without any risk, healthy individuals with a family risk of an unspecified affective disorder and healthy individuals with a positive family history of bipolar disorder [13]. Meyer and Hautzinger [22] established a connection between high values on the Hypomanic Personality Scale and more frequent patient reports of manic and hypomanic episodes in the subsequent clinical interview. However, this connection did not pertain to other mental disorders, which the authors viewed as an indication for the validity of the scale for bipolar disorders. Yet another difficulty for the diagnosis of a bipolar prodrome comes from different symptomatology corresponding with the wide range of ages of onset. For example, childhood bipolar disorders are characterized by slightly different symptoms of manic and depressive episodes than the ones in adulthood; whereas the symptomatology of adolescent and adult bipolar disorders is quite similar. Manic episodes in children show a more frequent fluctuation of symptoms and often include mixed states. The euphoria often found in adults is missing in children, and is replaced by increased irritability. The depressive syndrome manifests itself more with vegetative symptoms such as headaches, abdominal pains and increased tiredness. Additionally childhood bipolar disorder is characterized by higher frequency of manic and depressive episodes than adult bipolar disorder. Moreover, in contrast to studies which showed that depressive episodes are the first to occur at the development of bipolar disorders, Faedda et al. [15] found depressive symptoms in pediatric bipolar disorder to be reported least often by parents as symptoms at onset. Parents rather reported dysphoric-mania or mixed states. Chang et al. [12] singled out mood dysregulation and disruptive behavior as characteristic for the risk of bipolar disorder in offspring. Thus symptomatic changes and developments over time can complicate the assessment and diagnosis of the bipolar prodrome considerably. Nevertheless, it has to be considered that pediatric bipolar disorder may be a different clinical and neurobiological entity than bipolar disorder in adulthood and accordingly the bipolar prodrome, so that the characteristics in children do not necessarily give information about the nature of the bipolar prodrome in adolescence. In addition to the number of psychiatric syndromes that may develop during adolescence and early adulthood and that constitute similar unspecific symptomatology as the bipolar syndrome (e.g., schizophrenia, unipolar depression, personality disorders,
neurotic maladaptations, etc.), it also has to be differentiated from ‘‘normal’’ pubertal or adolescent crises. 3.4. Further potential risk factors According to Angst et al. [4] a positive family history of mania was another independent, though weaker factor than the ‘‘ups and downs’’, contributing to the risk for bipolar disorder. It is known that children of one bipolar parent have a 15e30% increased risk for bipolar disorder. The risk increases to 50e75% for children whose parents both have bipolar disorder. Taking another approach, Angst et al. [5] conducted a prospective study in which they looked at specific characteristics of individuals who moved from a diagnosis of unipolar depression to bipolar disorder as opposed to those who did not. Male gender and early onset of the illness were the resulting risk factors for the transition into bipolar I disorder. For the transition to bipolar II disorder, being female, a later onset of the illness and a family history of mania were found to be the main risk factors. On the other hand Birmaher et al. [11] found children and adolescents with major depressive disorder to be at higher risk for the development of bipolar disorder in cases where they show psychotic features, psychomotor retardation, pharmacological induced hypomania or mania and/or family history for bipolar disorder. Meyer and Blechert [21] investigated differences in attention deficit of healthy controls, individuals with a risk for unipolar depressive disorder and individuals with a risk for bipolar disorder. The study produced an interesting group classification. The group at risk for a bipolar disorder consisted of individuals who showed values in the upper 10% on the Hypomanic Personality Scale but had no further risk factors such as a positive family history for bipolar disorder. There were no general differences in attention deficit between the group of individuals who were at risk for a depressive disorder and those at risk for a bipolar disorder, though lesser differences pointed to cognitive deficits in individuals with a possible risk for bipolar disorder. 4. Necessary steps toward an early diagnosis of bipolar disorders As the review demonstrates, more research has been done in recent years in order to find specific features of the bipolar prodrome, i.e. the risk for developing bipolar disorder. The next step, in an effort to systemize the existing results, is to develop an early recognition scale and to evaluate it in prospective case studies in early recognition centers as was done with the schizophrenia prodrome. The scale should encompass the following criteria, which should help identify a person who is at risk and who then should be followed, e.g., through a prospective study: Considering the results of a connection between the cyclothymic temperament and bipolar disorder, a cut-off score on the TEMPS-A Scale should be set which indicates an
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increased risk for bipolar illness. Preliminarily the cut-off score could be set according to the discriminating score for individuals with family history as found by Mendlowicz et al. [20]. This score may need to be changed if prospective studies yield a more precise score. An individual meeting this requirement should be expected to also exhibit: The frequent ‘‘ups and downs’’ are the most powerful known predictor to date. This predictor should be examined further and defined in more detail than has been the case thus far. It is possible that these ‘‘ups and downs’’ express subjectively perceived, acute changes in the form of more frequent or more severe mood swings. Alongside the ‘‘ups and downs’’, there should be identifiable current or past distinct depressive or anxious mood episodes. Even minor symptoms pointing toward a mania such as elated mood, irritability or racing thoughts should be probed for, though paying careful attention to the agespecific symptomatology. No minimal duration for and no consequences from the symptoms are necessary in order to qualify them. To raise the probability of an actual existing risk and to allow for a better differentiation to bipolar disorder in childhood, screening for a bipolar prodrome with an early recognition scale in case of suspicion should be conducted with individuals from the age of 15 on, keeping in mind that later onset might be equally typical for the bipolar prodrome and older individuals in equal potential risk for bipolar disorder. Family history should be most definitely explored and taken into account as an additional predictor.
A prospective follow-up of individuals presenting with such features can yield important insight into a more precise characterization of the risk for bipolar disorder and thus the bipolar prodrome. To better distinguish between a schizophrenic and a bipolar prodrome, it would also be beneficial to examine individuals at risk for bipolar disorder with the BSABS-P (Schultze-Lutter and Klosterko¨tter, Ko¨ln) and the SIPS (Structured Interview for Prodromal Symptoms) [23], i.e., to check for basic symptoms and attenuated psychotic symptoms. It is rather improbable that psychosocial factors can add to the differentiation. 5. Summary and future directions Current efforts at early recognition of bipolar disorder are of greatest clinical relevance, especially in terms of the course of the illness. It is an enormous challenge to research that is being addressed in increasing numbers of studies. Drawing on already available results, considerations for an early recognition scale were presented in this paper, with which individuals can be identified for risk of bipolar disorder better than has been possible to date. It was suggested to assess these individuals in the context of early recognition centers and follow them in order to receive detailed information about potential risk factors, so that this knowledge can be used in the
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[25] Simpson SG, Jamison KR. The risk of suicide with bipolar disorders. J Clin Psychiatry 1999;60(2):53e6. [26] Thompson KN, Conus PO, Ward JL, Phillips LJ, Koutsogiannis J, Leicester S, et al. Preliminary report: The initial prodrome to bipolar affective disorder: prospective case studies. J Affect Disord 2003;77: 79e85. [27] Yung AR, Phillips LJ, Yuen HP, McGorry PD. Risk factors for psychosis in an ultra high-risk group: psychopathology and clinical features. Schizophr Res. 2004;67(2-3):131e42.