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The death of Hagop Akiskal left a great void in all who knew him, and many of us knew him, indeed, all over the world. Hagop was an attentive clinician and innovative researcher as well as a mentor who accompanied the growth of many young psychiatrists, a researcher sometimes controversial, never predictable, whose reflections have changed the way of seeing and conceiving mental illness in recent decades. And, above all, a gifted visionary that changed the field of bipolar disorders for better and forever. He rawarded of several international prizes, including the Jean Delay Prize of the World Psychiatric Association in 2002 (perhaps the most prestigious award in the field of psychiatry).

Emotional dysregulation (ED) is a heterogenous construct with great relevance in psychiatric research and clinical practice. In the present study, we validated a 40-items version of the Reactivity, Intensity, Polarity and Stability questionnaire (RIPoSt-40), a self-report measure of ED.A non-clinical sample (N = 396) and two clinical samples of patients with cyclothymia (N = 120) and ADHD (N = 54) were recruited. Items were selected and subscales were derived based on inter-item correlations and PCA with promax rotation in the non-clinical sample. Test-retest reliability was assessed in a subsample (N = 60). Internal consistency and concurrent validity with TEMPS-M factors were evaluated in each sample. The three groups results were compared to ascertain discriminant validity.Four subscales were identified as measures of affective instability, emotional impulsivity, negative and positive emotionality. The first three subscales also sum up to a negative ED score comprising thirty items. Measures of reliability (test-retest r = 0.71-0.84) and internal consistency (Cronbach's α = 0.72-0.95) were generally high. Concurrent validity was supported by correlations with TEMPS-M factors. Discriminant validity was significant (p 0.001) with cyclothymic and ADHD patients showing higher scores for each subscale, except for positive emotionality.The non-clinical sample was recruited through a web-survey and mainly included young and highly educated subjects. Mood and anxiety comorbidity of the clinical samples were not taken into consideration.RIPoSt-40 questionnaire has proved to be a valid, reliable and useful tool to assess ED both in clinical and non-clinical contexts.

Background: Contrary to DSM-5 definition based on recurrence of low grade hypomanic and depressive symptoms, cyclothymia is better defined in a neurodevelopmental perspective as an exaggeration of cyclothymic temperament. Emotional dysregulation with extreme mood instability and reactivity is the core features of the complex symptomatology. Method: In the present article, we critically reviewed the literature on the diagnosis and treatment of cyclothymia, focusing on the temperamental and neurodevelopmental perspectives. Results: Current epidemiological and clinical research showed the high prevalence and the validity of cyclothymia as a distinct form of bipolarity, frequently associated with multiple comorbidities with anxiety, impulse control, substance use, and so called “personality” disorders. Many patients receive correct diagnosis and treatments after many years of illness, when the superposition of complications reduces the possibility of complete remission. A therapeutic model combining the focus on symptomatic presentations with a temperamental perspective seems to represent an effective approach for cyclothymic patients with complex clinical presentations. Conclusion: Cyclothymic mood instability is an understudied issue despite the evidence of its clinical relevance. Unresolved issues concern its diagnostic delimitation and the possible relationships with emotional dysregulation observed in other neurodevelopmental disorders. We need to confirm the specificity of the disorder and to improve its recognition in early phase of the life, especially in youth. Early recognition means avoiding unnecessary complications and establishing specific treatments and clinical management since the beginning.

Background : Several studies have shown temperament variants in suicidality. Yet, to our knowledge, the association between temperaments and suicide attempts has not been studied on a nationally representative level nor systematically in subjects with no mental disorders. Also, although hyperthymic temperament is recognized as protective of most mental disorders, its role in the protection from self-harm remains inconclusive. Methods : The study is based on nationally representative data of all Lebanese adults. Mental disorders were assessed using the Composite International Diagnostic Interview, whereas the five affective temperaments were assessed using the TEMPS-A. Results : Anxious temperament is a solid and strong risk factor for suicide attempts in subjects with (OR: 10.1) and without (OR: 9.0) mental disorders. Depressive (OR: 4.3) and irritable (OR: 5.1) temperaments are risk factors for suicide attempt among subjects with mental disorders. Hyperthymic temperament plays a dual role in females with mental disorders: while the hyperthymic trait “having self-confidence” is strongly protective of suicide attempts, “liking to be the boss”, “getting into heated arguments”, and “the right and privilege to do as I please” are hyperthymic risk traits for suicide attempts reflecting the “dark side” of the hyperthymic temperament. Interestingly, these three hyperthymic risk traits— in the absence of “having self-confidence” —are a universal risk for suicide attempt in females with mental disorder. Limitations : Social desirability could have led to the under-reporting of suicide attempts and mental disorders. Conclusions : The anxious temperament plays a strong role in predicting suicide attempts in the community, in the presence and absence of diagnosable mental disorders. The irritable and the depressive temperaments are additional risks in subjects with mental disorders. The dual role of the hyperthymic temperament is quite interesting: while it is protective of suicidal behavior, it also has a dark side in subjects with mental disorders.

Background Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial. Methods The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender. Results Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (−), excessive alcohol use (+), cyclothymic temperament (−), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+). Limitations The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations. Conclusions Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.

Background Studies on mixed depression have been conducted so far on the basis of DSM-IV manic symptoms, i.e., a list of 7 symptoms which may provide limited information on the subsyndromal features associated with a full depressive episode. Methods As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 102 (23.8%) were classified as mixed depressives (≥3 hypomanic symptoms), and 146 (34%) as pure depressives (0 hypomanic symptom), after exclusion of bipolar I patients; hypomanic symptoms were assessed with the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn–Carroll in a self assessment format. A narrower definition of mixed depression, resting on those MVAS-BP items referring to DSM-IV hypomanic symptoms was also tested, as a sensitivity analysis. Results Compared to pure depressives, mixed depressive patients had more psychotic symptoms, atypical features and suicide attempts during their index episode; their illness course was characterized by early age at onset, frequent episodes, rapid cycling, and comorbidities. Mixed depressive patients were more frequently bipolar with a family history of bipolar disorder, alcohol abuse, and suicide. A dose–response relationship was found between intradepression hypomania and several clinical features, including temperament measures. The following independent variables were associated with mixed depression: hyperthymic temperament, cyclothymic temperament, irritable temperament, and alcohol abuse. Using the narrower definition of mixed depression missed risk factors such as suicidality and comorbidities. Limitations The following are the limitations of this study: retrospective design, recall bias, lack of sample homogeneity, no cross-validation of findings by hetero-evaluation of hypomanic symptoms. Conclusions EPIDEP data showed the feasibility and face validity of self-assessment of intradepressive hypomania. They replicated previous findings on the severity and high suicidal risk of mixed depression profile. They confirmed, for mixed depression, that mixed states occur when mood episodes are superimposed upon temperaments of opposite polarity. They finally suggested that a definition of mixed depression only based on DSM-IV-TR hypomanic symptoms may not allow to identify the most unstable subforms of the entity.

Current research is mainly focused on ‘classical episodic’ forms of bipolar disorder (I and II). Despite its historical roots, cyclothymia is still neglected among the bipolar spectrum disorders. Contrary to DSM definition, based on the recurrence of low-grade episodes, cyclothymia is better defined as an exaggeration of cyclothymic temperament: early onset, complex temperament structure, high mood instability and reactivity, and rapid switching. Current epidemiological and clinical research has demonstrated the high prevalence and the validity of cyclothymia as a distinct form of bipolarity. In this article, the authors discuss their own clinical research and expertise on the understanding and medical management of cyclothymia. This is the beginning of challenging work concerning psychoeducation, clinical, phamacological and genetic research.

Objectives As only a few studies so far systematically reported on bipolar patients subtyped according to first-episode polarity, we took the opportunity of having at disposal a large sample of bipolar I patients to specify the characteristics of patients included in these subtypes, with a special focus on temperament and triggering events. Methods A total of 1089 consecutive DSM-IV bipolar I manic inpatients were subtyped in manic onset (MO), depressive onset (DO) and mixed onset (MXO), and assessed for demographic, illness course, clinical, psychometric, comorbidity and temperament characteristics. Results The main characteristics of MO patients were a hyperthymic temperamental predisposition, a first episode triggered by substance abuse and an illness course with pure, severe and psychotic mania. In comparison, DO patients had more depressive temperaments, a first episode triggered by stress and alcohol, an illness course with more episodes, cyclicity, suicide attempts, anxious comorbidity and residual symptoms. Although sharing characteristics with either MO or DO, MXO patients had more mixed episodes and cyclothymic temperament. Limitations The following are the limitations of this study: retrospective design, bias toward preferential enrolment of MO patients, and lack of information on the number and polarity of lifetime episodes. Conclusions Findings from this study tend to confirm most of the differences previously evidenced among patients subtyped according to first-episode polarity. Differences found in temperamental predisposition and illness onset triggering events are worth noting and may help target early preventive interventions as well as orientate the search for specific genetic risk factors.

Objective The aim of this study is to identify risk factors for suicide attempts including bipolarity. Method The paper presents the most recent data on suicide attempts and depression with or without hypomanic features from three French “Bipolact”, studies including 2249 patients with recurrent or resistant depression. Hypomania and BP-II disorder were defined by a score of 10 or more on the Hypomania Checklist-20. Attempters and non-attempters were compared, and multivariate logistic regression analyses were performed on all the significant variables obtained in univariate tests. Results Rates of suicide attempts and of a family history of suicide were higher in BP-II disorder. Suicide attempts were best explained by a family history of suicide and mood disorders, recurrence of depression, the “irritable–risk-taking” dimension of hypomania, substance abuse, and need of psychiatric treatment. Limitations The study does not deal with DSM-IV BP-II disorder. Conclusion Clinicians need to be familiarized with these risk factors.

Temperament has been demonstrated clinically to be linked to mental disorders. We aimed to determine the possible role of temperament in mental disorders in a national epidemiologic study. A nationally representative sample of adults (n=1320) was administered the Lebanese-Arabic version of the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego Autoquestionnaire (TEMPS-A), and the Arabic CIDI 3.0, as part of the LEBANON study. The association among temperaments and DSM-IV mood, anxiety, and impulse control disorders was assessed. The anxious temperament was shown to be a robust predictor of most disorders, especially within the anxiety and depressive clusters. The hyperthymic temperament had a uniquely protective effect on most mental disorders, with the exception of separation anxiety, bipolar, substance abuse and impulse control disorders. These effects were moderated by age and education. Temperaments, previously largely neglected in epidemiologic studies, could play a major role in the origin of mental disorders.

Risk factors that may be associated with suicide attempts in bipolar disorder are still a matter of debate. We compared demographic, illness course, clinical, and temperamental features of suicide attempters vs those of nonattempters in a large sample of bipolar I patients admitted for an index manic episode. One thousand ninety patients (attempters = 382, nonattempters = 708) were included in the study. Multivariate analysis evidenced 8 risk factors associated with lifetime suicide attempts as follows: multiple hospitalizations, depressive or mixed polarity of first episode, presence of stressful life events before illness onset, younger age at onset, no free intervals between episodes, female sex, higher number of previous episodes, and cyclothymic temperament. These characteristics may help identify subjects at risk for suicide attempt throughout the course of bipolar disorder. We finally propose to integrate such characteristics into a stress-diathesis model of suicidal behavior, adapted to bipolar patients.

Background: Despite numerous studies on the comorbidity of bipolar and anxiety disorders, there is no satisfactory psychopathological model for their overlap. Method: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode of bipolar I disorder were subtyped according to the presence or not of lifetime anxiety comorbidity and assessed for demographic, illness course, clinical, associated condition, temperament, and treatment characteristics. Results: Lifetime anxiety comorbidity, defined as presence of at least one anxiety disorder in lifetime, was found in 27.2% (n = 297) of the sample. Compared to patients without such a comorbidity (n = 793), those who had it experienced a higher number of mood episodes and suicide attempts in the previous year, more stressors, organic disorders and less free intervals; furthermore, they showed more temperaments with depressive features and complex treatment. At study entry, they also experienced manic episodes with higher levels of depression, psychosis and hostility. The following independent variables were associated with lifetime anxiety comorbidity: higher scores on the Montgomery-Åsberg Depression Rating Scale, depressive temperament, irritable temperament, higher scores on the Scale for the Assessment of Positive Symptoms, episodes without free intervals and at least one stressor before the index episode. Conclusions: Factors associated with lifetime anxiety comorbidity in bipolar I patients may be integrated into a comprehensive diathesis-stress model emphasizing the role of irritable temperament as a source of mood instability and stress, and interacting with other temperamental characteristics to trigger the outbreak of both anxiety and bipolar symptoms.

Introduction: Despite numerous explanatory hypotheses, few studies have involved a large national clinical sample examining risk factors in the occurrence of rapid cycling during the course of bipolar illness.Methods: From 1,090 manic bipolar I disorder inpatients included in a multicenter national study in France, 958 could be classified as rapid or non-rapid cyclers and assessed for demographic, illness course, clinical, psychometric, temperament, comorbidity, and treatment characteristics.Results: Rapid cycling bipolar disorder occurred in 9% (n=86) of the study group. Compared to nonrapid cyclers (n=872), patients with rapid cycling experienced the onset of their illness at a younger age, a higher number of prior episodes, more depression during the first episode, and more suicide attempts. At study entry, they also experienced manic episodes with more depressive and anxious symptoms, but less psychotic features. The following independent variables were associated with rapid cycling: longer duration of illness, antidepressant treatment, episodes with no free intervals, cyclothymic temperament, lower scores on the Scale for Assessment of Positive Symptoms and presence of thyroid disorder. Retrospective study limited to bipolar I disorder inpatients; several factors previously associated with rapid cycling were not assessed.Conclusion: Our findings may confirm previous descriptions, according to which rapid-cycling develops later in the course of illness following a sensitization process triggered by antidepressant use or thyroid dysfunction, in patients with a depression-mania-free interval course, and cyclothymic temperament.

Objective: We tested whether factors other than episode severity contributed to psychosis in mania. Method: Psychiatrists collected systematic clinical data on 1090 hospitalized DSM-IV manic patients in France, and completed the Mania Rating Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS). Results: Using DSM-IV specifiers, 21.9% were non-severe, 28.2% severe without psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis scored significantly higher (P

Background: The aim of this study was to determine a cutoff score on the Mania Rating Scale (MRS), which easily allows identification of severe mania in a population of manic patients to be included in clinical trials of antimanic drugs. Method: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode were subtyped according to the specifier for severity and assessed for demographic characteristics, illness course and clinical symptomatology. Using receiver-operating characteristic (ROC) analysis, the optimal threshold for severity was determined on the MRS. Results: In a French national clinical sample (n = 1,090), 851 cases were specified as severe and 239 as nonsevere (mild + moderate) mania according to DSM-IV criteria (307 without psychotic features, 544 with psychotic features). Patients with severe mania scored higher on the MRS but showed the same levels of scores on the Montgomery Asberg Depression Rating Scale compared to nonsevere cases. Many characteristics of the whole sample and of the psychotic group were found to be comparable, respectively, to those reported in recent epidemiological studies, which was particularly true for age, gender, age at onset, number of mood episodes and suicide attempts. The optimal ROC solution for separating severe from nonsevere mania was a cutoff score of 39 on the MRS. This cutoff score displayed a positive predictive value of 0.91. Conclusion: A cutoff score of 39 is proposed as a severity threshold for mania on the MRS by virtue of its ROC validation in a large representative sample of severe versus nonsevere manic patients whose severity was assessed according to DSM-IV subtyping.

Data emerging from both academic centers and from public and private outpatient facilities indicate that from 20% to 50% of all subjects that seek help for mood, anxiety, impulsive and addictive disorders turn out, after careful screening, to be affected by cyclothymia. The proportion of patients who can be classified as cyclothymic rises significantly if the diagnostic rules proposed by the DSM-5 are reconsidered and a broader approach is adopted. Unlike the DSM-5 definition based on the recurrence of low-grade hypomanic and depressive symptoms, cyclothymia is best identified as an exaggeration of cyclothymic temperament (basic mood and emotional instability) with early onset and extreme mood reactivity linked with interpersonal and separation sensitivity, frequent mixed features during depressive states, the dark side of hypomanic symptoms, multiple comorbidities, and a high risk of impulsive and suicidal behavior. Epidemiological and clinical research have shown the high prevalence of cyclothymia and the validity of the concept that it should be seen as a distinct form of bipolarity, not simply as a softer form. Misdiagnosis and consequent mistreatment are associated with a high risk of transforming cyclothymia into severe complex borderline-like bipolarity, especially with chronic and repetitive exposure to antidepressants and sedatives. The early detection and treatment of cyclothymia can guarantee a significant change in the long-term prognosis, when appropriate mood-stabilizing pharmacotherapy and specific psychological approaches and psychoeducation are adopted. The authors present and discuss clinical research in the field and their own expertise in the understanding and medical management of cyclothymia and its complex comorbidities.

Background Although included in successive editions of the DSM since its introduction in the IIIrd, the subtyping of manic episode into ‘with mood-congruent (MCP) versus mood-incongruent (MIP) psychotic features’ is yet to be fully validated. Methods One thousand and ninety consecutive manic patients were recruited at 19 medical centers in France from December 2000 to April 2002. Patients were systematically assessed for sociodemographic characteristics, illness course, phenomenology and had to fill out biphasic mood charts during the first study week. Results Five hundred forty-four manic patients were psychotic, 364 (33.4%) being MCP, 180 (16.5%) MIP. Although both groups scored high on the Mania Rating Scale, MIP patients had significantly more often been diagnosed as schizophrenic, or anxiety disorders, with long delays to first diagnosis as bipolar disorder. MIP were also significantly different in a variety of domains: 2:1 female/male ratio; shorter free intervals between episodes; more auditory hallucinations, reference, persecutory and somatic delusions; more stressors; more anger; higher depression scores and diurnal variation of mood, as well as anxious symptoms and hyperemotionality upon improvement. Conclusions MCP and MIP manias occurred in nearly half of this largest sample of manic patients ever reported. As postulated 150 years ago by Falret and Baillarger in France, free intervals, characterize both forms of circular insanity. Both are prevalent and severe remitting forms of mania, but the latter differs from the former by much shorter free intervals, greater instability of mood and mixed anxious-depressive features. This is compatible with the Vienna School hypothesis that dysphoric instability of the patient may induce emotional reactions in significant others, which, in turn, might lead to extremely paranoid and psychotic symptom formation of the MIP type in manic patients. From a phenomenologic perspective—arising understandably from emotional processes—these considerations would place MIP mania more in the circular affective rather than in the schizophrenic domain.

Background : Clinical presentations of depression in bipolar disorder are varied, inconsistent and often confusing. Most previous studies have focused on bipolar I (BP-I). Given that bipolar II (BP-II) is the more common bipolar phenotype, which is often confused with unipolar (UP), the aim of the current analyses is to delineate the symptomalogic differences between BP II vs. UP MDD in a large national sample. Methods : The data derived from the French National EPIDEP study ( n =452 DSM-IV major depressives), subdivided into BP-II ( n =196) and UP ( n =256). The BP II group included major depressives with both spontaneous and antidepressant-associated hypomania based on our finding of similarity in rates of familial bipolarity in the two subgroups. At index presentation, depression was assessed by the clinician (using HAM-D and the Rosenthal Atypical Depression Scale) and by the patient (using the Multi-Visual Analog Scale of Bipolarity, MVAS-BP). Principal component analyses (PCA with varimax rotation) were conducted on HAM-D and MVAS-BP in the total population and separately in BP-II and UP. We performed inter-group comparative tests (UP vs. BP-II) on factorial scores derived from PCAs and correlation tests between these factorial scores. Results : The PCA on “HAM-D+Rosenthal scale” showed the presence of nine major factors: F1-2 “weight changes”, F3-4 “sleep disturbances”, F5 “sadness–guilt”, F6 “retardation–fatigue”, F7 “somatic”, F8 “diurnal variation” and F9 “insight–delusion”. The PCA on MVAS-BP revealed the presence of eight principal components: F1 “psychomotor retardation”, F2 “central pain”, F3 “somatic”, F4 “social contact”, F5 “worry”, F6 “loss of interest”, F7 “guilt” and F8 “anger”. Despite uniformity in global intensity of depression, significant differences were observed as follows: higher score on “psychomotor retardation” ( p =0.03), “loss of interest” ( p =0.057) and “insomnia” ( p =0.05) in the UP group, and higher score on “hypersomnia” ( p =0.008) in the BP-II group. Correlation analyses between clinician- and self-rating revealed the presence of higher number of significant coefficients in the UP vs. BP-II group ( p ≤0.001). Limitation : A three-way comparison between BP-I, BP-II and UP may have yielded somewhat different results. Conclusion : Our data indicate greater psychomotor retardation, stability and uniformity in the clinical picture of strictly defined UP depression. By contrast, bipolar II depression appeared to be characterized, despite the hypersomnic tendency, by psychomotor activation. This would indicate greater mixed features than those observed in UP. Moreover, in BP-II, there was less agreement between clinician vs. self-rating on the presence of various features of depression. Taken together, these findings explain why BP-II depression is missed by clinicians as a genuine depression.

Background: In the present report deriving from the French national multi-site EPIDEP study, we focus on the characteristics of Bipolar II (BP-II), divided on the basis of cyclothymic temperament (CT). In our companion article ( Hantouche et al., 2003 , this issue), we found that this temperament in its self-rated version correlated significantly with hypomanic behavior of a risk-taking nature. Our aim in the present analyses is to further test the hypothesis that such patients—assigned to CT on the basis of clinical interview—represent a more “unstable” variant of BP-II. Methods: From a total major depressive population of 537 psychiatric patients, 493 were re-examined on average a month later; after excluding 256 DSM-IV MDD and 41 with history of mania, the remaining 196 were placed in the BP-II spectrum. As mounting international evidence indicates that hypomania associated with antidepressants belongs to this spectrum, such association per se did not constitute a ground for exclusion. CT was assessed by clinicians using a semi-structured interview based on Akiskal and Mallya (1987) in its French version; as two files did not contain full interview data on CT, the critical clinical variable in the present analyses, this left us with an analysis sample of 194 BP-II. Socio-demographic, psychometric, clinical, familial and historical parameters were compared between BP-II subdivided by CT. Psychometric measures included self-rated CT and hypomania scales, as well as Hamilton and Rosenthal scales for depression. Results: BP-II cases categorically assigned to CT ( n =74) versus those without CT ( n =120), were differentiated as follows: (1) younger age at onset ( P =0.005) and age at seeking help ( P =0.05); (2) higher scores on HAM-D ( P =0.03) and Rosenthal (atypical depressive) scale ( P =0.007); (3) longer delay between onset of illness and recognition of bipolarity ( P =0.0002); (4) higher rate of psychiatric comorbidity ( P =0.04); (5) different profiles on axis II (i.e., more histrionic, passive-aggressive and less obsessive-compulsive personality disorders). Family history for depressive and bipolar disorders did not significantly distinguish the two groups; however, chronic affective syndromes were significantly higher in BP-II with CT. Finally, cyclothymic BP-II scored significantly much higher on irritable-risk-taking than “classic” driven-euphoric items of hypomania. Conclusion: Depressions arising from a cyclothymic temperament—even when meeting full criteria for hypomania—are likely to be misdiagnosed as personality disorders. Their high familial load for affective disorders ( including that for bipolar disorder ) validate the bipolar nature of these “cyclothymic depressions.” Our data support their inclusion as a more “unstable” variant of BP-II, which we have elsewhere termed “BP-II 1/2.” These patients can best be characterized as the “darker” expression of the more prototypical “sunny” BP-II phenotype. Coupled with the data from our companion paper ( Hantouche et al., 2003 , this issue), the present findings indicate that screening for cyclothymia in major depressive patients represents a viable approach for detecting a bipolar subtype that could otherwise be mistaken for an erratic personality disorder. Overall, our findings support recent international consensus in favoring the diagnosis of cyclothymic and bipolar II disorders over erratic and borderline personality disorders when criteria for both sets of disorders are concurrently met.

Background : Although the construct of depression has been subjected to numerous factor analytic studies and phenomenological subtypes of clinical relevance have been delineated, this is not the case for mania. The few available studies have reported at least two factors, which consist of euphoric versus dysphoric-hostile subtypes. Our objective was to replicate and further enrich this literature. Methods : In the EPIMAN French National Study we systematically evaluated 104 DSM-IV hospitalized manic patients in four university centers in different regions of France. Psychiatrists completed the Beigel-Murphy Manic State Rating Scale (MSRS), as well as the HAM-D 17 , affective temperament scales, and the GAF Axis V from DSM-IV. Categorization of patients into pure versus dysphoric mania was made on the basis of clinical diagnosis, independent from psychometric measures. Results : On principal component analysis of the MSRS, three factors explained the largest variance: a global manic (23.3% variance), paranoid-hostile (14.8% variance), and psychotic (9.1% variance). After varimax rotation, we obtained seven independent factors: F1 Disinhibition-instability, F2 Paranoia-hostility, F3 Deficit, F4 Grandiosity-psychosis, F5 Elation-euphoria, F6 Depression, and F7 (Hyper)sexuality. We could not demonstrate significant correlations between the individual factors and impaired functioning on GAF. However, depressive and, to some extent, cyclothymic temperaments correlated with F6 Depression. Finally, intergroup comparisons between pure versus dysphoric mania diagnosed clinically showed high levels of F3 Deficit and F5 Elation in the pure, and of F6 Depression in dysphoric, mania; F2 Paranoia-hostility did not discriminate these two clinical forms of mania. Limitations : Although the present analyses on the Beigel-Murphy represent the largest sample studied to date, they are still underpowered and do not guarantee a stable factorial structure. Our findings are cross-sectional and require prospective validation. Conclusions : Our data suggest that ‘dysphoria’ as used in the literature to qualify mania is insufficiently precise, and is best further specified as ‘depressive’ versus ‘irritable.’ Moreover, our data extend the rich multidimensional phenomenology of mania beyond the existing literature: we submit that disinhibition-instability (a core ‘activation’ component) can, on the one hand, be associated with distinct emotional presentations (euphoric, depressive, or irritable-hostile), as well as psychotic and deficit symptomatology on the other.

Background: No systematic data exists on the phenomenology and psychometric aspects of hypomania. In this report we focus on the factor structure of hypomania and its relationships with cyclothymic temperament in unipolar (UP) and bipolar II (BP-II) spectrum (soft bipolar) patients. Method: The combined sample of UP and BP-II spectrum patients (n=427) derives from the French National multi-center study (EPIDEP). The study involved training 48 psychiatrists at 15 sites in France in a protocol based on DSM-IV phenomenological criteria for major depressive disorder, hypomania, and BP-II, as well as a broadened definition of soft bipolarity. Psychometric measures included Angst’s Hypomania Checklist (HCA) and Akiskal’s Cyclothymic Temperament (CT) Questionnaires. Results: In the combined sample of the UP and BP-II spectrum, the factor pattern based on the HCA was characterized by the presence of one hypomanic component. In the soft bipolar group (n=191), two components were identified before and after varimax rotation. The first factor (F-1) identified hypomania with positive (driven-euphoric) features, and the second factor (F-2) hypomania with greater irritability and risk-taking. In exploratory analyses, both factors of hypomania tentatively distinguished most soft BP subtypes from UP. However, F-1 was generic across the soft spectrum, whereas F-2 was rather specific for II-1/2 (i.e., BP-II arising from CT). CT, which was found to conform to a single factor among the soft bipolar patients, was significantly correlated only with irritable risk-taking hypomania (F-2). Limitation: In a study conducted in a clinical setting, psychiatrists cannot be kept blind of the data revealed in the various clinical evaluations and instruments. However, the systematic collection of all data tended to minimize biases. Conclusion: EPIDEP data revealed a dual structure of hypomania with ‘classic’ driven-euphoric contrasted with irritable risk-taking expressions distributed differentially across the soft bipolar spectrum. Only the latter correlated significantly with cyclothymic temperament, suggesting the hypothesis that repeated brief swings into hypomania tend to destabilize soft bipolar conditions.

Background: Because manic patients lack insight, they are generally considered unreliable observers of their own psychopathology. The present analyses sought to examine to what extent patient reports could improve formal diagnostic criteria for mania — and be validated against the Carroll–Klein (CK) psychobiological model of bipolarity. Method: 104 DSM-IV acutely manic (hospitalized) patients provided self-assessment on the Ahearn–Carroll scale, the Multiple Visual Analogue Scales of Bipolarity (MVAS-BP). A principal component analysis (PCA) was performed on MVAS-BP, and the data on factorial scores were then compared to dimensional scores according to the CK model and to factors on the Beigel–Murphy Manic State Rating Scale (MSRS) completed by psychiatrists. Results: The PCA identified a general factor accounting for 33% of the total variance; after varimax rotation, seven independent factors emerged, essentially in coherence with the signs and symptoms of DSM-IV mania, except for the ‘social disinhibition’ factor, which does not figure out as a distinct criterion in DSM-IV. Strong correlations were obtained (r≥0.80) between the four major factors of MVAS-BP and the four dimensional categories of the CK model: ‘Consummatory Reward’ with F1 ‘Elation and Inflated Self-esteem’ (r=0.93), ‘Incentive Reward’ with F2 ‘Activation’ (r=0.84), ‘Psychomotor Pressure’ with F3 ‘Acceleration’ (r=0.85), and ‘Central Pain’ with F4 ‘Anxiety–Depression’ (r=0.84). The F2 ‘Activation’ appeared to be strongly correlated (r≥0.70) to all categories of the CK model. Correlational analysis between the factor structure of MVAS-BP and the MSRS showed significant coefficients on the scores assessing the emotional factors of ‘Elation’ and ‘Depression.’ Among the MVAS-BP factors, only ‘Activation’ was correlated to the majority of clinician ratings as obtained by the MSRS. Conclusions: These findings provide overall construct validity to the DSM-IV criteria for mania. Self-assessment of this disorder appears feasible and potentially useful in practice; lack of insight, poor judgment, and distractibility obviously require assessment by a clinician. Although our data are correlational and require prospective validation, they nonetheless suggest that (1) activation should be raised to the status of the stem criterion for mania, (2) to specify mood as elated, depressive, anxious, or irritable, and (3) to give individual status to social disinhibition (indiscriminate gregariousness) as a core pathological behavior in mania. Combining clinician- and self-observation thus produces a more precise and complete phenomenology of mania. We finally submit that the foregoing reformulation provides a psychobiological basis to the manic construct as formulated in the Carroll-Klein model.

Background: This paper presents the methodology and clinical data in mid-stream from a French multi-center study (EPIDEP) in progress on a national sample of patients with DSM-IV major depressive episode (MDE). The aim of EPIDEP is to show the feasibility of validating the spectrum of soft bipolar disorders by practising clinicians. In this report, we focus on bipolar II (BP-II). Method: EPIDEP involves training 48 French psychiatrists in 15 sites; construction of a common protocol based on the criteria of DSM-IV and Akiskal (Soft Bipolarity), as well as criteria modified from the work of Angst (Hypomania Checklist), the Ahearn-Carroll Bipolarity Scale, HAM-D and Rosenthal Atypical Depression Scale; Semi-Structured Interview for Evaluation of Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal), family history (Research Diagnostic Criteria); and prospective follow-up. Results: Results are presented on 250 (of the 537) MDE patients studied thus far during the acute phase. The rate of BP-II disorder which was 22% at initial evaluation, nearly doubled (40%) by systematic evaluation. As expected from the selection of MDE by uniform criteria, inter-group comparison between BP-II vs unipolar showed no differences on the majority of socio-demographic parameters, clinical presentation and global intensity of depression. Despite such uniformity, key characteristics significantly differentiated BP-II from unipolar: younger age at onset of first depression, higher frequency of suicidal thoughts and hypersomnia during index episode, higher scores on Hypomania Checklist and cyclothymic and irritable temperaments, and higher switching rate under current treatment. Eighty-eight percent of cases assigned to cyclothymic temperament by clinicians (with a cut-off of 10/21 items on self-rated cyclothymia) were recognized as BP-II. Evaluation of this temperament by clinician and patient correlated at a highly significant level (r=0.73; p

Background Previous studies have shown that major depressive patients may differ in several features according to gender, but the existence of a specific male depressive syndrome remains controversial. Methods As part of the EPIDEP National Multisite French Study of 493 consecutive DSM-IV major depressive patients evaluated in at least two semi-structured interviews 1 month apart, 125 (27.7%) were of male gender, whereas 317 (72.3%) were female, after exclusion of bipolar I patients. Results Compared to women, men were more often married, had more associated mixed features, with more bipolar disorder NOS, more hyperthymic temperaments, and less depressive temperaments. Women had an earlier age at onset of depression, more depressive episodes and suicide attempts. A higher family loading was shown in men for bipolar disorder, alcohol use disorder, impulse control disorders and suicide, whereas their family loading for major depressive disorder was lower. Men displayed more comorbidities with alcohol use, impulse control, and cardiovascular disorders, with lower comorbidities with eating, anxiety and endocrine/metabolic disorders. The following independent variables were associated with male gender: hyperthymic temperament (+), alcohol use disorder (+), impulse control disorders (+), and depressive temperament (−). Limitations The retrospective design and the lack of specific tools to assess the male depressive syndrome. Conclusion Study findings may lend support to the male depression syndrome concept and draw attention to the role of hyperthymic temperament, soft bipolarity as well as comorbidities as determinants of this syndrome. The latter could help recognize an entity which is probably underdiagnosed, but conveys a high risk of suicide and cardiovascular morbidity.

Background In the past 20 years, much evidence has accumulated against the overly restrictive diagnostic concepts of hypomania in DSM-IV and DSM-IV-TR. We tested DSM-IV-TR and a broader modified version (DSM-IV-TRm) for their ability to detect bipolarity in patients who had been treated for bipolar disorders (BD) in psychiatric settings, and who now consulted general practitioners (GPs) for new major depressive episodes (MDE). Methods Bipolact II was an observational, single-visit survey involving 390 adult patients attending primary care for MDE (DSM-IV-TR criteria) in 201 GP offices in France. The participating GPs (53.3±6.5 years old, 80.1% male) were trained by the Bipolact Educational Program, and were familiar with the medical care of depressive patients. Results Of the 390 patients with MDE, 129 (33.1%) were previously known as bipolar patients (ICD-10 criteria). Most of the latter bipolar patients (89.7%) had previously been treated with antidepressants. Only 9.3% of them met DMS-IV-TR criteria for BD. Conversely, 79.1% of the 129 bipolar patients met DMS-IV-TRm criteria for BD and showed strong associations with impulse control disorders and manic/hypomanic switches during antidepressant treatment. Limitations Limited training of participating GPs, recall bias of patients, and the study not being representative for untreated bipolar patients. Conclusions Very few ICD-10 bipolar patients consulting French GPs for MDE met DSM-IV-TR criteria for bipolar diagnosis, which suggests that DSM-IV-TR criteria are insufficient and too restrictive for the diagnosis of BD. DSM-IV-TRm was more sensitive, but 20% of bipolar patients were undetected.

Background Many studies have used admixture analysis to separate age-at-onset (AAO) subgroups in bipolar patients, but few have looked at the phenomenological characteristics of these subgroups, in order to find out phenotypic markers. Methods Admixture analysis was applied to identify the model best fitting the observed AAO distribution of a sample of 1082 consecutive DSM-IV bipolar I manic inpatients who were assessed for demographic, clinical, course of illness, comorbidity, and temperamental characteristics. Results The model best fitting the observed distribution of AAO was a mixture of three Gaussian distributions. We could identify three AAO subgroups: early, intermediate, and late age-at-onset (EAO, IAO, and LAO, respectively). Patients in the EAO subgroup were more often single young males exhibiting severe mania with psychotic features, a subcontinuous course of illness with substance use and panic comorbidity, more suicide attempts, and temperamental components sharing hypomanic features. Patients with LAO showed a less severe picture with more depressive temperamental components, alcohol use and comorbid general medical conditions. A less typical phenotype was present in IAO patients. Limitations The following are the limitations of this study: retrospective design, and bias toward preferential enrollment of patients with manic predominant polarity. Conclusions This study confirms that bipolar I disorder can be subdivided into three subgroups based on AAO distribution and shows that patients from these subgroups differ in phenotypes.

Most groups of psycho-education are currently based and orientated toward the classical clinical picture of bipolarity, “Bipolar-I Disorder”, which includes intense to severe (hypo)mania phases (often leading to hospitalization). However, the reality of clinical practice shows another evidence: soft bipolar spectrum is probably the most frequent expression of this disorder. More than 40% of major depressions and 2/3 of recurrent or resistant depressions are part of this spectrum, which seems to be highly but neglected in pharmacological and especially in psychological treatment processes.

Background Recognition of Bipolar Spectrum at an academic, clinical, and national level has increased in recent times. Therefore there is a tremendous need for adequate and new research in the clinical and epidemiological domains. Some of these clinical works have been established through international collaborative work with European centers (Zurich, Paris, Pisa) and UCSD (San Diego). The Poster presents the most recent data on the development of the Hypomania Scale (HCL-20), which have been initiated in France (Epidep study).

Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. One thousand ninety manic patients included in the French National Study EPIMAN-II Mille were submitted to a cluster analysis on the basis of multiple variables related to the history of bipolar illness and symptoms of the current episode. Four clusters were identified: “classic mania” (29.3% of patients) with less severe mania; “psychotic mania” (22.7%) with psychotic symptoms, more severe mania, younger age and social impairment; “depressive mania” (30.4%) characterized by female gender, suicide attempts, high number of previous episodes and residual symptoms; and “dual mania” (17.6%) characterized by male gender, substance use, earlier onset and poor compliance. Patients groups also differed in manic symptoms, marital status, stressors preceding illness onset, prior diagnoses, first episode polarity and temperamental characteristics. Cross-sectional assessment of patients. In comparing our findings with those of four prior cluster analytic studies, we integrate clinical characteristics of mania subtypes found in this very large representative French sample in contemporary practice, we suggest how such convergence of data may help improve earlier recognition, differential response to different treatments, and prevention of these subtypes. We finally suggest that such subtyping might provide clues to phenotype delineation suitable for pharmacogenetic investigations.

"EPIMAN-II Thousand" is a national multi-site collaborative study dedicated to replicate and complete the previous EPIMAN study (Hantouche et al., 2003). It involved training 317 French psychiatrists working in different sites representative of all France. The study actually succeeded in recruiting 1090 cases admitted for acute mania (DSMIV criteria). The MRS was used to assess the intensity of mania and MADRS + CLDS (checklist of depressive symptoms, 10 items) for co-existing depression. Lifetime comorbid anxiety disorders were assessed by using the DSM-IV criteria, and the AMDP Anxiety Scale of Bobon. The full TEPMS-A French version (84 items, Hantouche et al., 2001) was used to assess the Affective Temperaments.

Background Few studies have been undertaken to ascertain the feasibility of using the bipolar (BP) spectrum in clinical practice. The only systematic national study is the French EPIDEP Study of consecutive inpatients and outpatients presenting with major depressive episodes (MDE). The protocol was developed in 1994 and implemented in 1995; publication of its first data began in 1998. This report provides the complete data set of the EPIDEP. Methods Forty-eight psychiatrists, practicing in 15 sites in four regions of France (Paris, Besancon, Bordeaux and Marseille), were all trained on a common protocol based on DSM-IV criteria for MDE ( n = 537) subdivided into BP-I (history of mania), BP-II (history of hypomania), as well as extended definitions of the “softer spectrum” beyond BP-I and BP-II. Measures tapping into this spectrum included the Hypomania Checklist (HCA), the cyclothymic (CT), depressive (DT) and hyperthymic (HT) temperament scales. These measures and course permitted post-hoc assignment of MDE in the bipolar spectrum, based in part on the Akiskal, H.S., Pinto, O., 1999. [The evolving bipolar spectrum: Prototypes I, II, III, IV. Psychiatr. Clin. North Am. 22, 517–534] proposal: depression with history of spontaneous hypomanic episodes (DSM-IV, BP-II), cyclothymic depressions (BP-II½), antidepressant-associated hypomania (BP-III) and hyperthymic depressions (BP-IV). «Strict UP» was thereby limited to an exclusion diagnosis for the remainder of MDE. Limitation In the clinical setting, psychiatrists cannot be entirely blind to the observations in the various clinical evaluations and instruments. However, the systematic multisite collection of such data tended to minimize any such biases. Results After excluding patients lost to follow-up, among 493 presenting with MDE with complete data files, the BP-II rate was estimated at index at 20%; 1 month later, systematic probing for hypomania doubled the rate of BP-II to 39%. The comparison between BP-II and UP showed differential phenomenology, such as hypersomnia, increased psychomotor activation, guilt feelings and suicidal thoughts in BP-II. Related data demonstrated the importance of CT in further qualifying of MDE to define a distinct, more severe (“darker”) BP-II½ variant of BP-II. Moreover, BP-III, arising from DT and associated with antidepressants, emerged as a valid soft bipolar variant on the basis of the phenomenology of hypomania and bipolar family history. Finally, we found preliminary evidence for the inclusion of BP-IV into the bipolar spectrum, its total hypomania score falling intermediate between BP-II and strict UP. Using this broader diagnostic framework, the bipolar spectrum (the combined “hard” BP-I phenotype, BP-II and the soft spectrum) accounted for 65% of MDE. Conclusion The EPIDEP study achieved its objectives by demonstrating the feasibility of identifying the bipolar spectrum at a national level, and refining its phenomenology through rigorous clinical characterization and validation of bipolar spectrum subtypes, including MDE with brief hypomanias, cyclothymia and hyperthymia. The spectrum accounted for two out of three MDE, making “strict UP” less prevalent than BP as redefined herein. Our findings were anticipated by Falret, who in 1854 had predicted that many melancholic patients in the community would 1 day be classified in his circular group. We also confirmed Baillarger's observation in the same year that episodes (in this study, hypomanic episodes) could last as short as 2 days. Our findings deriving from a systematic French national database a century and a half later invite major shifts in clinical and public health services, as well as in the future conduct of psychopharmacologic trials. In this respect, the systematic training of clinicians in four regions of France represents a national resource for affective disorders and can serve as a model to effect change in diagnostic practice in other countries.

Objective : To determine the prevalence and clinical characteristics of comorbid obsessive compulsive disorders and syndromes (OCD/OCS), compared with pure OCD/OCS among adults in the community. Method : Data were drawn from the Zurich Study, a longitudinal cohort study of 591 adults in the canton of Zurich. Comorbid OCD/OCS was compared with pure OCD/OCS groups in terms of distress, impairment, family history, suicide behavior and treatment using multivariable logistic regression analyses. Results : OCD was significantly comorbid with bipolar I/II and minor bipolar disorders, anxiety states (GAD, repeated panic attacks) and social phobia, whereas there was no clear association between OCD and major depressive disorder or phobias other than social phobia. Results suggest that comorbid OCD/OCS is common among adults in the community, with the majority of those with OCD/OCS having at least one comorbid mood or anxiety disorder with a prevalence of 7.4% compared to 4.8% of remaining OCD/OCS. Comorbidity of OCD/OCS and anxiety states was more common among women (85.6 %) and comorbidity with bipolar spectrum was more common among men (69.6%). Comorbid OCD/OCS was associated with significantly higher levels of treatment seeking, impairment,distress and suicidality compared with pure OCD/OCS. Comorbidity with bipolar disorders significantly increased the risk for alcohol abuse/dependence. Conclusion : Comorbidity of OCD/OCS with bipolar disorder and bipolar spectrum disorders is common and very probably explains the association between OCD and depression found in other studies. The early recognition of bipolar/cyclothymic OCD/OCS may help to prevent the abuse of/dependence on alcohol

Background Bipolar disorders (BP) are frequently diagnosed and treated as pure depression initially; accurate diagnosis often being delayed by 8 to 10 years. In prospective studies, the presence of hypomanic symptoms in adolescence is strongly predictive of later bipolar disorders. As such, an instrument for self-assessment of hypomanic symptoms might increase the detection of suspected and of manifest, but under-treated, cases of bipolar disorders. Methods The multi-lingual hypomania checklist (HCL-32) has been developed and is being tested internationally. This preliminary paper reports the performance of the scale in distinguishing individuals with BP (N = 266) from those with major depressive disorder (MDD; N = 160). The samples were adult psychiatry patients recruited in Italy (N = 186) and Sweden (N = 240). Results The samples reported similar clinical profiles and the structure for the HCL-32 demonstrated two main factors identified as “active/elated” hypomania and “risk-taking/irritable” hypomania. The HCL-32 distinguished between BP and MDD with a sensitivity of 80% and a specificity of 51%. Limitations Although the HCL-32 is a sensitive instrument for hypomanic symptoms, it does not distinguish between BP-I and BP-II disorders. Conclusions Future studies should test if different combinations of items, possibly recording the consequences of hypomania, can distinguish between these BP subtypes.

Background : Mood stabilizers (MS), especially Lithium, are used in augmentation strategies for resistant depression. However the broader bipolar spectrum (depressions with brief [i.e. 2 days] hypomania, cyclothymic and hyperthymic temperaments) has rarely been explored in such strategies. The aim of the current report is to search for predictive factors for response to mood stabilizers when used as augmentation therapy after excluding clear-cut hypomania and focusing on DSM-IV major depressive disorder (UP-MDD), which is best designated as apparently “unipolar”. Method : From the total sample of 452 major depressives (MDE) included in the French National study EPIDEP, 256 were classified as UP-MDD after eliminating DSM-IV bipolar II (≥4 days of hypomania); conservatively, we also excluded MDD with hypomania associated with antidepressants. Lifetime treatment history of UP-MDD revealed that 59 (23.3%) had received at least one MS (lithium, valpromide [French variant of divalproex], and carbamazepine) in the past; from this sub-population, 18 were considered retrospectively as good responders (30%, GR) versus 41 poor responders (70%, PR) to MS augmentation on the basis of the clinical judgment of the treating psychiatrist. Results : Comparative analyses between patients who received MS and those who did not, revealed the former group as having higher levels on the hypomania checklist and cyclothymic and depressive temperaments. The delay to MS installation was significantly longer in the PR versus GR. The profile of GR could be described as follows: younger current age, higher education; symptom-free interval between major episodes; and fewer prior depressive episodes and hospitalizations; and higher rate of MS prescription. However, no significant differences were obtained from hypomania assessment and affective temperament ratings (cyclothymic, hyperthymic, depressive). During the index (most recent) depressive episode, we obtained a significantly higher rating of “suicidal thoughts” associated with higher levels of “sadness–guilt,” psychomotor agitation, and lower “retardation–fatigue” (all from the HAM-D) in the PR group; better and faster response to current treatment (as prospectively assessed) were also observed in the GR. At this time, overall severity of depression was not linked to the quality of response to the MS. Limitations and conclusion : Despite its retrospective design, these analyses have important implications in the management of difficult or resistant “unipolar” depression by using MSs as augmentation strategy. Clinicians appeared to have used “subtle” hypomanic and cyclothymic features as a justification for augmentation. However, these features per se were not predictive of response to such augmentation. Instead, the profile of augmentation response to failed antidepressants appears to be an “activated depression” (significantly less retardation and withdrawal and higher agitation associated with greater intensity of painful and guilt-ridden sadness with suicidality), and the significantly higher rate of and earlier prescription of MSs in the course of recurrent MDD. These data suggest that resistant depressives should not stay on antidepressant or antidepressant combination for too long; MS augmentation must be instituted without much delay.

Introduction: Although several recent studies suggest that bipolar disorder most commonly begins during childhood or adolescence, the illness still remains under-recognized and under-diagnosed in this age group. As part of the French Bipolar network and in line with the hypothesis that juvenile depression is pre-bipolar (Akiskal, 1993), we evaluated the rate of onset of bipolar disorders in a naturalistic 2-year prospective study of consecutive, clinically depressed children and adolescents, and to test whether the cyclothymic temperament underlies such onset. Methods: Complete information was obtained from both parents and patients in 80 of 109 depressed children and adolescents assessed with Kiddie-SADS semi-structured interview, according to DSM IV criteria. They were also assessed with a new questionnaire on cyclothymic-hypersensitive temperament (CHT) from the TEMPS-A cyclothymic scale adapted for children (provided in Appendix A), and other assessment tools including the Child Depression Inventory (CDI), Young Mania Rating Scale, Clinical Global Assessment Scale (CGAS), and Overt Aggressive Scale (OAS). Results: Of the 80 subjects, 35 (43%) could be diagnosed as bipolar at the end of the prospective follow-up. This outcome was significantly more common in those with cyclothymic temperament measured at baseline. Most of these patients were suffering from a special form of bipolar disorder, characterized by rapid mood shifts with associated conduct disorders (CD), aggressiveness, psychotic symptoms and suicidality. Limitation: The primary investigator, who took care of the patients clinically, was not blind to the clinical and psychometric data collected. Since all information was collected in a systematic fashion, the likelihood of biasing the results was minimal. Conclusion: We submit that the CHT in depressed children and adolescents heralds bipolar transformation. Unlike hypomanic or manic symptoms, which are often difficult to establish in young patients examined in cross-section or by history, cyclothymic traits are detectable in childhood. Our data underscore the need for greater effort to standardize the diagnosis and treatment of pre-bipolar depressions in juvenile patients.

BACKGROUND: Notwithstanding the emerging literature on comorbidity between obsessive-compulsive disorder (OCD) and bipolar disorder, relatively few systematic data exist on the clinical characteristics of this interface and its treatment. The aim of the present study is to address this challenge as it appears in a setting of routine clinical practice. METHOD: The sample comprised 68 patients with comorbid DSM-IV diagnoses of OCD and major depressive episode admitted and treated at the day-hospital in the Department of Psychiatry at the University of Pisa (Pisa, Italy) during a 3-year period (January 1995-December 1998). Thirty-eight patients (55.8%) showed lifetime comorbid bipolar disorder (12 [31.6%] bipolar I and 26 [68.4%] bipolar II). Diagnoses and clinical features were collected by means of structured (Structured Clinical Interview for DSM-IV) and semistructured interviews (OCD-Interview). Assessments of drug treatments, clinical outcome, and adverse effects were made prospectively as part of routine clinical care throughout the course of their day-hospitalization. RESULTS: In contrast with non-bipolar OCD patients, OCD-bipolar patients showed a more episodic course with a greater number of concurrent major depressive episodes. They reported a significantly higher rate of sexual obsessions and significantly lower rate of ordering rituals. Furthermore, they reported more frequent current comorbidity with panic disorder-agoraphobia and abuse of different substances (alcohol, sedatives, nicotine, and coffee). Drug treatment with clomipramine and, to a lesser extent, with selective serotonin reuptake inhibitors was associated with hypomanic switches in OCD-bipolar patients, especially in those not concomitantly treated with mood stabilizers. A combination of multiple mood stabilizers was necessary in 16 OCD-bipolar patients (42.1%) and a combination of mood stabilizers with atypical antipsychotics was required in 4 cases (10.5%). OCD-bipolar patients tended to show a less positive outcome for mood symptomatology and general functioning. Three patients required hospitalization for severe mixed episode. CONCLUSION: In a tertiary care center, comorbidity between OCD and bipolar disorder is a significant clinical problem affecting a large number of patients and has a substantial impact on the clinical characteristics and treatment outcome of both disorders.

Background: This research derives from the French national multisite collaborative study on the clinical epidemiology of mania (EPIMAN). Our aim is to establish the validity of dysphoric mania along a “spectrum of mixity” extending into mixed mania with subthreshold depressive manifestations; to demonstrate the feasibility of obtaining clinically meaningful data on this entity on a national level; and to characterize the contribution of temperamental attributes and gender in its origin. Methods: EPIMAN involves training 23 French psychiatrists in four different sites, representing four regions of France; to rigorously apply a common protocol deriving from the criteria of DSM-IV and McElroy et al.; the use of such instruments as the Beigel-Murphy, Ahearn-Carroll, modified HAM-D; and measures of affective temperaments based on the Akiskal-Mallya criteria; obtaining data on comorbidity, and family history (according to Winokur's approach as incorporated into the FH-RDC); and prospective follow-up for at least 12 months. The present report concerns the clinical and temperamental features of 104 manic patients during the acute hospital phase. Results: Dysphoric mania (DM defined conservatively with fullblown depressive admixtures of five or more symptoms) occurred in 6.7%; the rate of dysphoric mania defined broadly (DM, presence of ≥2 depressive symptoms) was 37%. Depressed mood and suicidal thoughts had the best positive predictive values for mixed mania. In comparison to pure mania (0–1 depressive symptoms), DM was characterized by female over-representation; lower frequency of such typical manic symptomatology as elation, grandiosity, and excessive involvement; higher prevalence of associated psychotic features; higher rate of mixed states in first episodes; and complex temperamental dysregulation along primarily depressive, but also cyclothymic, and irritable dimensions; such irritability was particularly apparent in mixed mania at the lowest threshold of depressive admixtures of two symptoms only. Limitation: In a study involving hospitalized affectively unstable psychotic patients, it was difficult to assure that psychiatrists making the clinical diagnoses would be blind to the temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. Conclusions: Mixed mania, defined cross-sectionally by the simultaneous presence of at least two depressive symptoms, represents a prevalent and clinically distinct form of mania. Subthreshold depressive admixtures with mania actually appear to represent the more common expression of dysphoric mania. Moreover, an irritable dimension appears to be relevant to the definition of the expression of mixed mania with the lowest threshold of depressive symptoms. Neither an extreme, nor an endstage of mania, “mixity” is best conceptualized as intrusion of mania into its “opposite” temperament – especially that defined by lifelong depressive traits – and favored by female gender. These data suggest that reversal from a temperament to an episode of “opposite” polarity represents a fundamental aspect of the dysregulation that characterizes bipolar disorder. In both men and women with hyperthymic temperament, there appears “protection” against depressive symptom formation during a manic episode which, accordingly, remains relatively “pure”. Because men have higher rates of this temperament, pure mania is overrepresented in men; on the other hand, the depressive temperament in manic women seems to be a clinical marker for the well-known female tendency for depression, hence the higher prevalence of mixed mania in women.

Background: Many studies have found biological abnormalities in obsessive–compulsive disorder (OCD), although most of them have not been replicated. The investigation of melatonin rhythm may thus provide an indirect clue to neurotransmitter alterations, and allow a biological comparison with depression. Methods: The circadian variations of plasma melatonin, plasma cortisol, axillary temperature, motor activity, and obsessive–compulsive symptoms have been documented on a circadian basis in 8 patients with OCD compared to 8 paired healthy volunteers. Results: The circadian pattern of axillary temperature was slightly different in OCD patients when compared to control subjects. No significant difference between the two groups could be observed for any other variable studied. Conclusions: The discrepancies with previous studies are discussed on the basis of the methods used (patients and control subjects samples, biological measurement procedures). An alteration of temperature circadian rhythm hypothesis is suggested.

The current concept of Bipolar Spectrum is still evolving and much more interest is focused on the definition of Hypomania (BP-II Disorder) and especially Cyclothymic Disorder. In order to get the entire diagnosable range of bipolar conditions, the clinical approach must go beyond "polarity" of episodes: family history, age of onset, time course (circularity), level of recurrence, type of cyclicity (exogenous/endogenous), and especially affective temperaments. Clinical researches have been dedicated to explore affective temperaments and their role in psychopathology of mood disorders. Cyclothymia appears to be a likely precursor or a basic primary ingredient of the construct of soft bipolarity. The French studies directed by Hantouche and Akiskal showed that Cyclothymia is probably the most frequent expression of bipolar disorder, and represents a distinct entity with early onset, irritable ("dark") hypomania and high suicide risk. Despite these facts, there is a lot to learn about Cyclothymia. In the "psycho-education group therapy" model for Cyclothymia, elaborated in the CTAH, we recently addressed the following issues: - Links between Cycothymic Temperament and Hypomania, dimensionally explored by the HCL-32 (Angst) - Relationships between affective temperaments, especially Cyclothymic Temperament (assessed by TEMPS-A) and temperament (as measured by the Adult Temperament Questionnaire and the Affective Intensity Scale) - Role of Cyclothymia in the "schema-focused approach" (J. Young) - Expression of Cyclothymia through psychological vulnerabilities and interpersonal conflicts Preliminary data will be presented.

Bipolarity might be underdiagnosed by the DSM-IV. This could particularly pertain for young adults, when the disorder is in early stages and the manifestations of hypomania are not typical. Additionally, the current DSM-IV-based instruments are not sufficiently sensitive for detecting hypomania. Support comes from epidemiological and clinical studies, which showed that subthreshold BPD is common and clinically significant. In the National-Comorbidity-Survey-Replication (NCS-R) the overall prevalence of BPD increased from 2.1% up to 4.4% if subthreshold BPD was considered. Role impairment, comorbidity (alcohol abuse, panic disorder, impulse control), and family history of mania are the validators of subthreshold bipolarity. In the small prospective Zurich Study a stepwise broadening of the criteria for hypomania allocated almost half of the subjects with MDE to a broadly defined bipolar group. In bigger samples, such as 2300 patients presenting recurrent or resistant depressions, the hypomania rate, when dimensionnaly rated (by using the hypomania checklist) was more than 60%.DSM-IV “Bipolar II disorder” and “Cyclothymia” are still ill defined with a great confusion among the territory of “Soft Bipolar Spectrum”, and clinicians need a more practical approach.The Kahlbaum-Hecker syndrome of cyclothymia includes depressive (dysthymia), hypomanic (hyperthymia), and mixed hypomanic-depressive phases. According to French experts, Deny and Kahn (1909) supported the hypothesis that Cyclothymia represents a special constitution, which can be considered nowadays as particular affective temperament with close continuum with subtrheshold bipolarity.The great idea of Kahlbaum, Hecker, Deny is to combine the following variables: 1) premorbid temperament; 2) age of onset, 3) time course of an illness (cyclicity / intermittence). Applying this combination, bipolar spectrum could be currently divided into 2 categories: “Typical BP-I/II” (episodic mania or hypomania with free intervals) versus “Cyclothymia” (radically instable form with continuous ups and downs). This intra-bipolar dichotomy seems to be closer to the clinical reality of mood disturbances. Cyclothymia is probably the most frequent expression of bipolar disorder (more than 30% of major depressions). Repeated brief swings with high mood instability and rapid switching seemed to be a distinct entity with early onset, irritable (“dark”) hypomania and high suicide risk. This condition emerged as the most prevalent and severe expression of the bipolar spectrum.

The electronic version of this abstract is the complete one and can be found online at: http://www.annals-general-psychiatry.com/content/7/S1/S1