The role of affective temperaments in bipolar disorder: The solid role of the cyclothymic, the contentious role of the hyperthymic, and the neglected role of the irritable temperaments.

BACKGROUND: The aim of the present study is to evaluate the role of individual affective temperaments as clinical predictors of bipolarity in the clinical setting. METHODS: The affective temperaments of 1723 consecutive adult outpatients presenting for various symptoms to a university-based mental health clinical setting were assessed. Patients were administered the Hypomania Checklist-32 and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Auto-questionnaire (TEMPS-A) and were diagnosed by psychiatrists according to the DSM-5 criteria. TEMPS-A scores were studied as both continuous and normalized categorical z-scores from a previously established nationwide study on the general population of Lebanon. Simple and multiple binary logistic regressions were done on patients who have any of the DSM-5 defined bipolar types, as a combined group or separately, versus patients without any bipolar diagnosis. RESULTS: At the multivariable level and taking into account all temperaments, the irritable temperament is a consistent predictor of bipolar I and bipolar II disorders. Cyclothymic temperament also played a strong role in bipolarity but more decisively so in bipolar II and substance-induced bipolarity. The hyperthymic temperament had no role in bipolar I or bipolar II disorder.

Negative emotion dysregulation is linked to the intensity of suicidal ideation in a mixed inpatient sample.

BACKGROUND: Suicide has been associated with dysfunctional strategies for emotion regulation but, so far, research findings have been inconclusive. METHODS: To investigate how difficulties in emotion regulation impact suicidal ideation (SI) and behavior, 111 psychiatric inpatients were enrolled. Affective instability (AI), emotional impulsivity (EI), and negative and positive emotionality (NE and PE) were measured by the RIPoSt-40 questionnaire; the first three subscales have been summed to form a total negative emotion dysregulation (NED) score. RESULTS: In the sample, 55 subjects reported at least one-lifetime suicide attempt; 50 patients were diagnosed with mood-disorder (MD), 30 with the schizophrenia-spectrum disorder (SSD), and 15 with personality-disorder (PD). Diagnostic groups differed for NED scores (p=.008) but not for PE (p>0.05), with patients suffering from PD having higher scores (p=0.03). Compared to non-attempters, lifetime-suicide attempters were 6.5 times more likely to have a personality disorder (95% CI=1.34/31.83). Partial correlation analyses, controlling for the presence of suicide attempts, showed that lifetime SI-intensity score was significantly and positively associated with NED (r=.39, p<.001), AI (r=.40, p<.001), and NE (r=.42, p<.001). NED scores (p=.001) and the presence of lifetime suicide attempts (p<.001) were independently associated with lifetime SI-intensity scores. LIMITATIONS: The lack of a non-clinical control group and the cross sectional nature of the study limits the generalizability of the results. CONCLUSION: Our findings support the hypothesis that negative emotion dysregulation is independently associated with SI and behavior. Negative emotion dysregulation should be targeted in suicide prevention.

Risk factors associated with lifetime suicide attempts in bipolar I patients: findings from a French National Cohort.

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.

Psychopathological correlates of lifetime anxiety comorbidity in bipolar I patients: findings from a French national cohort.

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-Asberg 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.

Reactivity, Intensity, Polarity and Stability questionnaire (RIPoSt-40) assessing emotional dysregulation: Development, reliability and validity.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: 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. CONCLUSION: RIPoSt-40 questionnaire has proved to be a valid, reliable and useful tool to assess ED both in clinical and non-clinical contexts.

Factors associated with rapid cycling in bipolar I manic patients: findings from a French national study.

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 nonrapid 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.

Toward the delineation of mania subtypes in the French National EPIMAN-II Mille Cohort. Comparisons with prior cluster analytic investigations.

BACKGROUND: Knowledge about psychopathologic presentations of mania in current clinical practice has to be refined in order to improve diagnosis and treatment. METHODS: 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. RESULTS: 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. LIMITATIONS: Cross-sectional assessment of patients. CONCLUSIONS: 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.

Validation of a severity threshold for the Mania Rating Scale: a receiver-operating characteristic analysis.

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.

Diagnosis and Treatment of Cyclothymia: The "Primacy" of Temperament.

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.

The mood-instability hypothesis in the origin of mood-congruent versus mood-incongruent psychotic distinction in mania: validation in a French National Study of 1090 patients.

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.

Validating the bipolar spectrum in the French National EPIDEP Study: overview of the phenomenology and relative prevalence of its clinical prototypes.

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, Besançon, 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-II(1/2)), antidepressant-associated hypomania (BP-III) and hyperthymic depressions (BP-IV). <> 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-II(1/2) 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.

Bipolar II vs. unipolar depression: psychopathologic differentiation by dimensional measures.

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 < or =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.

Mood stabilizer augmentation in apparently "unipolar" MDD: predictors of response in the naturalistic French national EPIDEP study.

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 (> or =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.

The HCL-32: towards a self-assessment tool for hypomanic symptoms in outpatients.

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.

Cyclothymia reloaded: A reappraisal of the most misconceived affective disorder.

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.

Temperament and suicide: A national study.

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.

Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome.

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.

Factor structure of hypomania: interrelationships with cyclothymia and the soft bipolar spectrum.

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.