Characteristics of depressive patients according to family history of affective illness: Findings from a French national cohort.

BACKGROUND: Literature is scarce about the characteristics of mood disorder patients with a family history (FH) of affective illness. The aim of the current study was to compare the prominent features of depressive patients with a FH of mania (FHM), those of depressive patients with a FH of depression (FHD), and those of depressive patients with no FH of affective illness (FHO). 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, 45 (9.1%) were classified as FHM, 210 (42.6%) as FHD, and 238 (48.3%) as FHO. RESULTS: The main characteristics of FHM patients were a cyclothymic temperament, the presence of mixed features and diurnal variations of mood during depression, early sexual behaviour, a high number of mood episodes and hypomanic switches, high rates of suicide attempts and rapid cycling; diagnosis of bipolar disorder was more frequent in this group as well as comorbid obsessive compulsive disorder, posttraumatic stress disorder, bulimia, attention deficit/hyperactivity disorder and impulse control disorders. The FHD patients had more depressive temperament, generalized anxiety disorder, and anorexia nervosa. Compared to FHO, FHM and FHD showed an earlier age at onset, more comorbid anxiety disorders, as well as more psychotic features. LIMITATIONS: The following are the limitations of this study: retrospective design, recall bias, and preferential enrolment of bipolar patients with a depressive predominant polarity. CONCLUSIONS: In light of genetic studies conducted in affective disorder patients, our findings may support the hypothesis of genetic risks factors common to affective disorders and dimensions of temperament, that may extend to comorbid conditions specifically associated with bipolar or unipolar illness.

"Folie circulaire" vs "Folie à double forme": contribution from a French national study.

OBJECTIVE: To check whether the presence or not of free intervals between episodes could help differentiate subtypes of bipolar disorder, as suggested by the seminal controversy between Falret and Baillarger. METHODS: From 1090 bipolar I patients included in a French national study, 981 could be classified as with or without free intervals and assessed for demographic and illness characteristics. RESULTS: Compared with patients with free intervals (n=722), those without (n=259) had an earlier age at onset, more episodes, suicide attempts, cyclothymic and irritable temperaments. The following independent variables were associated with no free intervals: being single or divorced, delay to mood stabilizer treatment, multiple hospitalizations, incongruent psychotic features, panic and generalized anxiety disorder. CONCLUSION: "Folie à double forme" (without free intervals) and "folie circulaire" (with free intervals) may actually refer to early and later onset bipolar subtypes, insofar as most differences we found between them were previously evidenced between the latter two. We cannot, however, exclude that they might simply be two separate subtypes, whose main characteristics could be accounted for by different explanatory factors.

[Evaluation of affective temperaments in the postpartum depressive symptomatology]. / Evaluation des tempéraments affectifs dans la symptomatologie dépressive du post-partum.

INTRODUCTION: Postpartum depression (PPD) is a frequent psychiatric condition, but little is known about its potential bipolar nature and the implication of affective temperaments. The goal of this study is to estimate the prevalence of PPD and assess the affective temperamental profile of those affected. METHOD: The study was conducted in the department of gynecology and obstetrics of the CHU of Sfax, Tunisia. The selected population included all 213 consecutive admissions (mean age=29 years). Postpartum depressive symptomatology (SPPD) was assessed during the first week after delivery by using the Postnatal Edinburgh Scale Depression (EPDS) in its Arab version. The Arabic version of the Temperaments Auto-questionnaire of Memphis, Pisa, Paris, and San Diego (TEMPS-A) was simultaneously filled out by subjects. The subjects were divided into two subgroups, depressed (D+) versus not depressed (D-), for comparative analyses. For affective temperaments, dimensional (mean scores) and categorical (quartiles) approaches were used. RESULTS: Forty-one women (19,2%) had a score higher than 9 on the EPDS (group D+). Lower educational level, lower social and family support, dysfunctional marital relationship, problems with accepting the pregnancy and prior psychiatric disorders were significantly more present in the D+ group. The majority of the affective temperaments, excepting hyperthymic, were correlated between them. The EPDS scores were correlated with all temperamental scores, except for hyperthymic. Higher scores on the depressive, irritable, anxious and cyclothymic temperaments were observed in the group D+. Women belonging to the 3rd and 4th quartiles of the depressive, cyclothymic and irritable temperaments and those belonging to the 4th quartile of the anxious temperament were significantly more depressed. Cyclothymic and depressive temperaments seemed to influence the pregnancy acceptance. Other interactions were observed between SPPD, temperamental profiles and quality of marital relation, and family support. The opposite seems true for the hyperthymic temperament, which could be protective against SPPD through better psychosocial conditions. Multivariate regression analysis showed that cyclothymic and anxious temperaments are significant risk factors independently from psychosocial factors, such as problems with accepting the pregnancy, which seemed to be the most important risk factor. CONCLUSION: PPD represents a frequent disorder, which needs to be correctly screened and recognized especially with its temperamental attributes, a mixture of anxious, irritable, depressive and cyclothymic traits. This complex unstable temperament should be considered as a predisposing factor, which interacts also with other common risk factors.

[Resistant Obsessive Compulsive disorder (ROC): clinical picture, predictive factors and influence of affective temperaments]. / Toc résistant : caractéristiques cliniques, facteurs prédictifs et influence des tempéraments affectifs.

BACKGROUND: Despite significant advances in clinical research, Obsessive Compulsive Disorder, OCD represents a difficult to treat condition. The French Association of patients suffering from OCD, "AFTOC" is highly concerned by this issue. A new survey was implemented with the aim of exploring Resistant Obsessive Compulsive disorder "ROC". METHOD: Patients with OCD and members of the "AFTOC" were included in the survey. A self-rated file was elaborated in order to get the maximum of information on the clinical and therapeutic aspects and conditions of OCD. The full version of "TEMPS-A" was also included for assessment of affective temperaments. Statistical analyses were performed for inter-group comparison between "ROC" (resistant OCD) and good responders. Logistic regression analyses with "ROC" method were used to search for independent predictive factors to "ROC". RESULTS: The new survey of "AFTOC", "TOC & ROC" selected a sample of 360 patients, who are members of the association. The rate of "ROC" was 44.2%, 25.3% of Good Responders (GR), and 30.5% in between. Inter-group comparisons ("ROC" versus GR) showed significant higher rates of psychiatric admissions (49% versus 28%), and suicide attempts (26% versus 13%), greater numbers of doctors consulted (5.5 versus. 3.2), compulsions (4.6 versus 3.4), and psychiatric comorbidity (2.8 disorders versus. 2.0; notably agoraphobia, social anxiety and worry about appearance) in the "ROC" group. Assessment by full "TEMPS-A" scale revealed, significantly higher rates of Cyclothymic Temperament (63% versus 43%; p: 0.0003), Depressive Temperament (72% versus 53%; p: 0.004), and Irritable Temperament (21% versus 9%; p: 0.02) in the ROC group. Moreover, the mean global score on each of these temperaments was significantly higher in the "ROC" group. No difference was obtained in the rate or the mean score on the hyperthymic temperament scale. The most predictive factors of "ROC" were represented by "slow continuous course", "worsening under SRI", "worry about appearance", current age above 40 years and psychiatric admission. CONCLUSION: Our data provides a more precise clinical picture of "ROC", which should be initially explored through baseline severity, compulsive dominance, hoarding, special comorbidity such as recurrent depression, obsession of appearance, agoraphobia, social anxiety, and complex mixture of unstable affective temperament (cyclothymic, irritable, and depressive), and course of illness. Furthermore, vigilance towards the notion of worsening linked to drug therapy, and the increased suicide risk is warranted in the clinical management of "ROC".

A challenging task for assessment of checking behaviors in obsessive-compulsive disorder.

OBJECTIVE: The present study concerns the objective and quantitative measurement of checking activity, which represents the most frequently observed compulsions in obsessive-compulsive disorder (OCD). To address this issue, we developed an instrumental task producing repetitive checking in OCD subjects. METHOD: Fifty OCD subjects and 50 normal volunteers (NV) were administered a delayed matching-to-sample task that offered the unrestricted opportunity to verify the choice made. Response accuracy, number of verifications, and response time for choice taken to reflect the degree of uncertainty and doubt were recorded over 50 consecutive trials. RESULTS: Despite similar levels of performance, patients with OCD demonstrated a greater number of verifications and a longer response time for choice before checking than NV. Such behavioral patterns were more pronounced in OCD subjects currently experiencing checking compulsions. CONCLUSION: The present task might be of special relevance for the quantitative assessment of checking behaviors and for determining relationships with cognitive processes.

Clinical and psychometric characterization of depression in mixed mania: a report from the French National Cohort of 1090 manic patients.

BACKGROUND: Despite extensive research recently focused on mixed mania, it is uncertain as how best to define it clinically, psychometrically (which has major bearing on its prevalence), and the methodology needed for future research. This topic is also of historical interest, because Magnan (1890) [Magnan, V., 1890. La Folie Intermittente. G Masson, Paris.] suggested that "combined [mixed] states" linked Falret's "circular insanity" with Baillarger's "dual insanity" (both described in 1854). This work eventually led to the Kraepelinian synthesis of all manic, mixed, and depressive states into the unitary rubric of "manic-depressive insanity (1899/1921). METHOD: EPIMAN-II Thousand" (EPIMAN-II MILLE) is a French national collaborative study, which involved training 317 psychiatrists working in different sites representative of psychiatric practice in France. We recruited 1090 patients hospitalized for acute DSM-IV mania. assessed at index admission by the following measures: the Mania Rating Scale (MRS), the Beigel-Murphy Scale (MSRS), a newly derived checklist of depressive symptoms least contaminated by mania, MADRS for severity of depression, and the SAPS for psychotic features. RESULTS: The rate of mixed mania, as defined by at least 2 depressive symptoms, was 30%. Even with this broad definition, we found significantly higher female representation. This clinical sub-type of mania was characterized by high frequency of past diagnostic errors, particularly those of anxiety and personality disorders. Refined definition of co-exiting depression was obtained from an abbreviated version of the MADRS (6 items), with distinct "emotional-cognitive" symptoms, and "psychomotor inhibition" factors, both of which were separable from an "irritable" factor linked to lability and poor judgment. Mixed mania was psychometrically best identified by a MADRS score of 6 (80% sensitivity, 94% specificity) and validated by a mixed polarity of first episodes, a higher rate of recurrence, psychotic features, and suicide attempts. LIMITATION: Cross-sectional study. CONCLUSIONS: The data deriving from EPIMAN, the largest and only national study ever conducted on mania, provide definitive characterization of the clinical and psychotic structure of mixed mania, which accounts for 1 out of 3 patients who present with mania. This figure is more accurate than higher rates reported in the literature because, in describing "mixity", we eliminated depressive features that could be contaminated by mania. Despite the prominent affective features described herein, the bipolar nature of mixed mania is often missed, with the result that these patients are diagnosed as having anxiety and/or personality disorders. It is of great public health significance for psychiatrists to recognize the bipolar nature of this condition that has been known as a major phase of manic-depressive illness since at least Magnan, a disciple of Falret and Baillarger.

Toward a definition of a cyclothymic behavioral endophenotype: which traits tap the familial diathesis for bipolar II disorder?

BACKGROUND: Although the cyclothymic temperament appears to be related to the familial diathesis of bipolar disorder, exhibiting high sensitivity for bipolar II (BP-II) disorder, it is presently uncertain which of its constituent traits are specific for this disorder. METHODS: In a sample of 446 major depressive patients (BP-II and unipolar), in the French National EPIDEP study, the cyclothymic temperament was assessed by using clinician- and self-rated scales. We computed the frequency of individual traits and relative risk for family history of bipolarity. RESULTS: From both clinician- and self-rated scales, four items related to mood reactivity, energy, psychomotor and mental activity were significantly highly represented in the subgroup with positive family history of bipolarity. The item "rapid shifts in mood and energy" obtained the highest relative risk (OR=3.42) for positive family history of bipolarity. CONCLUSION: These findings delineate those cyclothymic traits which are most likely to tap a familial-genetic diathesis for BP-II, thereby identifying traits which can best serve as a behavioral endophenotype for this bipolar subtype. Such an endophenotype might underlie the cyclic course of bipolar disorder first described in France 150 years ago by Falret and Baillarger.

Validating affective temperaments in their subaffective and socially positive attributes: psychometric, clinical and familial data from a French national study.

BACKGROUND: One of the major objectives of the French National EPIDEP Study was to show the feasibility of systematic assessment of bipolar II (BP-II) disorder and beyond. In this report we focus on the utility of the affective temperament scales (ATS) in delineating this spectrum in its clinical as well as socially desirable expressions. METHODS: Forty-two psychiatrists working in 15 sites in four regions of France made semi-structured diagnoses based on DSM IV criteria in a sample of 452 consecutive major depressive episode (MDE) patients (from which bipolar I had been removed). At least 1 month after entry into the study (when the acute depressive phase had abated), they assessed affective temperaments by using a French version of the precursor of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS). Principal component analyses (PCA) were conducted on hyperthymic (HYP-T), depressive (DEP-T) and cyclothymic (CYC-T) temperament subscales as assessed by clinicians, and on a self-rated cyclothymic temperament (CYC-TSR). Scores on each of the temperament subscales were compared in unipolar (UP) major depressive disorder versus BP-II patients, and in the entire sample subdivided on the basis of family history of bipolarity. RESULTS: PCAs showed the presence of a global major factor for each clinician-rated subscale with respective eigenvalues of the correlation matrices as follows: 7.1 for HYP-T, 6.0 for DEP-T, and 4.7 for CYC-T. Likewise, on the self-rated CYC-TSR, the PCA revealed one global factor (with an eigenvalue of 6.6). Each of these factors represented a melange of both affect-laden and adaptive traits. The scores obtained on clinician and self-ratings of CYC-T were highly correlated (r=0.71). The scores of HYP-T and CYC-T were significantly higher in the BP-II group, and DEP-T in the UP group (P<0.001). Finally, CYC-T scores were significantly higher in patients with a family history of bipolarity. CONCLUSION: These data uphold the validity of the affective temperaments under investigation in terms of face, construct, clinical and family history validity. Despite uniformity of depressive severity at entry into the EPIDEP study, significant differences on ATS assessment were observed between UP and BP-II patients in this large national cohort. Self-rating of cyclothymia proved reliable. Adding the affective temperaments-in particular, the cyclothymic-to conventional assessment methods of depression, a more enriched portrait of mood disorders emerges. More provocatively, our data reveal socially positive traits in clinically recovering patients with mood disorders.

Toward a validation of a tripartite concept of a putative anxious temperament: psychometric data from a French national general medical practice study.

BACKGROUND: Although generalized anxiety disorder (GAD) is currently described as a time-limited state mental disorder, emerging evidence suggests that it is best considered as an exaggeration of a putative "anxious temperament" (AT). It is presently unknown whether it is a distinct or unitary construct of a melange of anxious traits related to Cluster-C personality disorders. METHODS: As part of a Franco-American collaborative study, we developed the 15-item Operational Criteria for Anxious Personality (OCAP), expanding criteria sets developed earlier by one of us (H.S.A.). The study, which was conducted in the French primary care medical sector, included 1112 young adults (18-40 years), seeking help for isolated anxious complaints, never treated before-and without any diagnosable disorder on the axis I of DSM-IV. As previous papers have reported the preliminary validity of OCAP, especially concurrent validity with the State-Trait Anxiety Inventory (STAI) (Speilberger), in this report, we focus on its full psychometric properties. RESULTS: The present data indicate a normal distribution of AT items, a satisfactory Chronbach's coefficient (0.64), and the presence at intake of three different subtypes of AT: "anxious-avoidant," "anxious-phobic," and "anxious-sensitive." After a prospective 6-month follow-up, the major criteria of AT were stable in 80% of cases, and for specific AT items, the stability rate varied between 65% and 80%; much of the unstable items were accounted by improvement during naturalistic treatment. The latter could explain the different factor structure obtained at follow-up, which tended to be less heterogeneous, and represented by one global factor. LIMITATION: We used a categorical (yes/no) rather than a Likert-type gradation of frequency and intensity of anxiousness items and relatively low number of items, especially for those involving worrying about one's own health or that of one's loved ones. CONCLUSIONS: Anxiousness as a temperamental dimension appears to involve putative subtypes along "worrying," "phobic," "sensitive" (and "avoidant") dimensions.

The cyclothymic temperament in healthy controls and familially at risk individuals for mood disorder: endophenotype for genetic studies?

BACKGROUND: The modern concept of affective disorders focuses increasingly on the study of subthreshold conditions on the border of manic or depressive episodes. Indeed, a spectrum of affective conditions spanning from temperament to clinical episodes has been proposed by the senior author. As bipolar disorder is a familial illness, an examination of cyclothymic temperament (CT) in controls and relatives of bipolar patients is of major relevance. METHODS: We recruited a total sample of 177 healthy symptom-free volunteers. These controls were divided into three groups. The first one is comprised of 100 normal subjects with a negative familial affective history (NFH); the second of 37 individuals, with positive affective family history (PFH); and a third of 40 subjects, with at least one sib or first-degree kin with bipolar disorder type I according to the DSM-IV (BPR). The last two groups defined at risk individuals. We interviewed all subjects with CT, as described by the senior author. RESULTS: We found a statistically significant difference in the rates of CT between the subjects in BPR versus others. CT was also more prevalent in the PFH compared with NFH. Additionally, the simple numeration of the CT traits exhibited gradation in the distribution of individuals inside the NFH, PFH and BPR. Finally, categorically defined CT and CT traits predominated in females. LIMITATION and CONCLUSION: Although not all relatives of bipolar probands were studied, our results exhibit an aggregation of CT in families with affective disorder-and more specifically those with bipolar background. These results allow us to propose the importance of including CT for phenotypic characterization of bipolar disorder. Furthermore, our results support a spectrum concept of bipolar disorder, whereby CT is distributed in ascending order in the well-relatives of those with depressive and bipolar disorders. We submit that this temperament represents a behavioral endophenotype, serving as a link between molecular and behavioral genetics.

Cyclothymic temperament as a prospective predictor of bipolarity and suicidality in children and adolescents with major depressive disorder.

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 , 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 ), 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.

Phenomenological and comorbid features associated in obsessive-compulsive disorder: influence of age of onset.

BACKGROUND: To explore clinical features of symptoms and comorbidity according to the age of onset of patients suffering from obsessive-compulsive disorder (OCD). METHODS: The survey involved collecting data from both patient members of an OCD association, and a sample of 175 OCD patients seen in OCD specialty practice. All the patients (n=617) responded to a questionnaire on family and personal psychiatric OCD history, phenomenological features of OCD and comorbidity. They were classified according to OCD age at onset [group early age of onset (EO): under 15, group late age of onset (LO): older than 15]. RESULTS: A higher percentage of patients from Group LO complained of OCD triggering by factors such as professional difficulties and childbirth (P<0.05); also they more often had (P=0.05) a sudden onset of symptoms. On the other hand, clinical features, such as superstition and magic thoughts, parasite obsessions and repeating, counting, hoarding, tapping/rubbing and collecting compulsions were significantly more frequent (P<0.05) in EO; likewise, history of tics was more frequent in this group. The existence of comorbid depression (at least one episode) did not show any significant difference between groups. However, depression preceding OCD was more frequent in LO. There was no significant difference in treatment response according to age of onset OCD. CONCLUSIONS: The results showed a clear association of EO with obsessions of superstition and parasites, repetitive compulsions and motor and vocal tics, whereas a sudden onset, triggering factors and a more frequent depression preceding OCD characterized LO.

[Hyperthymic and depressive temperaments study in controls, as a function of their familial loading for mood disorders]. / Etude des tempéraments dépressif et hyperthymique chez 165 sujets contrôles et à risque pour les troubles de l'humeur.

UNLABELLED: Since the two last decades, many authors have broadened the scope of mood disorders to include a larger bipolar spectrum which encompasses the sub-affective conditions, including temperaments. According to this view, the latter conditions represent milder or alternative expressions of the classic bipolar episodes. In successive elaborations, Akiskal et al. hypothesized a complex multicausal approach to bipolar disorder, and studied temperamental dysregulations, which could serve as risk factors for major episodes. Until recently, there have been several studies of patients populations, little is known in control populations. The aim of this report is to compare the rates of three affective temperaments (hyperthymic: TH; depressive: TD; irritable: TI) in non-ill subjects with different risk for mood disorders. (The cyclothymic temperament is studied as part of another report). METHODS: We recruited 185 individuals from: a) staff hospital; b) sibling of patients suffering from bipolar disorder, type I. Twenty subjects were excluded: 7 suffered from personal affective trouble; 12 exhibited cyclothymic traits; and one had familial schizophrenia. In the 165 remaining subjects, the temperamental characteristics were assessed by mean of the Akiskal and Mallya's criteria (1987, semi-structured interviews for affective temperaments, TH, TD, TI). Then, the population of controls was divided in 3 groups as a function of the familial loading for affective disorder and bipolar disorders: the first subgroup (AFN) was free of any antecedent ("super-normal controls", n=99); the second subgroup (AFP) had familial antecedents at the first or second degree (normal controls but at risk for affective disorder, n=33); the third subgroup (FBP) was composed of the siblings of bipolar I patients (subjects at high risk, n=33). Statistical procedures included standard and non-parametric methods: means standard deviation, Fisher's test, Mann-Whitney' and Kuskall-Wallis' tests, Spearman's correlation coefficient. As described by Placidi and collaborators (12), we also used the Z-score (temperamental score strictly higher than the second positive standard deviation: m + 2 sd). RESULTS: The general demographic characteristics show a higher frequency of women (p=0.02) but a similar mean age (p=0.296, NS) among the groups. The mean scores of the TH and TD are strongly and negatively correlated (Rho coefficient=- 0.397, p=0.01), exhibiting the internal coherence of the responses. The comparison of the temperamental characteristics among the 3 groups exhibits significant differences for the TH and TI (p=0.003). The mean scores are respectively: for the TH, 9.16 4.18 in AFN, 8.33 4.11 in AFP, and 12.16 5.28 in FBP; and for the TI, 8.94 2.25 in AFN, 9.39 2.63 in AFP, and 10.84 2.76 in FBP. Conversely, the TD scores do not significantly differ: 6.01 3.27 in AFN, 6.76 4.34 in AFP, and 7.94 5.28 in FBP. Beyond these first pass results, we also considered the distribution of the subjects as function of the Z-score and the different groups. We found that hyperthymic traits were almost exclusively among the FBP: 15.1% vs 3.0% in the other groups. For the TD, expressed in mean scores, the groups at risk for affective disorders (AFP and FBP) clearly display a percentage of subjects with a more substantial Z-score than the frequencies observed in the AFN: respectively 12.1%, 18.1% and 4.0% for the TD. Concerning traits of all three temperaments, as function of the demographic variables and the Z-score, they are generally predominant in males; however, the TH is more frequent in males only in the AFP and FBP groups (respectively: 8.3% vs none; 21.4% vs 10.5%). The TD is more prevalent among females in AFP and FBP (respectively: 8.3% vs 14.3%; 21.1% vs 14.8%). CONCLUSION: Our results clearly show temperamental dysregulations in the subjects at risk for affective disorders: (1) the levels of all three affective temperaments under study are significantly higher in subjects at risk for affective disorder, as compared to individuals free of a family antecedent; (2) the depressive temperament is prevalent in both AFP and FBP, whereas the hyperthymic is specific for FBP. As for Akiskal's model on the multicausal origin of the mood disorders, our data supports temperamental dysregulation as an important familial genetic factor in the vulnerability to manic depressive episodes. We further posit that such temperaments--more specifically, the hyperthymic--could serve as proximal phenotypes for full-blown bipolar disorder.

Cyclothymic OCD: a distinct form?

BACKGROUND: Clinical research on the comorbidity of obsessive compulsive disorder (OCD) and other anxiety disorders has largely focused on depression. However in practice, resistant or severe OCD patients not infrequently suffer from a masked or hidden comorbid bipolar disorder. METHOD: The rate of bipolar comorbidity in OCD was systematically explored among 453 members of the French Association of patients suffering from OCD (AFTOC) as well as a psychiatric sample of OCD out-patients (n=175). As previous research by us has shown the epidemiologic and clinical sample to be similar, we combined them in the present analyses (n=628). To assess mood disorder comorbidity, we used structured self-rated questionnaires for major depression, hypomania and mania (DSM-IV criteria), self-rated Angst's checklist of Hypomania and that for the Cyclothymic Temperament (French version developed by Akiskal and Hantouche). RESULTS: According to DSM-IV definitions of hypomania/mania, 11% of the total combined sample was classified as bipolar (3% BP-I and 8% BP-II). When dimensionally rated, 30% obtained a cut-off score >/=10 on the Hypomania checklist and 50% were classified as cyclothymic. Comparative analyses were conducted between OCD with (n=302) versus without cyclothymia (n=272). In contrast to non-cyclothymics, the cyclothymic OCD patients were characterized by more severe OCD syndromes (higher frequencies of aggressive, impulsive, religious and sexual obsessions, compulsions of control, hoarding, repetition); more episodic course; greater rates of manic/hypomanic and major depressive episodes (with higher intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions; and finally, a less favorable response to anti-OCD antidepressants and elevated rate of mood switching with aggressive behavior. LIMITATION: Hypomania and cyclothymia were not confirmed by diagnostic interview by a clinician. CONCLUSION: Our data extend previous research on "OCD-bipolar comorbidity" as a highly prevalent and largely under-recognized and untreated class of OCD patients. Furthermore, our data suggest that "cyclothymic OCD" could represent a distinct form of OCD. More attention should be paid to it in research and clinical practice.

Proposed multidimensional structure of mania: beyond the euphoric-dysphoric dichotomy.

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.

[Cyclothymic obsessive-compulsive disorder. Clinical characteristics of a neglected and under-recognized entity]. / Trouble obsessionnel compulsif cyclothymique. Caractéristiques cliniques d'une entité négligee et non reconnue.

OBJECTIVE: Clinical research is largely focused on depressive comorbidity in obsessional compulsive disorder (OCD). However some recent publications have suggested that bipolar comorbidity occurs in authentic OCD and its presence has a differential impact on the clinical picture and course of OCD. METHOD: Recent data from the collaborative survey conducted with AFTOC (French Association of patients suffering from OCD) have revealed a high rate of bipolar comorbidity in OCD: 30% for hypomania and 50% for cyclothymia. RESULTS: The present paper presents further comparative analyses between OCD with (n = 302) versus without cyclothymia (n = 272). The sub-group "Cyclothymic OCD" is characterized by a different clinical picture (higher frequency of aggressive, impulsive, religious and sexual obsessions, and compulsions of control, hoarding, repetition), episodic course, higher rate of major depressive episodes (with more intensity and recurrence) associated with higher rates of suicide attempts and psychiatric admissions, and less favorable response to anti-OCD treatments. CONCLUSION: These data suggested that cyclothymic OCD could represent a specific distinct variant form of OCD. More vigilance is needed toward this entity which is largely under-recognized in clinical practice.

[Bipolar obsessive-compulsive disorder: confirmation of results of the "ABC-OCD" survey in 2 populations of patient members versus non-members of an association]. / TOC bipolaire: confirmation des résultats de l'enquête "ABC-TOC" dans deux populations de patients adhérents versus non adhérents à une association.

Clinical data are largely focused on depressive comorbidity in OCD. However in practice, treating resistant or severe OCD sufferers revealed many cases who seem to have an authentic OCD with a hidden comorbid bipolar disorder. Most reports had evaluated the OCD comorbidity in unipolar and bipolar mood disorders (Kruger et al., 1995; Chen et Dilsaver, 1995). The only investigation in clinical population focused on the reverse issue was conducted in Pisa. Perugi et al. (1997) have showed in a consecutive series of 315 OCD outpatients, that 15.7% presented a bipolar comorbidity, mostly with BP-II disorder. Further analyses suggested that when comorbidity occurs with bipolar and unipolar depression, it has a differential impact on the clinical picture and course of OCD. The rate of bipolar comorbidity in OCD was analyzed in a recent epidemiological survey undertaken by the French Association of patients suffering from OCD (FA-OCD or AFTOC in French). In a sample of 453 OCD patients, 76% had suffered from a major depression, 11% from bipolar disorder (DSM IV mania or hypomania), 30% from hypomania (cases that obtained a score > or = 10 on the self-rated Angst Hypomania Checklist). According to the score > or = 10 on Self-rated Questionnaire for Cyclothymic Temperament, 50% were classified as cyclothymic. The self-assessment of soft-bipolar dimensions, such as hypomania and cyclothymia was previously validated in a multi-site study in major depression (Hantouche et al., 1998). Further analyses showed that comorbidity with soft bipolarity was characterized by significant interactions with high levels of impulsivity, anger attacks and suicidal behavior. In order to confirm these data, another cohort (n = 175 patients treated by psychiatrists for OCD) was formed and named "PSY-OCD". Comparative analyses between the two populations allowed showing very few demographic and clinical differences. The frequency rate of "bipolar OCD" was equivalent in both populations: BP-II disorder (DSM IV criteria) was present in 11% of FA-OCD and 16% of PSY-OCD. Furthermore using the Hypomania Checklist showed that BP-II disorder rate (score > or = 10) was higher: 32% of in both populations. Cyclothymic rate was also globally higher, but significant difference was obtained: 56% of FA-OCD versus 45% of PSY-OCD (p = 0.02). Moreover, mood switching rate under anti-OCD drugs was equivalent in both OCD populations (respectively 38% and 33%, p = ns). In case of BP comorbidity, patients had presented a greater number of concurrent major depressive episodes and suicidal attempts. When concurrent depression was considered, the rate diagnosis of soft bipolarity was 2.5 fold, and the number of suicidal attempts augmented by 7 fold (by comparison versus non-depressed OCD). Despite very early descriptions (since the beginning of the last century) of particular relationships between so-called "psychasthenia, folie de doute, folie raisonnante" and "circular and intermittent madness or cyclothymia", a few attention has been devoted to this complex pattern of comorbidity. The comparative data deriving from the collaborative survey with patients who are members of AFTOC and with a cohort of psychiatric outpatients, confirm the reality of bipolar-OCD comorbidity, which is largely under-recognized in clinical practice. More in depth analyses are now undertaken in order to investigate the characteristics of "bipolar OCD" by comparison to "non bipolar OCD".

[Frequency and clinical aspects of bipolar II disorder in a French multicenter study: EPIDEP]. / Fréquence et aspects cliniques du trouble bipolaire II dans une étude multicentrique française: EPIDEP.

This paper presents the definite data from a French multi-center study (EPIDEP). The aim of EPIDEP was to show the feasibility of validating the spectrum of soft bipolar disorders by practicing clinicians. In this report we focus on data concerning the frequency of BP-II disorder and the key characteristics of BP-II by systematic comparison versus Unipolar depression. EPIDEP involved training 48 french psychiatrists in 15 sites; it is based on a common protocol following the DSM IV criteria (Semi-Structured Interview for Hypomania and Major Depression), 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 Affective Temperaments (based on Akiskal-Mallya), self-rated Cyclothymia Scale (Akiskal). Comorbidity and family history (Research Diagnostic Criteria) were also obtained; EPIDEP was globally scheduled in two phases: Phase 1 devoted to recruiting major depressives, and phase 2 involved in more sophisticated assessment of soft bipolarity and administrating related measures. Results are presented on the total of 537 patients included at "visit 1" and 493 assessed for soft bipolarity at "visit 2". The BP-II global rate which was 21.7% at initial evaluation, nearly doubled (39.8%) by systematic evaluation of hypomania. Intergroup comparison versus unipolar depressives showed the following key characteristics of BP-II disorder: 1) distinct clinical presentation at index depressive episode despite uniformity in global intensity of depression (overrepresentation in BP-II of "suicidal thoughts", "guilt feelings", "depersonalisation-derealisation", "hypersomnia" "and weight gain"; and of "psychic anxiety" and "initial insomnia" in UP); 2) different course of illness with younger age of onset of first depression, higher rate of suicidal attempts, recurrency and hospitalisations; 3) more difficulties for recognition of the correct diagnosis; 4) more complex temperamental dysregulations (mixture of cyclothymic, hyperthymic and irritable traits which are highly represented in BP-II group); 5) higher rate in family history of mental disorders, especially bipolar disorders. Finally, EPIDEP data confirmed the diagnostic reliability of self-rating of hypomania and cyclothymia. With a systematic search of hypomania, almost 40% of major depressive episodes seen in psychiatric settings were classified as BP-II, of which only half were recognized by the clinicians at study inclusion. The BP-II validity as a distinct disorder from Unipolars was confirmed. Moreover, EPIDEP emphasized the reliability of self-rating in assessing soft-bipolarity (hypomania and cyclothymia). In total, EPIDEP data indicated that recognition of BP-II is feasible in diverse practice settings and proposed for clinicians some adapted clinical tools for assessing soft bipolarity.

[Obsessive-compulsive disorder in children induced by streptococcal infection]. / Le trouble obsessionnel compulsif chez l'enfant induit par une infection streptococcique.

FROM OBSESSIVE-COMPULSIVE DISORDER TO PANDAS: Obsessive-compulsive disorder (OCD) represents a potentially severe and handicapping disorder that affects several hundreds of thousands of children in France. OCD has, for many years, been considered as a neurosis resulting from mental conflicts. It is currently seen as a neurobiological disorder, the etiological substratum of which is more organic than mental. Recently a sub-type of OCD was isolated in children following infection by Group A b-hemolytic streptococci. This sub-type has been described as Paediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS). A NEW PHYSIOPATHOLOGICAL APPROACH: The putative dysimmune relationship between bacterial infection and neurotic disorder has led to the development of an original etiopathogenic model that may lead to new therapeutic strategies. The clinical case report of an adolescent presenting with trichotillomania associated with recurrent pharyngitis is a good illustration of this. PUBLISHED DATA: Data published in medical literature over the last 10 years indicates a 10% prevalence in the young suffering from OCD, i.e. 0.1 to 0.3% of the young population.

Toward a refined phenomenology of mania: combining clinician-assessment and self-report in the French EPIMAN study.

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 > or = 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 > or = 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.