Quality and readability of French on-line information about otitis media with effusion.

INTRODUCTION: Childhood otitis media with effusion (OME) is a frequent disease often misunderstood by parents. Information on the Internet is of variable quality and readability. The aim of this study was to measure the quality and readability of French websites related to OME. MATERIAL AND METHODS: An advanced Google search was conducted using the terms "Otite séro-muqueuse OR Otite séreuse". Quality was assessed on DISCERN criteria. Readability was assessed using Flesch Reading Ease Scoring (FRES), Flesch-Kincaid Grade Level (FKGL), the Simple Measure of Gobbledygook (SMOG) and a Fry graph. Medians and standard deviations were calculated. Correlation between quality and readability was assessed on Spearman r coefficient. RESULTS: The first ten websites meeting inclusion and exclusion criteria were evaluated. One had been updated during the last 12 months. Median DISCERN score was 49±13.7/80. Median FRES score was 46±9.5/100. Median USA grade-level estimated by FKGL and SMOG respectively was 11±1.7 and 12±1.5. Six websites had Fry score>12. One website showed high quality. One had a readability score in the target range (below 9th grade reading level (age 14-15)) according to FRES and FKGL. A suggestive correlation was found between lower SMOG readability and higher quality: r=0.72 (P=0.024). Three websites followed the most recent scientific guidelines. CONCLUSION: Online information about OME was of variable quality and readability. Good quality information tended to be less easily understandable by parents.

A highly stable sodium solid-state electrolyte based on a dodeca/deca-borate equimolar mixture.

Na2(B12H12)0.5(B10H10)0.5, a new solid-state sodium electrolyte is shown to offer high Na+ conductivity of 0.9 mS cm-1 at 20 °C, excellent thermal stability up to 300 °C, and a large electrochemical stability window of 3 V including stability towards sodium metal anodes, all essential prerequisites for a stable room-temperature 3 V all-solid-state sodium-ion battery.

Is psychosis in DSM-IV mania due to severity? The relevance of selected demographic and comorbid social-phobic features.

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 < 0.0001) than non-severe, but did not differ from the severe without psychosis. We found significant correlations between both the Hallucination and the Delusion subscores of the SAPS and the MRS, as well as correlations between age, single marital status, comorbid social phobia and psychotic mania. CONCLUSION: Apart from episode severity, social isolation - associated with younger age, single marital status and social phobia - seems to make a contribution to the origin of manic psychosis largely independent from such severity.

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.

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.

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.

[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.

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.

The feasibility of self-assessment of dysphoric mania in the French national EPIMAN study.

BACKGROUND: There is presently considerable uncertainty on how to best assess mixed mania. The present contribution explores the feasibility of discriminating manic and dysphoric manic states on the basis of self-rating in the acute phase of the illness. METHODS: In the French four-site national EPIMAN study of 104 patients devoted to the clinical evaluation and subclassification of mania, we used the Multiple Visual Analog Scales of Bipolarity (MVAS-BP, 26 items) of Ahearn-Carroll in a self-assessment format. The study was conducted on consecutive patients hospitalized for an acute DSM-IV mania. The severity of mania was measured by the Beigel-Murphy scale (MSRS) assessed by psychiatrists. When mania abated, temperaments according to Akiskal and Mallya were administered in their French version. RESULTS: Principal component analysis revealed a general factor explaining 33% of the variance and, after rotation, seven factors defining different dimensions of the phenomenology of mania. The factorial scores, as well as the dimensional scores of the Carrol-Klein model significantly distinguished pure versus dysphoric mania made on clinical grounds. Gender seemed to influence two factors: high 'anxious-depressive' score in females (which is in line with female overrepresentation in mixed mania), vs. high score in males on the 'gregariousness' factor (which represents social disinhibition of the hyperthymic temperament known to be more prevalent in men). LIMITATION: Cross-sectional correlational study in need of longitudinal validation. CONCLUSIONS: EPIMAN data deriving from a national clinical population showed the feasiblity and face validity of self-assessment in acute mania, in particular its dysphoric subtype. Temperament in women seemed to contribute to the genesis of mixed (dysphoric) mania in accordance with Akiskal's hypothesis of opposition of temperament and polarity of bipolar episodes in mixed states. Self-assessment was capable of capturing accurately the subthreshold depressive symptomatology of mixed mania, which can be missed in hetero-evaluation by hasty clinical interview.

Effect of ciprofibrate on fibrinogen synthesis in vitro on hepatoma cells and in vivo in genetically obese Zucker rats.

In this study, we have shown that oncostatin M and interleukin-6 induce a dose- and time-dependent increase in fibrinogen levels in the conditioned medium of human hepatoma cells (HepG2). When HepG2 cells were treated simultaneously with oncostatin M or interleukin-6 and ciprofibrate (100 nmol/l), the production of fibrinogen in the conditioned media was strongly affected and a significant decrease in the mRNA levels of the fibrinogen beta chain was observed. Oncostatin-M- and interleukin-6-induced fibrinogen release was inhibited in a dose-dependent manner by ciprofibrate and, to lesser extent, by bezafibrate, fenofibric acid and clofibric acid. In vivo, increased plasma and platelet levels of fibrinogen were observed in genetically obese Zucker rats (fa/fa) compared with Zucker lean (fa/-) rats. In these rats, a 14-day oral treatment with ciprofibrate (10 mg/kg, per. os.) induced a statistically significant decrease (P > 0.05) in plasma concentrations of total cholesterol and triglyceride but also in plasma and platelet levels of fibrinogen. In order to determine the consequences of such an effect on fibrinogen, the ability of ciprofibrate to affect venous stasis was determined in a stasis-induced venous thrombosis model in Zucker rats. Under low thrombogenic challenge, ciprofibrate significantly inhibited thrombus formation (67+/-12%, P > 0.05), demonstrating for the first time that a potent hypolipemic compound exhibits an antithrombotic effect.

Plasma lipoprotein distribution and lipid transfer activities in patients with type IIb hyperlipidemia treated with simvastatin.

The aim of the present study was to search in type IIb hyperlipidemic patients for putative concomitant effects of simvastatin on the physicochemical characteristics of low density lipoproteins (LDL) and high density lipoproteins (HDL), as well as on the activities of the cholesteryl ester transfer protein (CETP) and the phospholipid transfer protein (PLTP) that were determined in both endogenous lipoprotein-dependent and endogenous lipoprotein-independent assays. In a double-blind, randomized trial, patients received either placebo (one tablet/day; n = 12) or simvastatin (20 mg/day; n = 12) for a period of 8 weeks after a 5-week run-in period. Simvastatin, unlike placebo, reduced the lipid and apolipoprotein B contents of the most abundant LDL-1, LDL-2, and LDL-3 subfractions without inducing significant changes in the overall size distribution of LDL and HDL. Whereas simvastatin significantly increased PLTP activity in an endogenous lipoprotein-dependent assay (P < 0.01), no variation was observed in a lipoprotein-independent assay. Simvastatin significantly decreased plasma CETP activity in an endogenous lipoprotein-dependent assay (P < 0.01), and the reduction in plasma cholesteryl ester transfer rates was explained by a 16% drop in CETP mass concentration (P < 0.01). In contrast, the specific activity of CETP was unaffected by the simvastatin treatment reflecting at least in part the lack of significant alteration in plasma triglyceride-rich lipoprotein acceptors. The simvastatin-induced changes in plasma CETP mass levels correlated positively with changes in plasma CETP activity (r = 0.483, P = 0.0561), in total cholesterol levels (r = 0.769; P < 0.01), and in LDL-cholesterol levels (r = 0.736; P < 0.01). Whereas the observations suggest that simvastatin might exert concomitant beneficial effects on plasma CETP and LDL levels, neither plasma cholesteryl ester transfer activity nor plasma phospholipid transfer activity appeared as the main determinants of the LDL and HDL distribution profiles in type IIb hyperlipidemic patients.

Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP).

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 <0.0001). Cyclothymia and hypomania were also correlated significantly (r=0.51; p < 0.001). LIMITATION: In a study conducted in diverse clinical settings, it was not possible to assure that clinicians making affective diagnoses were blind to the various temperamental measures. However, bias was minimized by the systematic and/or semi-structured nature of all evaluations. CONCLUSION: With a systematic search for hypomania, 40% of major depressive episodes were classified as BP-II, of which only half were known to the clinicians at study entry. Cyclothymic temperamental dysregulation emerged as a robust clinical marker of BP-II disorder. These data indicate that clinicians in diverse practice settings can be trained to recognize soft bipolarity, leading to changes in diagnostic practice at a national level.

Gender, temperament, and the clinical picture in dysphoric mixed mania: findings from a French national study (EPIMAN).

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 > or = 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.