TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits

BACKGROUND: Temperament is an important factor in affective illness. There is some indication that mixed episodes result from an admixture of inverse temperamental factors (e.g. depressive and/or anxious) to a manic syndrome. To test this hypothesis, which has been first formulated by Akiskal [Clin. Neuropharmacol. 15 (Suppl. 1A) (1992) 632-633], we compared the temperament of non-acute bipolar affective patients with and without the history of a previous mixed episode. METHODS: Patients who had been hospitalized for a bipolar disorder were re-assessed at least 6 months after their last in-patient treatment. Those who met the criteria for a partially remitted or full affective or psychotic episode at re-assessment were excluded from the study. Data concerning illness history, current psychopathology (SCID-I interview), depression (BDI), mania (Self-Report Manic Inventory) and temperament (TEMPS-A scale) were obtained. Patients with and without a history of previous mixed episodes were compared. RESULTS: Of 49 eligible former patients, 22 subjects with and 23 subjects without a former mixed episode in bipolar affective disorder fulfilled the inclusion criteria. Subjects suffering from bipolar affective disorder exhibited significantly more depressive and anxious and less hyperthymic temperament, if they had experienced a mixed episode previously. Concerning cyclothymic and irritable temperament, bipolar affective patients with a former mixed episode presented non-significantly higher scores. Patients with a former mixed episode presented with higher depression scores than patients without such a history. No group differences were found concerning current mania scores. LIMITATIONS: (1). This is a preliminary report from an ongoing study. (2). Temperament had not been assessed premorbidly. (3). Although group comparisons revealed significant differences, these did not seem great enough to fully explain the emergence of a mixed episode. CONCLUSION: Our findings support the study's hypothesis that mixed episodes occur more often in subjects with an inverse temperament (e.g. depressive and anxious), although it cannot be ruled out that subsyndromal features of the bipolar illness had an effect on temperament assessment.     

Temperament in bipolar illness: impact on prognosis

OBJECTIVE: The present study was designed to investigate the relations between temperament and outcome in bipolar illness. METHODS: Seventy-two patients presenting with bipolar type I disorder were recruited from consecutive admissions and evaluated when euthymic. The criteria developed by Akiskal and Mallya (Criteria for the 'soft' bipolar spectrum: treatment implications. Psychopharmacol. Bull. 1987;23:68-73) were used to assess both depressive (DT) and hyperthymic temperaments (HT) in a dimensional approach. RESULTS: Multiple regression analysis showed that a higher DT score or a lower HT score were significantly associated with a greater number of episodes. Furthermore, a higher DT score was strongly associated with a higher percentage of major depressive episodes. Conversely, a higher HT score was associated with a trend to manic rather than depressive episodes. Suicide attempts appeared more frequent in the history of patients presenting with higher DT scores. CONCLUSIONS: Our findings strengthen the hypothesis that temperament is one of the main variables accounting for some features in the clinical evolution of bipolar disorder such as polarity of episodes. Furthermore, these findings are consistent with the hypothesis of a trait-state continuum between personality and affective episodes.     

The premorbid personality of patients with different subtypes of an affective illness. Statistical analysis of blind assignment of case history data to clinical diagnoses

On the basis of case history data, the assumption that there exists an association between the 'manic type' of personality and a predominantly manic course of an affective illness, and between the 'melancholic type' of personality and a unipolar depressive course of the illness was examined. Premorbid data were extracted from 42 case records, 10 of 'unipolar' manic subjects (the ratio of manic to depressive episodes greater than or equal to 4:1), 11 of typical bipolar I patients, 11 of bipolar II patients, and 10 of unipolar endogenous depressives. A rater (J.P.), blind to diagnosis and selection procedure, assigned case notes to personality types. Differences were predicted in terms of personality type between the two unipolar groups, the two bipolar groups and, due to the higher number of cases, also between the combined groups of 'unipolar' manic and bipolar I patients on the one hand, and unipolar depressive and bipolar II patients on the other. According to the Fisher test these predictions were fulfilled. Furthermore, in agreement with our hypotheses on the relationship between premorbid personality and course of the disease, the ratio of assignments to 'manic type' and 'melancholic type' decreased from 'unipolar' mania, to bipolar I and bipolar II disorders, and to unipolar depression.     

How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity?

BACKGROUND: History of high depressive recurrence (without history of mania/hypomania) has been proposed as a mood subtype close to bipolar disorders. Herein we test whether this is the best approach to this question. METHODS: We systematically evaluated consecutive 224 Major Depressive (MDD) and 336 Bipolar II Disorders (BP-II) outpatients in a private practice, by the SCID for DSM-IV (modified for better probing hypomania by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2005. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J. Clin. Psychiatry 66, 914-921]). We conducted univariate and multivariate analyses on such putative bipolar validators as early age at onset of first major depressive episode (before 21 years), high recurrence, family history for bipolar disorders, and depressive mixed states (mixed depression, i.e. depression plus concurrent hypomanic symptoms), in order to identify an MDD subgroup close to BP-II. RESULTS: All bipolar validators were independent predictors of BP-II. Early onset was the only variable which identified an MDD subgroup significantly associated with all bipolar validators. This MDD subgroup was similar to BP-II on age at onset and bipolar family history, and had a high frequency of mixed depression. A dose-response relationship was found between number of bipolar validators present in MDD, and bipolar family history loading among MDD relatives. LIMITATIONS: Study limited to outpatients. CONCLUSIONS: From among the bipolar validators, early age at onset of first major depression (<21 years) was superior to high recurrence (>4 depressive episodes) in identifying an MDD subgroup close to BP-II, which might be subsumed under the broad bipolar spectrum. Implications of unipolar-bipolar boundaries and genetic investigations are discussed.     

Evaluating the inter-episode stability of depressive mixed states

BACKGROUND: Depressive mixed state (DMX) is understudied, although this diagnostic concept may be of clinical and theoretical importance. Our goal was to provide preliminary evidence of the inter-episode stability of DMX. The inter-episode stability is known to be an important validator for establishing a distinct clinical entity. METHODS: Out of depressive patients consecutively hospitalized at our institute, those who experienced two or more hospitalizations due to discrete depressive recurrences during a 6-year period were selected. All depressive episodes were directly observed and assessed using a standardized rating instrument in terms of eight intra-episode manic symptoms (flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Assessments for subsequent episodes were performed blindly to those for previous episodes within each patient. RESULTS: The inter-episode stability of categorical DMX diagnoses and the number of intra-episode manic symptoms was moderate but significantly high. Approximately 50% of patients with DMX in the index episode obtained a DMX diagnosis in the second episode. Approximately 40% of the total variance of the number of intra-episode manic symptoms was explained by agreements across several depressive episodes. Depressive patients who experienced a diagnostic switch from unipolar to bipolar disorder had a higher frequency of DMX and a greater number of intra-episode manic symptoms in the index as well as subsequent episodes. LIMITATIONS: All consecutive patients were not followed up. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: The inter-episode stability of DMX may not be so high as is required for establishing a distinct clinical entity. However, the findings strongly suggest that some depressive patients have a long-lasting liability to DMX. It is important to determine whether such a liability to DMX is mediated by affective temperaments, as was originally hypothesized by Akiskal [J. Clin. Psychopharmacol. 16 (1996) 4S-14S]. DMX may be a risk factor to the diagnostic switch from unipolar to bipolar disorder.     

Re-evaluating the prevalence of and diagnostic composition within the broad clinical spectrum of bipolar disorders

Until recently it was believed that no more than 1% of the general population has bipolar disorder. Emerging transatlantic data are beginning to provide converging evidence for a higher prevalence of up to at least 5%. Manic states, even those with mood-incongruent features, as well as mixed (dysphoric) mania, are now formally included in both ICD-10 and DSM-IV. Mixed states occur in an average of 40% of bipolar patients over a lifetime; current evidence supports a broader definition of mixed states consisting of full-blown mania with two or more concomitant depressive symptoms. The largest increase in prevalence rates, however, is accounted for by 'softer' clinical expressions of bipolarity situated between the extremes of full-blown bipolar disorder where the person has at least one manic episode (bipolar I) and strictly defined unipolar major depressive disorder without personal or family history for excited periods. Bipolar II is the prototype for these intermediary conditions with major depressions and history of spontaneous hypomanic episodes; current evidence indicates that most hypomanias pursue a recurrent course and that their usual duration is 1-3 days, falling below the arbitrary 4-day cutoff required in DSM-IV. Depressions with antidepressant-associated hypomania (sometimes referred to as bipolar III) also appear, on the basis of extensive international research neglected by both ICD-10 and DSM-IV, to belong to the clinical spectrum of bipolar disorders. Broadly defined, the bipolar spectrum in studies conducted during the last decade accounts for 30-55% of all major depressions. Rapid-cycling, defined as alternation of depressive and excited (at least four per year), more often arise from a bipolar II than a bipolar I baseline; such cycling does not in the main appear to be a distinct clinical subtype - but rather a transient complication in 20% in the long-term course of bipolar disorder. Major depressions superimposed on cyclothymic oscillations represent a more severe variant of bipolar II, often mistaken for borderline or other personality disorders in the dramatic cluster. Moreover, atypical depressive features with reversed vegetative signs, anxiety states, as well as alcohol and substance abuse comorbidity, is common in these and other bipolar patients. The proper recognition of the entire clinical spectrum of bipolarity behind such 'masks' has important implications for psychiatric research and practice. Conditions which require further investigation include: (1) major depressive episodes where hyperthymic traits - lifelong hypomanic features without discrete hypomanic episodes - dominate the intermorbid or premorbid phases; and (2) depressive mixed states consisting of few hypomanic symptoms (i.e., racing thoughts, sexual arousal) during full-blown major depressive episodes - included in Kraepelin's schema of mixed states, but excluded by DSM-IV. These do not exhaust all potential diagnostic entities for possible inclusion in the clinical spectrum of bipolar disorders: the present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise impulse-ridden, intermittently explosive or agitated psychiatric conditions for which the bipolar connection is less established. The concept of bipolar spectrum as used herein denotes overlapping clinical expressions, without necessarily implying underlying genetic homogeneity. In the course of the illness of the same patient, one often observes the varied manifestations described above - whether they be formal diagnostic categories or those which have remained outside the official nosology. Some form of life charting of illness with colored graphic representation of episodes, stressors, and treatments received can be used to document the uniquely varied course characteristic of each patient, thereby greatly enhancing clinical evaluation.     

Dimensions underlying outcome criteria in bipolar I disorder

OBJECTIVE: Various subjective and objective criteria are used to assess outcome in bipolar disorder. In this study, we explored to what extent they reflect distinct categories and whether underlying dimensions can be identified. PATIENTS AND METHODS: One-hundred and twenty-one subjects with at least three episodes of bipolar I disorder (DSM-IV) were assessed on average 4.8 years after hospitalization. We assessed 14 variables reflecting different outcome criteria including subjective quality of life (SQOL), self-rated and observer-rated psychopathology, and functioning and disability. A principal component analysis was computed across all outcome variables. Identified dimensions were correlated with sociodemographic characteristics, illness history, premorbid adjustment and personality traits. RESULTS: Three outcome dimensions were identified, i.e. a 'general subjective', a 'functioning/disability' and a 'manic/psychotic symptoms' dimension. Together they explain 69% of the total variance. The 'general subjective' dimension consists of SQOL scales and self-rated depressive symptoms. It is associated with comorbid anxiety disorders and personality disorders, high neuroticism and not having been in hospital in the last year. The 'functioning/disability' dimension comprises of criteria reflecting negative symptoms, disability and low functioning. It is associated with more prior illness episodes and low premorbid adjustment. The 'manic/psychotic symptoms' dimension consists of observer-rated manic and positive psychotic symptoms. It is correlated with not currently taking a specific medication. LIMITATIONS: Cross-sectional design with a limited sample size. CONCLUSION: The findings indicate that outcome criteria in bipolar I disorder can be grouped into three distinct dimensions reflecting (1) subjective appraisals, (2) functioning/disability and (3) manic/psychotic symptoms. While measurement of psychotic/manic symptoms has become a matter of course, until now few studies have assessed disability or subjective appraisal in bipolar illness. Therefore important aspects of bipolar illness might be overseen. For a better understanding, we suggest that longitudinal studies of bipolar I disorders should consider all three dimensions of outcome and measure them separately.     

Efficacy and safety of aripiprazole in subpopulations with acute manic or mixed episodes of bipolar I disorder

BACKGROUND: This analysis was designed to assess the efficacy and safety of aripiprazole compared with placebo in subpopulations of patients with acute manic or mixed episodes of bipolar I disorder. METHODS: Acutely manic patients experiencing DSM-IV manic/mixed episodes of bipolar I disorder were pooled from two randomized, three-week, flexible-dose, double-blind, placebo-controlled trials (N=516) and stratified by disease severity (Young Mania Rating Scale, YMRS), episode type, presence or absence of psychotic features, episode frequency, age, gender, and baseline severity of depressive symptoms. Safety and treatment-emergent adverse-event analyses were also performed. RESULTS: Aripiprazole significantly reduced mean YMRS total scores at end point compared with placebo in patients with more severe or less severe illness, with mixed or manic episodes, with or without psychotic features, or with a history of rapid or non-rapid cycling (p<0.01 for each subpopulation); in men and women (p=0.001 for both); in patients in the 18-40 and 41-55 year age groups (por=5% of patients aged 18-40 years receiving aripiprazole were similar to those reported for the overall population. LIMITATIONS: This post hoc analysis utilized pooled data from two short-term studies. CONCLUSION: Efficacy of the second-generation antipsychotic aripiprazole was noted across a broad range of subpopulations often associated with treatment resistance in patients experiencing manic or mixed episodes of bipolar I disorder.     

Clinical characterization of depressive mixed state in bipolar-I patients: Pisa-San Diego collaboration

BACKGROUND: Although mixed states were classically described as various concomitant admixtures of depression and mania, the official current definitions in both DSM-IV and ICD-10 tend to restrict the concept to manic patients with full syndromal depression. Recent research has actually shown that mania with few depressive symptoms constitutes the most prevalent clinical presentation of mixed or dysphoric mania. Major depressive patients with few concomitant manic symptoms are not officially recognized within the current nosology. In this paper we attempt to delineate the clinical profile of such depressive mixed states in the context of bipolar I disorder. METHODS: In the Pisa day center, we studied 195 bipolar I patients who either met Pisa criteria for bipolar mixed state (n=159) or DSM-III-R criteria for major depressive episode (bipolar major depression or B-MD, n=36). Of the 159 patients identified by Pisa criteria as mixed state, 86 also met the criteria of the DSM-III-R for mixed episode (core mixed state or MS group), while 32 met the DSM III-R criteria for major depressive episode (provisionally defined as depressive mixed states, D-MS); the remaining patients (n=41, 25.7%) with predominatly manic picture were not included in the present comparisons. RESULTS: The three groups (B-MD, MS and D-MS) had close similarities in clinical and sociodemographic characteristics such as age, sex distribution, marital status, schooling, residence, age at onset, age of first treatment, age of first hospitalization, degree of chronicity of the index episode, stressor within the 6 months before the index episode, lifetime suicide attempts and premorbid temperament. First degree family history for bipolar illness and that for other mental disorders was also similar, except for major depression that was more common among the relatives of D-MS. MS and D-MS were further distinguished from B-MD by the fact that the latter followed a more 'cyclic' course with shorter yet greater number of episodes, and which began with a pure depressive episode; by contrast, MS and D-MS had fewer episodes of longer duration, less interepisodic remission, and tended to begin with a mixed episode. Incongruous psychotic features were more common in the two mixed groups compared to B-MD, and the most common features of the D-MS group were agitation, psychotic depression with irritable mood, pressured speech and/or flight of ideas. LIMITATION: It was not feasible to collect information blind to clinical status in patients with severe psychotic mood states. CONCLUSION: These data confirm the existence of psychotic agitated depressive mixed states with flight of ideas, distinct from cyclic retarded pure bipolar depressive states. The recognition of these affective states is clinically important to protect patients from the potentially harmful indiscriminate use of antidepressants and to provide them with the benefits of an anticonvulsant, a short-term neuroleptic, or ECT.     

The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention

BACKGROUND: Previous reports have shown a significant relationship between suicide ideation and mixed depression. The aim of this study was to explore the prevalence and clinical characteristics of mixed depression among non-violent suicide attempters. METHODS: Using a structured interview (modified Mini International Neuropsychiatric Interview) and assessing all the symptoms of 16 psychiatric diagnoses, the authors examined 100 consecutive nonviolent suicide attempters (aged 18-65) within 24 h after their attempts. Mixed depression was defined as a major depressive episode (MDE)/dysthymic disorder plus 3 or more co-occurring hypomanic symptoms, according to the definition validated by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2003a. Delineating depressive mixed states: Their therapeutic significance. Clin. Approaches Bipolar Disord. 2, 41-47, Akiskal, H.S., Benazzi, F., 2003b. Family history validation of the bipolar nature of depressive mixed states. J. Affect. Disord. 73, 113-122.]. RESULTS: Current mixed depression was present in 63.0% in the total sample, and in 70.8% among the 89 depressive suicide attempters. Irritability, distractibility and psychomotor agitation were present in more than 90% of the subjects with mixed depression. The rate of mixed depression was significantly higher among bipolar than non-bipolar depressive suicide attempters (90% vs. 62%). Patients with mixed depression had the following concurrent disorders: bipolar disorders 41.0%, panic disorder 30.0%, generalized anxiety disorder 89.0%, alcohol abuse/dependence 56.0%, and substance abuse 27.0%. Mixed depression versus non-mixed depression had the following significant associations (odds ratio=OR): females 2.4, bipolar II disorder 9.3, generalized anxiety disorder 41.3, irritability 101.6 and psychomotor agitation 61.1. LIMITATIONS: The study didn't include suicide attempters with very high risk of fatality. CONCLUSIONS: The important new finding of this study is the very high prevalence of mixed depression among depressed suicide attempters. The rates of mixed depression among bipolar and non-bipolar depressive suicide attempters were much higher than previously reported among nonsuicidal bipolar II and unipolar depressive outpatients, suggesting that suicide attempters come mainly from mixed depressives with predominantly bipolar II base. Irritability and psychomotor agitation were the strongest predictors of suicide attempt. From a public health standpoint, our data highlight the necessity of detecting and treating mixed (bipolar) depression in the prevention of suicidal behaviour.     

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.     

Recurrence rates of bipolar disorder during the postpartum period: a study on 276 medication-free Italian women

The postpartum period is considered a time of heightened vulnerability to bipolar disorder. The primary goal of this study was to examine the frequency and the polarity of postpartum episodes in a clinical sample of women with bipolar disorder who were medication-free during their pregnancies. In addition, we sought to examine whether there are differences in terms of clinical features of bipolar disorder between women with and without postpartum episodes. Lastly, we analyzed the potential relationship between polarity of the postpartum episodes and clinical features of bipolar disorder. The presence/absence of postpartum episodes and their characteristics were obtained from medical records of 276 women with bipolar disorder who were medication-free during their pregnancies. Two hundred seven women (75.0 %) had a history of one or more postpartum mood episodes: depressive (79.7 %), (hypo)manic (16.4 %), or mixed episodes (3.9 %). Psychotic symptoms during postpartum episodes were associated with depression in 37 (22.4 %) patients, with mania in 19 (67.8 %) patients, and with mixed episodes in 7 (87.5 %) patients. Postpartum manic and mixed episodes were significantly associated with type I disorder and with psychotic features. Our findings indicate high risk of clinically ascertained mood episodes during postpartum period in bipolar women who are not treated during pregnancy.     

Distinct seasonality of depressive episodes differentiates unipolar depressive patients with and without depressive mixed states

BACKGROUND: The bipolar nature of unipolar depression with depressive mixed states (DMX) needs further validation studies. The seasonality of depressive episodes is indicated to be different between unipolar and bipolar depressions. We therefore explored the seasonal pattern of depressive episodes in unipolar depressive patients with DMX. METHODS: The subjects were 958 consecutive depressive inpatients for a 6-year period. For defining DMX, previously validated operational criteria were used (2 or more of 8 manic or mania-related symptoms: flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Onsets of the index depressive episodes during each of the 12 calendar months were summed up over the 6-year for bipolar depressive patients (N = 95), and unipolar depressive patients with (N = 77) and without DMX (N = 786) separately. An appropriate statistic was used for testing seasonality. RESULTS: A significant seasonal variation with a large peak in spring was recognized in unipolar depression without DMX, while both bipolar depression and unipolar depression with DMX had a significant fall peak. The monthly distribution of depressive episodes was significantly different between unipolar depression without DMX and other 2 diagnostic categories. Similar results were obtained in separate analyses for each gender. LIMITATIONS: Further replication study using an epidemiological or outpatient sample is needed. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: Unipolar depression with DMX has a seasonal pattern similar to bipolar depression. The finding provides further evidence of the bipolar nature of unipolar depression with DMX.     

Effects of rapid cycling on response to lithium maintenance treatment in 360 bipolar I and II disorder patients

INTRODUCTION: Rapid cycling (RC) in bipolar disorders is widely believed to predict future morbidity and poor treatment response, although empirical testing of its predictive utility remains limited. METHODS: In 360 DSM-IV bipolar I (N=218) and II (N=142) disorder subjects (64% women) followed over an average of 13.3 years, we evaluated factors associated with RC status with bivariate and multivariate techniques, and response to lithium maintenance treatment (recurrence rates, time ill, survival analysis of time to recurrence on lithium). RESULTS: RC risk (15.6% of cases) was 5. 1-times greater in bipolar II vs. I subjects (30.3%/6.0%), in minor excess in women vs. men (17.9%/11.5%), and associated with premorbid cyclothymia, depressive first episodes, older onset age, and being employed or married. Before lithium, RC vs. non-RC cases had more mean total (3.9/1.2), manic, and depressive episodes/year, and greater percent time ill (60%/38%). During treatment, prior RC status was unrelated to time to first recurrence and other measures of morbidity and improvement including percent time ill, although depressive episodes were 2.7-times more frequent, and there was 13.7% less chance of full protection from all recurrences in RC cases. Limitations: The study is naturalistic, without random assignment or blind assessment. CONCLUSIONS: The RC bipolar subtype was strongly associated with type II diagnosis, higher average prelithium episode frequency and percent time ill, and weakly with female sex, but not with greater overall morbidity during treatment.     

The effect of the first manic episode in affective disorder: a case register study of hospitalised episodes.

BACKGROUND: It is poorly understood how the course of illness in depressive patients is affected by a manic episode. METHOD: The course of hospitalised episodes was compared for patients with depressive episodes only, patients who presented with a manic or circular first episode and patients who presented with a depressive first episode and later developed mania. The Danish psychiatric central register was used as a study base, including all hospital admissions with primary affective disorder in Denmark during 1971-1993. RESULTS: A total of 17,447 patients presented with a depressive first episode and 2903 patients with a manic or circular first episode. Among the 17,447 depressive patients, 762 patients presented with mania at later episodes (4.4%). Younger age at onset was associated with increased risk of developing mania. Patients who had a late first manic episode had the same rate of subsequent recurrence as patients with mania at first episode and this rate was higher than the rate of recurrence for patients who remained having depressive episodes only. Time since first manic episode was without importance in relation to the risk of subsequent recurrence. CONCLUSION: Patients who present with depression and later develop mania have from onset the same risk of recurrence as initially bipolar patients. LIMITATION: The data relate to admissions rather than episodes. CLINICAL RELEVANCE: Younger patients who present with depression have increased risk of developing bipolar disorder.     

Seasonal variation of mixed and pure episodes of bipolar disorder

BACKGROUND: Although seasonal patterns of manic episodes have been reported, the seasonal variation of mixed states of bipolar disorder has received little attention. In the current report we address that concern as well as the overall seasonality of manic episodes. METHODS: The seasonal pattern of 304 psychiatric hospital admissions for treatment of mixed or manic bipolar episodes over a 3-year period were analyzed employing two definitions of mixed manic states: DSM-III-R and an ROC derived definition. RESULTS: The frequency of all manic episodes combined peaked in early spring, with a nadir in late fall. Pure manic admissions showed a similar pattern. Mixed manic admissions had a significantly different pattern, with a peak in late summer and a nadir in November. The differences between pure and mixed manic admissions were demonstrated with the use of the ROC definition for mixed states. LIMITATIONS: Effects of medications and medication non-compliance may dampen natural seasonal patterns of episodes. CONCLUSIONS: The different seasonal pattern of mixed and pure manic episodes support the separation of mixed episodes as a distinct clinical subtype.     

Panic disorder and bipolar disorder: anxiety sensitivity as a potential mediator of panic during manic states

BACKGROUND: Panic disorder (PD) occurs at high rates in bipolar disorder and more commonly than in unipolar depression. Reports of PD onset during hypomania and depressive mania (i.e., mixed states) raise questions about whether the affective disturbances of bipolar disorder play a specific role in the exacerbation or onset of PD. Anxiety sensitivity (AS), a risk factor for PD appears greater in bipolar disorder compared to unipolar depression, although the association of specific mood states with AS remains unknown. METHODS: We examined the association of current mood state (i.e., mixed state, mania or hypomania, bipolar depression, unipolar depression, and euthymia) with Anxiety Sensitivity Index (ASI) scores in 202 individuals with bipolar disorder (n=110) or major depressive disorder (n=92). RESULTS: Current mood state was significantly associated with ASI score (Chi-square=21.2, df=4, p=0.0003). In multiple regression analyses, including covariates for comorbid anxiety disorders, current mania or hypomania was a significant predictor of ASI scores (p<0.04). Current mixed state tended toward a similar association (p<0.10). LIMITATIONS: Conclusions are limited by the study's cross-sectional nature and relatively small sample size. CONCLUSIONS: These findings of elevated AS during manic states, independent of comorbid anxiety disorders, provide preliminary support for the hypothesis that manic states contribute to risk for the development or exacerbation of PD, and that AS may contribute to the high prevalence and severity of PD comorbid with bipolar disorder.     

Affective temperaments are associated with specific clusters of symptoms and psychopathology: A cross-sectional study on bipolar disorder inpatients in acute manic,mixed, or depressive relapse

Background

The aim of this study was to assess whether different affective temperaments could be related to a specific mood disorder diagnosis and/or to different therapeutic choices in inpatients admitted for an acute relapse of their primary mood disorder.

Method

Hundred and twenty-nine inpatients were consecutively assessed by means of the Structured and Clinical Interview for axis-I disorders/Patient edition and by the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego auto-questionnaire, Young Mania Rating Scale, Hamilton Scale for Depression and for Anxiety, Brief Psychiatry Rating Scale, Clinical Global impression, Drug Attitude Inventory, Barratt Impulsiveness Scale, Toronto Alexithymia Scale, and Symptoms Checklist-90 items version, along with records of clinical and demographic data.

Results

The following prevalence rates for axis-I mood diagnoses were detected: bipolar disorder type I (BD-I, 28%), type II (31%), type not otherwise specified (BD-NOS, 33%), major depressive disorder (4%), and schizoaffective disorder (4%). Mean scores on the hyperthymic temperament scale were significantly higher in BD-I and BD-NOS, and in mixed and manic acute states. Hyperthymic temperament was significantly more frequent in BD-I and BD-NOS patients, whereas depressive temperament in BD-II ones. Hyperthymic and irritable temperaments were found more frequently in mixed episodes, while patients with depressive and mixed episodes more frequently exhibited anxious and depressive temperaments. Affective temperaments were associated with specific symptom and psychopathology clusters, with an orthogonal subdivision between hyperthymic temperament and anxious/cyclothymic/depressive/irritable temperaments. Therapeutic choices were often poorly differentiated among temperaments and mood states.

Limits

Cross-sectional design; sample size.

Conclusions

Although replication studies are needed, current results suggest that temperament-specific clusters of symptoms severity and psychopathology domains could be described.     

Risks associated with gender differences in bipolar I disorder

Background

Previous studies have demonstrated that bipolar patients may differ in several features according to gender, but a number of the differences found remain controversial.

Methods

The demographic, illness course, clinical, comorbidity and temperament characteristics of a total of 1090 consecutive DSM-IV bipolar I manic inpatients were compared according to gender.

Results

Bipolar illness in women was characterised by the predominance of depression, as indicated by a depressive polarity at onset, higher rates of mixed mania, more suicidal behaviour, and a greater number of temperaments with depressive propensities. In contrast, the manic component was found to predominate in men. Men also had an earlier onset of their illness. Women displayed more comorbidities with eating, anxiety, and endocrine/metabolic disorders, whereas men were more comorbid with alcoholism and other forms of substance abuse, neurological, and cancer disorders. The following independent variables were associated with male gender: being single (+), depressive temperament (−), excessive alcohol use (+), cyclothymic temperament (−), excessive other substance use (+), mood congruent psychotic features (+), and manic polarity at onset (+).

Limitations

The retrospective design and the sample being potentially not representative of the bipolar disorder population are limitations.

Conclusions

Findings from this study tend to confirm most of the differences previously observed among bipolar men and women. Furthermore, these results draw attention to the risks that may be specifically linked to gender differences in bipolar I patients.