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.     

Temperament and personality in bipolar I patients with and without mixed episodes

BACKGROUND: Personality and temperament are supposed to have an impact on the clinical expression and course of an affective disorder. There is some indication, that mixed episodes result from an admixture of inverse temperamental factors to a manic syndrome. In a preliminary report [Brieger, P., Roettig, S., Ehrt, U., Wenzel, A., Bloink, R., Marneros, A., 2003. TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits. J. Affect. Disord. 73, 99-104] we reported support for this assumption. The present study completes the preliminary results and compares patients with and without mixed episodes with respect to personality and personality disorders in addition. METHODS: Patients who had been hospitalized for bipolar I disorder were reassessed after 4.8 years. We examined temperament (TEMPS-A), personality (NEO-FFI) and frequency of personality disorders (SCID-II). Furthermore, illness-related parameters like age at first treatment, depressive and manic symptomatology, frequency and type of episodes and level of functioning were obtained and patients with and without mixed episodes were compared. RESULTS: Patients with (n=49) and without mixed episodes (n=86) did not differ significantly with regard to the illness-related parameters and personality dimensions. The frequency of personality disorders was significantly higher in patients with prior mixed episodes. With respect to temperament, scores of the depressive, cyclothymic, irritable and anxious temperament were significantly higher in patients with mixed episodes. LIMITATIONS: We were not able to assess premorbid temperament and premorbid personality. CONCLUSIONS: The findings of the present study support the assumption of Akiskal [Akiskal, H.S., 1992b. The distinctive mixed states of bipolar I, II, and III. Clin. Neuropharmacol. 15 Suppl 1 Pt A, 632-633.] that mixed episodes are more frequent in subjects with inverse temperament.     

Dysthymic and anxiety-related personality traits in bipolar spectrum illness

Anxious and dysthymic personality traits were measured in a euthymic, familial sample of bipolar (BPD) individuals and their affectively ill and unaffected relatives. According to the quantitative genetic model of bipolar spectrum illness [Evans, L., Akiskal, H.S., Keck, Jr., P.E., McElroy, S.L., Sadovnick, A.D., Remick, R.A., Kelsoe, J.R., 2005. Familiality of temperament in bipolar disorder: support for a genetic spectrum. J. Affect. Disord. 85, 153-168], these traits should be normally distributed with the bipolar disorder I (BPD I) group showing the highest and the unaffected relatives the least "pathological" scores. Three hundred individuals from 47 bipolar disorder families were administered a battery of personality questionnaires (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego; Temperament and Character Inventory; Affective Neuroscience Personality Scale) as well as a self-rating depression (Beck Depression Inventory) and mania (Altman Self-Rating Mania) scale. Out of the 300 participants, 58 were diagnosed with BPD I, 27 with bipolar disorder II (BPD II), 58 with recurrent major depression (MDE-R), 45 had one previous depressive episode (MDE-S), and 88 were unaffected. The BPD I group scored significantly higher than their unaffected relatives on the Harm Avoidance and Sadness scales of the TCI and ANPS, respectively, while the MDE-R but not the BPD samples scored significantly higher than unaffected relatives on the Anxious Temperament (AT) subscale of the TEMPS-A. In general, the mean dysthymic personality scores were highest in the BPD sample, followed by the MDE-R, MDE-S, and unaffected relative groups. Nevertheless, no significant personality differences were found between the psychiatrically-ill groups. While dysthymic temperament traits conform relatively well to the quantitative genetic model of affective illness, anxious traits as defined by the AT scale, are equally salient in BPD and unipolar depression.     

Familial rates of affective and substance use disorders in patients with first-episode mania

BACKGROUND: One explanation for the high co-occurrence between bipolar and substance use disorders is that substance abuse may precipitate affective symptoms in patients who otherwise may have not had the genetic risk for developing an affective illness. Previous studies comparing familial rates of affective illness between bipolar patients with and without alcohol use have provided conflicting results. We hypothesized that patients with bipolar disorder and antecedent alcohol abuse would have lower familial rates of affective illness than bipolar patients without antecedent alcohol abuse. METHODS: Family history data were obtained on 275 first-degree relatives of 51 patients hospitalized for a first manic episode using the Family History Research Diagnostic Criteria. RESULTS: Patients with bipolar disorder and antecedent alcohol abuse had lower familial rates of affective illness than patients with bipolar disorder without antecedent alcohol abuse (two-tailed Fisher's exact, P = 0.003). There was no statistically significant difference in the familial rates of affective illness between bipolar patients with and without antecedent drug abuse (other than alcohol). Patients with bipolar disorder and antecedent alcohol abuse had a significantly older age of onset of affective illness (27.6 years) than patients with bipolar disorder without antecedent alcohol abuse (20.6 years, z = 3.3, df = 1, P = 0.0009). There was no statistical difference in age of onset of affective illness between the patients with antecedent drug abuse and the patients without antecedent drug abuse. LIMITATIONS: Future studies with a larger number of bipolar patients, direct structured interviews of family members and better differentiation between substance abuse and dependence syndromes are needed to extend and replicate this pilot study. CONCLUSIONS: Our study suggests that there may be a subset of bipolar patients who have antecedent alcohol abuse and a subset who develop alcohol abuse after the onset of bipolar disorder. We further speculate that alcohol abuse may precipitate mania in some patients with bipolar disorder.     

Do puerperal psychotic episodes identify a more familial subtype of bipolar disorder? Results of a family history study

Bipolar women have a marked vulnerability to puerperal psychosis, an episode of mania or psychosis following childbirth. We have conducted a family history study to examine the question of whether a vulnerability to puerperal episodes of illness is a marker for a more familial form of bipolar disorder. A consecutive series of 103 bipolar disorder probands were recruited in a lithium clinic and given a semi-structured interview, including a detailed family history. For the 52 female probands, information was also obtained about the relationship of episodes to childbirth. The morbid risk of affective disorder in first-degree relatives of bipolar women who had suffered an episode of mania, hypomania or schizoaffective mania with onset within 6 weeks of childbirth was significantly higher than that in relatives of parous bipolar women with no episodes in relation to childbirth (P = 0.0077). Despite relatively small numbers, this study provides evidence to support the hypothesis that puerperal episodes identify a more familial subtype of bipolar 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.     

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.     

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.     

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 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.     

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.     

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 ≥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.     

Adult attachment in bipolar 1 disorder

Objectives. To determine how security of adult attachment style is related to the mania, major depression and euthymic mood states in bipolar 1 (BP1) disorder. Design. An observational cross‐sectional study. Method. One hundred and seven BP1 patients (34 in a manic type episode, 30 in major depressive episode, and 43 in remission) and 41 healthy controls similar in age, gender, reading age, and education were recruited. The groups were compared on self‐reported mean and preferred attachment style controlling for psychiatric comorbidity. Results. Preferred attachment style was insecure in 84 (78%) BP1 patients but only 13 (32%) healthy controls (χ²=34.3, df=3, and p<.001). Healthy controls reported higher secure attachment, lower anxious, and lower preoccupied attachment scores than all groups of patients with bipolar disorder, although the scores for secure attachment in mania and preoccupied attachment in euthymic patients were not significantly different from healthy controls. Overall, within the bipolar groups, anxious attachment style varied little with mood but mania was associated with higher secure and preoccupied attachment style, and depression with higher preoccupied and lower dismissing attachment style scores. Conclusions. Insecure attachment is found in most patients with BP1 disorder. Attachment style is affected by mood episodes so it should be assessed when a patient with bipolar disorder is in remission with minimal residual depressive or manic symptoms.     

Reliability and validity of TEMPS-A in a Japanese non-clinical population: application to unipolar and bipolar depressives

BACKGROUND: In Japan, TEMPS-A has gathered much attention, because Kraepelin's concepts on "fundamental states" of mood disorder and temperaments have been widely respected. METHOD: TEMPS-A was translated into Japanese (and after the approval of the English back translation by H.S.A.), it was administered to 1391 non-clinical subjects, and 29 unipolar and 30 bipolar patients in remission. Of the non-clinical sample, 426 were readministered the instrument again in 1 month. A control group matched for gender and age was drawn from the non-clinical sample. RESULTS: Regarding test-retest reliability, Spearman's coefficients for depressive, cyclothymic, hyperthymic, irritable and anxious temperaments were 0.79, 0.84, 0.87, 0.81 and 0.87, respectively; regarding internal consistency, Cronbach's alpha coefficients were 0.69, 0.84, 0.79, 0.83 and 0.87, respectively. The unipolar and bipolar groups showed significantly higher depressive, cyclothymic and anxious temperament scores than the control group. Curiously, the bipolar group showed significantly lower hyperthymic score than the control group; irritable temperament scores showed no significant differences. Depressive, cyclothymic, irritable and anxious temperament scores showed significant correlations with each other. Between the unipolar and bipolar groups, there was little difference regarding the temperament scores. Also the inter-temperament correlations showed the same pattern in the unipolar and bipolar groups. LIMITATION: The clinically well cohort was 70% male. CONCLUSION: TEMPS-A showed a high reliability and validity (internal consistency) in a Japanese non-clinical sample. By and large, the hypothesized five temperament structure was upheld. Depressive, cyclothymic and anxious temperaments showed concurrent validity with mood disorder. Irritable temperament may represent a subtype of depressive, cyclothymic or anxious temperaments. There may be a temperamental commonality between unipolar and bipolar disorders. TEMPS-A will open new possibilities for international research on mood disorder and personality traits.     

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.     

Does latitude as a zeitgeber affect the course of bipolar affective disorder?

Background

Bipolar disorder (BD) is characterized by recurrent episodes of mood dysregulations and depression is considered as the most frequent form of relapse. However, there is some evidence that in tropical countries, the course might be different with fewer depressive episodes. This study aims to examine the frequency of depressive and manic episodes in a sample of subjects with BD from India.

Methods

Index subjects and a reliable informant (a family member) were interviewed with Diagnostic Interview for Genetic studies and a life chart was drawn to ascertain the episodes of illness in addition to reviewing their clinical case records. The mean total episode frequency and the mean manic and depressive episode frequency were estimated for this study.

Results

Data on the total episode number and number of manic and depressive episodes separately was available in 439 subjects. The subjects had been ill for 7.45 years, had experienced an average of 3.29 episodes of mania and 1.08 episodes of depression. Thus episodes of mania were seen to be more frequent.

Conclusion

It has been increasingly recognized that circadian rhythm abnormalities could play an important role in the relapse and symptom expression of bipolar disorder. The mania predominance in the course of BD in this population contrasts from the depressive predominance in other studies. We suggest that this phenomenon could be a function of latitudinal gradient in the expression of BD using the zeitgeber hypothesis.     

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.     

Clinical variables related to antidepressant-induced mania in bipolar disorder

BACKGROUND: The development of mania or hypomania during antidepressant treatment is a serious complication of the clinical management of bipolar disorder (BP). The primary aim of this study was to evaluate the clinical variables related to antidepressant-induced mania or hypomania (AIM) in patients with BP. METHODS: DSM-IV BP-I or BP-II patients who had had at least one depressive episode treated with antidepressants were considered. Patients were subdivided into two groups according to the presence (n = 30) or absence (n = 106) of manic or hypomanic episodes occurring during antidepressant treatment. Possible predictive clinical variables of AIM were considered: gender, diagnostic subtype, age at onset, duration of illness, duration of untreated illness, type of antidepressant administered, number of previous spontaneous hypomanic or manic episodes, number of previous depressive episodes, presence of lifetime suicide attempts, presence of mood stabilizer treatments, presence of psychotic symptoms during spontaneous episodes, family history for psychiatric disorders in first degree relatives. Data were compared between the two groups, with (AIM+) and without (AIM-) antidepressant-induced mania, using Student's t tests and chi-square tests. RESULTS: The lack of mood stabilizer treatments during antidepressant therapy (chi-square = 37.602, df = 1, p < 0.001) and the exposure to tricyclic antidepressants (chi-square = 4.901, df = 1, p < 0.05) resulted significantly associated to the development of AIM. LIMITATIONS: This study was not done under controlled conditions and the relatively small sample studied warrants further replications. CONCLUSIONS: These results point out the risk of mania induction associated to the use of tricyclic antidepressants in BP patients, mainly in absence of adequate mood stabilizers.     

Affective temperaments as measured by TEMPS-A in patients with bipolar I disorder and their first-degree relatives: a controlled study

BACKGROUND: The aims of this study were to identify the dominant affective temperamental characteristics of patients with bipolar disorder (BP) and their clinically well first-degree relatives and to compare the prevalence rates of these temperaments with those in healthy control subjects. METHODS: One hundred bipolar I probands and their 219 unaffected first-degree relatives were enrolled in the study. The control group consisted of healthy subjects without any personal or family history of bipolar disorder, matched with the age and gender of the probands and first-degree relatives. To identify the dominant affective temperaments, the Turkish version of TEMPS-A scale was used. RESULTS: At least one dominant temperament was found in 26% of the proband group, in 21.9% of the relative group, and 6.0% and 10.0% of the control groups, respectively. The most noteworthy finding was that both the probands and their relatives had significantly higher frequency of hyperthymic temperament than the controls. LIMITATIONS: Temperament had not been assessed premorbidly in the probands with bipolar disorder. CONCLUSIONS: The study supports the familial, possibly genetic, basis for the hyperthymic temperament in the genesis of bipolar I dosorder. That the cyclothymic temperament was not similarly represented, may be due to the higher specificity of the cyclothymic temperament to the bipolar II sybtype (which we did not study). More research is needed on the relevance of cyclothymic and other temperaments to the genetics of bipolar disorders selected by rigorous subtyping along the clinical spectrum of bipolarity.     

Unipolar mania: a distinct disorder?

BACKGROUND: This study aimed to identify the differences between unipolar mania and classical bipolar disorder. METHODS: Patients with at least four manic episodes and at least 4 years of follow-up without any depressive episodes were classified as unipolar mania. This group was compared to other bipolar-I patients defined according to DSM-IV regarding their clinical and socio-demographic variables. RESULTS: The rate for unipolar mania as defined by the study criteria was found to be 16.3% in the whole group of bipolar-I patients. Unipolar manic patients tended to have more psychotic features and be less responsive to lithium prophylaxis compared to other bipolar-I patients. LIMITATIONS: Because it was a retrospective study, there may be some minor depressive episodes left unrecorded in the unipolar mania group despite careful and thorough investigation. In addition, even with our fairly strict criteria for the diagnosis of unipolar mania, the possibility of a future depressive episode cannot be excluded. CONCLUSIONS: Unipolar mania may be the presentation of a nosologically distinct entity.