Syndromes and phenomenological subtypes underlying acute mania: a factor analytic study of 576 manic patients

OBJECTIVE: There are no factor analytic studies specifically including symptoms representative of depressive inhibition among manic patients, although Kraepelin described several mixed affective states with depressive inhibition. There is controversy as to whether atypical manic features such as aggression, psychosis, and depression are likely to coexist among manic patients. The authors' goal was to examine this controversy. METHOD: They used a standardized instrument to assess the presence or absence of 37 psychiatric symptoms in 576 consecutive inpatients who were diagnosed as having DSM-IV manic episode, nonmixed or mixed. RESULTS: A principal-component analysis followed by varimax rotation extracted seven independent interpretable factors (depressive mood, irritable aggression, insomnia, depressive inhibition, pure manic symptoms, emotional lability/agitation, and psychosis) that were relatively stable across several patient groups. A subsequent cluster analysis identified four phenomenological subtypes underlying acute mania: pure, aggressive, psychotic, and depressive (mixed) mania. Several variables, including gender, suicidality, and outcome of treatments, significantly differentiated the subtypes. CONCLUSIONS: In patients with mania, depressive inhibition may be a salient syndrome independent of depressive mood, lending some support to Kraepelin's classification of mixed manic states on the basis of the permutations of three elements-thought disorder, mood, and psychomotor activity. Depressive inhibition, together with depressive mood and emotional lability/agitation, appears to be an important phenomenological element of mixed states. Atypical manic features such as aggression, psychosis, and depression are not likely to coexist, but they are likely separately to characterize several different subtypes potentially underlying acute mania.     

Leukocytosis and hypoalbuminemia in mixed bipolar states: evidence for immune activation

OBJECTIVE: Although activation of an immune response during major depressive episodes has been reported, less is known about changes during manic and mixed bipolar episodes. METHOD: Albumin and leukocyte levels were compared between subjects in manic and mixed bipolar episodes. Neutrophil, lymphocyte and monocyte levels were compared between the two groups. RESULTS: Albumin levels were lower in mixed manic subjects as opposed to pure manic subjects and in the combined groups levels were lower in females than in males. Leukocyte levels were higher in mixed manic patients compare with pure manic patients. Both neutrophil and monocyte levels were higher in the mixed manic patients but lymphocyte levels were no different. CONCLUSION: Leukocytosis and hypoalbuminemia during mixed manic states suggest immune activation in mixed mania similar to depression. This finding also tends to support the recognition of mixed mania as a distinct bipolar state.     

Qualitative differences in manic symptoms during mixed versus pure mania

Previous studies have compared demographic and clinical-outcome features of bipolar patients with mixed or pure mania. However, little is known about the potential differences in the nature and extent of manic symptoms in mania either with or without an accompanying depression. This study examined DSM-III-R manic symptoms in a cohort of 183 bipolar I inpatients hospitalized for mixed mania (diagnosed by broad or narrow criteria) or pure manic episodes. Inpatient charts were reviewed to determine the presence of individual affective symptoms. The results indicate that clinicians were more likely to diagnose a pure mania from the beginning to end of an episode than to diagnose a mixed mania from its beginning to end. Mixed-manic patients had significantly fewer manic symptoms than pure manic patients. Grandiosity, euphoria, pressured speech, and a decreased need for sleep were more prevalent during pure versus mixed mania. Grandiosity and a diminished need for sleep were especially notable during pure mania compared with mixed mania as defined by narrow criteria for mixed states. The observed differences in manic symptom profiles between mixed and pure mania may aid in the clinical assessment of dysphoric states among bipolar patients. The data also lend support to the use of broad diagnostic criteria for defining mixed mania as an entity phenomenologically distinct from pure mania.     

Mood patterns and classification in bipolar disorder

PURPOSE OF REVIEW: The aim of this review is to highlight recent studies that have questioned the current split of mood disorders into the categories of bipolar and depressive disorders. RECENT FINDINGS: A continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder was supported by several lines of evidence: depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support the splitting between mania/hypomania and depression); family history, major depressive disorder is the most common mood disorder in relatives of bipolar probands; lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; bipolar features in major depressive disorder; major depressive disorder shifting to bipolar disorders; history of manic/hypomanic symptoms in major depressive disorder and correlation between lifetime manic/hypomanic symptoms and depressive symptoms in major depressive disorder; factors of hypomania inside major depressive disorder; recurrent course of major depressive disorder; depression more common than mania and hypomania in bipolar disorders; trait mood lability in major depressive disorder. SUMMARY: This review of the recent findings on the relationship between bipolar disorders (especially bipolar II disorder) and depressive disorders seems to support a continuity among mood disorders, and runs against the current classification of mood disorders dividing them into independent categories. Further research is needed in the area, in part because of its possible treatment impact.     

A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states

Cerullo MA, Fleck DE, Eliassen JC, Smith MS, DelBello MP, Adler CM, Strakowski SM. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 2012: 14: 175–184. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally. Methods: fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole‐brain functional connectivity analysis was performed using the left and right amygdala as seed regions. Results: Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group. Conclusions: In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical–amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.     

A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders

Background:  There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years.
Method:  Detailed life-charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow-up was examined.
Results:  Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups.
Conclusions:  Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.     

Depressive and manic symptoms are not opposite poles in bipolar disorder

Johnson SL, Morriss R, Scott J, Paykel E, Kinderman P, Kolamunnage‐Dona R, Bentall RP. Depressive and manic symptoms are not opposite poles in bipolar disorder. Objective: This study of 236 individuals with bipolar disorders employed longitudinal analyses to determine whether the symptoms of mania and depression can be understood as one dimension (with depression and mania as opposites) or two relatively independent dimensions. Method: Weekly severity ratings of manic and depression were assessed using the Longitudinal Interval Follow‐up Evaluation‐II for 72 weeks. The within‐subjects correlation of manic and depressive severity was examined using random effects regression. Results: Contrary to the one‐dimension model, mania and depression symptoms were not negatively related. Indeed, the correlations of mania with depressive symptoms were quite small. Conclusion: The data suggest that depressive and manic symptoms are not opposite poles. Rather depressive and manic symptoms appear to fluctuate relatively independently within bipolar disorder.     

Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by > or = 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.     

Phenomenology of mixed states: a principal component analysis study

OBJECTIVES: To contribute to the definition of external and internal limits of mixed states and study the place of dysphoric symptoms in the psychopathology of mixed states. METHODS: One hundred and sixty-five inpatients with major mood episodes were diagnosed as presenting with either pure depression, mixed depression (depression plus at least three manic symptoms), full mixed state (full depression and full mania), mixed mania (mania plus at least three depressive symptoms) or pure mania, using an adapted version of the Mini International Neuropsychiatric Interview (DSM-IV version). They were evaluated using a 33-item inventory of depressive, manic and mixed affective signs and symptoms. RESULTS: Principal component analysis without rotation yielded three components that together explained 43.6% of the variance. The first component (24.3% of the variance) contrasted typical depressive symptoms with typical euphoric, manic symptoms. The second component, labeled 'dysphoria', (13.8%) had strong positive loadings for irritability, distressing sensitivity to light and noise, impulsivity and inner tension. The third component (5.5%) included symptoms of insomnia. Median scores for the first component significantly decreased from the pure depression group to the pure mania group. For the dysphoria component, scores were highest among patients with full mixed states and decreased towards both patients with pure depression and those with pure mania. CONCLUSIONS: Principal component analysis revealed that dysphoria represents an important dimension of mixed states.     

Discriminating primary clinical states in bipolar disorder with a comprehensive symptom scale

Objective: We assessed the spectrum and severity of bipolar symptoms that differentiated bipolar disorder (BD) clinical states, employing the Bipolar Inventory of Symptoms Scale (BISS) which provides a broader item range of traditional depression and mania rating scales. We addressed symptoms differentiating mixed states from depression or mania/hypomania. Method: One hundred and sixteen subjects who met DSM‐IV‐TR criteria for BD and were currently in a depressed, manic/hypomanic, mixed episode, or recovered state were interviewed using the BISS. Results: A subset of manic items differed between mixed episodes and mania/hypomania or depression. Most anxiety items were more severe in mixed subjects. BISS Depression and Manic subscales differentiated episodes from recovered status. The majority of depression and manic symptoms differentiated mood states in the predicted direction. Mixed episodes had overall greater mood severity than manic/hypomanic episodes or depressed episodes. Conclusion: These results indicate that a small subset of symptoms, several of which are absent in DSM‐IV‐TR criteria and traditional rating scales for bipolar studies, aid in distinguishing mixed episodes from depressive or manic/hypomanic episodes. The results also support the utility of a comprehensive BD symptom scale in distinguishing primary clinical states of BD.     

'Bipolar missed states': the diagnosis and clinical salience of bipolar mixed states

OBJECTIVE: To explore diagnostic and treatment issues concerning bipolar mixed states. METHOD: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed. RESULT: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression. CONCLUSIONS: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression. Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications. Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.     

Development and validation of the Affective Self Rating Scale for manic, depressive, and mixed affective states

Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery-Asberg Depression Rating Scale (MADRS), Hypomania Interview Guide-Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states.     

Diagnostic dilemmas and clinical correlates of mixed states in bipolar disorder

Patients with bipolar disorder frequently have varying degrees of mixed states rather than pure episodic manic and depressive episodes. However, DSM-IV-TR and ICD-10 criteria do not fully account for patients' varying presentations; currently, there is no consensus on whether mixed states is a distinct, categorically different type of mania or whether it is a transitional state between depression and mania. Inconsistent diagnostic criteria can be problematic for clinicians when treating patients.     

Development and validation of the Affective Self Rating Scale for manic,depressive, and mixed affective states

Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery–Åsberg Depression Rating Scale (MADRS), Hypomania Interview Guide—Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states.     

Mania: sympathoadrenal function and clinical state

We investigated sympathoadrenal and sympathetic nervous system activity, catecholamine disposition, and clinical state in 19 hospitalized manic patients. Severity of the core manic syndrome, anxiety, and hostility correlated with 24-hour urinary excretion of epinephrine relative to its metabolites, but only weakly with norepinephrine. Agitation, however, correlated most strongly and significantly with norepinephrine. Eight of the patients had mixed states: concurrent manic and depressive syndromes. There were no differences between mixed and pure manic patients with respect to catecholamine or metabolite excretion or precursor/product ratios, but mixed manic patients tended to have higher excretion of norepinephrine and had increased variance with respect to catecholamine measures. These data suggest that the function of the adrenal medulla, whether directly or indirectly, is important in the symptoms of both mixed and pure mania.     

Hypocholesterolemia during mixed manic episodes

Background An association of relatively low serum cholesterol with both depression and suicide has been reported. Depressive symptoms, including suicidality, are defining features of mixed mania. Few studies have considered differences in cholesterol levels in subjects during mixed bipolar episodes. Methods Fasting serum cholesterol levels obtained from 174 subjects evaluated during mixed and pure manic episodes were compared using ANOVA statistics. Sex was included in the analysis and age was used as a covariate. Cholesterol levels in the total manic cohort and in the mixed and pure manic subgroups were compared with national norms. Results Fasting serum cholesterol levels were lower in the mixed manic subtype compared to the pure manic subtype. As expected, cholesterol levels increased with age. No differences were noted between males and females. Cholesterol levels were lower in both the mixed and pure manic subtypes when compared with national norms. Conclusion Fasting serum cholesterol levels are low in manic patients, especially during mixed bipolar episodes. Cholesterol, which has been reported to be a negative acute phase reactant, may be lower during mixed states as a result of an immune activation. Received: 18 July 2001 / Accepted: 22 April 2002     

Emotional hyper-reactivity as a fundamental mood characteristic of manic and mixed states.

BACKGROUND: The relationship between depression and mania remains poorly understood and is responsible for much of the confusion about mixed states. The difficulty in conceptualizing opposite states such as euphoric and depressive moods during the same episode may account for the considerable differences in reported frequencies of mixed states, among acutely manic patients. It is possible that the fundamental mood characteristic of mania is not tonality of mood (e.g. euphoric, irritable or depressed mood), but rather the intensity of emotions. METHOD: We interviewed 30 patients hospitalized for a manic episode, asking about their symptoms during the episode, using the list of symptoms for manic and depressive episode of the DSM-IV criteria. Emotional hyper-reactivity, defined as an increase in the intensity of all emotions, was assessed using the Hardy Scale. Manic symptoms were also assessed by a clinician using the Beck-Rafaelsen Mania Scale. RESULTS: This study showed that most of the manic episodes presented many dysphoric symptoms, more particularly depressive mood (33%), irritability (53%), anxiety (76%), and recurrent thoughts of death or suicidal ideation (33%). However, only 10% of our sample met the criteria for mixed state. The other symptoms reported by patients and included in the DSM-IV criteria for depressive mood are common between depressive and manic episodes. All patients (100%) reported that they felt all their emotions with an unusual intensity. CONCLUSION: We suggest that the most appropriate way to define mood in manic states is as a function of intensity, and not as a function of tonality. This definition circumvents the arbitrary dichotomy between mania and mixed state. With this definition, manic episodes can be described as being more or less dysphoric, with the actual characteristics of dysphoria encompassing irritability, anxiety, or depressive affect. This point could be extremely helpful in discriminating mixed state or dysphoric mania from depression.     

Anticonvulsants in bipolar disorder.

In recent years, a number of anticonvulsants have been more rigorously investigated for their potential mood-stabilizing properties. They are heterogeneous in their mechanisms of action and in their efficacy in the various mood states in bipolar illness (Table 3). At present, evidence from well-controlled studies supports the role of DIV and CBZ in the treatment of acute mania. DIV seems to have better efficacy than lithium in mixed mania or mania associated with depressive symptoms and is recommended as a first-line pharmacologic option in acutely manic or mixed manic patients. Neither CBZ nor DIV have robust evidence supporting their efficacy in the treatment of acute bipolar depression, although DIV clearly possesses beneficial effects on depressive symptomatology and prophylaxis against depressive episodes during long-term treatment. Results from a large study indicate that LAM has significant efficacy in bipolar depression without the associated risks of cycle acceleration or manic/hypomanic switches. LAM should be considered a primary option in patients with bipolar depression and in bipolar II patients with rapid cycling. DIV is recommended as a first-line option in bipolar I patients with rapid cycling. LAM has proven efficacy in the prophylaxis of bipolar I disorder and should be considered along with lithium or DIV as treatment of choice in the long-term management of bipolar disorder. For the other anticonvulsants, including CBZ and OXC, there is still inadequate evidence of efficacy as monotherapy in the long-term management of bipolar disorder. Even less data exist for other available AEDs, and consensus is growing that someAEDs (eg, GBP) have little or no specific effect in bipolar disorder. Despite the progress made in the past decade, a wider therapeutic armamentarium is critically needed, because a large proportion of bipolar patients do not respond to acute treatments during a manic or depressive episode and have frequent relapse and recurrences during long-term treatment. As additional AEDs become available, rigorously designed and large-scale studies examining AEDs as monotherapy and AEDs in combination therapies versus placebo must be undertaken to assess efficacy and safety more adequately to provide better guidance for the clinician faced with the management of this challenging mood disorder.     

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS: Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS: Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS: Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.     

Symptom profile consistency in recurrent manic episodes

Few studies have addressed whether symptom profiles remain consistent between episodes of mania. Those that have done so focused on mood only and adopted the strictly categorical approach. We evaluated 77 subjects during two discrete manic episodes (mean interval, 2 years, 2 weeks). Episodes were characterized on five established symptom factors of mania and on overall severity of classic manic symptoms (i.e., excluding dysphoric symptoms). Pearson correlation coefficients were computed to compare symptom profiles across episodes. Four symptom factors (dysphoria, hedonic activation, psychosis, and irritable aggression) were significantly correlated across episodes, as was manic severity. Psychomotor symptoms were not significantly correlated. Manic symptomatology remains generally similar in bipolar subjects during different episodes. The characterization of manic episodes by the empirical dimensions of symptom factors, as suggested by Kraepelin nearly a century ago, may provide additional information for biological and treatment response studies of manic states that is not captured by categorical subtype diagnosis focused solely on mood symptoms (i.e., mixed v pure manic episodes).