Clinical importance of inter-episode symptoms in patients with bipolar affective disorder

A literature review was performed to determine whether inter-episode symptoms are of clinical importance in the management of bipolar disorder. Inter-episode symptoms are easy to miss but observational studies confirm that they are related to impaired function and reduced survival to full relapse. Randomised, controlled trials with lithium carbonate, and two studies exploring psychological treatments to recognise and treat prodromal symptoms of manic or depressive relapse, suggest some inter-episode symptoms are worth recognising because they are associated with reduced manic relapse and improved function. A classification is proposed to inform attempts at management of inter-episode symptoms in bipolar disorder patients, both clinically, and for future research. However, promotion of well-being in bipolar disorder patients does not require all symptoms to be treated. In other patients, the presence of inter-episode symptoms may be a marker of resistance to treatment. Finally, the mechanism by which inter-episode symptoms might lead to relapse, or even lead directly to functional impairment, awaits convincing explanation and empirical support.     

Obsessive-compulsive disorder in bipolar disorder patients with first manic episode

BACKGROUND: Evidence indicates that obsessive--compulsive disorder (OCD) co-occurs with schizophrenia and bipolar disorder (BD) at a higher rate than in the general population. The inflated rate of comorbidity may result from chronic illness, antipsychotic therapy or treatment-seeking behavior. To control for these factors we evaluated the prevalence of OCD in patients with first-episode acute mania who met DSM-IV criteria for BD-I, and compared them with our previously reported group of first-episode schizophrenia patients. METHOD: Fifty-six BD-I patients with a first-episode of acute mania were screened for OCD and additional comorbid disorders using the Structured Clinical Interview for DSM-IV Axis-I disorders and appropriate rating scales. RESULTS: Only one patient (1.8%) met DSM-IV criteria for OCD, and two (3.6%) met criteria for sub-threshold OCD. In contrast, there was a substantial aggregation of substance use disorders 32.1% (N=8), anxiety disorders, other than OCD 26.8% (N=15) and eating disorders 14.3% (N=8). LIMITATIONS: Small sample size, cross-sectional nature of the assessments and the inclusion of only BD-I patients. CONCLUSION: The rate of OCD in first-episode BD-I patients did not differ significantly from that found in the general population and was substantially lower than in previously reported first-episode schizophrenia patients (1.8% vs. 14%). We suggest that a preferential association of OCD with schizophrenia early in the course of illness represents a pathophysiological linkage between the two disorders, and putatively a specific schizo-obsessive subtype. In contrast, OCD in BD-I may stand for "true" comorbidity. Large-scale parallel comparative evaluations of comorbidity in BD-I and schizophrenia may contribute to the search for specific pathophysiological mechanisms of distinct comorbid-related subsets in either disorder.     

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.     

Prediction of treatment response in bipolar, manic disorder

We examined the records of 53 patients with a diagnosis of bipolar affective disorder, manic. Thirteen patients were refractory to lithium carbonate treatment. Clinical variables hypothesized to have value in predicting response including the presence of elation, grandiosity, paranoia, irritability, delusions and hallucinations did not predict treatment response.     

Clinical subtypes of severe bipolar mixed states

Objective

The aim of the present study was to identify different clinical subtypes in severe, treatment resistant bipolar mixed state (MS).

Method

The sample comprised 202 Bipolar I patients currently in MS referred for an Electro-convulsive Therapy (ECT) trial and evaluated in the first week of hospitalization and one week after the ECT course. Principal component factor analysis (PCA) followed by Varimax rotation was performed on 21 non-overlapping items selected from Hamilton rating-scale for depression (HAMD) and from Young mania rating-scale (YMRS) at baseline evaluation. Cluster subtypes derived from the factor scores were compared in clinical variables and final HAMD, YMRS, Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores.

Results

The principal-component analysis extracted 6 interpretable factors explaining 55.9% of the total variance. Cluster analysis identified four groups, including respectively 63 (31.2%) subjects with Agitated-Irritable Mixed-Depression, 59 (29.2%) with Psychotic Mixed-Mania, 17 (8.5%) with Anxious-Irritable-Psychotic Mixed-Mania, and 63 (31.2%) with Retarded-Psychotic Mixed-Depression. The four clusters were statistically distinct and did not show significant overlap in the main symptomatological presentation. Cluster subtypes reported differences in number of past mood episodes, duration of the current episode, suicide attempts, lifetime comorbidity with panic and eating disorders, baseline and final rating-scale scores and rate of remission after ECT trial.

Conclusions

Our study indicates that, at least in severe treatment resistant MS, multiple depressive and manic subtypes can be observed with substantial differences in terms of clinical presentation, course, associated comorbidities and treatment response.     

A prospective,longitudinal study of metabolic syndrome in patients with bipolar disorder and schizophrenia

Background

Although cross sectional studies have evaluated the prevalence of metabolic syndrome (MetS) in patients with bipolar patients (BPAD), data from longitudinal studies are limited.

Aim

To assess the prevalence of MetS in patients with BPAD, to observe the change in prevalence rate over a period of 6 months, to assess the prevalence of sub-threshold MetS (i.e., patients fulfilling one or two criteria of MetS) and to compare patients with BPAD and schizophrenia on the above mentioned parameters.

Methodology

Seventy five patients with BPAD and 53 patients with schizophrenia were initially evaluated for MetS and then followed up for a period of 6 months.

Results

According to consensus definition, prevalence of MetS at baseline was 40% in BPAD group and 32% in schizophrenia group. Over 6 months of follow-up the prevalence of MetS increased by 8% and 9.4% in the BPAD and the schizophrenia groups respectively. There was no significant difference between the two groups on any of the assessments. Another 28–32% of patients in the BPAD group also fulfilled two criteria and 13–17% fulfilled at least one criterion of MetS at different points of assessment. Similarly, 19–26% of the patients with schizophrenia met at least two and 23–26% of the patients fulfilled at least one criterion of MetS.

Limitation

The study was limited by small sample size, inclusion and the relatively short follow-up period.

Conclusion

40% patients with BPAD and 32% with schizophrenia have MetS and the prevalence of MetS increases by 8–9.4% over 6 months.     

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.     

Affect recognition across manic and euthymic phases of bipolar disorder in Han-Chinese patients

Patients with bipolar disorder (BD) have affect recognition deficits. Whether affect recognition deficits constitute a state or trait marker of BD has great etiopathological significance. The current study aims to explore the interrelationships between affect recognition and basic neurocognitive functions for patients with BD across different mood states, using the Diagnostic Analysis of Non-Verbal Accuracy-2, Taiwanese version (DANVA-2-TW) as the index measure for affect recognition. To our knowledge, this is the first study examining affect recognition deficits of BPD across mood states in the Han Chinese population.     

Serum neurotrophin-3 is increased during manic and depressive episodes in bipolar disorder

Accumulating evidence suggest that neural changes and cognitive impairment may accompany the course of bipolar disorder. Such detrimental effects of cumulative mood episodes may be related to changes in neurotrophins that take place during mood episodes but not during euthymic phases. The present study investigated serum neurotrophin-3 (NT-3) levels in patients with bipolar disorder during manic, depressed, and euthymic states, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum NT-3 levels were increased in manic (p<0.001) and depressed (p<0.001) BD patients, as compared with euthymic patients and normal controls. These findings suggest that the NT-3 signaling system may play a role in the pathophysiology of BD.     

Neuropsychological impairment among manic, depressed, and mixed-episode inpatients with bipolar disorder

Previous research has demonstrated broad neurobehavioral abnormalities in bipolar affective disorder (cf. G. Cassens, L. Wolfe, & M. Zola, 1990). However, there have been no comparisons of neuropsychological function across patients with manic, depressed, or mixed subtypes. In the present study, 37 manic, 24 mixed-episode, and 25 depressed bipolar I inpatients and 34 control subjects were administered a brief battery of neuropsychological tests. The multivariate and univariate effects of participant group on the neuropsychological measures were uniformly significant (p < .05). Planned contrasts revealed that the bipolar participants performed worse than the controls, and few differences existed between the 3 patient groups. Additionally, the bipolar groups were impaired on 50% of the test battery. These abnormalities were unlikely attributable to differences in psychiatric symptomatology, medical illness, comorbid psychiatric diagnoses, or medication status. Findings imply that acute mood disturbance during bipolar disorder yields significant neurobehavioral dysfunction.     

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.     

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.     

A narrative review of cross-sectional and prospective associations between self-schemas and bipolar disorder

The role of self-concept in bipolar disorder (BD) has not been well understood. The present review utilizes the notion of self-schema and interrogates existing research concerning evidence for cross-sectional and prospective associations between four schema-like constructs (i.e. trait self-esteem, dysfunctional beliefs concerning contingent self-worth, early maladaptive schemas and implicit self-esteem) and various facets of BD. Existing findings demonstrate various types of involvement of self-schemas in BD. Of particular clinical relevance, the present review suggests that low trait self-esteem and dysfunctional beliefs concerning contingent self-worth are risk factors for ongoing BD symptoms and mood episodes. The present review also yields important yet unaddressed questions with respect to the evaluative content of self-schemas associated with the hypo/manic phase of BD.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.