A prospective 4-5 year follow-up of juvenile onset bipolar disorder

OBJECTIVE: Data on outcome of juvenile onset bipolar disorder is limited. This study examined the course and outcome of bipolar disorder and assessed the rate and predictors of recovery and relapse in a sample of children and adolescents over a 4-5 year period. METHOD: Twenty-five consecutively ascertained subjects (9-16 years) with a diagnosis of mania (mean duration at intake of 4.6 +/- 3.9 weeks), were comprehensively assessed at baseline and at 6-month intervals using the Diagnostic Interview for Children and Adolescents (revised) (DICA-R), the Missouri Assessment for Genetic Interview in Children (MAGIC), the Young's Mania Rating Scale (YMRS) and the Children's Global Assessment (CGAS). The study phenotype required DSM-IV criteria of mania with elation and/or grandiosity as a criterion to distinguish them from those with attention deficit hyperactivity disorder. Subjects received the standard treatment as prescribed by their primary treating team. RESULTS: During the course of the study period, all 25 subjects (100%) recovered from the index episode. The mean time to recovery was 44 +/- 46 days. The mean duration of follow-up was 51.6 +/- 4.1 months. Sixteen subjects (64%) relapsed after a mean period of 18 +/- 16.4 months. A majority of the relapses (72.4%) were while the subjects were on treatment. CONCLUSIONS: Acute juvenile onset mania has a high rate of recovery and low chronicity. The relapse rate was high and most of these occurred in the first 3 years despite aggressive prophylactic treatment. The effectiveness of currently used thymoleptics, in particular lithium, in the prophylaxis of juvenile bipolar disorder needs to be evaluated in controlled studies.     

Four-year prospective outcome and natural history of mania in children with a prepubertal and early adolescent bipolar disorder phenotype

BACKGROUND: Diagnosis of child mania has been contentious. OBJECTIVE: To investigate natural history and prospective validation of the existence and long-episode duration of mania in children. DESIGN: Four-year prospective longitudinal study of 86 subjects with intake episode mania who were all assessed at 6, 12, 18, 24, 36, and 48 months. The phenotype was defined as DSM-IV bipolar I disorder (manic or mixed) with at least 1 cardinal symptom (elation and/or grandiosity) to ensure differentiation from attention-deficit/hyperactivity disorder. Parent and child informants were separately interviewed, by highly experienced research nurses, using the Washington University in St Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS). A Children's Global Assessment Scale score of 60 or less was needed to establish definite impairment. Treatment was by subjects' community practitioners. SETTING: Research unit in a university medical school. PARTICIPANTS: Subjects were obtained from psychiatric and pediatric sites by consecutive new case ascertainment, and their baseline age was 10.8 +/- 2.7 years. Onset of the baseline episode was 7.4 +/- 3.5 years. (Data are given as mean +/- SD.) MAIN OUTCOME MEASURES: Episode duration, weeks ill, recovery/relapse rates, and outcome predictors. RESULTS: Prospective episode duration of manic diagnoses, using onset of mania as baseline date, was 79.2 +/- 66.7 consecutive weeks. Any bipolar disorder diagnosis occurred during 67.1% +/- 28.5% of total weeks, during the 209.4 +/- 3.3 weeks of follow-up. Subjects spent 56.9% +/- 28.8% of total weeks with mania or hypomania (unipolar or mixed), and 38.7% +/- 28.8% of these were with mania. Major or minor depression and dysthymia (unipolar or mixed) occurred during 47.1% +/- 30.4% of total weeks. Polarity switches occurred 1.1 +/- 0.7 times per year. Low maternal warmth predicted faster relapse after recovery from mania (chi(2) = 13.6, P =.0002), and psychosis predicted more weeks ill with mania or hypomania (F(1,80) = 12.2, P =.0008). Pubertal status and sex were not predictive. (Data are given as mean +/- SD.) CONCLUSIONS: These findings validate the existence, long-episode duration, and chronicity of child mania. Differences from the natural history of adult bipolar disorder are discussed.     

The McLean-Harvard First-Episode Mania Study: prediction of recovery and first recurrence

OBJECTIVE: Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania. METHOD: Bipolar disorder patients (N=166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score /=8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed. RESULTS: By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse. CONCLUSIONS: Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors.     

A prospective study of bipolar disorder in children and adolescents from India

Bipolar disorder in adults is known to run an episodic course. However, little information exists on the long-term naturalistic course of bipolar disorder in juvenile populations. The present study was undertaken with the objectives of (i) documenting the rates of recovery and relapse, (ii) identifying the predictors of recovery and relapse and (iii) assessing the rates of comorbid conditions. A total of 30 subjects with onset of bipolar illness (according to DSM-III-R criteria) in childhood and adolescence were assessed systematically at baseline and 4 to 5 years later. All 30 subjects (100%) had recovered from their index episodes and none had exhibited chronicity. Twenty of the 30 subjects (67%) had relapsed, with most relapses occurring within 2 years of recovery from index episodes. No predictors of recovery and relapse could be identified. Conduct disorder was the only comorbid diagnosis in two subjects (7%). The main implication of our study, in view of the high rates of relapse in the crucial developmental phase of a young individual, is that long-term maintenance medication should be considered in juvenile bipolar patients, even if it is a first episode.     

Prediction of outcome in mania by mood-congruent or mood-incongruent psychotic features.

OBJECTIVE: The aim of this study was to determine the significance of mood congruence of psychotic features in mania as a predictor of outcome. METHOD: Fifty-four patients with bipolar disorder were followed prospectively for 4 years after recovery from an episode of mania with psychotic features. Assessments of residential and occupational status, interepisode symptoms, and episode recurrences were made at 6 and 48 months after recovery. Categorical outcomes were evaluated by logistic regression and recurrence risk with survival analysis. RESULTS: Mood-incongruent psychotic features during the index manic episode predicted a shorter time in remission at 4 years (hazard ratio = 2.6), and Schneiderian first-rank symptoms predicted poor residential status at 4 years (odds ratio = 20.1). CONCLUSIONS: Differentiation of mood congruence of psychotic features in mania evidently has prognostic validity and, therefore, has utility as a nosological characteristic.     

One-year recovery and relapse rates of children with a prepubertal and early adolescent bipolar disorder phenotype

OBJECTIVE: The study examined 1-year recovery and relapse rates for mania in subjects who met criteria for a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Outpatients identified by consecutive new-case ascertainment were assessed by means of separate child and parent interviews, consensus conferences, and blind best estimates. The definition of the prepubertal and early adolescent bipolar disorder phenotype was DSM-IV mania with elation and/or grandiosity as one criterion. RESULTS: Of 93 subjects seen at baseline, 89 were seen at 1 year (95.7% retention). The rate of recovery from mania was 37.1%, and the rate of relapse after recovery was 38.3%. No covariates were significantly associated with recovery or relapse. CONCLUSIONS: The low recovery and high relapse rates supported the study hypothesis of poor outcomes, which was made on the basis of similarity between the characteristics of the prepubertal and early adolescent bipolar disorder phenotype (long episode duration and high prevalence of mixed mania, psychosis, and rapid cycling) and those of severe bipolar disorder in adults.     

A randomized, placebo-controlled 12-month trial of divalproex and lithium in treatment of outpatients with bipolar I disorder. Divalproex Maintenance Study Group

BACKGROUND: Long-term outcomes are often poor in patients with bipolar disorder despite treatment; more effective treatments are needed to reduce recurrences and morbidity. This study compared the efficacy of divalproex, lithium, and placebo as prophylactic therapy. METHODS: A randomized, double-blind, parallel-group multicenter study of treatment outcomes was conducted over a 52-week maintenance period. Patients who met the recovery criteria within 3 months of the onset of an index manic episode (n = 372) were randomized to maintenance treatment with divalproex, lithium, or placebo in a 2:1:1 ratio. Psychotropic medications were discontinued before randomization, except for open-label divalproex or lithium, which were gradually tapered over the first 2 weeks of maintenance treatment. The primary outcome measure was time to recurrence of any mood episode. Secondary measures were time to a manic episode, time to a depressive episode, average change from baseline in Schedule for Affective Disorders and Schizophrenia-Change Version subscale scores for depression and mania, and Global Assessment of Function scores. RESULTS: The divalproex group did not differ significantly from the placebo group in time to any mood episode. Divalproex was superior to placebo in terms of lower rates of discontinuation for either a recurrent mood episode or depressive episode. Divalproex was superior to lithium in longer duration of successful prophylaxis in the study and less deterioration in depressive symptoms and Global Assessment Scale scores. CONCLUSIONS: The treatments did not differ significantly on time to recurrence of any mood episode during maintenance therapy. Patients treated with divalproex had better outcomes than those treated with placebo or lithium on several secondary outcome measures.     

Rates of response,euthymia and remission in two placebo-controlled olanzapine trials for bipolar mania

Objective:  Clinically meaningful recovery from acute mania may not be captured by conventionally reported response categorizations. We defined new and stringent criteria for remission in bipolar mania. Using a cohort of patients with acute mania randomized to treatment with either olanzapine or placebo, we contrasted remission rates to findings using previously reported but more lenient categorical outcome measures of response and euthymia.
Methods:  We pooled and reanalyzed results through 3 weeks from two published randomized double-blind trials of olanzapine versus placebo for treating acute bipolar mania ( 1, 2 ). Response was previously defined as ≥ 50% decrease from baseline to endpoint total Young Mania Rating Scale ( 3 ) (Y-MRS) scores, and euthymia as an endpoint total Y-MRS score of ≤ 12. In this report, remission required an endpoint total Y-MRS score of ≤ 7, and an endpoint total Hamilton Depression Rating Scale, (HAM-D21) ( 4 ) score of ≤ 7 and an endpoint Clinical Global Impression Scale – Bipolar version, CGI-BP ( 5 ), overall severity score of ≤ 2.
Results:  Olanzapine treated subjects achieved statistically significantly greater rates of clinical response, euthymia and remission than those assigned to placebo, 55% versus 29.5%, 50% versus 27%, and 18% versus 7%, respectively.
Conclusions:  Olanzapine monotherapy resulted in discernable clinical improvements in mania in over 50% of subjects and just under 20% of subjects achieved a near complete resolution of manic and accompanying depressive symptoms after 3 weeks of treatment. Full remission is an important but potentially elusive goal during short-term management of acute mania.     

Cycling into depression from a first episode of mania: a case-comparison study

OBJECTIVE: The characteristics of patients who cycle from mania to major depression and the frequencies of these cycles remain poorly understood. METHOD: This study compared 28 patients with a first episode of mania who cycled into a major depressive episode without recovery from their index episode and 148 patients with first-episode mania who did not cycle into depression. Patients were given extensive assessments at baseline and 6-, 12-, and 24-month follow-ups. Comparisons between the two groups were made on demographic variables, clinical ratings, and outcome variables. RESULTS: Approximately 16% of the patients with a first episode of mania cycled into major depression. Patients who cycled into depression were more likely to have higher depressive scores at admission and tended to have the mixed subtype of bipolar disorder. CONCLUSIONS: Patients with first-episode mania who score high for depression at admission may be at greater risk of cycling into a major depressive episode.     

Two-year prospective follow-up of children with a prepubertal and early adolescent bipolar disorder phenotype

OBJECTIVE: Longitudinal outcomes of bipolar disorder with onset in the late teenage years or in adulthood have been reported, but little is known about the natural history of childhood-onset mania. This study sought to provide rates and predictors of recovery and relapse in children with a prepubertal and early adolescent bipolar disorder phenotype. METHOD: Eighty-nine consecutively ascertained outpatient subjects (mean age=10.9 years [SD=2.7]) received comprehensive research assessments, including separate interviews of mothers about their children and of children about themselves, at baseline and at 6, 12, 18, and 24 months after baseline. The study phenotype required DSM-IV mania with elation and/or grandiosity as one criterion to distinguish the study phenotype from a diagnosis of mania based on criteria overlapping with those for attention deficit hyperactivity disorder and to ensure that subjects had at least one of the two cardinal features of mania (i.e., elation and/or grandiosity). Subjects were treated by their own community practitioners. RESULTS: The proportions of subjects who recovered from mania and who relapsed after recovery were 65.2% and 55.2%, respectively. The mean time to recovery was 36.0 weeks (SD=25.0). Relapse occurred after a mean of 28.6 weeks (SD=13.2). Living with an intact biological family significantly predicted rate of recovery, and a low level of maternal warmth significantly predicted rate of relapse. CONCLUSIONS: The relatively poor outcomes of these subjects may be related to their phenotypic resemblance to severely ill adults with bipolar disorder who have mixed mania, continuous rapid cycling, psychosis, and treatment-resistant psychopathology. A lower level of effectiveness of mood stabilizers in children cannot be ruled out. Although the significance of maternal warmth as a predictor is consistent with reports in adult mania, the significance of intact family as a predictor may be unique to childhood mania.     

Phenomenology and outcome of subjects with early- and adult-onset psychotic mania

OBJECTIVE: This study examined clinical differences between subjects with early-onset and adult-onset psychotic mania. METHOD: Subjects were from an epidemiologically derived, hospitalized sample who met criteria for definite bipolar disorder after 24 months of follow-up and whose index episode had been manic. Information collected regarding demographic characteristics, psychotic and depressive symptoms, childhood behavior problems and school functioning, substance/alcohol use disorders, and episode recurrence for two subgroups were compared: those whose illness first emerged before age 21 (early onset) (N=23) and those whose first episode occurred after age 30 (adult onset) (N=30). RESULTS: A larger proportion of the early-onset subjects were male, had childhood behavior disorders, had substance abuse comorbidity, exhibited paranoia, and experienced complete episode remission less frequently during 24-month follow-up than the adult-onset subjects. CONCLUSIONS: These data add to the body of evidence that has suggested that many subjects with early-onset psychotic mania have a more severe and developmentally complicated subtype of bipolar disorder.     

Neurocognitive test performance predicts functional recovery from acute exacerbation leading to hospitalization in bipolar disorder

OBJECTIVE: Bipolar disorder (BPD) is associated with significant functional morbidity at a rate which is particularly elevated among patients discharged from hospital. The aim of this study was to examine the degree to which neurocognitive test performance, measured following hospitalization for an acute affective episode, is predictive of functional recovery 1 year later. METHODS: Seventy-eight Zucker Hillside Hospital patients aged 18-59 years and having Structured Clinical Interview for DSM-IV diagnosis of bipolar I disorder (BPD I), bipolar II disorder (BPD II) or BPD not otherwise specified (NOS) confirmed through a rigorous diagnosis consensus procedure, underwent a comprehensive neurocognitive test battery after initial stabilization (baseline) and were followed for at least 12 months (follow-up). Hamilton Depression Rating Scale (HAM-D) and Clinician-Administered Rating Scale for Mania (CARS-M) ratings were made at baseline and follow-up. At follow-up, functionality was assessed using the Multidimensional Scale for Independent Functioning (MSIF). Logistic regression was used to examine the predictive value of each of six validated neurocognitive domains for determining functionality (MSIF) at follow-up. Baseline and follow-up HAM-D and CARS-M were entered as covariates as was number of days between baseline and follow-up. RESULTS: Attention and Ideational Fluency were significantly predictive of functional recovery 12 months later. Residual mania but not depression was associated with 12-month MSIF rating. Lithium and benzodiazepine treatment at the time of neurocognitive testing did not affect the results. CONCLUSIONS: This is the first study examining the predictive value of neurocognitive deficits, independent of residual mania or depression, for long-term functional recovery following hospitalization. Selective neurocognitive deficits are predictive of long-term functional recovery and, as such, should be candidate targets in treatment and rehabilitation programs.     

Twelve-month outcome in bipolar patients with and without personality disorders

BACKGROUND: We studied the 12-month course of illness after hospitalization for patients with a DSM-III-R diagnosis of bipolar disorder, manic or mixed episode, to identify the impact of a co-occurring personality disorder on measures of outcome. METHOD: Fifty-nine patients with bipolar disorder hospitalized for the treatment of a manic or mixed episode were recruited. Diagnostic, symptomatic, and functional evaluations were obtained at the index hospitalization. Personality disorders were assessed using the Structured Clinical Interview for DSM-III-R, personality disorders version (SCID-II). Patients were then reevaluated at 2, 6, and 12 months after discharge to assess syndromic, symptomatic, and functional recovery. Factors associated with outcome were identified using multivariate analyses. RESULTS: Survival analyses showed that in the 12-month follow-up period, subjects with bipolar disorder and co-occurring personality disorder were significantly less likely to achieve recovery. Logistic regression analyses indicated that both a diagnosis of personality disorder and noncompliance with treatment were significantly associated with lack of syndromic recovery. CONCLUSION: Co-occurring personality disorders in patients with bipolar disorder are associated with poor outcome after hospitalization for mania.     

The prognostic significance of "switching" in patients with bipolar disorder: a 10-year prospective follow-up study

OBJECTIVE: This study explored whether "switching" (i.e., the direct transition from one mood polarity to the other) has significant prognostic implications in patients with bipolar disorder. METHOD: Bipolar disorder patients (N=97) whose first prospectively observed episode included at least one mood polarity switch and 97 bipolar disorder patients whose index episode was monophasic were compared with respect to several demographic and historical variables, symptomatic features of the index episode, time to recovery from the index episode, time spent in an affective episode during a prospective observation period, and psychopathological and psychosocial outcome at a 10-year follow-up interview. RESULTS: Patients whose index episode included at least two mood polarity switches spent significantly more time in an affective episode during the observation period and had a significantly worse psychopathological and psychosocial outcome 10 years after recruitment than those whose index episode included only one mood polarity switch or was monophasic. Patients whose polyphasic index episode started with depression spent a significantly higher proportion of time in an affective episode and had a significantly worse 10-year outcome than those whose polyphasic index episode started with mania or hypomania. Retention of the switching pattern throughout the observation period was seen in 42.4% of patients whose index episode started with mania and in 65.2% of those whose index episode started with depression. CONCLUSIONS: An index episode including at least two mood polarity switches, especially if starting with depression, is associated with a poor long-term outcome in patients with bipolar disorder. This pattern represents a significant target for new pharmacological and psychosocial treatment strategies.     

Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study.

OBJECTIVE: This study assessed prospectively the pattern of recurrence of illness after recovery from an episode of major depression. METHOD: Seventy-two patients who had recovered from an episode of primary, nonbipolar, nonpsychotic major depression were evaluated bimonthly with the Comprehensive Psychopathological Rating Scale for a period ranging from 20 to 108 months (median = 66 months). New ("prospective") episodes were ascertained with a structured diagnostic interview. The probabilities of remaining well after the index episode and after the first prospective episode were assessed by the life-table method. The severity and duration of prospective episodes and the index episode were compared by linear regression analysis. RESULTS: The probability of remaining well after recovery from the index episode was 76% at 6 months, 63% at 1 year, and 25% at 5 years. The risk of recurrence was lower among patients receiving prophylactic treatment with antidepressants and/or lithium and among those with histories of fewer than three previous episodes. The probability of remaining well was significantly lower 2 years after the first prospective episode than 2 years after the index episode. A pattern of increasing severity from the index episode to the first, second, and third prospective episodes was observed and was not affected by treatment. CONCLUSIONS: Major depression has a high rate of recurrence, even when bipolar and psychotic cases are excluded. The highest rate is observed during the first months after recovery from an episode. Prophylactic drug treatment reduces the risk of recurrence but apparently does not affect the trend toward increasing severity of subsequent episodes.     

A 12-week, double-blind comparison of olanzapine vs haloperidol in the treatment of acute mania

BACKGROUND: This randomized controlled trial compares the efficacy and safety of olanzapine vs haloperidol, as well as the quality of life of patients taking these drugs, in patients with bipolar mania. METHODS: The design consisted of 2 successive, 6-week, double-blind periods and compared flexible dosing of olanzapine (5-20 mg/d, n = 234) with haloperidol (3-15 mg/d, n = 219). RESULTS: Rates of remission (Young-Mania Rating Scale score of < or =12 and 21-item Hamilton Rating Scale for Depression score of < or =8 at week 6) were similar for olanzapine- and haloperidol-treated patients (52.1% vs 46.1%, respectively; P =.15). For the subgroup of patients whose index episode did not include psychotic features, rates of remission were significantly greater for the olanzapine group compared with the haloperidol group (56.7% vs 41.6%, P =.04). Relapse into an affective episode (mania and/or depression) occurred in 13.1% and 14.8% of olanzapine- and haloperidol-treated patients, respectively (P =.56). Switch to depression occurred significantly more rapidly with haloperidol than with olanzapine when using survival analysis techniques (P =.04), and significantly more haloperidol-treated patients experienced worsening of extrapyramidal symptoms, as indicated by several measures. Weight gain was significantly greater in the olanzapine group compared with the haloperidol group (2.82 vs 0.02 kg, P<.001). The olanzapine group had significant improvement in quality of life on several dimensions compared with the haloperidol group. CONCLUSIONS: These data suggest that olanzapine does not differ from haloperidol in achieving overall remission of bipolar mania. However, haloperidol carries a higher rate of extrapyramidal symptoms, whereas olanzapine is associated with weight gain.     

Symptomatic and functional outcome 12 months after a first episode of psychotic mania: barriers to recovery in a catchment area sample

OBJECTIVE: Recent studies have shown that outcome in mania is worse than previously thought. Such studies have been conducted in selected samples with restrictive measures of outcome. We aimed to explore outcome and its predictors in a catchment area sample of first-episode psychotic mania of DSM-III-R bipolar I disorder. METHODS: Prospective 6 and 12 months follow-up was conducted with 87 DSM-III-R first-episode psychotic mania patients admitted to Early Psychosis Prevention and Intervention Centre between 1989 and 1997. Syndromic and symptomatic outcome were determined with the Brief Psychiatric Rating Scale; functional outcome with the Quality of Life Scale and Premorbid Adjustment Scale subitems. RESULTS: Symptomatic outcome was assessed in 67 patients at 6 months and 61 patients at 12 months, and functional outcome in 56 patients at 6 months and 49 patients at 12 months. Logistic regressions were conducted on 46 and 43 patients, respectively, to explore predictors of outcome. While 90% of patients achieved syndromic recovery at 6 and 12 months, 40% had not recovered symptomatically at 6 and 12 months, still presenting with anxiety or depression. A total of 66% of patients at 6 months and 61% of patients at 12 months failed to return to previous level of functioning. Age at intake, family history of affective disorder, illicit drug use and functional recovery at 6 months predicted functional outcome at 12 months. CONCLUSIONS: This study confirms poor symptomatic and functional outcome after first-episode psychotic mania. It suggests possible usefulness of early intervention strategies in bipolar disorders and need for developing specific interventions addressing anxiety, depression and substance abuse comorbidity.     

Subsyndromal depression is associated with functional impairment in patients with bipolar disorder

BACKGROUND: The purpose of this study was to assess whether a relationship exists between mild depressive symptoms and overall functioning in subjects with bipolar disorder. METHOD: Twenty-five male subjects with bipolar I disorder (DSM-III-R criteria), who had not experienced a DSM-III-R episode of mania, hypomania, or major depression for 3 months as determined using the Structured Clinical Interview for DSM-III-R, were evaluated for degree of depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and for overall functional status using the Global Assessment of Functioning (GAF, DSM-IV Axis V). RESULTS: GAF scores were significantly negatively correlated with HAM-D scores (r = -0.61, df = 23, p = .001), despite the fact that no patient had a HAM-D score high enough to be considered clinically depressed. CONCLUSION: The results of this study support a relationship between subsyndromal depressive symptoms and functional impairment in bipolar subjects, despite their not meeting threshold criteria for a major depressive episode. These findings raise the possibility that in some patients with bipolar disorder subsyndromal depressive symptoms might contribute to ongoing functional impairment.     

Course,outcomes, and psychosocial interventions for first‐episode mania

McMurrich S, Sylvia LG, Dupuy JM, Peckham AD, Peters AT, Deckersbach T, Perlis RH. Course, outcomes, and psychosocial interventions for first‐episode mania. Bipolar Disord 2012: 14: 797–808. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: The course of bipolar disorder tends to worsen over time, highlighting the importance of early intervention. Despite the recognized need for adjunctive psychosocial treatments in first‐episode mania, very few studies have evaluated psychological interventions for this period of significant risk. In this empirical review, we evaluate existing research on first‐episode bipolar disorder, compare this body of research to parallel studies of first‐episode schizophrenia, and identify strategies for future research. Methods: A comprehensive literature search of the MEDLINE and PsychINFO databases was conducted to identify studies of first‐episode mania, as well as first‐episode schizophrenia. Recovery and relapse rates were compared across studies. Results: In contrast to a number of studies of first‐episode schizophrenia, the authors identified only seven independent programs assessing first‐episode mania. Findings from these studies suggest that, while pharmacological treatment helps patients achieve recovery from acute episodes, it fails to bring patients to sustained remission. Early psychosocial intervention may be imperative in reducing residual symptoms, preventing recurrence of mood episodes, and improving psychosocial functioning. However, very few studies of psychosocial interventions for first‐episode mania have been systematically studied. Conclusions: Studies of first‐episode mania indicate a gap between syndromal/symptomatic and functional recovery. Novel psychosocial interventions for first‐episode mania may help bridge this gap, but require controlled study.     

Activation of indices of cell-mediated immunity in bipolar mania.

BACKGROUND: Evidence supports that macrophages as well as lymphocytes and their products may be involved in the pathophysiology of psychiatric disorders. Whether patients with bipolar disorder have activation or reduction of immunity during a manic episode remains unclear. METHODS: The purpose of this case-control study was to investigate the lymphocyte proliferation to phytohemagglutinin (PHA), concanavalin A, and pokeweed mitogen, and plasma levels of soluble interleukin-2 receptor (sIL-2R) and sIL-6R in patients with bipolar mania (DSM-III-R). The subjects were 23 physically healthy patients with Young Mania Rating Scale (YMRS) scores > or = 26 as well as aged < or = 45 years and 23 age- and gender-matched normal control subjects. The above immune variables were measured in acute mania and consequent remission (YMRS scores < or = 12) among bipolar patients. RESULTS: The lymphocyte proliferation to PHA and the plasma sIL-2R levels, but not sIL-6R, of bipolar patients were significantly higher in acute mania than in consequent remission. These elevations were not due to differences in medication status. Only in acute mania were the plasma sIL-2R levels of patients significantly higher than control subjects. A positive correlation between the changes of manic severity and plasma sIL-2R levels was observed. Remitted bipolar patients and normal control subjects did not differ in any of these measures. CONCLUSIONS: Cell-mediated immunity activation in bipolar mania was demonstrated and may be through a specifically state-dependent immune response.