Differences in incidence of suicide attempts during phases of bipolar I and II disorders

Background:  Differences in the incidence of suicide attempts during various phases of bipolar disorder (BD), or the relative importance of static versus time-varying risk factors for overall risk for suicide attempts, are unknown.
Methods:  We investigated the incidence of suicide attempts in different phases of BD as a part of the Jorvi Bipolar Study (JoBS), a naturalistic, prospective, 18-month study representing psychiatric in- and outpatients with DSM-IV BD in three Finnish cities. Life charts were used to classify time spent in follow-up in the different phases of illness among the 81 BD I and 95 BD II patients.
Results:  Compared to the other phases of the illness, the incidence of suicide attempts was 37-fold higher [95% confidence interval (CI) for relative risk (RR): 11.8–120.3] during combined mixed and depressive mixed states, and 18-fold higher (95% CI: 6.5–50.8) during major depressive phases. In Cox's proportional hazards regression models, combined mixed (mixed or depressive mixed) or major depressive phases and prior suicide attempts independently predicted suicide attempts. No other factor significantly modified the risks related to these time-varying risk factors; their population-attributable fraction was 86%.
Conclusions:  The incidence of suicide attempts varies remarkably between illness phases, with mixed and depressive phases involving the highest risk by time. Time spent in high-risk illness phases is likely the major determinant of overall risk for suicide attempts among BD patients. Studies of suicidal behavior should investigate the role of both static and time-varying risk factors in overall risk; clinically, management of mixed and depressive phases may be crucial in reducing risk.     

The clinical characteristics of DSM-IV bipolar I and II disorders: baseline findings from the Jorvi Bipolar Study (JoBS)

OBJECTIVE: To obtain a comprehensive view of the clinical epidemiology of bipolar I and II disorder in secondary-level psychiatric settings. METHODS: In the Jorvi Bipolar Study (JoBS), 1630 non-schizophrenic psychiatric in- and outpatients in three Finnish cities were screened for bipolar I and II disorders with the Mood Disorder Questionnaire. Diagnoses were made using semistructured SCID-I and -II interviews. Information collected included clinical history, current episode, symptom status, and other characteristics. RESULTS: A total of 191 patients with bipolar disorder (90 bipolar I and 101 bipolar II) were included in the JoBS. The majority of bipolar II (50.5%) and many bipolar I (25.6%) patients were previously undiagnosed; the remainder had a median 7.8 years delay from first episode to diagnosis. Despite several lifetime episodes, 26 and 58% of bipolar I and II patients, respectively, had never been hospitalized. A polyphasic episode was current in 51.3%, rapid cycling in 32.5%, and psychotic symptoms in 16.2% of patients. Mixed episodes occurred in 16.7% of bipolar I, and depressive mixed states in 25.7% of bipolar II patients. CONCLUSION: Even in psychiatric settings, bipolar disorders usually go undetected, or recognized only after a long delay. A significant proportion of not only bipolar II, but also bipolar I patients are never hospitalized. Polyphasic episodes and rapid cycling are prevalent in both types. Depressive mixed states are at least as common among bipolar II patients as mixed episodes among bipolar I.     

Difference in binocular rivalry rate between patients with bipolar I and bipolar II disorders

Objective:  When dissimilar figures are presented to each eye individually, perception alternates spontaneously between each monocular view. This phenomenon, known as binocular rivalry, has been used as a powerful tool to investigate conscious visual awareness. Of clinical relevance, Pettigrew and Miller ( Proc Biol Sci 1998; 265: 2141-2148 ) found slow perceptual alternation rates in patients with bipolar I disorder (BD-I). For a better understanding of differences between BD-I and bipolar II disorder (BD-II), we examined whether perceptual alternation rates of binocular rivalry differ between the two subtypes of bipolar disorder.
Methods:  The subjects comprised 25 healthy controls, 11 patients with BD-I, and 17 patients with BD-II. They underwent binocular rivalry examination. One-way analysis of variance was conducted to determine differences in the phase duration of binocular rivalry between the control, BD-I, and BD-II groups.
Results:  Significant differences were observed in the mean phase duration of binocular rivalry between the groups. Although the medication administered did not differ significantly between the BD-I and BD-II patients, the phase duration was significantly longer among the BD-I patients than the BD-II patients and controls, whereas no significant difference was observed in the phase duration between the BD-II patients and controls.
Conclusion:  The present results reveal a significant difference in the mean phase duration of binocular rivalry between subjects with BD-I and those with BD-II, suggesting the presence of some neurobiological difference between these two subtypes of bipolar disorder.     

Unipolar depression with bipolar family history: links with the bipolar spectrum

The aim of the present paper was to find if unipolar major depressive disorder (MDD) with bipolar family history could be included in the bipolar spectrum, by comparing it to unipolar MDD without bipolar family history, and to bipolar II disorder, on typical bipolar variables. A sample of 280 consecutive bipolar II outpatients, and a sample of 135 consecutive unipolar MDD outpatients, presenting for major depressive episode (MDE) treatment, were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn). Hypomanic symptoms during the MDE were systematically assessed. Clinical variables used to validate the inclusion of unipolar MDD with bipolar family history in the bipolar spectrum were young age of onset, many MDE recurrences, atypical features, and depressive mixed state (DMX; an MDE plus >2 concurrent hypomanic symptoms), following many previous studies reporting that these variables were typical features of bipolar disorders. Means were compared by t-test and frequencies by chi2 test (stata 7). Two-tailed P < 0.05 was chosen. Unipolar MDD with bipolar family history was present in 20% of MDD patients. Comparisons among unipolar MDD with bipolar family history (UP+BPFH), unipolar MDD without bipolar family history (UP-BPFH), and bipolar II (BPII), found that UP+BPFH versus UP-BPFH had a significantly lower age, lower age of onset, fewer recurrences, and more DMX; that UP+BPFH versus BPII had no significant differences (apart from recurrences); and that UP-BPFH versus BPII had significantly different age, age of onset, recurrences, atypical features, and DMX. Findings suggest that UP+BPFH shows many bipolar signs, and that it could therefore be included in the bipolar spectrum. Unipolar MDD with bipolar family history had a clinically significant 20.0% frequency in the unipolar MDD sample, supporting the clinical usefulness of this depression subtype. The subtyping of MDD based on bipolar family history could have treatment implications.     

Clinical predictors of unrecognized bipolar I and II disorders

OBJECTIVES: Bipolar disorder (BD) is correctly diagnosed in only 40-50% of patients. No previous study has investigated the characteristics of bipolar patients in psychiatric care with or without clinical diagnoses of BD. We investigated the demographic and clinical predictors of the absence of a clinical diagnosis of BD I and II among psychiatric patients. METHODS: In the Jorvi Bipolar Study, 1,630 psychiatric in- and outpatients were screened with the Mood Disorder Questionnaire. Suspected cases were diagnosed with the Structured Clinical Interview for DSM-IV Axis I Disorders-Patient version (SCID-I/P) for BD. Patients with no preceding clinical diagnosis of BD, despite previous manic, hypomanic or mixed phases and treatment in psychiatric care, were classified as undiagnosed. The clinical characteristics of unrecognized BD I patients (23 of 90 BD I patients) and BD II patients (47 of 93 BD II patients) were compared to those of patients who had been correctly diagnosed. RESULTS: No previous hospitalizations [odds ratio (OR) = 10.6, p = 0.001] or psychotic symptoms (OR = 4.4, p = 0.045), and the presence of rapid cycling (OR = 11.6, p = 0.001) predicted lack of BD I diagnosis. No psychotic symptoms (OR = 3.3, p = 0.01), female gender (OR = 3.0, p = 0.03), and shorter time in treatment (OR = 1.1, p = 0.03) predicted the lack of a BD II diagnosis. CONCLUSIONS: Correct diagnosis of BD I is related to the severe phases of illness leading to hospitalizations. In BD II, the illness factors may not be as important as time elapsed in treatment, a factor that often leads to a delay in diagnosis or none at all. Excessive reliance on typical and cross-sectional presentations of illness likely explain the non-recognition of BD. The challenge for correctly diagnosing bipolar patients is in outpatient settings.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

Latency and episodes before treatment: response to lithium maintenance in bipolar I and II disorders

Objectives: To test whether longer treatment-delays or more pretreatment illness episodes are followed by diminished response to lithium maintenance.

Methods: In 360 DSM-IV bipolar I (n=220) or II (n=140) patients, effects of latency from illness onset to starting lithium and number of pretreatment episodes were evaluated by survival analysis based on the number of months stable before a first recurrence on lithium. Factors associated with treatment latency were identified by regression modeling. Relationships of time, episode number, and morbidity before treatment to the overall proportion of time ill on lithium were also tested by nonparametric correlation.

Results: Latency to first lifetime lithium maintenance averaged 8.3 years, with 9.3 episodes/subject. Time stable before a first recurrence on lithium averaged 29.6 months and was unrelated to treatment latency (in terciles) or to a high (≥ten), intermediate (four–nine), or low (
Conclusions: Treatment latency and prelithium episode number were unrelated to morbidity during treatment. Although multiple untreated episodes can lead to severe disability, lithium evidently can greatly limit morbidity, even after years of delay and multiple episodes of bipolar illness.
     

Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Laterality of pain in migraine with comorbid unipolar depressive and bipolar II disorders

Objectives:  The purpose of the present study has been to examine differences in the laterality of pain in patients with migraine and comorbid unipolar depressive (UP) and bipolar II (BP II) disorders.
Methods:  Semi-structured interviews of 102 patients with major affective disorders were conducted, using DSM-IV criteria for affective disorders combined with Akiskal's criteria for affective temperaments and International Headache Society criteria for migraine. The group of patients reported on in the present study encompass 47 subjects with UP (n=24) or BP II (n=23) disorders. Fifteen of the bipolar II patients fulfilled DSM-IV criteria while eight were diagnosed according to the broader criteria of Akiskal.
Results:  Sixteen of the 38 patients with migraine headaches had bilateral pain or pain equally often on the left or right side while 22 had pain predominantly located on one side. Among the UP patients the pain was most often on the right side (8/10) while among the BP II patients the pain was most often on the left (9/12, p = 0.01). Apart from the presence of hypomanic symptoms in the BP II group there were no clinical or demographic characteristics that distinguished these two sub-groups of affective disorders.
Conclusions:  These results indicate that there may be a differential affection of the cerebral hemispheres in patients with migraine and comorbid unipolar depressive disorder versus patients with migraine and comorbid bipolar II disorder.     

Three times more days depressed than manic or hypomanic in both bipolar I and bipolar II disorder

OBJECTIVES: To assess the proportion of time spent in mania, depression and euthymia in a large cohort of bipolar subjects studied longitudinally, and to investigate depression/mania ratios in patients with bipolar I versus bipolar II disorder. METHODS: Clinician-adjusted self-ratings of mood were completed daily for one year for naturalistically treated outpatients with bipolar I (n = 405) or bipolar II (n = 102) disorder. Ratings were analyzed for mean time spent euthymic, depressed, manic, hypomanic, and cycling, and the percentages of time spent ill were compared between the two groups. RESULTS: Percentages of time spent ill for bipolar I versus II patients were: euthymia 47.7% versus 50.2%; depression 36.0% versus 37.0%; hypomania 11.5% versus 9.8%; mania 1.0% versus 0.2%; and cycling 3.7% versus 2.8%. The depression/mania ratio was 2.9 in the bipolar I and 3.8 in bipolar II sub-groups. CONCLUSIONS: Depression represents the predominant abnormal mood state for treated outpatients with bipolar I and II disorder. In contrast to other studies, we found that depression/mania ratios were of a similar magnitude, suggesting the same tendency towards mood instability in both sub-groups.     

Longitudinal outcome in patients with bipolar disorder assessed by life-charting is influenced by DSM-IV personality disorder symptoms

Objectives:  Few studies have examined the question of how personality features impact outcome in bipolar disorder (BD), though results from extant work and studies in major depressive disorder suggest that personality features are important in predicting outcome. The primary purpose of this paper was to examine the impact of DSM-IV personality disorder symptoms on long-term clinical outcome in BD.
Methods:  The study used a 'life-charting' approach in which 87 BD patients were followed regularly and treated according to published guidelines. Outcome was determined by examining symptoms over the most recent year of follow-up and personality symptoms were assessed with the Structured Clinical Interview for DSM-IV (SCID-II) instrument at entry into the life-charting study.
Results:  Patients with better outcomes had fewer personality disorder symptoms in seven out of 10 disorder categories and Cluster A personality disorder symptoms best distinguished euthymic and symptomatic patients.
Conclusions:  These results raise important questions about the mechanisms linking personality pathology and outcome in BD, and argue that conceptual models concerning personality pathology and BD need to be further developed. Treatment implications of our results, such as need for psychosocial interventions and treatment algorithms, are also described.     

Intra-episode hypomanic symptoms during major depression and their correlates

Recent studies have shown that 40-50% of major depressive disorders (MDD) may become bipolar with time. Intra-episode hypomanic symptoms in MDD may be a first step in this shift. The purpose of the present study was to find factors associated with intra-episode hypomanic symptoms in MDD. Two hundred and forty-three consecutive MDD outpatients were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV), Clinician Version (SCID-CV), as modified by Benazzi and Akiskal (J. Affect. Disord. 2003; 73: 33-38). History of hypomania and presence of hypomanic symptoms during major depressive episode (MDE) were systematically assessed. Intra-episode hypomanic symptoms were defined as an MDE combined with three or more hypomanic symptoms, following Akiskal and Benazzi (J. Affect. Disord. 2003; 73: 113-122). Major depressive disorder with intra-episode hypomanic symptoms (MDD + H) was compared to MDD without hypomanic symptoms on classic bipolar validators. It was found that MDD + H (usually irritability, distractibility, racing thoughts, psychomotor agitation, and more talkativeness) was present in 32.5% of patients. Patients with MDD + H versus MDD had significantly lower age at onset, more atypical depressions, and more bipolar family history. Recurrences were not significantly different. Multivariate logistic regression found that bipolar family history and atypical depression were significantly and independently associated with MDD + H. Findings suggest that MDD + H may be associated with a bipolar vulnerability. Duration of illness and recurrences do not seem to be important for the onset of MDD + H. Bipolar genetic vulnerability seems to be required for onset of intra-episode hypomanic symptoms in MDD. Intra-episode hypomanic symptoms might be the first step of a process leading to the switch of MDD to bipolar disorders. Predicting the switch might have important treatment implications, because antidepressants used alone may worsen the course of bipolar disorders. Prospective studies are required to support these findings and hypotheses.     

Recurrence of bipolar disorders and major depression

Objective: It is not known whether the risk of recurrence declines with time in bipolar disorders and in major depression. This study describes the life-long recurrence risk of bipolar I, bipolar II and major depressive disorders.Method: 160 bipolar-I, 60 bipolar-II and 186 depressive patients hospitalised between 1959 and 1963 were followed up every five years from 1965 to 1985. The course prior to the index hospitalisation was assessed in retrospect. The recurrence risk was computed by the multiplicative intensity model (Aalen et al. 1980).Results: The cumulative intensity curves for the transition from states of remission to new episodes remained linear over 30 to 40 years after onset, indicating a constant risk of recurrence over the life-span up to the age of 70 or more. The recurrence risk of bipolar disorders (0.40 episodes per year) was about twice that of depression (0.20 episodes per year); BP-II disorders had only a slightly higher recurrence risk than BP-I disorders. There were no significant gender differences in the course of either bipolar or depressive disorders.Conclusion: If long-term trials confirm its efficacy, these results support lifelong prophylactic treatment of severe types of mood disorders.     

Suicide attempts in bipolar I and bipolar II disorder: a review and meta-analysis of the evidence

Novick DM, Swartz HA, Frank E. Suicide attempts in bipolar I and bipolar II disorder: a review and meta‐analysis of the evidence. Bipolar Disord 2010: 12: 1–9. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objective: The prevalence of suicide attempts (SA) in bipolar II disorder (BPII), particularly in comparison to the prevalence in bipolar I disorder (BPI), is an understudied and controversial issue with mixed results. To date, there has been no comprehensive review of the published prevalence data for attempted suicide in BPII. Methods: We conducted a literature review and meta‐analysis of published reports that specified the proportion of individuals with BPII in their presentation of SA data. Systematic searching yielded 24 reports providing rates of SA in BPII and 21 reports including rates of SA in both BPI and BPII. We estimated the prevalence of SA in BPII by combining data across reports of similar designs. To compare rates of SA in BPII and BPI, we calculated a pooled odds ratio (OR) and 95% confidence interval (CI) with random‐effect meta‐analytic techniques with retrospective data from 15 reports that detailed rates of SA in both BPI and BPII. Results: Among the 24 reports with any BPII data, 32.4% (356/1099) of individuals retrospectively reported a lifetime history of SA, 19.8% (93/469) prospectively reported attempted suicide, and 20.5% (55/268) of index attempters were diagnosed with BPII. In 15 retrospective studies suitable for meta‐analysis, the prevalence of attempted suicide in BPII and BPI was not significantly different: 32.4% and 36.3%, respectively (OR = 1.21, 95% CI: 0.98–1.48, p = 0.07). Conclusion: The contribution of BPII to suicidal behavior is considerable. Our findings suggest that there is no significant effect of bipolar subtype on rate of SA. Our findings are particularly alarming in concert with other evidence, including (i) the well‐documented predictive role of SA for completed suicide and (ii) the evidence suggesting that individuals with BPII use significantly more violent and lethal methods than do individuals with BPI. To reduce suicide‐related morbidity and mortality, routine clinical care for BPII must include ongoing risk assessment and interventions targeted at risk factors.     

The continuum/spectrum concept of mood disorders: is mixed depression the basic link?

Background Mixed states, i.e., opposite polarity symptoms in the same mood episode, question the bipolar/unipolar splitting of mood disorders, and support a spectrum view. Study aim was assessing the distribution of intradepressive hypomanic symptoms between bipolar-II (BP-II) and major depressive disorder (MDD) depressions, and testing a dose–response relationship between number of intradepressive hypomanic symptoms and bipolar family history. No bi-modality, and a dose–response relationship, would not support a categorical distinction. Methods Consecutive 389 BP-II and 261 MDD depressed outpatients were interviewed by the structured clinical interview for DSM-IV, hypomania interview guide, and family history screen, by a mood specialist psychiatrist, in a private practice. Intradepressive hypomanic symptoms were systematically assessed. Mixed depression was defined as the combination of depression and three or more intradepressive hypomanic symptoms, a validated definition. Results BP-II, versus MDD, had significantly more intradepressive hypomanic symptoms. The distribution of intradepressive hypomanic symptoms between BP-II and MDD was not bi-modal but normal-like, and a dose–response relationship was found between the number of intradepressive hypomanic symptoms and bipolar family history. Conclusions Study findings question the categorical division of BP-II and MDD, and may support the spectrum view of mood disorders.     

Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry

Objective: To evaluate the prevalence of substance abuse dependence and/or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry.

Method: One hundred randomly selected registrants in a voluntary case registry for bipolar disorder were interviewed, using the Structured Clinical Interview for DSM‐IV Axis I Disorders, to validate the diagnosis of this registry. Corroborative information was obtained from medical records, family members and the treating psychiatrist. Eighty‐nine adults (18–65 years) met criteria for bipolar disorder (bipolar I=71, bipolar II=18) and were included in this analysis.

Results: Forty‐one (57.8%) subjects with bipolar I disorder abused, or were dependent on one or more substances or alcohol, 28.2% abused, or were dependent on, two substances or alcohol, and 11.3% abused or were dependent on three or more substances or alcohol. Nearly 39% of bipolar II subjects abused or were dependent on one or more substances, nearly 17% were dependent on two or more substances or alcohol, and 11% were dependent on three or more substances or alcohol. Alcohol was the most commonly abused drug among either bipolar I or II subjects.

Conclusions: Consistent with other epidemiologic and hospital population studies, this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and/or substance abuse dependence. Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects; however, as the number of bipolar II subjects was rather small, this suggestion needs confirmation.