Differences in incidence of suicide attempts between bipolar I and II disorders and major depressive disorder.

OBJECTIVES: Whether risk of suicide attempts (SAs) differs between patients with bipolar disorder (BD) and patients with major depressive disorder (MDD) is unclear. We investigated whether cumulative risk differences are due to dissimilarities in time spent in high-risk states, incidence per unit time in high-risk states, or both. METHODS: Incidence rates for SAs during various illness phases, based on prospective life charts, were compared between patients from the Jorvi Bipolar Study (n = 176; 18 months) and the Vantaa Depression Study (n = 249; five years). Risk factors and their interactions with diagnosis were investigated with Cox proportional hazards models. RESULTS: By 18 months, 19.9% of patients with BD versus 9.5% of patients with MDD had attempted suicide. However, patients with BD spent 4.6% of the time in mixed episodes, and more time in major depressive episodes (MDEs) (35% versus 21%, respectively) and in subthreshold depression (39% versus 31%, respectively) than those with MDD. Compared with full remission, the combined incidence rates of SAs were 5-, 25-, and 65-fold in subthreshold depression, MDEs, and BD mixed states, respectively. Between cohorts, incidence of attempts was not different during comparable symptom states. In Cox models, hazard was elevated during MDEs and subthreshold depression, and among patients with preceding SAs, female patients, those with poor social support, and those aged < 40 years, but was unrelated to BD diagnosis. CONCLUSIONS: The observed higher cumulative incidence of SAs among patients with BD than among those with MDD is mostly due to patients with BD spending more time in high-risk illness phases, not to differences in incidence during these phases, or to bipolarity itself. BD mixed phases contribute to differences involving very high incidence, but short duration. Diminishing the time spent in high-risk phases is crucial for prevention.

Concomitants of family histories of mood disorders and alcoholism in a clinical cohort of patients with bipolar I and II disorder.

We diagnosed 191 secondary-care outpatients and inpatients with DSM-IV BD I or II. Sociodemographic and clinical characteristics, including axis I and II comorbidity, neuroticism, and prospective life-chart were evaluated at intake and at 6 and 18 months. The family history (FH) of mood disorders, alcoholism, or any major psychiatric disorders among first-degree relatives was investigated in a semistructured interview. Most (74%) patients had some positive FH; 55% of mood disorder, 36% of alcoholism. Positive FH was associated with psychiatric comorbidity and depressive course in the proband. Based on a multinomial logistic regression model, patients with an FH of mood disorder and alcoholism had an odds ratio of 4.8 (p = 0.001) for having an anxiety disorder. Overall, the first-degree relatives of patients with BD have multiple types of mental disorders, which correlate with bipolar patients' course of illness and psychiatric comorbidity. The strongest associations are between FH of mood disorders and presence of comorbid anxiety disorders.

P2RX7 gene is associated consistently with mood disorders and predicts clinical outcome in three clinical cohorts.

We investigated the effect of nine candidate genes on risk for mood disorders, hypothesizing that predisposing gene variants not only elevate the risk for mood disorders but also result in clinically significant differences in the clinical course of mood disorders. We genotyped 178 DSM-IV bipolar I and II and 272 major depressive disorder patients from three independent clinical cohorts carefully diagnosed with semistructured interviews and prospectively followed up with life charts for a median of 60 (range 6-83) months. Healthy control subjects (n = 1322) were obtained from the population-based national Health 2000 Study. We analyzed 62 genotyped variants within the selected genes (BDNF, NTRK2, SLC6A4, TPH2, P2RX7, DAOA, COMT, DISC1, and MAOA) against the presence of mood disorder, and in post-hoc analyses, specifically against bipolar disorder or major depressive disorder. Estimates for time ill were based on life charts. The P2RX7 gene variants rs208294 and rs2230912 significantly elevated the risk for a familial mood disorder (OR = 1.35, P = 0.0013, permuted P = 0.06, and OR = 1.44, P = 0.0031, permuted P = 0.17, respectively). The results were consistent in all three cohorts. The same risk alleles predicted more time ill in all cohorts (OR 1.3, 95% CI 1.1-1.6, P = 0.0069 and OR 1.7, 95% CI 1.3-2.3, P = 0.0002 with rs208294 and rs2230912, respectively), so that homozygous carriers spent 12 and 24% more time ill. P2RX7 and its risk alleles predisposed to mood disorders consistently in three independent clinical cohorts. The same risk alleles resulted in clinically significant differences in outcome of patients with major depressive and bipolar disorder.

A prospective latent analyses study of psychiatric comorbidity of DSM-IV bipolar I and II disorders.

OBJECTIVE: To test two hypotheses of psychiatric comorbidity in bipolar disorder (BD): (i) comorbid disorders are independent of BD course, or (ii) comorbid disorders associate with mood. METHODS: In the Jorvi Bipolar Study (JoBS), 191 secondary-care outpatients and inpatients with DSM-IV bipolar I disorder (BD-I) or bipolar II disorder (BD-II) were evaluated with the Structured Clinical Interview for DSM-IV Disorders, with psychotic screen, plus symptom scales, at intake and at 6 and 18 months. Three evaluations of comorbidity were available for 144 subjects (65 BD-I, 79 BD-II; 76.6% of 188 living patients). Structural equation modeling (SEM) was used to examine correlations between mood symptoms and comorbidity. A latent change model (LCM) was used to examine intraindividual changes across time in depressive and anxiety symptoms. Current mood was modeled in terms of current illness phase, Beck Depression Inventory (BDI), Young Mania Rating Scale, and Hamilton Depression Rating Scale; comorbidity in terms of categorical DSM-IV anxiety disorder diagnosis, Beck Anxiety Inventory (BAI) score, and DSM-IV-based scales of substance use and eating disorders. RESULTS: In the SEM, depression and anxiety exhibited strong cross-sectional and autoregressive correlation; high levels of depression were associated with high concurrent anxiety, both persisting over time. Substance use disorders covaried with manic symptoms (r = 0.16-0.20, p < 0.05), and eating disorders with depressive symptoms (r = 0.15-0.32, p < 0.05). In the LCM, longitudinal intraindividual improvements in BDI were associated with similar BAI improvement (r = 0.42, p < 0.001). CONCLUSIONS: Depression and anxiety covary strongly cross-sectionally and longitudinally in BD. Substance use disorders are moderately associated with manic symptoms, and eating disorders with depressive mood.

Maintenance treatment received by patients with bipolar I and II disorders--a naturalistic prospective study.

BACKGROUND: We investigated the adequacy of maintenance phase pharmacotherapy received by psychiatric in- and outpatients with bipolar I or II disorder, including patients both with and without a clinical diagnosis of bipolar disorder (BD). METHODS: In the Jorvi Bipolar Study (JoBS), a naturalistic prospective 18-month study representing psychiatric in- and outpatients with DSM-IV BD I and II in three Finnish cities, we studied the adequacy of pharmacological treatment received by 154 patients during the first maintenance phase after index episode. Information on treatments prescribed during the follow-up was gathered in interviews and from psychiatric records. RESULTS: Of the patients with a maintenance phase in follow-up, adequate maintenance treatment was received by 75.3% for some time, but by only 61.0% throughout the maintenance phase and for 69.3% of the time (783/1129 patient months) indicated. Uninterrupted adequate maintenance treatment received was most strongly independently associated with having a clinical diagnosis of BD; other associations included inpatient treatment, rapid cycling and not having a personality disorder. LIMITATIONS: Adequacy of dosage, duration or serum concentrations were not estimated. Findings represent an upper limit for adequate treatment within the cohort. CONCLUSIONS: Provision or continuity of maintenance treatment was found to be compromised in more than one-third of BD patients during their first follow-up maintenance phase. As expected, clinical diagnosis of BD has a decisive role in determining adequacy of maintenance treatments. However, also rapid cycling may facilitate provision of adequate maintenance treatment, whereas outpatients and those with comorbid personality disorders may be disadvantaged subgroups.

Outcome of patients with major depressive disorder after serious suicide attempt.

OBJECTIVE: To investigate the outcome of subjects with major depressive disorder after serious suicide attempt and to examine the effect of psychotic symptoms on their outcome. METHOD: The study population included all individuals aged 16 years or older in Finland who were hospitalized with ICD-10 diagnoses of major depressive disorder and attempted suicide from 1996 to 2003 (N = 1,820). The main outcome measures were completed suicides, overall mortality, and repeated suicide attempts during drug treatment versus no treatment. RESULTS: During the 4-year follow-up period, 13% of patients died, 6% completed suicide, and 31% made a repeat suicide attempt. Subjects with major depression with psychotic features completed suicide more often than subjects without psychotic features during the follow-up (hazard ratio [HR] 3.32; 95% CI, 1.95 - 5.67). Antidepressant treatment reduced all-cause mortality by 24% (HR 0.74; 95% CI, 0.56 - 0.97) but did not reduce suicide mortality (HR 1.06; 95% CI, 0.71 - 1.58). CONCLUSIONS: Psychotic symptoms during major depressive episode increase the risk of completed suicide after serious suicide attempt. The quality of treatment for major depression with psychotic features after attempted suicide should be improved to prevent suicide.

How suicidal bipolar patients are depends on how suicidal ideation is defined.

BACKGROUND: Suicidal ideation indicates risk for suicidal acts. How different definitions and measures for suicidal ideation influence its prevalence, correlates and predictive validity among bipolar disorder (BD) patients is unknown. METHODS: Among the 191 BD patients in the Jorvi Bipolar Study (JoBS), suicidal ideation at baseline was measured using the Scale for Suicidal Ideation (SSI), Hamilton Depression Scale (HAM-D) item 3 and Beck Depression Inventory (BDI) item 9 and by asking whether patients had seriously considered suicide. The predictive value of different definitions of ideation on suicide attempts during a six-month follow-up was investigated. RESULTS: Altogether 74% of patients had suicidal ideation as defined in at least one of the above-mentioned ways, but only 29% met the criteria for all ways; agreement between definitions ranged from low to moderate (kappa coefficient 0.15 to 0.70). The correlates of suicidal ideation overlapped, but were not identical. Of the measures investigated, a baseline SSI score >or=8 had the best combination of sensitivity (0.81) and specificity (0.69) and a positive predictive value (PPV) of 32% for an attempted suicide during follow-up. LIMITATIONS: All plausible measures for suicidal ideation could not be investigated. CONCLUSIONS: Who is classified as having suicidal ideation depends strongly on the definition and means of measurement among BD patients. Different measures for ideation have the potential to cause inconsistency when correlates of suicidal ideation are investigated. For clinically predicting suicide attempts during the next few months, an SSI score >or=8 may best combine sensitivity and specificity.

Hopelessness across phases of bipolar I or II disorder: a prospective study.

BACKGROUND: Hopelessness, a key risk factor for suicidal behaviour overall, has been studied little among bipolar disorder (BD) patients. For purposes of prevention, it is important to know whether it is predominantly a patient's permanent trait or merely reflects the highly variable illness states. We investigated the degree to which hopelessness is trait- or state-related during the course of BD. METHODS: The Jorvi Bipolar Study (JoBS) is a naturalistic prospective study representing psychiatric in- and outpatients with DSM-IV BD I and II. Repeated measurements with the Beck Hopelessness Scale of 188 patients at baseline, 6 months and 18 months were analysed using a linear regression model with general estimation equations. Factors covarying with hopelessness during follow-up were investigated. RESULTS: Levels of hopelessness varied markedly between illness phases, being highest in depressive and mixed phases, and lowest in euthymia, hypomania or mania. Hopelessness was independently associated with concurrent severity of depression (estimate 0.231, p<0.001), anxiety (0.105, p<0.001), fewer manic symptoms (-0.096, p=0.001) and comorbid personality disorder (1.741, p=0.001). However, the strongest predictor of degree of hopelessness during follow-up was previous hopelessness (0.403, p<0.001). LIMITATIONS: After baseline, relatively few patients had manic, hypomanic, mixed or depressive mixed phases. Hopelessness was measured at only three time-points. CONCLUSIONS: Level of hopelessness varies markedly between patients in different phases of BD, but is also, to a degree, a permanent feature. Among BD patients, hopelessness appears to be both a trait- and state-related characteristic.

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.

Differences in outcome of DSM-IV bipolar I and II disorders.

OBJECTIVES: To investigate whether the course of bipolar disorder (BD) type II is more depressive than that of BD I, and, if so, to explore the underlying factors that cause this difference. METHODS: In a prospective, naturalistic study of 191 secondary care psychiatric in- and outpatients diagnosed in an acute phase of BD I or II, 160 patients (85.1%) were followed for 18 months. Using a life chart, the exact timing of symptom states in follow-up was examined. Differences between BD I (n = 75) and II (n = 85) in duration of index phase and episode, time to full remission and recurrence, and time in any mood episode were investigated. RESULTS: Patients with BD II spent a higher proportion of time ill (47.5% versus 37.7%; p = 0.02) and in depressive symptom states (58.0% versus 41.7%; p = 0.003) than BD I patients. This was a result of the higher proportion (61.7% versus 48.6%; p = 0.03) and mean number (1.69 versus 1.11; p = 0.006) of depressive illness phases in BD II, rather than of differences in the duration of depressive phases. Type of index phase strongly predicted the outcome. In linear regression models, both BD II and type of index phase predicted more time spent in depressive symptom states. CONCLUSIONS: In medium-term follow-up, BD II patients spend about 40% more time in depressive symptom states than BD I patients because a higher proportion of BD II patients have depressive phases and the frequency of these is higher. Differences in type of index phase may markedly confound differences in outcome between BD I and II.

Only half of bipolar I and II patients report prodromal symptoms.

BACKGROUND: Learning to detect prodromal symptoms is a key element of psychosocial treatment of bipolar disorder (BD). However, previous studies have described only prodromes of manic and depressive phases of BD I patients, while information on prodromes in BD II, or other phases is lacking. METHODS: The Jorvi Bipolar Study included 191 in- and outpatients with DSM-IV BD (90 BD I, 101 BD II) in any acute phase of illness at baseline. The prevalence, type and duration of preceding prodromes were investigated using open-ended questions. The effects of type I or II disorder, index phase, socio-demographic factors, comorbidity, illness history and other correlates on report and duration of prodromes were investigated. RESULTS: Prodromes were reported by 45.0% of BD I and 50.0% of BD II patients. The first prodromal symptom was usually mood congruent, but sometimes non-specific for mood or a symptom of anxiety; the median duration was 30.5 days. No differences between BD I and II, or between patients who did and those who did not report prodromes were found. Only Axis I comorbidity associated with longer prodromes, but not independently after adjusting for age, gender and type of phase. LIMITATIONS: The study was cross-sectional. Reporting prodromes depends on patients' insight which was likely affected by a sub-acute phase at time of interview. CONCLUSIONS: Only half of ordinary, secondary care bipolar patients are able to report prodromes. The chronic and fluctuating course of illness, and sometimes short time interval to full episode may limit the potentials of prodrome-based interventions.

Suicidal behaviour during different phases of bipolar disorder.

BACKGROUND: There are no previous studies comparing the prevalence and risk factors for suicidal behaviour during different phases of bipolar disorder. METHODS: In the Jorvi Bipolar Study (JoBS), 1630 psychiatric in- and outpatients were screened for bipolar disorders with the Mood Disorder Questionnaire. Using SCID I and II interviews, 191 patients were diagnosed with bipolar disorders (90 bipolar I, 101 bipolar II). Suicidal ideation was measured using the Scale for Suicidal Ideation (SSI). Prevalence and risk factors for ideation and attempts during different phases (depressive, mixed, depressive mixed and hypomanic/manic phases) were investigated. RESULTS: There were marked differences between phases regarding suicide attempts and level of suicidal ideation. Hopelessness predicted suicidal behaviour during the depressive phase, whereas a subjective rating of severity of depression and younger age predicted suicide attempts during mixed phases. LIMITATIONS: The relatively small sample size in some phases. CONCLUSIONS: Suicidal behaviour varied markedly between different phases of BD. Suicide attempts and suicidal ideation were related to phases which are associated with depressive aspects of the illness. Hopelessness and severity of depression were key indicators of risk in all phases.

Prospective study of risk factors for attempted suicide among patients with bipolar disorder.

OBJECTIVE: There are few prospective studies on risk factors for attempted suicide among representative samples of psychiatric patients with bipolar I and II disorders. We conducted a prospective study to investigate risk for suicide attempts among a secondary-level sample of psychiatric in- and outpatients with bipolar disorder (BD). METHODS: In the Jorvi Bipolar Study (JoBS), 1,630 psychiatric in- and outpatients from three Finnish cities were screened for BDs with the Mood Disorder Questionnaire (MDQ). Using the Structured Clinical Interview for DSM-IV Disorders (SCID)-I and -II, 191 patients were diagnosed with BDs (90 bipolar I and 101 bipolar II). Information on suicide attempts during the follow-up was obtained for 176 patients (92%) at the 6-month follow-up and for 160 patients (84%) at the 18-month follow-up. RESULTS: During the 18-month follow-up 20% of patients (35/176) attempted suicide. In a Cox regression model, baseline previous suicide attempts (OR 3.8, 95% CI 1.7-8.8; p = 0.001), hopelessness (OR 1.2, 95% CI 1.1-1.3; p < 0.001), depressive phase at index episode (OR 2.4, 95% CI 1.1-5.3; p = 0.03) and younger age at intake (OR 0.94, 95% CI 0.91-0.97; p < 0.001) were independent risk factors for suicide attempts during follow-up, whereas factors such as bipolar I or II, or comorbidity did not reach statistical significance. CONCLUSIONS: During a medium-term follow-up, as many as one-fifth of random psychiatric patients with BD attempted suicide, which highlights the public health importance of suicidal behavior in BD. Previous suicide attempts, hopelessness and depressive phase were the key indicators of risk.

Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder.

OBJECTIVE: To obtain a comprehensive view of differences in current comorbidity between bipolar I and II disorders (BD) and (unipolar) major depressive disorder (MDD), and Axis I and II comorbidity in BD in secondary-care psychiatric settings. METHOD: The psychiatric comorbidity of 90 bipolar I and 101 bipolar II patients from the Jorvi Bipolar Study and 269 MDD patients from the Vantaa Depression Study were compared. We used DSM-IV criteria assessed by semistructured interviews. Patients were inpatients and outpatients from secondary-care psychiatric units. Comparable information was collected on clinical history, index episode, symptom status, and patient characteristics. RESULTS: Bipolar disorder and MDD differed in prevalences of current comorbid disorders, MDD patients having significantly more Axis I comorbidity (69.1% vs. 57.1%), specifically anxiety disorders (56.5% vs. 44.5%) and cluster A (19.0% vs. 9.9%) and C (31.6% vs. 23.0%) personality disorders. In contrast, BD had more single cluster B personality disorders (30.9% vs. 24.6%). Bipolar I and bipolar II were similar in current overall comorbidity, but the prevalence of comorbidity was strongly associated with the current illness phase. CONCLUSIONS: Major depressive disorder and BD have somewhat different patterns in the prevalences of comorbid disorders at the time of an illness episode, with differences particularly in the prevalences of anxiety and personality disorders. Current illness phase explains differences in psychiatric comorbidity of BD patients better than type of disorder.