How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity?

BACKGROUND: History of high depressive recurrence (without history of mania/hypomania) has been proposed as a mood subtype close to bipolar disorders. Herein we test whether this is the best approach to this question. METHODS: We systematically evaluated consecutive 224 Major Depressive (MDD) and 336 Bipolar II Disorders (BP-II) outpatients in a private practice, by the SCID for DSM-IV (modified for better probing hypomania by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2005. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J. Clin. Psychiatry 66, 914-921]). We conducted univariate and multivariate analyses on such putative bipolar validators as early age at onset of first major depressive episode (before 21 years), high recurrence, family history for bipolar disorders, and depressive mixed states (mixed depression, i.e. depression plus concurrent hypomanic symptoms), in order to identify an MDD subgroup close to BP-II. RESULTS: All bipolar validators were independent predictors of BP-II. Early onset was the only variable which identified an MDD subgroup significantly associated with all bipolar validators. This MDD subgroup was similar to BP-II on age at onset and bipolar family history, and had a high frequency of mixed depression. A dose-response relationship was found between number of bipolar validators present in MDD, and bipolar family history loading among MDD relatives. LIMITATIONS: Study limited to outpatients. CONCLUSIONS: From among the bipolar validators, early age at onset of first major depression (<21 years) was superior to high recurrence (>4 depressive episodes) in identifying an MDD subgroup close to BP-II, which might be subsumed under the broad bipolar spectrum. Implications of unipolar-bipolar boundaries and genetic investigations are discussed.     

Suicide in subtypes of primary major depression

Among 100 consecutive suicide victims with primary major depression at the time of their suicide, 46% were found to have had bipolar II depression, 1% bipolar I disorder and 53% non-bipolar major depression. Since the lifetime prevalence rates of bipolar II and bipolar I depressions are relatively low compared to primary major non-bipolar depression, the present findings suggest that bipolar II disorder gives a particularly high risk of suicide among the different subtypes of primary major affective illness. Fifty-nine percent of the patients had medical contact during the depressive episode, but the depression was frequently undiagnosed, untreated or undertreated. The implications of these findings for suicide prevention are discussed briefly.     

Prevalence and comorbidity of affective disorders in persons making suicide attempts in Hungary: importance of the first depressive episodes and of bipolar II diagnoses

BACKGROUND: The purpose of this study was to investigate the prevalence and comorbidity of affective disorders, especially current major depressive episode and bipolar disorder among suicide attempters in Hungary. METHODS: Using a structured interview (Mini International Neuropsychiatric Interview) determining 16 Axis I psychiatric diagnoses defined by the DSM-IV and a semistructured interview collecting background information, the authors examined 100 consecutive suicide attempters, aged 18-65. RESULTS: Eighty-eight percent of the attempters had one or more current diagnoses on Axis I. In 69% it was major depressive episode and 60% of them were suffering their first episode. Thirty-five percent of the patients with current major depressive episode had had hypomanic (n=19) or manic (n=5) episodes in the past. Seventy percent of the individuals received two or more current diagnoses on Axis I. Eighty-six percent of all current Axis I disorders (except major depressive episode) were diagnosed together with a current major depressive episode. The diagnosis of current major depressive episode and the number of current psychiatric disorders was significantly and positively related to the number of suicide attempts, but the diagnosis of past major depressive episode was not. LIMITATIONS: This study included suicide attempters who had presented selfpoisoning, but not individuals with very high risk of fatality. CONCLUSIONS: In suicide attempters there is a very high prevalence of affective disorders, especially major depression, first episode of major depression and bipolar II disorder. This study underlines the importance of early detection and treatment of psychiatric disorders for the prevention of suicidal behavior.     

Agitated "unipolar" depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy

BACKGROUND: The nosologic status of agitated depression is unresolved. Are they unipolar (UP) or bipolar (BP)? Are they mixed states? Even more controversial is the notion that antidepressants might play some role in the suicidality of such patients (Akiskal and Mallya, 1987) [Akiskal, H.S., Mallya, G., 1987. Criteria for the "soft" bipolar spectrum: treatment implications. Psychopharmacol Bull. 23, 68-73]. METHODS: After excluding all patients with history of hypomanic episodes occurring outside the frame of a major depressive episode (MDE), even those with a shorter duration of hypomanic symptoms than stipulated in DSM-IV, the remaining consecutive 254 unipolar major depressive disorder (MDD) private adult (> 21 years old) outpatients were interviewed (off psychoactive drugs for 2 weeks) with the Structured Clinical Interview for DSM-IV (SCID-CV), the Hypomania Interview Guide (HIGH-C), and the Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed, with > or = 3 such symptoms required for a diagnosis of depressive mixed state (DMX). Agitated depression was defined as an MDE with HIGH-C psychomotor agitation score > or = 2. Logistic regression was used to study associations and control for confounding variables. RESULTS: In this strictly defined unipolar sample, agitated depression was present in 19.7%. Compared with its non-agitated counterpart, it had significantly fewer recurrences, less chronicity, higher rate of family history for bipolar disorder, and DMX; and, among the intra-depressive non-euphoric hypomanic symptoms (in decreasing order of frequency), distractibility, racing/crowded thoughts, irritable mood, talkativeness, and risky behavior. The most striking finding was the robust association between agitated depression and DMX (OR = 36.9). Furthermore, patients with psychomotor agitation had significantly higher rate of weight loss and suicidal ideation. Of DMX symptoms, we found an association between suicidal ideation, psychomotor activation, and racing thoughts. Agitated depression was tested by forward stepwise logistic regression versus all variables significantly different in the pairwise comparisons, yielding DMX, talkativeness, and suicidal ideation as the independent significant positive predictors. LIMITATIONS: No suicidal ideation scale was used. CONCLUSIONS: Agitated depression emerges as a distinct affective syndrome with weight loss, pressure of speech, racing thoughts and suicidal ideation. Psychomotor activation and racing thoughts during MDD independently predicted suicidal ideation. In this "unipolar" MDD sample, agitated depression had a strong clustering of intra-episode non-euphoric hypomanic symptoms (i.e. DMX) which, coupled with its association with bipolar family history, support its link with the bipolar spectrum. Agitated depression is therefore best regarded as "pseudo-unipolar." These findings overall accord with classical German concepts of agitated depression as a mixed state. Given that these patients are typically activated along the lines of risk-taking behavior, Kraepelin's rubric of "excited (mixed) depression" appears to us the preferred terminology over "agitated depression". CLINICAL IMPLICATIONS: The data reported herein, placed in the setting of the literature reviewed in the discussion suggest that the reports of increased risk of suicidal ideation and/or behavior in some depressed patients treated by antidepressant monotherapy or combinations thereof might be attributed to baseline psychomotor activation/agitation as part of an unrecognized bipolar mixed state. Whether antidepressants induce de novo suicidality in MDD cannot be answered without adequately powered prospective double-blind studies, unlikely to be conducted because of ethical constraints. Nonetheless, we submit that agitated, activated, or otherwise excited depressions (which we consider as depressive mixed states) overlap considerably with the so-called antidepressant "activation syndrome." Furthermore, the rare occurrence of suicidality on antidepressants should not obscure the fact that the advent of the new antidepressants is associated with worldwide decline in suicide rates. We finally wish to point out that our formal nosology (i.e. DSM-IV and ICD-10), in its failure to recognize the bipolar nature of depressive mixed states, thereby fails to shield pseudo-unipolar patients from antidepressant monotherapy, which is inappropriate for such patients.     

Temperament and personality in bipolar I patients with and without mixed episodes

BACKGROUND: Personality and temperament are supposed to have an impact on the clinical expression and course of an affective disorder. There is some indication, that mixed episodes result from an admixture of inverse temperamental factors to a manic syndrome. In a preliminary report [Brieger, P., Roettig, S., Ehrt, U., Wenzel, A., Bloink, R., Marneros, A., 2003. TEMPS-a scale in 'mixed' and 'pure' manic episodes: new data and methodological considerations on the relevance of joint anxious-depressive temperament traits. J. Affect. Disord. 73, 99-104] we reported support for this assumption. The present study completes the preliminary results and compares patients with and without mixed episodes with respect to personality and personality disorders in addition. METHODS: Patients who had been hospitalized for bipolar I disorder were reassessed after 4.8 years. We examined temperament (TEMPS-A), personality (NEO-FFI) and frequency of personality disorders (SCID-II). Furthermore, illness-related parameters like age at first treatment, depressive and manic symptomatology, frequency and type of episodes and level of functioning were obtained and patients with and without mixed episodes were compared. RESULTS: Patients with (n=49) and without mixed episodes (n=86) did not differ significantly with regard to the illness-related parameters and personality dimensions. The frequency of personality disorders was significantly higher in patients with prior mixed episodes. With respect to temperament, scores of the depressive, cyclothymic, irritable and anxious temperament were significantly higher in patients with mixed episodes. LIMITATIONS: We were not able to assess premorbid temperament and premorbid personality. CONCLUSIONS: The findings of the present study support the assumption of Akiskal [Akiskal, H.S., 1992b. The distinctive mixed states of bipolar I, II, and III. Clin. Neuropharmacol. 15 Suppl 1 Pt A, 632-633.] that mixed episodes are more frequent in subjects with inverse temperament.     

Antidepressant monotherapy in pre-bipolar depression; predictive value and inherent risk

OBJECTIVE: To identify specific treatment-emergent symptoms in response to antidepressant therapy in depression preceding bipolar disorder. METHODS: Retrospective chart review of response to antidepressants in "pre-bipolar" depression, compared to a matched unipolar sample. RESULTS: Family history of completed suicide (p=0.0003) and bipolar disorder (p=0.004) were more common in the pre-bipolar subgroup. Earlier age of onset of diagnosed depression (p=0.005) as well as even earlier episodes of untreated retrospectively diagnosed major depression (p<0.0001) were associated with a future bipolar course. The pre-bipolar group was less likely to respond to antidepressant treatment (p=0.009). Treatment-emergent "mixed" symptoms (two or more symptoms of DSM IV mania, mood lability, irritability/rage with co-existing depression) and in particular, "serious symptoms" (treatment emergent or increased agitation, rage or suicidality) occurred more commonly in the bipolar group. The two variables that best accounted for the between-group differences in logistic regression, were early age at first symptoms of depression and treatment-emergent agitation. CONCLUSIONS: Family history of completed suicide and/or bipolar disorder, early onset of depressive symptoms as well as treatment-emergent "mixed" symptoms are common in depression preceding the diagnosis of bipolar disorder.     

Dysthymic and anxiety-related personality traits in bipolar spectrum illness

Anxious and dysthymic personality traits were measured in a euthymic, familial sample of bipolar (BPD) individuals and their affectively ill and unaffected relatives. According to the quantitative genetic model of bipolar spectrum illness [Evans, L., Akiskal, H.S., Keck, Jr., P.E., McElroy, S.L., Sadovnick, A.D., Remick, R.A., Kelsoe, J.R., 2005. Familiality of temperament in bipolar disorder: support for a genetic spectrum. J. Affect. Disord. 85, 153-168], these traits should be normally distributed with the bipolar disorder I (BPD I) group showing the highest and the unaffected relatives the least "pathological" scores. Three hundred individuals from 47 bipolar disorder families were administered a battery of personality questionnaires (Temperament Evaluation of Memphis, Pisa, Paris, and San Diego; Temperament and Character Inventory; Affective Neuroscience Personality Scale) as well as a self-rating depression (Beck Depression Inventory) and mania (Altman Self-Rating Mania) scale. Out of the 300 participants, 58 were diagnosed with BPD I, 27 with bipolar disorder II (BPD II), 58 with recurrent major depression (MDE-R), 45 had one previous depressive episode (MDE-S), and 88 were unaffected. The BPD I group scored significantly higher than their unaffected relatives on the Harm Avoidance and Sadness scales of the TCI and ANPS, respectively, while the MDE-R but not the BPD samples scored significantly higher than unaffected relatives on the Anxious Temperament (AT) subscale of the TEMPS-A. In general, the mean dysthymic personality scores were highest in the BPD sample, followed by the MDE-R, MDE-S, and unaffected relative groups. Nevertheless, no significant personality differences were found between the psychiatrically-ill groups. While dysthymic temperament traits conform relatively well to the quantitative genetic model of affective illness, anxious traits as defined by the AT scale, are equally salient in BPD and unipolar depression.     

Gender, suicidality and bipolar mixed states in adolescents

BACKGROUND: The purpose of this study was to determine the relationship between mixed states and suicidality among adolescent outpatients presenting with a DSM-IV defined major depressive episode (MDE). METHODS: Two-hundred and forty-seven adolescents meeting the criteria for MDE were screened for the presence of concurrent, intra-MDE hypomania/mania (i.e., mixed states). All patients were asked whether they had current suicidal ideation or had recently attempted any self-destructive physical act associated with the thought of dying (i.e., a suicide attempt). The data were subjected to analysis using univariate logistic regression. RESULTS: One hundred of the 247 (40.5%) adolescents were bipolar type I or type II. Of these, 82% were in mixed states. Of the patients with suicidal ideation, 62.8% were girls, and of those with histories of a suicide attempt, 69.4% were girls. Girls had more than twice the risk of having suicidal ideation (OR=2.2, p=0.004) and nearly 3 times the risk of having histories of a suicide attempt than boys (OR=2.87, p<0.0001). Being in a mixed state per se did not predict either suicidal ideation or a suicide attempt among all of the 247 patients. However, mixed states apparently independently contributed to the risk of (non-fatal) suicidal behavior among girls only. Of the mixed states, girls had nearly 4 times the risk of having made a suicide attempt compared with those without mixed states (OR=3.9, p=0.003). Age, presence of psychotic features and family history of mood disorder had little or no bearing on suicidality. LIMITATIONS: Correlational chart review study, no data collection on Axis I and Axis II comorbidity and adverse life-events. CONCLUSIONS: This report of greater suicidality in adolescent girls in a mixed state parallels the well-known adult literature of high frequency of mixed states in women. The findings are of relevance to the controversy of antidepressants and suicidality in juvenile depressives in that they identify a vulnerable group. In line with earlier suggestions by the senior author [Akiskal, H.S., 1995. Developmental pathways to bipolarity: are juvenile-onset depressions pre-bipolar? J. Am. Acad. Child Adolesc. Psych. 34, 754-763], our data highlight the public health importance of the wider recognition of bipolar mixed states in juvenile patients masquerading as unipolar depression. Finally, it appears to us that it is the failure of our formal nosology on mixed states--rather than the antidepressants per se--which is the root problem in this controversy.     

Symptom components of standard depression scales and past suicidal behavior

BACKGROUND: Global severity on depression scales may obscure associations between specific symptoms and suicidal behavior. METHODS: We studied 298 persons with major depressive disorder. Factor analysis of the 24-item Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) was used to compare symptom clusters between past suicide attempters and non-attempters. RESULTS: Factor analyses extracted five HDRS and three BDI factors. Suicide attempters had significantly lower scores on an HDRS anxiety factor and higher scores on a BDI self-blame factor. The factor scores correlated with total number of suicide attempts and with known risk factors for suicidal behavior. LIMITATIONS: The differences in factor scores between suicide attempters and non-attempters were significant but modest and may be most relevant in suggesting areas for further clinical studies. Structured diagnostic interviews in this study may have limited the detection of Bipolar II or milder bipolar spectrum disorders. CONCLUSIONS: Depressed suicide attempters exhibit comparably severe mood and neuro-vegetative symptoms, but less anxiety and more intense self-blame than non-attempters. This clinical profile may help guide studies of biological correlates and of treatments to reduce suicide risk.     

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.     

Temperament traits in seasonal affective disorder, suicide attempters with non-seasonal major depression and healthy controls.

BACKGROUND: Very few studies have compared the temperament traits in matched suicidal and non-suicidal patients with major depression. METHODS: We compared the temperament traits in two matched groups of patients with major depressive disorder (MDD), MDD with seasonal subtype (SAD) without any suicide attempt (n = 23) and MDD without seasonal variation who attempted suicide (non-SAD SA), and compared the patients to matched healthy controls by using the Karolinska Scales of Personality (KSP) and the Marke-Nyman Temperament (MNT) questionnaires. RESULTS: Both the SAD and non-SAD SA groups showed significantly higher Somatic Anxiety, Muscular Tension, Psychasthenia, Irritability, Suspicion, and lower Socialization and Validity than the controls. The non-SAD SA group also showed significantly higher Psychic Anxiety, Detachment and Guilt as compared to controls. When the SAD and the non-SAD SA were compared, we found significantly higher Somatic Anxiety, Psychic Anxiety and Muscular Tension for the non-SAD SA group. CONCLUSIONS: Both SAD and non-SAD SA patients display different temperament profiles compared to controls and in comparison with each other and the suicide attempters show especially high trait anxiety and hostility. CLINICAL RELEVANCE: The results suggest that trait anxiety and hostility, but not impulsivity, are associated with suicidal behavior in major depression.     

Bipolar II illness: course and outcome over a five-year period

A five year semi-annual follow-up of patients with non-bipolar (N = 442), bipolar II (N = 64) and bipolar I (N = 53) major depression tracked the courses of prospectively observed major depressive, hypomanic and manic syndromes. In all three groups, depression was much more likely in any given week than was hypomania or mania. However, during the majority of weeks, no full syndrome was present and none of the groups exhibited evidence of continuing psychosocial deterioration. Though all three groups exhibited similar times to recovery from index and subsequent major depressive episodes, both bipolar groups had substantially higher relapse rates and developed more episodes of major depression, hypomania and mania. The two bipolar groups, in turn, differed by the severity of manic-like syndromes and thus remained diagnostically stable; the bipolar II patients were much less likely to develop full manic syndromes or to be hospitalized during follow-up. In conjunction with family study data showing that bipolar II disorder breeds true, these data support the separation of bipolar I and bipolar II affective disorder.     

Lower cerebrospinal fluid homovanillic acid levels in depressed suicide attempters

BACKGROUND: Studies suggest that the dopaminergic system is involved in the pathogenesis of major depression, Axis II disorders, and suicidal behavior. Depressed suicide attempters constitute a heterogenous group and important differences may exist between depressed suicide attempters with or without Axis II disorders. Therefore, we compared demographic and clinical parameters, and cerebrospinal fluid (CSF) homovanillic acid (HVA) levels in depressed suicide attempters without comorbid Axis II disorders, depressed non-attempters without comorbid Axis II disorders, and normal controls. METHODS: Thirty-one depressed subjects with a history of a suicide attempt, 27 depressed subjects without a history of a suicide attempt, and 50 healthy controls were included in the study. Subjects with comorbid Axis II disorders were excluded. Demographic and clinical parameters, and CSF HVA levels were examined. RESULTS: The two depressed groups did not differ with regard to depression, aggression, hopelessness, and total hostility scale scores. Depressed suicide attempters had higher current suicidal ideation scores compared to depressed non-attempters. Depressed suicide attempters had lower CSF HVA levels compared to depressed non-attempters (t = 4.4, df = 56, p < 0.0001) and to controls (t = -4.09, df = 79, p < 0.0001). There was no difference in CSF HVA levels between depressed non-attempters and controls (t < 1, df = 75, NS). CONCLUSIONS: Dopaminergic abnormalities are associated with suicidality but not with depression. The variability in the rates of comorbid Axis II disorders and in the prevalence of suicide attempters in different patient populations may affect both clinical and biological results of studies of mood disorders.     

Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes

BackgroundThere is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of ‘depressive mixed state.’ This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined.MethodsBipolar (type I or II) patients with an MDE at intake (N = 142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation.ResultsSubsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms.LimitationsThe findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment.ConclusionsThe presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality.     

Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters with major depression

BACKGROUND: Impulsiveness, hostility and aggressiveness are traits associated with suicidal behavior, but also with borderline personality disorder (BPD). The presence of large numbers of BPD subjects in past attempter samples may distort the relative importance of each of these traits to predicting suicidal behavior, and lead to prospective, biological and genetic models that systematically misclassify certain subpopulations of suicidal individuals. METHOD: Two hundred and seventy-five subjects with major depressive disorder (MDD), including 87 with co-morbid BPD (69 past suicide attempters, 18 non-attempters) and 188 without BPD (76 attempters, 112 non-attempters) completed standard impulsiveness, hostility and aggressiveness ratings. Differences between past suicide attempters and non-attempters were examined with the sample stratified by BPD status. RESULTS: As expected, BPD subjects scored significantly higher than non-BPD subjects on all three trait measures. Stratifying by BPD status, however, eliminated attempter/non-attempter differences in impulsiveness and hostility in both patient subgroups. Past suicide attempters in each of the two subgroups of patients were only distinguished by higher levels of aggressiveness. CONCLUSIONS: Once BPD is accounted for, a history of aggressive behavior appears to be the distinguishing trait characteristic of suicide attempters with major depression, rather than global personality dimensions such as impulsiveness or hostility. Aggressiveness, and not these related traits, may be the ideal target for behavioral, genetic and biological research on suicidal behavior, as well as for the clinical assessment of suicide risk.     

Clinical differences among depressed patients with and without a history of suicide attempts: findings from the STAR*D trial

BACKGROUND: This study sought to determine whether a history of suicide attempts among outpatients diagnosed with nonpsychotic major depressive disorder (MDD) is correlated with any difference in clinical presentation that should influence patient care. METHODS: Baseline data from the Sequenced Treatment Alternatives to Relieve Depression (STAR()D) trial on outpatients with MDD treated in primary and specialty care settings were used to model significant demographic and clinical correlates of suicide attempter status. RESULTS: Altogether, 16.5% of participants (n=667) reported prior suicide attempts. Controlling for age, gender, and depressive symptom severity, previous attempters had more current general medical conditions (micro=3.2 vs. 2.9, p<.0001), more current alcohol/substance abuse (p<.0001), and more work hours missed in the past week (26.2% vs. 18.2%, p<.0001) than non-attempters. On average, for the previously suicidal, the onset of MDD occurred 8.9 years earlier in life (p<.0001) and had included 1.2 additional depressive episodes (p=0.001) compared to those without prior suicidal behavior. Previous attempters also reported more current suicidal ideation (61.3% of previous attempters, adjusted OR 1.6, vs. 45.5% of nonattempters, p<.0001). LIMITATIONS: Presence or absence of a history of suicide attempts was determined only through self report. CONCLUSIONS: Those with a history of suicidal behavior suffer a greater burden of depressive illness. Earlier intervention and ongoing, aggressive care, including maintenance-phase pharmacotherapy, may be critical to mitigating the long-term consequences associated with this increased disease burden.     

Are BPI and BPII suicide attempters distinct neuropsychologically?

It is not clear if bipolar disorder I (BPI) and bipolar disorder II (BPII) represent the same disorder on a continuum of severity or two distinct syndromes. Neuropsychological functioning is a means of understanding similarities and differences between diagnostic groups. OBJECTIVE: To compare the neuropsychological functioning of depressed suicide attempters with BPI or BPII and healthy controls. METHODS: Fifty-one individuals with bipolar disorder (BPI n=32, BPII n=19) and a history of suicide attempt were compared with 58 healthy controls with respect to neuropsychological functioning in the following domains: motor functioning, psychomotor performance, attention, memory, working memory, impulsiveness and language fluency. RESULTS: Participants with BPI and BPII performed significantly more poorly than healthy controls on tests of Digit Symbol Test of psychomotor functioning, the N Back Test of working memory and the Go-No-Go Test of impulsiveness. Participants with BPI were significantly worse than controls but not those with BPII on the Test of Verbal Fluency. Participants with BPII performed significantly worse than either controls or those with BPI on the Simple Reaction Time Motor Test and the Stroop Test of attention. CONCLUSION: While participants with both BPI and BPII performed more poorly than healthy controls, individuals with BPII also performed more poorly than those with BPI on some tests suggesting that they may have a unique syndrome. The findings have implications for assessment and treatment in bipolar disorder.     

Bipolar mood disorders among Polish psychiatric outpatients treated for major depression

BACKGROUND: Significant proportion of patients treated for depression may have various types of bipolar mood disorders. The aim of the study was to assess the frequency of bipolar disorders among outpatients having at least one major depressive episode, treated by 96 psychiatrists, representing all regions of Poland. METHODS: The study included 880 patients (237 male, 643 female), identified to following diagnostic categories: bipolar I, bipolar II, bipolar spectrum disorder and major depressive disorder. RESULTS: Bipolar mood disorders were found in 61.2% of patients studied, bipolar I more frequent in men and bipolar II in women, and bipolar spectrum in 12% of patients. Patients with age ranges 19-49 and 50-65 years did not differ as to the percentage of diagnostic categories. Patients with bipolar mood disorders compared to major depressive disorder had significantly more frequent family history of bipolar disorder, premorbid hyper- or cyclothymic personality, early onset of depression, symptoms of hypersomnia and hyperphagia, psychotic depression, post-partum depression, and treatment-resistant depression. Bipolar spectrum patients had most clinical features similar to classic types of bipolar disorders. LIMITATIONS: Neither structured interview for family history, nor formal criteria for a number of clinical manifestations were used. The population treated by psychiatrists may not be representative and present a subgroup with more severe mood disorders. CONCLUSIONS: Bipolar mood disorders may be very prevalent among depressive outpatients treated by psychiatrists in Poland, which is confirmed by the results of recent studies. Bipolar patients (including bipolar spectrum) significantly differ from major depressive disorder as to numerous clinical features related mostly to depressive episode.     

Irritable-hostile depression: further validation as a bipolar depressive mixed state

BACKGROUND: "Hostile depression" has unofficially long been described as a depressive subtype, but since DSM-III, the affect has been made a defining characteristic of borderline personality disorder. The related affect of irritability in DSM-IV-TR subsumes various hostile nuances and is included in the stem question for mood disorders--especially for hypomanic episodes; in children, it is nonetheless a sign of depression. Then, there is the unofficial more general concept of depression with anger attacks, until recently ostensibly a "unipolar" (UP) disorder. A veritable tower of Babel indeed. In the present analyses, our aim was to extend previous research on irritable-hostile depression to more specific parameters of bipolarity and depressive mixed state (DMX). METHODS: Consecutive 348 bipolar-II (BP-II) and 254 unipolar (UP) major depressive disorder (MDD) outpatients (off psychoactive agents, including substances of abuse), were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Borderline personality, a confounding variable, rare in the FB setting, was excluded. Irritability was defined according to DSM-IV-TR, which includes various features of hostility and anger. Depressive mixed state (DMX) was defined as a major depressive episode (MDE) plus three or more concurrent intradepressive hypomanic symptoms, whether it occurred in BP-II or MDD. RESULTS: MDE with irritability was present in 59.7% (208/348) of BP-II and in 37.4% (95/254) of MDD (p=0.0000). In BP-II, MDE with, versus MDE without, irritability had significantly younger index age, higher rates of axis I comorbidity, atypical depressive features, and DMX. Upon logistic regression, we found a significant independent association between BP-II MDE with irritability and DMX. In UP, MDE with, versus without, irritability had significantly younger age and age at onset, higher rates of atypical depression, DMX, and bipolar family history. Logistic regression revealed a significant independent association between MDE with irritability and DMX. Given that we had excluded patients with borderline personality, the high prevalence of irritable-hostile depressives in this outpatient population means that hostility cannot be considered the signature of that personality. Factor analysis revealed independent "psychomotor activation" and "irritability-mental activation" factors. Odds ratios of irritability for DMX were highest in the "UP" MDD group (=12.2); for predicting DMX, irritability had the best psychometric profile of sensitivity of 66.3% and a specificity of 86.1% for this group as well. LIMITATION: We did not use specific instruments to measure irritable, hostile, and angry affects. CONCLUSIONS: These analyses show that irritable-hostile depression is distinct from agitated depression. Whether arising from a BP-II or MDD baseline, irritable-hostile depression emerges as a valid entity with strong links to external bipolar validators, such as bipolar family history. Irritable-hostile phenomenology in depression appears to be a strong clinical marker for a DMX. Irritable-hostile depression as a variant of DMX deserves the benefit of what seems to work best in practice, i.e., anticonvulsant mood stabilizers and/or atypical antipsychotics. Formal treatment studies are very much needed.     

Clinical characterization of depressive mixed state in bipolar-I patients: Pisa-San Diego collaboration

BACKGROUND: Although mixed states were classically described as various concomitant admixtures of depression and mania, the official current definitions in both DSM-IV and ICD-10 tend to restrict the concept to manic patients with full syndromal depression. Recent research has actually shown that mania with few depressive symptoms constitutes the most prevalent clinical presentation of mixed or dysphoric mania. Major depressive patients with few concomitant manic symptoms are not officially recognized within the current nosology. In this paper we attempt to delineate the clinical profile of such depressive mixed states in the context of bipolar I disorder. METHODS: In the Pisa day center, we studied 195 bipolar I patients who either met Pisa criteria for bipolar mixed state (n=159) or DSM-III-R criteria for major depressive episode (bipolar major depression or B-MD, n=36). Of the 159 patients identified by Pisa criteria as mixed state, 86 also met the criteria of the DSM-III-R for mixed episode (core mixed state or MS group), while 32 met the DSM III-R criteria for major depressive episode (provisionally defined as depressive mixed states, D-MS); the remaining patients (n=41, 25.7%) with predominatly manic picture were not included in the present comparisons. RESULTS: The three groups (B-MD, MS and D-MS) had close similarities in clinical and sociodemographic characteristics such as age, sex distribution, marital status, schooling, residence, age at onset, age of first treatment, age of first hospitalization, degree of chronicity of the index episode, stressor within the 6 months before the index episode, lifetime suicide attempts and premorbid temperament. First degree family history for bipolar illness and that for other mental disorders was also similar, except for major depression that was more common among the relatives of D-MS. MS and D-MS were further distinguished from B-MD by the fact that the latter followed a more 'cyclic' course with shorter yet greater number of episodes, and which began with a pure depressive episode; by contrast, MS and D-MS had fewer episodes of longer duration, less interepisodic remission, and tended to begin with a mixed episode. Incongruous psychotic features were more common in the two mixed groups compared to B-MD, and the most common features of the D-MS group were agitation, psychotic depression with irritable mood, pressured speech and/or flight of ideas. LIMITATION: It was not feasible to collect information blind to clinical status in patients with severe psychotic mood states. CONCLUSION: These data confirm the existence of psychotic agitated depressive mixed states with flight of ideas, distinct from cyclic retarded pure bipolar depressive states. The recognition of these affective states is clinically important to protect patients from the potentially harmful indiscriminate use of antidepressants and to provide them with the benefits of an anticonvulsant, a short-term neuroleptic, or ECT.