Delineating bipolar II mixed states in the Ravenna-San Diego collaborative study: the relative prevalence and diagnostic significance of hypomanic features during major depressive episodes

BACKGROUND: Depressive mixed state (DMX), defined by hypomanic features during a major depressive episode (MDE) is under-researched. Accordingly, study aims were to find DMX prevalence in unipolar major depressive disorder (MDD) and bipolar II depressive phase, to delineate the most common hypomanic signs and symptoms during DMX, and to assess their sensitivity and specificity for the diagnosis of DMX and bipolar II. METHODS: 161 unipolar and bipolar II MDE psychotropic drug- and substance-free consecutive outpatients were interviewed during an MDE with the Structured Clinical Interview for DSM-IV. DMX was defined at two threshold levels as an MDE with two or more (DMX2), and with three or more (DMX3) simultaneous intra-episode hypomanic signs and symptoms. RESULTS: DMX2 was present in 73.1% of bipolar II, and in 42.1% of unipolar MDD (P<0.000); DMX3 was present in 46.3% of bipolar II, and in 7.8% of unipolar MDD (P<0.000). The most common hypomanic manifestations during MDE were irritability, distractibility, and racing thoughts. Irritability had the best combination of sensitivity and specificity for the diagnosis of DMX2 and DMX3. Various combinations of irritability, distractibility, and racing thoughts correctly classified the highest number of DMX2 and DMX3, and had the strongest predictive power. DMX2 had high sensitivity and low specificity for bipolar II, whereas DMX3 had low sensitivity (46.3%) and high specificity (92.1%). LIMITATIONS: Single interviewer, cross-sectional assessment, and interviewing clinician not blind to patients' unipolar vs. bipolar status. CONCLUSIONS: When conservatively defined (>or = 3 intra-episode hypomanic signs and symptoms during MDE), DMX is prevalent in the natural history of bipolar II but uncommon in unipolar MDD. These findings have treatment implications, because of growing concerns that antidepressants may worsen DMX, which in turn may respond better to mood stabilizers. These data also have methodological implications for diagnostic practice: rather than solely depending on the vagaries of the patient's memory for past hypomanic episodes, the search for hypomanic features--ostensibly elation would not be one of those--during an index depressive episode could enhance the detection of bipolar II in otherwise pseudo-unipolar patients. Strict adherence to current clinical diagnostic interview instruments (e.g. the SCID) would make such detection difficult, if not impossible.     

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.     

Distinct seasonality of depressive episodes differentiates unipolar depressive patients with and without depressive mixed states

BACKGROUND: The bipolar nature of unipolar depression with depressive mixed states (DMX) needs further validation studies. The seasonality of depressive episodes is indicated to be different between unipolar and bipolar depressions. We therefore explored the seasonal pattern of depressive episodes in unipolar depressive patients with DMX. METHODS: The subjects were 958 consecutive depressive inpatients for a 6-year period. For defining DMX, previously validated operational criteria were used (2 or more of 8 manic or mania-related symptoms: flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Onsets of the index depressive episodes during each of the 12 calendar months were summed up over the 6-year for bipolar depressive patients (N = 95), and unipolar depressive patients with (N = 77) and without DMX (N = 786) separately. An appropriate statistic was used for testing seasonality. RESULTS: A significant seasonal variation with a large peak in spring was recognized in unipolar depression without DMX, while both bipolar depression and unipolar depression with DMX had a significant fall peak. The monthly distribution of depressive episodes was significantly different between unipolar depression without DMX and other 2 diagnostic categories. Similar results were obtained in separate analyses for each gender. LIMITATIONS: Further replication study using an epidemiological or outpatient sample is needed. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: Unipolar depression with DMX has a seasonal pattern similar to bipolar depression. The finding provides further evidence of the bipolar nature of unipolar depression with DMX.     

Are treatment emergent suicidality and decreased response to antidepressants in younger patients due to bipolar disorder being misdiagnosed as unipolar depression?

While antidepressants have been demonstrated to be a safe and effective treatment for unipolar major depressive disorder (MDD) in adults, the use of antidepressants to treat children and adolescents is controversial. There is a paucity of evidence to suggest that antidepressants are effective when used to treat children and adolescents and some recent placebo-controlled evidence has suggested that antidepressant treatment increases suicidality in this population. MDD is a very broad construct, and includes many clinical subtypes. Bipolar Disorder (BD) has an earlier age of onset than MDD. The initial polarity of illness in bipolar disorder is frequently depression. Patients are more likely to first present for treatment during the depressive phase of the illness than during manic or hypomanic phases. It is probable that a substantial portion of depressed children and adolescents may not suffer from unipolar MDD but may have a bipolar spectrum disorder. There are few trials supporting the efficacy of antidepressants in bipolar disorder, and some evidence that they may induce rapid cycling, switching and mania. Antidepressant induced mania is often mixed, with admixtures of manic and depressive features. An increased suicide risk is a particular feature of mixed states, potentially explaining why suicidal ideation can emerge with antidepressant treatment. Antidepressants are unlikely to somehow act differently in children than they do in adults. A more plausible explanation is that incipient bipolar disorder is often not diagnosed early in children and adolescents and the differential effects of antidepressants in this group is a result of differing diagnostic casemixes.     

Family history validation of the bipolar nature of depressive mixed states

BACKGROUND: Recent data indicate that depressive mixed states (DMX), major depressive episode (MDE) plus few concurrent hypomanic symptoms are common in clinical practice but omitted in DSM-IV. Our aims were to find the sensitivity and specificity of DMX for the diagnosis of bipolar II disorder, and validate it against familial bipolarity. METHODS: 377 consecutive private outpatients presenting with psychoactive drug-free MDE were interviewed with the Structured Clinical Interview for DSM-IV (Clinician Version). History of past hypomanic episodes and presence of hypomanic symptoms during the index MDE were systematically recorded. Of these, 226 were bipolar II and 151 unipolar. DMX3 was defined as an MDE plus three or more intra-episodic hypomanic symptoms. RESULTS: DMX3 was present in 58.4% of bipolar II, and 23.1% of unipolar patients. It was significantly associated with variables distinguishing bipolar from strictly defined unipolar disorders (younger age at onset, more MDE recurrence, more atypical features, more bipolar II family history). Unipolar DMX3 (MDE with documented hypomania solely intra-episodically) was not significantly different from bipolar II MDE on age at onset, atypical features, and bipolar II family history. CONCLUSIONS: Results support the inclusion of DMX3 (bipolar II and 'unipolar') into the bipolar spectrum. Adding the 23% of the UP-DMX3 to the roster of less-than-manic outpatient depressives will boost the rate of bipolarity in this outpatient depressive population to a respectable 70%, the highest rate yet reported for the bipolar spectrum below the threshold of mania.     

Is there a continuity between bipolar and depressive disorders?

BACKGROUND: Recent studies questioned the current categorical split of mood disorders into bipolar disorders (BP) and depressive disorders (MDD). METHODS: Medline database search of papers from the last 10 years on the categorical-dimensional classification of mood disorders. Various combinations of the following key words were used: mood disorders, bipolar, unipolar, major depressive disorder, spectrum, category/categorical, classification, continuity. Only English language clinical papers were included, review papers were excluded, similar papers selected by quality. The number of papers found was 1,141. The number of papers selected was 109. RESULTS: The continuity/spectrum between BP (mainly BP-II) and MDD was supported by the following findings:(1) high frequency of mixed states (mixed mania, mixed hypomania, mixed depression, i.e. co-occurring depression and noneuphoric manic/hypomanic symptoms) because opposite polarity symptoms in the same episode do not support a hypomania/mania-depression splitting; (2) MDD was the most common mood disorder in BP probands' relatives; (3) no bimodal distribution of distinguishing symptoms between BP and MDD; (4) bipolar signs not uncommon in MDD; (5) many MDD shifting to BP; (6) many lifetime manic/hypomanic symptoms in MDD; (7) correlation between lifetime manic/hypomanic symptoms and MDD symptoms; (8) hypomania factors in MDD; (9) MDD often recurrent; (10) similar cognitive style.The categorical distinction between BP (mainly BP-I) and MDD was supported by the following findings: (1) BP more common in BP probands' relatives; (2) lower age at BP onset; (3) females as common as males in BP-I, more common than males in MDD; (4) BP-I depression more atypical and retarded, MDD depression more sleepless and agitated; (5) BP more recurrent. CONCLUSIONS: Focusing on mood spectrum's extremes (BP-I vs. MDD), a categorical distinction seems supported. Focusing on midway disorders (BP-II and MDD plus bipolar signs), a continuity/spectrum seems supported. Results seem to support both a categorical and a dimensional view of mood disorders.     

Atypical depression with hypomanic symptoms

BACKGROUND: Depressive mixed states (major depressive episodes with some hypomanic symptoms) (DMS) are not classified in DSM-IV and are understudied. The aims of this study were to find the prevalence and clinical features of DMS in atypical depression. METHODS: A total of 87 bipolar II and unipolar depressed outpatients were interviewed within the DSM-IV Structured Clinical Interview. RESULTS: More than two hypomanic symptoms were present in 50.0% of the atypical and 20.3% of the non-atypical depression cases (P=0.006). DMS mainly included irritable mood, distractibility, racing thoughts, and increased talking. LIMITATIONS: There was a single interviewer, and it was a non-blind, cross-sectional assessment, with bipolar II reliability. CONCLUSIONS: Findings have treatment implications, as antidepressants may worsen DMS, and mood stabilizers may improve it.     

The close link between suicide attempts and mixed (bipolar) depression: implications for suicide prevention

BACKGROUND: Previous reports have shown a significant relationship between suicide ideation and mixed depression. The aim of this study was to explore the prevalence and clinical characteristics of mixed depression among non-violent suicide attempters. METHODS: Using a structured interview (modified Mini International Neuropsychiatric Interview) and assessing all the symptoms of 16 psychiatric diagnoses, the authors examined 100 consecutive nonviolent suicide attempters (aged 18-65) within 24 h after their attempts. Mixed depression was defined as a major depressive episode (MDE)/dysthymic disorder plus 3 or more co-occurring hypomanic symptoms, according to the definition validated by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2003a. Delineating depressive mixed states: Their therapeutic significance. Clin. Approaches Bipolar Disord. 2, 41-47, Akiskal, H.S., Benazzi, F., 2003b. Family history validation of the bipolar nature of depressive mixed states. J. Affect. Disord. 73, 113-122.]. RESULTS: Current mixed depression was present in 63.0% in the total sample, and in 70.8% among the 89 depressive suicide attempters. Irritability, distractibility and psychomotor agitation were present in more than 90% of the subjects with mixed depression. The rate of mixed depression was significantly higher among bipolar than non-bipolar depressive suicide attempters (90% vs. 62%). Patients with mixed depression had the following concurrent disorders: bipolar disorders 41.0%, panic disorder 30.0%, generalized anxiety disorder 89.0%, alcohol abuse/dependence 56.0%, and substance abuse 27.0%. Mixed depression versus non-mixed depression had the following significant associations (odds ratio=OR): females 2.4, bipolar II disorder 9.3, generalized anxiety disorder 41.3, irritability 101.6 and psychomotor agitation 61.1. LIMITATIONS: The study didn't include suicide attempters with very high risk of fatality. CONCLUSIONS: The important new finding of this study is the very high prevalence of mixed depression among depressed suicide attempters. The rates of mixed depression among bipolar and non-bipolar depressive suicide attempters were much higher than previously reported among nonsuicidal bipolar II and unipolar depressive outpatients, suggesting that suicide attempters come mainly from mixed depressives with predominantly bipolar II base. Irritability and psychomotor agitation were the strongest predictors of suicide attempt. From a public health standpoint, our data highlight the necessity of detecting and treating mixed (bipolar) depression in the prevention of suicidal behaviour.     

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.     

Evaluating the inter-episode stability of depressive mixed states

BACKGROUND: Depressive mixed state (DMX) is understudied, although this diagnostic concept may be of clinical and theoretical importance. Our goal was to provide preliminary evidence of the inter-episode stability of DMX. The inter-episode stability is known to be an important validator for establishing a distinct clinical entity. METHODS: Out of depressive patients consecutively hospitalized at our institute, those who experienced two or more hospitalizations due to discrete depressive recurrences during a 6-year period were selected. All depressive episodes were directly observed and assessed using a standardized rating instrument in terms of eight intra-episode manic symptoms (flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Assessments for subsequent episodes were performed blindly to those for previous episodes within each patient. RESULTS: The inter-episode stability of categorical DMX diagnoses and the number of intra-episode manic symptoms was moderate but significantly high. Approximately 50% of patients with DMX in the index episode obtained a DMX diagnosis in the second episode. Approximately 40% of the total variance of the number of intra-episode manic symptoms was explained by agreements across several depressive episodes. Depressive patients who experienced a diagnostic switch from unipolar to bipolar disorder had a higher frequency of DMX and a greater number of intra-episode manic symptoms in the index as well as subsequent episodes. LIMITATIONS: All consecutive patients were not followed up. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: The inter-episode stability of DMX may not be so high as is required for establishing a distinct clinical entity. However, the findings strongly suggest that some depressive patients have a long-lasting liability to DMX. It is important to determine whether such a liability to DMX is mediated by affective temperaments, as was originally hypothesized by Akiskal [J. Clin. Psychopharmacol. 16 (1996) 4S-14S]. DMX may be a risk factor to the diagnostic switch from unipolar to bipolar disorder.     

Correlates of suicidal ideation in dysphoric mania

BACKGROUND: Previous investigations have reported that suicidal ideation and behavior are more prevalent during mixed than pure mania. Uncertainties exist about whether suicidality in mania arises from multiple concurrent depressive symptoms, or rather, as a categorical phenomenon, reflecting dysphoria without necessarily a full major depression. To elucidate the relationship between suicidal ideation and dysphoric mania, we analyzed clinical and demographic features associated with suicidal versus nonsuicidal dysphoric manic inpatients. METHODS: Records were reviewed for 100 DSM-III-R bipolar I manic inpatients at the Payne Whitney Clinic of New York Hospital from 1991-1995. All had > or = 2 concomitant depressive symptoms (other than suicidality). Affective and psychotic symptoms, past suicide attempts, prior illness, and related clinical/demographic variables were assessed by a standardized protocol. RESULTS: Suicidal ideation was significantly more common among dysphoric manics who were caucasian, took antidepressant medications in the week prior to admission, had histories of alcohol abuse/dependence, and made past suicide attempts. Suicidal ideation was evident for nearly half of dysphoric manic patients with < or = 3 depressive symptoms who did not meet DSM criteria for a mixed state. No individual manic or depressive symptoms other than dysphoric mood were more common among suicidal than nonsuicidal patients. LIMITATIONS: Findings from this retrospective study require confirmation using a prospective assessment. Treatments were naturalistic and may have differentially influenced hospital course and illness characteristics. Factors related to suicide attempts (rare in this cohort) or completions (not a focus of this study) may differ from those related only to suicidal ideation. CONCLUSIONS: Caucasian dysphoric manic patients with past suicide attempts and substance abuse may have a significantly elevated risk for suicidality, even when full major depression does not accompany mania. Suicidality is a clinically important consideration in a majority of dysphoric manic patients.     

Association between the so-called “activation syndrome” and bipolar II disorder,a related disorder,and bipolar suggestive features in outpatients with depression

Background

Activation syndrome (AS) is a cluster of symptoms listed by the US Food and Drug Administration as possible suicidality precursors during antidepressant treatment. We aimed to clarify whether AS is associated with bipolar II disorder (BP-II) and its related disorder, i.e., bipolar disorder not otherwise specified (BP-NOS), which are often mistreated as major depressive disorder (MDD), as well as bipolar suggestive features in outpatients with depression.

Methods

The frequency of AS, bipolar suggestive features, and background variables in consecutive outpatients with a major depressive episode (MDE) due to BP-II/BP-NOS or MDD, who were naturalistically treated with antidepressants, were investigated and analyzed retrospectively.

Results

Of 157 evaluable patients (46 BP-II/BP-NOS, 111 MDD), 39 (24.8%) experienced AS. Patients with BP-II/BP-NOS experienced AS significantly more frequently than patients with MDD (52.2% of BP-II/BP-NOS vs. 13.5% of MDD, p<0.01). Univariate analysis revealed that BP-II/BP-NOS diagnosis, cyclothymic temperament, early age at onset of first MDE, psychiatric comorbidities, and depressive mixed state (DMX) were significantly associated with AS development in the entire sample. Multivariate analysis revealed that BP-II/BP-NOS diagnosis and DMX were independent risk factors for AS.

Limitations

This is a retrospective and naturalistic study; therefore, patient selection bias could have occurred.

Conclusions

Cautious monitoring of AS is needed during antidepressant trials in patients with BP-II/BP-NOS. Clinicians should re-evaluate underlying bipolarity when they confront AS. Antidepressants should be avoided for treating a current DMX beyond the unipolar–bipolar dichotomy. Prospective studies are needed to confirm these results.     

Profiles of "manic" symptoms in bipolar I, bipolar II and major depressive disorders

BACKGROUND: Classical authors such as Kraepelin, as well as the emerging literature during the past decade, indicate that manic-like signs and symptoms are present to a variable degree in all mood disorders. Current nosography does not differentiate between them and only the number of symptoms or severity is used for classification. This is particularly true for mania and hypomania. This paper will analyze the patterns of manic symptoms in bipolar I (BP-I), bipolar II (BP-II) and major depressive disorders (MDD), to test the hypothesis that mania and hypomania have different profiles, and ascertain which excitatory manic phenomena do occur in unipolar MDD. METHODS: Six hundred and fifty-two inpatients (158 BP-I, 122 BP-II and 372 MDD) were assessed using the operational criteria for psychotic illness checklist (OPCRIT) [Arch. Gen. Psychiatry 48 (1991) 764] with a lifetime perspective. Manic or hypomanic symptoms were investigated and compared between BP-I, BP-II and MDD. RESULTS: When compared with BP-II, BP-I disorder had a higher prevalence of reckless activity, distractibility, psychomotor agitation, irritable mood and increased self-esteem. These five symptoms correctly classified 82.8% of BP-I and 80.1% of BP-II patients. One or two manic symptoms were observed in more than 30% of major depressive patients; psychomotor agitation was the most frequent manifestations present in 18% of the MDD group. LIMITATIONS: We did not control for severity of symptoms, nor for neuroleptic use that could produce akathisia. CONCLUSIONS: This study suggests that mania and hypomania can be differentiated in their symptom profiles, and highlights the presence of few manic symptoms, particularly psychomotor agitation, in MDD. From the standpoint of number of manic signs and symptoms, controlling for psychomotor agitation did not substantially change the predictive power of the remaining manic symptoms. Given that excitatory manic signs and symptoms are present to a decreasing degree in BP-I, BP-II and MDD, these disorders can be proposed to lie along a dimensional model. Overall, these data are compatible with the concept of a bipolar spectrum, whereby each of the affective subtypes requires specific genetic factors.     

The dark side of bipolarity: detecting bipolar depression in its pleomorphic expressions

The depressive expressions of bipolar disorders have long been neglected. Current data, from both clinical and epidemiologic studies, indicate that such expressions far exceed the manic forms in both cross-section and during follow-up course. Thus, mania occurs in 1% of the population at large; bipolar depression afflicts at least 5 times more people. Much of the new literature on this subject has emphasized its high prevalence, morbidity, and mortality. There has been relatively less attention paid to the phenomenology of bipolar depression as it presents clinically. This special issue (volume 84/2-3, 2005) is devoted to a systematic data-based in-depth examination of the different clinical expressions of bipolar depression including, among others, retarded depression, agitated and/or activated depression, mood-labile depression, irritable-hostile depression, atypical depression, anxious depression, depressive mixed state, and resistant depression. Both bipolar I (BP-I), and the more prevalent yet relatively understudied bipolar II (BP-II), are covered. We trust that this extensive coverage of the "darker" side of bipolarity will set the stage for a much needed renaissance in its complex phenotypic expressions-and its delimitation from unipolar depression (UP). The phenomenology of BP-I depression ranges from depressive stupor to agitated psychosis, whereas UP depression expresses itself in psychic anxiety, and insomnia, as well as retardation. BP-II compared with UP is more likely to have atypical features, mood lability, hostility, activation, biographical instability, multiple anxiety comorbidities, suicidal tendencies, and to be rated as less "objectively" depressed. These findings are complex and do not fully agree with the conventional characterization of BP as retarded and UP as anxious and agitated. The inconsistency between the conventional and the phenomenology described herein is largely due to depressive mixed states, which tend to destabilize BP-II, and may account for the "contradictory" relationships of affect, sleep, drive, and psychomotor activity in mood disorders.     

Suicidality and sleep disturbances

STUDY OBJECTIVES: A growing body of research indicates that sleep disturbances may be specifically linked to suicidal behaviors. It remains unclear, however, whether this link is largely explained by depressive symptoms. The present study investigated the relationship between suicidality, depression, and sleep complaints in a clinical outpatient setting. DESIGN AND SETTING: Upon admission, 176 outpatients completed measures on sleep disturbances, suicidal symptoms, and depression. Several sleep disturbances were evaluated with regard to suicidal ideation, including insomnia, nightmares, and sleep-related breathing symptoms. MEASUREMENTS AND RESULTS: Regression analyses revealed that insomnia and nightmare symptoms were associated with both depressive symptoms and suicidality. Sleep-related breathing symptoms were associated with depressive symptoms, but did not show an association with suicidal ideation. After controlling for depressive symptoms, only nightmares demonstrated an association with suicidal ideation. This relationship emerged as a nonsignificant trend (P = .06). Nightmares were particularly associated with suicidality among women compared with men. Posthoc analyses revealed that, after controlling for sex and depressive symptoms, nightmare symptoms were significantly associated with suicidality (P = .04). CONCLUSIONS: Although insomnia and nightmares were significantly associated with depressive and suicidal symptoms, after controlling for additional variables, such as depression and sex, only nightmares remained associated with suicidality. This association was slightly stronger among women compared with men.     

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.     

Decline in suicidal ideation among patients with MDD is preceded by decline in depression and hopelessness

BACKGROUND: Suicidal ideation is likely to represent a phase preceding suicidal acts among most suicidal patients with major depressive disorder (MDD). Factors predicting reversal of the suicidal process are unknown. Our aim was to test the hypothesis that a decline in suicidal ideation is preceded by a decline in hopelessness among patients with MDD. METHOD: Of the 269 Vantaa Depression Study patients with DSM-IV MDD, 103 patients scored > or = 6 points at baseline on the Scale for Suicidal Ideation (SSI). Seventy of these patients were followed-up weekly either until they scored zero points on the SSI, or up to 26 weeks. RESULTS: The median duration for a decline of suicidal ideation to zero was 2.2 months after baseline. The level of baseline suicidal ideation, depressive symptoms, and the presence of any personality disorder predicted duration of suicidal ideation. A decline in both depression (BDI) and hopelessness (HS) independently predicted a decline in suicidal ideation. LIMITATIONS: Due to study design, we do not know if suicidal ideation relapsed after the first time the patient reached zero score in the SSI. CONCLUSIONS: Among patients with major depressive disorder having suicidal ideation, the decline in suicidal ideation is independently predicted by preceding declines in the levels of both depressive symptoms as well as hopelessness. The findings are consistent with possible causal roles of declines in depression and hopelessness in reversing the suicidal process.     

Irritable psychomotor elation in depressed inpatients: a factor validation of mixed depression

BACKGROUND: Early authors described hypomanic symptoms as mixed features in depressive episode, but this syndrome has not been sufficiently explored in previous studies. METHODS: 958 consecutive depressed patients were assessed by using a standardized method in terms of 43 psychiatric symptoms at hospitalization. RESULTS: A principal component analysis, followed by varimax rotation, extracted six interpretable factors: typical vegetative symptoms, depressive retardation/loss of feeling, hypomanic syndrome, anxiety, psychosis, and depressive mood/hopelessness. The extracted factor structure was relatively stable among several patient groups. There was no evidence that the hypomanic factor was exaggerated by antidepressant pretreatments before hospitalization. Bipolar diagnoses were associated with higher scores on depressive retardation and hypomanic symptoms, and a lower score on anxiety. LIMITATIONS: Psychiatric syndromes and their interrelationships, found in the present study, may be strongly influenced by the rating instrument used. The sample of this study was depressed inpatients. The results should not be generalized for depressed outpatients or epidemiological depressed populations. CONCLUSIONS: Hypomanic symptoms, as characterized by the flight of ideas, racing thought, increased drive, excessive social contact, irritability, and aggression are a salient syndrome in acutely ill depressed patients, lending support to the factor validity of mixed depression. The symptoms may not be related to pretreatments with antidepressants, or comorbidity of substance abuse, suggesting that they reflect various natural phenomenological manifestations of depressive episodes. Anxiety is unlikely to play a major role in the core phenomenological features of mixed depression. Hypomanic symptoms during a depressive episode were more represented in bipolar disorders, which may serve for further clarifications of latent bipolarity in unipolar depression, and prediction of switch into maniform states under biological depression treatments.