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.     

The dual factor structure of self-rated MDQ hypomania: energized-activity versus irritable-thought racing

BACKGROUND: Bipolar II is diagnosed in a clinically depressed patient by documenting history of hypomania. Therefore, it is of great significance for both clinical and research purposes to characterize the factor structure of hypomania. METHODS: Among consecutive depressive outpatients-126 major depressives and 187 bipolar II-diagnosed by the Structured Clinical Interview for DSM-IV (Clinician Version), 181 who had clinically recovered from depression were administered the Mood Disorder Questionnaire (MDQ of. Am. J. Psychiatry 157, 1873). The MDQ is a newly developed, psychometrically validated self-report screening instrument for bipolar spectrum disorders. It screens for lifetime history of manic/hypomanic symptoms by including yes/no items covering all DSM-IV symptoms of mania/hypomania. The MDQ symptom interrelationships were studied by principal component analysis with varimax rotation. RESULTS: Hypomanic symptoms occurring in >50% were racing thoughts, increased energy and social activity, and irritability. Factor analysis revealed two factors: 'Energized-Activity' (eigenvalue=3.1) and 'Irritability-Racing Thoughts' (eigenvalue=1.5). LIMITATIONS: Cross-sectional assessment. CONCLUSIONS: Self-assessment of past hypomanic symptoms by patients, during clinical remission from depression, revealed two independent hypomanic factors, neither of which comprised euphoria. Hypomanic behavior appears to be more fundamental for the diagnosis of hypomania than elated mood accorded priority in DSM-IV; of hypomanic moods, irritability had greater significance than elation. It would appear that self-report of euphoria is less likely when hypomanias are brief (>or=2 vs. >or=4 days). The main implication for busy clinical practice is that energized activity and irritable mood associated with racing thoughts represent the modal experiences of hypomania among bipolar II outpatients; euphoria is neither sensitive, nor pathognomonic, in the diagnosis of these patients. These conclusions accord with recommendations made many years ago for the diagnosis of hypomania among cyclothymic patients [. Am. J. Psychiatry 134, 1227].     

Refining the evaluation of bipolar II: beyond the strict SCID-CV guidelines for hypomania

BACKGROUND: The prevalence of bipolar II disorder in depressed outpatients is much higher than previously reported, a finding probably related to systematic probing for past hypomania by trained clinicians. Our objective was to further refine the strict SCID-CV guidelines for hypomania in depressed outpatients. METHODS: 168 consecutive outpatients presenting with major depression were systematically interviewed with the SCID-CV about all past hypomanic behavior, irrespective of duration and initial negative response to the screening question on mood. Once typical hypomanic behaviors were elicited, the patient was re-questioned about mood change. RESULTS: The prevalence of bipolar II was 61.3%. Bipolar II, so-defined, was indistinguishable at age of onset, recurrence, and atypical features from a previous sample of 251 BP-II patients interviewed by the same clinician (FB) without the present modification of the stem question on mood, and which had yielded a prevalence of 45% in the same outpatient clinic. LIMITATIONS: Single interviewer, and cross-sectional assessment. CONCLUSIONS: Systematic probing for all past hypomanic symptoms and behaviors, independently of the answer to the screening question on mood, can elicit hypomanic features that would otherwise be discarded by strict adherence to the SCID-CV. A net gain of 16% in the diagnosis of BP-II can thereby be achieved.     

Towards a reconceptualization of mixed states, based on an emotional-reactivity dimensional model

BACKGROUND: DSM-IV criteria for mixed states may be too restrictive and may actually exclude patients who do not meet the full criteria for a manic and depressive state. Using this DSM-IV definition, many patients who are considered depressed may have mixed features, which can explain why some bipolar depressive states can worsen with antidepressants and can be improved by mood stabilizers or atypical antipsychotics. A dimensional approach not exclusively focused on the tonality of affect would help to define a broader entity of mixed states. The aim of this study was to apply a dimensional model to bipolar episodes and to assess the overlap between the groups defined using this model and using categorical diagnosis. METHOD: We assessed 139 DSM-IV acutely ill bipolar I patients with MAThyS (Multidimensional Assessment of Thymic States by Henry et al. in press), a scale that assesses five quantitative dimensions exploring excitatory and inhibition processes, and that is not focused on tonality of mood but on emotional reactivity. We studied the relationship between clusters defined by statistical analyses and DSM-IV bipolar mood states. RESULTS: This study showed the existence of three clusters. Cluster 1 was characterized by an inhibition in all dimensions and corresponded to the depressive cluster (more than 90% of patients met the criteria for DSM-IV Major Depressive Episode (MDE)). Cluster 2 showed a general excitation and was mainly DSM-IV manic or hypomanic patients (90%). Cluster 3 (Mixed) was more complex and the diagnosis included MDE (56%) in most of the cases associated with manic or hypomanic symptoms, mixed states (18%) defined by DSM-IV criteria, and manic or hypomanic states (25%). Emotional reactivity was relevant to distinguish Cluster 1 (Depressive), exhibiting emotional hypo-reactivity, from Cluster 2 (Manic) and 3 (Mixed), characterized by emotional hyper-reactivity. Sadness was reported equally in all three clusters. CONCLUSION: A dimensional approach using the concept of emotional reactivity seems appropriate to define a broad mixed state entity in patients who would be diagnosed with MDE according to DSM-IV. Further studies are needed to test the relevance of this model in therapeutic strategies.     

Major depressive disorder with anger: a bipolar spectrum disorder?

BACKGROUND: Depression with anger may be more common in bipolar disorders. The aim of the study was to assess whether major depressive disorder (MDD) with anger could be included in the bipolar spectrum, by comparing it to MDD without anger and to bipolar II disorder. METHODS: Consecutive outpatients (281 bipolar II disorder and 202 MDD) presenting for major depressive episode (MDE) treatment were interviewed with the DSM-IV structured clinical interview. Clinical variables used to support the inclusion of MDD with anger in the bipolar spectrum were age of onset, many MDE recurrences, atypical features of depression, depressive mixed state (an MDE plus some concurrent hypomanic symptoms), and bipolar family history. RESULTS: Frequency of MDE with anger was 50.5% [61.2% in bipolar II, and 35.6% in MDD (z = 5.5, p = 0.0000, 95% CI 16.8-43.3%)]. Logistic regression of MDE with anger (dependent variable) versus bipolar variables showed that MDE with anger was significantly associated with all bipolar variables, apart from recurrences. MDD with anger, compared with MDD without anger, had significantly lower age of onset, more marked depressive mixed state, a bipolar family history with more cases, but comparable atypical features and Global Assessment of Functioning scores. MDD with anger, compared with bipolar II disorder, had significantly higher age of onset, less atypical features, and a bipolar family history with less cases. CONCLUSIONS: MDE with anger was common in outpatients (more in bipolar II disorder). MDD with anger may be midway between MDD without anger and bipolar II disorder, and might be included into the bipolar spectrum. However, MDD with anger does not appear to be associated with the often reported negative response to monotherapy with antidepressants.     

Toward validation of atypical depression in the community: results of the Zurich cohort study

AIMS: This paper (1) examines the validity of the atypical subtype of depression in a community-based longitudinal cohort study, (2) presents estimates of the prevalence and sex differences of DSM-IV atypical depression and a newly more broadly defined atypical syndrome in the community and (3) compares the clinical correlates and treatment patterns of those with atypical depression with other depressives. METHODS: The Zurich cohort study is comprised of 591 subjects selected from a population-based cohort of young adults representative of the canton of Zurich in Switzerland, who were screened in 1978 with the Symptom Checklist 90-R [L.R. Derogatis (1977)] and followed prospectively with five interviews between 1979 and 1993. Atypical depression was defined on a spectrum ranging from atypical major to minor to atypical depressive symptoms alone. RESULTS: The rate of DSM-IV atypical major depressive episodes in this community is 4.8% and for major atypical depression syndrome is 7.3%. Whereas there was no marked sex difference for nonatypical features, there was a significant female preponderance for DSM-IV and broadly defined atypical depressive subtypes. Systematic investigation of the diagnostic criteria for atypical depression revealed that a nonhierarchical definition of atypical depression with respect to mood reactivity yielded as valid a syndromic definition as the current hierarchy based on mood reactivity as an essential feature. Very high comorbidity (odd ratios>2.0) was found with seasonality, bipolar II, social phobia, binge eating, neurasthenia and sociopathy. LIMITATIONS: Atypical depression was not defined à priori, its criteria were derived from two sections of the Zurich interview. CONCLUSIONS: Atypical depression has high population prevalence and substantial significance in terms of clinical severity, impairment, and service use. The intriguing finding that the sex difference in depression may be attributed to atypical features of depression will need further investigation. Overall, our data indicate that the atypical subtype of depression is a valid entity based on evidence from such traditional indicators of validity as inclusion criteria and indicators of course. However, there are some problems with discriminatory validity from other disorders. Although comorbidity with these disorders may in part reflect an operational artifact of symptom overlap, further work needs to be done in distinguishing atypical depression from bipolar II.     

Self-reported data from patients with bipolar disorder: impact on minimum episode length for hypomania

OBJECTIVE: Some investigators have suggested decreasing the minimum hypomania episode length criterion from 4 days, as in the DSM-IV, to 2 days. Using daily self-reported mood ratings, we studied the impact of changing the length requirement on the number of hypomanic episodes in patients with bipolar disorder. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software (30,348 total days, mean 150 days). Episodes of hypomania and days of hypomania outside of episodes were determined. RESULTS: Decreasing the minimum duration criterion for an episode of hypomania from 4 to 2 days doubled the mean percent of days in a hypomanic episode for each patient (4% to 8%), doubled the number of patients with a hypomanic episode (44 to 96) and increased the number of hypomanic episodes for all patients about three-fold (129 to 404). With a minimum episode length of 4 days, bipolar I patients were more likely to report hypomania outside episodes than bipolar II patients (p=0.010), but with a length of 2 or 3 days there was no significant difference in the distribution of hypomania outside of episodes by diagnosis. With a 2-day length, about one-third (36%) of hypomania remained outside of an episode. LIMITATIONS: Self-reported data, computer access, relatively short length, fewer bipolar II than bipolar I patients. CONCLUSION: As the minimum length for an episode of hypomania decreases, there was a large increase in both the number of episodes and number of patients with episodes. One-day hypomania outside of episodes occurs frequently in both bipolar I and bipolar II disorder.     

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.     

The high prevalence of bipolar spectrum disorders in young adults with recurrent depression: toward an innovative diagnostic framework

BACKGROUND: Young adults with early-onset major depressive disorder (MDD) may be at high risk of progression to bipolar disorder. Although hypomanic symptoms are common in young people with depression, many do not reach the strict DSM-IV and ICD-10 criteria for hypomania. We used an emerging innovative framework for bipolar spectrum to evaluate this question. METHODS: Consecutive referrals to a psychiatric outpatient clinic at a university health service were assessed for recurrent episodes of depression. DSM-IV diagnoses were based on a SCID-1 interview. We used two approaches to delineate bipolar spectrum. The first focused on bipolar spectrum disorder (BSD, as defined by Ghaemi et al. [Can. J. Psychiatry 47 (2002) 125]), and the second on a symptoms perspective based on MDD with a history of hypomanic symptoms, using a 15-point hypomanic symptoms checklist with a cut-off > or =8 or more symptoms (modified from J. Affect. Disord. 73 (2003) 39 and J. Affect. Disord. 73 (2003) 73). Data were also obtained on family history of affective disorder, course and number of episodes of depression, symptom severity, psychosocial functioning, suicidality and deliberate self-harm, and drug and alcohol use. RESULTS: High rates of bipolar and bipolar spectrum disorder were identified. Under DSM-IV, 14 subjects (16.1%) had bipolar affective disorder and 73 subjects (83.9%) had recurrent MDD. Depending on the method used to diagnose bipolar spectrum, between 47.1% and 77.0% of the total cohort could be so diagnosed. Hypomanic symptom counts, irrespective of duration, yielded the highest estimates for bipolar spectrum. High rates of pharmacological hypomania were also identified: 12 subjects (16.4%) with recurrent MDD group reported this, and all could be diagnosed with bipolar spectrum. LIMITATIONS: The reliability of using the 15-point hypomanic scale for the diagnostic assignments was not tested. All subjects were recruited from a university health service and, given the affluence of their parents, findings may not generalise to other populations. Most importantly, because bipolar family history and pharmacological hypomania were part of the diagnostic criteria of the BSD group, they could not be used as external validators for Ghaemi's BSD construct. CONCLUSIONS: Bipolar disorders emerge as extremely common in this cohort of young adults with recurrent depression. Antidepressant-induced hypomania and high scores on a hypomanic symptoms checklist help to identify patients who are likely to have a bipolar spectrum illness, but who do not meet DSM-IV criteria for bipolar disorder. This is a preliminary study, and further evidence from external validating strategies are needed to verify the bipolar status of these patients in a larger and unselected cohort representing a broader socio-economic demographic profile.     

Atypical symptoms in hospitalised patients with major depressive episode: frequency, clinical characteristics, and internal validity

OBJECTIVE: The objective was (1) to assess the frequency of atypical depression (AD) in depressed inpatients; (2) to compare clinical features of patients with atypical and nonatypical depression (Non-AD) (3) to evaluate the meaning of single psychopathological symptoms with special respect to mood reactivity. METHOD: Diagnoses of 1073 inpatients were assessed according to DSM-IV using SCID (Structured Clinical Interview for the DSM-IV) and AMDP (Association for Methodology and Documentation). Diagnosis of atypical depression was defined according to criteria of the DSM-IV specifier for AD. All patients were rated using HAMD-21 (Hamilton Depression Scale). RESULTS: A high percentage of patients met criteria for AD (15.3%, 95% CI 13.0-17.9%). Women were more likely to suffer from AD (OR=1.54, p=0.037). There were no significant differences between AD and Non-AD patients regarding age, HAMD total baseline score, and diagnosis of any bipolar illness. In terms of psychopathology patients with AD were significantly more likely to suffer from somatic anxiety, somatic symptoms, guilt, genital symptoms, depersonalisation and suspiciousness as defined by HAMD-21 items. Interestingly, mood reactivity was not found to be significantly associated with the presence of two or more additional symptoms of AD. LIMITATIONS: Results were assessed by a post-hoc analysis, based on prospectively collected data. Compared to other inpatient samples with MDE, prevalence of bipolar disorder was rather low. CONCLUSION: (1) Frequency of AD may be underestimated, especially in inpatient samples. Further studies of inpatient samples are recommended. (2) Quality of distinct anxiety symptoms may be different in both groups, with AD patients being more likely to suffer from somatic symptoms and somatic anxiety. The presence of suspiciousness and even paranoid phenomena may not exclude a diagnosis of AD, but may be related to rejection sensitivity. (3) The mandatory presence of mood reactivity for the diagnosis of AD needs further consideration, regarding its validity for the concept.     

Assessing the community prevalence of bipolar spectrum symptoms by the mood disorder questionnaire

BACKGROUND: The goal of this study was to assess the frequency and spectrum of symptoms related to bipolar disorders in a community sample by means of a self-rating questionnaire. METHOD: The Mood Disorder Questionnaire, a self-rating scale which evaluates DSM-IV manic/hypomanic symptoms, was administered to a community sample of 1,034 individuals recruited through advertisements. Symptom interrelationships were studied by factor analysis. RESULTS: 275 individuals (26.6%) reported moderate or severe impairment due to the symptoms. Manic/hypomanic symptoms were present in a high proportion of individuals. Factor analysis found a two-factor structure of bipolar spectrum symptoms (an elevated mood overactivity factor, and an irritable behavior factor). CONCLUSION: The findings of this study highlight the need of complementing clinical investigations on the bipolar spectrum with community studies. Subclinical manic-hypomanic symptoms may be present also in allegedly unipolar patients and may have implications on the course of illness.     

Role of risperidone in bipolar II: an open 6-month study

BACKGROUND: Since treatment approaches thought to be useful for mania are presumably suitable for hypomania as well, little systematic research has been done on the treatment of hypomanic episodes and their long-term outcome. As systematic trials have shown that the atypical antipsychotic risperidone may be effective and safe in the treatment of acute mania, we decided to conduct an open-label study of its effectiveness and tolerability in hypomania associated with bipolar II. METHODS: Forty-four DSM-IV bipolar II patients with Young Mania Rating Scale (YMRS) scores above 7 were included and followed-up for 6 months. Efficacy was measured by means of the YMRS and the Clinical Global Impression for Bipolar Disorder (CGI-BD). Treatment-emergent depression was measured by the Hamilton Depression Rating Scale (HDRS-17), and the Udvalg for Kliniske Unders?gelser (UKU) subscale was used for neurological/extrapyramidal side-effects. RESULTS: Thirty-four patients completed the trial. The mean dose of risperidone at endpoint was 2.8 mg/day. Last observation-carried-forward analysis showed significant reduction of YMRS scores from the first week of treatment, which continued until the endpoint (P<0.0001). At 6-month follow-up, 60% of patients were assymptomatic according to the CGI. The 32% who received risperidone in monotherapy seemed to respond equally well. Risperidone, as used in this study, appeared to be most protective against hypomanic than depressive recurrences. Nine patients (12%) had a depressive relapse during 6-month follow-up, one patient (2%) had an hypomanic relapse and another (2%) had both. No patients developed tardive dyskinesia during the duration of the study. Although most patients received risperidone in combination with standard mood-stabilizers, only three patients discontinued risperidone because of other side-effects. LIMITATIONS: In the absence of a placebo arm, it is uncertain to what extent the foregoing results could be ascribed to spontaneous remission of bipolar II disorder. CONCLUSIONS: Risperidone, either in combination with mood-stabilizers or alone was well-tolerated in bipolar II patients, who presented in a hypomanic state, and appeared efficacious. Further controlled research on the role of atypical antipsychotics in the treatment of less-than-manic forms of bipolar illness is warranted.     

Atypical depression: a variant of bipolar II or a bridge between unipolar and bipolar II?

BACKGROUND: Although increasing data link atypical depression (AD) to the bipolar spectrum, controversies abound about the extent of the overlap. In particular, the Columbia group, which has pioneered in providing data on operational clarity and pharmacological specificity of atypical depressions, has nonetheless consistently avoided studying its discriminatory validity from bipolar II (BP-II). Accordingly, we undertook a full scale validation of such a link in a large clinical sample of BP-II and unipolar (UP) major depressive disorder (MDD). METHODS: Consecutive 348 BP-II and 254 MDD outpatients presenting with major depressive episodes (MDE) were interviewed off psychoactive drugs with a modified Structured Clinical Interview for DSM-IV, the structured Family History Screen and the Hypomania Interview Guide. We used the DSM-IV criteria for "atypical features" specifier. Depressive mixed state was defined as > or =3 concurrent hypomanic signs and symptoms during MDE. Bipolar validators were age at onset, high depressive recurrence, depressive mixed state and bipolar family history (types I and II). Univariate and multivariate logistic regression were used to examine associations and control for confounding variables. RESULTS: Frequency of AD was 43.0% in the combined BP-II and MDD sample. AD, versus non-AD, had significantly higher rates of BP-II. AD was significantly associated with all bipolar validators, among which family history was the most robust. A dose-response relationship was found between number of atypical symptoms during MDE and bipolar family history loading. The association between bipolar family history and number of atypical symptoms remained significant after controlling for the confounding effect of BP-II. Bipolar family history was strongly associated with the atypical symptoms of leaden paralysis and hypersomnia. CONCLUSION: These results confirm a strong link between AD and bipolar validators along psychopathologic and familial grounds. From a practical standpoint, AD is best viewed as a variant of BP-II. Clinicians confronted with MDE patients presenting with atypical features should strongly consider a BP-II diagnosis. In a more hypothetical vein, atypicality-or some associated features thereof-might serve as a nosologic bridge between UP and BP-II.     

Self-reported data from patients with bipolar disorder: frequency of brief depression

OBJECTIVE: Patients with bipolar disorder often report depressive symptoms that do not meet the DSM-IV criteria for an episode. Using daily self-reported mood ratings, we studied how changing the length requirement to that typical of recurrent brief depression (2-4 days) would impact the number of depressed episodes. METHOD: 203 patients (135 bipolar I and 68 bipolar II by DSM-IV criteria) recorded mood daily using ChronoRecord software on a home computer (30,348 total days; mean 150 days). Episodes of depression and days of depression outside of episodes were determined. Symptom intensity (mild versus moderate or severe) was investigated within and outside of depressive episodes. RESULTS: Decreasing the minimum duration criterion for an episode of depression to 2 days increased the number of patients with a depressed episode two and a half times (52 to 131), and quadrupled both the number of depressed episodes per patient (0.62 to 2.88) and the number of depressed episodes for all patients (125 to 584). With a 2-day episode length, 34% of days of depression remained outside an episode. The ratio of days with severe symptoms within episodes remained consistent (about 25%) in spite of decreasing the episode length to 2 days. Considering only days with severe symptoms, about 25% remained outside of episodes even with a 2-day length. None of the results distinguished bipolar I from bipolar II disorder. LIMITATIONS: Self-reported data, computer access required, relatively short study length, no control group. CONCLUSION: Brief depressive episodes and single days of depression outside of episodes occur frequently in both bipolar I and bipolar II disorder. Moderate or severe symptoms occur during brief episodes at a ratio similar to that for episodes that meet the DSM-IV criteria.     

Bipolar II depression in late life: prevalence and clinical features in 525 depressed outpatients

BACKGROUND: Late-life bipolar II depression has not been well studied. The aim of the present study was to find the prevalence of late-life (50 years or more) bipolar II depression among unipolar and bipolar depressed outpatients, and to compare it with bipolar II depression in younger patients, looking for differences supporting the subtyping of bipolar II depression according to age at onset. METHODS: Consecutive 525 patients presenting for treatment of a major depressive episode were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. RESULTS: Among patients less than 50 years, 53.4% had bipolar II depression. Among patients 50 years or more, 32.9% had bipolar II depression (significant difference). Atypical features were present in 60.9% of bipolar II patients less than 50 years, and in 26.1% of those 50 years or more (significant difference). Bipolar II patients 50 years or more had significantly higher age at onset than those less than 50 years. Bipolar II and unipolar patients 50 years or more were not significantly different, apart from comorbidity. Bipolar II patients less than 50 years had significantly more atypical features than unipolar ones. LIMITATIONS: Single interviewer, single nonblind assessment, cross-sectional assessment, exclusion of substance abuse and severe personality disorder patients, comorbidity not systematically assessed, modification of DSM-IV duration criterion for hypomania. CONCLUSIONS: Findings suggest that bipolar II depression and atypical features are less common in late life. Differences in age at onset and atypical features support the subtyping of bipolar II depression according to age at onset.     

Exploring aspects of DSM-IV interpersonal sensitivity in bipolar II

BACKGROUND: The aim of the study was to find the prevalence of interpersonal rejection sensitivity (IRS) (a personality trait in DSM-IV) in bipolar II and unipolar depression. METHODS: 557 consecutive unipolar and bipolar II outpatients, presenting for depression treatment, were interviewed with the DSM-IV Structured Clinical Interview and the Global Assessment of Functioning Scale. DSM-IV atypical features criteria (which include IRS) were followed. RESULTS: IRS was significantly more common in bipolar II than in unipolar patients (37.8% vs. 20.5%, odds ratio 2.3, P=0.0000). Sensitivity and specificity for bipolar II diagnosis were 37.8% and 79.4%. CONCLUSIONS: IRS personality trait seems to be more common in bipolar II than in unipolar depression. LIMITATIONS: reliability of bipolar II diagnosis, non-blind, cross-sectional assessment, single interviewer.     

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.     

Prevalence and clinical correlates of residual depressive symptoms in bipolar II disorder

BACKGROUND: Most patients with unipolar and bipolar I disorder have residual symptoms, despite successful treatment. The appraisal of subsyndromal symptomatology has important implications for pathophysiological models of disease and relapse prevention. Residual symptoms in bipolar II disorder were studied insufficiently. The study of residual symptoms in bipolar II disorder is important, because many depressed outpatients may suffer from it and because bipolar II disorder may be distinct from type I. The study aims were to assess the prevalence and clinical correlates of persistent residual depressive symptoms in bipolar II disorder. METHODS: 138 consecutive patients with bipolar II disorder and 83 unipolar disorder outpatients, presenting for major depressive episode treatment in private practice, were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders - Clinician's Version. Study variables were persistent (more than 2 years) residual depressive symptoms, age, gender, age at onset, illness duration, recurrences, axis I comorbidity, severity, psychotic, melancholic and atypical features. RESULTS: The prevalence of residual depressive symptoms was 44.9% in bipolar II disorder and 43.3% in unipolar disorder. Residual depressive symptoms in bipolar II and unipolar disorders were significantly and positively associated with illness duration and recurrences. CONCLUSIONS: Persistent residual depressive symptoms were common in bipolar II disorder. Residual unipolar and bipolar II depressive symptoms were related to duration of illness and number of recurrences. Reducing these variables could reduce and prevent residual symptoms. A mechanism of kindling (more mood episodes leading to worse outcome) could be that of leaving a larger and larger amount of residual symptoms after the acute episode has subsided.     

The bipolar spectrum: a clinical reality in search of diagnostic criteria and an assessment methodology.

Failure to recognize subthreshold expressions of mania contributes to the frequent under-diagnosis of bipolar disorder. There are several reasons for the lower rate of recognition of subthreshold manic symptoms, when compared to the analogous pure depressive ones. These include the lack of subjective suffering, enhanced productivity, ego-syntonicity, and diurnal and seasonal rhythmicity associated with many of the manic and hypomanic symptoms, and the psychiatrists' tendency to subsume persistent or even alternating symptoms among personality disorders. Furthermore, the central diagnostic importance placed on alterations in mood distracts clinicians from paying attention to other more subtle but clinically meaningful symptoms, such as changes in energy, neurovegetative symptoms and distorted cognitions. Although officially accepted in both ICD-10 and DSM-IV, we believe bipolar II disorder is underdiagnosed because of inattention to symptoms of hypomania. Moreover, by requiring the presence of both full-blown hypomanic and major depressive episodes, current nosology fails to include symptoms or signs which are mild and do not meet threshold criteria. There is already agreement in the field that such symptoms are important for depression. We now propose that attention should also be devoted to mild symptomatic manifestations of a manic diathesis, even if such manifestations may sometimes enhance quality of life. The term 'spectrum' is used to refer to the broad range of such manifestations of a disorder from core symptoms to temperamental traits. Spectrum manifestations may be present during, between, or even in the absence of, an episode of full-blown disorder. We have developed a structured clinical interview to assess the mood spectrum (SCI-MOODS) to evaluate the whole range of depressive and manic symptoms. This instrument is currently undergoing psychometric testing procedures. Similar to the SCID interview, the SCI-MOODS interview provides a separate rating for each of the major DSM-IV symptoms, but the latter also identifies and rates subthreshold and atypical manifestations. This paper presents the concept of a subthreshold bipolar disorder and discusses the potential epidemiological, diagnostic and therapeutic relevance of such a spectrum conditions. We also describe the SCI-MOODS interview used reliably to identify the occurrence of a bipolar spectrum condition. Obviously a great deal of systematic research needs to be conducted to ascertain the reliability and validity of subthreshold bipolarity as summarized in this paper and embodied in our instrument.     

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.