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.     

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.     

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.     

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.     

Is migraine in unipolar depressed patients a bipolar spectrum trait?

BACKGROUND: It is well known that affective disorders and migraine often coexist in the same patients, and some information is available indicating that migraine is particularly prevalent in bipolar II disorder. The aims of this study were to compare the clinical features in unipolar depressed patients with and without comorbid migraine to bipolar patients. METHODS: Semi-structured interview of 201 patients with major affective disorders, using DSM-IV criteria for affective disorders combined with Akiskal's criteria for affective temperaments, and IHS-criteria for migraine. RESULTS: Compared to the group of patients having unipolar depressions without comorbid migraine (n = 51) the group with unipolar depression and migraine (n = 63) had a higher number of depressive episodes (4.5 vs. 2.5, P = 0.017), significantly higher prevalences of affective temperaments (46% vs. 16%, P = 0.001), irritability (70% vs. 45%, P = 0.008), seasonal variation (22% vs. 5%, P = 0.017), agoraphobia (44% vs. 26%, P = 0.036), asthma (25% vs. 6%, P = 0.006) and migraine in family (59% vs. 29%, P = 0.002). The clinical features of unipolar depressed patients with comorbid migraine resemble the bipolar II patients (n = 51) in this sample. LIMITATIONS: Non-blind, cross-sectional assessment. CONCLUSIONS: These results indicate that there may be important clinical differences between unipolar depressed patients with and without comorbid migraine, possibly indicating that migraine in depressed patients is a bipolar spectrum trait.     

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 prevalence and clinical correlates of anger attacks during depressive episodes in bipolar disorder

BACKGROUND: Anger attacks, characterized by sudden episodes of intense anger with autonomic arousal, have been described in patients with major depressive disorder (MDD). This study compared the prevalence and clinical significance of anger attacks in unipolar versus bipolar depression. METHODS: Using the questionnaire of Fava et al. [Psychopharmacol. Bull. 27(3) (1991) 275-279], we assessed rates of anger attacks among outpatients with MDD (n=50) or bipolar disorder (BPD) (n=29) who were currently in a pure depressive episode. RESULTS: Anger attacks were significantly more common among bipolar (62%) than unipolar (26%) depressed individuals. In a multiple logistic regression, the presence of anger attacks emerged as a significant predictor of bipolarity. LIMITATIONS: This preliminary finding should be confirmed in a larger sample. CONCLUSIONS: These results suggest that anger attacks may be a common feature of bipolar depression.     

Temperament in the clinical differentiation of depressed bipolar and unipolar major depressive patients

OBJECTIVE: To examine differences in temperament profiles between patients with recurrent unipolar and bipolar depression. METHOD: Depressed individuals with recurrent major depressive disorder (MDD) (n = 94) and those with bipolar (n = 59) disorders (about equally divided between types I and II) were recruited by newspaper advertisement, radio and television announcements, flyers and newsletters, and word of mouth. All patients were interviewed using the Structured Clinical Interview for DSM III-R (SCID) and had the severity of their depressive episode assessed by means of the 17-item Hamilton Rating Scale for Depression. All patients filled out the TEMPS-A, a validated instrument. RESULTS: Temperament differences between bipolar and MDD patients were examined using MANCOVA. Overall significant effect of the fixed factor (bipolar vs. unipolar) was noted for the temperament scores [Hotelling's F((5,142)) = 2.47, p < 0.05]. Overall effects were found for age [F((5,142)) = 2.40, p < 0.05], but not for gender and severity of depression [F((5,142)) = 1.65, p = 0.15 and F((5,142)) = 0.66, p = 0.66, respectively]. Dependent variables included the five subscales of the TEMPS-A, but only the cyclothymic temperament scores showed significant between-group differences. LIMITATION: Small bipolar subsample cell sizes did not permit to test the specificity of the findings for bipolar II vs. bipolar I patients. CONCLUSION: The finding that the clyclothymic subscale is significantly elevated in the bipolar vs. the unipolar depressive group supports the theoretical assumptions upon which the scale is based, and suggests that it might become a useful tool for clinical and research purposes.     

Social rhythm disruption and stressful life events in the onset of bipolar and unipolar episodes

BACKGROUND: An association between social rhythm disruption (SRD) and onset of manic episodes has recently been observed. Whether other types of bipolar (depressive and cycling) or unipolar depressive episodes are similarly related to SRD is unclear, as is the association between severely threatening life events and onset of bipolar manic, depressed and cycling episodes. METHODS: Bipolar patients with purely manic (N= 21), purely depressed (N = 21) and cycling (N = 24) episodes, and 44 patients with recurrent unipolar depression, were interviewed with the Bedford College Life Events and Difficulties Schedule. The presence of severe and SRD events during the year prior to index episode onset was then determined. RESULTS: More manic than cycling and unipolar subjects experienced SRD events during 8- and 20-week pre-onset periods, and severe events during 20-week pre-onset periods. Controlling for age and prior number of episodes left most findings unchanged. An earlier finding of more manic subjects with SRD events in an 8-week pre-onset versus control period was also replicated. CONCLUSIONS: It appears that manic onsets are influenced by stressful life events, especially those involving SRD, in a unique manner compared to onsets of other types of bipolar and unipolar episodes. Onset of bipolar cycling episodes, in contrast, seems to be relatively unaffected by SRD or severe life events. These findings refine the hypothesis that SRD may precipitate onset of affective episodes to be specific to manic onsets.     

Concordance of symptoms in recurrent depressive episodes

The presence or absence of 12 depressive symptoms was examined in 93 bipolar and 108 unipolar patients who had two discrete episodes of major depression over a 5-year period. For each symptom the concordance of its presence or absence across episodes was low. The agreement observed was largely that to be expected by chance. A substantial amount of concordance was obtained if differences in episode intensity (propensity to have symptoms) were taken into account. This suggests that although there may be factors related to depression which remain stable across episodes, symptom presentation is moderated by other factors, such as intensity, which vary from episode to episode.     

Clinical and prognostic implications of seasonal pattern in bipolar disorder: a 10-year follow-up of 302 patients

BACKGROUND: More than 20% of bipolar patients may present with seasonal pattern (SP). Seasonality can alter the course of bipolar disorder. However, to date, long-term follow-up studies of bipolar patients presenting with SP are scarce. We present a 10-year follow-up study comparing clinical and demographic features of bipolar patients with and without SP. METHOD: Three hundred and twenty-five bipolar I and II patients were followed up for at least 10 years. SP was defined according to DSM-IV criteria. Clinical variables were obtained from structured interviews with the patients and their relatives. Patients with and without SP were compared regarding clinical and sociodemographic variables and a stepwise logistic regression was performed. RESULTS: Seventy-seven patients (25.5%) were classified as presenting with SP, while 225 (74.5%) were considered as presenting with no significant seasonal variation. Twenty-three patients (7%) were excluded from the study because it was unclear whether they had seasonality or not. There were no differences between groups regarding demographic variables. Patients with SP predominantly presented with bipolar II disorder, depressive onset, and depressive predominant polarity. The greater burden of depression did not correlate with indirect indicators of severity, such as suicidality, hospitalizations or psychotic symptoms. CONCLUSIONS: Our study links the presence of SP with both bipolar II disorder and predominant depressive component. However, we could not find any difference regarding functionality or hospitalization rates. Modifications in the criteria to define SP are suggested for a better understanding of bipolar disorder.     

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.     

A systematic review of manic and depressive prodromes

BACKGROUND: This paper explores whether individuals with a mood disorder can identify the nature and duration of depressive and manic prodromes. METHODS: Seventy-three publications of prodromal symptoms in bipolar and unipolar disorders were identified by computer searches of seven databases (including MEDLINE and PsycLIT) supplemented by hand searches of journals. Seventeen studies (total sample=1191 subjects) met criteria for inclusion in a systematic review. RESULTS: At least 80% of individuals with a mood disorder can identify one or more prodromal symptoms. There are limited data about unipolar disorders. In bipolar disorders, early symptoms of mania are identified more frequently than early symptoms of depression. The most robust early symptom of mania is sleep disturbance (median prevalence 77%). Early symptoms of depression are inconsistent. The mean length of manic prodromes (>20 days) was consistently reported to be longer than depressive prodromes (<19 days). However, depressive prodromes showed greater inter-individual variation (ranging from 2 to 365 days) in duration than manic prodromes (1-120 days). LIMITATIONS: Few prospective studies of bipolar, and particularly unipolar disorders have been reported. CONCLUSIONS: Early symptoms of relapse in affective disorders can be identified. Explanations of the apparent differences in the recognition and length of prodromes between mania and bipolar depression are explored. Further research on duration, sequence of symptom appearance and characteristics of prodromes is warranted to clarify the clinical usefulness of early symptom monitoring.     

Subsyndromal depressive symptoms in patients with bipolar and unipolar disorder during clinical remission

BACKGROUND: Subsyndromal depressive symptoms seem to be quite prevalent in mood disorders although very few studies have assessed them in patients considered to be in remission by clinical and psychometric criteria. This study sought to evaluate the presence of subsyndromal depressive symptoms in bipolar and unipolar patients in clinical remission. METHODS: One-hundred seventy-six patients with DSM-IV bipolar (62 bipolar I, 58 bipolar II) or unipolar mayor depression (n=58) in clinical remission and 60 healthy subjects were assessed using several psychometric instruments including the 17 items Hamilton Depression Rating Scale (HDRS). To be considered in clinical remission patients assessed with the Clinical Impression for Bipolar Disorder-Modified (CGI-BP-M) had to be stable for 6 months and scoring 6 or less in the Young Mania Rating Scale (YMRS) and 8 or less in the HDRS. RESULTS: Both Unipolar Disorder (UD) and Bipolar Disorder (BD) patients in clinical remission presented statistically significant higher HRSD scores, than healthy subjects. The HRSD scores were statistically higher in UD patients under remission than in BD patients. The subsyndromal symptoms more strongly associated with a clinical diagnosis of either UD or BD were Depressed Mood, Somatic Anxiety, Impact on Work and Activities, Psychic Anxiety, Gastrointestinal and Somatic Symptoms, Retardation during the Interview and Genital Symptoms. CONCLUSION: Subsyndromal depressive symptoms are present in affective disorder patients, both UD and BD, who apparently are in clinical remission. Remitted unipolar patients may have more residual symptoms than bipolar patients, particularly in items related to anxiety and somatic complaints.     

The premorbid personality of patients with different subtypes of an affective illness. Statistical analysis of blind assignment of case history data to clinical diagnoses

On the basis of case history data, the assumption that there exists an association between the 'manic type' of personality and a predominantly manic course of an affective illness, and between the 'melancholic type' of personality and a unipolar depressive course of the illness was examined. Premorbid data were extracted from 42 case records, 10 of 'unipolar' manic subjects (the ratio of manic to depressive episodes greater than or equal to 4:1), 11 of typical bipolar I patients, 11 of bipolar II patients, and 10 of unipolar endogenous depressives. A rater (J.P.), blind to diagnosis and selection procedure, assigned case notes to personality types. Differences were predicted in terms of personality type between the two unipolar groups, the two bipolar groups and, due to the higher number of cases, also between the combined groups of 'unipolar' manic and bipolar I patients on the one hand, and unipolar depressive and bipolar II patients on the other. According to the Fisher test these predictions were fulfilled. Furthermore, in agreement with our hypotheses on the relationship between premorbid personality and course of the disease, the ratio of assignments to 'manic type' and 'melancholic type' decreased from 'unipolar' mania, to bipolar I and bipolar II disorders, and to unipolar depression.     

Seasonality in a community sample of bipolar, unipolar and control subjects

BACKGROUND: This study examined seasonality in a community sample of five diagnostic groups: normal subjects, those with non-seasonal depression (NSD), seasonal depression (SD), non-seasonal bipolar disorder (NSBD) and seasonal bipolar disorder (SBD). METHODS: Telephone interviews were conducted across the Province of Ontario. Seasonal changes in mood and behaviour were determined using the Seasonal Pattern Assessment Questionnaire (SPAQ). Five additional seasonality items consisting of depressive symptoms were included in the interview. The mean global severity of seasonality (GSS) scores were obtained and the entire inventory of 11 seasonality items were compared across the identified groups. RESULTS: The mean GSS score for the controls was 5.2 (S.D. = 4.0), 8.0 (S.D. = 4.9) for NSD, 10.5 (S.D. = 3.9) for SD, 10.5 (S.D. = 5.4) for NSBD and 13.4 (S.D. = 5.4) for SBD. These scores differed significantly (F = 61.68, df = 4, p < 0.001). For the majority of the individual items, the SBD group rated the highest degree of seasonal fluctuation, while the NSBD and SD groups had nearly identical item scores. LIMITATIONS: Limitations in this study include the relatively small number of subjects in the NSBD and SBD groups, and the inherent limitations in a telephone interview. CONCLUSIONS: Individuals with bipolar disorder experience greater seasonality than those with depression or healthy controls. Even the non-seasonal bipolar group had as much seasonal fluctuation as the seasonal depression group, which has important implications for the management of bipolar illness.     

Life events, difficulties and onset of depressive episodes in later life.

BACKGROUND: The importance of stressful life events and long-term difficulties in the onset of episodes of unipolar depression is well established for young and middle-aged persons, but less so for older people. METHOD: A prospective case-control study was nested in a large community survey of older people. We recruited 83 onset cases during a 2-year period starting 2 1/2 years after the survey, via screening (N = 59) and GP monitoring (N = 24), and 83 controls, a random sample from the same survey population. We assessed depression with the PSE-10 and life stress exposure with the LEDS. RESULTS: Risk of onset was increased 22-fold by severe events and three-fold by ongoing difficulties of at least moderate severity. Severe events accounted for 21% of all episodes but ongoing difficulties for 45%. The association of onset with life stress, often health-related such as death, major disability and hospitalization of subject or someone close, was most pronounced in the cases identified by screening. While a clear risk threshold for events was found between threat 2 and 3 (on a scale of 1-4), the risk associated with difficulties increased more gradually with severity of difficulty. Compared with controls, severe events involved a larger risk for cases without a prior history of depression (OR = 39.48) than for cases with (OR = 8.86). The opposite was found for mild events (OR = 2.94 in recurrent episodes; OR = 1.09 in first episodes). The impact of ongoing difficulties was independent of severity of episode and history of depression. CONCLUSION: Although the nature of life stress in later life, in particular health-related disability and loss of (close) social contacts, is rather different from that in younger persons, it is a potent risk factor for onset of a depressive episode in old age. Severe events show the largest relative risk, but ongoing difficulties account for most episodes. The association of severe events with onset tends to be stronger in first than in recurrent episodes. Mild events can trigger a recurrent episode but not a first one.     

Prevalence and correlates of bipolar II disorder in major depressive patients at a psychiatric outpatient clinic in Hong Kong

BackgroundWestern studies indicate a high prevalence of bipolar II disorder defined by a Research Diagnostic Criteria 2-day hypomania duration criterion (30 to 61%) amongst clinically depressive patients. The situation in Chinese patients with depression is unknown.Methods64 (52.5% response rate) patients first presenting to a Hong Kong public psychiatric outpatient clinic in 2005 with a diagnosis of major depression were recruited. The SCID and Family History Screen were administered.ResultsDSM-IV bipolar II was found in 20.5% of depressive outpatients; 35.9% had bipolar II disorder defined by RDC 2-day duration criterion for hypomania. Family bipolarity, age of onset, and depressive recurrence distinguished bipolar II subjects from unipolar depressives irrespective of duration criteria chosen for hypomania.LimitationsSample size was limited.ConclusionsBipolar II disorder is common amongst Chinese depressive outpatients. The evaluation method and 2-day duration criterion for hypomania were supported by bipolar validators. Replication using larger samples is needed to arrive at a more representative prevalence estimate and to enable more refined nosological evaluation.     

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.