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.     

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.     

Multiple dimensions of familial psychopathology affect risk of mood disorder in children of bipolar parents.

The aim of our study was to determine whether familial loading of unipolar disorder, bipolar disorder, and substance use disorder are associated with DSM-IV mood disorders in adolescents at risk for bipolar disorder. One hundred and forty adolescents aged 12-21 years of 86 bipolar parents participated in the study. Lifetime DSM-IV diagnoses of the bipolar offspring were assessed with the Schedule for Affective Disorders and Schizophrenia for School Age Children Kiddie-SADS-Present and Lifetime Version (SADS-PL). Parents were interviewed using the Family History Research Diagnostic Criteria (FH-RDC) which were used to calculate a continuous familial loading score (FL) for unipolar disorder, bipolar disorder, and for substance use disorder in first- and second-degree relatives of the adolescents. FL for unipolar disorder and substance use disorder were strong and independent predictors for lifetime mood disorders in the adolescents. The gender adjusted hazard ratios for mood disorders in the children were 1.5 (95% confidence interval (CI) = 1.2-2.0) for FL of unipolar disorder and 1.8 (95% CI = 1.3-2.4) for FL of substance use disorder. Expression of mood disorders in children of bipolar parents varies with the degree of additional FL of unipolar disorder and substance use disorder in the extended family.     

The impact of generalized anxiety disorder and stressful life events on risk for major depressive episodes

BACKGROUND: Both generalized anxiety disorder (GAD) and stressful life events (SLEs) are established risk factors for major depressive disorder, but no studies exist that examine the interrelationship of their impact on depressive onsets. In this study, we sought to analyze the joint effects of prior history of GAD and recent SLEs on risk for major depressive episodes, comparing these in men and women. METHOD: In a population-based sample of 8068 adult twins, Cox proportional hazard models were used to predict onsets of major depression from reported prior GAD and last-year SLEs rated on long-term contextual threat. RESULTS: For all levels of threat, prior GAD increases risk for depression, with a monotonic relationship between threat level and risk. While females without prior GAD consistently show higher depressive risk than males, this is no longer the case in subjects with prior GAD who have experienced SLEs. Rather, males appear to be more vulnerable to the depressogenic effects of both prior GAD and SLEs. CONCLUSION: The effects of prior GAD and SLEs jointly increase the risk of depression in both sexes, but disproportionately so in males.     

Early risk factors and adult person--environment relationships in affective disorder

BACKGROUND: Lower cognitive ability, higher neuroticism and symptoms of anxiety and depression in childhood predict non-psychotic disorder in adulthood. This study examined whether these early risk factors act by modifying relationships with life events close to disease onset in adulthood. METHODS: Childhood measures of neuroticism (N) (including maternal N), cognitive ability (CA) and symptoms of anxiety and depression were measured in a national British birth cohort of 5362 individuals born in the week 3-9 March, 1946. At ages 36 and 43 years, mental state examinations were carried out by trained interviewers, and subjects were asked about the occurrence of stressful life events in the previous year (SLE). RESULTS: The effect of aggregated SLEs on mental health was greater in women, in individuals with higher childhood N and poorer childhood mental health. Higher maternal N was also associated with greater sensitivity to SLEs, independent of subject's N, suggesting possible familial transmission of vulnerability. In addition, higher childhood N predicted, independent of later mental health, greater likelihood of reported exposure to SLEs. In general, individuals with higher childhood CA also reported more SLEs. CONCLUSIONS: The results suggest that early risk factors for affective disorder exert effects by modifying person-environment relationships close to onset of adult symptoms. Sensitivity to life events may be transmitted from parents to offspring; psychopathological continuity over the life-span may be explained in part by continuity of altered stress sensitivity.     

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.     

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.     

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

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

Premenstrual mood symptoms: study of familiality and personality correlates in mood disorder pedigrees

We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.     

Reliability and validity of TEMPS-A in a Japanese non-clinical population: application to unipolar and bipolar depressives

BACKGROUND: In Japan, TEMPS-A has gathered much attention, because Kraepelin's concepts on "fundamental states" of mood disorder and temperaments have been widely respected. METHOD: TEMPS-A was translated into Japanese (and after the approval of the English back translation by H.S.A.), it was administered to 1391 non-clinical subjects, and 29 unipolar and 30 bipolar patients in remission. Of the non-clinical sample, 426 were readministered the instrument again in 1 month. A control group matched for gender and age was drawn from the non-clinical sample. RESULTS: Regarding test-retest reliability, Spearman's coefficients for depressive, cyclothymic, hyperthymic, irritable and anxious temperaments were 0.79, 0.84, 0.87, 0.81 and 0.87, respectively; regarding internal consistency, Cronbach's alpha coefficients were 0.69, 0.84, 0.79, 0.83 and 0.87, respectively. The unipolar and bipolar groups showed significantly higher depressive, cyclothymic and anxious temperament scores than the control group. Curiously, the bipolar group showed significantly lower hyperthymic score than the control group; irritable temperament scores showed no significant differences. Depressive, cyclothymic, irritable and anxious temperament scores showed significant correlations with each other. Between the unipolar and bipolar groups, there was little difference regarding the temperament scores. Also the inter-temperament correlations showed the same pattern in the unipolar and bipolar groups. LIMITATION: The clinically well cohort was 70% male. CONCLUSION: TEMPS-A showed a high reliability and validity (internal consistency) in a Japanese non-clinical sample. By and large, the hypothesized five temperament structure was upheld. Depressive, cyclothymic and anxious temperaments showed concurrent validity with mood disorder. Irritable temperament may represent a subtype of depressive, cyclothymic or anxious temperaments. There may be a temperamental commonality between unipolar and bipolar disorders. TEMPS-A will open new possibilities for international research on mood disorder and personality traits.     

Absence of interactions between social support and stressful life events in the prediction of major depression and depressive symptomatology in women

BACKGROUND: While high levels of social support (SS) are associated with a decreased risk for major depression (MD) or less depressive symptomatology, and stressful life events (SLEs) have a substantial causal relationship with MD, uncertainty remains as to whether a main-effect or a buffering model best explains the nature of the relationship among SS, MD and SLEs. METHOD: Using two waves of interview data on 2,163 female twin pairs from a population-based twin registry, and discrete time survival analysis with both logistic and linear regression models, we examine the ability of interactions between eight dimensions of SS and 16 categories of stressful life events to predict MD onset and levels of depressive symptomatology. RESULTS: In the presence of a significant effect of a SLE on MD (beta > or = 100), we found evidence for seven interactions out of a possible 93, of which none involved buffering effects. Similarly, examination of depressive symptomatology detected a total of two interactions (both buffering) out of possible 28. We found no evidence, beyond what would be expected by chance, for the existence of buffering effects where either MD or depressive symptomatology was used as the dependent variable. CoNCLUSIONS: There is little evidence to suggest the presence of the buffering effect of social support in the face of adverse life events for women. We suggest that it is important to use alternative models (multiplicative and additive) to examine data, to investigate the match between stressors and social resources, and to investigate fully whether detected interactions actually represent a buffering effect.     

The DSM-IV and ICD-10 categories of recurrent [major] depressive and bipolar II disorders: evidence that they lie on a dimensional spectrum

BACKGROUND: Presently it is a hotly debated issue whether unipolar and bipolar disorders are categorically distinct or lie on a spectrum. We used the ongoing Ravenna-San Diego Collaboration database to examine this question with respect to major depressive disorder (MDD) and bipolar II (BP-II). METHODS: The study population in FB's Italian private practice setting comprised consecutive 650 outpatients presenting with major depressive episode (MDE) and ascertained by a modified version of the Structured Clinical Interview for DSM-IV. Differential assignment of patients into MDD versus BP-II was made on the basis of discrete hypomanic episodes outside the timeframe of an MDE. In addition, hypomanic signs and symptoms during MDE (intra-MDE hypomania) were systematically assessed and graded by the Hypomania Interview Guide (HIG). The frequency distributions of the HIG total scores in each of the MDD, BP-II and the combined entire sample were plotted using the kernel density estimate. Finally, bipolar family history (BFH) was investigated by structured interview (the Family History Screen). RESULTS: There were 261 MDD and 389 BP-II. As in the previous smaller samples, categorically defined BP-II compared with MDD had significantly earlier age at onset, higher rates of familial bipolarity (mostly BP-II), history of MDE recurrences (>or=5), and atypical features. However, examining hypomania scores dimensionally, whether we examined the MDD, BP-II, or the combined sample, kernel density estimate distribution of these scores had a normal-like shape (i.e., no bimodality). Also, in the combined sample of MDE, we found a dose-response relationship between BFH loading and intra-MDE hypomania measured by HIG scores. LIMITATIONS: Although the interviewer (FB) could not be blind to the diagnostic status of his private patients, the systematic rigorous interview process in a very large clinical population minimized any unintended biases. CONCLUSIONS: Unlike previous studies that have examined the number of DSM-IV hypomanic signs and symptoms both outside and during MDE, the present analyses relied on the more precise hypomania scores as measured by the HIG. The finding of a dose-response relationship between BFH and HIG scores in the sample at large strongly suggests a continuity between BP-II and MDD. Our data indicate that even in those clinically depressed patients without past hypomanic episodes (so-called "unipolar" MDD), such scores are normally rather than bimodally distributed during MDE. Moreover, the absence of a 'zone of rarity' in the distribution of hypomanic scores in the combined total, MDD and BP-II MDE samples, indicates that MDD and BP-II exist on a dimensional spectrum. From a nosologic perspective, our data are contrary to what one would expect from a categorical unipolar-bipolar distinction. In practical terms, intra-MDE hypomania and BFH, especially in recurrent MDD, represent strong indicators of bipolarity.     

A downscaled practical measure of mood lability as a screening tool for bipolar II

BACKGROUND: Current data indicate a strong association between Cyclothymic temperament (and its more ultradian counterpart of mood lability) and Bipolar II (BPII). Administration of elaborate measures of temperament are cumbersome in routine practice. Accordingly, the aim of the present analyses was to test if a practical measure of mood lability was unique to BPII, in comparison with major depressive disorder (MDD). METHODS: Using the Structured Clinical Interview for DSM-IV Axis I Disorders, Clinician Version as modified by us [J. Affect. Disord. 73 (2003) 33; Curr. Opin. Psychiatry 16 (2003) S71], we interviewed 62 consecutive BPII outpatients, as well as their 59 MDD counterparts during a major depressive episode (MDE). Hypomanic symptoms during MDE were systematically assessed: three or more such symptoms defined depressive mixed state (DMX3) on the basis of previous work by us [J. Affect. Disord. 73 (2003) 113]. A downscaled definition of trait mood lability was adapted from Akiskal et al. [Arch. Gen. Psychiatry 52 (1995) 114] and Angst et al. [J. Affect. Disord. 73 (2003) 133], requiring a positive response to one of two queries on whether one is a person with frequent "ups and downs" in mood, and whether such mood swings occur for no reason. The patients selected for inclusion had not received neuroleptics and antidepressants for at least 2 weeks prior to the index episode, they were free of substance and alcohol abuse, and did not meet the DSM-IV criteria for borderline personality disorder (BPD). Associations between mood swings and clinical variables were tested by logistic regression (STATA 7). RESULTS: Mood swings were endorsed by 50.4% of the entire sample: 62.9% of BPII and 37.2% of MDD (p = 0.0047). This practical measure of mood lability was significantly associated with BPII, lower age at onset, high depressive recurrences, atypical features, and DMX3. When controlled for number of major affective episodes, mood swings were still significantly associated with BP-II. Sensitivity and specificity of mood swings for predicting BPII were 62.9% and 62.7%, respectively. LIMITATION: The low specificity of trait mood lability for BPII diagnosis is probably due to the fact that we used a downscaled simplified measure of this trait. CONCLUSIONS: On the other hand, the relatively high sensitivity of our downscaled measure of mood lability for predicting BPII supports its usefulness as a screening tool for this diagnosis. The lack of association between self-reported mood lability and number of major mood episodes indicates that such lability does not reflect the perception of history of frequent episodes, and that it has some validity as a trait indicator. Given that our sample excluded patients meeting the DSM-IV criteria for BPD, contradicts the opinion of the latter manual that such mood lability represents its pathognomonic characteristic that distinguishes it from BPII. The bipolar nature of mood lability is further supported by significant associations with external validating criteria for bipolarity. Overall, these data indicate that in the differential diagnosis between MDD and BPII, trait mood lability favors the latter at a significant statistical level.     

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.     

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.     

Is comorbid borderline personality disorder in patients with major depressive episode and bipolarity a developmental subtype? Findings from the international BRIDGE study

BackgroundThe nature of the relationship between bipolar disorder (BD) and borderline personality disorder (BPD) is controversial. The aim of this study was to characterize the clinical profile of patients with BD and comorbid BPD in a world-wide sample selected during a major depressive episode (MDE).MethodsFrom a general sample of 5635 in and out-patients with an MDE, who were enrolled in the multicenter, multinational, transcultural BRIDGE study, we identified 2658 subjects who met bipolarity specifier criteria. Bipolar specifier patients with (BPD+) and without (BPD?) comorbid BPD were compared on diagnostic, socio-demographic, familial and clinical characteristics.Results386 patients (14.5%) met criteria for BPD. A diagnosis of BD according to DSM-IV criteria was significantly more frequent in the BPD? than in BPD+, while similar rates in the two groups occurred using DSM-IV-Modified criteria. A subset of the BD criteria with an atypical connotation, such as irritability, mood instability and reactivity to drugs were significantly associated withthe presence of BPD. BPD+ patients were significantly younger than BPD? bipolar patients for age, age at onset of first psychiatric symptoms and age at first diagnosis of depression. They also reported significantly more comorbid Alcohol and Substance abuse, Anxiety disorders, Eating Disorder and Attention Deficit Hyperactivity Disorder. In comparison with BPD?, BPD+ patients showed significantly more psychotic symptoms, history of suicide attempts, mixed states, mood reactivity, atypical features, seasonality of mood episodes, antidepressants induced mood lability and irritability, and resistance to antidepressant treatments.LimitationsCenters were selected for their strong mood disorder clinical programs, recall bias is possible with a cross-sectional design, and participating psychiatrists received limited training.ConclusionsWe confirm in a large sample of BD patients with MDE the high prevalence of patients who meet DSM-IV criteria for BPD. Further prospective researches should clarify whether the mood reactivity and instability captured by BPD DSM-IV criteria are distinguishable from the subjective mood of an instable, dysphoric, irritable manic/hypomanic/mixed state or simply represent a phenotypic variant of BD, related to developmental factors.     

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.     

Psychological and immunological predictors of genital herpes recurrence

The relationships among stressful life experience, mood, helper-inducer (CD4+) and suppressor-cytotoxic (CD8+) T cells and genital herpes simplex virus (HSV) recurrence were investigated prospectively in 36 patients with recurrent HSV. The following factors were measured monthly for six months: stressful life experience (including current acute and ongoing stressors, residual effects of previous stressors, and anticipation of future stressors), negative mood, health behaviors, other possible HSV triggers, HSV recurrences, and the proportion of CD4+ and CD8+ cells (in half the sample). Results averaging monthly scores over the six-month study period indicated that: 1) subjects with high levels of stressful experience had a lower proportion of both CD4+ and CD8+ cells, 2) subjects with high levels of depressive mood, anxiety, or hostility had a lower proportion of CD8+ cells, and 3) subjects with high levels of depressive mood who did not report many symptoms of other infections had a higher rate of HSV recurrence. A model is proposed linking depressive mood, CD8+ cells, and HSV recurrence.     

Seasonal variations in bipolar disorder admissions and the association with climate: a population-based study

OBJECTIVE: Although seasonal influences on bipolar disorder admissions have long been observed, the issues of seasonality on different subtypes of mood episodes and the effects of associated climatic parameters remain controversial. This study sets out to examine seasonal variations in bipolar disorder admissions and the association with climate in Taiwan, a subtropical area with fairly constant weather conditions. METHODS: This retrospective population-based study uses the Taiwan National Health Insurance Research Database for 1999-2003, identifying 15,060 admissions for bipolar disorder, comprising of 8631 manic, 2078 depressive and 4351 mixed/unspecified episodes. The auto-regressive integrated moving average model was applied to examine the presence of seasonality and the association with climate in each subtype of mood episodes. RESULTS: Admission peaks were noted during spring/summer, early winter and early spring, for manic, depressive and mixed/unspecified episodes, respectively, while the associations with climatic parameters varied between the subtypes of mood episodes. CONCLUSIONS: Seasonality in bipolar disorder does exist for all subtypes of mood episodes. The distinct seasonal patterns and various associations with the climatic parameters imply different underlying mechanisms for the onset of each subtype of mood episodes. The association between admission rates and certain climatic variables found in this study is informative and could pave the way for future studies aimed at exploring the influence of climate on the psychopathology of bipolar patients as well as the underlying mechanisms.     

Bipolar mood disorders among Polish psychiatric outpatients treated for major depression

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