Recurrence Of Major Depressive Episodes Research Articles

Predicting recurrence of major depressive episodes using the Depression Implicit Association Test: A Canadian biomarker integration network in depression (CAN-BIND) report

Identifying clinically relevant predictors of depressive recurrence following treatment for Major Depressive Disorder (MDD) is critical for relapse prevention. Implicit self-depressed associations (SDAs), defined as implicit cognitive associations between elements of depression (e.g., sad, miserable) and oneself, often persist following depressive episodes and may represent a cognitive biomarker for future recurrences. Thus, we examined whether SDAs, and changes in SDAs over time, prospectively predict depressive recurrence among treatment responders in the CAN-BIND Wellness Monitoring for MDD Study, a prospective cohort study conducted across 5 clinical centres. A total of 96 patients with MDD responding to various treatments were followed an average of 1.01 years. Participants completed the Depression Implicit Association Test (DIAT) – a computer-based measure of SDAs – every 8 weeks on a tablet device. Survival analyses indicated that greater SDAs at baseline and increases in SDAs over time predicted shorter time to MDD recurrence, even after accounting for depressive symptom severity. The findings show that SDAs are a robust prognostic indicator of risk for MDD recurrence, and that the DIAT may be a feasible and low-cost clinical screening tool. SDAs also represent a potential mechanism underlying the course of recurrent depression and are a promising target for relapse prevention interventions.

A novel study design for investigating relapse prevention in major depressive disorder: Preliminary data from the open-label period of a phase 4 vortioxetine study

BackgroundTraditional randomized withdrawal studies have assessed the efficacy of antidepressants for reducing relapse and recurrence of major depressive episodes (MDEs) but have not compared dose reduction, increase, or maintenance within the same study. MethodsHere we present the development, implementation, and preliminary data from the open-label period of an ongoing phase 4, non-traditional, randomized withdrawal study. Designed to evaluate the efficacy of vortioxetine across its approved dose range for relapse prevention, the study enrolled adult patients with recurrent major depressive disorder (MDD), Montgomery-Åsberg Depression Rating Scale (MADRS) ≥ 26, and history of ≥2 MDEs. After a 16-week, open-label, fixed-dose (vortioxetine 10 mg once daily) period, patients meeting response criteria (≥50% reduction in MADRS total score, Weeks 8–16) and remission criteria (MADRS total score ≤12, Weeks 14 and 16) were randomized to vortioxetine 5, 10, or 20 mg, or placebo in a 32-week double-blind treatment period. ResultsOf 1106 patients enrolled, 510 completed the open-label period (mean age: 45.7 years; mean MADRS = 5.0; predominantly female, white, and never smokers) and were eligible for randomization in the ongoing double-blind period. LimitationsStudy is ongoing; only data from the open-label period are available for evaluation. ConclusionsPreliminary analysis suggests that patient baseline characteristics were not a factor in response to and stabilization with vortioxetine during the open-label period. The lack of flexibility in dosing, however, may have reduced the number of patients qualifying for randomization. This study design may provide useful information for optimizing the long-term efficacy and tolerability of vortioxetine treatment for MDD.

Self-abnormality in patients with depression

Self-abnormality in patients with depression has been confirmed in a lot of research results. Negative self-referential processing of depression is associated with higher follow-up depressive symptoms and predicts the recurrence of major depressive episodes. Both self-processing and self-recognition are impaired in depression. The overgeneral autobiographical memory is also a risk factor for onset and maintenance of depression. This review examined self-abnormalities of depression from self-face recognition, self-referential processing and autobiographical memory and summarized the problems of current researches and the future research trends, and may provide insight to explore the self-abnormalities of depression patients comprehensively. Key words: Depression; Self-abnormality; Self-face recognition; Self-referential processing; Autobiographical memory

Investigation of associations between recurrence of major depressive disorder and spinal posture alignment: A quantitative cross-sectional study

The aim of this study was to investigate associations between poor spinal posture and the recurrence of major depressive episodes and severity of symptoms in patients with major depressive disorder (MDD). This was a cross-sectional quantitative study of MDD patients. Outpatients were recruited from consecutive admissions at a mood disorders unit of a tertiary psychiatric hospital. Of 136 MDD patients, 72 (53 women, 19 men; mean age, 42.4±9.1years) met all the criteria and completed the study. Forty-one patients were classified with a recurrent episode (RE) of MDD and 31 with a single episode (SE). Quantitative assessments of postural deviations were made using photogrammetry, including kyphosis, shoulder protraction, and head inclination. The severity of depressive episodes was assessed using the Hamilton Depression Rating Scale. The diagnosis and classification of patients were performed according to DSM-IV-TR and SCID criteria. Multivariate analysis of variance indicated that the RE group had greater anterior head inclination (35.39; SD: 1.57), greater scapular abduction (1.69; SD: 0.93), and worse thoracic kyphosis (139.38; SD: 1.19) than the SE group (p<0.001 for all). Multivariate analysis of covariance showed an interaction between the severity of depressive symptoms and the degree of thoracic kyphosis (p=0.002). Recurrence of depressive episodes is associated with measures of postural misalignment.

Negative Self-Referential Processing Predicts the Recurrence of Major Depressive Episodes

Most individuals who develop Major Depressive Disorder (MDD) will experience a recurrent depressive episode; we know little, however, about cognitive mechanisms that increase the likelihood of recurrence. In the current study we examined whether negatively biased self-referential processing, negative life events, baseline depressive symptoms, and psychotropic medication use predicted the onset of a subsequent depressive episode in a longitudinal study of women with a history of recurrent MDD. Higher levels of depressive symptoms at baseline predicted experiencing a greater number of negative life events which, in turn, tended to predict recurrence of depression. Importantly, after accounting for other associations, negatively biased self-referential processing contributed unique variance to the likelihood of experiencing a depressive episode over the next three years. Thus, negatively biased self-referential processing appears to be a significant risk factor for the recurrence of depressive episodes and may be an important target for interventions aimed at preventing future episodes.

Attentional bias temporal dynamics in remitted depression.

Theory implicates attentional bias (AB) or dysregulated attentional processing of emotional information in the recurrence of major depressive episodes. However, empirical study of AB among remitted depressed patients is limited in scope and has yielded mixed findings. Mixed findings may be accounted for by how the field has conceptualized and thereby studied AB. We propose that a novel temporal dynamic process perspective on AB may help disambiguate extant findings and elucidate the nature of AB in remitted depression. Thus, we reexamined Dot Probe data among remitted depressed patients (RMD; n = 328) and nondepressed controls (NDC; n = 82) that previously yielded null effects when AB was quantified by means of the traditional aggregated mean bias score (Vrijsen et al., 2014). We reanalyzed data using a novel computational approach that extracts a series of bias estimations from trial to trial (Zvielli, Bernstein, & Koster, 2015). Key features of these dynamic process signals revealed moderate to excellent reliability relative to the traditional aggregated mean bias scores. These features of AB dynamics-specifically temporal variability in AB including AB toward and away from emotional stimuli-were significantly elevated among RMDs relative to NDCs. Moreover, among RMDs, a greater number of past depressive episodes were associated with elevation in these features of AB dynamics. Effects were not accounted for by residual depressive symptoms or social anxiety symptoms. Findings indicate that dysregulation in attentional processing of emotional information reflected in AB dynamics may be key to depression vulnerability. (PsycINFO Database Record

EPA-0745 – The evolutif course of the first depressive episode

Introduction Major depression is a debilitating and recurrent disorder with a substantial lifetime risk and a high social cost. Aims - To establish the course of the first major depressive episode (MDE) in a population of students. - To identify the various factors involved in this process. Methods Retrospective and descriptive study on 40 students followed in Psychopedagogie’ consultation in the department of Psychiatry B, Hedi chaker hospital in Sfax Tunisia from 2009 to 2013. The statistical analysis was performed by the SPSS (version 18). Results The average age of the group was 22,8 years. Twenty-three women (57,5%) were included. All of patients were single. The socioeconomic level of the group was fair in 62,5% of cases. Twelve subjects had a family history of psychiatric illness. Prevalence of unipolar depression was 82,5%. Majority of patients were treated with only pharmacological means (77,5%). The general evolutif course in our subjects tends to improvement (37,5%). Six patients had a complete recovery. The persistence of residual symptoms was found in 12 patients. Deterioration in social and professional functioning was reported in12 patients. Six patients have had relapse. The recurrence of MDE was reported in 2 patients. Chronicity was founded in 4 patients. Two patients had a new suicide risk. One patient had an emergence of mood episode. No patient had spontaneous improvement. Nine patients have stopped the follow. The main reason of worsening was the emergence of an intercurrent stress factor (52,5%). Conclusion The negative impact of depression in our patients explains the necessity of a well adapted management.

Long term outcome of primary care depression

We conducted a follow up over 23 years of depressed patients originally presenting to general practice in 1981 and studied in detail at that time. Aims were to assess the long term course and outcome of depression in primary care. Patterns of recovery and recurrence of major depressive episodes, together with other aspects of course, treatment and current state, were assessed at interview. 78% (129) of the original sample were traced to current general practice and outcome data obtained on 54. One third had a prior history of depression. Interview data were obtained on 37 patients. Time to recovery from baseline averaged 10.3 months. The recurrence rate was 64% (23). Most participants suffered at least 2 further episodes that were frequently chronic lasting 2 years on average. Time before first recurrence appeared considerably longer than in comparable psychiatric inpatient samples. No participants were continuously ill. Although loss to follow up limits our conclusions, the course of primary care depression appears worse than suggested by previous, shorter follow ups. Our data suggest that long term risk of a recurrence may be high, but with recurrence delayed.

P01-197 Looking for the cyclothymic temperament within major depressive patients: under-recognising the bipolar spectrum?

Background:Under-recognised bipolar spectrum disorder is going to be one of the most important debates in new articles and researches. Recent data, enlarging bipolar criteria to temperament, family history and more, try to help clinicians in the recognition of the broader spectrum of bipolarity and so getting the most adequate therapeutic attitude.Methods:Consecutive 86 Tunisian patients who meet the DSM IV criteria for major depressive episode (MDE) were interviewed with the temperament evaluation of Memphis,Pisa,Paris and San Diego in order to assess the frequency of cyclothymic temperament (CT).Then we compared the distribution of bipolar criteria, as defined by Akiskal between cyclothymic depressive patients and non cyclothymic ones.Finally the evolution under antidepressants was studied using the GFE:the global functioning evaluation.Results:34.9% of patients meet the criteria of cyclothymic temperament and compared to the 65.1% who did not, they had significantly lower age of onset, higher recurrence of MDE, more atypical features and more suicidal attempts and comorbidities (anxious disorders and drug abuse).Family history of bipolar disorder was more frequently found within the cyclothymic group as well as psychotic symptoms but not with a significant difference. Finally 71.4% of the non cyclothymic patients improved under antidepressants (GFE score &gt;= 70) compared to only 26.6% in the group of cyclothymic ones.Conclusion:If we consider the large criteria of bipolarity and the concept of an affective spectrum, the prevalence of bipolar disorder become higher than previously believed, making clinicians reconsider the relevance of the diagnostic of unipolar trouble and the pertinence of the antidepressant treatment.

Quetiapine and classical mood stabilizers in the long-term treatment of Bipolar Disorder: A 4-year follow-up naturalistic study

Background The aim of this naturalistic study was to compare the effectiveness of quetiapine and classical mood stabilizers, as mono- or combination therapy, in the long-term treatment of Bipolar Disorder (BD). Methods 232 DSM-IV BD I ( n = 91) or BD II ( n = 141) patients, treated and followed up for four years, were studied. Mood stabilizers were chosen by the treating psychiatrists on the basis of their clinical judgement. The sample was subdivided into 6 treatment groups: quetiapine ( n = 41), lithium ( n = 39), sodium valproate ( n = 73), lamotrigine ( n = 31), quetiapine plus lithium ( n = 25), and quetiapine plus sodium valproate ( n = 23). Throughout the 4-year follow-up period patients were assessed monthly, or whenever a recurrence occurred, by the administration of HAMD-21 and of the YMRS. Primary outcome measures were the duration of euthymia and the cumulative proportion of subjects who maintained euthymia. Kaplan–Meier survival analyses were done to tabulate and compare the differences in survival distributions across the different treatment groups (Log-Rank Mantel–Cox test). Results The combined treatments with quetiapine plus lithium or sodium valproate were more effective overall in maintaining euthymia, (percentages of patients who maintained euthymia: 29.3% for quetiapine, 46.2% for lithium, 32.9% for sodium valproate, 41.9% lamotrigine, 80% for quetiapine plus lithium, and 78.3% for quetiapine plus sodium valproate). In addition, quetiapine monotherapy was as effective as lithium monotherapy or combination treatment with lithium or sodium valproate in preventing the recurrence of major depressive episodes. Limitation The main limitations of the study are the lack of randomized, controlled conditions and the low doses of quetiapine used. Conclusion If the results from this study will be replicated, there will be important implications for the use of quetiapine in the long-term treatment of BD.

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Perimenopausal Depression

A tetrachoric factor analysis validation of mixed depression

Background Mixed depression, i.e. a Major Depressive Episode plus co-occurring manic/hypomanic symptoms, has recently become the focus of research. However, its diagnostic validity and bipolar nature are still not firmly supported. A bipolar nature could have significant treatment impacts. Study aim The aim was to psychometrically validate the concept of, and the bipolar nature, of mixed depression, by using (for the first time) tetrachoric factor analysis of its hypomanic symptoms. Methods Consecutive 441 Bipolar II Disorder (BP-II), and 289 Major Depressive Disorder (MDD) outpatients were cross-sectionally assessed for Major Depressive Episode (MDE) and concurrent hypomanic symptoms (as binary variables) when presenting for treatment of depression, by a mood disorder specialist psychiatrist (FB), using the Structured Clinical Interview for DSM-IV (as modified by [Akiskal HS, Benazzi F. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J Clin Psychiatry 2005; 66: 914–921.]) in a private practice. Consecutive 275 remitted BP-II were also assessed for past hypomania. Mixed depression was defined as co-occurrence of MDE and 3 or more, usually subthreshold, hypomanic symptoms. Results In multivariable logistic regression, BP-II independent predictor variables were young onset age, MDE recurrences, mixed depression, and bipolar family history. Factor analysis of past hypomania symptoms found three factors: an “irritable mental overactivity” factor, an “elevated mood” factor, and a “motor overactivity” factor. Factor analysis of intradepression hypomanic symptoms in BP-II, and in MDD, found two similar mental and motor overactivity factors. Multivariate regression of the intradepression hypomanic factors versus bipolar validators, such as bipolar family history and young onset age, found significant associations. Discussion Findings could support the diagnostic validity, and the bipolar nature, of mixed depression, on the basis of the close similarities found between the factor structure of inter-depression hypomania and intra-depression hypomanic symptoms. Impacts on treatment of a bipolar nature of mixed depression may be significant (e.g. more use of mood stabilising agents, less/no use of antidepressants).

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 (≥ 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.

Bipolar family history of the hypomanic symptoms and dimensions of mixed depression

Background There are no data on the bipolar family history (BPFH) of the hypomanic symptoms and dimensions of mixed depression (defined as a depression plus concurrent hypomanic symptoms). These data may be important for the genetics of mixed depression. The study aim was to investigate the BPFH of the hypomanic symptoms of mixed depression. Methods Consecutive 243 bipolar II disorder (BP II) and 189 major depressive disorder (MDD) outpatients, presenting for treatment of a major depressive episode (MDE), were interviewed using the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen. Mixed depression was defined as an MDE plus 3 or more intra-MDE hypomanic symptoms (following a definition validated by Akiskal and Benazzi [J Affect Disord 2003;73:113-22]). Results Major depressive episode with BPFH vs MDE without BPFH had significantly more BP II, lower age of onset, more MDE recurrences, more atypical depressions, more mixed depressions, and more intra-MDE hypomanic symptoms (irritability, racing/crowded thoughts, psychomotor agitation, more talkativeness, distractibility). Factor analysis of intra-MDE hypomanic symptoms found 2 factors (dimensions): one factor including psychomotor agitation and more talkativeness, and one factor including racing/crowded thoughts, irritability, and distractibility. Logistic regression showed that mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions. There was a dose-response relationship between number of intra-MDE hypomanic symptoms and BPFH loading (marked increase at n = 3) in the entire BP II and MDD sample. Conclusions Findings showed that hypomanic symptoms were more common in the MDE with BPFH of BP II and of MDD, suggesting that a bipolar vulnerability may be required for mixed depression. Mixed depression was more strongly associated with BPFH than hypomanic symptoms and dimensions, suggesting that it could be the focus of future FH studies.

Depressive Mixed State: A Feature of the Natural Course of Bipolar II (and Major Depressive) Disorder?

Background: Depressive mixed state (DMX), i.e., a combination of hypomanic and depressive symptoms during the same episode, has recently seen a rebirth of studies after Kraepelin’s description. Kraepelin observed, in an inpatient sample, that DMX was related to the number of episodes and to duration of manic-depressive insanity (illness). Study Aim: The aim was to test Kraepelin’s observations in a very different sample. Methods: 563 consecutive outpatients with major depressive episode (MDE) – 320 with bipolar II disorder and 243 with major depressive disorder – were interviewed, in a private practice, by the Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal (2003). Hypomanic symptoms during MDE were systematically assessed in patients while off psychoactive drugs. DMX was dimensionally defined, following Akiskal and Benazzi (2003), as an MDE plus 3 or more combined hypomanic symptoms. Kraepelin’s examples of DMX, i.e., agitated depression (MDE plus psychomotor agitation) and depression with flight of ideas (MDE plus racing thoughts) were also tested. Univariate and multivariate logistic regression was used to study associations. Results: DMX was present in 49.5% of the patients. Multiple logistic regression of DMX versus MDE recurrences and duration of illness, controlled for age, found a strong and significant association only between DMX and duration of illness. The same association was found between agitated depression and duration of illness (but not in depression with racing thoughts). Limitation: There was only a single interviewer. Discussion: The findings support Kraepelin’s observation of a link between DMX and durations of illness, but not that between DMX and recurrences. Onset of DMX could be more related to the natural course of manic-depressive illness than to a kindling process.

A longitudinal population-based study of treated and untreated major depression.

Few studies have investigated the factors associated with different outcomes in individuals with major depressive episode (MDE) in relation to mental health service utilization. This study was to, in depressed individuals who used and did not use mental health services, 1) compare the demographic, psychosocial, and clinical characteristics; 2) estimate the risk of MDE in a 6-year follow-up period; and 3) identify the factors associated with the persistence/recurrence of MDE. This was a population- based longitudinal analysis. Participants included the longitudinal cohort of the Canadian National Population Health Survey who reported MDE at the baseline survey (n = 609). MDE was measured by the Composite International Diagnostic Interview-Short Form for Major Depression. In the 6-year follow-up period, 49.8% of participants with treated depression developed subsequent MDE; 28.7% of those with untreated depression reported MDE. Multivariate analyses showed that, among those who reported the use of mental health services, childhood and adulthood traumatic events and functional impairment were related to the recurrence of MDE. Among those who did not use mental health services, reported negative life events and the severity of depressive symptoms were predictive of recurrent MDE. The risk of the recurrence of MDE and associated factors differ in mental health service users and nonusers. Future studies need to confirm these results and to identify service barriers for those who do not use the services and who are at a high risk of MDE.

Bipolar II disorder family history using the family history screen: findings and clinical implications

Psychiatric family history of bipolar II disorder is understudied. The aims of the current study were to find the psychiatric family history of bipolar II patients using a new structured interview, the Family History Screen by Weissman et al (2000), and to find bipolar disorders family history predicting power for the diagnosis of bipolar II. One hundred sixty-four consecutive unipolar major depressive disorder (MDD) and 241 consecutive bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV (SCID). The Family History Screen was used. Sensitivity and specificity of predictors of the diagnosis of bipolar II (bipolar [type I and II] family history, bipolar II family history, atypical depression, depressive mixed state, many MDE recurrences, early onset) were studied. Bipolar II subjects had significantly more bipolar I, more bipolar II (50.7%), more MDE, and more social phobia in first-degree relatives than did unipolar subjects. Bipolar II subjects had many more first-degree relatives with bipolar II than with bipolar I. Among the predictors of the diagnosis of bipolar II, bipolar II family history had the highest specificity (82.8%), while early onset had the highest sensitivity. Discriminant analysis of predictor variables found that bipolar II family history and early onset were highly significant predictors. In conclusion, bipolar II family history was common in bipolar II patients, and it had high specificity for predicting bipolar II. If detected, it could reduce bipolar II misdiagnosis by inducing careful probing for a history of hypomania.

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.

Unipolar depression with bipolar family history: links with the bipolar spectrum.

The aim of the present paper was to find if unipolar major depressive disorder (MDD) with bipolar family history could be included in the bipolar spectrum, by comparing it to unipolar MDD without bipolar family history, and to bipolar II disorder, on typical bipolar variables. A sample of 280 consecutive bipolar II outpatients, and a sample of 135 consecutive unipolar MDD outpatients, presenting for major depressive episode (MDE) treatment, were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn). Hypomanic symptoms during the MDE were systematically assessed. Clinical variables used to validate the inclusion of unipolar MDD with bipolar family history in the bipolar spectrum were young age of onset, many MDE recurrences, atypical features, and depressive mixed state (DMX; an MDE plus >2 concurrent hypomanic symptoms), following many previous studies reporting that these variables were typical features of bipolar disorders. Means were compared by t-test and frequencies by chi2 test (stata 7). Two-tailed P < 0.05 was chosen. Unipolar MDD with bipolar family history was present in 20% of MDD patients. Comparisons among unipolar MDD with bipolar family history (UP+BPFH), unipolar MDD without bipolar family history (UP-BPFH), and bipolar II (BPII), found that UP+BPFH versus UP-BPFH had a significantly lower age, lower age of onset, fewer recurrences, and more DMX; that UP+BPFH versus BPII had no significant differences (apart from recurrences); and that UP-BPFH versus BPII had significantly different age, age of onset, recurrences, atypical features, and DMX. Findings suggest that UP+BPFH shows many bipolar signs, and that it could therefore be included in the bipolar spectrum. Unipolar MDD with bipolar family history had a clinically significant 20.0% frequency in the unipolar MDD sample, supporting the clinical usefulness of this depression subtype. The subtyping of MDD based on bipolar family history could have treatment implications.

Clinical differences between bipolar II depression and unipolar major depressive disorder: lack of an effect of age

Background: Inconsistent clinical differences were reported in bipolar II versus unipolar depression. Age difference may be a confounding factor. Study aims were to describe the clinical and family history features of bipolar II versus unipolar depression, and to control for the possible counfounding effect of age on clinical features. Methods: Consecutive 126 unipolar and 187 bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. Variables studied were gender, age, age of onset, MDE recurrences, axis I comorbidity, MDE severity, psychotic, melancholic, and atypical features, depression chronicity, melancholic, atypical, and hypomanic symptoms, depressive mixed state-DMX3 (MDE+three or more concurrent hypomanic symptoms), and mood disorders family history. The effect of age on clinical differences was controlled by logistic regression (by adding age as an independent variable after each independent variable). Results: Bipolar II had significantly lower age, lower age of onset, more recurrences, more atypical features, more DMX3, more family history of bipolar II and MDE. Almost all the clinical differences found significant in the first analysis resulted still significant when controlled for age. Limitations: Single interviewer, non-blind, cross-sectional assessment, bipolar II diagnosis based on history. Conclusions: Results confirmed previous findings, and showed that bipolar II—unipolar MDE clinical differences were not related to age.