Anger attacks in major depressive disorder and serum levels of homocysteine.

BACKGROUND: Increased levels of homocysteine have been associated with anger and depression separately. We investigated the association of anger attacks in major depressive disorder (MDD) with serum levels of homocysteine. METHODS: Homocysteine serum levels were measured in 192 outpatients with nonpsychotic MDD, mean age 39.9 +/- 10.7 (range 19-65), 53% women, at baseline of an open-trial antidepressant treatment. We used the Massachusetts General Hospital Anger Attacks Questionnaire to evaluate anger attacks, the Structured Clinical Interview for DSM-III-R Axis I Disorders-Patient Edition (SCID-I/P) to diagnose MDD and the 17-item Hamilton Rating Scale for Depression to measure depression severity. RESULTS: In the multiple regression analysis split by anger attacks adjusted for parameters of depression, creatinine, vitamin B(12), folate, age, smoking, and alcohol consumption, serum levels of homocysteine were positively correlated with length of current major depressive episode (t value, 3.01; 95% confidence interval [CI], .09 to .43; p = .004) and HAM-D-17 scores (t value, 2.48; 95% CI, .07 to 0.64; p = .016) in patients with anger attacks but not in those without anger attacks. CONCLUSIONS: Anger attacks in MDD may moderate the relationship of homocysteine serum levels with the severity and length of the depressive episode. Future studies are warranted to confirm and clarify the nature of this moderating effect.     

Anger Attacks in Depressed Turkish Outpatients

Anger attacks have been described as sudden spells of anger accompanied by symptoms of autonomic activation and have been experienced by patients as uncharacteristic of them and inappropriate to the situations in which they had occurred. The aim of this study was to assess the prevalence of anger attacks in a non-Western depressed population. We also wanted to see whether depression in patients with anger attacks was qualitatively different from depression without anger attacks. The Anger Attacks Questionnaire, designed by Fava et al. to assess these attacks, was administered to 88 medication-free consecutive outpatients diagnosed as major depression according to DSM-IV criteria by two psychiatrists. The patients also were assessed by the Beck Depression Inventory, the Beck Anxiety Inventory, the Beck Hopelessness Scale, and the Spielberger's State-Trait Anger Expression Inventory. Forty-three (49%) of these patients had reported having anger attacks. The patients with anger attacks were significantly more depressed and anxious than patients without anger attacks. Anger-out and trait anger measures were significantly higher in depressed patients with anger attacks than patients without anger attacks. Patients with anger attacks also scored higher in hopelessness measure and there was a trend toward statistical significance. Our results are in line with previous literature which show, that anger attacks are prevalent in depressed patients. We also conclude that patients with anger attacks constitute a more depressed population than those without anger attacks. Severity of depression emerges as the strongest predictor of the presence of anger attacks in our study.     

Mood patterns and classification in bipolar disorder

PURPOSE OF REVIEW: The aim of this review is to highlight recent studies that have questioned the current split of mood disorders into the categories of bipolar and depressive disorders. RECENT FINDINGS: A continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder was supported by several lines of evidence: depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support the splitting between mania/hypomania and depression); family history, major depressive disorder is the most common mood disorder in relatives of bipolar probands; lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; bipolar features in major depressive disorder; major depressive disorder shifting to bipolar disorders; history of manic/hypomanic symptoms in major depressive disorder and correlation between lifetime manic/hypomanic symptoms and depressive symptoms in major depressive disorder; factors of hypomania inside major depressive disorder; recurrent course of major depressive disorder; depression more common than mania and hypomania in bipolar disorders; trait mood lability in major depressive disorder. SUMMARY: This review of the recent findings on the relationship between bipolar disorders (especially bipolar II disorder) and depressive disorders seems to support a continuity among mood disorders, and runs against the current classification of mood disorders dividing them into independent categories. Further research is needed in the area, in part because of its possible treatment impact.     

Family history validation of a definition of mixed depression

PURPOSE: The study aim was to test different definitions of mixed depression, defined as a depression with concurrent hypomanic symptoms. METHODS: Consecutive 245 non-tertiary care outpatients with bipolar II disorder (BP-II) and 189 non-tertiary care outpatients with major depressive disorder (MDD) were interviewed (off psychoactive drugs) using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis I Disorders-Clinician Version, Hypomania Interview Guide (HIG), and Family History Screen when presenting for major depressive episode (MDE) treatment. Intra-MDE hypomanic symptoms were systematically assessed. Mixed depression was defined as an MDE with concurrent hypomanic symptoms. Receiver operating characteristic (ROC) analysis and multivariate analysis were used to test different definitions of mixed depression (dimensional and categorical ones). Factor analysis was also used. Bipolar family history was the validator. FINDINGS: Bipolar II disorder, vs MDD, had significantly more intra-MDE hypomanic symptoms (racing/crowded thoughts, irritable mood, psychomotor agitation, more talkativeness, and increased goal-directed and risky activities). Major depressive episode plus 3 or more hypomanic symptoms was present in 68.7% of BP-II and 42.3% of MDD. A "motor activation" factor, including psychomotor agitation and talkativeness, and a "mental activation" factor including racing/crowded thoughts were found. Different definitions (dimensional and categorical ones) of mixed depression were tested vs bipolar family history as validator (ie, MDE plus more than 1, 2, 3, and 4 concurrent hypomanic symptoms, MDE plus psychomotor agitation, MDE plus racing thoughts). Major depressive episode plus more than 1 hypomanic symptom had the highest sensitivity but the lowest specificity. Instead, MDE plus more than 4 hypomanic symptoms had the lowest sensitivity and the highest specificity. The better-balanced combination of sensitivity and specificity was shown by MDE plus more than 2 hypomanic symptoms. The same definition also showed the highest ROC area value. Multivariate regression of bipolar family history vs different mixed depression definitions found that the only strong and significant predictor was MDE plus more than 2 hypomanic symptoms. A dose-response relationship was found between the number of hypomanic symptoms during MDE and the bipolar family history loading. CONCLUSIONS: Mixed depression (MDE plus 3 or more hypomanic symptoms) was common in BP-II and MDD. A dimensional definition based on 3 or more hypomanic symptoms during depression was the most supported by using bipolar family history as validator. The study of mixed depression may be important for its possible impact on treatment (antidepressants could increase hypomanic symptoms, and mood stabilizers and antipsychotics could control hypomanic symptoms during antidepressant treatment).     

The relation between anger expression, depression, and somatic symptoms in depressive disorders and somatoform disorders

BACKGROUND: In previous studies, the relationship between either anger suppression and depression or anger suppression and somatic symptoms was examined. However, the relationship between anger expression, depression, and somatic symptoms was not examined in depressive disorders and somatoform disorders. METHOD: The DSM-IV-diagnosed subjects included 73 patients with depressive disorders and 47 patients with somatoform disorders. The Anger Expression Scale was used to assess the level of anger expression or suppression. The severity of depression was assessed using the Symptom Checklist-90-Revised (SCL-90-R). The Somatization Rating Scale and the SCL-90-R somatization subscale were used to assess the severity of somatic symptoms. Data were collected from March 2000 to March 2001. RESULTS: The results of the path analyses showed that in depressive disorder patients, anger expression had a stronger effect on somatic symptoms through depression than did anger suppression, although both anger expression and anger suppression had a significant indirect effect on somatic symptoms. The depressive disorder group also showed a significant but negative direct effect of anger suppression on anger expression in the path from anger suppression to anger expression to depression to somatic symptoms. However, only anger suppression had an indirect effect on somatic symptoms through depression in somatoform disorder patients. CONCLUSIONS: The results suggest that anger expression might play a more predominant role in depression and somatic symptoms of depressive disorder patients than anger suppression, but only anger suppression might be associated with depression and somatic symptoms of somatoform disorder patients. In addition, incomplete anger suppression followed by anger expression is likely to be associated with depression and somatic symptoms in depressive disorders.     

Prevalence of anger attacks in depressive and anxiety disorders: Implications for their construct?

Aims: The present study explores anger attacks in depressive and anxiety disorders for their prevalence and some of the clinical and psychosocial correlates. Methods: The sample comprised of patients with ICD‐10‐diagnosed depressive and anxiety disorders (n = 328). All the subjects were given a demographic and clinical profile sheet, the Irritability Depression Anxiety Scale, World Health Organization Quality of Life – BREF Version and the Anger Attack Questionnaire. Using the Anger Attack Questionnaire they were divided into two groups – with anger attacks (n = 170) and without anger attacks (n = 158) – in order to study the differential profile of the two groups. Results: Anger attacks were associated with more anxiety and irritability, and poorer quality of life. Frequency of anger attacks had a positive correlation with depression, irritability and aggression, and a negative correlation with education, income, and quality of life. Panic attacks, somatic anxiety and psychological domain of quality of life predicted the categorization of subjects into those with and without anger attacks. Conclusion: Anger attacks are common among depressive and anxiety disorder cases and have a negative impact on quality of life. Status of anger attacks as either linked to anxiety and/or depression, or as an independent syndrome needs further study.     

Challenging the unipolar–bipolar division: Does mixed depression bridge the gap?

BACKGROUND: Mixed states, i.e., opposite polarity symptoms in the same mood episode, question the categorical splitting of mood disorders in bipolar disorders and unipolar depressive disorders, and may support a continuum between these disorders. Study aim was to find if there were a continuum between hypomania (defining BP-II) and depression (defining MDD), by testing mixed depression as a 'bridge' linking these two disorders. A correlation between intradepressive hypomanic symptoms and depressive symptoms could support such a continuum, but other explanations of a correlation are possible. METHODS: Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were interviewed, cross-sectionally, with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (to assess intradepressive hypomanic symptoms) and the Family History Screen, by a mood disorders specialist psychiatrist in a private practice. Patients presented voluntarily for treatment of depression when interviewed drug-free and had many subsequent follow-ups after treatment start. Mixed depression (depressive mixed state) was defined as the combination of MDE (depression) and three or more DSM-IV intradepressive hypomanic symptoms (elevated mood and increased self-esteem were always absent by definition), a definition validated by Akiskal and Benazzi. RESULTS: BP-II, versus MDD, had significantly lower age at onset, more recurrences, atypical and mixed depressions, bipolar family history, MDE symptoms and intradepressive hypomanic symptoms. Mixed depression was present in 64.5% of BP-II and in 32.1% of MDD (p=0.000). There was a significant correlation between number of MDE symptoms and number of intradepressive hypomanic symptoms. A dose-response relationship between frequency of mixed depression and number of MDE symptoms was also found. CONCLUSIONS: Differences on classic diagnostic validators could support a division between BP-II and MDD. Presence of intradepressive hypomanic symptoms by itself, and correlation between intradepressive hypomanic symptoms and depressive symptoms could instead support a continuum. Other explanations of such a correlation are possible. Depending on the method used, a BP-II-MDD continuum could be supported or not.     

低年级大学生中与愤怒特质相关联的躯体化:家庭亲密度和适应性的调节作用

背景:22%至58%的患者在初级保健机构主诉躯体症状.既往研究发现躯体化与愤怒特质和家庭功能相关.然而,有关研究却非常缺乏,特别是评估家庭功能在愤怒特质如何成为躯体主诉中的调节作用.目的:本研究的目的是验证家庭亲密度和适应性的变化是否调节愤怒特质和躯体化之间的关系强度.方法:采用横断面研究设计并从上海一所综合性大学招募2008名大学生.所有参加者完成问卷,包括采用症状自评量表(SCL-90)、状态-特质愤怒表达量表2(STAXI-2中文版)、家庭亲密度和适应性量表第二版(FACES II中文版)来评估其当前的躯体化程度、愤怒特质与家庭功能.采用分层线性回归分析(进入)分别对男性和女性验证家庭亲密度和适应性对愤怒和躯体化之间的关联性的调节作用.结果:躯体症状在男性女性中均与抑郁和愤怒特质以预期的方向显著相关.家庭亲密度和家庭适应性与躯体症状呈负相关.女大学生家庭亲密度对愤怒特质和躯体化之间的联系起到调节作用,而男大学生家庭亲密度的调节作用是轻微的.变量目前抑郁症状矫正后,家庭适应能力的调节作用在男性和女性中均没有显著性.结论:容易愤怒是躯体化的一个独立预测因素.对于女性来说,较高的家庭凝聚力是一种保护因素,可以减少愤怒特质对躯体症状的影响.没有当前抑郁的共病的话,家庭适应性在一定程度上可以避免有愤怒倾向的个体发展为躯体化.家庭凝聚力培养、家庭灵活性培养和抑郁治疗相结合的干预措施可能对有愤怒特质的躯体化患者更有效.     

Inositol augmentation of lithium or valproate for bipolar depression

OBJECTIVE: Despite promising new therapies, bipolar depression remains difficult to treat. Up to half of patients do not respond adequately to currently approved treatments. This study evaluated the efficacy of adjunctive inositol for bipolar depression. METHODS: Seventeen participants with DSM-IV criteria for bipolar depression and a 17-item Hamilton Rating Scale for Depression (HRSD) > or =15 on proven therapeutic levels of lithium or valproate for >2 weeks were randomized to receive double-blind inositol or placebo for 6 weeks. At the end of double-blind treatment, subjects were eligible for an 8-week open-label trial of inositol. RESULTS: Response was defined a priori as >50% reduction in the HRSD and a Clinical Global Impression of 1-2. Four of nine subjects (44%) on inositol and zero of eight subjects on placebo met response criteria (p = 0.053). There was no difference between groups in the average change score for the HRSD or Young Mania Rating Scale (YMRS). Response to inositol was highly variable. Of nine subjects randomized to inositol, two had >50% worsening in HRSD scores at the end of treatment, three had no change and four had >50% improvement. Those who had worsening in depressive symptoms on inositol had significantly higher scores at baseline on the YMRS total score and irritability, disruptive/aggressive behavior and unkempt appearance items. CONCLUSIONS: There was a trend for more subjects on inositol to show improvement in bipolar depression symptoms, but, on average, inositol was not more effective than placebo as an adjunct for bipolar depression. Baseline levels of anger or hostility may be predictive of clinical response to inositol.     

Various forms of depression

The current subtyping of depression is based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed, Text Revision (DSM-IV-TR) categorical division of bipolar and depressive disorders. Current evidence, however, supports a dimensional approach to depression, as a continuum/spectrum of overlapping disorders, ranging from bipolar I depression to major depressive disorder. Types of depression which have recently been the focus of most research will be reviewed: bipolar II depression, mixed depression, agitated depression, atypical depression, melancholic depression, recurrent brief depression, minor depressive disorder, seasonal depression, and dysthymic disorder. Most research has focused on bipolar II depression, mixed depression (defined by depression and superimposed manic/hypomanic symptoms), and atypical depression. Mixed depression, by its combination of opposite polarity symptoms, has been found to be common by systematic probing for co-occurring manic/hypomanic symptoms. Mixed depression is a treatment challenge for clinicians, because antidepressants alone (ie, not protected by mood-stabilizing agents) may worsen its manic/hypomanic symptoms, such as irritability and psychomotor agitation, which the Food and Drug Administration (FDA) has listed as possible precursors to suicidality.     

Pramipexole for bipolar II depression: a placebo-controlled proof of concept study.

BACKGROUND: The original serotonergic and noradrenergic hypotheses do not fully account for the neurobiology of depression or mechanism of action of effective antidepressants. Research implicates a potential role of the dopaminergic system in the pathophysiology of bipolar disorder. The current study was undertaken as a proof of the concept that dopamine agonists will be effective in patients with bipolar II depression. METHODS: In a double-blind, placebo-controlled study, 21 patients with DSM-IV bipolar II disorder, depressive phase on therapeutic levels of lithium or valproate were randomly assigned to treatment with pramipexole (n = 10) or placebo (n = 11) for 6 weeks. Primary efficacy was assessed by the Montgomery-Asberg Depression Rating Scale. RESULTS: All subjects except for one in each group completed the study. The analysis of variance for total Montgomery-Asberg Depression Rating Scale scores showed a significant treatment effect. A therapeutic response (>50% decrease in Montgomery-Asberg Depression Rating Scale from baseline) occurred in 60% of patients taking pramipexole and 9% taking placebo (p =.02). One subject on pramipexole and two on placebo developed hypomanic symptoms. CONCLUSIONS: The dopamine agonist pramipexole was found to have significant antidepressant effects in patients with bipolar II depression.     

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.     

Intra-episode hypomanic symptoms during major depression and their correlates

Recent studies have shown that 40-50% of major depressive disorders (MDD) may become bipolar with time. Intra-episode hypomanic symptoms in MDD may be a first step in this shift. The purpose of the present study was to find factors associated with intra-episode hypomanic symptoms in MDD. Two hundred and forty-three consecutive MDD outpatients were interviewed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV), Clinician Version (SCID-CV), as modified by Benazzi and Akiskal (J. Affect. Disord. 2003; 73: 33-38). History of hypomania and presence of hypomanic symptoms during major depressive episode (MDE) were systematically assessed. Intra-episode hypomanic symptoms were defined as an MDE combined with three or more hypomanic symptoms, following Akiskal and Benazzi (J. Affect. Disord. 2003; 73: 113-122). Major depressive disorder with intra-episode hypomanic symptoms (MDD + H) was compared to MDD without hypomanic symptoms on classic bipolar validators. It was found that MDD + H (usually irritability, distractibility, racing thoughts, psychomotor agitation, and more talkativeness) was present in 32.5% of patients. Patients with MDD + H versus MDD had significantly lower age at onset, more atypical depressions, and more bipolar family history. Recurrences were not significantly different. Multivariate logistic regression found that bipolar family history and atypical depression were significantly and independently associated with MDD + H. Findings suggest that MDD + H may be associated with a bipolar vulnerability. Duration of illness and recurrences do not seem to be important for the onset of MDD + H. Bipolar genetic vulnerability seems to be required for onset of intra-episode hypomanic symptoms in MDD. Intra-episode hypomanic symptoms might be the first step of a process leading to the switch of MDD to bipolar disorders. Predicting the switch might have important treatment implications, because antidepressants used alone may worsen the course of bipolar disorders. Prospective studies are required to support these findings and hypotheses.     

The potential relationship between levels of perceived stress and subtypes of major depressive disorder (MDD)

OBJECTIVE: We wanted to explore whether major depressive disorder (MDD) subtypes (melancholic depression, atypical depression, double depression, and MDD with anger attacks) were related to levels of perceived stress, as measured by the Perceived Stress Scale (PSS). METHOD: Our sample [n = 298; female = 163 (55%); mean age 40.1 +/- 10.5 years] consisted of out-patients with MDD. The Structured Clinical Interview for DSM-III-R, the 17-item Hamilton Rating Scale for Depression, the Anger Attack Questionnaire, and the PSS were administered prior to initiating treatment. RESULTS: Depressed women had significantly higher levels of perceived stress (P = 0.02) than depressed men. Greater severity of depression at baseline was significantly related to higher levels of perceived stress (P < 0.0001). After adjusting for age, gender, and severity of depression at baseline, higher levels of perceived stress were significantly related to the presence of anger attacks (P < 0.0001; t = -4.103) as well as to atypical depression (P = 0.0013; t = 3.26). CONCLUSION: Out-patients with MDD who are more irritable and/or present with atypical features have higher levels of perceived stress, indicating a potential reactive component to their depression.     

Major depressive episodes with hypomanic symptoms are common among depressed outpatients

Depressive mixed states (major depressive episodes [MDE] with some hypomanic symptoms) are not classified in DSM-IV. The aim of the present study was to determine the prevalence of depressive mixed states in depressed outpatients, and to compare bipolar II with unipolar depressive mixed states. Seventy consecutive bipolar II and unipolar depressed outpatients were interviewed using the DSM-IV Structured Clinical Interview (SCID). At least one hypomanic symptom was present in 90% of patients, and three or more in 28.5%. Symptoms of depressive mixed states included irritable mood, distractibility, racing thoughts, and increased talking. Bipolar II subjects had more concurrent hypomanic symptoms (three or more in 48.7% v 3.2%, P = 0.000). Depressive mixed states with three or more hypomanic symptoms correctly classified 70.0% of bipolar II subjects. These findings have important treatment implications, as antidepressants may worsen the symptoms of depressive mixed states, and mood stabilizers can be useful.     

Clinical indicators for the use of antidepressants in the treatment of bipolar I depression

Objectives:  Current guidelines provide little practical information on the clinical characteristics of bipolar I patients who are likely to benefit from the combination of a mood stabilizer and an antidepressant. Rather, guidelines simply state that an adjunctive antidepressant is recommended in cases of 'severe' depression. Our objective was to evaluate the clinical and demographic differences between patients who remitted on a mood stabilizer alone and patients who subsequently required an adjunctive antidepressant to achieve stabilization.
Methods:  We retrospectively compared the pharmacological treatment strategies of 39 patients with bipolar I disorder who were in a current depressive episode. Patients who did not respond to mood stabilizer monotherapy were prescribed an adjunctive antidepressant. We evaluated the clinical differences at baseline and week 1, 2 and 3 of treatment between patients stabilizing on a mood stabilizer alone and patients that did not remit until they subsequently received an adjunctive antidepressant.
Results:  Patients who required an adjunctive antidepressant had significantly higher total Hamilton Depression Rating (HRS-D) scores at week 1, 2 and 3 of treatment, but not at baseline. Patients who remitted on mood stabilizer monotherapy were more likely to be married, achieved stabilization in less time, presented with higher Young Mania Rating Scale (YMRS) scores, and experienced the previous episode of depression more recently than patients who required an antidepressant.
Conclusions:  Our findings suggest that rapid improvement after achieving a therapeutic dose of a mood stabilizer is clinically significant and represents a surrogate endpoint in the treatment of bipolar I depression. Larger, prospective, and controlled studies are needed to verify our results and to identify additional indicators for a mood stabilizer and antidepressant combination treatment strategy.     

Development and validation of the Affective Self Rating Scale for manic, depressive, and mixed affective states

Most rating scales for affective disorders measure either depressive or hypomanic/manic symptoms and there are few scales for hypomania/mania in a self-rating format. We wanted to develop and validate a self-rating scale for comprehensive assessment of depressive, manic/hypomanic and mixed affective states. We developed an 18-item self-rating scale starting with the DSM-IV criteria for depression and mania, with subscales for depression and mania. The scale was evaluated on 61 patients with a diagnosis of affective disorder, predominantly bipolar disorder type I, using Montgomery-Asberg Depression Rating Scale (MADRS), Hypomania Interview Guide-Clinical version (HIGH-C) and Clinical Global Impression scale, modified for bipolar patients (CGI-BP) as reference scales. Internal consistency of the scale measured by Cronbach's alpha was 0.89 for the depression subscale and 0.91 for the mania subscale. Spearman's correlation coefficients (two-tailed) between the depression subscale and MADRS was 0.74 (P<0.01) and between mania subscale and HIGH-C 0.80 (P<0.01). A rotated factor analysis of the scale supported the separation of symptoms in the mania and depression subscale. We established that the self-rating scales sensitivity to identify mixed states, with combined cut-offs on the MADRS and HIGH-C as reference, was 0.90 with a specificity of 0.71. The study shows that the Affective Self Rating Scale is highly correlated with ratings of established interview scales for depression and mania and that it may aid the detection of mixed affective states.     

Fenfluramine challenge in unipolar depression with and without anger attacks

We have previously hypothesized that patients with major depression and anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks. We wanted to compare the prolactin response to fenfluramine challenge, as an indirect measure of central serotonergic function, in depressed patients with and without anger attacks. We recruited 37 outpatients (22 men and 15 women; mean age: 39.5+/-10.5) with DSM-III-R major depressive disorder, diagnosed with the SCID-P. Their initial 17-item Hamilton Rating Scale for Depression score was >/=16. Patients were classified as either having or not having anger attacks with the Anger Attacks Questionnaire. All patients received a single-blind placebo challenge followed by a fenfluramine challenge (60 mg orally) the next day. Plasma prolactin measurements were obtained with double antibody radioimmunoassay before and after both placebo and fenfluramine challenges, and fenfluramine and norfenfluramine blood levels after each challenge were determined by gas chromatography. Of the 37 study participants, 17 (46%) were classified as having anger attacks. There were no significant differences in age, gender, fenfluramine, or norfenfluramine blood levels between depressed patients with and without anger attacks. Depressed patients with anger attacks showed a significantly blunted prolactin response to fenfluramine challenge compared to patients without anger attacks. As previous studies have shown blunted prolactin responses to fenfluramine in impulsive aggression among patients with personality disorders, our results support our hypothesis that depressed patients with anger attacks may have a relatively greater serotonergic dysregulation than depressed patients without these attacks.     

Mixed depression: a clinical marker of bipolar-II disorder

BACKGROUND: Recent studies have found that mixed depression [i.e., a major depressive episode (MDE) plus intra-MDE hypomanic symptoms] is common in bipolar-II disorder (BP-II), and not uncommon in major depressive disorder (MDD) depressed outpatients. Study aim was to test the predictive power for the diagnosis of BP-II of several dimensional definitions of mixed depression, searching for a clinical marker which could reduce the current underdiagnosis of BP-II. METHODS: Consecutive 348 BP-II and 254 MDD depressed outpatients were interviewed by the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Intra-MDE hypomanic symptoms were systematically assessed. Mixed depression was defined as an MDE plus intra-MDE hypomanic symptoms. RESULTS: Dimensional definitions of mixed depression (at least 2, 3, 4, 5 or more intra-MDE hypomanic symptoms) were tested for predicting BP-II. A definition requiring 2 or more hypomanic symptoms had the highest sensitivity, the lowest specificity, and the lowest positive predictive value. A definition requiring 5 or more hypomanic symptoms had the highest specificity, the lowest sensitivity, and the highest positive predictive value. The most balanced combination of sensitivity and specificity was found for a definition requiring 3 or more hypomanic symptoms. This definition had the highest positive predictive value, and the highest ROC area (i.e., the best global performance). This definition had also the most balanced combination of sensitivity and specificity for predicting bipolar family history. In order to validate this definition as a clinical marker of BP-II, as bipolar validators were used BP-II, young onset, many recurrences, atypical depression features, and bipolar family history (the most important one). Univariate logistic regression found that this definition was associated with most bipolar validators, especially bipolar family history. Multiple logistic regression found that bipolar family history was its strongest predictor. CONCLUSIONS: Findings suggest that a definition of mixed depression requiring 3 or more intra-MDE hypomanic symptoms may be a useful clinical marker for predicting the diagnosis of BP-II. Presence of mixed depression should lead to skillful probing for history of hypomania, which would probably reduce the BP-II misdiagnosed as MDD. Findings may also impact treatment of BP-II, as intra-MDE hypomanic symptoms may become more severe by antidepressants alone, and mood stabilising agents may be required before (or concurrently with) antidepressants.     

The relationship of major depressive disorder to bipolar disorder: Continuous or discontinuous?

Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin’s unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.