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

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

Prevalence and clinical significance of subsyndromal manic symptoms, including irritability and psychomotor agitation, during bipolar major depressive episodes

BackgroundThere is increasing evidence that subsyndromal manic symptoms occur frequently during bipolar major depressive episodes (MDEs) and may be a subtle form of ‘depressive mixed state.’ This paper examines the prevalence and clinical characteristics of MDEs with subsyndromal manic symptoms. The specific effects of overt irritability and psychomotor agitation are examined.MethodsBipolar (type I or II) patients with an MDE at intake (N = 142) were compared based on the presence or absence of concurrent subsyndromal manic symptoms. The groups were further subdivided by the presence of symptoms of overt irritability and/or psychomotor agitation.ResultsSubsyndromal manic symptoms during bipolar MDEs were highly prevalent (76.1%), and were associated with significantly increased severity of depression/dysphoria in the intake episode, longer episode duration, and more suicidal ideation and behavior (past, current, and during long-term follow-up). Overt irritability and psychomotor agitation were the most prevalent subsyndromal manic symptoms (co-occurring in 57% and 39% of MDEs, respectively), and accounted for most of the negative effects associated with subsyndromal manic symptoms.LimitationsThe findings need to be confirmed in larger samples, which also examine the relationship to adequate antidepressant and/or mood stabilizing treatment.ConclusionsThe presence of one or more subsyndromal manic symptoms appears to be the modal presentation of bipolar MDEs and a marker for a subtle form of bipolar mixed depressive state. In particular, patients with symptoms of overt irritability and/or psychomotor agitation should be monitored closely to avoid serious clinical outcomes such as longer affective episodes, exacerbation of manic symptoms syndromal mania, and heightened suicidality.     

Distinct seasonality of depressive episodes differentiates unipolar depressive patients with and without depressive mixed states

BACKGROUND: The bipolar nature of unipolar depression with depressive mixed states (DMX) needs further validation studies. The seasonality of depressive episodes is indicated to be different between unipolar and bipolar depressions. We therefore explored the seasonal pattern of depressive episodes in unipolar depressive patients with DMX. METHODS: The subjects were 958 consecutive depressive inpatients for a 6-year period. For defining DMX, previously validated operational criteria were used (2 or more of 8 manic or mania-related symptoms: flight of idea, logorrhea, aggression, excessive social contact, increased drive, irritability, racing thoughts, and distractibility). Onsets of the index depressive episodes during each of the 12 calendar months were summed up over the 6-year for bipolar depressive patients (N = 95), and unipolar depressive patients with (N = 77) and without DMX (N = 786) separately. An appropriate statistic was used for testing seasonality. RESULTS: A significant seasonal variation with a large peak in spring was recognized in unipolar depression without DMX, while both bipolar depression and unipolar depression with DMX had a significant fall peak. The monthly distribution of depressive episodes was significantly different between unipolar depression without DMX and other 2 diagnostic categories. Similar results were obtained in separate analyses for each gender. LIMITATIONS: Further replication study using an epidemiological or outpatient sample is needed. Bipolar I and II patients were combined due to a small number of bipolar II patients in this sample. CONCLUSION: Unipolar depression with DMX has a seasonal pattern similar to bipolar depression. The finding provides further evidence of the bipolar nature of unipolar depression with DMX.     

The significance of psychotic features in manic episodes: a report from the NIMH collaborative study

BACKGROUND: Psychotic features in the context of major depressive syndromes have correlates in symptom severity, acute treatment response and long-term prognosis. Little is known as to whether psychotic features have similar importance when they occur within manic syndromes. METHODS: These data derive from a multi-center, long-term follow-up of patients with major affective disorder. Raters conducted follow-up interviews at 6-month intervals for the first 5 years and annually thereafter. A sub-set of probands participated in a family study in which all available, adult, first-degree relatives were interviewed as well. RESULTS: Of 139 who entered the study in an episode of mania, 90 patients had psychotic features. Symptom severity ratings at intake were more severe for this group. Though time to first recovery and time to first relapse did not distinguish the groups, psychotic features were associated with a greater number of weeks ill during follow-up and the strength of this association was similar to that seen for psychotic features within depressed patients described in an earlier publication. Patients with psychotic mania at intake did not differ significantly from those with nonpsychotic mania by response to acute lithium treatment, suicidal behavior during follow-up, or risks for affective disorder among first-degree relatives. Psychotic features within manic syndromes were not associated with high psychosis ratings during follow-up. In contrast, when psychotic features accompanied depressive syndromes, they strongly predicted the number of weeks with psychosis during follow-up, particularly among individuals whose episodes at intake were less acute. CONCLUSIONS: As with major depressive syndromes, psychotic features in mania are associated with greater symptom severity and higher morbidity in the long-term. Psychotic features are much less predictive of future psychosis when they occur within a manic syndrome than when they occur within a depressive syndrome.     

Family history validation of the bipolar nature of depressive mixed states

BACKGROUND: Recent data indicate that depressive mixed states (DMX), major depressive episode (MDE) plus few concurrent hypomanic symptoms are common in clinical practice but omitted in DSM-IV. Our aims were to find the sensitivity and specificity of DMX for the diagnosis of bipolar II disorder, and validate it against familial bipolarity. METHODS: 377 consecutive private outpatients presenting with psychoactive drug-free MDE were interviewed with the Structured Clinical Interview for DSM-IV (Clinician Version). History of past hypomanic episodes and presence of hypomanic symptoms during the index MDE were systematically recorded. Of these, 226 were bipolar II and 151 unipolar. DMX3 was defined as an MDE plus three or more intra-episodic hypomanic symptoms. RESULTS: DMX3 was present in 58.4% of bipolar II, and 23.1% of unipolar patients. It was significantly associated with variables distinguishing bipolar from strictly defined unipolar disorders (younger age at onset, more MDE recurrence, more atypical features, more bipolar II family history). Unipolar DMX3 (MDE with documented hypomania solely intra-episodically) was not significantly different from bipolar II MDE on age at onset, atypical features, and bipolar II family history. CONCLUSIONS: Results support the inclusion of DMX3 (bipolar II and 'unipolar') into the bipolar spectrum. Adding the 23% of the UP-DMX3 to the roster of less-than-manic outpatient depressives will boost the rate of bipolarity in this outpatient depressive population to a respectable 70%, the highest rate yet reported for the bipolar spectrum below the threshold of mania.     

The precipitants of manic/hypomanic episodes in the context of bipolar disorder: a review

Background

Mania/hypomania is the hallmark feature of bipolar disorder. This paper aims to review the current evidence in relation to factors hypothesised to precipitate bipolar mania/hypomania, and suggest areas for future research.

Methods

A selective review of original and review papers was conducted. The electronic databases ‘PsycINFO’ and ‘PubMed’ were searched using the following search strings: “bipolar disorder” or “mania” or “hypomania” or “manic-depression” with “triggers” or “precipitants” or “precedents” or “predictors”.

Results

There is evidence that goal attainment events, antidepressant medication, disrupted circadian rhythms, spring/summer seasonal conditions, and more tentatively, stressful life events and high emotional expression, may precipitate bipolar mania/hypomania in susceptible individuals. Evidence from case reports and clinical observations are also reported.

Discussion

The pathways to bipolar mania/hypomania may be many and varied, and many of these pathways may be outside the awareness of individuals with bipolar disorder. Greater awareness of the broad number of precipitating factors is needed to inform self-management and psycho-educational programs to build resilience to further episodes. Future research is needed to explore what other factors may precipitate bipolar mania/hypomania, and to determine why some factors may precipitate mania/hypomania in some individuals with bipolar I or II disorder but not in others.     

High rate of unrecognized bipolar mixed states among destitute Hispanic adolescents referred for "major depressive disorder"

OBJECTIVE: To ascertain the rate of bipolarity among adolescent Hispanic youths referred for the treatment of "major depressive disorder" (MDD) in a community mental health clinic (CMHC) in which the threshold for referral was moderate to severe impairment. METHODS: The patients were 49 consecutively presenting Hispanic adolescents (33 girls and 16 boys with a range of 12-17 years), many of whom had histories of unruly, hostile and/or assaultive behavior; indeed, 1 out of 3 had been referred to the CMHC from the "First-Time Offenders Program." Upon evaluation at the CMHC triage unit, all were diagnosed as MDD rendered by a licensed paramedical mental health professional managing this unit. They were subsequently evaluated by a psychiatrist using the Structured Clinical Interview for DSM-IV. RESULTS: Seventeen (51.5%) of the girls and 10 (62.5%) of the boys met the DSM-IV criteria for bipolar disorder. Among the bipolars, 44.4% were bipolar II and 55.6% bipolar I; 74.1%% had mixed states and 40.7% were psychotic (not mutually exclusive categories). Euphoric mania was virtually absent in this population. LIMITATION: Data on social deviance was based on chart review. Nonetheless, given that a third had already entered the juvenile justice system upon referral validates the accuracy of characterizing this population as at least moderately impaired from the social deviance standpoint. CONCLUSIONS: Hispanic adolescents referred with a presumptive diagnosis of MDD must be carefully assessed for the presence of occult bipolarity using a structured interview. Concurrent aggressiveness and depression should tip mental health clinicians towards bipolarity--especially mixed states. Such activated-hostile depressive (and/or manic) mixed states may in part underlie the social deviance in these patients. Given that these destitute youth are often simultaneously encountered in the juvenile justice system, undetected bipolarity among Hispanic adolescents initially regarded to have MDD represents a matter of grave public health importance. Appropriate training for mental health staff to recognize bipolar spectrum disorders in CMHCs should be mandated.     

Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament.

In an attempt to improve the classification of Bipolar II disorders, we have examined a consecutive series of 687 primary major depressives: 5.1% gave a past history of mania (Bipolar I), 13.7% met our operational criteria for hypomania (Bipolar II), and the remaining 81.2% were provisionally categorized as 'unipolar.' Although Bipolar II was in some respects intermediate between Bipolar I and Unipolar, gender, familial bipolar history, age at onset and course characteristics generally supported its closer kinship to bipolar illness. Seventy one of the unipolars (10.3% of the total series) further met our operational criteria for hyperthymic temperament (U-HT), leaving behind a purer unipolar group of 487 major depressives. With respect to the proportion having male gender and bipolar family history, U-HT was similar to Bipolar I and II, and all three differed significantly from pure unipolar; as for age at onset, number of episodes and related indices of course, BI and BII were similar, and U-HT was closer to pure unipolar. These findings suggest that major depressive episodes arising from a hyperthymic temperament (constituting 12.4% of the 'unipolar' universe by conventional definition) are 'genotypically' closer to Bipolar II defined by hypomania, and course-wise similar to other unipolars.     

Serum brain-derived neurotrophic factor is decreased in bipolar disorder during depressive and manic episodes

Genetic and pharmacological studies have suggested that brain-derived neurotrophic factor (BDNF) may be associated with the pathophysiology of bipolar disorder (BD). The present study investigated serum BDNF levels in manic, depressed, euthymic BD patients and in matched healthy controls, using an enzyme-linked immunosorbent assay (sandwich-ELISA). Serum BDNF levels were decreased in manic (p = 0.019) and depressed (p = 0.027) BD patients, as compared with euthymic patients and controls. Serum BDNF levels were negatively correlated with the severity of manic (r = −0.37, p = 0.005) and depressive (r = −0.30, p = 0.033) symptoms. These findings further support the hypothesis that the BDNF signaling system may play a role in the pathophysiology of BD.     

The development of major depressive episodes during the course of dysthymic and episodic major depressive disorders: a retrospective examination of life events

BACKGROUND: The present study examined whether stressful life events are associated with the development of major depressive episodes (MDEs) in a longitudinal, retrospective study of dysthymic and episodic major depressive disorders. METHODS: Sixty-seven outpatients with DSM-III-R dysthymia and 38 outpatients with non-chronic major depression were followed up 30-60 months after entry into the study. Follow-up assessments included a modified version of Paykel's (1997) Interview for Recent Life Events (IRLE) and Keller et al.'s (1987) Longitudinal Interval Follow-up Evaluation. Life events were assessed retrospectively in the 6 months before the most recent MDE or in the 6 months before follow-up for patients without a MDE. RESULTS: In dysthymic patients, MDEs were significantly associated with a new life event in the context of an ongoing chronic stressor. In episodic major depressive patients, relapses were associated with new life events regardless of an ongoing chronic stressor. LIMITATIONS: This was a retrospective study. It was also a conservative test of the association between life events and MDEs as the follow-up period over which life events were assessed was long, increasing the possibility of forgetting; events occurring less than 1 month before relapse were excluded to avoid confounding the event with the MDE; life events were assessed for a more distant time period for patients who experienced MDEs than those who did not; and an abbreviated version of the IRLE was used which may have failed to identify less severe events. CONCLUSIONS: This study suggests that life events may play a role in the onset of MDEs in persons with dysthymic disorder and those with major depressive disorder. Thus, clinicians should monitor dysthymic patients after a stressful life event, particularly if it occurs in the context of a chronic, ongoing stressor.     

Profiles of "manic" symptoms in bipolar I, bipolar II and major depressive disorders

BACKGROUND: Classical authors such as Kraepelin, as well as the emerging literature during the past decade, indicate that manic-like signs and symptoms are present to a variable degree in all mood disorders. Current nosography does not differentiate between them and only the number of symptoms or severity is used for classification. This is particularly true for mania and hypomania. This paper will analyze the patterns of manic symptoms in bipolar I (BP-I), bipolar II (BP-II) and major depressive disorders (MDD), to test the hypothesis that mania and hypomania have different profiles, and ascertain which excitatory manic phenomena do occur in unipolar MDD. METHODS: Six hundred and fifty-two inpatients (158 BP-I, 122 BP-II and 372 MDD) were assessed using the operational criteria for psychotic illness checklist (OPCRIT) [Arch. Gen. Psychiatry 48 (1991) 764] with a lifetime perspective. Manic or hypomanic symptoms were investigated and compared between BP-I, BP-II and MDD. RESULTS: When compared with BP-II, BP-I disorder had a higher prevalence of reckless activity, distractibility, psychomotor agitation, irritable mood and increased self-esteem. These five symptoms correctly classified 82.8% of BP-I and 80.1% of BP-II patients. One or two manic symptoms were observed in more than 30% of major depressive patients; psychomotor agitation was the most frequent manifestations present in 18% of the MDD group. LIMITATIONS: We did not control for severity of symptoms, nor for neuroleptic use that could produce akathisia. CONCLUSIONS: This study suggests that mania and hypomania can be differentiated in their symptom profiles, and highlights the presence of few manic symptoms, particularly psychomotor agitation, in MDD. From the standpoint of number of manic signs and symptoms, controlling for psychomotor agitation did not substantially change the predictive power of the remaining manic symptoms. Given that excitatory manic signs and symptoms are present to a decreasing degree in BP-I, BP-II and MDD, these disorders can be proposed to lie along a dimensional model. Overall, these data are compatible with the concept of a bipolar spectrum, whereby each of the affective subtypes requires specific genetic factors.     

The prevalence of major depressive and bipolar disorders in Hungary Results from a national epidemiologic survey

In order to estimate the prevalence of affective disorders in Hungary a sample of the Hungarian adult population (18–64 years) selected at random was interviewed using the Diagnostic Interview Schedule (DIS) which generated DSM-III-R diagnoses. The lifetime rate for Major Depressive Disorder (MDD) was 15.1%, and for Bipolar Disorders (BD) 5.1%. The female-to-male ratio was 2.7 for MDD and nearly equal for BD. The 1-year and 1-month period prevalence rates were 7.1% and 2.6% for MDD and 0.9% and 0.5% for manic episodes. A higher rate of divorced or separated persons was found among individuals with a lifetime diagnosis of MDD. Besides these, the lifetime diagnosis of BD coexisted with higher rates of the never-married state. The highest hazard rate for the development of BD or MDD was in the range 15–19 years but in MDD another peak was also found in the range 45–50 years. The first peak was characteristic of the recurrent, and the other one of the single form of MDD. Insomnia, loss of energy, decreased interest, concentration problems were the most common symptoms during the depressive episode, independent of polarity. Higher rates of lifetime diagnosis of dysthymia and all kinds of anxiety disorder were revealed among persons with MDD. BD was associated with GAD (Generalized Anxiety Disorder), and panic disorder more often than chance.     

Clinical characterization of depressive mixed state in bipolar-I patients: Pisa-San Diego collaboration

BACKGROUND: Although mixed states were classically described as various concomitant admixtures of depression and mania, the official current definitions in both DSM-IV and ICD-10 tend to restrict the concept to manic patients with full syndromal depression. Recent research has actually shown that mania with few depressive symptoms constitutes the most prevalent clinical presentation of mixed or dysphoric mania. Major depressive patients with few concomitant manic symptoms are not officially recognized within the current nosology. In this paper we attempt to delineate the clinical profile of such depressive mixed states in the context of bipolar I disorder. METHODS: In the Pisa day center, we studied 195 bipolar I patients who either met Pisa criteria for bipolar mixed state (n=159) or DSM-III-R criteria for major depressive episode (bipolar major depression or B-MD, n=36). Of the 159 patients identified by Pisa criteria as mixed state, 86 also met the criteria of the DSM-III-R for mixed episode (core mixed state or MS group), while 32 met the DSM III-R criteria for major depressive episode (provisionally defined as depressive mixed states, D-MS); the remaining patients (n=41, 25.7%) with predominatly manic picture were not included in the present comparisons. RESULTS: The three groups (B-MD, MS and D-MS) had close similarities in clinical and sociodemographic characteristics such as age, sex distribution, marital status, schooling, residence, age at onset, age of first treatment, age of first hospitalization, degree of chronicity of the index episode, stressor within the 6 months before the index episode, lifetime suicide attempts and premorbid temperament. First degree family history for bipolar illness and that for other mental disorders was also similar, except for major depression that was more common among the relatives of D-MS. MS and D-MS were further distinguished from B-MD by the fact that the latter followed a more 'cyclic' course with shorter yet greater number of episodes, and which began with a pure depressive episode; by contrast, MS and D-MS had fewer episodes of longer duration, less interepisodic remission, and tended to begin with a mixed episode. Incongruous psychotic features were more common in the two mixed groups compared to B-MD, and the most common features of the D-MS group were agitation, psychotic depression with irritable mood, pressured speech and/or flight of ideas. LIMITATION: It was not feasible to collect information blind to clinical status in patients with severe psychotic mood states. CONCLUSION: These data confirm the existence of psychotic agitated depressive mixed states with flight of ideas, distinct from cyclic retarded pure bipolar depressive states. The recognition of these affective states is clinically important to protect patients from the potentially harmful indiscriminate use of antidepressants and to provide them with the benefits of an anticonvulsant, a short-term neuroleptic, or ECT.     

混合特征对抑郁发作患者复发影响的1年随访

目的:探索抑郁发作患者复发的危险因素及混合特征对抑郁发作患者复发的影响。方法:2015年8月1日-2017年9月30日,在北京某三级甲等精神专科医院选取符合DSM-Ⅳ标准的抑郁发作患者357例进行基线测查并在基线后1年进行随访评估其复发情况。基线测查包括收集患者一般人口学资料、既往治疗情况和是否具有混合特征及其数目,采用汉密顿抑郁量表、杨氏躁狂量表等量表评估病情。单因素初步分析混合特征及其他因素对抑郁发作患者复发风险的影响,多因素logistic回归分析进一步分析复发的影响因素。结果:31.1%的患者一年内复发,多因素logistic回归分析显示,12月末的服药依从性是抑郁发作患者复发的保护因素(OR=0.53,95%CI:0.28～0.99),既往发病次数(OR=1.19,95%CI:1.01～1.39)、具有混合特征的个数(OR=1.54,95%CI:1.19～2.00)是抑郁发作复发的危险因素。结论:既往发病次数及抑郁发作时具有的混合特征个数是患者疾病复发的危险因素。     

Response to antidepressants in major depressive disorder with melancholic features: the CRESCEND study

BackgroundThis study aimed to determine whether major depressive disorders with melancholic and without melancholic features differ with respect to their responses to treatment with antidepressants.MethodsFrom a nationwide sample of 18 hospitals in South Korea, 559 presenting patients with major depressive disorder were recruited. The DSM-IV based Structured Clinical Interview was administered for confirmatory diagnoses and depression subtypes with/without melancholic features. After baseline evaluation, they received naturalistic clinician-determined antidepressant interventions. Assessment scales for evaluating depression (HAMD), anxiety (HAMA), global severity (CGI-s), and functioning (SOFAS) were administered at baseline and re-evaluated at 1, 2, 4, 8, and 12 weeks later.ResultsAt baseline, the 243 (43.5%) participants with melancholic features were more likely to have a previous history of depression, and had higher HAMA and lower SOFAS scores. After adjustment for baseline status, participants with melancholic features were more likely to achieve and to experience shorter times to CGI-s remission and associated with an enhanced global symptomatic remission with any antidepressant treatment. They were more likely to achieve and to experience shorter times to CGI-s remission and this difference was strongest in those receiving selective serotonin reuptake inhibitor (SSRI) antidepressants treatment.LimitationsThe study was observational, and the treatment modality was naturalistic.ConclusionsThese findings suggest a faster and more evident global response to pharmacotherapy in melancholia compared to other depressive syndromes, particularly where SSRI agents are used.     

Increased serum glial cell line-derived neurotrophic factor immunocontent during manic and depressive episodes in individuals with bipolar disorder

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor from the transforming growth factor β family, which plays a role in the development and function of hippocampal cells. Preclinical studies suggest that changes in neurotrophic growth factor systems might be involved in the pathophysiology of mood disorders including bipolar disorder (BD) [E.J. Nestler, M. Barrot, R.J. DiLeone, A.J. Eisch, S.J. Gold, L.M. Monteggia, Neurobiology of depression, Neuron 34 (2002) 13–25]. This is the first study to analyze GDNF immunocontent in BD subjects across different mood states, including mania, depression, and remission (euthymia). Fourty-four bipolar patients (14 depressed, 15 manic, and 15 euthymic) and 14 healthy controls, diagnosed according to the Structural Clinical Interview for DSM-IV were studied. Serum GDNF immunocontent was measured using Western blotting. Serum GDNF immunocontent was increased in manic (F = 42.31; p = 0.001; one-way ANOVA) and depressed (F = 42.31; p = 0.004; one-way ANOVA) bipolar patients, but not in euthymic patients as compared with controls. Our results indicate that changes in GDNF immunocontent occur during acute major affective episodes in bipolar subjects. These results further support the role of neurotrophins in the pathophysiology of bipolar disorder. Whether the observed increase in GDNF immunocontent correspond to a pathological or an adaptive response remains to be determined.