Recognizing thyrotoxicosis in a patient with bipolar mania: a case report

Background

A thyroid stimulating hormone level is commonly measured in patients presenting with symptoms of mania in order to rule out an underlying general medical condition such as hyperthyroidism or thyrotoxicosis. Indeed, many cases have been reported in which a patient is initially treated for bipolar mania, but is later found to have a thyroid condition. Several case reports have noted the development of a thyroid condition in bipolar patients either on lithium maintenance treatment or recently on lithium treatment.

Case presentation

We review a case in which a patient with a long history of bipolar disorder presents with comorbid hyperthyroidism and bipolar mania after recent discontinuation of lithium treatment.

Conclusion

Physicians should consider a comorbid hyperthyroidism in bipolar manic patients only partially responsive to standard care treatment with a mood stabilizer and antipsychotic.     

Cannabis et trouble bipolaire : recherche d’une association à partir d’une revue de la littérature

Introduction

It has been established that cannabis use is involved in the emergence and evolution of psychotic disorders. Although cannabis use is very frequent in mood disorders, there has been a considerable debate about the association observed between these two disorders. This review aims to clarify the relation between cannabis use and bipolar disorder, in order to unveil a possible causality and find the effect of cannabis on the prognosis and expression of bipolarity.

Methods

The review used MedLine database using the keywords “cannabis” or “marijuana” and “bipolar” or “mania” or “depression”. This search found 36 articles who were clinically relevant to the subject and were included and discussed in this review.

Results

The first studies discussing the link between cannabis use and psychotic disorders reveal manic features in the substance abuse group, hence suggesting a possible association between cannabis use and bipolar disorder, in favor of triggering a manic episode. According to the studies, between 25 and 64% of bipolar patients are cannabis users, and the prevalence is higher in younger and male patients. The risk of developing a mood disorder is higher among cannabis users compared to the general population. This substance abuse in bipolar disorders would increase the frequency and duration of manic episodes without changing the total duration of mood episodes. In a first episode of bipolar disorder, the use of cannabis would increase the rate of relapses of manic episodes and worsen the prognosis of the disorder.

Discussion

The frequency of substance abuse in bipolar disorders is higher than the prevalence in the general population, and cannabis is one of the most used illegal substances in the worldwide. Hence, the association between cannabis use and bipolar disorders is frequent. Cannabis users may experience euphoria, relaxation and subjective feelings of well-being; this substance may also have antiepileptic effect, which may explain some of the effects of cannabis on bipolar disorders. In fact, the use of cannabis would increase the frequency and duration of manic episodes in bipolar patients without increasing the total duration of mood episodes, suggesting a possible antidepressing and mood stabilizing effects. This impact of cannabis on mood disorders and its possible pharmacological effect is still controversial and needs further experiencing to be proved.     

Antibiomania : penser au syndrome maniaque secondaire à une antibiothérapie

Introduction

Antibiomania is characterized by the emergence of a manic episode in reaction to antibiotics. Although relatively uncommon, this kind of side effect is observed in a growing number of cases and mostly occurs in patients who do not have a history of bipolar disorder. Several dozen cases have been reported showing the onset of manic symptoms after taking antibiotics. The antibiotic most frequently involved is clarithromycin.

Is antidepressant-associated mania always an evidence of a bipolar spectrum disorder? A case report and review of the literature

Objective

The authors consider the clinical implications of characterizing every case of antidepressant-induced mania as evidence of an underlying bipolar diathesis.

Method

The authors report the case of a 45-year-old man, with no personal or family history of bipolar symptoms, who developed manic symptoms after sertraline initiation for a first lifetime depressive episode.

Results

The patient's manic symptoms resolved rapidly with cessation of sertraline. His depressive symptoms responded to mirtazapine, and he had no further mood episodes during 2-year follow-up.

Discussion

It may not always be appropriate to identify selective serotonin reuptake inhibitor-induced manic symptoms as pathognomonic for the bipolar diathesis, particularly as the bipolar formulation has distinct implications for future pharmacologic choices.     

A comparison of life events in patients with unipolar disorder or bipolar disorder and controls

Objective

The present study aimed to explore the association between stressful life events (LEs) and the development of affective psychopathology.

Method

Thirty patients with unipolar disorder and 30 patients with bipolar disorder were compared to 60 matched healthy controls in regard to the rate of stressful LEs. Assessment measures included the Beck Depression Inventory, the Adult Life Events Questionnaire, and the Childhood Life Events List.

Results

The entire sample of affective patients had more LEs in general, more negative LEs, and more loss-related LEs in the year preceding their first depressive episode as compared with normal controls. Subjects with unipolar disorder had more positive LEs and more achievement LEs, whereas subjects with bipolar disorder had more uncontrollable LEs in the year preceding the first depressive episode. The relationship between LEs and manic episodes was prominent in the year preceding the first manic episode, with subjects with bipolar disorder reporting more LEs in general and more ambiguous events in that year. Almost no significant differences on LE frequency were observed in the year before the last depressive and manic episodes in the patient groups with unipolar and bipolar disorder. A significant relationship was found between childhood LEs and the development of affective disorders in adulthood, with patients with unipolar disorder exhibiting less positive and achievement LEs.

Conclusions

In both the unipolar and the bipolar groups, the major impact of LEs on the onset of affective disorders was found in the year before the first depressive or manic episodes. This suggests that the accumulation of stressful LEs at this crucial period contributes to the precipitation of a pathological response mechanism. Once established, this mechanism would be reactivated in the future by even less numerous and less severe stressors, compatible with the kindling hypothesis.     

There is no association between the serotonin receptor gene and bipolar I disorder in the Korean population

Abstract

Objective: Despite the close relationship between the functional polymorphism C(-1019)G (rs6295) of the serotonergic 1A receptor (5-HT1A) and mood, few studies have investigated the relationship between rs6295 and bipolar disorder. Aims: In this study, we aimed to investigate whether rs6295 is associated with clinical prognosis and treatment response in patients with bipolar I disorder acute manic episodes. Methods: One hundred twenty-eight patients with bipolar I disorder and one hundred sixty-eight healthy controls were recruited. Associations between patients with bipolar I disorder and healthy controls were compared. In addition, age at onset, number of admissions, and treatment response, including response rate, mean changes in manic symptoms, number of anti-manic agents and the total dosage of mood stabilizers for acute manic symptoms were compared between the rs6295 GG and CG+ CC groups in patients with bipolar I disorder. We conducted a separate subgroup analysis according to gender. Results: There were no differences in frequency between patients and controls. In patients with bipolar disorder, clinical prognosis and treatment response were no different between GG and CG+ CC groups. However, in a subgroup analysis according to gender, male, but not female, patients in the GG group had a longer duration of illness and a greater number of both previous episodes and psychiatric ward admissions than did the GC+ CC group. Conclusions: Further studies should investigate the relationship between 5-HT1A polymorphisms and bipolar disorder in terms of mood episode and gender.     

Extreme attributions predict transition from depression to mania or hypomania in bipolar disorder

Background

Relatively little is known about psychological predictors of the onset of mania among individuals with bipolar disorder, particularly during episodes of depression. In the present study we investigated attributional style as a predictor of onset of hypomanic, manic or mixed episodes among bipolar adults receiving psychosocial treatment for depression. We hypothesized that “extreme” (i.e., excessively pessimistic or optimistic) attributions would predict a greater likelihood of developing an episode of mood elevation.

Method

Outpatients with DSM-IV bipolar I or II disorder (N = 105) enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomly allocated to one of three types of intensive psychotherapy for depression or a brief psychoeducational intervention. Patients completed a measure of attributional style at baseline and were followed prospectively for up to one year. All analyses were by intent to treat.

Results

Logistic regressions and Cox proportional hazards models indicated that extreme (both positively- and negatively-valenced) attributions predicted a higher likelihood of (and shorter time until) transition from depression to a (hypo)manic or mixed episode (ps < .04), independent of the effects of manic or depressive symptom severity at baseline. Extreme attributions were also retrospectively associated with more lifetime episodes of (hypo)mania and depression (ps < .05).

Conclusions

Evaluating extreme attributions may help clinicians to identify patients who are at risk for experiencing a more severe course of bipolar illness, and who may benefit from treatments that introduce greater cognitive flexibility.     

A positive relationship between ambient temperature and bipolar disorder identified using a national cohort of psychiatric inpatients

Objective

This study characterizes the positive relationship between daily temperature and bipolar disorder in a cohort of Taiwanese psychiatric inpatients.

Methods

Meteorological data, provided by the Central Weather Bureau (CWB) of Taiwan, were interpolated to create representative estimates of mean diurnal temperatures for 352 townships. Psychiatric inpatient admissions enrolled in the national health-care insurance system were retrieved from the 1996–2007 Psychiatric Inpatient Medical Claim (PIMC) dataset. The generalized linear mixed models with Poisson distribution were used to evaluate the relative risks of mean diurnal temperature with respect to increased admissions for bipolar disorder, while adjusting for internal correlations and demographic covariates.

Results

Increased relative risks of bipolar disorder admissions were associated with the increasing trends of temperature over 24.0 °C (50th ‰), especially for adults and females. The highest daily diurnal temperatures above 30.7 °C (99th ‰) had the greatest risks of bipolar hospitalizations.

Conclusion

Understanding the increase of bipolar disorder admissions occurring in extreme heat is important in the preparation and prevention of massive recurrences of bipolar episodes.     

Bipolar disorder and criminal offending: a data linkage study

Purpose

The current study explored criminal offending among people diagnosed with bipolar disorder with and without comorbid substance use and compared this with a community sample with no history of bipolar disorder.

Methods

A case-linkage design was used to compare patterns of officially recorded criminal offending between 1,076 people with bipolar disorder drawn from a state-wide psychiatric case register with a community comparison group.

Results

Those with bipolar disorder were significantly more likely than community members to be charged with, convicted of, and be found guilty of, violent, non-violent and intermediate level criminal offences. Those with a comorbid substance use disorder were two times more likely than those without a substance use disorder to offend; both groups had a significantly higher chance of offending than the community sample. Females with bipolar disorder were significantly more likely to have been convicted of violent offences, irrespective of substance use. Significant interactions were found between bipolar disorder and substance use for males and females with respect to violent offending and for males with respect to non-violent offending.

Conclusions

There is a statistically significant association between bipolar disorder and the likelihood of having a criminal history. Co-occurring substance use differentially impacts on the likelihood of criminal offending for males and females.     

Devenir des troubles bipolaires et place du trouble dysphorique prémenstruel dans le DSM-5

In the field of bipolar disorders, the fifth edition of the DSM has clarified the definition of manic mood, which includes irritability and expansiveness. This elevated mood is associated with increased goal-directed activity or energy. A full manic episode that emerges during an antidepressant treatment (e.g., medication, electroconvulsive therapy) is now sufficient evidence for a manic episode diagnosis and therefore for a bipolar disorder I diagnosis. If so a mood-stabilizer treatment is required. The DSM-5 authors call for more caution in case of hypomanic episodes induced by antidepressant treatment, especially if only one or two symptoms are present. On the other hand, if there are psychotic features, the episode is, by definition, manic. Several studies have judged the bereavement exclusion criteria irrelevant to fulfil the diagnosis of major depressive episode, that is why this exclusion criteria has disappeared from DSM-5. This might help for a better management of major depressive episode in case of mourning. The lack of consensual definition of mixed state led to the suppression of the mixed episode in this new edition of the DSM. It is however possible to specify the mixed features in manic, hypomanic and depressive episodes. This decision is in coherence with Emil Kraepelin's inheritance. In fact, Kraepelin himself described several mixed states, essentially as transition states between the two main clinical pictures (mania and depression) of the manic-depressive illness. In this perspective, clinical pictures such as agitated depression, dysphoric manic or hypomanic episodes can be reconsidered and one can hope that studies will be conducted to deepen the knowledge of those episodes from a clinical, physiopathological and therapeutic point of view. Finally the premenstrual dysphoric disorder has moved from the appendix B (for the research) of the DSM-IV to the “diagnostic criteria and codes” (section II) of the DSM-5. This disorder is quite frequently associated with bipolar disorder II whose prognosis it worsens while complicating its therapeutic management. In the paper, the premenstrual dysphoric disorder is described on an historical, clinical, physiopathological and therapeutic level, within the limits of current knowledge about this uncommon psychiatric syndrome. Its DSM-5 diagnostic criteria are also summarized and commented upon. This official entry of the premenstrual dysphoric disorder in the DSM-5 shows the willingness of the American Psychiatric Association to incorporate uncommon psychiatric syndromes in its diagnostic classification.     

Sex difference in symptomatology of manic episode

Objective

Studies addressing sex differences in the symptoms and course of bipolar affective disorder had been investigated across different phase of bipolar affective disorder. There are few studies in manic phase that have reported inconsistent results. Therefore, we investigated sex difference in symptom presentation of manic episode.

Methods

A total of 150 male and 50 female subjects meeting criteria for manic episode according to International Statistical Classification of Diseases, 10th Revision Diagnostic Criteria for Research, giving written informed consent, were included for the study. Those with comorbid major medical or psychiatric disorders were excluded. All the patients were assessed on Scale for Manic States.

Results

Multivariate analysis of variance using all the items of Scale for Manic Symptoms showed significant sex difference (Pillai's Trace F_20,179 = 5.154, P < .001), with large effect size (η² = .365). In men, there was significantly higher motor activity, psychosis, grandiosity, contact, and humor, whereas mood lability, depressed mood, guilt, suicide, anxiety, and dress scores were higher in women. Discriminant analysis showed that 84% of men and 72% of women could be correctly classified using the Scale for Manic Symptoms. Stepwise logistic regression analysis showed anxiety, guilt, and dress positively predicted female sex and the model explained 24% to 36% of variance.

Conclusion

Symptom presentation of mania differs across sex and a predominance of anxiety and depressive symptoms was found in women, whereas increased psychomotor activity was prevalent in men.     

Manic episode in epilepsy and bipolar I disorder: a comparative analysis of 13 patients

PURPOSE: To determine whether the manic episode of patients with epilepsy has different characteristics from manic episode of patients with bipolar disorder. METHODS: Interictal manic episodes in patients with epilepsy (epilepsy group) were compared with mood disorders in patients with bipolar I disorder (bipolar group), as defined by the DSM-IV. There were 13 patients (five women and eight men) in each group. RESULTS: Five epilepsy patients had relatives with epilepsy and/or convulsions, and four bipolar patients had relatives with mood disorders. In the epilepsy group, two had substance-related or organic factors associated with the episodes besides epilepsy, and two exhibited a postictal manic state that had the same symptoms as those of their interictal manic episodes. Ten patients of the epilepsy group had dependent-childish behavior. The epilepsy group had fewer severe mood episodes than the bipolar group. Ten epilepsy patients had fluctuating mood disturbances, and eight had rapid cycling of mood episodes. The epileptogenic zone was in the frontal and/or temporal lobes of eight patients and in multiple lobes of two others; it could not be localized in the three remaining patients. CONCLUSIONS: The clinical features of the interictal manic episodes in the epilepsy group were different from those in the bipolar group. The manic episodes of the epilepsy group appeared heterogeneous in their causal factors. An epileptogenic zone in the frontal and temporal lobes seems to play an important role in the mood episodes of the majority of patients with epilepsy.     

Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on prospective mood ratings in 539 outpatients

OBJECTIVE: To detect risk factors for rapid cycling in bipolar disorder, the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective. METHOD: Outpatients with bipolar I disorder (N=419), bipolar II disorder (N=104), and bipolar disorder not otherwise specified (N=16) were prospectively evaluated with daily mood ratings for 1 year. Subjects were classified as having rapid cycling (defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year) or not having rapid cycling, and the two groups' demographic and retrospective and prospective illness characteristics were compared. Associated factors were also evaluated in relationship to episode frequency. RESULTS: Patients with rapid cycling (N=206; 38.2%) significantly differed from those without rapid cycling (N=333) with respect to the following independent variables: history of childhood physical and/or sexual abuse, bipolar I disorder subtype, number of lifetime manic or depressive episodes, history of rapid cycling, and history of drug abuse. The prevalence of these characteristics increased progressively with episode frequency. The proportion of women was greater than the proportion of men only among patients with eight or more episodes per year. The average time spent manic/hypomanic increased as a function of episode frequency, but the average time spent depressed was comparable in patients with one episode and in those with more than one episode. Brief episodes were as frequent as full-duration DSM-IV-defined episodes. CONCLUSIONS: A number of heterogeneous risk factors were progressively associated with increasing episode frequency. Depression predominated in all bipolar disorder patients, but patients with rapid cycling were more likely to be characterized by manic features. The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency.     

Atypical antipsychotics in bipolar disorder: systematic review of randomised trials

Background

Atypical antipsychotics are increasingly used for treatment of mental illnesses like schizophrenia and bipolar disorder, and considered to have fewer extrapyramidal effects than older antipsychotics.

Methods

We examined efficacy in randomised trials of bipolar disorder where the presenting episode was either depression, or manic/mixed, comparing atypical antipsychotic with placebo or active comparator, examined withdrawals for any cause, or due to lack of efficacy or adverse events, and combined all phases for adverse event analysis. Studies were found through systematic search (PubMed, EMBASE, Cochrane Library), and data combined for analysis where there was clinical homogeneity, with especial reference to trial duration.

Results

In five trials (2,206 patients) participants presented with a depressive episode, and in 25 trials (6,174 patients) the presenting episode was manic or mixed. In 8-week studies presenting with depression, quetiapine and olanzapine produced significantly better rates of response and symptomatic remission than placebo, with NNTs of 5–6, but more adverse event withdrawals (NNH 12). With mania or mixed presentation atypical antipsychotics produced significantly better rates of response and symptomatic remission than placebo, with NNTs of about 5 up to six weeks, and 4 at 6–12 weeks, but more adverse event withdrawals (NNH of about 22) in studies of 6–12 weeks. In comparisons with established treatments, atypical antipsychotics had similar efficacy, but significantly fewer adverse event withdrawals (NNT to prevent one withdrawal about 10). In maintenance trials atypical antipsychotics had significantly fewer relapses to depression or mania than placebo or active comparator. In placebo-controlled trials, atypical antipsychotics were associated with higher rates of weight gain of ≥7% (mainly olanzapine trials), somnolence, and extrapyramidal symptoms. In active controlled trials, atypical antipsychotics were associated with lower rates of extrapyramidal symptoms, but higher rates of weight gain and somnolence.

Conclusion

Atypical antipsychotics are effective in treating both phases of bipolar disorder compared with placebo, and as effective as established drug therapies. Atypical antipsychotics produce fewer extrapyramidal symptoms, but weight gain is more common (with olanzapine). There is insufficient data confidently to distinguish between different atypical antipsychotics.     

Gender differences in the phenomenology of bipolar disorder

OBJECTIVES: To investigate gender differences in the phenomenology of episodes in bipolar disorder as according to ICD-10. METHODS: All patients who got a diagnosis of a manic episode/bipolar disorder in a period from 1994 to 2002 at the first outpatient treatment ever or at the first discharge from psychiatric hospitalization ever in Denmark were identified in a nationwide register. RESULTS: Totally, 682 outpatients and 1037 inpatients got a diagnosis of a manic episode/bipolar disorder at the first contact ever. Significantly more women were treated as outpatients than as inpatients. Women were treated for longer periods as inpatients but not as outpatients. In both settings, the prevalence of depressive versus manic/mixed episodes was similar for men and women and the severity of manic episodes (hypomanic /manic without psychosis/manic with psychosis) and the severity of depressive episodes (mild/moderate/severe without psychosis/severe with psychosis) did not differ between genders. The prevalence of psychotic symptoms at first contact was the same for both genders. Among patients treated in outpatient settings more men than women presented with comorbid substance abuse and among patients treated during hospitalization more women than men presented with mixed episodes. CONCLUSIONS: Besides differences in the prevalence of mixed episodes and comorbid substance abuse few gender differences are found among patients presenting with a manic episode/bipolar disorder at first contact in psychiatric inpatient or outpatient hospital settings.     

Traitement pharmacologique du trouble bipolaire chez l’enfant et l’adolescent

Objective

To review the options for acute and maintenance pharmacological treatment of bipolar disorder in children and adolescents.

Avis critique sur la place du lithium dans les recommandations professionnelles sur la prise en charge du trouble bipolaire

Objectives

In the last few decades, from the discovery of lithium, an increasing number of drugs have been approved for the treatment of bipolar disorders. Guidelines have been established to help clinicians make a relevant choice of medication in specific clinical circumstances. The aim of this article is to review the place of lithium in the recent guidelines for the treatment of bipolar disorder.

Materials and methods

We reviewed the recently published guidelines in English and in French for the management of bipolar disorder. Electronic library and Web-based searches were performed using recognized tools (MEDLINE, PubMED and EMBASE) to identify guidelines that have been published since 2006. In addition, other sources of information known to us, such as national agency reports, were searched.

Results

Since 2006, seven sets of guidelines have been established or updated by official scientific societies. The different guidelines are in agreement on the choice of lithium to be used as a first-line treatment for mania. The efficacy of lithium in combination with second-generation antipsychotic in the management of manic episodes has made these associations first-line choices in some guidelines. However, choosing a combination from the outset for the management of mania will depend on whether the Task Force that developed the guidelines gives priority to efficacy or tolerance and not on the guidelines methodology, which is used. For the treatment of bipolar depressive episode, the only drug recommended in monotherapy as first-line treatment by all guidelines is quetiapine. The place of lithium in this indication is controversial and only some guidelines recommend lithium in monotherapy as first-line strategy. The recommendation grade of lithium depends on how the results of the studies are interpreted by the Task Force elaborating the guideline. Guidelines disagree on the first-line treatment choice in mixed state. Some guidelines make no distinction between treatments of classic mania and that of mixed state. The other guidelines consider lithium to be less efficacious in this indication. For the long-term treatment, all guidelines take into consideration the predominant mood polarity of the patient. Lithium is considered to have an important role in preventive strategies for bipolar disorder whatever the predominant mood polarity. However, it is perceived as a more effective treatment in the prevention of manic episodes than depressive episodes.

Conclusions

Lithium remains a gold standard treatment in the recently published practice guidelines. The main differences between the guidelines on its use are related to methodological discrepancies and interpretation of the scientific data by the Task Force that developed the guidelines.     

Elevation of cerebrospinal fluid interleukin-1β in bipolar disorder

Background

In recent years, a role for the immune system in the pathogenesis of psychiatric diseases has gained increased attention. Although bipolar disorder appears to be associated with altered serum cytokine levels, a putative immunological contribution to its patho-physiology remains to be established. Hitherto, no direct analyses of cerebrospinal fluid (CSF) cytokines in patients with bipolar disorder have been performed.

Methods

We analyzed CSF cytokine concentrations in euthymic patients with diagnosed bipolar disorder type I (n = 15) or type II (n = 15) and healthy volunteers (n = 30) using an immunoassay-based protein array multiplex system.

Results

The mean interleukin (IL)-1β level (4.2 pg/mL, standard error of the mean [SEM] 0.5) was higher and the IL-6 level (1.5 pg/mL, SEM 0.2) was lower in euthymic bipolar patients than in healthy volunteers (0.8 pg/mL, SEM 0.04, and 2.6 pg/mL, SEM 0.2, respectively). Patients with 1 or more manic/hypomanic episodes during the last year showed significantly higher levels of IL-1β (6.2 pg/mL, SEM 0.8; n = 9) than patients without a recent manic/hypomanic episode (3.1 pg/mL, SEM 1.0; n = 10).

Limitations

All patients were in an euthymic state at the time of sampling. Owing to the large variety of drugs prescribed to patients in the present study, influence of medication on the cytokine profile cannot be ruled out.

Conclusion

Our findings show an altered brain cytokine profile associated with the manifestation of recent manic/hypomanic episodes in patients with bipolar disorder. Although the causality remains to be established, these findings may suggest a pathophysiological role for IL-1β in bipolar disorder.     

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.