Testing new diagnostic criteria for hypomania.

BACKGROUND: A recent series of studies has questioned DSM-IV diagnostic criteria for hypomania, suggesting that overactivity (increased goal-directed activity) should have priority over mood change as stem criterion. Angst has suggested new criteria for hypomania, giving priority to overactivity. Study aim was to test the validity of Angst's diagnostic criteria for hypomania. METHODS: A consecutive sample of remitted 213 DSM-IV bipolar-II disorder (BP-II) and major depressive disorder (MDD) outpatients were re-diagnosed, during a follow-up visit, by the Structured Clinical Interview for DSM-IV (yes/no structured questions on hypomanic symptoms, skip-out instruction of stem question on mood change not followed, in order to assess all past hypomanic symptoms), by a mood disorder specialist psychiatrist in a private practice. Angst's stem diagnostic criteria for hypomania were tested versus DSM-IV hypomania: 1) overactivity plus at least 3 of the 7 DSM-IV hypomanic symptoms 2) overactivity plus at least 2 of the 7 DSM-IV hypomanic symptoms. RESULTS: DSM-IV criteria for hypomania were met by 137 patients, overactivity plus 2/7 was met by 146 patients, and overactivity plus 3/7 was met by 135 patients. Of the patients with overactivity plus 2/7, 83.5% also met DSM-IV criteria for hypomania, and of the patients with overactivity plus 3/7 86.6% also met DSM-IV criteria for hypomania. Logistic regression of DSM-IV hypomania versus overactivity plus 2/7 found odds ratio (OR) = 17.6, and versus overactivity plus 3/7 found OR = 18.8. Comparisons between DSM-IV hypomania and Angst's criteria for hypomania showed that there were no significant differences on age, gender, symptom structure of hypomania, number of episodes, episodes duration, and episodes level of functioning. Associations (ORs) between the stem criterion of each definition of hypomania and hypomanic symptoms were often strong. DSM-IV hypomania stem criterion was closely associated with overactivity (OR = 15.4), and Angst's hypomania stem criteria were closely associated with mood change (OR = 7.6 for overactivity plus 2/7, OR = 14.3 for overactivity plus 3/7). CONCLUSIONS: Results support Angst's criteria for hypomania based on overactivity (overactivity plus 3/7 seems more supported). These criteria do not seem to lead to overdiagnosing hypomania. Previous studies supported the upgrading of overactivity among DSM-IV hypomanic symptoms. Angst's diagnostic criteria may positively impact the treatment of depression. It has been shown that focusing the probing for history of hypomania more on overactivity than on mood change reduces the false-negative BP-II. By using Angst' criteria for hypomania, clinicians may reduce the current high misdiagnosis of BP-II as MDD and the related mistreatment.     

Frequency of bipolar spectrum in 111 private practice depression outpatients

Background Mood disorders included into the bipolar spectrum are increasing, and overactivity (increased goal-directed activity) has reached the status of mood change for the diagnosis of hypomania in the recent studies by Angst (2003) and Akiskal (2001). Study aim was to find frequency of bipolar spectrum in remitted depressed outpatients by including sub-syndromal hypomania. Methods 111 depression-remitted outpatients were interviewed for history of hypomania and hypomanic symptoms with the Structured Clinical Interview for DSM-IV-Clinician Version (a partly semistructured interview), as modified by Benazzi and Akiskal (2003). Bipolar I patients were not included. All past hypomanic symptoms (especially overactivity) were systematically assessed.Wording of the questions could be changed to increase/check understanding.Subsyndromal hypomania was defined as an episode of overactivity (increased goal-directed activity) plus at least 2 hypomanic symptoms. Results Frequency of bipolar II (BPII) was 68/111 (61.2%, 95% confidence interval 52% to 69.8 %), frequency of major depressive disorder (MDD) was 43/111. The most common hypomanic symptom was overactivity. In the MDD sample, sub-syndromal hypomania was present in 39.5% (15.3% of the entire sample), and had 4 median symptoms. Bipolar spectrum frequency was 76.5% (95% confidence interval 67.9% to 83.5 %). Overactivity had higher sensitivity than elevated mood for predicting BPII diagnosis. Limitations Single interviewer. Conclusions By systematic probing more focused on past overactivity than mood change, and by inclusion of sub-syndromal hypomania, bipolar spectrum frequency was higher than the near 1 to 1 ratio versus MDD reported up to now (Angst et al. 2003). Given the wide confidence interval, the value in the depression population should be around 70%. Better probing skills by clinicians, and use of semi-structured interviews could much reduce the current high underdiagnosis of BPII and related disorders in usual clinical practice.     

Is overactivity the core feature of hypomania in bipolar II disorder?

BACKGROUND: Recent studies found that overactivity (increased goal-directed activities) may be as important as mood change (elevated and/or irritable mood) for the diagnosis of mania/hypomania (on family history and psychometric grounds), questioning DSM-IV-TR criteria always requiring mood change and listing overactivity among the other symptoms. The aim of the study was to find out if overactivity was at least as important as mood change for the diagnosis of hypomania. SAMPLING AND METHODS: A consecutive sample of 137 bipolar II disorder (BP-II) and 76 major depressive disorder remitted outpatients were interviewed with the Structured Clinical Interview for DSM-IV by a senior clinical and research psychiatrist in a private practice. Patients were asked if they had had hypomanic symptoms and episodes, and which were the most common hypomanic symptoms during the various episodes. The study aim had not been planned when variables were collected for different study goals. RESULTS: Overactivity was the most common hypomanic symptom in BP-II, more common than elevated mood, and had the strongest association with BP-II among all the hypomanic symptoms (overactivity odds ratio = 15.4, elevated mood odds ratio = 12.6). Three factors were found: an 'elevated mood' factor including elevated mood and increased self-esteem; a 'mental activation' factor including racing/crowded thoughts, and a 'behavioral activation' factor including overactivity. There was no relationship between overactivity and mood change. Irritable mood was not associated with overactivity and elevated mood. BP-II was present in 21.6%of patients without a history of overactivity, and in 81.0% of patients with a history of overactivity. BP-II was present in 25.0% of patients without elevated mood, and in 63.3% of patients with elevated mood. As a predictor of BP-II, overactivity had a sensitivity of 90.5%, a specificity of 61.8%, and a positive predictive value of 81.0% (elevated mood: 72.2, 82.8, and 88.3%, respectively). Five or more hypomanic symptoms had the most balanced combination of sensitivity (82.4%) and specificity (85.5%) for BP-II, and a positive predictive value of 91.1%. Overactivity was present in 89.5% of patients with a history of > or = 5 hypomanic symptoms, while elevated mood was present in 76.6%. CONCLUSIONS: Theresults seem to support the view that overactivity may be a core feature of hypomania, suggesting the upgrading of overactivity to a stem criterion for hypomania.     

Factor structure of recalled DSM-IV hypomanic symptoms of bipolar II disorder

The DSM-IV-TR definition of hypomania in bipolar II disorder (BP-II) has yet to show its validity. The aim of the current study was to find the factor structure of hypomania by using DSM-IV-TR symptoms, and to assess the DSM-IV-TR definition of hypomania. One hundred ninety-seven consecutive BP-II remitted outpatients were interviewed by the Structured Clinical Interview for DSM-IV (SCID-CV) as modified by Benazzi and Akiskal (2003) and by Benazzi (2003), in a private practice, assessing the symptoms that were more common during past hypomanic episodes. The factor structure of hypomania was studied by principal component factor analysis. Almost all patients reported overactivity (increased goal-directed activity) during hypomania, and less commonly elevated mood. Overactivity plus three or more symptoms identified 89.3% of DSM-IV-TR BP-II. Factor analysis found three factors: factor 1, including racing thoughts ("mental activation"); factor 2, including elevated mood ("high mood"); and factor 3, including overactivity ("behavioral activation"). Elevated mood was correlated only with two of the nine DSM-IV-TR hypomanic symptoms. The three-domains structure of hypomania by Kraepelin (i.e., increased mood, thought, and activity) was found in the DSM-IV-TR definition of hypomania, partly supporting its list of symptoms. However, DSM-IV-TR priority given to mood change for the diagnosis of hypomania was not supported. An upgrading of overactivity to at least a priority level similar to mood change was supported by (1) its high frequency, (2) its utility to diagnose BP-II, and (3) by factor analysis showing that elevated mood (the "prototypical" symptom of hypomania in DSM-IV-TR) correlated with few symptoms, and that three factors (of which only one included elevated mood) were present.     

Diagnosis of bipolar II disorder: a comparison of structured versus semistructured interviews

BACKGROUND: Reliability of bipolar II (BPII) disorder diagnosis is still a problem. Recent studies have shown that semistructured interviews by clinicians are better than structured interviews by nonclinicians for BPII diagnosis. The aim of the study was to find the degree of agreement in the diagnosis of BPII between the Structured Clinical Interview for DSM-IV (SCID) and a semistructured interview based on DSM-IV criteria done by an expert clinician. METHODS: One hundred eleven remitted major depressive episode (MDE) outpatients were interviewed first with the SCID and soon after that with a semistructured interview following DSM-IV criteria (based on clinical evaluation). Bipolar I (BPI) patients were excluded. RESULTS: By the SCID, 24 patients were diagnosed BPII (21.6%) and 30 were diagnosed BPI (27.0%). By the semistructured interview, 68 patients were diagnosed BPII (61.2% of the entire sample) and none BPI. Agreement between the SCID BPII diagnosis and the semistructured interview BPII diagnosis was 51.3% (meaning one in two missed). Sensitivity and specificity of the SCID BPII diagnosis for the semistructured BPII diagnosis were 29.4% and 90.7%, respectively. Overactivity (increased goal-directed activity) was the most common hypomanic symptom. In the group with overactivity (n=76), a semistructured interview BPII diagnosis was present in 77.6%, while a SCID BPII diagnosis was present in only 22.3%. Sensitivity and specificity of overactivity for BPII diagnosis were 86.7% and 60.4%, respectively, while elevated mood had sensitivity of 60.2% and specificity of 86.0%. CONCLUSIONS: Findings support a diagnosis of BPII based on a semistructured interview by an expert clinician versus a fully structured interview. Overactivity priority level for the diagnosis of hypomania is supported by the present findings.     

The continuum/spectrum concept of mood disorders: is mixed depression the basic link?

Background Mixed states, i.e., opposite polarity symptoms in the same mood episode, question the bipolar/unipolar splitting of mood disorders, and support a spectrum view. Study aim was assessing the distribution of intradepressive hypomanic symptoms between bipolar-II (BP-II) and major depressive disorder (MDD) depressions, and testing a dose–response relationship between number of intradepressive hypomanic symptoms and bipolar family history. No bi-modality, and a dose–response relationship, would not support a categorical distinction. Methods Consecutive 389 BP-II and 261 MDD depressed outpatients were interviewed by the structured clinical interview for DSM-IV, hypomania interview guide, and family history screen, by a mood specialist psychiatrist, in a private practice. Intradepressive hypomanic symptoms were systematically assessed. Mixed depression was defined as the combination of depression and three or more intradepressive hypomanic symptoms, a validated definition. Results BP-II, versus MDD, had significantly more intradepressive hypomanic symptoms. The distribution of intradepressive hypomanic symptoms between BP-II and MDD was not bi-modal but normal-like, and a dose–response relationship was found between the number of intradepressive hypomanic symptoms and bipolar family history. Conclusions Study findings question the categorical division of BP-II and MDD, and may support the spectrum view of mood disorders.     

A tetrachoric factor analysis validation of mixed depression

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

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.     

A new bipolar spectrum concept: a brief review

Angst J, Gamma A. A new bipolar spectrum concept: a brief review. Bipolar Disord 2002: 4(Suppl. 1): 11–14. © Blackwell Munksgaard, 2002
Research on the broad bipolar spectrum is dependent on the definition of hypomania. We recently proposed a new, softer syndromal definition with clinical validity. This broadens the diagnosis of bipolar II (BP-II) disorder at the expense of major depressive disorder (MDD). There is evidence for a third group of suspected BP-II manifesting major depression plus hypomanic symptoms. The two bipolar-II groups together are as prevalent as MDD. A new concept of minor bipolar disorder embracing dysthymia, minor and recurrent brief depression with hypomanic syndromes and symptoms is discussed. Some methodological pitfalls of research on drug-induced hypomania as an element of the bipolar spectrum are also summarized.     

Impact of temperamental mood lability on depressive mixed state

BACKGROUND: Cyclothymic temperament (which includes mood lability) is common in bipolar II disorder (BP-II). Depressive mixed state (DMX), a major depressive episode (MDE) mixed with intra-episode hypomanic symptoms (3 or more, according to a recently validated definition), was found to be common in BP-II and not uncommon in major depressive disorder (MDD). The study aim was to find the impact of temperamental mood lability (TML) on DMX. METHODS: Consecutive 148 BP-II and 117 MDD outpatients presenting for MDE treatment were interviewed by the Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal to reduce the false negative BP-II. Intra-MDE hypomanic symptoms were systematically assessed. Kraepelin, Angst, and Akiskal's definitions of temperamental mood lability (i.e., frequent up and down fluctuations of mood between major mood episodes since young age) were followed. RESULTS: DMX was present in 61.5%, TML in 52.8%. In the DMX sample, TML was present in 57.6%, and in the non-DMX sample TML was present in 45.0% (OR = 1.6, 95% CI = 1.0-2.7). In the DMX sample, independent predictors of DMX with TML were BP-II and young age at onset. Intra-MDE hypomanic symptoms, and MDE, melancholic and atypical symptoms were not significantly different between DMX patients with TML and DMX patients without TML, apart from more temperamental interpersonal sensitivity in DMX patients with TML (OR = 2.0, 95% CI = 1.0-3.8). DISCUSSION: DMX patients with TML had a younger onset age, suggesting that TML may facilitate the onset of DMX or that it may be a precursor of DMX. The association of BP-II with DMX, TML, and interpersonal sensitivity can make the course of BP-II more unstable and its treatment more complex.     

A continuity between bipolar II depression and major depressive disorder?

BACKGROUND: A recent series of studies has questioned the current categorical split of mood disorders into bipolar and depressive disorders. Mixed states, especially mixed depression (i.e., depression plus co-occurring, noneuphoric, hypomanic symptoms) might support a continuity between bipolar II (BP-II) depression and major depressive disorder (MDD). The aim of the study was to assess the distribution of intradepressive hypomanic symptoms rating between BP-II and MDD depressions. A bi-modal distribution would support a categorical distinction, and no bi-modality would support continuity. METHODS: Consecutive 389 BP-II and 261 MDD major depressive episode (MDE) outpatients were interviewed (off psychoactive drugs) with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide (HIG, to assess intradepressive hypomanic symptoms), and the Family History Screen, by a mood specialist psychiatrist in a private practice. Mixed depression was defined as MDE plus 3 or more intradepressive, noneuphoric hypomanic symptoms, a definition validated by Akiskal and Benazzi. The distribution of intradepressive hypomanic symptoms rating was studied by Kernel density estimate and by histogram. RESULTS: BP-II depression, versus MDD depression, had significantly lower age at onset, was significantly more likely to be atypical and mixed, had more depression recurrences, and a higher bipolar family history loading. BP-II depression, versus MDD depression, had significantly more irritability, racing/crowded thoughts, distractibility, psychomotor agitation, talkativeness, increased goal-directed activity, and excessive risky activities. HIG scores were significantly higher in BP-II. The distribution of intradepressive hypomanic symptoms rating showed no bi-modality in the entire depression sample. CONCLUSIONS: Interpretation of study findings relies on the method used to define a categorical disorder. By using classic diagnostic validators (such as family history and age at onset), BP-II and MDD depressions would seem to be distinct disorders. Instead, by using the 'bi-modality' approach, a continuity would seem to be supported. Which of these methods for classification is the best has yet to be shown.     

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.     

A relationship between bipolar II disorder and borderline personality disorder?

BACKGROUND: The relationship between DSM-IV-TR borderline personality disorder (BPD) and bipolar disorders, especially bipolar II disorder (BP-II), is still unclear. Many recent reviews on this topic have come to opposite or different conclusions. STUDY AIM: The aim was to test the association between hypomania symptoms and BPD traits, as hypomania is the defining feature of BP-II in DSM-IV-TR. METHODS: During follow-up visits in a private practice, consecutive 138 remitted BP-II outpatients were re-diagnosed by a mood disorder specialist psychiatrist, using the Structured Clinical Interview for DSM-IV (as modified by Benazzi and Akiskal for better probing hypomania). Soon after, patients self-assessed (blind to interviewer) the SCID-II Personality Questionnaire for BPD. Associations and confounding were tested by logistic regression, between each criteria symptom of hypomania (apart from "racing thoughts" and "distractibility", not assessed as probing focused mainly on behavioral, observable signs), and the entire set of BPD traits. Multivariate regression was also used to jointly regress the entire set of hypomanic symptoms on the entire set of BPD traits. RESULTS: Mean (SD) age was 39.0 (9.8) years, females were 76.3%. Frequency of BPD traits ranged between 17% and 66% (e.g. impulsivity trait 41%, affective instability trait 63%), mean (SD) number of traits was 4.2 (2.3). The most common episodic hypomanic symptoms were elevated mood (91%) and overactivity (93%); frequency of excessive risky, impulsive activities (impulsivity) was 62%. By logistic regression the only significant association was between the episodic impulsivity of hypomania and the trait impulsivity of BPD. Multivariate regression of the entire set of hypomanic symptoms jointly regressed on the entire set of BPD traits was not statistically significant. DISCUSSION: The core feature of BP-II, i.e. hypomania, does not seem to have a close relationship with BDP traits in the study setting, partly running against a strong association between BPD and BP-II and a bipolar spectrum nature of BPD.     

Agitated depression: a valid depression subtype?

PURPOSE: The diagnostic validity of agitated depression (AD, a major depressive episode (MDE) with psychomotor agitation) is unclear. It is not classified in DSM-IV and ICD-10 classification of mental and behavioural disorder (ICD-10). Some data support its subtyping. This study aims to test the subtyping of AD. METHODS: Consecutive 245 bipolar-II (BP-II) and 189 major depressive disorder (MDD) non-tertiary-care MDE outpatients were interviewed (off psychoactive drugs) with Structured Clinical Interview for DSM-IV Axis I Disorders--Clinician Version (SCID-CV), Hypomania Interview Guide (HIGH-C), and Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed. AD was defined as an MDE with psychomotor agitation. Mixed AD was defined as an MDE with four or more hypomanic symptoms (including agitation). FINDINGS: AD was present in 34.7% of patients. AD was mixed in 70.1% of AD patients. AD, vs. non-AD, had significantly (at alpha = 0.05) lower age at onset, more BP-II, females, atypical depressions, bipolar-I (BP-I) and BP-II family history, and was more mixed; racing/crowded thoughts, irritability, more talkativeness, and risky behaviour were significantly more common. Mixed AD, vs. non-AD, had significantly (at alpha = 0.01) lower age at onset, more intra-MDE hypomanic symptoms, BP-II, females, atypical depressions, BP-II family history, and specific hypomanic symptoms (distractibility, racing thoughts, irritable mood, more talkativeness, risky activities). Mixed AD, vs. non-mixed AD, had significantly more intra-MDE hypomanic symptoms (by definition), more recurrences, and more specific hypomanic symptoms (by definition). Non-mixed AD, vs. non-AD, had significantly more intra-MDE hypomanic symptoms and more talkativeness. CONCLUSIONS: AD was common in non-tertiary-care depression outpatients, supporting its diagnostic utility. AD and many bipolar diagnostic validators were associated, supporting its link with the bipolar spectrum. Mixed AD, but not non-mixed AD, had differences vs. non-AD similar to those of AD, suggesting that psychomotor agitation by itself may not be enough to identify AD as a subtype. Findings seem to support the subtyping of mixed AD. This subtyping may have important treatment impact, as antidepressants alone might increase agitation.     

Symptoms of depression as possible markers of bipolar II disorder

Underdiagnosis and misdiagnosis of bipolar-II disorder (BP-II) as a major depressive disorder (MDD) are frequently reported. The study aim was to find which symptoms of depression could be possible cross-sectional markers of BP-II, in order to reduce underdiagnosing BP-II. METHODS: Consecutive 379 BP-II and 271 MDD major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV, the Hypomania Interview Guide, and the Family History Screen, by a senior psychiatrist in a private practice. Inside-MDE hypomanic symptoms (elevated mood and increased self-esteem always absent by definition) were systematically assessed. Mixed depression was defined as an MDE plus 3 or more inside-MDE hypomanic symptoms, a definition validated by Akiskal and Benazzi. RESULTS: The MDE symptoms significantly more common in BP-II versus MDD were weight gain, increased eating, hypersomnia, psychomotor agitation, worthlessness, and diminished ability to concentrate. The inside-MDE hypomanic symptoms significantly more common in BP-II were distractibility, racing/crowded thoughts, irritability, psychomotor agitation, more talkativeness, increased risky and goal-directed activities. Multiple logistic regression showed that hypersomnia, racing/crowded thoughts, irritability, and psychomotor agitation were independent predictors of BP-II. Irritability had the most balanced combination of sensitivity and specificity predicting BP-II. Psychomotor agitation had the highest specificity but the lowest sensitivity. Racing/crowded thoughts had the highest sensitivity but the lowest specificity. These symptoms had a similar positive predictive value (PPV) for BP-II, which was around 70% (PPV is more clinically useful than sensitivity and specificity), which in turn was similar to the PPV of mixed depression and atypical depression (two diagnostic clinical markers of BP-II). All possible combinations of these symptoms had a PPV similar to that of the individual symptoms. The validity as BP-II markers of these symptoms was supported by a significant association with bipolar family history. CONCLUSIONS: Hypersomnia, racing/crowded thoughts, irritability, and psychomotor agitation may be useful, cross-sectional markers of BP-II. Finding these symptoms in depression should lead the clinician to careful probing for history of hypomania, which should reduce the BP-II misdiagnosed as MDD. Results may also have treatment impacts, as antidepressants used alone (i.e., no concurrent mood stabilising agent) in BP-II depression misdiagnosed as MDD may increase cycling.     

A prediction rule for diagnosing hypomania

Background

Missing the diagnosis of past hypomania, and thus of bipolar II disorder, is common. Study aim was to find a ‘prediction rule’ for facilitating the diagnosis of past hypomania.

Methods

In an outpatient psychiatry private practice (non-tertiary care), a consecutive sample of 275 bipolar II disorder (BP-II) remitted patients, and consecutive, independent, sample of 138 major depressive disorder (MDD) remitted patients, had been interviewed for different study goals during follow-up visits by a senior bipolar-trained psychiatrist. Using the Structured Clinical Interview for DSM-IV, modified and validated by Benazzi and Akiskal [Benazzi F (2007). Lancet 369: 935–945] to improve the probing for past hypomania, patients had been questioned about the most common symptoms and duration of recent threshold and subthreshold hypomanic episodes. The sample was retrospective in nature. A prediction rule was tested. This is a score resulting from the sum of the weighted scores of each hypomanic symptom which was an independent predictor of hypomania. Its cutoff score for discriminating hypomania was based on the highest figure of correctly classified hypomanias and on the most balanced combination of sensitivity and specificity. A second, independent sample of 138 BP-II and 71 MDD remitted outpatients was tested to replicate the findings.

Results

By univariate logistic regression, hypomanic symptoms distinguishing BP-II and MDD included ‘increase in goal-directed activity’ (overactivity) (OR = 28.3), ‘elevated mood’ (OR = 14.9), ‘increased talkativeness’ (OR = 9.2), ‘inflated self-esteem’, ‘decreased need for sleep’, ‘excessive risky activities’, and ‘irritable mood’. By multivariable logistic regression, the independent predictors of hypomania resulted ‘increase in goal-directed activity’ (OR = 14.9, weighted score = 15), ‘elevated mood’ (OR = 7.5, weighted score = 7), ‘increased talkativeness’ (OR = 3.6, weighted score = 4); ‘irritable mood’, ‘inflated self-esteem’, ‘decreased need for sleep’, and ‘excessive risky activities’ had ORs between 2.04 and 2.39, with a weighted score = 2. The prediction rule showed that the cutpoint score ≥ 21 had the highest figure of correctly classified hypomanias (88%, ROC area = 0.94), showing the most balanced combination of sensitivity (87%) and specificity (89%). This prediction rule, tested on the second sample, found that the same cutoff score  ≥ 21 correctly classified the highest figure of hypomanias (94%, ROC area = 0.97), showing the most balanced combination of sensitivity (93%) and specificity (95%). To cross this cutoff score, overactivity was always required (as the sum of the scores of elevated mood and of the other symptoms did not reach this cutoff). However, scores 10 to 20 correctly classified only slightly lower figures of hypomanias.

Conclusions

A prediction rule for hypomania was tested. The scores of overactivity plus at least some hypomanic symptom (among elevated mood, irritability, inflated self-esteem, less sleep, talkativeness, excessive risky activities) correctly classified 88% of hypomanias. Instead, elevated mood without overactivity, plus even all the other symptoms, did not reach the best figure of correctly classified. However, lower cutoff scores, up to 10, classified slightly lower figures of hypomanias, but with less balanced combinations of sensitivity and specificity. These findings may have diagnostic utility, because BP-II versus MDD is likely to be a more severe disorder. This prediction rule, if replicated and fine-tuned in different settings, may help clinicians better probing past hypomania, thus reducing the common misdiagnosis of BP-II as MDD.     

Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity

The definitions of bipolar-I (BP-I) and bipolar-II (BP-II) disorders are currently under revision by the APA and by the WHO. We provide evidence of a revised set of criteria for bipolar disorders and major depressive disorder (MDD) which could serve to strengthen the construct and predictive validity of both disorders and enable more incisive studies of treatments and courses of both disorders. In the diagnostic Bridge Study of 5,635 patients with major depressive episodes from 18 countries (Europe, North Africa, Near East and Far East) leading psychiatrists in each country assessed a pre-specified group of symptoms, illness course, family history and duration of episodes; these data allowed tests of several definitions of bipolarity. The primary revised specifier diagnosis of BP-I disorder included manic episodes based on an additional category A criterion (increased activity/energy) and did not apply any exclusion criteria. The revised BP-II disorders included hypomanic episodes of 1–3 days. Family history and illness course validators (history of mania/hypomania among first degree relatives, 2 or more lifetime episodes and first symptoms having occurred before age 30) discriminated clearly between patients with bipolar-I or bipolar-II disorders meeting bipolarity specifier criteria and those with MDD. Specifier definitions provided better discrimination between MDD and the two bipolar subgroups. Patterns of concurrent comorbidities also differed significantly between patients meeting criteria for MDD compared with those meeting bipolar specifier criteria. Comorbidity patterns differed between bipolar-I and bipolar-II patients. This study provides evidence for the validity of modified (specifier) BP-I and BP-II definitions that incorporate illness course and family history which reduce ambiguities of major depressive episodes between bipolar-I and bipolar-II disorders and MDD.     

Impulsivity in bipolar-II disorder: Trait,state, or both?

BACKGROUND: In bipolar-II (BP-II) disorder impulsivity (defined as excessive risky activities by DSM-IV-TR) is one of the symptoms of hypomania. It is unclear if impulsivity is also a trait in BP-II. STUDY AIM: The aim was to test if impulsivity was also a trait in BP-II. METHODS: Consecutive 136 remitted BP-II outpatients (assessed when presenting for depression by a mood disorder specialist psychiatrist using the Structured Clinical Interview for DSM-IV), self-assessed trait impulsivity during follow-ups, using the Personality Questionnaire of the Structured Clinical Interview for DSM-IV Axis II Disorders, in a private practice. Trait mood swings were also self-assessed, using the TEMPS-A. A trait nature of impulsivity in BP-II could be supported by finding (1) a relatively high frequency, (2) association between trait impulsivity and symptoms of past hypomania, especially impulsivity, (3) dose-response relationship between number of past hypomania symptoms and trait impulsivity, and (4) association between trait impulsivity and trait mood swings (a trait feature of BP-II). RESULTS: Trait impulsivity was present in 41.1% of BP-II. BP-II with, versus BP-II without, trait impulsivity had significantly more males, trait mood swings, past hypomania symptoms (irritable mood, talkativeness, increased goal-directed activity), and excessive risky activities (i.e. state impulsivity), corresponding to an irritable risky overactivity. Past state impulsivity and trait impulsivity were significantly associated. Number of past hypomania symptoms and trait impulsivity were significantly correlated. A dose-response relationship was found between number of past hypomania symptoms and trait impulsivity. DISCUSSION: Findings suggest that trait impulsivity may be a feature of BP-II. Limitation of self-assessment of personality traits should be taken into account. Findings may have treatment impacts, as the combination of trait impulsivity and mood swings may facilitate relapses and mixed states, which mood stabilising agents could prevent/delay.     

Classifying mood disorders by age-at-onset instead of polarity

BackgroundPolarity is the pillar of the current categorical unipolar–bipolar division of mood disorders. However, genetic studies on these polarity-based phenotypes have been largely inconclusive. Recent clinical and epidemiological studies seem to support more of a continuum than a splitting of mood disorders. A reshaping of the classification of mood disorders thus seems required. Age-at-onset and recurrence have been suggested to be more clinically and genetically useful in the phenotyping of mood disorders.Study aimTo test a classification of mood disorders based on age-at-onset, and to delineate its phenotypes.MethodsA total of 441 consecutive bipolar II disorder (BP-II) and 289 unipolar major depressive disorder (MDD) outpatients, presenting for treatment of a major depressive episode (MDE) in a clinical and research private practice, were assessed by a mood disorder specialist psychiatrist (FB) using a Structured Clinical Interview for the DSM-IV, modified for better probing past hypomania [Benazzi, F. Bipolar disorder—focus on bipolar II disorder and mixed depression. Lancet 2007a;369: 935–945]. The sample was divided according to age-at-onset. Age-at-onset was defined by the age at onset of the first MDE. Early-age-at-onset (EO) was defined as age at onset before 21 years, late-age-at-onset (LO) as onset at or after age 21 years. The study's current goal had not been planned when data were recorded between 1999 and 2006. Variables were compared in EO versus LO mood disorders, investigating phenotype differences. The main focus was on ‘classic’ diagnostic validators: MDE clinical picture, gender, course, and family history. Age, gender, BP-II, and mania/hypomania family history (possible confounding) were controlled for in the analyses. Logistic regression was used.ResultsFirst, EO was regressed on each variable, one at a time, to find significant associations. Second, EO was regressed on all of the variables whose odds ratio (OR) was statistically significant in the previous analyses in order to find independent predictors. Independent predictors of EO mood disorder were history of hypomania, high recurrence, atypical depression, and family history of mania/hypomania. Controlling for BP-II (in addition to age and gender) did not impact the findings. The highest OR was that between EO and high recurrence (OR = 4.00). Distinguishing MDE symptoms of EO mood disorder included hypersomnia and psychomotor agitation when controlling for age and gender, and, by controlling also for BP-II, hypersomnia only.DiscussionA close association among EO mood disorder, high recurrence, and bipolarity (history of hypomania, family history of mania/hypomania) was found. Compared to most previous studies testing EO versus LO in bipolar (mainly BP-I) or in unipolar MDD samples, the present study tested a mixed BP-II and MDD sample and controlled for polarity, reducing, as much as possible, the impact of polarity on the findings. EO (below age 21 years) was distinguished by hypersomnic depression, high recurrence, high history of hypomania, and high history of mania/hypomania. Replications are needed, especially in mixed samples also including BP-I. Results, if replicated, could have implications not only for clinical and genetic studies, but also for treatment (e.g., mood stabilizers could have better long-term effects than antidepressants in EO mood disorders, antidepressants could have negative long-term effects on EO).