The early diagnosis of bipolar II disorder remains difficult in clinical practice, hence the importance of psychometric tests.

To detect hypomania in patients followed for a major depressive disorder (MDD) and to determine factors which are correlated with it.

This was a cross-sectional, descriptive and analytical study. It involved 40 psychiatric outpatients, who were followed for MDD (isolated or recurrent episode) at the Hedi Chaker University Hospital in Sfax (Tunisia), from January 26 to February 10, 2020. The study was conducted using a questionnaire and the Angst Hypomania Checklist-20 (HCL-20).

The sex ratio (M/F) was 0.66 with an average age of 54.8 years. MDD started at an average age of 41.45 years. According to HCL-20, half of our sample had hypomania. The presence of hypomania was correlated with young age (p = 0.022), academic failure (p = 0.038) and smoking (p = 0.003). In addition, there was a statistically significant relationship between the presence of hypomania and the characteristics of the disease: number of depressive episodes ≥ 2 (p = 0.013), psychotic features (p = 0.038), melancholic features (p=0,025) and premature discontinuation of treatment (p = 0.003).

Our study confirmed that bipolar depression is still underdiagnosed and poorly treated. Questioning a patient about a history of hypomania would be a delicate task and would require the help of a scale, in particular the HCL -20.

DSM-IV definition of hypomania of bipolar-II disorder (BP-II), which includes elevated/irritable mood change as core feature (i.e., it must always be present), is not based on sound evidence.

Following classic descriptions of hypomania, was to test if hypomania could be diagnosed on the basis of its number (9) of DSM-IV symptoms, setting no-priority symptom.

Consecutive 422 depression-remitted outpatients were re-interviewed by a mood specialist psychiatrist using the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinician Version [a semi-structured interview modified by Benazzi and Akiskal (J Affect Disord, 2003; J Clin Psychiatry, 2005) to improve the probing for BP-II] in a private practice. History of episodes of subthreshold (i.e., 2 or more symptoms) and threshold (i.e., meeting DSM-IV criteria of elevated mood plus at least 3 symptoms, or irritable mood plus at least 4) hypomania, lasting at least 2 days, and which were the most common symptoms during the episodes, were systematically assessed.

Bipolar-II disorder (BP-II) patients (according to DSM-IV criteria, apart from hypomania duration) were 260, and major depressive disorder (MDD) patients were 162. Mood change was present in all BP-II by definition. The most common symptoms were overactivity, which was present in almost all BP-II, followed by elevated mood and racing thoughts. ROC analysis of the number of hypomanic symptoms predicting BP-II found that a cut point of 5 or more symptoms over 9 had the best combination of sensitivity (90%) and specificity (84%), and the highest figure of correctly classified (87%) BP-II. History of episodes of 5 or more hypomanic symptoms was met by almost all BP-II.

Single interviewer.

Following classic descriptions of hypomania, not setting any priority among the three basic domains of hypomania (mood, thinking, behavior), results suggest that a cutoff number of 5 symptoms over 9 (of those listed by DSM-IV) could be used to diagnose hypomania of BP-II. Diagnosing hypomania by counting a checklist of symptoms should make it easier to diagnose BP-II, and should reduce the current high misdiagnosis of BP-II as MDD, significantly impacting the treatment of depression.

The current categorical split of mood disorders in bipolar disorders and depressive disorders has recently been questioned. Two highly unstable personality features, i.e. the cyclothymic temperament (CT) and borderline personality disorder (BPD), have been found to be more common in bipolar II (BP-II) disorder than in major depressive disorder (MDD). According to Kraepelin, temperamental instability was the ‘foundation’ of his unitary view of mood disorders.

The aim was to assess the distributions of the number of CT and borderline personality items between BP-II and MDD. Finding no bi-modal distribution (a ‘zone of rarity’) of these items would support a continuity between the two disorders.

Study setting: an outpatient psychiatry private practice. Interviewer: A senior clinical and mood disorder research psychiatrist. Patient population: A consecutive sample of 138 BP-II and 71 MDD remitted outpatients. Assessment instruments: The structured clinical interview for DSM-IV Axis I Disorders-Clinician Version (SCID-CV), the SCID-II Personality Questionnaire for self-assessing borderline personality traits (BPT) by patients, the TEMPS-A for self-assessing CT by patients. Interview methods: Patients were interviewed with the SCID-CV to diagnose BP-II and MDD, and then patients self-assessed the questions of the Personality Questionnaire relative to borderline personality, and the questions of the TEMPS-A relative to CT. As clinically significant distress or impairment of functioning is not assessed by the SCID-II Personality Questionnaire, a diagnosis of BPD could not be made, but BPT could be assessed (i.e. all BPD items but not the impairment criterion). The distribution of the number of CT and BPT items was studied by Kernel density estimate.

CT and BPT items were significantly more common in BP-II versus MDD. The Kernel density estimate distributions of the number of CT and BPT items in the entire sample had a normal-like shape (i.e. no bi-modality).

The expected finding, on the basis of previous studies and of the present sample features, was a clustering of CT and BPT items on the BP-II side of the curves. Instead, no bi-modality was present in the distributions of the number of CT and BPT items in the entire sample, showing a normal-like shape. By using the bi-modality approach, a continuity between BP-II and MDD seems supported, questioning the current categorical splitting of BP-II and MDD based on classic diagnostic validators.

To review the diagnostic validity and utility of mixed depression, i.e. co-occurrence of depression and manic/hypomanic symptoms.

PubMed search of all English-language papers published between January 1966 and December 2006 using and cross-listing key words: bipolar disorder, mixed states, criteria, utility, validation, gender, temperament, depression-mixed states, mixed depression, depressive mixed state/s, dysphoric hypomania, mixed hypomania, mixed/dysphoric mania, agitated depression, anxiety disorders, neuroimaging, pathophysiology, and genetics. A manual review of paper reference lists was also conducted.

By classic diagnostic validators, the diagnostic validity of categorically-defined mixed depression (i.e. at least 2–3 manic/hypomanic symptoms) is mainly supported by family history (the current strongest diagnostic validator). Its diagnostic utility is supported by treatment response (negative effects of antidepressants). A dimensionally-defined mixed depression is instead supported by a non-bi-modal distribution of its intradepression manic/hypomanic symptoms.

Categorically-defined mixed depression may have some diagnostic validity (family history is the current strongest validator). Its diagnostic utility seems supported by treatment response.

As psychotic agitated depression is now a well-described form of mixed state during the course of bipolar I disorder, we sought to investigate the diagnostic validity of a new definition for agitated (mixed) depression in bipolar II (BP-II) and major depressive disorder (MDD).

Three hundred and thirty six consecutive outpatients presenting with major depressive episodes (MDE) but without history of mania were evaluated with the Structured Clinical Interview for DSM-IV when presenting for the treatment of MDE. On the basis of history of hypomania they were assigned to BP-II (n = 206) vs. MDD (n = 130). All patients were also examined for hypomania during the current MDE. Mixed depression was operationally defined by the coexistence of a MDE and at least two of the following excitatory signs and symptoms as described by Koukopoulos and Koukopoulos (Koukopoulos A, Koukopoulos A. Agitated depression as a mixed state and the problem of melancholia. In: Akiskal HS, editor. Bipolarity: beyond classic mania. Psychiatr Clin North Am 1999;22:547–64): inner psychic tension (irritability), psychomotor agitation, and racing/crowded thoughts. The validity of mixed depression was investigated by documenting its association with BP-II disorder and with external variables distinguishing it from unipolar MDD (i.e., younger age at onset, greater recurrence, and family history of bipolar disorders). We analyzed the data with multivariate regression (STATA 7).

MDE plus psychic tension (irritability) and agitation accounted for 15.4%, and MDE plus agitation and crowded thoughts for 15.1%. The highest rate of mixed depression (38.6%) was achieved with a definition combining MDE with psychic tension (irritability) and crowded thoughts: 23.0% of these belonged to MDD and 76.9% to BP-II. Moreover, any of these permutations of signs and symptoms defining mixed depression was significantly and strongly associated with external validators for bipolarity. The mixed irritable-agitated syndrome depression with racing-crowded thoughts was further characterized by distractibility (74–82%) and increased talkativeness (25–42%); of expansive behaviors from the criteria B list for hypomania, only risk taking occurred with some frequency (15–17%).

These findings support the inclusion of outpatient-agitated depressions within the bipolar spectrum. Agitated depression is validated herein as a dysphorically excited form of melancholia, which should tip clinicians to think of such a patient belonging to or arising from a bipolar substrate. Our data support the Kraepelinian position on this matter, but regrettably this is contrary to current ICD-10 and DSM-IV conventions. Cross-sectional symptomatologic hints to bipolarity in this mixed/agitated depressive syndrome are virtually absent in that such patients do not appear to display the typical euphoric/expansive characteristics of hypomania—even though history of such behavior may be elicited by skillful interviewing for BP-II. We submit that the application of this diagnostic entity in outpatient practice would be of considerable clinical value, given the frequency with which these patients are encountered in such practice and the extent to which their misdiagnosis as unipolar MDD could lead to antidepressant monotherapy, thereby aggravating it in the absence of more appropriate treatment with mood stabilizers and/or atypical antipsychotics.

Given its diverse disease courses and symptom presentations, multiple phenotype dimensions with different biological underpinnings are expected with bipolar disorders (BPs). In this study, we aimed to identify lifetime BP psychopathology dimensions. We also explored the differing associations with bipolar I (BP-I) and bipolar II (BP-II) disorders.

We included a total of 307 subjects with BPs in the analysis. For the factor analysis, we chose six variables related to clinical courses, 29 indicators covering lifetime symptoms of mood episodes, and 6 specific comorbid conditions. To determine the relationships among the identified phenotypic dimensions and their effects on differentiating BP subtypes, we applied structural equation modeling.

We selected a six-factor solution through scree plot, Velicer's minimum average partial test, and face validity evaluations; the six factors were cyclicity, depression, atypical vegetative symptoms, elation, psychotic/irritable mania, and comorbidity. In the path analysis, five factors excluding atypical vegetative symptoms were associated with one another. Cyclicity, depression, and comorbidity had positive associations, and they correlated negatively with psychotic/irritable mania; elation showed positive correlations with cyclicity and psychotic/irritable mania. Depression, cyclicity, and comorbidity were stronger in BP-II than in BP-I, and they contributed significantly to the distinction between the two disorders.

We identified six phenotype dimensions; in addition to symptom features of manic and depressive episodes, various comorbidities and high cyclicity constructed separate dimensions. Except for atypical vegetative symptoms, all factors showed a complex interdependency and played roles in discriminating BP-II from BP-I.