On-line estimation and detection of abnormal substrate concentrations in WWTPs using a software sensor: a benchmark study.

In this paper, a new approach for on-line monitoring and detection of abnormal readily biodegradable substrate (S(s)) and slowly biodegradable substrate (X(s)) concentrations, for example due to input of toxic loads from the sewer, or due to influent substrate shock load, is proposed. Considering that measurements of S(s) and X(s) concentrations are not available in real wastewater treatment plants, the S(s) / X(s) software sensor can activate an alarm with a response time of about 60 and 90 minutes, respectively, based on the dissolved oxygen measurement. The software sensor implementation is based on an extended Kalman filter observer and disturbances are modelled using fast Fourier transform and spectrum analyses. Three case studies are described. The first one illustrates the fast and accurate convergence of the extended Kalman filter algorithm, which is achieved in less than 2 hours. Furthermore, the difficulties of estimating X(s) when off-line analysis is not available are depicted, and the S(s) / X(s) software sensor performances when no measurements of S(s) and X(s) are available are illustrated. Estimation problems related to the death-regeneration concept of the activated sludge model no.1 and possible application of the software sensor in wastewater monitoring are discussed.

Melancholia and atypical depression in the Zurich study: epidemiology, clinical characteristics, course, comorbidity and personality.

OBJECTIVE: A comparison of psychiatric, psychological and somatic characteristics in specified subgroups of major depressive episodes (MDE). METHOD: In a stratified community sample of young adults investigated prospectively from age 20/21 to 40/41, we defined four MDE subgroups: i) DSM-IV melancholia or atypical depression (the 'combined group'), ii) pure melancholia, iii) pure atypical depression, and iv) unspecified MDE. RESULTS: The cumulative incidence rates of the four groups were 4.1%, 7.1%, 3.5% and 8.2% respectively. Women were over-represented in the combined and atypically depressed group. In 56 of 117 (47.9%) cases, melancholia was longitudinally associated with atypical MDE (n = 84) (OR = 11.9). CONCLUSION: Melancholic MDE was more severe than atypical MDE although the two groups shared many characteristics. The longitudinal overlap of melancholia with atypical depression in almost half of all cases calls for comparative analyses of combined, pure and unspecified MDE.

Does temperamental instability support a continuity between bipolar II disorder and major depressive disorder?

BACKGROUND: 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. STUDY AIM: 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. RESULTS: 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). CONCLUSIONS: 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.

Toward a validation of a new definition of agitated depression as a bipolar mixed state (mixed depression).

PURPOSE: 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). MATERIALS AND METHODS: 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). RESULTS: 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%). CONCLUSIONS: 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.

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 and Akiskal. 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. 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.). 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.

Depressive mixed state: testing different definitions.

The aim of this study was to test different definitions of depressive mixed state (DMX) (major depressive episode (MDE) with some concurrent hypomanic symptoms), to find which one could better define DMX. Unipolar and bipolar II MDE outpatients (n = 168) were interviewed with the DSM-IV Structured Clinical Interview. Depressive mixed state was defined as a MDE with two or more (DMX2), and as a MDE with three or more (DMX3) concurrent hypomanic symptoms. DMX2 was present in 71.8% bipolar II patients, and in 41.5% unipolar (P < 0.01). DMX3 was present in 46.6% of bipolar II, and in 7.6% unipolar patients (P < 0.01). DMX2 and DMX3 had almost the same significant and non-significant associations with study variables (diagnosis, gender, age, age at onset, illness duration, MDE recurrences, axis I comorbidity, MDE severity, depression chronicity, hypomanic, MDE, psychotic, melancholic, and atypical symptoms and features). DMX3 was more strongly associated with bipolar II than DMX2 (odds ratio 10.4 vs 3.5). Findings suggest that DMX3 may be a better definition of DMX due to its stronger association with bipolar II disorder. Findings have important clinical and treatment implications because antidepressants may worsen DMX, and the presence of DMX may induce clinicians to assess systematically and carefully the history of past hypomania.

Sensitivity and specificity of clinical markers for the diagnosis of bipolar II disorder.

Bipolar II disorder is common in depressed outpatients, but the diagnosis may have low reliability because it is often based on history of hypomania. The aim of the present study was to test sensitivity and specificity for bipolar II diagnosis of some reported markers of bipolar II: atypical features, depressive mixed state, young age at onset, recurrences, and interpersonal rejection sensitivity. A total of 161 consecutive unipolar (n = 64) and bipolar II (n = 97) outpatients with major depressive episode (MDE) were interviewed using the Structured Clinical Interview for DSM-IV (SCID). Depressive mixed state was defined as a MDE with two or more (DMX2) or with three or more (DMX3) concurrent hypomanic symptoms. DMX3 and atypical features had the highest specificity (92.1% and 82.8%, respectively) and predictive power (0.69 and 0.64), but low sensitivity (46.3%, 45.3%). Concurrent presence of DMX3 and atypical features increased sensitivity (67.0%), reduced specificity (76.5%), and increased predictive power (0.75). Age at onset, recurrences, and interpersonal rejection sensitivity, concurrent with DMX3 and atypical features, increased the predictive power only slightly. Thus, two cross-sectional features of a MDE, such as DMX3 and atypical symptoms, alone or in combination, may strongly support bipolar II diagnosis, and it appears that DMX3 is the best of the two. The low reliability of bipolar II diagnosis based on history of hypomania may be improved by two cross-sectional clinical markers.

Age at onset of bipolar II depressive mixed state.

Depressive mixed state (DMS) (a major depressive episode [MDE] with some concurrent hypomanic symptoms) is understudied. The aims of the study were to find if the prevalence of DMS, and its clinical correlates, in bipolar II depressed outpatients changed according to bipolar II age at onset. A consecutive sample of 92 bipolar II MDE outpatients were interviewed with the Structured Clinical Interview for DSM-IV. DMS was defined as an MDE with two or more concurrent hypomanic symptoms (DMS2). Prevalence of DMS2 in bipolar II with onset after 30 and 40 years was significantly lower than prevalence in bipolar II with onset before 31 and 41 years. There was a significant negative association between DMS2 and age at onset. There were no significantly different clinical correlates between DMS2 in bipolar II with onset after 30 and before 31 years. Limitations of the study include use of a single interviewer, non-blind assessment, cross-sectional design and bipolar II diagnosis based on history. DMS2 was more likely in bipolar II with a younger age at onset. Different bipolar II ages at onset did not have an effect on DMS2 clinical correlates.

Bipolar II depression in late life: prevalence and clinical features in 525 depressed outpatients.

BACKGROUND: Late-life bipolar II depression has not been well studied. The aim of the present study was to find the prevalence of late-life (50 years or more) bipolar II depression among unipolar and bipolar depressed outpatients, and to compare it with bipolar II depression in younger patients, looking for differences supporting the subtyping of bipolar II depression according to age at onset. METHODS: Consecutive 525 patients presenting for treatment of a major depressive episode were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning Scale. RESULTS: Among patients less than 50 years, 53.4% had bipolar II depression. Among patients 50 years or more, 32.9% had bipolar II depression (significant difference). Atypical features were present in 60.9% of bipolar II patients less than 50 years, and in 26.1% of those 50 years or more (significant difference). Bipolar II patients 50 years or more had significantly higher age at onset than those less than 50 years. Bipolar II and unipolar patients 50 years or more were not significantly different, apart from comorbidity. Bipolar II patients less than 50 years had significantly more atypical features than unipolar ones. LIMITATIONS: Single interviewer, single nonblind assessment, cross-sectional assessment, exclusion of substance abuse and severe personality disorder patients, comorbidity not systematically assessed, modification of DSM-IV duration criterion for hypomania. CONCLUSIONS: Findings suggest that bipolar II depression and atypical features are less common in late life. Differences in age at onset and atypical features support the subtyping of bipolar II depression according to age at onset.

Factor analysis of the Montgomery Asberg Depression Rating Scale in 251 bipolar II and 306 unipolar depressed outpatients.

Symptomatological differences between bipolar II (n = 251) and unipolar (n = 306) depressed outpatients, interviewed with the Structured Clinical Interview for DSM-IV, were studied by Montgomery Asberg Depression Rating Scale factor analysis. Different factors were found in bipolar II [factor 1 (apparent sadness, reported sadness), factor 2 (reduced sleep, reduced appetite), factor 3 (concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts)], and in unipolar [factor 1 (apparent sadness, reported sadness, inability to feel, suicidal thoughts), factor 2 (concentration difficulties, lassitude, inability to feel, pessimistic thoughts), factor 3 (inner tension, reduced sleep)]. Different factor structure (between bipolar II and unipolar depression) supports previous findings that response to antidepressants and biology may be different in bipolar II and unipolar depression.

Prevalence and clinical correlates of residual depressive symptoms in bipolar II disorder.

BACKGROUND: Most patients with unipolar and bipolar I disorder have residual symptoms, despite successful treatment. The appraisal of subsyndromal symptomatology has important implications for pathophysiological models of disease and relapse prevention. Residual symptoms in bipolar II disorder were studied insufficiently. The study of residual symptoms in bipolar II disorder is important, because many depressed outpatients may suffer from it and because bipolar II disorder may be distinct from type I. The study aims were to assess the prevalence and clinical correlates of persistent residual depressive symptoms in bipolar II disorder. METHODS: 138 consecutive patients with bipolar II disorder and 83 unipolar disorder outpatients, presenting for major depressive episode treatment in private practice, were interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders - Clinician's Version. Study variables were persistent (more than 2 years) residual depressive symptoms, age, gender, age at onset, illness duration, recurrences, axis I comorbidity, severity, psychotic, melancholic and atypical features. RESULTS: The prevalence of residual depressive symptoms was 44.9% in bipolar II disorder and 43.3% in unipolar disorder. Residual depressive symptoms in bipolar II and unipolar disorders were significantly and positively associated with illness duration and recurrences. CONCLUSIONS: Persistent residual depressive symptoms were common in bipolar II disorder. Residual unipolar and bipolar II depressive symptoms were related to duration of illness and number of recurrences. Reducing these variables could reduce and prevent residual symptoms. A mechanism of kindling (more mood episodes leading to worse outcome) could be that of leaving a larger and larger amount of residual symptoms after the acute episode has subsided.

Atypical depression with hypomanic symptoms.

BACKGROUND: Depressive mixed states (major depressive episodes with some hypomanic symptoms) (DMS) are not classified in DSM-IV and are understudied. The aims of this study were to find the prevalence and clinical features of DMS in atypical depression. METHODS: A total of 87 bipolar II and unipolar depressed outpatients were interviewed within the DSM-IV Structured Clinical Interview. RESULTS: More than two hypomanic symptoms were present in 50.0% of the atypical and 20.3% of the non-atypical depression cases (P=0.006). DMS mainly included irritable mood, distractibility, racing thoughts, and increased talking. LIMITATIONS: There was a single interviewer, and it was a non-blind, cross-sectional assessment, with bipolar II reliability. CONCLUSIONS: Findings have treatment implications, as antidepressants may worsen DMS, and mood stabilizers may improve it.

Is 4 days the minimum duration of hypomania in bipolar II disorder?

DSM-IV requires that bipolar II disorder has hypomania with a minimum duration of 4 days, a cutoff not based on data. The study aim was to test if hypomania lasting 2 to 3 days could identify a group of bipolar II with typical clinical features of bipolar disorders. Consecutively, 65 unipolar and 103 bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV. Almost all had had 2 to 3 days of hypomania, and all had had more than one hypomania. Typical clinical variables distinguishing bipolar from unipolar disorders (age at onset, atypical features, and recurrences) were compared. Bipolar II had significantly lower age at onset, more recurrences, and more atypical features. Findings suggest that hypomania lasting 2 to 3 days may identify a bipolar II group having typical features of bipolar disorders.

Early-onset versus late-onset bipolar II chronic depression.

Age at onset is an important dimension in the classification of mood disorders. Recent findings on early-onset (EO) versus late-onset (LO) unipolar chronic depressions support this subtyping. The aim of the present study was to determine clinical differences between EO and LO bipolar II chronic depression and to support this subtyping also in bipolar II. Eighty-seven consecutive bipolar II chronic depression outpatients were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery Asberg Depression Rating Scale, and the Global Assessment of Functioning scale. EO cut-offs were 21 and 23 years of age. Variables, studied with linear and logistic regression, were age, gender, age at onset, illness duration, recurrences, atypical, melancholic, and psychotic features, axis I comorbidity, and severity. Lower age at onset was significantly associated with lower age, longer illness duration, less psychosis, less severity, more atypical features, and more axis I comorbidity. Results support the subtyping of bipolar II chronic depression in EO and LO on the basis of different clinical features.

Course and outcome of bipolar II disorder: a retrospective study.

To study course and outcome of Bipolar II disorder, 217 major depressive episode (MDE) patients were interviewed with Structured Clinical Interview for DSM-IV. Patients with more than three MDE and patients with fewer MDE were compared. Patients with more than three MDE were 77.8%. Comparisons, controlled for confounding effects of age and illness duration, found that patients with many MDE had significantly lower age at onset and more chronicity. Results support subtyping of Bipolar II in a small good-outcome group, and a large moderate-poor-outcome group.

The clinical picture of bipolar II outpatient depression in private practice.

Uncertainties exist about whether depressive episodes differ phenomenologically in unipolar and bipolar II patients. The aim of the present study was to better define the clinical picture and course of bipolar II depression. Three hundred and ninety-nine consecutive outpatients, presenting for treatment of unipolar and bipolar II depression, were interviewed with the Structured Clinical Interview for DSM-IV, the Montgomery-Asberg Depression Rating Scale and the Global Assessment of Functioning Scale. Bipolar II depression had significantly lower age at onset, more recurrences and more patients with DSM-IV atypical features. Gender, duration of illness, psychosis, chronicity, severity, axis I comorbidity, melancholic features, individual atypical symptoms and other symptoms of depression were not significantly different. The presence of DSM-IV atypical features predicted bipolar II diagnosis with 63% probability.

Major depressive episodes with hypomanic symptoms are common among depressed outpatients.

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