Impact on suicidality of the borderline personality traits impulsivity and affective instability.

BACKGROUND: The aim of this study was to test the impact on suicidality (suicide threats, attempts) of the borderline personality disorder (BPD) traits impulsivity and affective instability in mood disorders. METHODS: In a general psychiatry private practice (nontertiary care), consecutive remitted, non-substance-abusing outpatients--138 with bipolar II disorder (BP II) and 71 with major depressive disorder (MDD)--self-assessed using the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) Questionnaire. RESULTS: The frequency (higher in BP II) of suicidality was 14%; impulsivity, 37%; and affective instability, 58%. The suicidality-positive patients (n = 30), when compared with the suicidality-negative patients (n = 179), had more BP II, more impulsivity (odds ratio [OR], 5.5; 95% confidence interval [CI], 2.3 to 13.3), and more affective instability (OR, 2.4; 95% CI, 0.99 to 6.0). Logistic regression of suicidality vs impulsivity and affective instability (controlled for BP II; age; and interactions among BP II, age, impulsivity, and affective instability), showed that impulsivity was a strong independent predictor of suicidality (OR, 4.3; 95% CI, 1.7 to 10.6), and that affective instability was not an independent predictor of suicidality (OR,1.6; 95% 0.6 to 4.1). BP II showed neither confounding nor interactions. CONCLUSION: Results showed a strong independent impact of impulsivity-but not affective instability-on suicidality in BPD. No confounding by mood and substance disorders supported the BPD nature of these associations.

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 > or = 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 > or =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.

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

BACKGROUND: Polarity 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 AIM: To test a classification of mood disorders based on age-at-onset, and to delineate its phenotypes. METHODS: A 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. RESULTS: First, 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. DISCUSSION: A 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).

Does hypomania distinguish bipolar II disorder from major depressive disorder?

BACKGROUND: Recent epidemiological/clinical studies have not found clear boundaries between bipolar II disorder (BP-II) and major depressive disorder (MDD), as subsyndromalhypomanic episodes were more common than syndromalhypomania. The aim of the study was to test if hypomania could still be used to split categorically BP-II and MDD. METHODS: 274 consecutive remitted BP-II and 129 MDD outpatients were interviewed by the Structured Clinical Interview for DSM-IV on the most common symptoms and duration of hypomanic episodes (lasting at least 2 days, having at least 2 symptoms), in a private practice. RESULTS: As expected by definition, BP-II versus MDD had significantly more episodic hypomanic symptoms. However, MDD had episodes of subsyndromalhypomanic symptoms (median number of symptoms 3). In the entire sample, frequency of episodes of hypomanic symptoms, according to the number of symptoms per episode, was normally, not bimodally,distributed. A grading(r = 0.57, p < 0.001) of the number of episodic hypomanic symptoms was found. DISCUSSION: Findings question the splitting of BP-II and MDD based on hypomania, as hypomania (at least as defined by DSM-IV) seems more a dimensional than a categorical disorder.

Does psychomotor agitation in major depressive episodes indicate bipolarity? Evidence from the Zurich Study.

BACKGROUND: Kraepelin's partial interpretation of agitated depression as a mixed state of "manic-depressive insanity" (including the current concept of bipolar disorder) has recently been the focus of much research. This paper tested whether, how, and to what extent both psychomotor symptoms, agitation and retardation in depression are related to bipolarity and anxiety. METHOD: The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N = 591) (aged 20 at first interview) by six interviews over 20 years (1979-1999). Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 (five interviews) on the basis of the observed and reported behaviour within the interview section on depression. Psychiatric diagnoses were strictly operationalised and, in the case of bipolar-II disorder, were broader than proposed by DSM-IV-TR and ICD-10. As indicators of bipolarity, the association with bipolar disorder, a family history of mania/hypomania/cyclothymia, together with hypomanic and cyclothymic temperament as assessed by the general behavior inventory (GBI) [15], and mood lability (an element of cyclothymic temperament) were used. RESULTS: Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety. Longitudinally, agitation and retardation were significantly associated with each other (OR = 1.8, 95% CI = 1.0-3.2), and this combined group of major depressives showed stronger associations with bipolarity, with both hypomanic/cyclothymic and depressive temperamental traits, and with anxiety. Among agitated, non-retarded depressives, unipolar mood disorder was even twice as common as bipolar mood disorder. CONCLUSION: Combined agitated and retarded major depressive states are more often bipolar than unipolar, but, in general, agitated depression (with or without retardation) is not more frequently bipolar than retarded depression (with or without agitation), and pure agitated depression is even much less frequently bipolar than unipolar. The findings do not support the hypothesis that agitated depressive syndromes are mixed states. LIMITATIONS: The results are limited to a population up to the age of 40; bipolar-I disorders could not be analysed (small N).

Cyclothymic temperament: the impact of age.

BACKGROUND: Cyclothymic temperament (CT) is a more or less 'permanent' instability of mood, thinking and activity (behaviour), which is frequent in bipolar disorders. Testing the impact of age on CT items, as has been done in many mood disorders, could further define its features. The aim of the study was to test the relationship between age and CT items. METHODS: During follow-up visits in a private practice, 209consecutive remitted bipolar II (BP-II, n = 138) and major depressive disorder (MDD, n = 71) outpatients were re-diagnosed by a mood disorder specialist psychiatrist, using the Structured Clinical Interview for DSM-IV (blind to patients), and self-assessed CT was evaluated by the TEMPS-A questionnaire (blind to interviewer). RESULTS: Mean (SD) age was 39.1 (10.0) years (median 39, range 16-63 years). BP-II had significantly more CT items. Logistic regression tested the association between each CT item and age. Of the 17 CT items, 8 showed a trend (p < 0.10) or significant association with age. Among these items, there were items suggested to be core features of CT, i.e. instability of mood and energy: 'moods and energy either high or low', 'constantly switching between being lively and sluggish' and 'being sad and happy at the same time'. However, other CT items related to mood and energy instability, i.e. 'sudden shifts in mood and energy' and 'mood often changing for no reason', were not significantly associated with age. DISCUSSION: Study findings suggest that age may have an impact on some CT items related to mood and energy, which might become more common with age (according to the item's wording), and that many CT items may not be impacted by age, suggesting more stability.

Is a family history of bipolar disorder a risk factor for migraine among affectively ill patients?

AIMS: The aim was to determine whether having a family history of bipolar disorder (BPD) or unipolar major depressive disorder (MDD) is associated with an increased likelihood of having migraine headaches. METHODS: Latino adults received structured diagnostic interviews. Family history was determined by live interview of first-degree relatives or interview by proxy. All patients met the criteria for major depressive episode (MDE) at the time of assessment. The method of diagnosing migraine had sensitivity and specificity of 87 and 50%, respectively. Logistic regression was used to test for associations and control for confounding. RESULTS: In total, 153 patients met the criteria for MDD and 87 for BPD. Patients with MDD who had a family history of BPD were 4.3 times more likely to have migraine headaches than those who did not (OR=4.34, z=3.02, p=0.003, 95% CI=1.67-11.27). Patients with BPD who had a family history of BPD were 3 times more likely to have migraine than those who did not (OR=2.99, z=2.45, p=0.014, 95% CI=1.25-7.19). Within the entire group of patients, those with a family history of BPD were 4.4 times more likely to have migraine headaches than those who did not (OR = 4.38, p<0.0001, z=4.72, 95% CI=2.37-8.09). A family history of MDD was not associated with an increased risk of having migraine. CONCLUSION: Regardless of a patient's polarity, having a family history of BPD is associated with an increased risk of having migraine headache.

Bipolar disorder--focus on bipolar II disorder and mixed depression.

Bipolar II disorder (recurrent depressive and hypomanic episodes) and related disorders (united in the bipolar spectrum) are understudied, despite a prevalence of about 5% in the community and about 50% in depressed outpatients. The apparent increase in prevalence of the bipolar spectrum is related to several changes in diagnostic criteria, including improved probing for history of hypomania (focused more on overactivity than on mood change), lower minimum duration of hypomania, and inclusion of unipolar depressions with bipolar signs (eg, family history of bipolar disorder, mixed depression). Prevalence of mixed depression, a combination of depression and manic or hypomanic symptoms, is high in patients with bipolar disorders. Controlled studies are needed to investigate treatment of mixed depression; antidepressants can worsen manic and hypomanic symptoms, and mood stabilising agents might be necessary.

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.

Defining 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, it is still unclear if its definition should be based on specific manic symptoms or on a number/score of manic symptoms. Different definitions may have different diagnostic utility, such as treatment impacts. STUDY AIM: Study aim was to test which definition of mixed depression was more supported, by using, as diagnostic validator, early age at onset on the basis of previous studies supporting its bipolar nature. METHODS: Consecutive 336 Bipolar II Disorder (BP-II), and 224 Major Depressive Disorder (MDD) outpatients were cross-sectionally assessed for major depressive episode (MDE) and concurrent DSM-IV hypomanic symptoms when presenting for treatment of depression, by a mood disorder specialist psychiatrist using the Structured Clinical Interview for DSM-IV as modified by Akiskal and Benazzi (J Clin Psychiatry, 2005) and the Hypomania Interview Guide (HIG), in a private practice. Mixed depression was defined as co-occurrence of MDE and hypomanic symptoms. Early age at onset (EO) below 21 years was used as diagnostic validator. RESULTS: Multivariable logistic regression of EO versus all within-MDE hypomanic symptoms, controlled for BP-II, showed that no specific symptom was independently associated with EO. By ROC analysis versus EO, the best combination of sensitivity and specificity, and the highest figure of correctly classified, were shown by a cutoff number >=3 symptoms, and by a cutoff HIG score >=8. Both cutoffs had similar strength of association with EO. Mixed depression defined by >=3 within-MDE hypomanic symptoms (A), or by a HIG score >=8 (B), were more frequent in EO group versus LO group (A: 70.5% versus 49.8%; B: 60.7% versus 40.9%; p<0.001), and in BP-II versus MDD (A: 72.3% versus 39.7%; p<0.001; positive predictive value for BP-II=73.1%; B: 63.9% versus 29.0%; p<0.001; positive predictive value for BP-II=76.7%). DISCUSSION: Findings could support the diagnostic validity of a definition of mixed depression based on a cutoff number/score of within-depression hypomanic symptoms versus one based on specific symptoms, complementing and supporting previous studies using bipolar family history as validator. Diagnosing mixed depression has treatment impacts, such as careful use of antidepressants added to mood stabilising agents or no use of antidepressants, as recently shown by large naturalistic and controlled studies.

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).

How best to identify a bipolar-related subtype among major depressive patients without spontaneous hypomania: superiority of age at onset criterion over recurrence and polarity?

BACKGROUND: History of high depressive recurrence (without history of mania/hypomania) has been proposed as a mood subtype close to bipolar disorders. Herein we test whether this is the best approach to this question. METHODS: We systematically evaluated consecutive 224 Major Depressive (MDD) and 336 Bipolar II Disorders (BP-II) outpatients in a private practice, by the SCID for DSM-IV (modified for better probing hypomania by Akiskal and Benazzi [Akiskal, H.S., Benazzi, F., 2005. Optimizing the detection of bipolar II disorder in outpatient private practice: toward a systematization of clinical diagnostic wisdom. J. Clin. Psychiatry 66, 914-921]). We conducted univariate and multivariate analyses on such putative bipolar validators as early age at onset of first major depressive episode (before 21 years), high recurrence, family history for bipolar disorders, and depressive mixed states (mixed depression, i.e. depression plus concurrent hypomanic symptoms), in order to identify an MDD subgroup close to BP-II. RESULTS: All bipolar validators were independent predictors of BP-II. Early onset was the only variable which identified an MDD subgroup significantly associated with all bipolar validators. This MDD subgroup was similar to BP-II on age at onset and bipolar family history, and had a high frequency of mixed depression. A dose-response relationship was found between number of bipolar validators present in MDD, and bipolar family history loading among MDD relatives. LIMITATIONS: Study limited to outpatients. CONCLUSIONS: From among the bipolar validators, early age at onset of first major depression (<21 years) was superior to high recurrence (>4 depressive episodes) in identifying an MDD subgroup close to BP-II, which might be subsumed under the broad bipolar spectrum. Implications of unipolar-bipolar boundaries and genetic investigations are discussed.

Dissociative experiences differentiate bipolar-II from unipolar depressed patients: the mediating role of cyclothymia and the Type A behaviour speed and impatience subscale.

BACKGROUND: Dissociative symptoms are often seen in patients with mood disorders, but there is little information on possible association with subgroups and temperamental features of these disorders. METHODS: The Dissociative Experience Scale was administered to 85 patients with a DSM-IV Major Depressive Disorder (MDD) or Bipolar-II Disorder (BP-II). Both broad-spectrum dissociation (DES total score) and clearly pathological forms of dissociation (DES-Taxon) were assessed. Temperament was assessed using Akiskal and Mallya;s criteria of Affective Temperaments and the Jenkins Activity Survey (JAS) for Type A Behaviour. RESULTS: Sixty-five patients gave valid answers to DES. The mean DES and DES-T scores were higher in BP-II (16.8 and 12.7 respectively) compared to MDD (9.0 and 5.7); DES odds ratio (OR)=1.58 (95% CI 1.15-2.18) and DES-T OR=1.60 (95% CI 1.14-2.25) using univariate logistic regression analyses. There was no significant difference in DES score in patients with (n=30) and without an affective temperament (n=35): mean (95% CI), 13.5 vs. 10.5 (-7.8 to 1.9), p=0.224. However the subgroup with a cyclothymic temperament (n=18) had higher DES scores (mean (95% CI): 17.8 vs. 9.7 (2.9-13.3), p=0.003), compared to patients without such a temperament. There was no significant difference in DES scores for patients with (n=35) or without (n=28) a Type A behaviour pattern (JAS>0): mean (95% CI) 12. 7 vs. 10.9 (-6.8 to 3.3), p=0.491), but a positive JAS factor S score (speed and impatience subscale) was associated with significantly higher DES scores than a negative S-score: mean (95% CI) 14.9 vs. 9.0 (1.1-10.7), p=0.017), and this was still significant (p=0.005) using multiple linear regression of DES scores vs. the JAS subscale scores. DES-T scores were significantly higher in patients with OCD (n=9) (mean (95% CI) 18.4 vs. 6.6 (6.0-17.7), p<0.001); eating disorder (n=13) (14.0 vs. 6.8 (1.8-12.6), p=0.009), psychotic symptoms during depressions (n=9) (16.6 vs. 6.9 (3.7-15.8), p=0.002), and in those with a history of suicide attempt (n=28) (11.9 vs. 5.4 (2.2-10.8), p=0.003), but only OCD was an independent predictor after multiple linear regression of DES-T scores vs. all co-morbid disorders (p=0.043). LIMITATIONS: The major limitation of the present study is a non-blind evaluation of affective diagnosis and temperaments, and assessment in a non-remission clinical status. CONCLUSIONS: Dissociative symptoms measured with the Dissociative Experience Scale are associated with bipolar features, using formal DSM-IV criteria, cyclothymic temperament and the speed and impatience subscale of the JAS.

Pain complaints in latino adults of mexican origin with and without major depressive episode: a cross-sectional study.

BACKGROUND: The aim of this retrospective, cross-sectional study was to determine the prevalence of 5 pain complaints among Latino adults of Mexican origin meeting the criteria for major depressive episode (MDE). METHOD: In a mental health clinic for the indigent, consecutively evaluated Latino adults of Mexican origin received structured diagnostic psychiatric interviews based on modules extracted from the Structured Clinical Interview for DSM-IV Axis I Disorders-Clinical Version. All were specifically asked whether they had experienced headache, backache, abdominal pain, myalgia, or arthralgia "in the last week." Patients meeting the criteria for MDE were compared to patients without MDE from the same clinic. Associations and statistical significance of the differences between groups were determined using logistic regression models. The data were collected between August 2003 and November 2004. RESULTS: Two hundred ten patients had an MDE, and 35 individuals without an MDE comprised the comparison group. Eighty-eight percent of the patients with MDE versus 53% of the controls had at least 1 pain complaint (p < .0001). Patients with MDE were 8.3 times more likely to have 1 or more pain complaints than the comparison patients (p < .0001). The significant relationship between depression and pain applied when we examined those with ≥ 2, ≥ 3, and ≥ 4 pain complaints. Twenty-eight percent of the MDE subjects had all 5 pain complaints compared to 3% of subjects without MDE (p = .013). CONCLUSIONS: The method of assessment of the presence of pain led to the detection of a remarkably high prevalence of pain complaints. The findings presented have important implications not only for the practice of those who are widely recognized as being primary care physicians but also for practitioners of all clinical disciplines.

Continuous distribution of atypical depressive symptoms between major depressive and bipolar II disorders: dose-response relationship with bipolar family history.

BACKGROUND: Despite the categorical position of formal diagnostic approaches (i.e. ICD-10 and DSM-IV) to mood disorders, atypical depression (AD) occupies an ambiguous position between major depressive (MDD) and bipolar II (BP-II) disorders. METHODS: Three hundred and eighty-nine and 261 consecutive BP-II and MDD patients, respectively, presenting for treatment of depression in an Italian private practice, were interviewed by a mood specialist psychiatrist using the Structured Clinical Interview for DSM-IV Axis I Disorders - Clinician Version as modified by the authors to improve the probing for hypomania. Familial bipolarity was measured by the Family History Screen. AD was defined, according to DSM-IV, as a major depressive episode with the 'atypical features' specifier. RESULTS: BP-II, versus MDD, had the usual distinguishing features (i.e. earlier age at onset, higher rate of depressive recurrences, AD symptoms, and bipolar family history). Such categorical distinction notwithstanding, the distribution of the number of AD symptoms between BP-II and MDD depressions, studied by Kernel estimate, was continuous, showing no bimodality. Furthermore, there was a dose-response relationship between such symptoms and bipolar family history. CONCLUSIONS: The continuous distribution of a distinct clinical feature (i.e. atypical symptoms) between BP-II and MDD supports a dimensional view of depressive disorders. Our data could also be interpreted as providing further support for the subclassification of AD within the bipolar spectrum.

Reviewing the diagnostic validity and utility of mixed depression (depressive mixed states).

OBJECTIVE: To review the diagnostic validity and utility of mixed depression, i.e. co-occurrence of depression and manic/hypomanic symptoms. METHODS: 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. RESULTS: 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. DISCUSSION: Categorically-defined mixed depression may have some diagnostic validity (family history is the current strongest validator). Its diagnostic utility seems supported by treatment response.

Differential patterns of lifetime multiple anxiety disorder comorbidity between Latino adults with bipolar I and major depressive disorders.

BACKGROUND: To determine the lifetime rates of panic disorder, obsessive-compulsive disorder (OCD), social phobia, and posttraumatic stress disorder (PTSD) among adult Latino patients with major depressive disorder (MDD) and bipolar disorder (BPD), and whether there are dose-response relationships between loading for comorbid anxiety disorders, the probability of having BPD, and attributes of severity of illness. METHODS: In a public sector clinic for the indigent located in a semiclosed rural community, 187 consecutively presenting affectively ill Latino patients were evaluated by use of the Structured Clinical Interview for DSM-IV. Polarity and the lifetime prevalence of panic disorder, OCD, social phobia, and PTSD were determined. Logistic regression was used to test associations. Trends in positive predictive values (PPVs) and likelihood ratios were assessed to determine whether dose-response relationships existed between loading for comorbid anxiety disorders and the likelihood of having BPD as opposed to MDD, psychosis, suicidal ideation, and suicide attempts. RESULTS: Of 187 subjects, 118 (63.1%) had MDD and 69 (36.9%) had BPD. The odds ratio of a patient with BPD, relative to MDD, of having panic disorder was 4.6 (p< .0001), OCD 7.6 (p< .0001), social phobia 6.0 (p< .0001) and PTSD 5.3 (p< .0001). The PPV of having BPD was 91.3% and of having psychotic features 83.0% if one had all four anxiety disorders. There was a dose-response relationship between loading for comorbid anxiety disorders and the likelihood of having had a suicide attempt (but not suicidal ideation). CONCLUSIONS: As previously reported by us for juvenile patients, Latino adults with BPD had a remarkably high risk of having each anxiety disorder relative to patients with MDD. The results indicate that the risk of having BPD, having a psychosis, and making a suicide attempt becomes increasingly great as the number of comorbid anxiety disorders increases. These data, which are consistent with the notion of anxious bipolarity, provide further support for a possible anxious diathesis in bipolar disorder.

Bipolar II disorder : epidemiology, diagnosis and management.

Bipolar II disorder (BP-II) is defined, by DSM-IV, as recurrent episodes of depression and hypomania. Hypomania, according to DSM-IV, requires elevated (euphoric) and/or irritable mood, plus at least three of the following symptoms (four if mood is only irritable): grandiosity, decreased need for sleep, increased talking, racing thoughts, distractibility, overactivity (an increase in goal-directed activity), psychomotor agitation and excessive involvement in risky activities. This observable change in functioning should not be severe enough to cause marked impairment of social or occupational functioning, or to require hospitalisation. The distinction between BP-II and bipolar I disorder (BP-I) is not clearcut. The symptoms of mania (defining BP-I) and hypomania (defining BP-II) are the same, apart from the presence of psychosis in mania, and the distinction is based on the presence of marked impairment associated with mania, i.e. mania is more severe and may require hospitalisation. This is an unclear boundary that can lead to misclassification; however, the fact that hypomania often increases functioning makes the distinction between mania and hypomania clearer. BP-II depression can be syndromal and subsyndromal, and it is the prominent feature of BP-II. It is often a mixed depression, i.e. it has concurrent, usually subsyndromal, hypomanic symptoms. It is the depression that usually leads the patient to seek treatment.DSM-IV bipolar disorders (BP-I, BP-II, cyclothymic disorder and bipolar disorder not otherwise classified, which includes very rapid cycling and recurrent hypomania) are now considered to be part of the 'bipolar spectrum'. This is not included in DSM-IV, but is thought to also include antidepressant/substance-associated hypomania, cyclothymic temperament (a trait of highly unstable mood, thinking and behaviour), unipolar mixed depression and highly recurrent unipolar depression.BP-II is underdiagnosed in clinical practice, and its pharmacological treatment is understudied. Underdiagnosis is demonstrated by recent epidemiological studies. While, in DSM-IV, BP-II is reported to have a lifetime community prevalence of 0.5%, epidemiological studies have instead found that it has a lifetime community prevalence (including the bipolar spectrum) of around 5%. In depressed outpatients, one in two may have BP-II. The recent increased diagnosing of BP-II in research settings is related to several factors, including the introduction of the use of semi-structured interviews by trained research clinicians, a relaxation of diagnostic criteria such that the minimum duration of hypomania is now less than the 4 days stipulated by DSM-IV, and a probing for a history of hypomania focused more on overactivity (increased goal-directed activity) than on mood change (although this is still required for a diagnosis of hypomania). Guidelines on the treatment of BP-II are mainly consensus based and tend to follow those for the treatment of BP-I, because there have been few controlled studies of the treatment of BP-II. The current, limited evidence supports the following lines of treatment for BP-II. Hypomania is likely to respond to the same agents useful for mania, i.e. mood-stabilising agents such as lithium and valproate, and the second-generation antipsychotics (i.e. olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole). Hypomania should be treated even if associated with overfunctioning, because a depression often soon follows hypomania (the hypomania-depression cycle). For the treatment of acute BP-II depression, two controlled studies of quetiapine have not found clearcut positive effects. Naturalistic studies, although open to several biases, have found antidepressants in acute BP-II depression to be as effective as in unipolar depression; however, one recent large controlled study (mainly in patients with BP-I) has found antidepressants to be no more effective than placebo. Results from naturalistic studies and clinical observations on mixed depression, while in need of replication in controlled studies, indicate that antidepressants may worsen the concurrent intradepression hypomanic symptoms. The only preventive treatment for both depression and hypomania that is supported by several, albeit older, controlled studies is lithium. Lamotrigine has shown some efficacy in delaying depression recurrences, but there have also been several negative unpublished studies of the drug in this indication.

Delineation of the clinical picture of Dysphoric/Mixed Hypomania.

BACKGROUND: While Mixed Depression (i.e. depression plus subthreshold concurrent manic/hypomanic symptoms) has recently seen a wave of studies, little is known about Dysphoric/Mixed Hypomania (i.e. combination of syndromal hypomania and depression) compared to Bipolar I Disorder Mixed State (i.e. combination of syndromal mania and depression). STUDY AIM: To delineate the clinical picture of Dysphoric/Mixed Hypomania. METHODS: Consecutive 441 Bipolar II Disorder (BP-II) Major Depressive Episode (MDE) outpatients were cross-sectionally assessed for depression and concurrent hypomanic symptoms when presenting for treatment of depression, by a mood disorder specialist psychiatrist (FB), using the Structured Clinical Interview for DSM-IV, in a private practice. Consecutive 275 remitted BP-II were also assessed for the clinical picture of past (recalled) Hypomania. Dysphoric Hypomania was defined as the co-occurrence of DSM-IV irritable mood Hypomania and MDE. RESULTS: Frequency of Dysphoric Hypomania was 17.0%, and it was 66.4% for Mixed Depression. Irritable mood, always present by definition in Dysphoric Hypomania, was present in 65.9% of recalled Hypomania and elevated mood in 81.4%. Dysphoric Hypomania had significantly more racing/crowded thoughts, and much less increased goal-directed activity. Functioning was always impaired in Dysphoric Hypomania (by definition), while it was improved in most recalled Hypomanias. Factor structure was different: recalled Hypomania had three factors ('elevated mood', 'irritability and racing/crowded thoughts', 'goal-directed and risky overactivity'), Dysphoric Hypomania had five factors ('depressive vegetative symptoms', 'low mood and psychomotor agitation', 'risky activities', 'loss of interest', 'racing/crowded thoughts and suicidality'). DISCUSSION: Dysphoric Hypomania was uncommon among depressed outpatients (while Mixed Depression was common). Its clinical picture was closer to depression than to hypomania. If it were seen as a simple depression, antidepressants could be used alone (i.e. not protected by mood stabilising agents), risking the worsening of intra-depression irritable hypomania (which was related to suicidality). Systematic assessment of intra-depression hypomanic symptoms is supported.

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.