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Background Adolescents with bipolar disorder (BD) are often misdiagnosed with major depressive disorder (MDD), which delays the introduction of appropriate treatment resulting in adverse outcomes. This study examined the psychometric properties of the 33-item Hypomania Checklist (HCL-33) and its accuracy to distinguish BD from MDD in adolescents. Method A total of 248 participants (171 MDD and 77 BD patients) were recruited from a university-affiliated hospital in China. Depression was measured with the Hamilton Depression Rating Scale. All participants completed the assessment with the HCL-33. Results A two-factor structure was found for the HCL-33, which explained 30.2% of the total variance. The internal consistency and split half reliability of the total scale were acceptable. The optimal cut-off value of 18 generated sensitivity of 0.52 and specificity of 0.73 for distinguishing BD from MDD. Conclusion The HCL-33 seems to be a useful screening instrument to distinguish BD from depressed adolescents. However, considering certain less than robust psychometric properties, the HCL-33 needs to be modified and further refined for adolescent patients.

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch) Due to its heterogeneous phenomenology, obsessive-compulsive disorder (OCD) has been subtyped. However, these subtypes are not mutually exclusive. This study presents an alternative subtyping approach by deriving non-overlapping OCD subtypes. A pure compulsive and a mixed obsessive-compulsive subtype (including subjects manifesting obsessions with/without compulsions) were analyzed with respect to a broad pattern of psychosocial risk factors and comorbid syndromes/diagnoses in three representative Swiss community samples: the Zurich Study (n = 591), the ZInEP sample (n = 1500), and the PsyCoLaus sample (n = 3720). A selection of comorbidities was examined in a pooled database. Odds ratios were derived from logistic regressions and, in the analysis of pooled data, multilevel models. The pure compulsive subtype showed a lower age of onset and was characterized by few associations with psychosocial risk factors. The higher social popularity of the pure compulsive subjects and their families was remarkable. Comorbidities within the pure compulsive subtype were mainly restricted to phobias. In contrast, the mixed obsessive-compulsive subtype had a higher prevalence and was associated with various childhood adversities, more familial burden, and numerous comorbid disorders, including disorders characterized by high impulsivity. The current comparison study across three representative community surveys presented two basic, distinct OCD subtypes associated with differing psychosocial impairment. Such highly specific subtypes offer the opportunity to learn about pathophysiological mechanisms specifically involved in OCD.

Background DSM-5 and ICD-11 define mixed depression as the presence of non-overlapping symptoms of opposite polarity during a major depressive episode. However, such a definition has generated controversy. Methods 2720 patients with major depression, enrolled in BRIDGE–II–MIX cross-sectional study, were subdivided in clusters using a k-medoids algorithm based on 32 clinical features. Clinical variables were compared among clusters. Stepwise logistic regression and random forest predictor importance estimates were used to identify which features best predicted cluster membership. Data-driven criteria were compared with DSM-5 mixed specifier and previously proposed research-based criteria (RBDC). Results Two clusters were identified (MDE ± MX), mainly reflecting differences in current manic symptoms. As expected, MDE + MX showed higher rates of comorbidities and bipolar features, more previous depressive episodes and suicide attempts, shorter duration of current MDE and lower age at onset. Seven clinical features among the original 32 proved to be the best predictors of cluster membership. Derived criteria perfectly allocated subjects in clusters, requiring at least four features out of the following seven: irritability, emotional lability, psychomotor agitation, distractibility, mood reactivity, absence of reduced appetite, and absence of psychomotor retardation. RBDC showed a better performance than DSM-5 in identifying MDE + MX subjects. Conclusion Our results strongly suggest a predominant role for overlapping “manic” symptoms in defining mixed depressive states. Mixed depression is better identified by the presence of excitatory features shared with mania and atypical features rather than by non-overlapping manic symptoms.

Background:Bipolar disorder (BD) is often misdiagnosed as major depressive disorder (MDD) in older patients. This study examined the psychometric properties of the 33-item Hypomania Checklist (HCL-33) and its accuracy to differentiate BD from MDD among older adults.Method:A total of 215 depressed older patients were recruited; 107 were diagnosed with BD (71 with BD-type I and 36 with BD-type II) and 108 with MDD. Principal components analysis (PCA) was used to explore the factor structure of the HCL-33. Cronbach’s alpha was calculated to test the internal consistency. Intra-class correlation coefficient (ICC) was used to measure test-retest reliability. The receiver operating characteristic (ROC) analysis was used to generate the optimal cut-off value to differentiate between BD and MDD.Results:Two factors were identified in the PCA analysis accounting for 33.9% of the total variance. The Cronbach’s alpha value for the HCL-33 was 0.912, with 0.922 for factor I and 0.664 for factor II. The test-retest reliability was excellent (ICC: 0.891). The optimal cut-off of the HCL-33 total score for discriminating between MDD and BD was 14, with a sensitivity of 88.8% and specificity of 82.4%.Conclusion:The HCL-33 had satisfactory reliability and validity and could be used to distinguish BD from MDD in older adults.

Background The aim was to quantify and to compare the associations between longitudinal changes in pain and depression in different chronic pain conditions. Methods Data were retrieved from 6 observational cohort studies. From baseline to the 6-month follow-up, the score changes on the Short Form (36) Health Survey (SF-36) bodily pain (pain) and the SF-36 mental health (depression) scales (0=worst, 100=best) were quantified, using partial correlations obtained by multiple regression. Adjustment was performed by age, living alone/with partner, education level, number of comorbidities, baseline pain and baseline depression. Results Stronger associations were found between changes in levels of pain and depression for neck pain after whiplash (n = 103, mean baseline pain=21.4, mean baseline depression=52.5, adjusted correlation r = 0.515), knee osteoarthritis (n = 177, 25.4, 64.2, r = 0.502), low back pain (n = 134, 19.0, 49.4, r = 0.495), and fibromyalgia (n = 125, 16.8, 43.2, r = 0.467) than for lower limb lipedema (n = 68, 40.2, 62.6, r = 0.452) and shoulder arthroplasty (n = 153, 35.0, 76.4, r = 0.292). Those correlations were somewhat correlated to baseline pain (rank r=–0.429) and baseline depression (rank r=–0.314). Limitations The construct of the full range of depressive symptoms is not explicitly covered by the SF-36. Conclusions Moderate associations between changes in pain and depression levels were demonstrated across 5 of 6 different chronic pain conditions. The worse the pain and depression scores at baseline, the stronger those associations tended to be. Both findings indicate a certain dose-response relationship – an important characteristic of causal interference. Relieving pain by treatment may lead to the relief of depression and vice versa.

Background The Clinical descriptions and diagnostic guidelines for the ICD-11 Classification of mental and behavioural disorders should soon be finalized. To measure their potential impact, the new proposed definitions of bipolar disorders in ICD-11 were applied to data from the Zurich cohort study and compared with the definitions of ICD-10 and DSM-5. Results We found little difference between ICD-11 and ICD-10 in the identification of subjects with bipolar disorders, but compared to DSM-5 a considerable increase in the diagnosis of hypomanic episodes and therefore of bipolar-II disorders. Conclusions Compared to ICD-10 and DSM-5 the definition of hypomanic episodes according to ICD-11 represents important progress. A higher prevalence of BP-II disorder makes sense from a clinical point of view. Further transcultural research is needed into whether out-patient treatment should be included as a criterion for hypomania. Pure mania is unfortunately missing as an independent and codable disorder in the international diagnostic manuals, whether ICD-11 or DSM-5.

Diagnostic criteria for a major depressive episode capture heterogeneous presentations across unipolar (UD) and bipolar (BD) and first-onset (FDE) depression. We evaluated the contribution of each depressive and (hypo)manic symptom to worse functioning in UD/BD/FDE subgroups.A post-hoc analysis of the BRIDGE-II-Mix study. Acutely depressed patients were stratified into UD, BD and FDE. Each (hypo)manic or depressive symptom was included in a diagnosis-specific logistic regression model with functioning as dependent variable. Better/worse functioning was set with median diagnosis-specific GAF scores cutoffs. All p values were two-tailed. Statistical significance was set at p 0.05.A total of 2768/2811 depressed individuals were enrolled. In BD (N = 716), "recurrent thoughts of death" (OR 2.48, p 0.0001) and "feelings of worthlessness" (OR 2.28, p 0.0001) among depressive symptoms, "aggressiveness" (OR 1.67, p = 0.022) as the unique (hypo)manic symptom, significantly contributed to worse functioning. In UD (N = 1357), "depressed mood" (OR 5.6, p = 0.031) and "diminished interest or pleasure" (OR 4.77, p 0.0001) among depressive, "grandiosity" (OR 3.5, p = 0.014) among (hypo)manic symptoms, most significantly contributed to worse functioning. In FDE (N = 677) "recurrent thoughts of death" (OR 1.99, p 0.0001) and "insomnia/hypersomnia" (OR 1.88, p = 0.039) among depressive, "grandiosity" (OR 5.98, p = 0.038) as (hypo)manic symptoms significantly contributed to worse functioning.The post-hoc and cross-sectional design do not allow for prognostic or causal inferences.Key depressive and (hypo)manic symptoms distinctively associate with worse functional outcome in acute depression, with differential diagnostic-specific magnitude of effect. Core depressive symptoms are associated with worse functioning in unipolar depression, but not in bipolar or first-episode depression.

A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p p p

OBJECTIVES The "Bipolar Disorders: Improving Diagnosis, Guidance, and Education" (BRIDGE-II-Mix) study aimed to estimate the frequency of mixed states in patients with a major depressive episode (MDE) according to different definitions and to compare their clinical validity, looking into specific features such as rapid cycling (RC). METHODS Psychiatric symptoms, socio-demographic, and clinical variables were collected from a sample of 2811 MDE patients, of which 726 (25.8%) were diagnosed with bipolar disorder (BD). The characteristics of bipolar patients with RC (BD-RC) and without (BD-NRC) RC were compared. RESULTS Of 726 BD patients, 159 (21.9%) met DSM-5 criteria for RC. BD-RC group presented a higher number of lifetime depressive episodes (p

BACKGROUND: psychomotor agitation (PA) or retardation (PR) during major depressive episodes (MDEs) have been associated with depression severity in terms of treatment-resistance and course of illness.OBJECTIVES: we investigated the possible association of psychomotor symptoms (PMSs) during a MDE with clinical features belonging to the bipolar spectrum.METHODS: the initial sample of 7689 MDE patients was divided into three subgroups based on the presence of PR, PA and non-psychomotor symptom (NPS). Univariate comparisons and multivariate logistic regression models were performed between subgroups.RESULTS: 3720 patients presented PR (48%), 1971 shown PA (26%) and 1998 had NPS (26%). In the PR and PA subgroups, the clinical characteristics related to bipolarity, along with the diagnosis of Bipolar Disorder (BD), were significantly more frequent than in the NPS subgroup. When comparing PA and PR patients, the former presented higher rates of bipolar spectrum features, such as family history of BD (OR=1.39, CI=1.20-1.61), manic/hypomanic switches with antidepressants (OR=1.28, CI=1.11-1.48), early onset of first MDE (OR=1.40, CI=1.26-1.57), atypical (OR=1.23, CI=1.07-1.42) and psychotic features (OR=2.08, CI=1.78-2.44), treatment with mood-stabilizers (OR=1.39, CI=1.24-1.55), as well as a BD diagnosis according to both the DSM-IV criteria and the bipolar specifier criteria. When logistic regression model was performed, the clinical features that significantly differentiated PA from PR were early onset of first MDE, atypical and psychotic features, treatment with mood-stabilizers and a BD diagnosis according to the bipolar specifier criteria.CONCLUSIONS: PMSs could be considered as markers of bipolarity, illness severity, and treatment complexity, particularly if PA is present. This article is protected by copyright. All rights reserved.

Accurate age of onset (AOO) measurement is vital to etiologic and preventive research. While AOO reports are known to be subject to recall error, few population-based studies have been used to investigate agreement in AOO reports over more than a decade. We examined AOO reports for depression, back/neck pain, and daily smoking, in a population-based cohort spanning 29 years. A stratified sample of participants from Zurich, Switzerland (n = 591) completed a psychiatric and physical health interview 7 times between 1979, at ages 20 (males) and 21 (females), and 2008. We used one-way ANOVA to estimate intraclass correlations (ICCs) and weighted mixed models to estimate mean change over time and test for interactions with sex and clinical characteristics. Stratum-specific ICCs among those with 2 + reports were 0.19 and 0.29 for depression, 0.46 and 0.35 for back pain, and 0.66 and 0.75 for smoking. The average yearly increases in AOO report from the wave of first 12-month diagnosis or reported smoking, estimated in mixed models, were 0.57 years (95% confidence interval: 0.35, 0.79) for depression, 0.44 (95%CI: 0.28, 0.59) years for back pain, and 0.08 (95%CI: 0.03, 0.14) years for smoking. Initial impairment and frequency of treatment were associated with differences in average yearly change for depression. There is substantial variability in AOO reports over time and systematic increase with age. The degree of increase may differ by outcome, and for some outcomes, by participant clinical characteristics. Future studies should identify predictors of AOO report stability to ultimately benefit etiologic and preventive research.

Background Given that several studies have found the gender difference in depression to be rooted in psychosocial forces and others have shown the difference to be due to a gender difference in somatic depression, we compared the gender difference in somatic depression among respondents who reported no relative depressed with that of all other depressed respondents. Methods Respondents in a representative sample from the Zurich study who met criteria for somatic depression and reported no relatives (first-degree, or parents, or mothers, or fathers in separate analyses) with depression were compared to other depressed respondents as to gender. Results The gender difference in the prevalence of depression among respondents with somatic depression who reported no relatives with depression (whether the relatives were all first-degree, or any parent, or mothers only or fathers only) was significantly greater than the gender difference in depression among other respondents Limitations The measure of depression among relatives was based upon reports of the respondents. Conclusion All or almost all of the gender difference in depression in this representative sample.is due to a gender difference in somatic depression among respondents who reported no depressed relative. Somatic depression may be a disorder distinct from depression without significant additional somatic symptomatology. If so, it is likely that it should be treated differently.

Although the DSM-5 has suggested the two new categories of Persistent Depressive Disorders (PDD) and Other Specified Depressive Disorders (OSDD), no study so far has applied the DSM-5 criteria throughout the range of depressive disorders. The aims of the present study were to 1) establish the lifetime prevalence of specific depressive disorders according to the new DSM-5 definitions in a community sample, and 2) determine their clinical relevance in terms of socio-demographic characteristics, comorbidity, course and treatment patterns. The semi-structured Diagnostic Interview for Genetic Studies was administered by masters-level psychologists to a random sample of an urban area (n=3720). The lifetime prevalence was 15.2% for PDD with persistent major depressive episode (MDE), 3.3% for PDD with pure dysthymia, 28.2% for Major Depressive Disorder (MDD) and 9.1% for OSDD. Subjects with PDD with persistent MDE were the most severely affected, followed by those with recurrent MDD, single episode MDD, PDD with pure dysthymia and OSDD and finally those without depressive disorders. Our data provide further evidence for the clinical significance of mild depressive disorders (OSDD), but cast doubt on the pertinence of lumping together PDD with persistent MDE and the former DSM-IV dysthymic disorder within the new PDD category.

Cel pracyKwestionariusz oceny objawów hipomaniakalnych (Hypomania Checklist-HCL) stał się ważnym narzędziem do oceny objawów hipomanii u osób z chorobami afektywnymi i populacji ogólnej. Kwestionariusz HCL-33, zawierający 33 objawy, to nowy instrument, który posiada wersję dla oceny przez obserwatora z zewnątrz. Celem niniejszego badania jest ocena zgodności między samooceną pacjenta i oceną przez osobę z zewnątrz (członków rodziny i inne bliskie osoby) przy użyciu skali HCL-33 u polskich pacjentów z chorobą afektywną dwubiegunową (ChAD).MetodaAnalizowano dane uzyskane od 81 pacjentów z ChAD będących w eutymii, rekrutowanych z Kliniki Psychiatrii Dorosłych UM w Poznaniu oraz Zakładu Zaburzeń Afektywnych Katedry Psychiatrii CM UJ w Krakowie. Wszyscy pacjenci wypełnili kwestionariusz HCL-33, a dla każdego pacjenta, osoba znacząca (bliska) wypełniła HCL-33 w wersji dla oceny zewnętrznej.WynikiSpośród 33 objawów, wystarczającą zgodność (czynnik kappa WnioskiUzyskane wyniki wskazują na zgodność samooceny i oceny zewnętrznej w 27 objawach (82%) kwestionariusza HCL-33. Przyszły status objawów co do których nie wykazano wystarczającej spójności powinien zostać poddany dyskusji. Ograniczeniem badania jest stosunkowo mała liczba badanych, rekrutowanych z zaledwie dwóch ośrodków, co może nie być reprezentatywne dla populacji polskiej.

Major Depressive Episode (MDE) is a transdiagnostic nosographic construct straddling Major Depressive (MDD) and Bipolar Disorder (BD). Prognostic and treatment implications warrant a differentiation between these two disorders. Network analysis is a novel approach that outlines symptoms interactions in psychopathological networks. We investigated the interplay among depressive and mixed symptoms in acutely depressed MDD/BD patients, using a data-driven approach. We analyzed 7 DSM-IV-TR criteria for MDE and 14 researched-based criteria for mixed features (RBDC) in 2758 acutely depressed MDD/BD patients from the BRIDGE-II-Mix study. The global network was described in terms of symptom thresholds and symptom centrality. Symptom endorsement rates were compared across diagnostic subgroups. Subsequently, MDD/BD differences in symptom-network structure were examined using permutation-based network comparison test. Mixed symptoms were the most central and highly interconnected nodes in the network, particularly agitation followed by irritability. Despite mixed symptoms, appetite gain and hypersomnia were significantly more endorsed in BD patients, associations between symptoms were highly correlated across MDD/BD (Spearman's r = 0.96, p0.001). Network comparison tests showed no significant differences among MDD/BD in network strength, structure, or specific edges, with strong edges correlations (0.66-0.78). Upstream differences in MDD/BD may produce similar symptoms networks downstream during acute depression. Yet, mixed symptoms, appetite gain and hypersomnia are associated to BD rather than MDD. Symptoms during mixed-MDE might aggregate according to 2 different clusters, suggesting a possible stratification within mixed states. Future symptom-based studies should implement clinical, longitudinal, and biological factors, in order to establish tailored therapeutic strategies for acute depression.

We study models for recurrent events with special emphasis on the situation where a terminal event acts as a competing risk for the recurrent events process and where there may be gaps between periods during which subjects are at risk for the recurrent event. We focus on marginal analysis of the expected number of events and show that an Aalen-Johansen type estimator proposed by Cook and Lawless is applicable in this situation. A motivating example deals with psychiatric hospital admissions where we supplement with analyses of the marginal distribution of time to the competing event and the marginal distribution of the time spent in hospital. Pseudo-observations are used for the latter purpose.

The prevalence of autumn/winter seasonality in depression has been documented in the longitudinal Zurich cohort study by five comprehensive diagnostic interviews at intervals over more than 20 years (N = 499). Repeated winter major depressive episodes (MDE—unipolar + bipolar) showed a prevalence of 3.44% (5× more women than men), whereas MDE with a single winter episode was much higher (9.96%). A total of 7.52% suffered from autumn/winter seasonality in major and minor depressive mood states. The clinical interviews revealed novel findings: high comorbidity of Social Anxiety Disorder and Agoraphobia within the repeated seasonal MDE group, high incidence of classic diurnal variation of mood (with evening improvement), as well as a high rate of oversensitivity to light, noise, or smell. Nearly twice as many of these individuals as in the other MDE groups manifested the syndrome of atypical depression (DSM-V), which supports the prior description of seasonal affective disorder (SAD) as presenting primarily atypical symptoms (which include hypersomnia and increase in appetite and weight). This long-term database of regular structured interviews provides important confirmation of SAD as a valid diagnosis, predominantly found in women, and with atypical vegetative symptoms.

Resistance and worsening of depression in response to antidepressants (ADs) are major clinical challenges. In a large international sample of patients with major depressive disorder (MDD), we aim to explore the possible associations between different patterns of response to ADs and bipolarity. A total of 2811 individuals with a major depressive episode (MDE) were enrolled in the BRIDGE-II-MIX study. This post-hoc analysis included only 1329 (47%) patients suffering from MDD. Patients with (TRD-MDD, n = 404) and without (NTRD-MDD, n = 925) history of resistance to AD treatment and with (n = 184) and without (n = 1145) previous AD-induced irritability and mood lability (AIM) were compared using Chi-square, t-Student's test and logistic regression models. TRD-MDD patients resulted significantly associated with higher rates of AIM, psychotic features, history of suicide attempts, emotional lability and impulsivity, comorbid borderline personality disorder and polipharmacological treatment, compared to NTRD-MDD group. In comparison to NAIM-MDD patients, subjects in the AIM-MDD group showed significantly higher rates of first-degree family history for BD, previous TRD, atypical features, mixed features, psychiatric comorbidities, lifetime suicide attempts and lower age at first psychiatric symptoms. In addition, patients with AIM presented more often almost all the hypomanic symptoms evaluated in this study. Among these latter symptoms, logistic regressions showed that distractibility, impulsivity and hypersexuality were significantly associated with AIM-MDD. In conclusion, in MDD patients, a lifetime history of resistance and/or irritability/mood lability in response to ADs was associated with the presence of mixed features and a possible underlying bipolar diathesis.

Objective This study primarily focused on the relationship between comorbid attention deficit-hyperactivity disorder (ADHD), mixed features and bipolarity in major depressive patients. Methods The sample comprised 2777 patients with Major Depressive Episode (MDE) enrolled in a multicentre, multinational study originally designed to assess different definitions of mixed depression. Socio-demographic, familial and clinical characteristics were compared in patients with (ADHD + ) and without (ADHD-) comorbid ADHD. Results Sixty-one patients (2.2%) met criteria for ADHD. ADHD was associated with a higher number of (hypo)manic symptoms during depression. Mixed depression was more represented in ADHD + patients than in ADHD- using both DSM-5 and experimental criteria. Differences were maintained after removing overlapping symptoms between (hypo)mania and ADHD. ADHD in MDE was also associated with a variety of clinical and course features such as onset before the age of 20, first-degree family history of (hypo)mania, past history of antidepressant-induced (hypo)manic switches, higher number of depressive and affective episodes, atypical depressive features, higher rates of bipolarity specifier, psychiatric comorbidities with eating, anxiety and borderline personality disorders. Limitations The study was primarily designed to address mixed features in ADHD, with slightly reduced sensitivity to the diagnosis of ADHD. Other possible diagnostic biases due to heterogeneity of participating clinicians. Conclusions In a sample of major depressive patients, the comorbid diagnosis of current ADHD is associated with bipolar diathesis, mixed features, multiple psychiatric comorbidity and a more unstable course. Further prospective studies are necessary to confirm the possible mediating role of temperamental mood instability and emotional dysregulation in such a complex clinical presentation.

Background current classifications of mood disorders focus on polarity rather than recurrence, separating bipolar disorder from major depressive disorder (MDD). The aim of the present study is to explore the possible relationships between number and frequency of depressive episodes and clinical variables associated to bipolarity, in a large sample of MDD patients. Methods the clinical characteristics of 7055 patients with MDD were analyzed and compared according to the number and frequency of depressive episodes. Two stepwise backward logistic regression model were used to identify the predictive value of clinical features based on the presence of high number (≥3 episodes) and high frequency (≥3 episodes/year) of depressive episodes. Results high-recurrence and high-frequency MDD patients showed greater family history for bipolar disorder, higher prevalence of psychotic features, more suicide attempts, higher rates of treatment resistance and mood switches with antidepressants (ADs) and higher rates of bipolarity diagnosis according to Angst criteria, compared to low-recurrence and low-frequency patients. Logistic regressions showed that a brief current depressive episode, a previous history of treatment resistance and AD-induced mood switches, a diagnosis of bipolarity and comorbid borderline personality disorder were the variables associated with both high-recurrence and high-frequency depression. Limitations the study participating centers were not randomly selected and several variables were retrospectively assessed. Conclusions even in the absence of hypomanic/manic episodes, high-recurrence and high-frequency MDD seem to be in continuity with the bipolar spectrum disorders in terms of clinical features and, perhaps, treatment response.

Background:Bipolar disorder (BD) is difficult to diagnose in the early stages of the illness, with the most frequent misdiagnosis being major depressive disorder (MDD). We aimed to use a regional homogeneity (ReHo) approach with resting-state functional magnetic resonance imaging (rs-fMRI) to investigate the features of spontaneous brain activity in MDD patients screening positive on the 32-item Hypomania Checklist (HCL-32).Methods:Nineteen MDD patients screening positive (HCL-32(+); 9 males; 24.9 ± 5.7 years) and 18 patients screening negative (HCL-32(-); 9 males; 27.1 ± 6.7 years), together with 24 healthy controls (HC; 11 males; 26.4 ± 3.9 years) were studied. ReHo maps were compared and an receiver operating characteristic (ROC) analysis was conducted to confirm the utility of the identified ReHo differences in classifying the patients. Results The MDD versus HC showed different ReHo in many brain areas, especially in the frontal and parietal cortex. The HCL-32(+) versus HCL-32(-) showed significant increase of ReHo in the right medial superior frontal cortex, left inferior parietal cortex and middle/inferior temporal cortex, and decrease of ReHo in the left postcentral cortex and cerebellum. ROC analysis showed good sensitivity and specificity for distinguishing these two subgroups of MDD. Limitations Recruited patients were all on antidepressants and standard mania rating scales were not used to assess their hypomanic symptoms. Conclusions:The rs-fMRI measurement of ReHo in distributed brain regions may be putative biomarkers which could differentiate subthreshold BD from MDD.

In the prospective long-term Zurich study, we re-examined the hypothesized association between mental health problems in women and the transition through menopausal stages. One hundred sixty-eight women from a population-based Swiss community cohort were prospectively followed up from age 21 to 50. At age 50, the occurrence of hot flushes/night sweats and sleep disturbances was significantly more frequent in peri- and post-menopausal women. Irritability/nervousness was increased only in peri-menopausal women, but that association was accounted for by neuroticism trait scores at age 30. Transitions to peri- or post-menopause were not related to changes in either the prevalence rates of DSM major depressive episode or anxiety disorders, or the course of psychopathological syndromes as assessed by the Symptom Checklist 90 - Revised. The null associations held when adjusting for duration of reproductive period or age at menopause. Preceding mental health problems between ages 21 and 41, increased neuroticism trait scores at age 30, and concurrent psychosocial distress were significantly related to mental health problems occurring between ages 41 and 50. Depending upon the cut-off point that was chosen, the arbitrary dichotomization of a continuous depression outcome produced spurious associations with the menopausal transition. We conclude that mental health problems between ages 41 and 50 are probably not directly related to the menopausal transition, and that previously reported associations could be false positives due to inadequate dichotomizations, reporting bias, undisclosed multiple adjustments or overfitting.

The relationship between the two syndromes neurasthenia and depression is of interest in the context of burnout, which, although not a diagnosis, is often treated in psychiatry. This study defines major depressive episodes according to DSM-5 and neurasthenia by ICD-10 symptom criteria, and both syndromes on the basis of a 2-week minimum duration. The study includes all subjects of the Zurich epidemiological study who had taken part in the last five interviews (1986-2008) and compares three groups, pure depression, pure neurasthenia and their combination (neurasthenic depression), applying nonparametric statistics. The three groups did not differ in common validators: age of onset, course, a family history for depression and anxiety/panic. Psychiatric comorbidity was also very similar, with the exception of suicide attempts and substance abuse, which were less frequent in the pure neurasthenic group. Somatic comorbidity was also highly comparable, except for stomach problems, which were more common in subjects with neurasthenic syndromes. Surprisingly, the well-known preponderance of depression in women was explained by the association with neurasthenic syndromes. The proposed new diagnosis of neurasthenic depression could help diagnose subjects treated for burnout but needs replication by other representative studies.

Background Numerous studies have examined determinants leading to preponderance of women in major depressive disorder (MDD), which is particularly accentuated for the atypical depression subtype. It is thus of interest to explore the specific indirect effects influencing the association between sex and established depression subtypes. Methods The data of 1624 subjects with a lifetime diagnosis of MDD derived from the population-based PsyCoLaus data were used. An atypical (n=256), a melancholic (n=422), a combined atypical and melancholic features subtype (n=198), and an unspecified MDD group (n=748) were constructed according to the DSM-IV specifiers. Path models with direct and indirect effects were applied to the data. Results Partial mediation of the female-related atypical and combined atypical-melancholic depression subtypes was found. Early anxiety disorders and high emotion-orientated coping acted as mediating variables between sex and the atypical depression subtype. In contrast, high Body Mass Index (BMI) served as a suppression variable, also concerning the association between sex and the combined atypical-melancholic subtype. The latter association was additionally mediated by an early age of MDD onset and early/late anxiety disorders. Limitations The use of cross-sectional data does not allow causal conclusions. Conclusions This is the first study that provides evidence for a differentiation of the general mechanisms explaining sex differences of overall MDD by depression subtypes. Determinants affecting the pathways begin early in life. Since some of them are primarily of behavioral nature, the present findings could be a valuable target in mental health care.

Objectives Although clinical evidence suggests important differences between unipolar mania and bipolar-I disorder (BP-I), epidemiological data are limited. Combining data from nine population-based studies, we compared subjects with mania (M) or mania with mild depression (Md) to those with BP-I with both manic and depressive episodes with respect to demographic and clinical characteristics in order to highlight differences. Methods Participants were compared for gender, age, age at onset of mania, psychiatric comorbidity, temperament, and family history of mental disorders. Generalized linear mixed models with adjustment for sex and age as well as for each study source were applied. Analyses were performed for the pooled adult and adolescent samples, separately. Results Within the included cohorts, 109 adults and 195 adolescents were diagnosed with M/Md and 323 adults and 182 adolescents with BP-I. In both adult and adolescent samples, there was a male preponderance in M/Md, whereas lifetime generalized anxiety and/panic disorders and suicide attempts were less common in M/Md than in BP-I. Furthermore, adults with mania revealed bulimia/binge eating and drug use disorders less frequently than those with BP-I. Conclusions The significant differences found in gender and comorbidity between mania and BP-I suggest that unipolar mania, despite its low prevalence, should be established as a separate diagnosis both for clinical and research purposes. In clinical settings, the rarer occurrence of suicide attempts, anxiety, and drug use disorders among individuals with unipolar mania may facilitate successful treatment of the disorder and lead to a more favorable course than that of BP-I disorder.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. Background Misdiagnosis of bipolar disorder (BD) is common in clinical practice, leading to inappropriate treatment and detrimental consequences. The 33-item Hypomania Checklist (HCL-33) is a newly developed screening instrument for hypomanic symptoms in patients with BD. The 33-item Hypomania Checklist-external assessment (HCL-33-EA) is a version of the HCL-33 for carers of patients with mood disorders. In this study, the psychometric properties of the HCL-33-EA in a Chinese population were explored. Method A total of 182 inpatients and 240 carers were recruited in this study. Patients were diagnosed with bipolar depression or major depressive disorder (MDD) according to the International Classification of Diseases (ICD-10). The patients completed the HCL-33, while their carers filled out the HCL-33-EA. Results The HCL-33-EA showed high internal consistency (Cronbach's alpha = 0.876) with two-factorial dimensions. Paired samples t-test revealed that the mean score of the HCL-33-EA was significantly lower than that of the HCL-33 (t = 10.1, p

Frontiers in Psychiatry, 9, ISSN:1664-0640

Background: Generalized anxiety disorder (GAD) is generally considered to be a chronic condition, waxing and waning in severity; however prospective investigation of the course of GAD in community samples is lacking. This study seeks to fill that gap, by identifying the whole spectrum of generalized anxiety syndromes, sub-typing them according to their duration and frequency of occurrence, and evaluating their long-term course and outcome in the community. Method: The prospective Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults (N=591) (aged 20years at first interview) by six interviews over a period of 20years (1979-1999). GAD syndromes were defined by DSM-III symptom criteria without applying any exclusion criteria. A spectrum of generalized anxiety was defined by duration: 6months (DSM-IV), 1month (DSM-III), ≤2weeks (with weekly occurrence over one year), and anxiety symptoms. From 1978 (screening) to 1999 the annual presence of symptoms and treatment was assessed. Persistence of anxiety was defined by the almost daily presence of symptoms over the previous 12months. Results: The annual incidence of DSM-III GAD increased considerably between the ages of 20 and 40. The average age of onset of symptoms was 15.6years; in 75% of cases it occurred before the age of 20. 75 of 105 DSM-III GAD cases had at least one follow-up. At their individual last follow-up, 12 of those 75 subjects (16%) were re-diagnosed as having GAD, 22 (29%) manifested subthreshold syndromes or anxiety symptoms, while 39 cases, the majority, (52%) were symptom-free; 5 of the 12 re-diagnosed GAD cases were persistent (corresponding to 7% of all 75 initial GAD cases). In their twenties they were treated at some time in 6% of all years, but in their thirties this figure rose to 12%. At their individual last follow-up 26% of 6-month GAD subjects and 22% of 1-month GAD subjects were still being treated. Treated vs. non-treated subjects did not differ in terms of gender but did differ in severity, persistence and in comorbidity with bipolar-II disorder, social phobia, obsessive-compulsive syndromes and substance-use disorders. Limitations: Results are based on a relatively small sample and cannot be generalized to adults aged over 40years. Conclusions: The course of DSM-III-defined GAD may not be chronic, as previously suggested, but mainly recurrent with intervening symptom-free periods of recovery in about half of cases. Over a period of 20years there was more improvement than progression within the anxiety spectrum

: Objectives: : The question whether bipolar I disorder should be subdivided into a preponderantly manic group (M) with no depression or only mild depression (Md) and a nuclear manic-depressive group (MD) has been rarely studied although the problem was raised more than 50 years ago. This paper seeks to elucidate this question by contributing further data. Methods: : 406 patients with mood disorders hospitalised at some time during the period 1959-1963 were followed-up every five years until 1985; mortality data were collected up to 1997. Data on episodes, outcome, suicides and attempted suicides, alcohol and substance abuse/dependence and long-term medication, as well as on personality (melancholic and manic type) were collected. Major mood disorders were subclassified according to their hospitalisation for depression (D) and/or mania (M). Results: : 30 manic patients (M/Md), 130 bipolar I (MD), 60 bipolar II patients (Dm) and 186 major depressive patients (D) were compared. The manic group differed from the bipolar I group in several variables: better school achievement, milder course of the illness (fewer recurrences), significantly less suicidality and a trend to less chronicity and more recovery. Manic patients required less long-term medication than bipolars and they differed in personality types from bipolars, the personality of manic patients being more often of the manic rather than the melancholic type, they were also more aggressive than bipolars. The family history data showed that the overall morbidity risk of first degree relatives of manic patients was significantly lower than that of bipolar patients. Conclusions: : In accord with several other studies our data point to the existence of a more manic (M/Md) group of bipolar subjects. The diagnosis predicts a better course, lower suicidality and fewer and different treatment needs than does nuclear bipolar I (MD) disorder. The M/Md groups, as clinically interesting subgroups of the mood spectrum, should become a target of further research

Several recent studies have found an association between conduct problems and bipolar disorder in adolescents. However, prospective studies are rare and most do not apply multivariable analysis strategies to control for important variables (e.g. socio-demographics). The aim of this study was to test the association between certain conduct problems and bipolar disorders. The sample consisted of 591 adolescents (male and female) representative for 2,600 persons from the Canton of Zurich in Switzerland. Data were prospectively collected through an interviewing procedure, with the first screening taking place at the age of 19-20. The incidence rate was computed using sampling weights, and risk factors of bipolar II disorder were estimated using a multivariable logistic regression model. The 9-year incidence rate of bipolar II disorder in the canton of Zurich was 8.4% (n = 65). Adolescents and children showing behavior such as repeated running away from home and physical fighting were 2.6-3.5 times more likely to experience a bipolar II disorder than those with no indication of conduct problems. Sensitivity analysis showed that the conduct problems were not the result of low socio-economic status.

Objectives: To investigate continuity and change of self-reported physical and psychological complaints in young adults over a period of 20years. Study design and setting: The Zurich Study - a long-term panel survey in psychiatric epidemiology - is based on a stratified sample of 591 subjects born in 1958 (women) and 1959 (men). The sample strata combine SCL-90-R high-scorers and low-scorers in a 2:1 ratio. Up to now, the Zurich Study has included six interviews between 1979 and 1999, i.e. 20 years of life in young adults. We analysed the longitudinal frequency data of a variety of physical and psychological complaints, as well as information about subjective suffering and use of professional help. The analyses utilised on the McNemar's test, the Q-test and Markov chain models. Results: Sleep disorders, depression, menstruation, backache, headache, stomach and bowel complaints yielded cumulative prevalence rates of 80% or higher. Physical and psychological complaints systematically differ with respect to the change patterns between 1979 and 1999. Moreover, strong differences were found in view of subjective suffering and use of professional help. Conclusions: Even though many self-reported physical and psychological complaints are very common in young adulthood, the underlying dynamics and the implications largely differ. It seems to be crucial whether respondents use somatic glasses or psychological lenses

Growing evidence for the spectrum concept of most mental disorders, particularly mood disorders, has challenged the arbitrary distinctions inherent in the contemporary categorical diagnostic classification system. Detection of manic symptoms in the context of episodes of depression is particularly important because of the implications for differential treatment of bipolar vs unipolar depression. The purpose of this study is to characterize the magnitude and clinical correlates of subthreshold manic syndromes or symptoms among people with major depressive disorder (MDD) compared to those without a history of manic symptoms. We defined two subthreshold manifestations—manic syndrome or symptoms—that did not include a criterion for duration. In the context of MDD, we found that the clinical correlates of those with the subthreshold manic syndrome were more similar to those with bipolar-II disorder than to MDD alone, whereas those with manic symptoms only were intermediate between those with subthreshold manic syndrome and MDD alone. These results confirm the spectrum concept of mania and suggest that a manic syndrome should be considered when evaluating people with MDD.

ObjectiveTo determine minimal clinically important differences (MCIDs) for improvement and worsening in various health dimensions in knee osteoarthritis under conservative therapy.MethodsHealth, symptoms and function were assessed by the generic Short Form 36 and the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index in n=190 patients with knee osteoarthritis before and after comprehensive rehabilitation intervention (3-month follow-up). By means of construct-specific transition questions, MCIDs were defined as the difference between the ‘slightly better/worse’ and the ‘almost equal’ transition response categories according to the ‘mean change method’. The bivariate MCIDs were adjusted for sex, age and baseline score to obtain adjusted MCIDs by multivariate linear regression. They were further standardised as (baseline) effect sizes (ESs), standardised response means (SRMs) and standardised mean differences (SMDs) and compared with the minimal detectable change with 95% confidence (MDC95).ResultsMultivariate, adjusted MCIDs for improvement ranged from 2.89 to 16.24 score points (scale 0–100), corresponding to ES=0.14 to 0.63, SRM=0.17 to 0.61 and SMD=0.18 to 0.72. The matching results for worsening were –5.80 to –12.68 score points, ES=–0.30 to –0.56, SRM=–0.35 to –0.52 and SMD=–0.35 to –0.58. Almost all MCIDs were larger than the corresponding MDC95s.ConclusionsThis study presents MCIDs quantified according to different methods over a comprehensive range of health dimensions. In most health dimensions, multivariate adjustment led to higher symmetry between the MCID levels of improvement and worsening. MCIDs expressed as standardised effect sizes (ES, SRM, SMD) and adjusted by potential confounders facilitate generalisation to the results of other studies.