UNASSIGNED: There is limited literature on the prevalence of mixed features in patients with depression, especially from countries in Asia. Our aim was to evaluate the prevalence of \"mixed features\" in patients with first-episode depression.
UNASSIGNED: Patients with first-episode depression were evaluated for the presence of mixed features as per the Diagnostic and Statistical Manual (DSM)-5 criteria. They were additionally evaluated on Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS).
UNASSIGNED: About one-sixth (16%) of the patients fulfilled the DSM-5 criteria for the mixed features specifier. The most common manic/hypomanic clinical feature was increased talkativeness or pressure of speech, followed by elevated expansive mood (12.5%), and inflated self-esteem or grandiosity was the least common feature (8.7%). Those with mixed features had higher prevalence of comorbid tobacco dependence and psychotic symptoms. In terms of frequency of depressive symptoms as assessed on HDRS, compared to those without mixed features, those with mixed features had higher frequency of symptoms such as depressed mood, insomnia during early hours of morning, work and activities, agitation, gastrointestinal somatic symptoms, genital symptoms, hypochondriasis, and poorer insight.
UNASSIGNED: Mixed features specifier criteria were fulfilled by 16% patients with first-episode depression. This finding suggests that the extension of this specifier to depression can be considered as a useful step in understanding the symptom profile of patients with depression.

BACKGROUND: There is a lack of data on the mixed specifier from developing countries like India.
OBJECTIVE: In this background, the present study aimed to evaluate the prevalence of \"mixed specifier\" in patients with unipolar depression and bipolar depression. The additional aim was to evaluate the sociodemographic and clinical correlates of the mixed specifier.
METHODS: 110 patients (51 diagnosed with current episode unipolar depression and 59 diagnosed with current episode bipolar depression) were evaluated on DSM-5 criteria for mixed specifier for depression, Clinically Useful Depression Outcome Scale, Koukopoulos Mixed Depression Rating Scale, Hamilton depression rating scale (HDRS) and Young mania rating scale.
RESULTS: According to DSM-5, 11 (21.56%) out of the 51 patients with unipolar depression fulfilled at least 3 out of the 7 criteria for the mixed specifier for depression, and 14 (23.72%) out of 59 patients with bipolar depression fulfilled the criteria for the mixed specifier, with no significant difference in the prevalence across the 2 groups. There was no significant difference in the sociodemographic and clinical profile of those with and without mixed features in both unipolar and bipolar depression groups. However, those with mixed and without mixed features differ on certain depressive symptoms as assessed on HDRS.
CONCLUSIONS: About one-fifth of patients with unipolar and bipolar depression have mixed features during the acute phase of depression.

A useful scale for identification of mixed features in major depressive episodes (MDE) patients is urgent in China. This study aimed to evaluate the reliability and validity of the Chinese version of the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (Chinese-CUDOS-M) in MDE patients.
A total of 152 MDE patients were recruited and assessed using Chinese-CUDOS-M, Patient Health Questionnaire-9 (PHQ-9) and 32-item Hypomania Checklist (HCL-32). Principal component analysis (PCA) and exploratory factor analysis (EFA) were conducted. The predictive validity was calculated by the area under the receiver operating characteristic curve (AUROC).
The Cronbach\'s alpha of Chinese-CUDOS-M was 0.85. PCA showed three common factors with eigenvalue greater than 1; the eigenvalue of factor I was 4.96, with 38.1% of variance explanation. Chinese-CUDOS-M depression subscale was associated with PHQ-9 (r = 0.83, p<0.01), and manic subscale was associated with HCL-32 (r = 0.73, p< 0.01). AUROC of the Chinese-CUDOS-M for patients with mixed depression was 0.90 (95%CI: 0.85-0.95), with a cut-off value of 7, sensitivity of 0.95, and specificity of 0.73. Furthermore, AUROC was 0.88 in patients with major depressive disorder (MDD), with a cut-off value of 7, sensitivity of 0.96, and specificity of 0.71. AUROC was 0.92 in bipolar disorder (BD) depression patients, with a cut-off value of 9, sensitivity of 0.89, and specificity of 0.87.
Our study shows that the Chinese-CUDOS-M can identify mixed features in both MDD and BD depression with satisfactory reliability and validity.

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, p<0.001). 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.

According to the DSM-5, \"reduction in the need for sleep\" is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0<0.005). Moreover, SLEEP+ had significantly higher rates of mixed-state specifiers than SLEEP- (all 0 < 0.006). A significant contribution to hypersomnia in our regression model was driven by metabolic-related features, such as \"current bulimia\" (OR = 4.21) and \"overweight/obese BMI (OR = 1.42)\". Globally, hypersomnia is associated with poor outcome in acute depression. Hypersomnia is strongly associated with mixed features and bipolarity. Metabolic aspects could influence the expression of hypersomnia, worsening the overall clinical outcome. Along with commonly used screening tools, detection of hypersomnia has potential, costless discriminative validity in the differential diagnosis unipolar and bipolar depression.

The purpose of this study was to evaluate the prevalence of mixed features using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and to examine how patients with mixed states would be classified using the DSM-5.
In total, 12 hospitals participated in this study, and data on the demographic characteristics and clinical diagnoses of patients treated between October 2013 and September 2016 were obtained. We reviewed the data for opposite-polarity symptoms according to the DSM-5 criteria and the research-based diagnostic criteria.
Of the 859 patients included in the final analysis, the prevalence of mixed features in patients with major depressive episodes based on the DSM-5 remained low. Patients with major depressive disorder were more likely to be classified as experiencing anxious distress and/or a cluster-B personality disorder in mixed state patients not diagnosed with DSM-5 mixed features, whereas more mixed state patients with bipolar disorder were diagnosed with mixed features using the DSM-5.
The prevalence of mixed features did not increase significantly when the DSM-5 was used, and patients with mixed states were more likely to be classified as having anxious distress and/or a cluster-B personality disorder in addition to mixed features.

This study primarily focused on the relationship between comorbid attention deficit-hyperactivity disorder (ADHD), mixed features and bipolarity in major depressive patients.
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.
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.
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.
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.

Although bipolar disorder (BD) is a fundamentally cyclical illness, a divided model of BD that emphasizes polarity over cyclicity has dominated modern psychiatric diagnostic systems since their advent in the 1980s. However, there has been a gradual return to conceptualizations of BD which focus on longitudinal course in the research community due to emerging supportive data. Advances in longitudinal statistical methods promise to further progress the field.
The current study employed hidden Markov modeling to uncover empirically derived manic and depressive states from longitudinal data [i.e. Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale responses across five occasions from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study], estimate participants\' probabilities of transitioning between these states over time (n = 3918), and evaluate whether clinical variables (e.g. rapid cycling and substance dependence) predict participants\' state transitions (n = 3229).
Analyses identified three empirically derived mood states (\'euthymic,\' \'depressed,\' and \'mixed\'). Relative to the euthymic and depressed states, the mixed state was less commonly experienced, more temporally unstable, and uniquely associated with rapid cycling, substance use, and psychosis. Individuals assigned to the mixed state at baseline were relatively less likely to be diagnosed with BD-II (v. BD-I), more likely to present with a mixed or (hypo)manic episode, and reported experiencing irritable and elevated mood more frequently.
The results from the current study represent an important step in defining, and characterizing the longitudinal course of, empirically derived mood states that can be used to form the foundation of objective, empirical attempts to define meaningful subtypes of affective illness defined by clinical course.

Current classifications separate Bipolar (BD) from Major Depressive Disorder (MDD) based on polarity rather than recurrence. We aimed to determine bipolar/mixed feature frequency in a large MDD multinational sample with (High-Rec) and without (Low-Rec) >3 recurrences, comparing the two subsamples.
We measured frequency of bipolarity/hypomanic features during current depressive episodes (MDEs) in 2347 MDD patients from the BRIDGE-II-mix database, comparing High-Rec with Low-Rec. We used Bonferroni-corrected Student\'s t-test for continuous, and chi-squared test, for categorical variables. Logistic regression estimated the size of the association between clinical characteristics and High-Rec MDD.
Compared to Low-Rec (n = 1084, 46.2%), High-Rec patients (n = 1263, 53.8%) were older, with earlier depressive onset, had more family history of BD, more atypical features, suicide attempts, hospitalisations, and treatment resistance and (hypo)manic switches when treated with antidepressants, higher comorbidity with borderline personality disorder, and more hypomanic symptoms during current MDE, resulting in higher rates of mixed depression according to both DSM-5 and research-based diagnostic (RBDC) criteria. Logistic regression showed age at first symptoms < 30 years, current MDE duration ≤ 1 month, hypomania/mania among first-degree relatives, past suicide attempts, treatment-resistance, antidepressant-induced swings, and atypical, mixed, or psychotic features during MDE to associate with High-Rec.
Number of MDEs for defining recurrence was arbitrary; cross-sectionality did not allow assessment of conversion from MDD to BD.
High-Rec MDD differed from Low-Rec group for several clinical/epidemiological variables, including bipolar/mixed features. Bipolarity specifier and RBDC were more sensitive than DSM-5 criteria in detecting bipolar and mixed features in MDD.

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. The present post-hoc analysis evaluated the association between obesity and the presence of mixed features and bipolarity.
A total of 2811 MDE subjects were enrolled in a multicenter cross-sectional study. In 2744 patients, the body mass index (BMI) was evaluated. Psychiatric symptoms, and sociodemographic and clinical variables were collected, comparing the characteristics of MDE patients with (MDE-OB) and without (MDE-NOB) obesity.
Obesity (BMI ≥30) was registered in 493 patients (18%). In the MDE-OB group, 90 patients (20%) fulfilled the DSM-IV-TR criteria for bipolar disease (BD), 225 patients (50%) fulfilled the bipolarity specifier criteria, 59 patients (13%) fulfilled DSM-5 criteria for MDEs with mixed features, and 226 patients (50%) fulfilled Research-Based Diagnostic Criteria for an MDE. Older age, history of (hypo)manic switches during antidepressant treatment, the occurrence of three or more MDEs, atypical depressive features, antipsychotic treatment, female gender, depressive mixed state according to DSM-5 criteria, comorbid eating disorders, and anxiety disorders were significantly associated with the MDE-OB group. Among (hypo)manic symptoms during the current MDE, psychomotor agitation, distractibility, increased energy, and risky behaviors were the variables most frequently associated with MDE-OB group.
In our sample, the presence of obesity in patients with an MDE seemed to be associated with higher rates of bipolar spectrum disorders. These findings suggest that obesity in patients with an MDE could be considered as a possible marker of bipolarity.