Mixed features presentation in bipolar disorder (BD) represents the most severe form of the disease. BD may lead to cognitive and functional deterioration, a process known as neuroprogression, which appears to be exacerbated by increased serum levels of CCL11, a neuroprogression-related cytokine. Metabolic syndrome (MetS) is highly prevalent in BD, and it is known that the presence of MetS may increase inflammation, which may contribute to increased CCL11 levels, and consequently impact on the severity of the disorder. What is not known is whether the MetS mediates the association between CCL11 levels and the presence of mood episodes with mixed features in BD. Therefore, the aim of this study was to investigate the mediating effect of MetS on the relationship between CCL11 levels and the presence of mood episodes with mixed features in BD, in a population-based study. This is a cross-sectional study that included 184 young adults, 92 with BD and 92 populational controls, matched by sex and age. BD diagnosis was assessed using the Mini International Neuropsychiatric Interview - PLUS. Mood episodes with mixed features was defined according to DSM-IV and DSM-5 criteria. MetS was defined according to the National Cholesterol Education Program (NCEP/ATP III). Substance use was assessed through the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). CCL11 serum levels were analyzed using the multiplex analysis method Luminex 200™ system. The mediation model was tested using the MedMod module of the JAMOVI 2.4.8 software. Mediation analysis indicated a trend towards significance of MetS mediating the association between CCL11 and the presence of a mood episode with mixed features in BD (p = 0.065). Individuals with BD presenting with a mood episode with mixed features and MetS may have accelerated neuroprogression due to the influence of MetS on CCL11 levels, therefore, assessing for MetS occurrence in this population and implementing early interventions to prevent its development may be effective ways of delaying cognitive impairments related to this cytokine.

A commonly used measure to assess mixed features in depressed patients is the Young Mania Rating Scale (YMRS), which only partially aligns with the DSM-5 criteria. Different algorithms on the YMRS have been used to approximate the DSM-5 mixed features criteria. In the present report from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we examined the agreement and validity of different approaches towards assessing the mixed features specifier.
Three hundred nine depressed psychiatric patients were interviewed with the Structured Clinical Interview for DSM-IV, the DSM-5 Mixed Features Specifier Interview (DMSI) and the YMRS. Seven definitions of mixed features were examined, two based on the DMSI and five from the YMRS.
The prevalence of mixed features varied 8-fold amongst the 7 definitions. The level of agreement between the YMRS definitions and the DMSI was poor. For each definition, mixed features were significantly more common in patients with bipolar disorder than major depressive disorder. A family history of bipolar disorder was significantly associated with the DMSI assessment of mixed features but none of the YMRS approaches.
The ratings on the measures were not independent of each other. The sample size was too small to compare the patients with bipolar I and bipolar II disorder.
While there was evidence of validity for both the DSM-5 and YMRS approaches towards identifying mixed features, the 2 approaches are not interchangeable. The algorithm on the YMRS used to classify patients has a significant impact on prevalence.

Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression.
Inpatients with a current major depressive episode were included. Data on socio-demographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depressive and manic (mixed) symptoms, respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD.
We included 206 people (mean age: 48.4 ± 18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two-thirds of the sample (N = 137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05).
Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may help clinicians to better contextualize AD in the context of major depressive episodes.

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.

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal-ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical \"multi-omic\" measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point-of-care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features - especially during depressive episodes - and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally-oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point-of-care.

BACKGROUND: The criteria of the Diagnostic and Statistical Manual of Mental Disorders 5th edition \"with mixed features specifier\" (DSM-5 MFS) are considered controversial since they include only typical manic symptoms. By contrast, Koukopoulos developed an alternative model of mixed depression (MxD) focusing primarily on the excitatory component.
OBJECTIVE: To compare DSM-5 MFS and Koukopoulos\' MxD (KMxD) in terms of prevalence, associated clinical variables, and discriminative capacity for bipolar depression in patients with major depressive episode (MDE).
METHODS: A total of 300 patients with MDE-155 with major depressive disorder and 145 with bipolar disorder (BD)-were recruited. The discriminative capacity of DSM-5 MFS and KMxD criteria for BD was estimated using the area under the curves of receiver operating characteristic (ROC_AUC). The clinical variables associated with these two diagnostic constructs were assessed by performing a logistic regression.
RESULTS: A total of 44 and 165 patients met the DSM-5 MFS and KMxD criteria, respectively. The ROC_AUCs and their confidence intervals for BD according to DSM-5 MFS and KMxD were 77.0% (72.0%-82.1%) and 71.9% (66.2%-77.7%), respectively. The optimal thresholds (combining sensitivity and specificity measures) for BD diagnosis were ≥1 (77%/68%) for DSM-5 MFS and ≥3 symptoms (78%/66%) for KMxD. However, considering the DSM-5 MFS cut-off (≥3 symptoms), the specificity (97%) increased at the expense of sensitivity (26%).
CONCLUSIONS: KMxD and DSM-5-MFS showed an overlapping discriminative capacity for bipolar depression. The current diagnostic threshold of DSM-5 MFS did not prove to be very inclusive, if compared with the greater diagnostic sensitivity of KMxD, which also yielded better association with clinical variables related to mixedness.

暂无摘要。

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.

This study aims to explore the reliability, validity, and feasibility of Clinically Useful Depression Outcome Scale (CUDOS) in screening mixed features in patients diagnosed with mania.
A total of 109 patients with (hypo-) manic episode were recruited. The reliability of Chinese version of CUDOS (CUDOS-C) were analyzed with Cronbach\'s alpha and intraclass correlation coefficient (ICC). Spearman correlation coefficient was used to analyze the validity by comparing the correlation between CUDOS-C and Patient Health Questionnaire-9 (PHQ-9), 32-item Hypomania Checklist (HCL-32). The score of MINI (hypo-) manic episode with mixed features-DSM-5 Module-Chinese version(MINI-M-C) ≥ 2 was considered as the gold standard of mixed features, and the receiver operating characteristic (ROC) curve analysis was used to calculate the optimal cut-off values of CUDOS-C score.
The Cronbach\'s alpha value of CUDOS-C was 0.898, and the ICC of CUDOS-C test-retest was 0.880 (95% CI: 0.812-0.923, p < .05).The CUDOS-C score was significantly correlated with PHQ-9 score (r = 0.893, p = .000), but not with HCL-32 score(r = 0.088, p = .364).The area under ROC curve was 0.909 (95% CI: 0.855 to 0.963, p < .001) for CUDOS-C identifying mixed features in mania. The optimal cut-off value was 11 with a sensitivity of 0.854 and a specificity of 0.868. The CUDOS-C (score ≥ 12) identified 40.4% of the patients with mixed features, which was higher than those diagnosed by clinicians (18.3%) and screened using MINI-M-C (37.6%).
The results indicate the CUDOS-C is a reliable and valid self-administered questionnaire for assessing depressive symptoms and screening patients with mixed mania.