This article introduces the concept proposed by the eminent second-generation Japanese psychopathologist Tadao Miyamoto in 1992 that the manic-depressive mixed state is the basic psychopathology of manic-depressive illness. When Kraepelin first established the dichotomy between schizophrenia and manic-depressive illness, mania and depression were placed in a symmetrical relationship. Now, in Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), manic-depressive illness is divided into two distinct categories: bipolar and related disorders, and depressive disorders. Miyamoto pointed out that even in the average depressed state there is a manic-depressive mixed state and listed the following findings. The depressed mood of depression is itself a major fluctuation, but is constantly subject to more or less subtle fluctuations or swaying. What occurs in association with the incessant fluctuations of mood dysphoria are restlessness, agitation, irritability, and excitement, which manifest in a unique way in combination with a depressive mood. In depressive delusions, ideations of belittlement are developed in an exaggerated manner. Miyamoto concluded that mixed states are not incidental or accessory to manic-depressive illness; on the contrary, they may form a core component of manic-depressive illness.

Mixed depressive states are defined by the co-presence of depressive and manic symptoms. They represent extremely variable conditions from the point of view of clinical expressiveness and are difficult to recognize, ranging from clear schizophrenic-like psychoses and pseudodemented pictures to subsyndromal psychopathology. At the basis of the extreme variability of depressive pictures with mixed features are the different combinations that depressive and manic symptoms can assume. Furthermore, the intensity of depressive symptoms and manic symptoms, combined, can be variable, a factor that contributes to making the picture even more variable. Each form of mixed depressive state therefore presents its own specific symptomatic characteristics and specific difficulties in differential diagnosis and each form requires a different therapeutic strategy. In this work we have distinguished four possible specific subtypes of mixed depressive states, describing their specific clinical presentation and the therapeutic options most supported by the literature with the aim of contributing to a better recognition of mixed depressive states, to avoid incorrect diagnoses at patient and treatments that are useless if not worsening.

The debate on mixed states (MS) has been intense for decades. However, several points remain controversial from a nosographic, diagnostic, and therapeutic point of view. The different perspectives that have emerged over the years have turned into a large, but heterogeneous, literature body. The present review aims to summarize the evidence on MS, with a particular focus on mixed depression (MxD), in order to provide a guide for clinicians and encourage the development of future research on the topic. First, we review the history of MS, focusing on their different interpretations and categorizations over the centuries. In this section, we also report alternative models to traditional nosography. Second, we describe the main clinical features of MxD and list the most reliable assessment tools. Finally, we summarize the recommendations provided by the main international guidelines for the treatment of MxD. Our review highlights that the different conceptualizations of MS and MxD, the variability of clinical pictures, and the heterogeneous response to pharmacological treatment make MxD a real challenge for clinicians. Further studies are needed to better characterize the phenotypes of patients with MxD to help clinicians in the management of this delicate condition.

BACKGROUND: Depending on the classification system used, 5-40% of manic subjects present with concomitant depressive symptoms. This post-hoc analysis evaluates the hypothesis that (hypo)manic subjects have a higher burden of depression than non-(hypo)manic subjects.
METHODS: Data from 806 Bipolar I or II participants of the Stanley Foundation Bipolar Network (SFBN) were analyzed, comprising 17,937 visits. A split data approach was used to separate evaluation and verification in independent samples. For verification of our hypotheses, we compared mean IDS-C scores ratings of non-manic, hypomanic and manic patients. Data were stored on an SQL-server and extracted using standard SQL functions. Linear correlation coefficients and pivotal tables were used to characterize patient groups.
RESULTS: Mean age of participants was 40 ± 12 years (range 18-81). 460 patients (57.1%) were female and 624 were diagnosed as having bipolar I disorder (77.4%) and 182 with bipolar II (22.6%). Data of 17,937 visits were available for analyses, split into odd and even patient numbers and stratified into three groups by YMRS-scores: not manic < 12, hypomanic < 21, manic < 30. Average IDS-C sum scores in manic or hypomanic states were significantly higher (p < .001) than for non-manic states. (Hypo)manic female patients were likely to show more depressive symptoms than males (p < .001). Similar results were obtained when only the core items of the YMRS or only the number of depressive symptoms were considered. Analyzing the frequency of (hypo)manic mixed states applying a proxy of the DSM-5 mixed features specifier extracted from the IDS-C, we found that almost 50% of the (hypo)manic group visits fulfilled DSM-5 mixed features specifier criteria.
CONCLUSIONS: Subjects with a higher manic symptom load are also significantly more likely to experience a higher number of depressive symptoms. Mania and depression are not opposing poles of bipolarity but complement each other.

Background and Objectives: Unstable mixed episodes or rapid switching between opposite affective poles within the scope of short cycles was first characterized in 1967 by S. Mentzos as complex polymorphous states with chaotic overlap of manic and depressive symptoms. Well-known examples include antidepressant-induced mania/hypomania and rapid/ultra-rapid/ultradian cycling, when clinicians observe an almost continuous mixed state with a constant change of preponderance of manic or depressive symptoms. Achieving stable remission in these cases is challenging with almost no data on evidence-based treatment. When mood stabilizers are ineffective, electroconvulsive therapy (ECT) has been suggested. Objectives: After reviewing the evidence from available literature, this article presents our own clinical experience of ECT efficacy and tolerability in patients with ultra-rapid cycling bipolar disorder (BD) and unstable mixed states. Materials and Methods: We conducted an open, one-year observational prospective study with a \"mirror image\" design, including 30 patients with rapid and ultra-rapid cycling BD on long-term mood stabilizer treatment (18 received lithium carbonate, 6 on valproate and 6 on carbamazepine) with limited effectiveness. A bilateral ECT course (5-10 sessions) was prescribed for regaining mood stability. Results: ECT was very effective in 12 patients (40%) with a history of ineffective mood stabilizer treatment who achieved and maintained remission; all of them received lithium except for 1 patient who received carbamazepine and 2 with valproate. Nine patients (30%) showed partial response (one on carbamazepine and two on valproate) and nine patients (30%) had no improvement at all (four on carbamazepine and two on valproate). For the whole sample, the duration of affective episodes was significantly reduced from 36.05 ± 4.32 weeks in the year prior to ECT to 21.74 ± 12.14 weeks in the year post-ECT (p < 0.001). Depressive episodes with mixed and/or catatonic features according to DSM-5 specifiers were associated with a better acute ECT response and/or long-term mood stabilizer treatment outcome after ECT. Conclusions: ECT could be considered as a useful option for getting mood instability under control in rapid and ultra-rapid cycling bipolar patients. Further randomized trials are needed to confirm these results.

Apparent comorbidity between Bipolar Disorder (BD) and Obsessive-Compulsive Disorder (OCD) is a common condition, but its meaning has not been clarified yet. The present study aimed to evaluate the pattern of occurrence of obsessive-compulsive symptoms (OCS) in the different phases of BD. One hundred and sixty-five BD patients, 62 (37.5%) euthymic, 34 (20.6%) in hypomanic/manic phase, 43 (26%) in depressive phase and 26 (15.7%) in mixed state, were assessed with the Yale-Brown Obsessive-Compulsive Scale (YBOCS), the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Ruminative Response Scale (RRS). In the whole sample, the severity of OCS was associated to the severity of depressive symptoms. The highest severity of OCS (YBOCS total score) was observed in the mixed group and the lowest scores in the hypomanic/manic group. Our findings suggest that OCS in BD patients appear as a state-dependent phenomenon cycling with the mood phases, particularly exacerbating in the context of depressive and mixed states.

The Araki-Lieb inequality is commonly used to calculate the entropy of subsystems when they are initially in pure states, as this forces the entropy of the two subsystems to be equal after the complete system evolves. Then, it is easy to calculate the entropy of a large subsystem by finding the entropy of the small one. To the best of our knowledge, there does not exist a way of calculating the entropy when one of the subsystems is initially in a mixed state. For the case of a two-level atom interacting with a quantized field, we show that it is possible to use the Araki-Lieb inequality and find the von Neumann entropy for the large (infinite) system. We show this in the two-level atom-field interaction.

暂无摘要。

UNASSIGNED: Treatment-resistant depression (TRD) and treatment-resistant bipolar depression (TRBD) poses a significant clinical and societal burden, relying on different operational definitions and treatment approaches. The detection of clinical predictors of resistance is elusive, soliciting clinical subtyping of the depressive episodes, which represents the goal of the present study.
UNASSIGNED: A hundred and thirty-one depressed outpatients underwent psychopathological evaluation using major rating tools, including the Hamilton Rating Scale for Depression, which served for subsequent principal component analysis, followed-up by cluster analysis, with the ultimate goal to fetch different clinical subtypes of depression.
UNASSIGNED: The cluster analysis identified two clinically interpretable, yet distinctive, groups among 53 bipolar (resistant cases = 15, or 28.3%) and 78 unipolar (resistant cases = 20, or 25.6%) patients. Among the MDD patients, cluster \"1\" included the following components: \"Psychic symptoms, depressed mood, suicide, guilty, insomnia\" and \"genitourinary, gastrointestinal, weight loss, insight\". Altogether, with broadly defined \"mixed features,\" this latter cluster correctly predicted treatment outcome in 80.8% cases of MDD. The same \"broadly-defined\" mixed features of depression (namely, the standard Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition-DSM-5-specifier plus increased energy, psychomotor activity, irritability) correctly classified 71.7% of BD cases, either as TRBD or not.
UNASSIGNED: Small sample size and high rate of comorbidity.
UNASSIGNED: Although relying on different operational criteria and treatment history, TRD and TRBD seem to be consistently predicted by broadly defined mixed features among different clinical subtypes of depression, either unipolar or bipolar cases. If replicated by upcoming studies to encompass also biological and neuropsychological measures, the present study may aid in precision medicine and informed pharmacotherapy.

Operational definitions of mania are based on expert consensus rather than empirical data. The aim of this study is to identify the key domains of mania, as well as the relevance of the different signs and symptoms of this clinical construct.
A review of latent factor models studies in manic patients was performed. Before extraction, a harmonization of signs and symptoms of mania and depression was performed in order to reduce the variability between individual studies.
We identified 12 studies fulfilling the inclusion criteria and comprising 3039 subjects. Hyperactivity was the clinical item that most likely appeared in the first factor, usually covariating with other core features of mania, such as increased speech, thought disorder, and elevated mood. Depressive-anxious features and irritability-aggressive behavior constituted two other salient dimensions of mania. Altered sleep was frequently an isolated factor, while psychosis appeared related to grandiosity, lack of insight and poor judgment.
Our results confirm the multidimensional nature of mania. Hyperactivity, increased speech, and thought disorder appear as core features of the clinical construct. The mood experience could be heterogeneous, depending on the co-occurrence of euphoric (elevated mood) and dysphoric (irritability and depressive mood) emotions of varying intensity. Results are also discussed regarding their relationship with other constitutive elements of bipolar disorder, such as mixed and depressive states.