Patients selection for psychiatric neurosurgery: pitfalls and considerations.

Neurosurgical interventions (destructive or neuromodulation) are considered as a therapeutic option for patients with treatment resistant mental disorders. However, the issues of indications and contraindications for psychiatric surgery, method and patient selection remain unresolved. This article discusses possible problems and contradictions in the selection of patients, the need for an interdisciplinary team to work to solve the question of the feasibility of using neurosurgical methods. The authors have identified the main problems that increase the risks of selection and lead to a lack of results or low efficiency of neurosurgical intervention, namely: (1) diagnostic errors or inaccuracies; (2) inconclusive data on therapeutic resistance; (3) lack of a common understanding of the goals and desired results among participants in the selection of patients for neurosurgery. Possible predictors of surgical outcome and ethical issues are also discussed. Neurosurgical interventions as a treatment option for psychiatric disorders are not officially approved in most countries. So an appropriate algorithm for patient selection and clear criteria for outcome measures are needed.

Gamma Knife capsulotomy for correction of obsessive-compulsive symptoms in a patient with schizophrenia: Case report.

The treatment of mental illnesses that are resistant to conservative therapy poses a serious problem. Surgical methods with proven efficacy have been proposed for only a small group of psychiatric diseases, while in practice non-classical clinical situations are seen rather often. A 36-year-old man with a 18-year history of "schizophrenia with a predominant obsessive-compulsive syndrome" was referred to the Burdenko National Medical Research Center of Neurosurgery for consideration of neurosurgical treatment. Based on results of longitudinal independent evaluations of the patient in several specialized clinical centers the disease was considered resistant to medical therapy. Radiosurgical procedure was performed by means of Leksell Gamma Knife Perfexion™ (Elekta AB; Stockholm, Sweden). Ventral portion of the anterior limb of internal capsule was targeted with two 4-mm isocenters on each side, with prescription dose at 50% isodose line of 80 Gy and a maximal dose of 160 Gy. No obvious complications or side effects were noted during 13-month follow-up after radiosurgery. Gradual clinical improvement was observed with 25% reduction of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score at 13 months after treatment. Similarly, the Hospital Anxiety and Depression Scale (HADS) anxiety and depression scores decreased by 24% and 58%, respectively. This is the first published case of radiosurgical treatment of a psychiatric disorder in Russia. It demonstrates the potential efficacy of Gamma Knife capsulotomy for non-classical forms of obsessive-compulsive disorder comorbid with schizophrenia. Nevertheless, definitive conclusions about the reliability of this radiosurgical indication can only be made based on the results of larger studies.

The detrimental effects of smoking on the course and outcome in adults with bipolar disorder-A narrative review.

Background: Smoking is a substantial and avoidable risk for physical disability and premature death. Despite a declining tobacco use in the community of developed countries, smoking remains abundant in people with mental disorders. This narrative review highlights the epidemiology, consequences and treatment options of tobacco use disorder (TUD) and nicotine dependence (ND) in people with bipolar disorder (BD). Methods: The authors conducted a Medline literature search from 1970 to November 2022 using MeSH terms "bipolar disorder" x "smoking" or "nicotine" or "tobacco" that retrieved 770 results. Search results were complemented by additional literature retrieved from examining cross references and by hand search in text books. Finally, 92 references were considered as essential and selected for the educational purpose of this review. Summary of findings: Lifetime and point prevalence of smoking in people with BD is in the range of 45-70% and thus about 2-3 times more frequent in BD than in community samples. Smoking, TUD and ND have a detrimental impact both on mental and physical health as well as mortality in people with BD. In the absence of large controlled studies in comorbid BD and TUD or ND, pharmacological treatment follows the individual guidance for each disorder. Community-based psychosocial interventions for TUD and ND appear to be suitable in people with BD, too, as well as Cognitive Behavioral (CBT) or Acceptance and Commitment (ACT) based psychotherapies. Conclusions: Smoking is a modifiable risk factor causing increased risks both for mental and physical health in BD, and deserves more attention in treatment. More treatment research into pharmacological and psychosocial interventions in comorbid BD and TUD or ND are still needed to deliver evidence-based recommendations to physicians.

Functioning Problems in Persons with Schizophrenia in the Russian Context.

Assessing functionality in schizophrenia from a biopsychosocial perspective is essential to generate treatments that respond to the needs of the individual in his/her context. This research aims to assess the prevalence of functioning problems and their association with socio-demographic and clinical variables in a sample of Russian individuals with schizophrenia, using the International Classification of Functioning, Disability, and Health as a framework. An empirical cross-sectional study assessed the functioning of 40 individuals with schizophrenia using the International Classification of Functioning, Disability, and Health Core Set for schizophrenia. For the Body functions component, the highest prevalence of problems was found in b144 Memory functions (75%) and b140 Attention functions (70%). In the Activities and participation component, the greatest limitations were in d770 Intimate relationships (79.3%) and d240 Handling stress and other psychological demands (82.5%). In the Environmental factors, the most frequent problems were in e110 Products or substances for personal consumption (25%) and e460 Societal attitudes (22.5%); when scored as facilitators, the highest rated categories were e125 Products and technology for communication (100%) and e165 Assets (100%). These results may guide the design of specific treatments for these individuals and serve as a starting point for further studies in similar contexts and in other regions in Russia.

Stress, anxiety, depression and burnout in frontline healthcare workers during two peaks of COVID-19 pandemic in Russia.

PURPOSE: In this study we aimed to assess the range of psychopathological symptoms (anxiety, stress, depression, burnout) and risk factors in frontline HCWs during spring and autumn outbreaks of the new coronavirus infection in Russian Federation. METHODS: We conducted two independent, cross-sectional hospital-based online surveys. Data of 2195 HCWs were collected between May 19th and May 26th 2020 and between October 10th and October 17th 2020. Stress, anxiety, depression, burnout and perceived stress were assessed using the Russian versions of SAVE-9 and GAD-7, PHQ-9, MBI and PSS-10 scales. Logistic regression analysis was performed to determine the influence of different variables. RESULTS: The study revealed the rates of anxiety, stress, depression, emotional exhaustion and depersonalization and perceived stress as 32.3%, 31.1%, 45.5%, 74.2%, 37.7%,67.8%, respectively. Moreover, 2.4% of HCWs reported suicidal thoughts. The rate of anxiety was higher in October 2020 compared with May 2020. Revealed risk factors included: female gender, younger age, being a physician, working for over a week, living outside of Moscow or Saint Petersburg, being vaccinated against COVID-19. CONCLUSION: These results demonstrate the need for urgent supportive programs for HCWs fighting COVID-19 that fall into higher risk factors groups and its increasing importance over time.

Incidence of the Diagnosis of Anxiety Disorders in the Russian Federation: Results of a Web-Based Survey of Psychiatrists.

INTRODUCTION: According to the official Russian source, in 2017 only 0.27% of the population of Russia was diagnosed with International Classification of Diseases, tenth revision (ICD-10) F4 category disorders (neurotic, stress-related and somatoform disorders), despite these disorders being among the most prevalent mental disorders worldwide. Here we report the results of a large-scale survey among Russian psychiatrists with the primary objective to assess the proportion of psychiatrists who use the diagnoses of interest (mixed anxiety and depression disorder [MADD], adjustment disorder [AdD], panic disorder [PD], agoraphobia, generalized anxiety disorder [GAD], social phobia, simple phobia, acute stress disorder and posttraumatic stress disorder) and compare results with those of a recent World Psychiatric Association (WPA) and World Health Organization (WHO) survey. We also compared the incidence of these diagnoses between state and non-state psychiatric services in Russia. METHODS: Mean proportions and distribution of proportions of participants who made diagnoses of interest at different rates were calculated and compared with the results of the recent WPA and WHO survey. Risk ratios (RR) of the incidence of these diagnoses made at a frequency of at least once a week were calculated to compare state and non-state psychiatric services. The 95% confidence intervals of the RRs were calculated using the Koopman asymptotic score method. RESULTS: Responses of 960 Russian psychiatrists were included in the analysis. Of these 95, 89 and 87% reported making diagnoses of MADD, AdD and PD, respectively, during the preceding 12 months, a far larger proportion compared to other disorders of interest. In general, a significantly smaller proportion of participants in our survey made diagnoses of anxiety disorders compared to respondents in the international WPA-WHO survey. Based on RRs, diagnoses of MADD, AdD, PD, GAD and acute stress disorder were less frequently made in the state-operated psychiatric service. CONCLUSION: Our survey revealed a serious underdiagnosis of anxiety disorders in Russia that may be associated with complex factors that include, but are not limited to the current stigma associated with the state-operated psychiatric service, which is still the exclusive source of official statistical data in Russia.

Electroconvulsive Therapy (ECT) in Bipolar Disorder Patients with Ultra-Rapid Cycling and Unstable Mixed States.

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.

Assessment and Treatment of Negative Symptoms in Schizophrenia-A Regional Perspective.

Clinicians and researchers consider that there are a variety of symptoms that constitute negative symptoms in schizophrenia, and they may use different definitions for the same symptoms. These differences are also reflected in a variety of negative symptom rating scales. Both research and clinical work are negatively affected by the lack of consensus regarding the symptoms that constitute negative symptoms in schizophrenia. Leading research groups have investigated ways to reduce heterogeneity in the domain of negative symptoms in schizophrenia; however, little attention has been paid to regional differences in the concepts of negative symptoms in schizophrenia. The objective of this review was to collect and summarize information about the assessment and treatment of negative symptoms of schizophrenia in Central and Eastern Europe (CEE). Nineteen experts from 17 countries in CEE participated in this project. The participants collected information about their countries, including the following: (1) the most important publications about negative symptoms in schizophrenia (irrespective of the time of their publication); (2) the most frequently used negative symptom of schizophrenia in clinical practice; (3) definitions of frequently used negative symptoms; and (4) treatment of negative symptoms in schizophrenia. The participating experts/countries most frequently reported the following five negative symptoms: avolition, blunted affect, alogia, asociality, and anhedonia. Several experts also considered other symptoms as belonging to the negative symptom domain, such as a decrease in energy level and changes in personality. The importance of evaluating the long-term course and the relationship between negative symptoms and other symptom domains was also noted. No noticeable differences were reported in the treatment of negative symptoms compared to currently published guidelines and algorithms. The most frequently reported negative symptoms included those defined by the NIMH-MATRICS consensus statement on negative symptoms and recently endorsed in a guidance paper of the European Psychiatric Association. The main differences in the concepts, names, and definitions of primary negative symptoms, especially those related to personality changes, and to the evaluation of the long-term course and relationship between different symptom domains in CEE compared to the current English language literature deserve the attention of psychiatrists and other professionals in this field.

Primary and Secondary Negative Symptoms in Schizophrenia.

The negative symptoms of schizophrenia include volitional (motivational) impairment manifesting as avolition, anhedonia, social withdrawal, and emotional disorders such as alogia and affective flattening. Negative symptoms worsen patients' quality of life and functioning. From the diagnostic point of view, it is important to differentiate between primary negative symptoms, which are regarded as an integral dimension of schizophrenia, and secondary negative symptoms occurring as a result of positive symptoms, comorbid depression, side effects of antipsychotics, substance abuse, or social isolation. If secondary negative symptoms overlap with primary negative symptoms, it can create a false clinical impression of worsening deficit symptoms and disease progression, which leads to the choice of incorrect therapeutic strategy with excessive dopamine blocker loading. Different longitudinal trajectories of primary and secondary negative symptoms in different schizophrenia stages are proposed as an important additional discriminating factor. This review and position paper focuses primarily on clinical aspects of negative symptoms in schizophrenia, their definition, phenomenology, factor structure, and classification. It covers the historical and modern concepts of the paradigm of positive and negative symptoms in schizophrenia, as well as a detailed comparison of the assessment tools and psychometric tests used for the evaluation of negative symptoms.

Characterization of rapid cycling bipolar patients presenting with major depressive episode within the BRIDGE-II-MIX study.

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 < 0.001) with shorter duration of depressive episodes, and more psychiatric comorbidities, as well as higher rates of atypical features (p = 0.016) and concomitant (hypo)manic symptoms (irritable mood (p = 0.001); risky behavior (p = 0.005); impulsivity (p = 0.006); and psychomotor agitation (p = 0.029)). Patients with RC had a worse functioning (p = 0.033), more obesity (p = 0.003), and were significantly more likely to be treated with three or more drugs (p = 0.007). CONCLUSIONS: Important clinical differences between bipolar patients with and without a RC include more depressive morbidity, higher incidence of anxiety disorders, addiction, bulimia, and borderline personality disorder, as well as atypical features during depression and symptoms such as irritability, risky behavior, impulsivity, and agitation. RC patients had poorer functioning than patients without RC, more obesity, and had to be treated with more drugs.

Stress and Anxiety among Healthcare Workers Associated with COVID-19 Pandemic in Russia.

BACKGROUND: Mental health of medical workers treating patients with COVID-19 is an issue of increasing concern worldwide. The available data on stress and anxiety symptoms among healthcare workers during the COVID-19 are relatively limited and have not been evaluated in Russia yet. SUBJECTS AND METHODS: The cross-sectional anonymous survey included 1,090 healthcare workers. Stress and anxiety symptoms were assessed using Stress and Anxiety to Viral Epidemics - 9 (SAVE-9) and Generalized Anxiety Disorder - 7 (GAD-7) scales. Logistic regression, Kaiser-Meyer-Olkin two component factor model, Cronbach's alpha and ROC-analysis were performed to determine the influence of different variables, internal structure and consistency, sensitivity and specificity of SAVE-9 compared with GAD-7. RESULTS: The median scores on the GAD-7 and SAVE-9 were 5 and 14, respectively. 535 (49.1%) respondents had moderate and 239 (21.9%) had severe anxiety according to SAVE-9. 134 participants (12.3%) had severe anxiety, 144 (13.2%) had moderate according to GAD-7. The component model revealed two-factor structure of SAVE-9: "anxiety and somatic concern" and "social stress". Female gender (OR - 0.98, p=0.04) and younger age (OR - 0.65, p=0.04) were associated with higher level of anxiety according to regression model. The total score of SAVE-9 with a high degree of confidence predicted the GAD-7 value in comparative ROC analysis. CONCLUSIONS: Healthcare workers in Russia reported high rates of stress and anxiety. The Russian version of the SAVE-9 displayed a good ratio of sensitivity to specificity compared with GAD-7 and can be recommended as a screening instrument for detection of stress and anxiety in healthcare workers.

Factors associated with single versus multiple suicide attempts in depressive disorders.

BACKGROUND: Many risk factors for suicidal behavior have been identified. Much less has been done to associate risk factors with recurrence of suicidal behavior. METHODS: We compared prevalence of 30 potential risk factors among 8496 depressive patient-subjects from the BRIDGE consortium with no (NSA, n = 6267), one (1SA, n = 1123), or repeated (≥2) suicide attempts (RSA, n = 1106). RESULTS: Prevalence of most factors ranked: RSA ≥ 1SA > NSA, with a notable opposite trend for the diagnosis of type II bipolar disorder (BD). Factors independently and significantly more present among RSA than 1SA subjects were: borderline personality, substance abuse, mood-switching with antidepressant treatment, female sex, and unsatisfactory response to antidepressant treatment. There also were notably strong associations of RSA with type I or probable BD and associated factors, including family history of BD, young onset, mixed and psychotic features. LIMITATIONS: Potential effects of treatment on risk of suicidal acts could not be evaluated adequately, as well as associations between levels of suicidal behavior and eventual death by suicide. CONCLUSIONS: In a large cohort of depressive patients, there were significant associations not only with suicidal behavior generally, but also with the intensity of suicide attempts.

Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study.

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 < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression.

Symptom networks in acute depression across bipolar and major depressive disorders: A network analysis on a large, international, observational study.

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.

"Do depressive and manic symptoms differentially impact on functioning in acute depression? Results from a large, cross-sectional study".

BACKGROUND: 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. METHODS: 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. RESULTS: 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. LIMITATIONS: The post-hoc and cross-sectional design do not allow for prognostic or causal inferences. CONCLUSIONS: 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.

The role of different patterns of psychomotor symptoms in major depressive episode: Pooled analysis of the BRIDGE and BRIDGE-II-MIX cohorts.

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: A total of 3720 patients presented PR (48%), 1971 showed 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: Psychomotor symptoms could be considered as markers of bipolarity, illness severity, and treatment complexity, particularly if PA is present.

Patterns of response to antidepressants in major depressive disorder: Drug resistance or worsening of depression are associated with a bipolar diathesis.

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.

Relationships between recurrence and polarity in major depressive disorders: Pooled analysis of the BRIDGE and BRIDGE-II-MIX cohorts.

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.

The role of overlapping excitatory symptoms in major depression: are they relevant for the diagnosis of mixed state?

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.

Sultans of Swing: A Reappraisal of the Intertwined Association Between Affective Lability and Mood Reactivity in a Post Hoc Analysis of the BRIDGE-II-MIX Study.

OBJECTIVE: This post hoc analysis of the BRIDGE-II-MIX study is aimed at evaluating affective lability (AL) as a possible clinical feature of mixed depression and assessing the relationship with atypical depressive features, particularly mood reactivity (MR). METHODS: In the BRIDGE-II-MIX multicenter, cross-sectional study, 2,811 individuals suffering from a major depressive episode (MDE; DSM-IV-TR criteria), in the context of bipolar I or II disorder (BD-I, BD-II, respectively) or major depressive disorder, were enrolled between June 2009 and July 2010. Patients with (MDE-AL, n = 694) and without (MDE-noAL, n = 1,883) AL and with (MDE-MR, n = 1,035) or without (MDE-noMR, n = 1,542) MR were compared through χ² test or Student t test. Stepwise backward logistic regression models, respectively testing AL and MR as the dependent variable, were performed to differentiate the 2 clinical constructs. RESULTS: AL was positively associated with BD-I (P < .001) and BD-II (P < .001), with DSM-5 mixed (DSM-5-MXS) (P < .001) and atypical (DSM-5-AD) features (P < .001) and negatively associated with MDD (P < .001). In the logistic regression models, MR was the variable most significantly associated with AL and vice versa (P < .001 for both). AL was positively associated with severity of mania and DSM-5-MXS and negatively correlated with severity of depression, while MR was better predicted by atypical symptoms such as hyperphagia, hypersomnia, and leaden paralysis and correlated with both comorbid anxiety disorders and DSM-5-MXS. CONCLUSIONS: Mixed and atypical depression may lie on the same continuum. MR and AL could represent the underlying matrix, bridging the gap between mixed and atypical depression.