Mixed Episodes Research Articles

Significant roles of aged dust aerosols on rapid nitrate formation under dry conditions in a semi-arid city

Mineral dust can accelerate secondary aerosol formation under humid conditions. However, it is unclear whether it can promote secondary aerosol formation under dry conditions. To investigate this issue, two years of comprehensive observations was conducted at a semi-arid site, near the dust source regions. Three types of episodes were selected: dust, anthropogenic-dominated, and mixed (mixed with dust and anthropogenic aerosols). Compared to anthropogenic-dominated episodes under humid conditions, rapid nitrate formation was still observed in mixed episodes under dry conditions, suggesting that active metallic oxides in dust, such as titanium dioxide, could promote photochemical reactions of nitrogen dioxide. The detailed evolutionary processes are further illustrated by a typical dust-to-mixed episode. After the arrival of the dust, titanium sharply increased ten-fold and rapid nitrate formation was observed, together with a rapid increase in the two most important photochemical pollutants, ozone and peroxyacetyl nitrate. The increased secondary organic carbon further illustrated that the suspended dust particles accelerated the atmospheric oxidative capacity, thereby enhancing secondary aerosol formation and eventually leading to haze pollution. These results differ from those in humid regions and therefore expand the scientific understanding of the impact of dust aerosols on haze pollution under dry conditions.

A Prospective Comparison of Bipolar I and II Subjects with and without Comorbid Cannabis Use Disorders from the COGA Dataset.

The comorbidity of alcohol and substance use disorders among persons with bipolar disorder is elevated, as indicated by epidemiological and clinical studies. Following alcohol use, cannabis is the most frequently used and abused illicit substance among bipolar individuals, and such use may lead to comorbid cannabis use disorders (CUD). Previous research indicated that CUDs were related to a more severe course of bipolar disorder and higher rates of other comorbid alcohol and substance use disorders. Few studies, however, have conducted longitudinal research on this comorbidity. The aim of this study is to investigate the influence of CUD on the course of bipolar I and II individuals during a 5-year follow-up. The characteristics of bipolar disorder, cannabis use disorders, and other alcohol and substance use disorders, as well as comorbid mental disorders, were assessed using a standardized semi-structured interview (SSAGA) at both baseline and the 5-year follow-up. N = 180 bipolar I and II patients were subdivided into groups of with and without comorbid cannabis use disorders (CUD). Of the 77 bipolar I and 103 bipolar II patients, n = 65 (36.1%) had a comorbid diagnosis of any CUD (DSM-IV cannabis abuse or dependence). Comorbid bipolar patients with CUD had higher rates of other substance use disorders and posttraumatic stress disorders, more affective symptoms, and less psychosocial functioning at baseline and at 5-year follow-up. In contrast to previously reported findings, higher rates of anxiety disorders and bipolar disorder complications (e.g., mixed episodes, rapid cycling, and manic or hypomanic episodes) were not found. The effect of CUD on other substance use disorders was confirmed using moderation analyses. A 5-year prospective evaluation of bipolar patients with and without CUD confirmed previous investigations, suggesting that the risk of other substance use disorders is significantly increased in comorbid individuals. CUD has a moderation effect, while no effect was found for other mental disorders. Findings from this study and previous research may be due to the examination of different phenotypes (Cannabis use vs. CUD) and sample variation (family study vs. clinical and epidemiological populations).

Polysubstance addiction patterns among 7,989 individuals with cocaine use disorder

To characterize polysubstance addiction (PSA) patterns of cocaine use disorder (CoUD), we performed a latent class analysis (LCA) in 7,989 participants with a lifetime DSM-5 diagnosis of CoUD. This analysis identified three PSA subgroups among CoUD participants (i.e., low, 17%; intermediate, 38%; high, 45%). While these subgroups varied by age, sex, and racial-ethnic distribution (p<0.001), there was no difference with respect to education or income (p>0.05). After accounting for sex, age, and race-ethnicity, the CoUD subgroup with high PSA had higher odds of antisocial personality disorder (OR= 21.96 vs. 6.39, difference-p=8.08✕10-6), agoraphobia (OR= 4.58 vs. 2.05, difference-p= 7.04✕10-4), mixed bipolar episode (OR= 10.36 vs. 2.61, difference-p= 7.04✕10-4), posttraumatic stress disorder (OR= 11.54 vs. 5.86, difference-p= 2.67✕10-4), antidepressant medication use (OR= 13.49 vs. 8.02, difference-p= 1.42✕10-4), and sexually transmitted diseases (OR= 5.92 vs. 3.38, difference-p= 1.81✕10-5) than the low-PSA CoUD subgroup. These findings underscore the importance of modeling PSA severity and comorbidities when examining the clinical, molecular, and neuroimaging correlates of CoUD.

Disability and its correlates among persons with bipolar disorder: Exploratory findings from the bipolar disorder course and outcome study from India (BiD-CoIN study).

This study aimed to evaluate the disability and its correlates in persons with Bipolar Disorder during the remission phase. As part of the multicentric study, 773 patients with bipolar disorder, currently in clinical remission, were evaluated for disability on the Indian Disability Assessment Evaluation Scale. About one-fifth of the participants had some level of disability in the domain of self-care, one-third had some level of disability in the interpersonal domain, one-fourth had some level of disability in communication and understanding, and a maximum proportion (43.7%) had some disability in the domain of work. Overall, about one-fifth (18.4%) were considered to have a benchmark disability (i.e., disability >40%). In terms of correlates, those with a disability had a short duration of current remission, a higher number of manic and mixed episodes, a higher mean number of total episodes, spent more time in the episodes, had lower severity of the depressive episodes, higher residual depressive and manic symptoms, had overall higher manic affective morbidity, had a higher level of cognitive deficits, and had poorer insight. A significant proportion of patients with bipolar disorder have disability in work domain, and the presence of residual symptoms of either polarity are associated with higher level of disability.

Dynamic time warp analysis of individual symptom trajectories in individuals with bipolar disorder.

Manic and depressive mood states in bipolar disorder (BD) may emerge from the non-linear relations between constantly changing mood symptoms exhibited as a complex dynamic system. Dynamic Time Warp (DTW) is an algorithm that may capture symptom interactions from panel data with sparse observations over time. The Young Mania Rating Scale and Quick Inventory of Depressive Symptomatology were repeatedly assessed in 141 individuals with BD, with on average 5.5 assessments per subject every 3-6 months. Dynamic Time Warp calculated the distance between each of the 27 × 27 pairs of standardized symptom scores. The changing profile of standardized symptom scores of BD participants was analyzed in individual subjects, yielding symptom dimensions in aggregated group-level analyses. Using an asymmetric time-window, symptom changes that preceded other symptom changes (i.e., Granger causality) yielded a directed network. The mean age of the BD participants was 40.1 (SD 13.5) years old, and 60% were female participants. Idiographic symptom networks were highly variable between subjects. Yet, nomothetic analyses showed five symptom dimensions: core (hypo)mania (6 items), dysphoric mania (5 items), lethargy (7 items), somatic/suicidality (6 items), and sleep (3 items). Symptoms of the "Lethargy" dimension showed the highest out-strength, and its changes preceded those of "somatic/suicidality," while changes in "core (hypo)mania" preceded those of "dysphoric mania." Dynamic Time Warp may help to capture meaningful BD symptom interactions from panel data with sparse observations. It may increase insight into the temporal dynamics of symptoms, as those with high out-strength (rather than high in-strength) could be promising targets for intervention.

Predominant polarity in bipolar affective disorder and its impact on cognition and quality of life.

Bipolar mood disorder or bipolar affective disorder (BPAD) is a chronic illness characterized by phases of mania/hypomania, depression, or mixed episodes. The course of bipolar mood disorder is relapsing in nature. It is associated with high comorbidity rates, a large number of premature deaths due to suicide, and a worse social and work performance. All of those characteristics entail a significant economic impact due to both direct and indirect costs and require an effective diagnostic and therapeutic approach. Lifetime prevalence of BPAD is approximately 4% worldwide. Various attempts have been made to define "predominance" of polarity in BPAD. Our study tries to highlight the existence of predominant polarity by comparing effects of the same on substance consumption, cognitive abilities, quality of life, and preponderance of specific polarity to specific gender. After Institutional Ethics Committee Approval and written informed consent, patients who were diagnosed with BPAD attending out-patient department of a tertiary care hospital in Mumbai were recruited. A total of 57 participants were enrolled. The World Health Organization Quality of Life - Brief Scale (WHOQOL BREF) and the Montréal Cognitive Assessment (MoCA) were both used to evaluate the patients' quality of life and cognitive ability, respectively. Men exhibited manic predominant polarity, while women had depressive predominant polarity, with P value of. 003. Regarding age, illness length, education, substance abuse, family history, and suicide attempts, there was no discernible difference in the polarities. The outcome of female bipolar patients may be improved if the clinician is mindful of the burden of depression, risk of misdiagnosis, and variable therapy response. Interestingly, our study found no significant difference between MoCA scores of those with depressive and manic polarity. Substantial MoCA score differences were found between the groups with depressive polarity and no polarity. Men were observed to experience more manic episodes. More women in the study experienced predominantly depressive polarity, highlighting the need to probe for a past history of hypomania or mixed episodes to avoid misdiagnosis as unipolar depression in them. Manic predominate polarity performed better in the physical and psychological domains of the post hoc test for quality-of-life BREF scale. There were substantial MoCA score differences between the groups with depressive polarity and no polarity, with the depressive polarity showing more cognitive decline.

0642 Effect of Iloperidone on Sleep Symptoms in Bipolar Patients with Manic and Mixed Episodes: A Randomized, Placebo Controlled Study

Abstract Introduction Iloperidone, a dopamine D2 receptor and serotonin 5HT2A receptor antagonist, was evaluated for the treatment of acute manic and mixed episodes associated with bipolar I disorder in adults in a phase 3 clinical trial. A core symptom of bipolar I disorder is disturbance in sleep. During manic episodes this commonly presents as reduced need for sleep with studies finding that 69%–99% of bipolar individuals report a lessened need for sleep or difficulties in falling and/or staying asleep. Here we present a post hoc analysis evaluating iloperidone effects on the sleep component of the Young Mania Rating Scale (YMRS) in patients with bipolar I disorder which addresses both sleep and the reduced need for sleep in that component. Methods This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study of iloperidone in patients with acute manic or mixed episodes associated with bipolar I disorder. Patients received four weeks of double-blind treatment. The primary analysis demonstrating an overall improvement from baseline YMRS score in iloperidone assigned patients versus placebo assigned patients (p = 0.000008) at the end of the study (week 4). A YMRS item level analysis evaluated changes on YMRS single items including the sleep component in the intent-to-treat population (N = 392) using a mixed-effects model for repeated measures approach. Results The least squares mean difference (LSMD) in change from baseline to day 28 was statistically significant on the YMRS sleep component in favor of iloperidone versus placebo (iloperidone = -1.26, placebo = -0.95; p = 0.008). Conclusion In addition to improving overall mania symptoms as reported by the YMRS, improvements were also seen in iloperidone treated patients in the sleep component which at baseline included assessments of both decreased sleep and decreased need or denial of the need for sleep. Support (if any) This work was supported by Vanda Pharmaceuticals Inc.

Cariprazine (Vraylar) for adjunctive treatment of depression.

The FDA has approved the second-generation antipsychotic drug cariprazine (Vraylar — Abbvie) for adjunctive treatment of major depressive disorder (MDD) in adults. Cariprazine was previously approved for treatment of schizophrenia and bipolar depression, and for acute treatment of manic or mixed episodes associated with bipolar I disorder.

Mood Stabilizers: An Overview

Bipolar disorder, a mental illness that affects mood, behavior, and motivation is characterized by alternating depressive and manic (hypomanic) episodes (some mixed episodes include both types of symptoms), with periods of remission between episodes. Symptoms and progress vary across patients. Treatment includes anti-seizure medications and maintenance therapy to prevent seizures. Classically, lithium carbonate and valproate are the most commonly used medications; however, in addition to lamotrigine, atypical antipsychotics including aripiprazole, quetiapine, and lurasidone are being used in recent years. Theoretically, patients are administered monotherapy; however, it is not uncommon to use combination treatment in clinical practice.

Pediatric Bipolar Disorder: A Practical Guide for Clinicians.

Pediatric bipolar disorder (PBD) is a controversial clinical entity and it still needs to be satisfactorily defined. Having a polymorphous presentation and associated with numerous symptoms of comorbid psychiatric illnesses often diagnosed during childhood and adolescence, including attention deficit hyperactivity disorder, its symptoms do not completely parallel those of bipolar disorder in adults. The clinician must be able to reach a diagnosis of PBD in the presence of fluctuating and atypical symptoms, especially in children, who tend to experience mixed episodes and very rapid cycles. Historically a key symptom for diagnosing PBD is episodic irritability. Proper diagnosis is critical due to the gravity of its prognosis. Clinicians may find supporting evidence for a diagnosis through careful study of the medical and developmental history of the young patient in addition to psychometric data. Treatment prioritizes psychotherapeutic intervention and assigns important roles to family involvement and a healthy lifestyle.

Economic Outcomes with Adjunctive Cariprazine and Other Atypical Antipsychotics in Patients with Major Depressive Disorder

AbstractIntroductionPatients with major depressive disorder (MDD) who have inadequate responses to antidepressants (ADs) can benefit from augmentation with atypical antipsychotics (AAs). Cariprazine, a D3/D2 receptor partial agonist, is approved for schizophrenia and for manic, mixed, or depressive episodes associated with bipolar I disorder. Cariprazine is also currently under investigation for the adjunctive treatment of MDD. The aim of this retrospective cohort study was to describe healthcare resource utilization (HCRU) and associated medical costs with cariprazine and other adjunctive AA therapies for MDD.MethodsIBM® MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid databases were searched for claims made from 01-Jan-2018 to 31-Mar-2021. The study population included adults (≥18 years) who met the following criteria: ≥1 inpatient claim with an MDD diagnosis or ≥2 outpatient claims that were &gt;30 days apart; ≥1 AD therapy after MDD diagnosis; ≥1 branded or generic adjunctive AA (with AD); enrollment for ≥6 and ≥12 months for baseline and follow-up analyses, respectively. Branded AAs were analyzed individually; generic AAs were grouped. MDD-related HCRU outcomes per person over the 12-month follow-up period included inpatient stays, inpatient costs, office visits, and office visit costs, with adjusted pairwise comparisons between cariprazine and other AAs. Statistical significance was defined as the 95% confidence interval (CI) for the estimated mean ratio (EMR) of comparator AA to cariprazine not including 1 (i.e., value indicating no difference).ResultsAnalyses included 46,197 patients, with AA cohorts as follows: generics (n=39,410, including mostly aripiprazole and quetiapine); brexpiprazole (n=3,249); lurasidone (n=1,795); cariprazine (n=1,051); quetiapine-XR (n=644). A majority of patients across cohorts were women (range, 65.7% to 75.4%). Inpatient stays were statistically significantly fewer with cariprazine than all other AA therapies (EMR range [95% CI]: 1.7 [1.2–2.3] to 2.9 [2.1–3.9] for brexpiprazole and generics, respectively). Inpatient costs were lower for cariprazine than other branded AAs and statistically significantly lower compared to generics (2.4 [1.6–4.1]). Office visits were fewer with cariprazine than all other AAs and significantly lower than generics (1.1 [1.03–1.2]), lurasidone (1.3 [1.2–1.4]), and brexpiprazole (1.4 [1.2–1.5]). Office visit costs were also lower for cariprazine than all other AAs and statistically significantly lower than lurasidone (1.2 [1.03–1.5) and brexpiprazole (1.4 [1.2–1.6]).ConclusionsThe results of this study suggest that in patients with MDD, adjunctive treatment with cariprazine is associated with statistically significantly lower HCRU for certain outcomes and numerically lower medical costs compared to other branded AAs, along with statistically significantly lower HCRU and medical costs versus generic Aas.FundingAbbVie

Cariprazine for the Adjunctive Treatment of Major Depressive Disorder: Results of a Randomized Phase 3 Placebo-Controlled Study (Study 301)

AbstractBackgroundPatients with major depressive disorder (MDD) often do not respond to antidepressant (ADT) monotherapy; adjunctive treatment is often used to address this unmet need. Cariprazine (CAR), a dopamine D3-preferring D3/D2 and serotonin 5-HT1A receptor partial agonist approved to treat adults with manic, mixed, or depressive episodes of bipolar I disorder, is under investigation as adjunctive therapy for patients with MDD.MethodsThis randomized, double-blind, phase 3 placebo (PBO)-controlled study assessed the efficacy, safety, and tolerability of CAR 1.5 and 3 mg/d as an adjunct to ADT in adult patients with MDD (18–65 years) and inadequate response to ADT alone (NCT03738215). The primary endpoint was change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score. Hamilton Depression Rating Scale (HAMD-17), Hamilton Anxiety Rating Scale (HAM-A), and Clinical Global Impressions (CGI) were also assessed. Treatment response was defined as at least 50% decrease in MADRS total score at week 6.ResultsPatients (n=751) in the modified intent-to-treat population were randomly assigned to CAR 1.5 mg/d+ADT (n=250), CAR 3 mg/d+ADT (n=252), or PBO+ADT (n=249). Mean age was 44.8 years and 73.4% were female; mean baseline total scores were: MADRS=32.5, HAMD-17=25.9, HAM-A= 21.4. Overall, 89.7% of patients completed the study; rates of discontinuation due to adverse events (AEs) and lack of efficacy were 3.6% and 0.5%, respectively. The difference in MADRS total score change from baseline to week 6 was statistically significant after multiplicity adjustment for CAR 1.5 mg/d vs PBO (-14.1 vs -11.5; adjusted P=.0050), but not for CAR 3 mg/d (-13.1; P=.0727). Differences for CAR 1.5 mg/d vs PBO were observed by week 2 (nominal P=.0453) and maintained at weeks 4 (nominal P&lt;.0001) and 6 (nominal P=.0025). At week 6, more CAR 1.5 mg/d patients (44%) than PBO patients (34.9%) responded to treatment (nominal P=.0446). Greater improvement in the CGI-I scores was observed for CAR 1.5 (nominal P=.0026) and 3 mg/d (nominal P=.0076) vs PBO. At week 6, improvement in HAMD-17 total score reached nominal significance for CAR 1.5 mg/d vs PBO (-13.1 vs -11.1; nominal P=.0017), but not for CAR 3 mg/day (-12.2; P=.0783). HAM-A improvement was greater for CAR 1.5 mg/d vs PBO (nominal P=.0370). There were no deaths; 2 serious AEs occurred in each group (CAR: kidney infection, social stay hospitalization; PBO: depression, multiple sclerosis). The most common CAR AEs (≥5% and twice PBO) were akathisia and nausea.ConclusionCariprazine 1.5 mg/d was effective as adjunctive treatment in adults with MDD and inadequate response to ADT. Cariprazine was generally well tolerated, with a safety profile that was consistent with other indications. Together with results from a prior flex-dose study, these results suggest that adjunctive cariprazine may be an effective option for patients with inadequate response to ADT alone.FundingAbbVie

The longitudinal trajectory of emotional cognition in subgroups of recently diagnosed patients with bipolar disorder

Although cross-sectional studies show heterogeneity in emotional cognition in bipolar disorder (BD), the temporal course within subgroups is unclear. In this prospective, longitudinal study we assessed the trajectories of emotional cognition subgroups within a 16-month follow-up period in recently diagnosed BD patients compared to healthy controls (HC). Recently diagnosed BD patients and HC underwent comprehensive emotional and non-emotional testing at baseline and again at follow-up. We employed hierarchical cluster analysis at baseline to identify homogenous emotional cognition subgroups of patients, and changes across the subgroups of BD and HC were assessed with linear mixed-model analyses. We found two emotional cognition subgroups: subgroup 1 (65%, n = 179), showing heightened negative emotional reactivity in neutral and negative social scenarios and faster recognition of emotional facial expressions than HC (ps<0.001, n = 190), and subgroup 2 (35%, n = 96) showing blunted reactivity in positive social scenarios, impaired emotion regulation, poorer recognition of positive and slower recognition of all facial expressions than HC (ps≤.03). Subgroup 1 exhibited normalization of the initial emotional cognition abnormalities in follow-up. In contrast, subgroup 2 showed a lack of improvement in reactivity positively-valenced emotional information. Patients in subgroup 2 presented more and longer mixed episodes during the follow-up time and were more often prescribed lithium. One third of patients display blunted emotional reactivity, impaired emotion regulation abilities and facial expression recognition difficulties also show persistent impairments and poorer course of illness. This subgroup may indicate a need for earlier and more targeted therapeutic interventions.

Smartphone App Shows Promise in Some Patients With Bipolar I

Smartphone App Shows Promise in Some Patients With Bipolar I

A comparative meta-analysis of peripheral 8-hydroxy-2′-deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) levels across mood episodes in bipolar disorder

ObjectiveOxidative DNA damage has been associated with the pathophysiology of bipolar disorder (BD) as one of the common pathways between increased medical comorbidity and premature aging in BD. Previous evidence shows increased levels of oxidatively induced DNA damage markers, 8-hydroxy-2′-deoxyguanosine (8-OHdG) or its tautomer 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG), in patients with BD in comparison to healthy individuals. With the current research, we aim to analyze data on peripheral (blood or urine) 8-OHdG/8-oxo-dG levels across mood states of BD using a meta-analytical approach. MethodA literature search was conducted using the databases PubMed, Scopus, and Web of Science to identify eligible studies (January 1989 to July 2022). Relevant studies were systematically reviewed; a random-effects meta-analysis and a meta-regression analysis were conducted. ResultsThe current meta-analysis included 12 studies consisting of 808 BD patients (390 in euthymia, 156 in mania, 137 in depression, 16 in mixed episode, 109 not specified) and 563 healthy controls. BD patients that were currently depressed had significantly higher levels of 8-OHdG/8-oxo-dG than healthy controls, while euthymic or manic patients did not differ from healthy controls. A meta-regression analysis showed sex distribution (being female) and older age to be significantly related to increased 8-OHdG/8-oxo-dG levels. ConclusionOur findings suggest that 8-OHdG/8-oxo-dG may be a state-related marker of depression in BD and may be affected by older age and female gender.

A Rare Case of Porencephaly with Seizure Disorder, Organic Personality Change and Agitated Depression

Porensefali, serebral yarım küredeki kistler/boşluklar ile karakterize bir merkezi sinir sistemi bozukluğudur. Nöbetler, parezi, öğrenme güçlükleri, zeka geriliği ve nadiren psikiyatrik belirtiler gibi çeşitli klinik belirtilere sahiptir. Psikiyatrik belirtiler arasında psikoz en sık görülen belirtidir. Psikiyatrik sendromlarla başvuran porensefali ile ilgili sadece birkaç vaka raporu vardır. Bu vaka sunumunda nöbet bozukluğu, organik kişilik değişikliği ve ajite depresyon ile benzersiz bir porensefali vakasının tartışılması amaçlandı.

Weight gain as a secondary effect of Olanzapine, and its interference in treatment adherence: a case report.

IntroductionOlanzapine is a second generation antipsychotic that is approved for the treatment of schizophrenia, bipolar disorder type 1 as monotherapy, or as an add-on to lithium or valproate (manic or mixed episodes), and it is also used off label for acute anxiety, insomnia… It is one of the most effective antipsychotics but concerns remain due to its significant metabolic adverse effects. Olanzapine has one of the highest rates of weight gain among all antipsychotic drugs, which challenges patient’s adherence to treatment.ObjectivesReview how much influence Olanzapine has on weight gain, its influence in treatment adherence and alternatives in clinical practice.MethodsPresentation of a patient’s case and review of existing literature, in regards to Olanzapine and its repercussions on weight gain and the old and new alternatives available right now.ResultsOlanzapine is an effective antipsychotic, however, it causes secondary effects that complicate treatment, especially weight gain. In the case presented, the patient does gain weight with Olanzapine and adherence is compromised. In these cases, professionals try to look for alternatives, either to try another drug or use adjunct treatment. In this patient, a change to lithium was made. In the last few years, adjunct treatment has gained traction, like for example: metformin and topiramate. The latest discovery in this matter are opioid antagonists: single dose oral tablet Olanzapine/samidorphan.ConclusionsEven though Olanzapine is one of the most effective antipsychotics and medications in mental health, its impact on patients’ weight hinders treatment continuity. The use of other already known medications and the appearance of new ones, that reduce weight gain probability, are the possible ways forward.Disclosure of InterestNone Declared

Mixed States and Suicidality in Bipolar Disorder: Results from the Stanley Foundation Bipolar Treatment Network

IntroductionMixed states in bipolar disorder (BD) are characterized by the simultaneous occurrence of both manic and depressive features. Growing evidence suggests that they are associated with longer duration of illness, increased relapse risk, and higher prevalence of comorbidities. Suicide risk among BD patients is up to 20–30 times greater than in the general population, although there is not a univocal consensus in whether mixed states should be considered as a high-risk state for suicide.ObjectivesThe objective of this study was to identify whether depressive and hypo/manic episodes with mixed features, are associated with more frequent suicidal behavior or ideation when compared to pure hypo/manic and depressive ones. We hypothesized that suicidal ideation or behavior would be more common in those experiencing mixed symptoms. We subsequently also tested whether gender or bipolar subtype moderated the relation between mood and suicidality.MethodsIn a naturalistic study, 903 adult BD outpatients participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,213 visits for 7 years. The scores at the Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and at the Young Mania Rating Scale (YMRS), administered at each visit, were used to define the mood episode. Given partial overlap of items between these scales, analyses were also conducted by removing overlapping items. The presence of suicidality was evaluated through the 18th item of the IDS-C (Suicidal Ideation).ResultsDuring the observation period, up to 60.7% of subjects had at least one visit with suicidal ideation or behavior, broadly defined as a score ≥ 1 at the 18th item of the IDS-C. The distribution of suicidality among visits in different mood states is reported in Figure 1 (N° of visits in which suicidality was detected by mood state at the time of visit). Depressive symptoms were associated with suicidal ideation and behavior either during mixed depression and hypo/mania (p &lt; 0.0001). Hypomanic or manic symptoms appeared to be related to suicidality only during hypo/mania, either pure or mixed (p 0.007). When overlapping items between the two psychometric scales were removed results seemed to confirm these hypotheses. Moreover, male gender appeared to have a protective role against suicidal ideation when hypo/manic (p 0.002).Image:ConclusionsThe primary role of depressive symptoms in predicting suicidal risk was confirmed by our results, which however suggest that mixed symptoms relate to suicidal ideation and behavior more intensely than pure hypo/manic symptoms. More importantly, hypo/manic symptoms did not appear to have a protective role during mixed episodes. Future studies considering also deaths by suicide are required in order to better clarify the role of mixity on suicidality.Disclosure of InterestNone Declared

The impact of COVID-19 pandemic on inpatient admissions for bipolar disorder

IntroductionIn 2019, there were 39.5 million patients suffering from bipolar disorder worldwide, resulting in around 8.5 million disability-adjusted life years (DALYs) and in a significant economic burden. Bipolar disorder is known to be susceptible to factors that disrupt biological and social rhythms. The COVID-19 pandemic and the measures taken to control it, such as social distancing, home confinement and lockdowns, pose a risk to the stability of bipolar patients. Other factors, for example, reduced access to treatment and stress associated with the disease could also contribute to relapses. Studies have shown that, in 2020, more people with bipolar disorder were hospitalised compared to previous years, including patients without previous history of hospitalizations.ObjectivesThis study aims to assess the impact of the COVID-19 pandemic on inpatient admissions for bipolar disorder.MethodsSocio-demographic and clinical data were collected from electronic medical records. A retrospective observational study of patients who were admitted to a psychiatric ward between March 2019 and February 2021 was conducted. The characteristics of patients admitted before the pandemic (March 2019 to February 2020) and after (March 2020 to February 2021) were compared statistically.ResultsA total of 850 patient admissions were obtained, 15% of which had a main diagnosis of bipolar disorder. The authors will analyze all the variables in the population admitted. The authors expect to find differences between patients hospitalized before and after the beginning of the pandemic, both in clinical presentation (manic, depressive or mixed episode), psychiatric history, comorbidities, suicide attempts and socio-demographic factors.ConclusionsThe COVID-19 pandemic had a significant impact on mental health on a global level, plenty of which is still unknown. The findings of this study will likely show the effects of this crisis on bipolar disorder patients.Disclosure of InterestNone Declared

Mixed Features in Bipolar Disorder: assessing symptoms profiles and their relation with DSM-5 criteria

IntroductionMixed states, the co-occurrence of manic and depressive symptoms, were recognized and described from the time of antiquity. DSM-5 first, and DSM-5-TR after, introduced the ‘’mixed features’’ specifier, defined by the presence of at least three non-overlapping opposite-pole symptoms during a syndromic depressive, hypomanic, or manic episode. Various manifestations, including irritability, distractibility, anxiety, psychomotor agitation, were excluded from the specifier, since they can occur during both depressive and hypo/manic episodes and other mental illnesses.ObjectivesThe objective of this study was to evaluate the phenomenology and prevalence of mixed states among bipolar disorder (BD) patients. We first assessed the frequency of specific features during different mood states. Then, we estimated the prevalence of mixed states by applying DSM-5 criteria, comparing it qualitatively with the one detected from psychometric questionnaires.MethodsIn a naturalistic study, 903 adult outpatients with BD participating in the Stanley Foundation Bipolar Network were followed longitudinally across 14,213 visits for 7 years. The scores at the Inventory of Depressive Symptomatology–Clinician-Rated Version (IDS-C) and at the Young Mania Rating Scale (YMRS), administered at each visit, were used to define the mood episode and to assess the frequency of specific symptoms. In addition, we applied DSM-5 criteria for “with mixed features” to our sample, to examine a DSM-5-based construct.ResultsSpecific symptomatic profiles differentiate mixed states from pure ones (Figure 1 and 2). Mainly, a higher prevalence of irritability was found during mixed episodes, both depressive and hypo/manic, compared to pure depression (0.60 vs. 1.20, p &lt; 0,001) and hypo/mania (0.82 vs. 1.54, p &lt; 0,001), as reported at the 6th item of IDS-C.Figure 1. Individual YMRS items scores in visits with pure depression, mixed depression, pure hypo/mania and mixed hypo/mania.Figure 2. Individual IDS-C items scores in visits with pure depression, mixed depression, pure hypo/mania and mixed hypo/mania.Image:Image 2:ConclusionsPreliminary results of the present study showed that symptoms like irritability are strongly prevalent during mixed states. Moreover, the DSM-5 diagnostic criteria for “with mixed features” specifier for any of the mood episodes detected lower rates of mixed states, hence this criteria may yield inadequate sensitivity in recognizing patients suffering from such conditions.Disclosure of InterestNone Declared