Reply to correspondence to "Algorithm or not for pharmacological treatment of mania during hospitalisation".

This is a letter to the editor on the "Correspondence on "An algorithm for pharmacological treatment of mania during hospitalisation" Dan Med J 2024;71(5):A08230525.

Correspondence on "An algorithm for pharmacological treatment of mania during hospitalisation".

This is a letter to the editor on the article "An algorithm for pharmacological treatment of mania during hospitalisation" Dan Med J 2024;71(5):A08230525.

Risk of Incident Psychosis and Mania With Prescription Amphetamines.

OBJECTIVE: Amphetamine prescribing has increased in the United States in recent years. Previous research identified an increased risk of incident psychosis with prescription amphetamines. The purpose of this study was to examine the impact of dose levels of prescription amphetamines on the risk of this rare but serious adverse outcome. METHODS: A case-control study using electronic health records was conducted to compare the odds of incident psychosis or mania with past-month exposure to prescription amphetamines. Case subjects were patients ages 16-35 hospitalized at McLean Hospital for incident psychosis or mania between 2005 and 2019. Control subjects were patients with an initial psychiatric hospitalization for other reasons, most commonly depression and/or anxiety. Amphetamine doses were converted to dextroamphetamine equivalents and divided into terciles. Secondary analyses evaluated the odds of psychosis or mania with methylphenidate use. RESULTS: Among 1,374 case subjects and 2,748 control subjects, the odds of psychosis and mania were increased for individuals with past-month prescription amphetamine use compared with no use (adjusted odds ratio=2.68, 95% CI=1.90-3.77). A dose-response relationship was observed; high doses of amphetamines (>30 mg dextroamphetamine equivalents) were associated with 5.28-fold increased odds of psychosis or mania. Past-month methylphenidate use was not associated with increased odds of psychosis or mania compared with no use (adjusted odds ratio=0.91, 95% CI=0.54-1.55). CONCLUSIONS: Although use of hospitalized control subjects excludes individuals with less severe disease, leading to selection bias, the study results suggest that caution should be exercised when prescribing high doses of amphetamines, with regular screening for symptoms of psychosis or mania.

Deletion of histamine H2 receptor in VTA dopaminergic neurons of mice induces behavior reminiscent of mania.

Hyperfunction of the dopamine system has been implicated in manic episodes in bipolar disorders. How dopaminergic neuronal function is regulated in the pathogenesis of mania remains unclear. Histaminergic neurons project dense efferents into the midbrain dopaminergic nuclei. Here, we present mice lacking dopaminergic histamine H2 receptor (H2R) in the ventral tegmental area (VTA) that exhibit a behavioral phenotype mirroring some of the symptoms of mania, including increased locomotor activity and reduced anxiety- and depression-like behavior. These behavioral deficits can be reversed by the mood stabilizers lithium and valproate. H2R deletion in dopaminergic neurons significantly enhances neuronal activity, concurrent with a decrease in the γ-aminobutyric acid (GABA) type A receptor (GABAAR) membrane presence and inhibitory transmission. Conversely, either overexpression of H2R in VTA dopaminergic neurons or treatment of H2R agonist amthamine within the VTA counteracts amphetamine-induced hyperactivity. Together, our results demonstrate the engagement of H2R in reducing VTA dopaminergic activity, shedding light on the role of H2R as a potential target for mania therapy.

Altered emotion perception in insomnia, anxiety, depression, mania, psychotic experiences and schizotypal symptoms: a dataset.

This data resource provides evidence concerning the prevalence of perceptual alterations of emotional faces amongst individuals experiencing symptoms of insomnia, anxiety, depression, mania, psychotic experiences, and schizotypal tendencies. More specifically, we explored the categorisation accuracy (whether the displayed emotion was correctly identified), misperception (which emotion an incorrect judgment was perceived to be), intensity (extent of the emotion signal strength) and emotional valence (the extent and direction of perceived affect) of six facial expressions of emotion from the Karolinska Directed Emotional Faces database. Complete data from N = 572 respondents are included. The dataset is available to other researchers and is provided on Figshare. Information concerning the data records, usage notes, code availability and technical validation are presented. Finally, we present demographic and correlational data concerning psychiatric symptoms and alterations in the perception of emotional faces.

Adalimumab-induced manic episode in an adolescent with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic inflammatory rheumatic disease in children, and adalimumab is one of the primary treatment options. Although it is widely used for inflammatory diseases, there is limited research on its safety and efficacy in patients with psychiatric disorders or in those with inflammatory diseases who also have comorbid psychiatric conditions. CASE REPORT: We report a 12-year-old adolescent boy who presented with emotional instability for 1 year, exacerbated leading to hospital admission in the past month. Upon detailed evaluation after admission, it was found that the patient's emotional fluctuations may be related to the use of Adalimumab. Follow-up after psychiatric inpatient treatment revealed that the patient did not experience emotional excitement again after discontinuing Adalimumab. CONCLUSIONS: Although tumor necrosis factor-α inhibitors have positive effects on the emotional, cognitive, and physical functions of patients with inflammatory diseases, their use may induce mood swings in patients with comorbid mood disorders. This is particularly important for adolescents with rapid mood changes, where greater caution is required. Further research is necessary to clarify the correlation between the adverse effects of these drugs and their impact on patients with bipolar disorder.

Case identification and healthcare utilization in the years prior to a first mania diagnosis.

BACKGROUND: There is limited evaluation of approaches to identify patients with new onset bipolar affective disorder (BPAD) when using administrative datasets. METHODS: Using the Massachusetts All-Payer Claims Database (APCD), we identified individuals with a 2016 diagnosis of bipolar disorder with mania and examined patterns of psychiatric and medical care over the preceding 48 months. RESULTS: Among 4806 individuals aged 15-35 years with a 2016 BPAD with mania diagnosis, 3066 had 48 months of historical APCD data, and of those, 75 % involved information from ≥2 payors. After excluding individuals with historical BPAD or mania diagnoses, there were 583 individuals whose 2016 BPAD with mania diagnosis appeared to be new (i.e., 34 new diagnoses per 100,000 individuals aged 15-35 years). Most individuals received medical care, e.g., 98 % had outpatient visits, 76 % had Emergency Department (ED) visits, and 50 % had mental health-related ED visits during the 48 months prior to their first mania diagnosis. One-third (37.2 %) had a depressive episode before their initial BPAD with mania diagnosis. LIMITATIONS: Study was conducted in one state among insured individuals. We used administrative data, which permits evaluation of large populations but lacks rigorous, well-validated claims-based definitions for BPAD. There could be diagnostic uncertainty during illness course, and clinicians may differ in their diagnostic thresholds. CONCLUSIONS: Careful examination of multiple years of patient history spanning all payors is essential for identifying new onset BPAD diagnoses presenting with mania, which in turn is critical to estimating population rates of new disease and understanding the early course of disease.

Full-spectrum efficacy of cariprazine across manic and depressive symptoms of bipolar I disorder in patients experiencing mood episodes: Post hoc analysis of pooled randomized controlled trial data.

INTRODUCTION: Patients with bipolar I disorder may experience mood destabilization or treatment-emergent affective switch (TEAS) from one symptom pole to the other spontaneously or following treatment. Optimal treatment should address symptoms from both poles without precipitating destabilization. METHODS: These were pooled post hoc analyses of data from randomized, double-blind, placebo-controlled studies of cariprazine 3-12 mg/d for bipolar I mania (NCT00488618, NCT01058096, NCT01058668) and cariprazine 1.5 mg/d or 3 mg/d for bipolar I depression (NCT01396447, NCT02670538, NCT02670551). Changes from baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) total score at week 6 and Young Mania Rating Scale (YMRS) total score at week 3 were analyzed in each indication using a mixed-effects model for repeated measures. Percentages of patients with increasing levels of endpoint response and TEAS (bipolar mania = MADRS total score ≥ 19; bipolar depression = YMRS score ≥ 16) were determined. RESULTS: Cariprazine significantly reduced manic and depressive symptoms in patients with bipolar I disorder mood episodes. In patients with a manic episode and up to mild baseline depressive symptoms, cariprazine also significantly reduced depressive symptoms. In patients with a depressive episode and manic symptoms in remission at baseline, numerical reduction (without statistical significance) in YMRS indicated no worsening of mania. In both indications, cariprazine-treated patients had numerically greater response rates (presenting symptom pole) than placebo-treated patients; lower percentages of cariprazine- than placebo-treated patients had TEAS at visits where data were collected. LIMITATIONS: Post hoc analysis. CONCLUSION: Results suggested that cariprazine had full-spectrum efficacy across symptoms from both poles in patients with bipolar I disorder mood episodes; TEAS risk was low. Patient-level response suggested that improvement was clinically relevant.

Transitional photoperiod induces a mania-like behavior in male mice.

This study aimed to investigate the behavioral responses and circadian rhythms of mice to both rapid and gradual increases in photoperiod, mimicking the transition from winter to summer, which is associated with a heightened prevalence of hospitalizations for mania and suicidal behavior. Behavioral tests were performed in C57BL/6 male mice exposed to a transitional photoperiod, from short to long durations. To determine if circadian rhythms are affected, we measured spontaneous locomotor activity and body temperature. Mice exhibited heightened exploratory and risk-taking behaviors compared with equatorial and static long (16:8 h of light-dark cycle for several days) groups. These behaviors were prevented by lithium. Spontaneous locomotor activity and body temperature rhythms persisted and were effectively synchronized; however, the relative amplitude of activity and interdaily stability were diminished. Additionally, the animals displayed increased activity during the light phase. Photoperiodic transition modulates behavior and circadian rhythms, mirroring certain features observed in bipolar disorder patients. This study introduces an animal model for investigating mania-like behavior induced by photoperiodic changes, offering potential insights for suicide prevention strategies and the management of mood disorders.

Functional network characteristics in anxiety- and mania-based subgroups of bipolar I disorder.

BACKGROUND: Bipolar disorder I (BD-I) is a heterogeneous disorder with a high prevalence of comorbid anxiety. The aim of this study was to investigate whether anxiety and mania symptoms define distinct subgroups within BD-I and to explore potential differences in functional network characteristics between these subgroups. METHODS: Subgroups were identified using scores from clinical anxiety and mania scales. After dimension reduction of these scores, data-driven clustering analysis with cross-validation was employed to reveal the existence of subgroups. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were pre-processed using fMRIPrep. After parcellation and network construction, global and regional graph theoretical measures were calculated per subgroup. RESULTS: Clustering results revealed that, based on anxiety symptomatology, subjects fell into two distinct subgroups, whereas mania symptoms divided subjects into four unique subgroups. These subgroups varied notably on several symptom scales. Network assortativity was significantly associated with anxiety subgroups. Post-hoc pairwise comparisons did not reveal significant global functional network differences between the anxiety subgroups or between mania subgroups. Regional network differences between clinical subgroups were especially apparent for strength and degree in the temporal and frontal lobes. LIMITATIONS: Small sample size of some subgroups is a limitation of this study as is the categorical rather than continuous representation of anxiety and mania symptoms. CONCLUSIONS: BD-I populations may be stratified into robust subgroups based on anxiety and mania symptoms, showing differences in functional network connectivity. Our findings highlight new avenues of research for investigating heterogeneity in psychiatric populations.

[Prolonged and chronic endogenous manic and manic-delusional states (psychopathology, typology, dynamics, clinic)]. / Zatyazhnye i khronicheskie endogennye maniakal'nye i maniakal'no-bredovye sostoyaniya (psikhopatologiya, tipologiya, dinamika, klinika).

OBJECTIVE: A clinical and psychopathological analysis, nosological differentiation of prolonged and chronic manic and manic-delusional states (PMDS) within the framework of the paroxysmal course of endogenous psychoses, determination of the patterns of their development, diagnostic criteria and prognosis. MATERIAL AND METHODS: The study included 76 female patients (average age 37.2±8.3 years) who were hospitalized for endogenous mental illnesses with a paroxysmal course that occurred with the clinical picture of PMDS. The patients were divided into two groups: clinical (n=43) and follow-up (n=33). Clinical-psychopathological, clinical-follow-up, psychometric, statistical methods were used. RESULTS: A clinical and dynamic typology of PMDS has been developed, according to which 2 groups have been identified: «monomorphic¼ PMDS and «polymorphic¼ PMDS. «Monomorphic¼ PMDS included 2 subtypes - «acute¼ and «chronified¼ and were characterized by the same clinical picture that remained unchanged throughout, while «polymorphic¼, which also included 2 subtypes - «developing¼ and «double mania subtype¼, were characterized by the variability of clinical picture. «Acute¼ and «developing¼ subtypes of PMDS predominantly developed in schizoaffective psychosis and bipolar disorder; the «chronified¼ subtype and the «double mania¼ subtype were more often observed within the framework of the schizoaffective variant of paroxysmal-progressive schizophrenia. CONCLUSION: The clinical and dynamic structure of PMDS is heterogeneous and differs in psychopathological structure, as well as in the level of stability of symptoms and characteristics of its course. The developed clinical typology of PMDS is prognostically significant and provides information about the further dynamics of the disease.

[THE ROLE OF STRESS IN MANIC-PSYCHOTIC EPISODE DURING THE TERROR ATTACK OF OCTOBER 7 - CASE REPORT].

INTRODUCTION: The bio-psycho-social model is mostly used to understand the etiology and pathogenesis of psychiatric disorders. Even though in our era, the biological factors became more dominant in the field, the stress-diathesis model is quite acceptable to explain and understand the evolution of psychotic as well as affective disorders. BACKGROUND: In this case report we present a patient, in her late 40's, admitted to our department with a manic-psychotic episode for the first time in her life, after the massive terror attack of October 7, and in which we suggest that the signs and symptoms might be explained using the psycho-dynamic theory. CONCLUSIONS: We conclude suggesting that the equilibrium of the bio-psycho-social model, should be adjusted in the context of time and space, especially during a situation of catastrophic scale in the patient environment. DISCUSSION: Although stress is a risk factor for the development of affective disorders and especially manic-psychotic episodes, there is scarce literature to support it. On the other hand, psycho-dynamic theories sometimes consider stressful life events as a causative factor for the development of depressive as well as manic episodes.

Unlocking treatment success: predicting atypical antipsychotic continuation in youth with mania.

PURPOSE: This study aimed to create and validate robust machine-learning-based prediction models for antipsychotic drug (risperidone) continuation in children and teenagers suffering from mania over one year and to discover potential variables for clinical treatment. METHOD: The study population was collected from the national claims database in China. A total of 4,532 patients aged 4-18 who began risperidone therapy for mania between September 2013 and October 2019 were identified. The data were randomly divided into two datasets: training (80%) and testing (20%). Five regularly used machine learning methods were employed, in addition to the SuperLearner (SL) algorithm, to develop prediction models for the continuation of atypical antipsychotic therapy. The area under the receiver operating characteristic curve (AUC) with a 95% confidence interval (CI) was utilized. RESULTS: In terms of discrimination and robustness in predicting risperidone treatment continuation, the generalized linear model (GLM) performed the best (AUC: 0.823, 95% CI: 0.792-0.854, intercept near 0, slope close to 1.0). The SL model (AUC: 0.823, 95% CI: 0.791-0.853, intercept near 0, slope close to 1.0) also exhibited significant performance. Furthermore, the present findings emphasize the significance of several unique clinical and socioeconomic variables, such as the frequency of emergency room visits for nonmental health disorders. CONCLUSIONS: The GLM and SL models provided accurate predictions regarding risperidone treatment continuation in children and adolescents with episodes of mania and hypomania. Consequently, applying prediction models in atypical antipsychotic medicine may aid in evidence-based decision-making.

Subclinical hypomanic experiences in young adults after sleep deprivation are independent of depressive disorders, chronotype or 5-HTTLPR polymorphism.

INTRODUCTION: The acute antidepressant effect of sleep deprivation (SD) in patients with depressive disorders has been studied for more than 60 years. However, hypomanic mood swings after partial or total SD have also been described in people without diagnosed mental disorders. Studying this phenomenon in the general population may yield insights about the mechanisms of therapeutic SD, mania and bipolar disorders. METHODS: A cross-sectional sample of young adults was recruited and classified into those who described having regularly occurring subclinical hypomanic experiences (ROHE) after SD and those who did not. History of psychiatric and physical illness, with screening for depression and mania, as well as alcohol or drug consumption, family history of depressive disorders or suicide, 5-HTTLPR polymorphism, and MEQ-SA chronotype were collected. RESULTS: A total of 251 participants were included; 39.0% indicated regularly having subclinical hypomanic experiences after SD. These experiences were not associated with depressive or mania screening, history of psychiatric illness, family history, 5-HTTLPR polymorphism, or MEQ-SA chronotype. CONCLUSIONS: ROHE after non-therapeutic SD seem to be a relatively common phenomenon in young adults, independent of depressive mood state. Our results suggest that therapeutic SD may depend on a physiological phenomenon of subclinical affective disturbance after SD that affects a part of the general population, independent of psychiatric diagnosis. Further studies could elucidate associated factors and contribute to our understanding of (hypo-)manic mood states.

Sleep profiles of different psychiatric traits.

Disturbed sleep comes in many forms. While the key role of sleep in mental health is undisputed, our understanding of the type of sleeping problems that manifest in the early stages of psychiatric disorders is limited. A sample without psychiatric diagnoses (N = 440, 341 women, 97 men, 2 non-binaries; Mage = 32.1, SD = 9.4, range 18-77) underwent a comprehensive assessment, evaluating eight sleep features and 13 questionnaires on common psychiatric complaints. Results revealed that traits of affect disorders, generalized anxiety, and ADHD had the worst sleep profiles, while autism disorder, eating disorder, and impulsivity traits showed milder sleep issues. Mania was the only trait associated with an overall better sleep profile. Across traits, insomnia and fatigue dominated and sleep variability was least prominent. These findings provide support for both transdiagnostic and disorder-specific targets for prevention and treatment.

A Nationwide Target Trial Emulation Assessing the Risk of Antidepressant-Induced Mania Among Patients With Bipolar Depression.

OBJECTIVE: Antidepressants are commonly used to treat bipolar depression but may increase the risk of mania. The evidence from randomized controlled trials, however, is limited by short treatment durations, providing little evidence for the long-term risk of antidepressant-induced mania. The authors performed a target trial emulation to compare the risk of mania among individuals with bipolar depression treated or not treated with antidepressants over a 1-year period. METHODS: The authors emulated a target trial using observational data from nationwide Danish health registers. The study included 979 individuals with bipolar depression recently discharged from a psychiatric ward. Of these, 358 individuals received antidepressant treatment, and 621 did not. The occurrence of mania and bipolar depression over the following year was ascertained, and the intention-to-treat effect of antidepressants was analyzed by using Cox proportional hazards regression with adjustment for baseline covariates to emulate randomized open-label treatment allocation. RESULTS: The fully adjusted analyses revealed no statistically significant associations between treatment with an antidepressant and the risk of mania in the full sample (hazard rate ratio=1.08, 95% CI=0.72-1.61), in the subsample concomitantly treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.63-2.13), and in the subsample not treated with a mood-stabilizing agent (hazard rate ratio=1.16, 95% CI=0.65-2.07). Secondary analyses revealed no statistically significant association between treatment with an antidepressant and bipolar depression recurrence. CONCLUSIONS: These findings suggest that the risk of antidepressant-induced mania is negligible and call for further studies to optimize treatment strategies for individuals with bipolar depression.

Does the clinical picture of bipolar disorder in the pediatric population depend on sex?

BACKGROUND: In the current literature the influence of sex on the clinical presentation of the bipolar disorder (BD) in adults has been indicated. It was of the interest whether such a phenomenon is also present in the pediatric population. METHODS: The authors collected retrospective clinical data in 288 patients hospitalized on the psychiatry ward aged 10-17 years; 80.2 % females and 19.8 % males. RESULTS: No sex differences were observed in the age of onset, the time from the onset of symptoms to the diagnosis of BD, the number of symptoms during hospital stay, or family history of psychiatric disorder (U Mann-Whitney's p > 0.05). In males the most frequently recorded first episode of BD was mania or hypomania (51 %), and in females, a depressive episode (51 %). The main reason for the hospitalization in boys was episodes of mania (63 %), then mixed episodes (30 %), and depression (7 %). Whereas girls were most often hospitalized due to mixed episodes (52 %), less frequently depression (22 %), and mania (26 %). Co-morbid psychiatric disorders were found more often in boys than in girls (63 % vs 45 %; χ2p-value>0.05). The co-occurrence of the dissocial personality, borderline, tic disorders, pervasive developmental disorders and hyperkinetic disorders was different in both sexes. LIMITATIONS: The main limitations of the study are the very high proportion of female subjects and the retrospective character of the study. CONCLUSIONS: It seems that the clinical presentation of BD in the pediatric population can somewhat depend on the sex of the patients.

Perinatal risk factors and subclinical hypomania: A prospective community study.

BACKGROUND: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population. METHODS: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. RESULTS: Prenatal alcohol exposure (ß = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (ß = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (ß = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (ß = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history. LIMITATIONS: Familial confounding could not be fully adjusted for. Rater reports include some biases. CONCLUSIONS: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts.