Search

Background. Several studies have found an association between indicators of fetal growth and/or obstetric complications and schizophrenia but only a few studies have investigated the possible association between these factors and bipolar disorder. Furthermore, the results of these studies have been contradictory. The aim of this study was to investigate whether the risk of bipolar disorder is associated with exposure to indicators of fetal growth. Method. A national population nested case-control study based on Danish longitudinal register databases was carried out. Conditional logistic regression was used, controlling for potential confounding factors such as parental age at birth, socio-economic indicators and psychiatric history. We identified 196 cases, and each case was time-, age- and sex-matched with 25 normal population-based controls. All cases were between the ages of 12 and 26 years at the time of diagnosis, were born between 1973 and 1983 and were admitted and diagnosed between 1987 and 1999. Results. During the study period 1973-1983, none of the individual variables available for analyses (birthweight, birth length, gestational age and number of previous pregnancies in the mother) was associated with receiving a diagnosis of bipolar disorder. Conclusions. None of the indicators of fetal growth under study could be identified as risk factors for bipolar disorder, suggesting that the etiologies of schizophrenia and bipolar disorder, at least in part, are different. [ABSTRACT FROM AUTHOR]

Lithium is the primary choice for preventing bipolar disorder relapses, endorsed by guidelines. A recent systematic review by Ulrichsen et al. showed limitations in assessing its specific impact, but data supports lithium's effectiveness in managing symptoms and preventing relapse. Comprehensive guidelines and research are crucial for its continued use.

Background: Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample., Methods: Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001., Results: The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger., Conclusion: UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition., (© 2023. The Author(s).)

Background: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints., Methods: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function., Results: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures., Limitations: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin., Conclusions: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients., Competing Interests: Conflict of interest GMG is emeritus NIHR Senior Investigator and has consulted for Beckley Psytech, Boehringer Ingelheim, Clerkenwell Health, EVApharm, H Lundbeck A/S, Janssen Global Services, Novartis, Ocean Neurosciences, P1vital, Sage Therapeutics, Servier, Takeda and WebMD. STA has consulted for COMPASS Pathways, Genomind, Janssen Global Services, LivaNova, Neuronetics, and Sage Therapeutics. CD has consulted for AbbVie and Corcept Therapeutics. CD has received grant funding from Beckley Psytech, Relmada Therapeutics, and Sage Therapeutics. BWD has consulted for Cerebral Therapeutics, Greenwich Biosciences, Myriad Genetic Laboratories, Otsuka America Pharmaceutical, Sage Therapeutics, and Sophren Therapeutics. BWD has received grant funding from Boehringer Ingelheim, COMPASS Pathways, Otsuka America Pharmaceutical, and the Usona Institute. DF has received grant funding from MindMed, Neurolief, Perception Neuroscience, and Relmada Therapeutics. DF holds a patent for psychedelic drug treatment of neuropsychiatric disorders and cerebral palsy. DJH has consulted for Reset Pharmaceuticals. DJH has received grant funding from Assurex, Intra-Cellular Therapies, Marinus Pharmaceuticals, COMPASS Pathways, Relmada Pharmaceuticals, and Beckley Foundation. MIH owns shares in Mindset Pharma. MIH has received consultancy fees from Psyched Therapeutics and the Wake Network. JRK has consulted for Clerkenwell Health and has received grant funding from the Health Research Board (ILP-POR-2022-030). RWL has participated in speaking engagements for H Lundbeck A/S, Janssen Global Services, and Teva Pharmaceuticals. TP has consulted for Atai Life Sciences, CB21 Pharma, and GH Research. TP is a principal investigator at Ketabon GmbH and MAPS Europe BV. TP is a fiduciary officer at the PSYRES Foundation, Psyon, and the Society for the Promotion of Neuroscience Research. DR is honorary board chair of the nonprofit organization MAPS Deutschland. RAS has consulted for Clexio Biosciences and GH Research and has received grant funding from Janssen Pharmaceuticals. JCS has consulted for Alkermes, Johnson & Johnson, and Merck. JCS has received grant funding from MindMed and Relmada Therapeutics. MW and SZ have participated in speaking engagements for COMPASS Pathways and Janssen Pharmaceuticals. GMG, JT, LM, NKT, OR, SS, BS, HHT, SW, and EM own shares in COMPASS Pathways. GMG, MA, JCB, MC, MRL-J, EM, LM, SM, OR, BS, HJS, JRS, HHT, NKT, JT, RIW, MBY, SCS, SW, and EM are current or past employees of COMPASS Pathways. OA, BWD, CD, DF, MIH, DJH, JCS, and SZ have received grant funding from COMPASS Pathways. STA, OA, CD, BWD, DF, DJH, MIH, JRK, RWL, TP, DR, RAS, JCS, MS, MW, AHY, and SZ were site investigators or sub-investigators for COMPASS Pathways during the clinical trial and received funding to conduct the study. AHY is employed by King's College London; Honorary Consultant South London and Maudsley NHS Foundation Trust (NHS UK). AHY was editor of Journal of Psychopharmacology and Deputy Editor for BJPsych Open. AHY participated in paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Boehringer Ingelheim, Eli Lilly, LivaNova, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS Pathways, Sage, Novartis, Neurocentrx. AHY was principal investigator in the Restore-Life VNS registry study funded by LivaNova, ESKETINTRD3004 funded by Janssen Research & Development, LLC, and “The Effects of Psilocybin on Cognitive Function in Healthy Participants”. AHY is principal investigator for Novartis MDD study MIJ821A12201 and additional studies for COMPASS Pathways. AHY has received grant funding from NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK); and Janssen (UK) EU Horizon 2020. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Describe symptoms before and at time of register-diagnosis in children and adolescents., Methods: A random sample was selected for chart-review from a Danish nationwide cohort of patients <18 years registered with an incident ICD-10 register-diagnosis of single hypomanic/manic episode or bipolar disorder between 1995 and 2014. Patients with symptoms which adequately documented a BD diagnosis in the chart were included for analysis., Results: 521 were diagnosed in the study period. A random sample of 25% were selected, and 106 charts were possible to retrieve, with 48 chart reviews resulting in confirmation of diagnosis. Time from first reported affective symptoms to diagnosis was 2.6 ± 2.7 years for depressive symptoms, 2.5 ± 2.9 years for mixed symptoms, 1.4 ± 1.6 years for hypomanic symptoms, and 0.4 ± 0.5 years for manic symptoms. A hierarchical clustering analysis revealed three patient-profiles: primarily hypomanic/manic, primarily depressive, and more rare, primarily mixed profile. Frequently reported symptoms prior to diagnosis include anhedonia (79%), irritability (71%), hyperactivity (62.5%), decreased energy (62.5%), and psychotic symptoms (52%).Symptoms of ADHD (19%), comorbid ADHD (15%), symptoms of anxiety (52%), comorbid anxiety (4%), suicidal thoughts (50%), suicide attempts (8%), cutting (23%), substance misuse (21%), and criminal activity (10%) were reported before incident BD diagnosis., Conclusion: The observed patient-profiles leading to diagnosis were primarily manic or depressive, resembling presentations in adults. The presence of ADHD, anxiety, suicide attempts, cutting, and criminal activity prior to diagnosis emphasizes the need for treatment of children and adolescents with affective symptoms. The gap from appearance of the symptoms to diagnosis suggests a window for earlier treatment.

Background: Psilocybin is being studied for use in treatment-resistant depression., Methods: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits)., Results: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups., Conclusions: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.)., (Copyright © 2022 Massachusetts Medical Society.)

Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth., Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer., Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001)., Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The use of randomized clinical trials, in particular placebo-controlled trials, for drug approval, is the subject of long-standing debate in the scientific community and beyond. This study offers consensus recommendations from clinical and academic experts to guide the selection of clinical trial design in psychiatry. Forty-one highly cited clinical psychiatrists and/or researchers participated in a Delphi survey. Consensus statements were developed based on the findings of a published, peer-reviewed systematic review. Participants evaluated statements in two survey rounds, following the Delphi method. The expert panel achieved consensus on 7 of 21 recommendations regarding the use of randomized clinical trials. The endorsed recommendations were: (i) Results from placebo-controlled trials are the most reliable and (ii) are necessary despite the growing placebo-effect; (iii) it is ethical to enroll patients in placebo-arms when established treatment is available, if there is no evidence of increased health risk; (iv) There is a need to approve new drugs with the same efficacy as existing treatments, but with different side-effect profiles; (v) Non-inferiority trials incur an increased risk of approving ineffective medications; (vi) The risk of approving an ineffective drug justifies trial designs that incur higher costs, and (vii) superiority trials incur the risk of rejecting potentially efficacious treatments. The endorsed recommendations inform the choice of trial-design appropriate for approval of psychopharmacological drugs. The recommendations strongly support the use of randomized clinical trials in general, and the use of placebo-controlled trials in particular., Competing Interests: Declaration of Competing Interest Guy M. Goodwin is a NIHR Emeritus Senior Investigator, holds shares in P1vital and P1Vital products and has served as consultant, advisor or CME speaker in the last 3 years for Beckley Psytech, Clerkenwell Health, Compass pathways, Evapharma, Janssen, Lundbeck, Medscape, Novartis, P1Vital, Sage, Servier. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Michael Berk is supported by a NHMRC Senior Principal Research Fellowship (1156072). MB has received Grant/Research Support from the NIH, Cooperative Research Centre, Simons Autism Foundation, Cancer Council of Victoria, Stanley Medical Research Foundation, Medical Benefits Fund, National Health and Medical Research Council, Medical Research Futures Fund, Beyond Blue, Rotary Health, A2 milk company, Meat and Livestock Board, Woolworths, Avant and the Harry Windsor Foundation, has been a speaker for Abbot, Astra Zeneca, Janssen and Janssen, Lundbeck and Merck and served as a consultant to Allergan, Astra Zeneca, Bioadvantex, Bionomics, Collaborative Medicinal Development, Janssen and Janssen, Lundbeck Merck, Pfizer and Servier – all unrelated to this work. Andreas Meyer-Lindenberg has received consultant fees from: Boehringer Ingelheim, Elsevier, Brainsway, Lundbeck Int. Neuroscience Foundation, Lundbeck A/S, The Wolfson Foundation, Bloomfield Holding Ltd, Shanghai Research Center for Brain Science, Thieme Verlag, Sage Therapeutics, v Behring Röntgen Stiftung, Fondation FondaMental, Janssen-Cilag GmbH, MedinCell, Brain Mind Institute, Agence Nationale de la Recherche, CISSN (Catania Internat. Summer School of Neuroscience), Daimler und Benz Stiftung, American Association for the Advancement of Science, Servier International. Additionally, he has received speaker fees from: Italian Society of Biological Psychiatry, Merz-Stiftung, Forum Werkstatt Karlsruhe, Lundbeck SAS France, BAG Psychiatrie Oberbayern, Klinik für Psychiatrie und Psychotherapie Ingolstadt, med Update GmbH, Society of Biological Psychiatry, Siemens Healthineers, Biotest AG -All unrelated to this work. Terence A. Ketter has been a consultant to Otsuka Pharmaceuticals, Sunovion Pharmaceuticals, Abbvie, and Alkermes. Joseph Goldberg has been a consultant to BioXCel, Otsuka, Sage Pharmaceuticals, Sunovion, and WebMD, and served on the speaker boards for Allergan, Intracellular Therapies, and Sunovion. Rif S. El-Mallakh is on the speaker bureau of Alkermes, Eisai, Indivior, Intra-Cellular Therapeutics, Janssen, Lundbeck, Noven, Otsuka, Sunonvion, and Teva. Lakshmi N Yatham has been on speaker/advisory boards for, or has received research grants from Abbvie, Alkermes, Allergan, CANMAT, CIHR, DSP, Merck, and Sanofi Rasmus W. Licht has within the preceding three years served an advisory board of Janssen Cilag and Sagw, and received speaker honorarium from Astra-Zeneca, Jannsen-Cilag, Servier and Lundbeck Allan H. Young has been employed by King's College London; Honorary Consultant SLaM (NHS UK). Young has participated in paid lectures and advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS Allan H. Young's independent research funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health.Consultant to Johnson & Johnson and Livanova. Received honoraria for attending advisory boards and presenting talks at meetings organized by LivaNova. Prof. Alessandro Serretti is or has been consultant/speaker for: Abbott, Abbvie, Angelini, Astra Zeneca, Clinical Data, Bo- heringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier. Ayşegül Yildiz has nothing to declare. Jean Michel Azorin has received honoraria or research or educational conference grants from Lundbeck and Otsuka. Othman Sentissi has received advisory board honoraria or research or educational conference from Otsuka, Lilly, Lundbeck, Sandoz, Janssen and Sunovion on an institutional account for research and teaching. Prof. Gordon Parker has received lecture fees and board member honoraria from Otsuka, Servier and Lundbeck. Dr. David Bond has received consulting fees and/or research grants from Alkermes, Myriad Genetics, the National Institutes of Health, the University of Minnesota Department of Psychiatry and Behavioral Sciences, and the University of Minnesota Foundation. Prof. Giulio Perugi has received grant/research support from Eli Lilly & Co.; is on the speaker/advisory board of Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Eli Lilly & Co., Jannsen-Cilag, and Lundbeck; and has acted as consultant of AstraZeneca, Eli Lilly & Co., and Lundbeck. Prof. Eduard Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB- Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Galenica, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, and Takeda. Dina Popovic has served as a speaker and/or medical writer and/or consultant and/or has participated in advisory boards for Bristol-Myers Squibb, Dexel, Merck Sharp & Dohme, Janssen-Cilag, Lundbeck, Ferrer, and Forum Pharmaceuticals. None of the remaining authors have conflicts of interest to declare., (Copyright © 2022 Elsevier B.V. and ECNP. All rights reserved.)

Affect integration is defined as the capacity to comprehend emotional experiences as meaningful and to convert this knowledge into well-adjusted motivation, communication and behavior. Thus, affect integration is considered essential for personal adjustment and well-being, and it has been operationalized through the Affect Integration Inventory. However, the validity of this questionnaire has been examined only in non-clinical respondents. Therefore, the purpose of this study was to investigate the psychometric properties of the questionnaire in a sample of patients with personality disorders (n = 87). The internal structure and consistency were addressed using Cronbach's alpha and confirmatory factor analysis. To determine aspects of convergent and discriminant validity, the correlations between the scores on the questionnaire and the scores on content-related questionnaires and scales were examined. Finally, scores from the clinical respondents and existing data from a previously collected non-clinical sample (n = 157) were compared to evaluate the external validity. The overall results demonstrated satisfactory internal consistency, a consistent factor structure, and systematic patterns of convergent and discriminant validity. Additionally, the findings indicated that the instrument clearly differentiated the clinical sample from the non-clinical sample., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This narrative review addresses the challenges of how to identify and treat bipolar depression. Bipolar depression, i.e. depressive episode(s) as part of bipolar disorder, can be differentiated from unipolar depression only through the previous course of illness. A correct diagnosis therefore may be delayed. The pharmacotherapy of bipolar depression differs from that of unipolar depression due to a high risk of recurrence of either hypomanic/manic or depressive episodes or mood instability. Therefore, long periods of specialized treatment will often be required. Both bipolar and unipolar depression will often benefit from adjunctive social and psychological interventions.

Bipolar disorder (BD) might be associated with higher infection rates of coronavirus disease (COVID-19) which in turn could result in worsening the clinical course and outcome. This may be due to a high prevalence of somatic comorbidities and an increased risk of delays in and poorer treatment of somatic disease in patients with severe mental illness in general. Vaccination is the most important public health intervention to tackle the ongoing pandemic. We undertook a systematic review regarding the data on vaccinations in individuals with BD. Proportion of prevalence rates, efficacy and specific side effects of vaccinations and in individuals with BD were searched. Results show that only five studies have investigated vaccinations in individuals with BD, which substantially limits the interpretation of overall findings. Studies on antibody production after vaccinations in BD are very limited and results are inconsistent. Also, the evidence-based science on side effects of vaccinations in individuals with BD so far is poor., Competing Interests: Declaration of Competing Interest As the article is a review on the literature, there is generally no conflict of interest in respect to this article. Nevertheless, some of the authors had relationships with different companies or served as consultants in the last three years. MM has served as consultant, or CME speaker for Angelini. EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Abbott, AbbVie, Angelini, Boehringer-Ingelheim, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Janssen, Lundbeck, Novartis, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda, outside the submitted work. LM declares that he has received lecture honoraria from Lundbeck pharmaceutical. No other equity ownership, profit-sharing agreements, royalties, or patent. CC has been a consultant and/or advisor to or has received honoraria from: Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Medscape, Merck, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He is also a stock option holder of LB Pharma. AF is /has been a consultant and/or a speaker and/or has received research grants from Angelini, Apsen, Boheringer Ingelheim, Daiichi Sankyo, Doc Generici, Glaxo Smith Kline, Italfarmaco, Lundbeck, Janssen, Mylan, Neuraxpharm, Otsuka, Pfizer, Recordati, Sanofi Aventis, Sunovion, Vifor. MB has received institutional grants from Deutsche Forschungsgemeinschaft (DFG), Bundesministerium für Bildung und Forschung (BMBF), and European Commission. He served in advisory boards for GH Research, Janssen-Cilag, neuraxpharm, Novartis, Sandoz, Shire International, Sumitomo Dainippon, Sunovion, and Takeda, and received speaker honoraria for Aristo, Hexal, Janssen Pharmaceutica NV, Janssen-Cilag, and Sunovion, outside the submitted work. REN has received research grants from H. Lundbeck and Otsuka Pharmaceuticals for clinical trials, received speaking fees from Bristol-Myers Squibb, Astra Zeneca, Janssen & Cilag, Lundbeck, Servier, Otsuka Pharmaceuticals, Teva A/S, and Eli Lilly and has acted as advisor to Astra Zeneca, Eli Lilly, Lundbeck, Otsuka Pharmaceuticals, Takeda, and Medivir, and has acted as investigator for Janssen-Cilag, Lundbeck, Boehringer, Compass and Sage. RW Licht has within the preceding three years served an advisory board of Janssen Cilag and Sage and has received speaker honorarium from Astra-Zeneca, Jannsen-Cilag, Servier, Lundbeck and Teva. No known conflicts of interest in respect to this article from all other authors., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

According to the literature, avoidant personality disorder (APD) is often overlooked in research on personality disorders. In the present study, patients with APD were compared to patients with borderline personality disorder (BPD) with respect to emotional dysfunction. Emotional dysfunction was operationalized through the Affect Integration Inventory. Sixty-one patients receiving treatment at specialized outpatient hospital facilities for either BPD (n = 25) or APD (n = 36) (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) were included in a cross-sectional study. Supporting our expectations of no difference in the global capacity for affect integration between groups, the estimated difference was 0.00 (95% confidence interval [CI] [-0.53, 0.53]). On the other hand, the expected increased dysfunction in APD regarding Expression could not be confirmed. Furthermore, problems with specific affects distinguished the groups; integration of Interest was worse in APD (p = 0.01), whereas integration of Jealousy was worse in BPD (p = 0.04). In terms of prototypical modes of experiencing affects, APD was characterized by decreased access to the motivational properties of Interest (p < 0.01), while BPD was more driven by Interest (p < 0.01), Anger (p < 0.01), and Jealousy (p = 0.01). In conclusion, even though the two disorders are characterized by similar overall levels of emotional dysfunction, they differ systematically and predictably regarding specific affects and modes of experiencing. These findings carry implications for the understanding of emotional dysfunction in APD and BPD, suggesting specific areas of emotional dysfunction that could be targeted in tailored psychotherapeutic interventions., (© 2021 The Authors. Scandinavian Journal of Psychology published by Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Objective: To investigate the accuracy of a diagnosis of pediatric bipolar disorder in the Danish National Register compared to the patient charts. Second, we reported on the occurrence of a diagnosis of pediatric bipolar disorder during the study period., Methods: All persons appearing in the Danish nationwide registers between 1995 and 2014 with an incident ICD-10 diagnosis of single hypomanic/manic episode or a diagnosis of bipolar disorder (summarized as bipolar disorder [BD]) before turning 18 years were identified ( n  = 521) and a random sample ( n  = 131) hereof was selected for chart review. Each chart was reviewed by two independent Schedules for Clinical Assessment in Neuropsychiatry (SCAN) certified raters to assess whether symptoms documented in the chart were consistent with a formal diagnosis of BD according to the ICD-10 criteria or not., Results: The formal diagnostic criteria for BD according to the ICD-10 were fulfilled in 48 charts (45.3%, 95% CI: [36.1%, 54.8%]) out of 106 reviewable charts, age at index = 16.4 ± 1.6 (range = 9.1-18.3) years. Cohen's Kappa ranged from 94.4% to 100%. The estimate of a lifetime prevalence up till the current age for bipolar disorder for those of aged 5-18 years, was 0.019% in 2014., Conclusion: Less than half of the register-based pediatric BD diagnoses were confirmed by chart review, which was lower than expected. The occurrence of a register diagnosis of pediatric BD was relatively low.

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries., Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries)., Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01., Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed., (© 2021. The Author(s).)

Background and Objectives: Emotional dysfunction is considered a key component in personality disorders; however, only few studies have examined the relationship between the two. In this study, emotional dysfunction was operationalized through the Affect Integration Inventory, and the aim was to examine the relationships between the level of affect integration and the levels of symptom distress, interpersonal problems, and personality functioning in patients diagnosed with personality disorder according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Materials and Methods: Within a hospital-based psychiatric outpatient setting, 87 patients with personality disorder referred for treatment were identified for assessment with the Affect Integration Inventory and other measures (e.g., the Symptom Checklist-90, Revised, the Inventory of Interpersonal Problems 64 circumplex version, and the Severity Indices of Personality Problems). Results: The analyses revealed that problems with affect integration were strongly and statistically significantly correlated with high levels of symptom distress, interpersonal problems, and maladaptive personality functioning. Additionally, low scores on the Affect Integration Inventory regarding discrete affects were associated with distinct and differentiated patterns of interpersonal problems. Conclusion: Taken together, emotional dysfunction, as measured by the Affect Integration Inventory, appeared to be a central component of the pathological self-organization associated with personality disorder. These findings have several implications for the understanding and psychotherapeutic treatment of personality pathology. Furthermore, they highlight the importance of considering the integration of discrete affects and their specific contributions in the conceptualization and treatment of emotional dysfunction in patients with personality disorders.

This narrative review summarizes and discusses the implications of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and the upcoming International Classification of Diseases (ICD)-11 classification systems on the prevalence of bipolar disorder and on the validity of the DSM-5 diagnosis of bipolar disorder according to the Robin and Guze criteria of diagnostic validity. Here we review and discuss current data on the prevalence of bipolar disorder diagnosed according to DSM-5 versus DSM-IV, and data on characteristics of bipolar disorder in the two diagnostic systems in relation to extended Robin and Guze criteria: 1) clinical presentation, 2) associations with para-clinical data such as brain imaging and blood-based biomarkers, 3) delimitation from other disorders, 4) associations with family history / genetics, 5) prognosis and long-term follow-up, and 6) treatment effects. The review highlights that few studies have investigated consequences for the prevalence of the diagnosis of bipolar disorder and for the validity of the diagnosis. Findings from these studies suggest a substantial decrease in the point prevalence of a diagnosis of bipolar with DSM-5 compared with DSM-IV, ranging from 30-50%, but a smaller decrease in the prevalence during lifetime, corresponding to a 6% reduction. It is concluded that it is likely that the use of DSM-5 and ICD-11 will result in diagnostic delay and delayed early intervention in bipolar disorder. Finally, we recommend areas for future research., (Copyright © 2021. Published by Elsevier B.V.)

Bipolar disorder (BD) is a major healthcare and socio-economic challenge. Despite its substantial burden on society, the research activity in BD is much smaller than its economic impact appears to demand. There is a consensus that the accurate identification of the underlying pathophysiology for BD is fundamental to realize major health benefits through better treatment and preventive regimens. However, to achieve these goals requires coordinated action and innovative approaches to boost the discovery of the neurobiological underpinnings of BD, and rapid translation of research findings into development and testing of better and more specific treatments. To this end, we here propose that only a large-scale coordinated action can be successful in integrating international big-data approaches with real-world clinical interventions. This could be achieved through the creation of a Global Bipolar Disorder Foundation, which could bring government, industry and philanthropy together in common cause. A global initiative for BD research would come at a highly opportune time given the seminal advances promised for our understanding of the genetic and brain basis of the disease and the obvious areas of unmet clinical need. Such an endeavour would embrace the principles of open science and see the strong involvement of user groups and integration of dissemination and public involvement with the research programs. We believe the time is right for a step change in our approach to understanding, treating and even preventing BD effectively., (Copyright © 2020. Published by Elsevier B.V.)

Background: Diagnostic stability of bipolar disorder (BD) in children and adolescents, beyond the first contact has been investigated sparsely. The aim of this study was to investigate the diagnostic stability of BD in children and adolescents using over two decades of nationwide register-based data, and to examine factors associated with change from BD to schizophrenia (ICD-10: F20.x), schizoaffective disorder (ICD-10: F25.x) or other primary psychotic disorders (ICD-10 F23.x-24.x and F28.x-29.x)., Methods: Danish register-based data for all incident BD patients diagnosed prior to age 18 years, between January 1st 1995 and December 31st 2014 (N = 519). We graphically illustrated diagnostic change at different follow-up times and studied variables associated with diagnostic change after 3-year follow-up using Poisson regression with robust standard error estimates., Results: The diagnosis of incident BD was relatively stable. The diagnosis did not change for 93% of those followed for at least 6 months, and remained unchanged for 86% and 73% of those followed at least 3 years and 10 years, respectively. In patients followed for at least 3 years after index BD (N = 478), the risk of diagnostic change was 61% higher in males versus females. The risk of diagnostic change for patients diagnosed during hospitalization was 74% higher compared to patients diagnosed at outpatient clinics/emergency rooms. The risk of diagnostic change for patients abusing substances other than alcohol and cannabis was 173% higher compared to patients not abusing such substances. The risk of diagnostic change for patients previously diagnosed with schizophrenia or related diagnosis was 257% higher compared to patients not having been diagnosed with such diagnosis previously, while the risk of diagnostic change in offspring of parents with schizophrenia or related diagnosis was 126% higher compared to patients who did not have parents diagnosed with such disorders., Conclusion: Overall, the stability of the BD diagnosis in the Danish nationwide healthcare registers was high. Factors associated with risk of diagnostic change within 3 years of the initial diagnosis were being male, diagnosis given during hospitalization, substance abuse other than alcohol and cannabis, and a prior diagnosis of schizophrenia or related diagnosis in the patient or in their parents.

Background: The efficacy of antidepressant treatment is fair, but the efficacy is considerably lower in patients failing two or more trials underscoring the need for new treatment options. Our study evaluated the augmenting antidepressant effect of 8-weeks transcranial pulsed electromagnetic field (T-PEMF) therapy in patients with treatment-resistant depression., Methods: A multicenter 8-week single-arm cohort study conducted by the Danish University Antidepressant Group., Results: In total, 58 participants (20 men and 38 women) with a moderate to severe depression as part of a depressive disorder according to ICD-10 who fulfilled criteria for treatment resistance were included, with 19 participants being nonresponders to electroconvulsive therapy during the current depressive episode. Fifty-two participants completed the study period. Scores on the Hamilton Depression Scale 17-items version (HAM-D17) decreased significantly from baseline (mean = 20.6, SD 4.0) to endpoint (mean = 12.6, SD 7.1; N = 58). At endpoint, utilizing a Last Observation Carried Forward analysis, 49 and 28% of those participants with, respectively, a nonchronic current episode (≤2 years; N = 33) and a chronic current episode (>2 years; N = 25) were responders, that is, achieved a reduction of 50% or more on the HAM-D17 scale. At endpoint, respectively, 30 and 16% obtained remission, defined as HAM-D17 ≤ 7. On the Hamilton Scale 6-item version (HAM-D6), respectively, 51 and 16% obtained remission, defined as HAM-D6 ≤ 4., Conclusions: The findings indicate a potential beneficial role of T-PEMF therapy as an augmentation treatment to ongoing pharmacotherapy in treatment-resistant depression.

Objectives: Comparing outcomes of bipolar disorder (BD) with schizophrenia (SCZ) and psychiatrically healthy controls (PHC), contrasting pediatric-onset with adult-onset disorders., Methods: A nationwide cohort study, including patients with an incident diagnosis of BD or SCZ registered in the Danish National Patient Registry and corresponding PHCs. Outcomes were (a) duration of hospitalization, (b) psychiatric admissions, (c) psychiatric outpatient contacts, (d) bone-fracture-related healthcare contacts, (e) self-harm-related healthcare contacts (including suicide and non-suicidal self-injuries), and (f) criminal charges. Incidence rate ratios (IRRs), adjusted for age at first psychiatric contact, substance abuse and parental psychiatric illness, were calculated, comparing pediatric-onset BD (5-17 years) and adult-onset BD (18-39 years) with age- and sex-matched SCZ patients and PHC., Results: Pediatric-onset BD (n = 349) performed better than 1:1-matched pediatric-onset SCZ (n = 349) on all six outcomes (IRR = 0.30 for self-harm-related contacts (P < 0.001) to IRR = 0.86 for criminal charges (P = 0.05). Similar, but less pronounced results were observed comparing 1:1-matched adult-onset BD (n = 5515) with adult-onset SCZ (n = 5515) IRR = 0.58 for psychiatric outpatient contact (P < 0.001) to IRR = 0.93 for criminal charges (P < 0.001), except for more bone-fracture-related contacts in adult-onset BD (IRR = 1.13, P < 0.01). Comparing pediatric-onset BD (n = 365) to 1:3-matched PHC (n = 1095), only self-harm-related contacts differed significantly (IRR = 2.80, P < 0.001). Conversely, comparing adult-onset BD (n = 6005) with 1:3-matched PHC (n = 18 015), self-harm-related contacts (IRR = 16.68, P < 0.001), bone fractures (IRR = 1.74, P < 0.001), and criminal charges (IRR = 2.03, P < 0.001) were more common in BD., Conclusion: BD was associated with poorer outcomes than PHC, but better outcomes than SCZ. Furthermore, outcomes were more favorable in pediatric-onset BD when indirectly contrasted to adult-onset BD., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: To systematically review the existing trials on optimal serum levels for lithium for maintenance treatment of bipolar disorder and to develop clinical recommendations., Methods: Systematic literature search. Discussion of major characteristics, limitations, methodological quality, and results of selected trials. Delphi survey consisting of clinical questions and corresponding statements. For statements endorsed by at least 80% of the members, consensus was considered as having been achieved., Results: With strict inclusion criteria no studies could be selected, making it difficult to formulate evidence-based recommendations. After loosening the inclusion criteria 7 trials were selected addressing our aims at least to some extent. Four of these studies suggest better efficacy being associated with lithium serum levels in a range above a lower threshold around 0.45/0.60 and up to 0.80/1.00 mmol/L. These findings support the outcome of the Delphi survey., Conclusions: For adults with bipolar disorder there was consensus that the standard lithium serum level should be 0.60-0.80 mmol/L with the option to reduce it to 0.40-0.60 mmol/L in case of good response but poor tolerance or to increase it to 0.80-1.00 mmol/L in case of insufficient response and good tolerance. For children and adolescents there was no consensus, but the majority of the members endorsed the same recommendation. For the elderly there was also no consensus, but the majority of the members endorsed a more conservative approach: usually 0.40-0.60 mmol/L, with the option to go to maximally 0.70 or 0.80 mmol/L at ages 65-79 years, and to maximally 0.70 mmol/L over age 80 years., (© 2019 The Authors. Bipolar Disorders Published by John Wiley & Sons Ltd.)

Background: Lithium has been used clinically for 70 years, mainly to treat bipolar disorder. Competing treatments and exaggerated impressions about complexity and risks of lithium treatment have led to its declining use in some countries, encouraging this update about its safe clinical use. We conducted a nonsystematic review of recent research reports and developed consensus among international experts on the use of lithium to treat major mood disorders, aiming for a simple but authoritative guide for patients and prescribers., Main Text: We summarized recommendations concerning safe clinical use of lithium salts to treat major mood disorders, including indications, dosing, clinical monitoring, adverse effects and use in specific circumstances including during pregnancy and for the elderly., Conclusions: Lithium continues as the standard and most extensively evaluated treatment for bipolar disorder, especially for long-term prophylaxis.