Search

On September 27, 1922, Ernst Rüdin gave an address to the Annual Conference of the German Society of Genetics entitled "Regarding the Heredity of Mental Disturbances." Published in a 37-page article, Rüdin reviewed the progress in the field of Mendelian psychiatric genetics, then hardly more than a decade old. Topics included (a) the status of Mendelian analyses of dementia praecox and manic-depressive insanity which had expanded to include two and three locus and early polygenic models and sometimes included, respectively, schizoid and cyclothymic personalities; (b) a critique of theories for the explanation of co-occurrence of different psychiatric disorders within families; and (c) a sharp methodologic critique of Davenport and Rosanoff's contemporary work which emphasized Rüdin's commitment to careful, expert phenotyping, a primary focus on well-validated psychiatric disorders and not broad spectra of putatively inter-related conditions, and an emphasis on rigorous statistical modeling as seen in his continued collaboration with Wilhelm Weinberg., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Lithium remains the "gold standard" for both acute and maintenance treatment of bipolar disorder (BD), a serious life-long condition characterised by recurrent episodes of depressed and manic mood states. However, lithium has a very narrow therapeutic range (0.4-1.2 mmol L -1 ) and despite its effectiveness in preventing and reducing mood swings and suicidality, it is a potentially hazardous drug. While it is crucial to carefully monitor lithium plasma levels, the current techniques of lithium monitoring are cumbersome and require frequent blood tests with the consequent discomfort which results in patients evading treatment. Therefore, development of low-cost and facile lithium detection techniques that can be translated into point-of-care devices for personal monitoring will be a major advance in the management of BD. In the current study, we present colorimetric determination of lithium therapeutic levels utilizing test paper strips, based on its reaction with the chromogenic agent Quinizarin. Exposure of Quinizarin-dipped test papers to samples of interstitial fluid (ISF) or dH 2 O spiked with therapeutic concentrations of lithium resulted in colour changes that were monitored using optical spectroscopy. The acquired spectra from the test papers show spectral variations which are related to lithium concentrations in spiked samples of dh 2 O and artificial ISF with a coefficient of determination ( R ) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.2 ) of 0.9 and 0.8, respectively. Altogether, the spectrophotometric and colorimetric analyses demonstrated strong correlations between the observed colour changes and the concentrations of lithium present in the sample. Therefore, this study has demonstrated that Quinizarin-treated cellulose-based papers are suitable for the precise detection of changes in lithium therapeutic levels. This method is simple and very convenient and serves as a foundation for the future development of a paper-based colorimetric sensor for monitoring of lithium therapeutic levels in ISF and other non-invasive biological fluids.

Introduction: Lithium treatment is considered the gold standard for the long-term management of bipolar disorder and recurrent unipolar depression. It is also extremely effective in other psychiatric conditions characterized by impulsivity and aggression, and for the prevention of suicidal behaviours., Areas Covered: This paper provides a scoping review and an expert commentary regarding the use of lithium in adult patients. Available information about efficacy, tolerability, dosing, and switching is analyzed, and the strategies that may be most useful in real-world clinical settings are highlighted., Expert Opinion: Lithium is effective on different domains of bipolar disorder, including the long-term prevention of recurrences of affective episodes, management of acute mania as well as in the prophylaxis of all affective episodes. Lithium has been defined a 'forgotten drug,' since its use in routine clinical practice has been declined over the last 20 or 30 years. Reasons for this trend include lack of adequate training on the management of lithium side effects. Considering its efficacy, use of lithium in ordinary clinical practice should be promoted. Several strategies, such as using slow-release formulations, can be easily implemented in order to minimize lithium side effects and improve its tolerability profile.

Background: The clinical effects of smartphone-based interventions for bipolar disorder (BD) have yet to be established., Objectives: To examine the efficacy of smartphone-based interventions in BD and how the included studies reported user-engagement indicators., Methods: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random-effects meta-analysis to calculate the standardized difference (Hedges' g) in pre-post change scores between smartphone intervention and control conditions. The study was pre-registered with PROSPERO (CRD42021226668)., Results: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta-analyses comparing the pre-post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta-analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user-engagement indicators., Conclusion: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Background: Developing treatments for cognitive impairment is key to improving the functioning of people with mood disorders. Neuroimaging may assist in identifying brain-based efficacy markers. This systematic review and position paper by the International Society for Bipolar Disorders Targeting Cognition Task Force examines the evidence from neuroimaging studies of pro-cognitive interventions., Methods: We included magnetic resonance imaging (MRI) studies of candidate interventions in people with mood disorders or healthy individuals, following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis 2020 statement. Searches were conducted on PubMed/MEDLINE, PsycInfo, EMBASE, Cochrane Library, and Clinicaltrials.gov from inception to 30th April 2021. Two independent authors reviewed the studies using the National Heart, Lung, Blood Institutes of Health Quality Assessment Tool for Controlled Intervention Studies and the quality of neuroimaging methodology assessment checklist., Results: We identified 26 studies (N = 702). Six investigated cognitive remediation or pharmacological treatments in mood disorders (N = 190). In healthy individuals, 14 studies investigated pharmacological interventions (N = 319), 2 cognitive training (N = 73) and 4 neuromodulatory treatments (N = 120). Methodologies were mostly rated as 'fair'. 77% of studies investigated effects with task-based fMRI. Findings varied but most consistently involved treatment-associated cognitive control network (CCN) activity increases with cognitive improvements, or CCN activity decreases with no cognitive change, and increased functional connectivity. In mood disorders, treatment-related default mode network suppression occurred., Conclusions: Modulation of CCN and DMN activity is a putative efficacy biomarker. Methodological recommendations are to pre-declare intended analyses and use task-based fMRI, paradigms probing the CCN, longitudinal assessments, mock scanning, and out-of-scanner tests., (© 2022 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that can affect up to 2.6% of the population. Most of these people will have at least one other psychiatric disorder, often diagnosed with a delay or not recognized at all. This study describes the epidemiology, diagnostic difficulties and potential treatment of patients with ASD and comorbid bipolar disorder (BD). The prevalence of bipolar disorder in ASD is estimated at 5-8%. The study with the most numerous group included 700,000 children out of which 9,062 fulfilled ASD criteria at 16 - BD was found to be 6 times more prevalent in this group compared to the control group. Many factors affect the diagnosis. Patients with ASD often have limited insight into understanding the complex emotional states and difficulty in expressing them due to their impairment. The symptoms of bipolar disorder are in their case unspecific and differ from those occurring in the general population, which makes it difficult to make proper diagnosis. Despite the lack of research on the group of patients with ASD, psychometric tools designed to evaluate the general population are used to examine patients. This work aims to show the current state of knowledge and highlight areas that require further investigation.

The paper examines 1037 publications on bipolar disorder (BD) during the years 2000-19 from India, as listed in the Scopus database. India's publications constituted 2.27 % share of global output (45,624 publications) in the study period of 20 years. India does not figure in the top 10 countries in terms of research output on BD. The number of publications on BD from India increased from 13 in 2000 to 107 in 2019, registering 14.44 % annual average growth, higher than world's growth of 6.02 %. India's 10-year cumulative publications increased from 264 during 2000-09 to 773 during 2010-19, registering 192.8 % absolute growth, much higher than world cumulative growth of 63.27 %. India's publications on BD averaged citation impact per paper of 14.24, which decreased from 25.38 to 10.43 from 2000-09 to 2010-19. Maximum numbers of papers from India on BD were published by researchers from National Institute of Mental Health and Neurosciences, Bangalore (222 papers),Post Graduate Institute of Medical Education and Research, Chandigarh(118 papers), and AII India Institute of Medical Sciences, New Delhi (79 papers). Lady Harding Medical College, New Delhi (36.20 and 2.54), Schizophrenia Research Foundation, Chennai (27.45 and 1.93), and King George's Medical University, Lucknow (25.21 and 1.77) were the most significant organizations in terms of citation per paper and relative citation index. Maximum number of papers were published in Indian Journal of Psychiatry (101 papers), followed by Asian Journal of Psychiatry (88 papers) and Indian Journal of Psychology Medicine (34 papers)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD., Method: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD., Results: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding., Conclusion: Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Abstract Background Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a ‘forgotten drug’ and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common “misconceptions” and “stereotypes” associated with lithium treatment; we also provide a list of “good reasons” for using lithium in ordinary clinical practice to overcome those false myths. Main text A narrative search of the available literature has been performed entering the following keywords: “bipolar disorder”, “lithium”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding”. The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients’ groups suffering from bipolar disorder; (3) Drug–drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. Conclusions In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Although the etiology of bipolar disorder remains uncertain, multiple studies examining neuroimaging, peripheral markers and genetics have provided important insights into the pathophysiologic processes underlying bipolar disorder. Neuroimaging studies have consistently demonstrated loss of gray matter, as well as altered activation of subcortical, anterior temporal and ventral prefrontal regions in response to emotional stimuli in bipolar disorder. Genetics studies have identified several potential candidate genes associated with increased risk for developing bipolar disorder that involve circadian rhythm, neuronal development and calcium metabolism. Notably, several groups have found decreased levels of neurotrophic factors and increased pro-inflammatory cytokines and oxidative stress markers. Together these findings provide the background for the identification of potential biomarkers for vulnerability, disease expression and to help understand the course of illness and treatment response. In other areas of medicine, validated biomarkers now inform clinical decision-making. Although the findings reviewed herein hold promise, further research involving large collaborative studies is needed to validate these potential biomarkers prior to employing them for clinical purposes. Therefore, in this positional paper from the ISBD-BIONET (biomarkers network from the International Society for Bipolar Disorders), we will discuss our view of biomarkers for these three areas: neuroimaging, peripheral measurements and genetics; and conclude the paper with our position for the next steps in the search for biomarkers for bipolar disorder.

Background: Longitudinal mood instability is the essential feature of bipolar disorder, however most rating scales are cross sectional in nature, and focus on acute symptoms. By contrast, the NIMH Life Chart Methodology (LCM) characterizes in detail the severity, duration, and frequency of mood episodes. Adherence to daily rating, however, tends to be low. In this study an online version of the LCM, designed to enhance adherence, was compared to the standard paper version., Methods: Patients from a mood disorders specialty clinic were randomized to the standard LCM or an online, open-source adaptation. The online version used hypertext links embedded in a daily email as the primary rating interface. Participants rated for 90 days. The total number of days rated and the number of days with complete data were compared for the two groups., Results: Forty-eight patients participated in the study. The online group rated approximately twice as many days compared to the standard group (44.3 versus 20.4, p=.029). The online group also entered complete data for a larger portion of days (55.2% versus 27.7%, p=.039)., Limitations: This was a small, short-term study. The implications for longer-term rating are unclear., Conclusions: Despite the advantages of documenting mood fluctuation on a daily basis, the LCM is not commonly used, in part because ensuring adequate adherence can be resource intensive. An easily accessible online adaptation that utilizes email checking behavior can make this tool available to a wider range of patients.

Background: Lithium medication is considered to be the first-line treatment for bipolar disorder as a monotherapy, and for treatment-resistant depression with lithium augmentation. However, because of potential toxicity, lithium levels must be monitored frequently. Recent studies have demonstrated a significant correlation between lithium levels measured in serum and those detected in oral fluid, suggesting that oral fluid analysis may represent an easy, noninvasive means to monitor lithium levels. The aim of this study was to evaluate the analytical performance of rapid assays for lithium measurements in oral fluid., Methods: Levels of lithium in oral fluid from psychiatric patients (n = 108 in total) taking lithium medications were quantified using 2 rapid techniques: an automated clinical chemistry analyzer and a novel, commercially available colorimetric lithium assay. These results were compared with those obtained using inductively coupled plasma optical emission spectrometry (ICP-OES)., Results: The mean and median oral fluid lithium levels in this cohort were 1.43-1.61 mM and 1.32-1.52 mM, respectively, depending on the method, with the overall range, across all methods, being 0.213-4.42 mM. Linear regression analysis showed excellent agreement between the oral fluid values measured using ICP-OES and the colorimetric method (r 2 value = 0.926; P < 0.0001; slope = 1.084 ± 0.038). Similarly, excellent agreement was observed between ICP-OES and the automated method (r 2 = 0.872; P < 0.0001; slope = 1.019 ± 0.057)., Conclusions: These results demonstrate that lithium levels in oral fluid can be rapidly and reliably quantified using colorimetric approaches. These findings may facilitate the development of point-of-care lithium monitoring systems for use in oral fluid., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Although the cyclic nature of bipolarity is almost by definition a network system, no research to date has attempted to scrutinize the relationship of the two bipolar poles using network psychometrics. We used state-of-the-art network and machine learning methodologies to identify symptoms, as well as relations thereof, that bridge depression and mania., Methods: Observational study that used mental health data (12 symptoms for depression and 12 for mania) from a large, representative Canadian sample (the Canadian Community Health Survey of 2002). Complete data (N = 36,557; 54.6% female) were analysed using network psychometrics, in conjunction with a random forest algorithm, to examine the bidirectional interplay of depressive and manic symptoms., Results: Centrality analyses pointed to symptoms relating to emotionality and hyperactivity as being the most central aspects of depression and mania, respectively. The two syndromes were spatially segregated in the bipolar model and four symptoms appeared crucial in bridging them: sleep disturbances (insomnia and hypersomnia), anhedonia, suicidal ideation, and impulsivity. Our machine learning algorithm validated the clinical utility of central and bridge symptoms (in the prediction of lifetime episodes of mania and depression), and suggested that centrality, but not bridge, metrics map almost perfectly onto a data-driven measure of diagnostic utility., Conclusions: Our results replicate key findings from past network studies on bipolar disorder, but also extend them by highlighting symptoms that bridge the two bipolar poles, while also demonstrating their clinical utility. If replicated, these endophenotypes could prove fruitful targets for prevention/intervention strategies for bipolar disorders., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Purpose: To investigate serum levels of VEGF, IGF-1 and FGF-2, and relationships with several clinical characteristics in children and adolescents with autism spectrum disorder (ASD) with and without bipolar disorder (BD)., Method: 40 subjects with ASD + BD as study group, and 40 subjects with ASD as control group were included. Serum levels of VEGF, IGF-1, and FGF-2 were measured using commercial enzyme-linked immunosorbent assay kits., Results: The study group was significantly higher than the control group in terms of ASD severity, self-harming behavior and sleep disturbance. Serum VEGF and FGF-2 levels were significantly higher in the ASD + BD group than in the control group. There was no significant difference in serum IGF-1 levels between the two groups. There was no correlation between VEGF, IGF-1 and FGF-2 serum levels and ASD severity in the study group. However there was a negative correlation between VEGF levels and age at first diagnosis of BD, and a positive correlation between IGF-1 levels and the number of bipolar episodes in the study group., Conclusion: Growth factors like VEGF and FGF-2 may be potential biomarkers of bipolar disorder in young subjects with ASD. Given the difficulty of clinical management of BD in young subjects with ASD, potential biomarkers would help clinicians in the diagnosis and follow up of BD in this special population. Further research is needed whether VEGF and FGF-2 can be potential biomarkers in the clinical management of young subjects with ASD and BD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders that can affect up to 2.6% of the population. Most of these people will have at least one other psychiatric disorder, often diagnosed with a delay or not recognized at all. This study describes the epidemiology, diagnostic difficulties and potential treatment of patients with ASD and comorbid bipolar disorder (BD). The prevalence of bipolar disorder in ASD is estimated at 5-8%. The study with the most numerous group included 700,000 children out of which 9,062 fulfilled ASD criteria at 16 - BD was found to be 6 times more prevalent in this group compared to the control group. Many factors affect the diagnosis. Patients with ASD often have limited insight into understanding the complex emotional states and difficulty in expressing them due to their impairment. The symptoms of bipolar disorder are in their case unspecific and differ from those occurring in the general population, which makes it difficult to make proper diagnosis. Despite the lack of research on the group of patients with ASD, psychometric tools designed to evaluate the general population are used to examine patients. This work aims to show the current state of knowledge and highlight areas that require further investigation. [ABSTRACT FROM AUTHOR]

Boven published, in 1915, his MD thesis at the University of Lausanne in which he examined 60 3- to 4-generation pedigrees ascertained from admitted patients with dementia praecox (DP) and manic-depressive insanity (MDI). He asked three questions: (i) were DP and MDI hereditary? (ii) were they the same or distinct conditions? and (iii) were they Mendelian disorders? Based on the rarity of environmental precipitants severe enough to cause disorder onset and the pattern of disorders in relatives, Boven concluded that both disorders were inherited. He found that MDI largely ran in families through direct transmission across generations while DP was only common in collateral relatives. Both pedigrees contained a substantial number of "psychopathic" (personality disordered) relatives in which DP and MDI pedigrees typically had, respectively, paranoid, and dysthymic/cyclothymic features. Boven concludes that their inheritance is largely distinct but not exclusive, as some pedigrees contained cases of both disorders. With assistance from Wilhelm Weinberg, Boven applied algebraic models with proband correction to rates of DP and MDI in sibships and found the results inconsistent with Mendelian transmission. His study represents among the first examinations, using "modern" methods, of the familial relationship between DP and MDI and the first published in French., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

Objectives: Cognitive impairment is a core feature of bipolar disorder (BD) and major depressive disorder (MDD). Deficits in processing speed (PS) and sustained attention (SA) may be particularly impaired and may underpin a broader profile of deficits, however current knowledge of the nature of these impairments is limited by heterogeneous results in the literature. Few reviews to date have attempted to disentangle sources of heterogeneity to assess the presence and magnitude of impairments in PS and SA in BD and MDD., Methods: One hundred and three studies were reviewed to examine performance in tests of PS and SA in BD (n = 3452) and MDD (n = 5461) compared to healthy controls (n = 8016). Neuropsychological methodology used in the literature was summarised. Data were meta-analysed to assess impairments in PS and SA for each neuropsychological test separately. Subgroup analysis was performed across mood states to investigate sources of heterogeneity., Results: Impairments were found across most neuropsychological tests, with small to large effect sizes for BD (range: d = 0.19-0.96) and MDD (range: d = 0.29-0.86). Impairments were present in symptomatic states and euthymia in most cases. Some outcome measures were not impaired in euthymia. Heterogeneity was observed for most neuropsychological tests and remained after separating by mood state. There inadequate data to meta-analyse some outcome measures, particularly for symptomatic groups., Conclusion: Impairments in PS and SA in BD and MDD can be observed across most neuropsychological tests. Future research should further investigate the nature of these impairments across mood states, controlling for clinical confounds., (© 2023 The Authors. Bipolar Disorders published by John Wiley & Sons Ltd.)

Aims: We aimed to investigate whether peripheral T-cell subsets could be a biomarker to distinguish major depressive disorder (MDD) and bipolar disorder (BD)., Methods: Medical records of hospitalized patients in the Department of Psychiatry, the First Affiliated Hospital, Zhejiang University School of Medicine, from January 2015 to September 2020 with a discharge diagnosis of MDD or BD were reviewed. Patients who underwent peripheral blood examination of T-cell subtype proportions, including CD3+, CD4+, CD8+ T-cell, and natural killer (NK) cells, were enrolled. The Chi-square test, t-test, or one-way analysis of variance were used to analyze group differences. Demographic profiles and T-cell data were used to construct a random forest classifier-based diagnostic model., Results: Totally, 98 cases of BD mania, 459 cases of BD depression (BD-D), and 458 cases of MDD were included. There were significant differences in the proportions of CD3+, CD4+, CD8+ T-cell, and NK cells among the three groups. Compared with MDD, the BD-D group showed higher CD8+ but lower CD4+ T-cell and a significantly lower ratio of CD4+ and CD8+ proportions. The random forest model achieved an area under the curve of 0.77 (95% confidence interval: 0.71-0.83) to distinguish BD-D from MDD patients., Conclusion: These findings imply that BD and MDD patients may harbor different T-cell inflammatory patterns, which could be a potential diagnostic biomarker for mood disorders., (© 2023 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)

The present perspective paper addresses and discusses whether cognitive dysfunction in bipolar disorder qualifies as a diagnostic intermediate phenotype using the Robin and Guze criteria of diagnostic validity. The paper reviews current data within (1) delineation of the clinical intermediate phenotype, (2) associations of the intermediate phenotype with para-clinical data such as brain imaging and blood-based data, (3) associations to family history / genetics, (4) characteristics during long-term follow-up, and (5) treatment effects on cognition. In this way, the paper identifies knowledge gaps and suggests recommendations for future research within each of the five areas. Based on the current state of knowledge, we conclude that cognitive dysfunction does not qualify as a diagnostic intermediate phenotype or endophenotype for bipolar disorder, although promising new evidence points to emotion and reward processing abnormalities as possible putative endophenotypes.

Background: The goals of this study were to introduce psychological well-being as an important subject of inquiry in bipolar disorder, to compare well-being in a cohort of patients with bipolar disorder with that of a normative sample, and to assess whether common measures of well-being and mood measure empirically distinct phenomena., Methods: Participants were outpatients with bipolar I disorder in remission (N=37) from the Enhancing Emotion Regulation in Bipolar Disorder (EERBD) study and a matched community normative sample from the Midlife in the United States (MIDUS) survey (N=6297). The Psychological Well-Being Scale (PWBS) was used to measure psychological well-being. We calculated means and SD of scores on the PWBS and evaluated the differences between the scores of the bipolar I and community samples. We also tested the association between raw and change scores in depression [Hamilton Rating Scale for Depression (HAM-D)] and eudaimonic well-being (PWBS) using Spearman correlation coefficients., Results: The MIDUS survey sample (N=6297) was 48% male, with a mean age of 47 years (SD=13 y). The EERBD sample (N=37) was 27% male, with a mean age of 41 years (SD=11 y). In the bipolar sample, the baseline mean score on the HAM-D was 12.7 (SD=6.0) and the mean score on the Young Mania Rating Scale was 6.1 (SD=6.2). The baseline mean sum score on the PWBS in the normative community MIDUS sample was 100 (SD=14), while that of the bipolar I EERBD sample was 79 (SD=15) at baseline, 84 (SD=13) posttreatment, and 84 (SD=12) at the 3-month follow-up assessment. The effect sizes of the differences at all timepoints were large (Hedges g=1.42 at baseline, 1.11 at the end of treatment, and 1.06 at the 3-mo follow-up). No association was found between the PWBS and depression scores., Conclusions: Outpatients with bipolar disorder in remission demonstrated substantially impaired psychological well-being, despite low levels of depressive symptoms, compared with a normative community sample., Competing Interests: L.S. receives funding from NIH, PCORI, Samsung, and Takeda and royalties from New Harbinger. A.A.N. has financial interests at Alkermes, Jazz Pharma, Sage Pharma, Otsuka, Neuronetics, Acadia Pharm, Esai, Myriad, Sunovion, Neurostar, Merck, Ginger, and Protogenics. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The provincial Liberal government, then led by McCullagh's good friend Premier Mitchell Hepburn, quickly moved to oppose the action and the I Globe and Mail i soon became a gramophone strongly supporting Hepburn's attack on the UAW. The McCullagh-King relationship Bourrie describes was not positive, with the wily King thinking McCullagh hopelessly naïve and the restless McCullagh convinced that King was too cautious and yesterday's man. [Extracted from the article]

Background: Bipolar disorder (BD) is commonly associated with cognitive impairments, that directly contribute to patients' functional disability. However, there is no effective treatment targeting cognition in BD. A key reason for the lack of pro-cognitive interventions is the limited insight into the brain correlates of cognitive impairments in these patients. This is the first study investigating the resting-state neural underpinnings of cognitive impairments in different neurocognitive subgroups of patients with BD., Method: Patients with BD in full or partial remission and healthy controls (final sample of n = 144 and n = 50, respectively) underwent neuropsychological assessment and resting-state functional magnetic resonance imaging. We classified the patients into cognitively impaired (n = 83) and cognitively normal (n = 61) subgroups using hierarchical cluster analysis of the four cognitive domains. We used independent component analysis (ICA) to investigate the differences between the neurocognitive subgroups and healthy controls in resting-state functional connectivity (rsFC) in the default mode network (DMN), executive central network (ECN), and frontoparietal network (FPN)., Results: Cognitively impaired patients displayed greater positive rsFC within the DMN and less negative rsFC within the ECN than healthy controls. Across cognitively impaired patients, lower positive connectivity within DMN and lower negative rsFC within ECN correlated with worse global cognitive performance., Conclusion: Cognitive impairments in BD seem to be associated with a hyper-connectivity within the DMN, which may explain the failure to suppress task-irrelevant DMN activity during the cognitive performance, and blunted anticorrelation in the ECN. Thus, aberrant connectivity within the DMN and ECN may serve as brain targets for pro-cognitive interventions., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

In the first two decades of the 20th century, a new approach to psychiatric genetics research emerged in Germany from three roots: (i) the wide-spread acceptance of Kraepelin's diagnostic system, (ii) increasing interest in pedigree research, and (iii) excitement about Mendelian models. We review two relevant papers, reporting analyses of, respectively, 62 and 81 pedigrees: S. Schuppius in 1912 and E. Wittermann in 1913. While most prior asylum based studies only reported a patient's "hereditary burden," they examined diagnoses of individual relatives at a particular place in a pedigree. Both authors focused on the segregation of dementia praecox (DP) and manic-depressive insanity (MDI). Schuppius reported that the two disorders frequently co-occurred in his pedigrees while Wittermann found them to be largely independent. Schuppius was skeptical of the feasibility of evaluating Mendelian models in humans. Wittermann, by contrast, with advice from Wilhelm Weinberg, applied algebraic models with proband correction to DP in his sibships with results consistent with autosomal recessive transmission. While he had less data, Wittermann suggested that MDI was likely an autosomal dominant disorder. Both authors were interested in other disorders or traits appearing in pedigrees dense with DP (e.g., idiocy) or MDI (e.g., highly excitable individuals)., (© 2023 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.)

To date, bipolar disorder (BD) genetic studies and polygenic risk scores (PRSs) for BD are based primarily on populations of European descent (EUR) and lack representation from other ancestries including Latin American (LAT). Here, we describe a new LAT cohort from the Mayo Clinic Bipolar Biobank (MCBB), a multisite collaboration with recruitment sites in the United States (EUR; 1,443 cases and 777 controls) and Mexico and Chile (LAT; 211 cases and 161 controls) and use the sample to explore the performance of a BD-PRS in a LAT population. Using results from the largest genome-wide association study of BD in EUR individuals, PRSice2 and LDpred2 were used to compute BD-PRSs in the LAT and EUR samples from the MCBB. PRSs explained up to 1.4% (PRSice) and 4% (LDpred2) of the phenotypic variance on the liability scale in the LAT sample compared to 3.8% (PRSice2) and 3.4% (LDpred2) in the EUR samples. Future larger studies should further explore the differential performance of different PRS approaches across ancestries. International multisite studies, such as this one, have the potential to address diversity-related limitations of prior genomic studies and ultimately contribute to the reduction of health disparities., (© 2023 Wiley Periodicals LLC.)

Lithium intoxication is still an undefined and underestimated disease, especially those cases requiring extracorporeal treatment. Lithium is a monovalent cation with small molecular mass of 7 Da that has been regularly and successfully used since 1950 in the treatment of mania and bipolar disorders. However, its careless assumption can lead to a wide spectrum of cardiovascular, central nervous system and kidney diseases in case of acute, acute on chronic and chronic intoxications. In fact, lithium serum range is strict between 0.6 and 1.3 mmol/L, with a mild lithium toxicity observed at the steady-state of 1.5-2.5 mEq/L, moderate toxicity when lithium reaches 2.5-3.5 mEq/L, and severe intoxication with observed serum levels > 3.5 mEq/L. Its favorable biochemical profile allows the complete filtration and partial reabsorption in the kidney due to the similarity to sodium and also the complete removal by renal replacement therapy, that should be considered in specific poisoning conditions. In this narrative and updated review we discussed a clinical case of lithium intoxication, the different pattern of diseases attributable to excessive lithium load and the current indications for extracorporeal treatment., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: Persons with schizophrenia, schizoaffective, or bipolar I disorder are more likely to die by suicide compared to the general population. Dysfunctional attitudes have been shown to be significant predictors of cognitive vulnerability to depression, hopelessness, and poor problem-solving skills, which predict suicidal ideation. Dysfunctional attitudes are common in persons with schizophrenia spectrum disorders (SSDs) and bipolar I. The Reasons for Living Inventory (RFLI) examines distinct reasons for not dying by suicide. This study's objectives were to examine the relationship between the RFLI subscales and dysfunctional attitudes among persons with SSDs and bipolar I. We hypothesized significant positive correlations between two RFLI subscales (Fear of Suicide and Fear of Social Disapproval) and total score on the Dysfunctional Attitude Scale (DAS). We did not expect significant correlations between other subscales., Design and Methods: This correlational, cross-sectional study examined baseline scores on the RFLI and dysfunctional attitudes (DAS) among N = 102 outpatients with SSDs or bipolar I., Results: Significant positive correlations were observed between RFLI subscales Fear of Suicide and Fear of Social Disapproval and DAS total scores. No other significant relationships were observed., Conclusions: Certain reasons for living (i.e. fear of suicide and social disapproval) may be associated with dysfunctional attitudes among persons with SSDs or bipolar I. These, in turn, may place these individuals at a greater risk for suicide by increasing their cognitive vulnerability. These findings may inform clinical treatment targets for persons with SSDs and bipolar I., (© 2023 The British Psychological Society.)

Exposure to early life trauma increases the risk of psychopathology later in life. Here we investigated if ANK3 mRNA levels influence the relationship between childhood trauma experiences and clinical characteristics in mental disorders. A sample of 174 patients with bipolar disorder and 291 patients with schizophrenia spectrum disorder were included. Patients were diagnosed using the Structured Clinical Interview for DSM-IV, and childhood trauma was assessed using the childhood trauma questionnaire. Age at illness onset and number of psychotic and affective episodes were assessed from interview and medical records. Current depressive symptoms were measured using the calgary depression scale for schizophrenia and the inventory for depressive symptomatology. ANK3 expression was analyzed in whole blood using the Illumina HumanHT-12 v4 Expression BeadChip. Analyses were carried out with the Process adjusted for confounders. Within the total sample, patients with both high ANK3 expression and with the most severe childhood sexual abuse had more manic/hypomanic episodes and an earlier age at onset of the first episode. ANK3 mRNA levels also moderated the relationship between emotional neglect and manic/hypomanic episodes. Our results suggest that ANK3 expression levels moderate the association between specific types of childhood trauma and affective traits in mental disorders., (© 2023. Springer Nature Limited.)

Posterior fossa arachnoid cysts (PFACs) are rare congenital abnormalities observed in 0.3 to 1.7% of the population and are traditionally thought to be benign. While conducting a neuroimaging study investigating cerebellar structure in bipolar disorder, we observed a higher incidence of PFACs in bipolar patients (5 of 75; 6.6%) compared to the neuronormative control group (1 of 54; 1.8%). In this report, we detail the cases of the five patients with bipolar disorder who presented with PFACs. Additionally, we compare neuropsychiatric measures and cerebellar volumes of these patients to neuronormative controls and bipolar controls (those with bipolar disorder without neuroanatomical abnormalities). Our findings suggest that patients with bipolar disorder who also present with PFACs may have a milder symptom constellation relative to patients with bipolar disorder and no neuroanatomical abnormalities. Furthermore, our observations align with prior literature suggesting an association between PFACs and psychiatric symptoms that warrants further study. While acknowledging sample size limitations, our primary aim in the present work is to highlight a connection between PFACs and BD-associated symptoms and encourage further study of cerebellar abnormalities in psychiatry., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study aims to use a bibliometric technique to evaluate the scientific output of gene and bipolar disorder research. The search query related to gene and bipolar disorder from the Scopus database identified 1848 documents from 1951 to 2020. The growth in the publications increased since early 1990, peaked in 2011, and started to decline thereafter. High occurrence in author keywords suggests that some research topics, such as "polymorphism", "linkage" and "association study" have waned over time, whereas others, such as "DNA methylation," "circadian rhythm," "" and "meta-analysis," are now the emerging trends in gene and bipolar disorder research. The USA was the country with the highest production followed by the UK, Canada, Italy and Germany. The leading institutions were Cardiff University in the UK, the National Institute of Mental Health (NIMH) in the USA, King's College London in the UK and the University of California, San Diego in the USA. The leading journals publishing gene and bipolar literature were the American Journal of Medical Genetics Neuropsychiatric Genetics, Molecular Psychiatry and Psychiatric Genetics. The top authors in the number of publications were Craddock N, Serretti A and Rietschel M. According to the co-authorship network analysis of authors, the majority of the authors in the same clusters were closely linked together and originated from the same or neighbouring country. The findings of this study may be useful in identifying emerging topics for future research and promoting research collaboration in the field of genetic studies related to bipolar disorder., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To investigate (i) the proportions of time with irritability and (ii) the association between irritability and affective symptoms and functioning, stress, and quality of life in patients with bipolar disorder (BD) and unipolar depressive disorder (UD)., Methods: A total of 316 patients with BD and 58 patients with UD provided self-reported once-a-day data on irritability and other affective symptoms using smartphones for a total of 64,129 days with observations. Questionnaires on perceived stress and quality of life and clinical evaluations of functioning were collected multiple times during the study., Results: During a depressive state, patients with UD spent a significantly higher proportion of time with presence of irritability (83.10%) as compared with patients with BD (70.27%) (p = 0.045). Irritability was associated with lower mood, activity level and sleep duration and with increased stress and anxiety level, in both patient groups (p-values<0.008). Increased irritability was associated with impaired functioning and increased perceived stress (p-values<0.024). In addition, in patients with UD, increased irritability was associated with decreased quality of life (p = 0.002). The results were not altered when adjusting for psychopharmacological treatments., Conclusions: Irritability is an important part of the symptomatology in affective disorders. Clinicians could have focus on symptoms of irritability in both patients with BD and UD during their course of illness. Future studies investigating treatment effects on irritability would be interesting., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)