Search

Background: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome., Methods: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses., Results: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort., Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends., Conclusions: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Social anxiety disorder (SAD) is a frequent comorbidity in first-episode psychosis (FEP) and may increase cognitive impairments. Cognitive remediation (CR) is an effective treatment for cognition, particularly in a group format. This study aims to assess the efficacy, acceptability and engagement of group CR on cognitive outcomes in FEP+SAD compared to group cognitive-behavioral therapy (CBT). Participants with FEP+SAD were randomized to group CR (n = 45) or CBT-SAD (n = 51). They were assessed for cognition at baseline, post-therapy and 3- and 6-month follow-up. The CR group additionally completed scale to assess perceived competency and enjoyment in CR. Linear mixed models for repeated measures were used for cognitive scores. Descriptive statistics and t-tests were used to summarize acceptability, perceived competency, and enjoyment, for CR completers and non-completers. The CR group performed significantly better than CBT on executive functions and visual memory at post-therapy compared to baseline. Twenty participants completed CR (44 %; mean 5.5 sessions). At week 1, CR non-completers presented higher levels of perceived competency. Completers reported higher enjoyment scores at the last session compared to the first session. Group CR is effective for cognitive outcomes in FEP+SAD, but acceptability and engagement present a challenge. Future studies are necessary to explore approaches promoting engagement., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for major depressive disorder (MDD); however, this treatment currently lacks reliable biomarkers of treatment response. TMS-evoked potentials (TEPs), measured using TMS-electroencephalography (TMS-EEG), have been suggested as potential biomarker candidates, with the N100 peak being one of the most promising. This study investigated the association between baseline N100 amplitude and 1 Hz right dorsolateral prefrontal cortex (R-DLPFC) accelerated rTMS (arTMS) treatment in MDD., Methods: Baseline TMS-EEG sessions were performed for 23 MDD patients. All patients then underwent 40 sessions of 1 Hz R-DLPFC (F4) arTMS over 5 days and a follow-up TMS-EEG session one week after the end of theses arTMS sessions., Results: Baseline N100 amplitude at F4 showed a strong positive association (p < .001) with treatment outcome. The association between the change in N100 amplitude (baseline to follow-up) and treatment outcome did not remain significant after Bonferroni correction (p = .06, corrected; p = .03, uncorrected). Furthermore, treatment responders had a significantly larger mean baseline F4 TEP amplitude during the N100 time frame compared to non-responders (p < .001). Topographically, after Bonferroni correction, F4 is the only electrode at which its baseline N100 amplitude showed a significant positive association (p < .001) with treatment outcome., Limitations: Lack of control group and auditory masking., Conclusion: Baseline N100 amplitude showed a strong association with treatment outcome and thus demonstrated great potential to be utilized as a cost-effective and widely adoptable biomarker of rTMS treatment in MDD., Competing Interests: Declaration of competing interest JZS, FMazza, DM, FMansouri, TR, RZ, MH, LF, HV, EBA do not report any conflict of interest. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magventure Inc. His work has been supported by the Canadian Institutes of Health Research (CIHR), the National Institute of Mental Health (NIMH), Brain Canada and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JD has received research support from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, the Canadian Institutes of Health Research (CIHR), the Klarman Family Foundation, NIH, the Ontario Brain Institute, the Toronto General and Western Hospital Foundation, and the Weston Family Foundation; he has received travel stipends from Lundbeck and ANT Neuro; he has served as an advisor for BrainCheck, Restorative Brain Clinics, and TMS Neuro Solutions, holds equity in Arc Health Partners, and is a co-founder of Ampa. JPM reports research support from the Brain & Behavior Research Foundation (BBRF), the Réseau Québécois sur le Suicide, les troubles de l'Humeur et les troubles Associés (RQSHA), the Canadian Research Initiative in Substance Misuse (CRISM), the Fonds de Recherche du Québec - Santé (FRQS), the Branch Out Neurological Foundation, and the Canadian Institutes of Health Research (CIHR). JDG has received research support from the Labatt Family Network, the CAMH Discovery Fund, the University of Toronto EMHSeed program, and the Tri-Council Canada-UK AI Initiative., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This cohort study investigated whether allostatic load (AL) is associated with treatment response to repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD). Pre-treatment blood samples measured AL across multiple systems. Pre- and post-treatment mood changes were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Associations between AL and treatment outcomes were explored. Higher pre-treatment AL was significantly associated with poorer post-treatment response status but was not significantly associated with smaller reduction in MADRS score after 4 weeks of treatment. Identifying biomarker profiles informed by the AL model could enhance treatment decisions in TRD, reducing risks associated with prolonged, ineffective rTMS trials and emphasizing the need for reliable predictive biomarkers., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: This short communication explores the interrelationships between depressed mood and sleep disturbances in one-year postpartum period., Methods: Utilizing data from the Interaction of Gene and Environment of Depression during PostPartum Cohort (IGEDEPP) involving 3310 French postpartum women, we employed a cross-lagged panel model (CLPM) to analyze the relationships between these two symptoms, across three time points (immediate postpartum [<1 week after delivery], early postpartum [<2 months after delivery], and late postpartum [2 months to 1 years after delivery])., Results: Depressed mood significantly influences sleep disturbances in late postpartum (β = 0.096, z-value = 7.4; p < 0.001) but not in early postpartum (p-value = 0.9). We found no cross-lagged influence of sleep disturbances on depressed mood in early (p = 0.066) or in late postpartum (p = 0.060). Moreover, depressed mood and sleep disturbances in immediate postpartum are predictive of similar symptoms in the two other postpartum periods (between each of the three periods, p = 0.006 and p < 0.001 for depressed mood, and p = 0.039 and p < 0.001 for sleep disturbances), thus demonstrating the stability of these symptoms over time., Limitations: Although conducted with a prospectively assessed cohort, this study faces limitations due to potential methodological biases., Conclusions: This study is a pioneering analysis of mutual causal interactions between depressed mood and sleep disturbances in the postpartum period, highlighting the need for vigilant monitoring, early detection, prevention of worsen outcomes and intervention on these symptoms., Competing Interests: Declaration of competing interest The authors report no conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Sex differences in sleep disturbances during major depressive episodes (MDE) have been suggested. This study compares the prevalence, sociodemographic characteristics, and psychiatric comorbidity associated with sleep complaints specific to each sex among adults with MDE. These findings are crucial for precise diagnosis, personalized treatment, and improved clinical outcomes., Methods: In a large nationally representative prospective survey, we used multi-adjusted logistic regression models including sociodemographic characteristics, psychiatric comorbidity, and depression severity to examine whether associations differ between men and women., Results: Among women, 93.3 % reported at least one type of sleep complaints (i.e., trouble falling asleep, early morning awakening or hypersomnia) while 91.0 % of men did, with respectively 78.3 % and 77.2 % of insomnia complaints, and 46.2 % and 41.3 % of hypersomnia complaints. Women with sleep complaints were more likely to be black, with lower individual incomes, have histrionic personality disorder or a specific phobia. Conversely, men with sleep complaints were more likely to have a lifetime diagnosis of mania spectrum disorder, generalized anxiety disorder, drug use disorder, as well as dependent and schizotypal personality disorders. Surprisingly, being "never married" has emerged as a protective factor against sleep complaints in women, while posing as a risk factor in men compared to other marital statuses. Differences and specificities were also noted concerning subtypes of insomnia and hypersomnia complaints., Limitations: The cross-sectional design means the associations found do not imply causality., Conclusions: These findings provide insights into the complex relationship between sleep and depression in men and women, highlighting the need for personalized interventions., Competing Interests: Declaration of competing interest Authors report no conflicts of interest related to this work., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

The object of this study is test whether mitochondrial blood-based biomarkers are associated with markers of metabolic syndrome in bipolar disorder, hypothesizing higher lactate but unchanged cell-free circulating mitochondrial DNA levels in bipolar disorder patients with metabolic syndrome. In a cohort study, primary testing from the FondaMental Advanced Centers of Expertise for bipolar disorder (FACE-BD) was conducted, including 837 stable bipolar disorder patients. The I-GIVE validation cohort consists of 237 participants: stable and acute bipolar patients, non-psychiatric controls, and acute schizophrenia patients. Multivariable regression analyses show significant lactate association with triglycerides, fasting glucose and systolic and diastolic blood pressure. Significantly higher levels of lactate were associated with presence of metabolic syndrome after adjusting for potential confounding factors. Mitochondrial-targeted metabolomics identified distinct metabolite profiles in patients with lactate presence and metabolic syndrome, differing from those without lactate changes but with metabolic syndrome. Circulating cell-free mitochondrial DNA was not associated with metabolic syndrome. This thorough analysis mitochondrial biomarkers indicate the associations with lactate and metabolic syndrome, while showing the mitochondrial metabolites can further stratify metabolic profiles in patients with BD. This study is relevant to improve the identification and stratification of bipolar patients with metabolic syndrome and provide potential personalized-therapeutic opportunities., Competing Interests: Declaration of competing interest Kassandra A. Zachos: none Jaehyoung Choi: none Ophelia Godin: none Timofei Chernega: none Haejin Angela Kwak: none Jae H. Jung: none Bruno Aouizerate: none Valérie Aubin: none Frank Bellivier: none Raoul Belzeaux R: none Philippe Courtet: none Caroline Dubertret: none Bruno Etain: none Emmanuel Haffen: none Antoine Lefrere A: none Pierre-Michel Llorca: none Emilie Olié: none Mircea Polosan: none Ludovic Samalin: none Raymund Schwan: none Paul Roux: none Caroline Barau: none Jean Romain Richard: none Ryad Tamouza: none Ana C. Andreazza: none Marion Leboyer: none, (Copyright © 2024. Published by Elsevier B.V.)

Sleep disturbances are well-known symptoms of major depressive disorder (MDD). However, the prospective risk of MDD in the presence of sleep disturbances in a general population-based cohort is not well known. This study investigated associations between both polysomnography (PSG)-based or subjective sleep features and incident MDD. Participants representative of the general population who had never had MDD completed sleep questionnaires (n = 2000) and/or underwent PSG (n = 717). Over 8 years' follow-up, participants completed psychiatric interviews enabling the diagnosis of MDD. Survival Cox models were used to analyze associations between sleep features and MDD incidence. A higher Epworth Sleepiness Scale and presence of insomnia symptoms were significantly associated with a higher incidence of MDD (hazard ratio [HR] [95 % confidence interval (CI)]: 1.062 [1.022-1.103], p = 0.002 and 1.437 [1.064-1.940], p = 0.018, respectively). Higher density of rapid eye movements in rapid eye movement (REM) sleep was associated with a higher incidence of MDD in men (HR 1.270 [95 % CI 1.064-1.516], p = 0.008). In women, higher delta power spectral density was associated with a lower MDD incidence (HR 0.674 [95 % CI 0.463-0.981], p = 0.039). This study confirmed the associations between subjective and objective sleep features and the incidence of MDD in a large community dwelling cohort., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hypersomnolence is common in major depressive disorder (MDD), associated with more severe episodes, suicide and antidepressant resistance. Nevertheless, few studies used polysomnography (PSG) and multiple sleep latency test (MSLT) to characterize these patients. In this context, we compared patients visiting a sleep center for hypersomnolence complaint with MDD (HSC/MDD+) and without MDD (HSC/MDD-)., Methods: HSC/MDD+ and HSC/MDD- groups were defined according to DSM-5 criteria and CES-D scale, and had a 30 h-PSG with ad libitum-sleep and PSG followed by MLST., Results: HSC/MDD+ had an increased self-declared total sleep time (sTST) of about 10 h30 similar to HSC/MDD- (630.8 ± 17.3 min-vs-616.5 ± 18.1 min, respectively, p = 0.39). Nevertheless, their objective TST (oTST) on ad libitum PSG was significantly longer and about 10 h50 (648.6 ± 23.9 min-vs-587.4 ± 19.0 min, respectively, p = 0.038). HSC/MDD+ also significantly better estimated their sleep duration, with a lower difference between their sTST and oTST compared to HSC/MDD- (10.0 ± 1.7 %-vs-17.4 ± 2.1 %, respectively, p = 0.009) and confirmed significantly more frequently the hypersomnia diagnosis -i.e. oTST>10H- (82.6 ± 8.1 %-vs-54.6 ± 10.9 %, respectively, p = 0.046). Using the Kupfer index (KI), we confirmed a reduced REM sleep latency in patients MDD/HSC+ (15.2 ± 10.0 %-vs-2.3 ± 2.3 %, respectively, p = 0.039). Both groups had comparable increased diurnal sleepiness assessed with the Epworth scale (14.1 ± 1.1-vs-14.8 ± 1.1, respectively, p = 0.65). HSC/MDD+ had less MSLT sleep latency <8 min (9.1 ± 5.1 %-vs-27.3 ± 6.8 %, respectively, p = 0.048)., Limitations: Retrospective cross-sectional study., Conclusions: HSC/MDD+ accurately estimated their sleep duration, objectively confirmed hypersomnia and may specifically had a decreased Kupfer index., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this work., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Although hospitalisation for COVID-19 is associated with a higher post-discharge risk of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BD), this risk has not been compared to that following hospitalisation for a reason other than COVID-19., Methods: Using data from France's National Health Data System (SNDS) database, we compared patients hospitalised for mood disorders in the 12 months following COVID-19/another reason hospitalisation., Results: 96,313 adult individuals were hospitalised for COVID-19, and 2,979,775 were hospitalised for another reason. In the 12 months post-discharge, 110,976 (3.83 %) patients were hospitalised for mood disorders. In unadjusted analyses, patients initially hospitalised for COVID-19 (versus another reason) were more likely to be subsequently hospitalised for a mood disorder (4.27 % versus 3.82 % versus, respectively, p < 0.0001). These patients were also more likely to have a history of mood disorders, especially depressive disorders (6.45 % versus 5.77 %, respectively, p < 0.0001). Women, older age, lower social deprivation, a history of mood disorders, longer initial hospitalisation (COVID-19 or other), and a higher level of clinical care during initial hospitalisation were all significantly associated with the risk of subsequent hospitalisation for MDD and BD. In contrast, after adjusting for all these factors, persons initially hospitalised for COVID-19 were less likely to be subsequently hospitalised for MDD (OR = 0.902 [0.870-0.935]; p < 0.0001). No difference between both groups was observed for BD., Limitations: Other reasons were not separately studied., Conclusions: After adjusting for confounding factors, initial hospitalisation for COVID-19 versus for another reason was associated with a lower risk of hospitalisation for a mood disorder., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Currently, there is a major challenge in distinguishing between unipolar and bipolar major depressive episode. A significant body of research has been dedicated to identifying biomarkers that can aid in this differentiation due to its crucial implications, particularly for therapeutic and prognostic purposes. Among the biomarkers of interest, markers related to sleep and circadian rhythms show promise and could potentially aid in making this distinction. Nevertheless, no study has simultaneously examined sleep-wake disorders, circadian rhythms, and seasonal patterns using both subjective and objective measures. This study aims to characterize and compare the sleep-wake and rhythm disorders including patients with unipolar major depressive episode (n = 72) and with bipolar major depressive episode (n = 43) using both subjective markers (using self-report questionnaires and sleep complaints) and objective markers (using actigraphy). Patients with unipolar major depressive episode seem to experience significantly poorer quality of sleep, more symptoms of insomnia and lower sleep efficiency compared to patients with bipolar major depressive episode. On the other hand, patients with bipolar major depressive episode exhibit significantly more symptoms of motor retardation and hypersomnia compared to patients with unipolar disorder. These results hold significant implications for identifying individuals with unipolar major depressive episode or bipolar major depressive episode using sleep and circadian markers, and for developing recommended and personalized therapeutic strategies., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest related to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Disturbances in sleep and circadian rhythmicity (CR) are frequent in individuals with bipolar disorders (BD). Very few studies explored the associations between psychotropic medications and these disturbances in euthymic BD. Therefore, we aimed at exploring the associations between several classes of medications (lithium, sedative/non-sedative Atypical Antipsychotics (AAP), anticonvulsants, antidepressants, benzodiazepines) and sleep disturbances and CR dimensions in a sample of euthymic individuals with BD., Methods: We included euthymic adults with BD type 1 or 2 assessed with 21 days of actimetry. We used a Principal Component Analysis (PCA) of sleep and CR estimates to generate dimensions to be studied in association with the current use of psychotropic medications, with adjustments for potential confounding factors., Results: We included individuals with BD-1 (n = 116) or BD-2 (n = 37). The PCA led to four dimensions of sleep and CR estimates. Benzodiazepines were associated with better sleep quality (p corrected  = 0.032). Aripiprazole was associated with less robust CR (p corrected  = 0.016), but with earlier peak of activity patterns (p corrected  = 0.020). Sedative AAPs were associated with better sleep quality, which was no longer significant after correction. We found no association between lithium or anticonvulsants and CR., Limitations: The cross-sectional design and the possible non-representativeness of the sample were limitations of our study., Conclusions: In euthymic individuals with BD, benzodiazepines may have a positive effect on sleep quality, while aripiprazole may have mixed effects on CR (less robust but with earlier peak of activity patterns). No association with lithium or anticonvulsants observed. Further studies are warranted to replicate and extend these results., Competing Interests: Declaration of competing interest All of the authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Suicide is a major health issue. Its prevalence is particularly high in subjects presenting major depression disorder (MDD), making this a key suicide-related risk factor. Suicide attempts in severe forms of MDD were assumed to be linked to impulsivity and loss of control. Nevertheless, we failed to find data specifically investigating the link between impulsivity and suicide risk in treatment-resistant depression (TRD). This study seeks to review this relationship., Method: Patients were recruited for a prospective cohort. Suicide risk and impulsivity were assessed using the International Neuropsychiatric Interview and Barratt Impulsiveness Scale, Version 10, respectively, while the severity of depressive symptoms was assessed using the Montgomery-Asberg Depression Rating Scale, anxiety with the State-Trait Anxiety Inventory and childhood maltreatment using the Childhood Trauma Questionnaire., Results: 220 TRD patients were enrolled in the study. The impulsivity score was correlated with self-esteem, marital status, professional status and anxiety. There was no direct link to suicide risk. However, impulsivity was associated with self-esteem (coefficient: -0.24; p value 0.043) and depressive symptom severity (coefficient: 0.; p value 0.045). The suicide risk was significantly correlated with depressive symptom severity (coefficient = 0.38, p < 0.001) and self-esteem (coefficient = -0.34, p = 0.01). Considering these correlations, we postulated that the effect of impulsivity on suicide risk could be mediated by self-esteem in terms of depressive symptom severity and we finally found a relevant mediation model within impulsivity having an indirect effect on suicide risk by impacting self-esteem and depressive symptoms with anxiety also playing a significant role as a covariable., Conclusion: We found that impulsivity could play an indirect role with the involvement of self-esteem and depressive symptoms and the contributing role of anxiety., Competing Interests: Declaration of competing interest AY received speaker's honoraria from AstraZeneca, Janssen, Lundbeck, Otsuka and Servier, and carried out clinical studies in relation to the development of Janssen and Lundbeck medicines unrelated to this work. J-BG received a speaker's honorarium from Servier. P-ML received grants, honoraria and consulting fees from Allergan, Gedeon Richter, Janssen- Cilag, Lundbeck, Otsuka, Recordati, Sanofi-Aventis and Teva. RRi received a speaker's honorarium from Janssen Cilag. FS received honoraria from Otsuka. EH acted in an advisory capacity, carried out clinical studies in relation to the development of a medicine, received funding for research and studies along with travel allowances, gave presentations at meetings and received remuneration for input from the following pharmaceutical companies: AstraZeneca, BMS, Cellgene, Euthérapie-Servier, Janssen, Elli Lilly, Lundbeck, LivaNova, Otsuka, Pfizer and Sanofi. WE-H received speaker's honoraria from Chugai, Eisai, Lundbeck, Janssen-Cilag, Otsuka and UCB unrelated to this work. BA received speaker's honoraria and/or a travel allowance from Lundbeck, Sanofi, Janssen-Cilag and Eli Lilly. He has also served on the advisory board of Janssen-Cilag. BE received honoraria for consulting activities for Sanofi. The remaining authors have no commercial or financial relationships to declare that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To assess the effectiveness of accelerated transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD) in a tertiary referral center in Quebec, Canada, focusing on a real-world clinical setting., Methods: We reviewed the data of 247 TRD patients treated between January 2012 and May 2022 who received accelerated TMS. Participants were adults diagnosed with unipolar or bipolar depression, resistant to at least two antidepressant trials, and assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS)., Results: Significant symptom reduction was found in the completer sample (N = 147), with 46.3 % of patients meeting post-treatment response criteria and 36.1 % achieving remission. Baseline severity of depression, age, and the number of antidepressant trials were key predictors of treatment outcomes. Patients who did not complete treatment had generally more severe depressive and anxious symptoms and greater treatment resistance. No significant differences in response rates were observed across different TMS coils., Conclusion: The study demonstrated the effectiveness and tolerability of accelerated TMS for TRD in a real-world clinical setting., Competing Interests: Declaration of Competing Interest The authors of the manuscript hereby declare that they have no competing interests to disclose in relation to the research, authorship, and publication of this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Catatonia is a severe psychomotor syndrome mainly associated with psychiatric disorders, such as mood disorders and schizophrenia. Seasonal patterns have been described for these psychiatric disorders, and a previous study conducted in South London showed for the first time a seasonal pattern in the onset of catatonia. In this study, we aim to extend those findings to a larger national sample of patients admitted to French metropolitan hospitals, between 2015 and 2022, and to perform subgroup analyses by the main associated psychiatric disorder. A total of 6225 patients diagnosed with catatonia were included. A seasonal pattern for catatonia diagnosis was described, using cosinor models. Two peaks of diagnoses for catatonic cases were described in March and around September-October. Depending on the associated psychiatric disorder, the seasonality of catatonia diagnosis differed. In patients suffering with mood disorders, peaks of catatonia diagnosis were found in March and July. For patients suffering with schizophrenia, no seasonal pattern was found., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Previous studies have noted the crucial role of excessive daytime sleepiness (EDS) in the course of depressive illness, and more recently, a few studies documented its strong associations with an increased risk of suicide. While insomnia is associated with heightened emotional reactivity, suicidal behaviors, and increased relapses and recurrence. Our main hypothesis is that major depressive episodes (MDE) with insomnia and EDS are associated with more severe manifestations of depression. However, to date, no study has directly compared MDE with insomnia without EDS (Ins), and MDE with insomnia with EDS (InsEDS) using both subjective biomarkers (administration of self-assessment questionnaires for psychiatric evaluation and sleep complaints) and objective biomarkers (of sleep and circadian rhythms (using actigraphy). The InsEDS group, compared to the Ins group, exhibited significantly increased suicidal ideation, larger seasonal impacts on mood, alterations in sleep duration, weight, appetite, energy levels, and social activities throughout the year. Furthermore, they had significant delayed onset of daily activity measured with actigraphy. These findings provided new insights into the link between suicide, sleep, alertness, and biological clock. They also hold significant implications for identifying individuals with more severe depressive manifestations and for developing tailored and personalized therapeutic strategies., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest related to this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Insomnia disorder is a mental disorder that includes various types of symptoms (e.g., insomnia initiating, worries, mood disturbances) and impairments (e.g., distress related to sleep alterations). Self-report questionnaires are the most common method for assessing insomnia but no systematic quantified analysis of their content and overlap has been carried out. We used content analysis and a visualization method to better identify the different types of clinical manifestations that are investigated by nine commonly used insomnia questionnaires for adults and the Jaccard index to quantify the degree to which they overlap. Content analysis found and visualized 16 different clinical manifestations classified into five dimensions ("Insomnia symptoms", "Insomnia-related symptoms", "Daytime symptoms", "Insomnia-related impairments", "Sleep behaviors"). The average Jaccard Index was 0.409 (moderate overlap in content). There is a lack of distinction between symptoms and impairments, and the assessment of sleep duration and hyperarousal symptoms remains overlooked. This preliminary analysis makes it possible to visualize the content of each of the nine questionnaires and to select the most appropriate questionnaire based on the issue to be addressed. Suggestions are made regarding the development of future questionnaires to better distinguish symptoms and impairments, and the different phenotypes of insomnia disorder., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Insomnia plays a critical role in the onset and maintenance of Major Depressive Episode (MDE). Cognitive behavioral therapy for insomnia (CBT-I) can successfully improve the sleep of patients with insomnia and MDE. Nonetheless, the factors influencing CBT-I's effects in MDE remain uncertain. This study aimed to identify predictors of insomnia improvement following CBT-I, as well as predictors of insomnia response, remission in patients with MDE and specific insomnia subtypes. Initially, we compared a 4-session weekly CBT-I treatment to baseline sleep education (SE) in a control group. This confirmed CBT-I's positive effects and the need to explore predictive factors. Notably, treatment-resistant depression (TRD) predicted reduced insomnia severity with CBT-I. Patients exhibiting seasonal fluctuations in depressive symptoms and sleep patterns throughout the year, or having daytime dysfunction, experienced enhanced CBT-I efficacy, especially for early awakenings insomnia. Conversely, shorter sleep duration predicted a less favorable response to CBT-I, less improvement in daytime dysfunction and sleep disturbance worries. Additionally, MDE with suicide attempts predicted a poorer improvement of daytime dysfunction. Further research is essential to comprehensively grasp the mechanisms behind CBT-I's heightened effectiveness in MDE patients with TRD and seasonal fluctuations., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest related to this study., (Copyright © 2023. Published by Elsevier B.V.)

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest in this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Bipolar disorder (BD) is a chronic and severe psychiatric disorder associated with significant medical morbidity and reduced life expectancy. In this study, we assessed accelerated epigenetic aging in individuals with BD using various DNA methylation (DNAm)-based markers. For this purpose, we used five epigenetic clocks (Horvath, Hannum, EN, PhenoAge, and GrimAge) and a DNAm-based telomere length clock (DNAmTL). DNAm profiles were obtained using Infinium MethylationEPIC Arrays from whole-blood samples of 184 individuals with BD. We also estimated blood cell counts based on DNAm levels for adjustment. Significant correlations between chronological age and each epigenetic age estimated using the six different clocks were observed. Following adjustment for blood cell counts, we found that the six epigenetic AgeAccels (age accelerations) were significantly associated with the body mass index. GrimAge AgeAccel was significantly associated with male sex, smoking status and childhood maltreatment. DNAmTL AgeAccel was significantly associated with smoking status. Overall, this study showed that distinct epigenetic clocks are sensitive to different aspects of aging process in BD. Further investigations with comprehensive epigenetic clock analyses and large samples are required to confirm our findings of potential determinants of an accelerated epigenetic aging in BD., Competing Interests: Declaration of Competing Interest None to be declared in links with this study., (Copyright © 2023. Published by Elsevier B.V.)

Background: Eating disorders (EDs) are liable to alter the disease course of bipolar disorder (BD). We explored the crossed clinical features between EDs and BD, particularly as a function of BD type (BD1 vs. BD2)., Methods: 2929 outpatients attending FondaMental Advanced Centers of Expertise were assessed for BD and lifetime EDs with a semi-structured interview, and their sociodemographic, dimensional and clinical data were collected according to a standardized procedure. For each ED type, bivariate analyses were used to investigate associations between these variables and the type of BD type followed by multinomial regressions with the variables associated with EDs and BDs after Bonferroni correction., Results: Comorbid EDs were diagnosed in 478 (16.4 %) cases, and were more prevalent in patients with BD2 than in those with BD1 (20.6 % vs. 12.4 %, p < 0.001). Regression models showed no difference according to the subtype of bipolar disorder on the characteristics of patients with anorexia nervosa (AN), bulimia nervosa (BN) or binge eating disorder (BED). After multiple adjustments, the factors differentiating BD patients with versus without ED were primarily age, gender, body mass index, more affective lability and comorbidity with anxiety disorders. BD patients with BED also scored higher regarding childhood trauma. BD patients with AN also showed higher risk of past suicide attempts than those with BED., Conclusions: In a large sample of patients with BD, we found a high prevalence of lifetime EDs, especially for the BD2 type. EDs were associated with several severity indicators, but not with BD type-specific characteristics. This should prompt clinicians to carefully screen patients with BD for EDs, regardless of BD and ED types., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests with regard to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Insomnia and its opposite hypersomnia are part of the diagnostic criteria for major depressive disorder (MDD). However, no study has investigated whether the postulated sleep alterations in clinical subtypes of MDD are reflected in polysomnography (PSG)-derived objective sleep measures. The objective of this study was to establish associations between the melancholic, atypical and unspecified subtypes of MDD and objective PSG-based sleep features. This cross-sectional analysis included 1820 community-dwelling individuals who underwent PSG and a semi-structured psychiatric interview to elicit diagnostic criteria for MDD and its subtypes. Adjusted robust linear regression was used to assess associations between MDD subtypes and PSG-derived objective sleep measures. Current melancholic MDD was significantly associated with decreased absolute delta power and sleep efficiency and with increased wake after sleep onset. Remitted unspecified MDD was significantly associated with increased rapid eye movements density. No other significant associations were identified. Our findings reflect that some PSG-based sleep features differed in MDD subtypes compared with no MDD. The largest number of significant differences were observed for current melancholic MDD, whereas only rapid eye movements density could represent a risk factor for MDD as it was the only sleep measure that was also associated with MDD in remitted participants., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Patients suffering from treatment-resistant depression (TRD) are at risk of suicide. Sleep and circadian rhythm alterations are widely recognized as core symptoms of major depressive disorder and are associated with suicidal ideation. Thus, sleep and circadian rhythm alterations may be targeted to prevent suicide., Methods: Patients were recruited from a prospective cohort of the French network of TRD expert centers. Mood, sleep and circadian rhythms were assessed at baseline; suicidal risk was assessed both at baseline and during a one-year follow-up with standardized subjective questionnaires., Results: Excessive daytime sleepiness (adjusted odds ratio aOR = 1.7(1-3.3), p = 0.04) and daytime dysfunction (aOR = 1.81(1.16-2.81), p = 0.0085) increased the risk of suicidal thoughts over the one-year follow-up period in patients with TRD after adjustment on age, gender, depression, trauma, anxiety, impulsivity, current daily tobacco smoking and body mass index. Hypnotics intake is associated with a reduced risk of suicidal ideation at one-year follow-up after the same adjustments (OR = 0.73(0.56-0.95), p = 0.019). Other associations between sleep quality or circadian rhythms and suicidal ideations at either baseline or one year did not remain significant in multivariate analyses after the same adjustments., Limitations: Sleep assessments were based on self-reported questionnaires rather than objective measures., Conclusions: Daytime sleepiness and dysfunction are predictors of suicidal ideations, whereas hypnotics intake is associated with a reduced risk of suicidal ideations. Diurnal symptoms of sleep disturbances are therefore red flags to target for preventing suicide in depressed patients, and hypnotics seem efficient in preventing suicide for patients with TRD., (Copyright © 2023. Published by Elsevier B.V.)

Background: The use of alcohol and nicotine can negatively impact the course of bipolar disorder (BD), but there is limited knowledge about how symptoms and sleep disturbances are related to concurrent nicotine use and non-pathological use of alcohol., Methods: We investigated how nicotine use and non-pathological use of alcohol relates to affective symptoms and sleep disturbances in 453 participants with BD without substance use disorders. Manic symptoms were assessed with the Young Mania Rating Scale, and depressive symptoms with The Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C). Sleep-related questions from IDS-C were used to create proxy variables for sleep disturbances, including Insomnia and Hypersomnia. Multinomial regression analysis was conducted to investigate the associations between nicotine use and sleep disturbances, controlling for possible confounders such as current use of illicit drugs and psychopharmacological treatment., Results: Depressive and manic symptoms were not associated with the concurrent level of alcohol or nicotine use. Individuals with medium and high levels of daily nicotine use had higher risk of insomnia than those without. Non-pathological alcohol use was not associated with sleep disturbances., Limitations: Sleep disturbances were based on items from the IDS-C questionnaire., Conclusion: We found an elevated risk for insomnia in individuals with BD and medium or high levels of daily nicotine use. We found no association between the level of affective symptoms and the level of use of alcohol or nicotine. The direction of the relationship between nicotine use and insomnia needs clarification, as it is highly relevant for treatment planning., Competing Interests: Conflict of interest The authors report no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

This study identified profiles of hospitalized patients with mental disorders (MD) based on their 3-year hospitalization patterns and clinical characteristics and compared sociodemographic profiles and other service use correlates as well as risk of death within 12 months after hospitalization. Quebec (Canada) medical administrative databases were used to investigate a 5-year cohort of 4,400 patients hospitalized for psychiatric reasons. Latent class analysis, chi-square tests and survival analysis were produced. Three profiles of hospitalized patients were identified based on hospitalization patterns and other patient characteristics. Profile 3 patients had multiple hospitalizations and early readmissions, worst health and social conditions, and used the most outpatient services. Profiles 2 and 1 patients had only one hospitalization, of brief duration in the case of Profile 2 patients, who had mainly common MD and made least use of psychiatric care. All Profile 1 patients were hospitalized for serious MD but received least continuity of physician care and fewest biopsychosocial interventions. Risk of death was higher for Profiles 3 and 2 versus Profile 1 patients. Interventions like early follow-up care after hospitalization for Profile 3, collaborative care between general practitioners and psychiatrists for Profile 2, and continuous biopsychosocial care for Profile 1 could be greatly improved., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Suicidal ideation (SI) is a major suicide risk factor; therefore, it is crucial to identify individuals with SI. Discrepancies between the clinicians and patients' estimation of SI may lead to under-evaluating the suicide risk. Yet, studies on discrepancies between self- and clinician-rated SI are lacking, although identifying the patients' sociodemographic and clinical characteristics associated with such discrepancies might help to reduce the under-evaluation risk. Therefore, the aim of this study was to identify features associated with SI rating discrepancies in patients with bipolar disorder (BD) because of the high prevalence of suicide in this population. Among the patients recruited by the French network of FondaMental expert centers for BD, patients with SI (i.e. ≥2 for item 12 of the Quick Inventory of Depressive Symptomatology-Self Report and/or ≥3 for item 10 of the clinician-rated Montgomery and Åsberg Depression Rating Scale) were selected and divided in concordant (i.e. SI in both self- and clinician-rated questionnaires; n = 130; 25.6%), and discordant (i.e. SI in only one questionnaire; n = 377; 74.4%). Depression severity was the feature most associated with SI evaluation discrepancy, especially in patients with SI identified only with the self-rated questionnaire. Clinician may under-evaluate SI presence in patients with low depression level., Competing Interests: Declaration of Competing Interest None of the authors declare conflict of interests related to this manuscript., (Copyright © 2023. Published by Elsevier B.V.)

Background and Objective: Repetitive transcranial magnetic stimulation (rTMS) is an effective and safe treatment for major depressive disorder (MDD). rTMS is in need of a reliable biomarker of treatment response. High frequency (HF) dorsolateral prefrontal cortex (DLPFC) rTMS has been reported to induce significant changes in the cardiac activity of MDD patients. Low frequency DLPFC rTMS has many advantages over HF-DLPFC rTMS and thus this study aims to further investigate the effect of low frequency 1 Hz right hemisphere (R)-DLPFC rTMS on the cardiac activity of MDD patients, as well as the potential of using electrocardiogram (ECG) parameters as biomarkers of treatment outcome., Methods: Baseline ECG sessions were performed for 19 MDD patients. All patients then underwent 40 sessions of accelerated 1 Hz R-DLPFC rTMS one week after the baseline session., Results: Heart rate (HR) significantly decreased from the resting period to the first and third minute of the 1 Hz R-DLPFC rTMS period. Resting HR was found to have a significant negative association with treatment outcome. Prior to Bonferroni correction, HR during stimulation and the degree of rTMS-induced HR reduction were significantly negatively associated with treatment outcome. No significant changes were observed for the heart rate variability (HRV) parameters., Limitations: Sample size (n = 19); the use of electroencephalography equipment for ECG; lack of respiration monitoring; relatively short recording duration for HRV parameters., Conclusion: This novel study provides further preliminary evidence that ECG may be utilized as a biomarker of rTMS treatment response in MDD., Trial Registration: ClinicalTrials.gov Identifier: NCT04376697., Competing Interests: Conflict of interest JZS, FM, KD, TR, RZ, MH, LF, HV do not report any conflict of interest. DMB receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he has been the site principal investigator for sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. ZJD has received research and equipment in-kind support for an investigator-initiated study through Brainsway Inc. and Magventure Inc. His work has been supported by the Canadian Institutes of Health Research (CIHR), the National Institutes of Mental Health (NIMH), Brain Canada and the Temerty Family and Grant Family and through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Institute. JD has received research support from the Arrell Family Foundation, the Buchan Family Foundation, Brain Canada, the Canadian Biomarker Integration Network in Depression, the Canadian Institutes of Health Research (CIHR), the Klarman Family Foundation, NIH, the Ontario Brain Institute, the Toronto General and Western Hospital Foundation, and the Weston Family Foundation; he has received travel stipends from Lundbeck and ANT Neuro; he has served as an advisor for BrainCheck, Restorative Brain Clinics, and TMS Neuro Solutions. JPM reports research grants from the Brain & Behavior Research Foundation (BBRF) Young Investigator Award and the Réseau Québécois sur le Suicide, les troubles de l'Humeur et les troubles Associés (RQSHA) as well as salary support for his graduate studies from the Branch Out Neurological Foundation. JDG has received research support from the Labatt Family Network, the CAMH Discovery Fund, the University of Toronto EMHSeed program, and the Tri-Council Canada-UK AI Initiative., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Intermittent theta burst stimulation (iTBS) using 600 pulses is an effective and FDA-cleared transcranial magnetic stimulation (TMS) protocol for major depressive disorder (MDD). Prolonged iTBS (piTBS) using 1,800 pulses could increase the effectiveness of TMS for MDD, but its real-world effectiveness is still debated. We assessed the safety, tolerability, and preliminary effectiveness of a 3x daily piTBS 1,800 pulses protocol delivered over 2 weeks in 27 participants. Only four participants (18.2%) achieved response, two of them achieving remission (9.1%). Five participants (18.5%) experienced tolerability issues. Future studies should focus on the neurophysiological effects of TBS protocols to determine optimal parameters., (Copyright © 2022. Published by Elsevier B.V.)

Background: The FACE-BD cohort is an observational cohort of individuals with bipolar disorders (BD) who benefited from a systematic evaluation with evidence-based treatment recommendations and who were followed-up every year for 3 years in France. The objectives were to describe the lifetime course of BD, associated psychiatric and somatic comorbidities, and cognition profile. This cohort aims to identify clinical/biological signatures of outcomes, trajectories of functioning and transition between clinical stages. This article summarizes 10 years of findings of the FACE-BD cohort., Method & Results: We included 4422 individuals, all having a baseline assessment, among which 61.2% had at least one follow-up visit at either one, two or three years. A subsample of 1200 individuals had at least one biological sample (serum, plasma, DNA). Assessments include family history of psychiatric disorders, psychiatric diagnosis, current mood symptoms, functioning, hospitalizations, suicidal attempts, physical health, routine blood tests, treatment history, psychological dimensions, medico-economic data and a cognitive assessment. Studies from this cohort illustrate that individuals with BD display multiple coexistent psychiatric associated conditions including sleep disturbances, anxiety disorders, substance use disorders and suicide attempts as well as a high prevalence of metabolic syndrome. During follow-up, we observed a 55% reduction of the number of days of hospitalization and a significant improvement in functioning., Conclusions: The FACE-BD cohort provides a strong research infrastructure for clinical research in BD and has a unique position among international cohorts because of its comprehensive clinical assessment and sustainable funding from the French Ministry of Health., (Copyright © 2022. Published by Elsevier B.V.)

Background: Bipolar disorder (BD) is a severe chronic psychiatric disorder affecting 0.5 to 1% of the population worldwide. To date, most studies have estimated the cost of BD via information sourced from insurance claims with limited information on clinical characteristics and course of BD. The aims of this study are (i) to estimate the direct healthcare cost associated with BD and to identify contributing factors and (ii) to study the evolution of cost during a two-year follow-up period., Method: We analyzed a sample of 1116 individuals with BD included in the Advanced Centers of Expertise in Bipolar Disorder cohort. We estimated the direct healthcare cost per year and per patient, and we identified the clinical features of patients with BD associated with higher direct healthcare costs. In a subsample of patients followed up for two years centers of expertise for BD, we studied the evolution of direct healthcare cost., Results: The average cost of bipolar disorder was € 6910 per year and per patient. Clinical features of BD, sociodemographic characteristics, and associated addiction were associated with higher direct healthcare costs. In the subsample of patients followed-up for two years, direct healthcare cost dropped by more than 50%, strongly suggesting the beneficial effect of specialized care organization., Limitation: We did not estimate indirect healthcare and intangible costs., Conclusion: Our study investigates the cost of BD and its evolution in a deeply phenotyped longitudinal sample. Cost-utility and cost-effectiveness analyses are required to inform resource allocation decisions and to promote innovative healthcare organizations., (Copyright © 2022. Published by Elsevier B.V.)

Background: Major depressive disorder (MDD) is a major public health problem. The retina is a relevant site to indirectly study brain functioning. Alterations in retinal processing were demonstrated in MDD with the pattern electroretinogram (PERG). Here, the relevance of signal processing and machine learning tools applied on PERG was studied., Methods: PERG - whose stimulation is reversible checkerboards - was performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards in 24 MDD patients and 29 controls at the inclusion. PERG was recorded every 4 weeks for 3 months in patients. Amplitude and implicit time of P50 and N95 were evaluated. Then, time/frequency features were extracted from the PERG time series based on wavelet analysis. A statistical model has been learned in this feature space and a metric aiming at quantifying the state of the MDD patient has been derived, based on minimum covariance determinant (MCD) mahalanobis distance., Results: MDD patients showed significant increase in P50 and N95 implicit time (p = 0,006 and p = 0,0004, respectively, Mann-Whitney U test) at the inclusion. The proposed metric extracted from the raw PERG provided discrimination between patients and controls at the inclusion (p = 0,0001). At the end of the follow-up at week 12, the difference between the metrics extracted on controls and patients was not significant (p = 0,07), reflecting the efficacy of the treatment., Conclusions: Signal processing and machine learning tools applied on PERG could help clinical decision in the diagnosis and the follow-up of MDD in measuring treatment response., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives Clinical practice guidelines (CPGs) for the treatment of bipolar disorder (BD) provide guidance to health care professionals and patients about the management of core aspects of BD. This study evaluated the overall quality of CPGs and examined the quantity, specificity, clarity and utility of recommendations about four key contemporary themes: sleep, circadian rhythms, activity and energy, and healthy lifestyles. Methods English language editions of CPGs for the treatment of BD were identified by a systematic search of the literature from 2007 onwards (i.e. 15 years). Blind independent ratings were combined to give consensus scores for the quality of each CPGs (using the 14-item International Center for Allied Health Evidence guideline checklist). Composite ratings of the quantity, specificity, clarity and utility of recommendations about the key themes were undertaken using a 0-3 scale. Results Twenty-five CPGs were eligible for review. Overall quality was high (median checklist score=10), but only 11 (44%) CPGs included even basic information about circadian rhythm disturbances. Combined scores for composite ratings about sleep and circadian rhythms were significantly correlated with overall quality of the CPG (sleep, r = 0.43; circadian rhythms, r = 0.42) but not with year of publication. Limitations No reliable scale exists for generating composite ratings of the four themes we examined. Conclusions Circadian rhythms and chronobiology represent neglected domains in CPGs. Incorporating this important theme into future editions of CPGs would aid health care professionals to identify, prevent, or intervene with these problems and improve outcomes for a significant proportion of individuals with BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Developing easy-to-access biomarkers is crucial in Major Depressive Disorder. The retina has already been suggested as relevant. However, there is a need for a global and local assessment of whole retinal function using a reproducible, standardized protocol allowing for comparison across studies. Our aim is to assess whole retinal function in patients with actual unipolar Major Depressive Episode (MDE) using pattern, flash and multifocal electroretinogram (ERG) according to the International Society for Clinical Electrophysiology of Vision standardized protocols., Methods: We assessed retinal function in 14 males and females with MDE, diagnosed based on the Diagnostic and Statistical Manual of Mental Disorders, and in age- and sex-matched healthy controls., Results: Comparing the patients with the controls, we observed the following using multifocal ERG: a significant increase in N1 peak time in ring 3 and a decrease in P1 amplitude in ring 2; using pattern ERG: a significant increase in P50 peak time; using flash ERG: a decrease in a- and b-wave peak time and an increase in the b-wave amplitude in dark-adapted 3.0, a decrease in a- and b-wave peak time and an increase in both wave amplitudes in light-adapted 3.0, and a decrease in the b-wave peak time in light-adapted flicker., Limitations: Sample size. Contribution of pharmacological treatments to the outcomes cannot be formally excluded., Conclusions: Patients with MDE exhibit delayed signaling in the central retina and hyperreactivity to light in the periphery. Central retinal function may be a marker of psychomotor retardation and cognitive impairment in MDE., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Psychiatric disorders, including schizophrenic spectrum disorders, are common in People Who Use Drugs (PWUD). Promoting adherence to medication among PWUD with dual diagnosis is challenging. We present the case of a treatment-disrupted patient suffering from schizophrenia with co-occuring multiple drug dependence to whom penfluridol - an oral long acting typical antipsychotic - was proposed at the Supervised Drug Consumption Room (SDCR) of Paris. Penfluridol quickly improved patient's psychotic symptoms, increased engagement in addiction care and helped maintaining the patient in "Housing First" program. In harm reduction structure, penfluridol can be seen as a "hook treatment" while maintaining therapeutic alliance and favoring patients' engagement in specific care., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The comorbidity of alcohol use disorder (AUD) and bipolar disorder (BD) has been repeatedly associated with poorer clinical outcomes than BD without AUD. We aimed to extend these findings by focusing on the characteristics associated with the sequence of onset of BD and AUD., Methods: 3,027 outpatients from the Fondamental Advanced Centres of Expertise were ascertained for BD-1, BD-2 and AUD diagnoses, including their respective ages at onset (AAOs, N =2,804). We selected the variables associated with both the presence and sequence of onset of comorbid AUD using bivariate analyses corrected for multiple testing to enter a binary regression model with the sequence of onset of BD and AUD as the dependent variable (AUD first - which also included 88 same-year onsets, vs. BD first)., Results: BD patients with comorbid AUD showed more severe clinical profile than those without. Compared to BD-AUD (N =269), AUD-BD (N =276) was independently associated with a higher AAO of BD (OR =1.1, p <0.001), increased prevalence of comorbid cannabis use disorder (OR =2.8, p <0.001) a higher number of (hypo)manic/mixed BD episodes per year of bipolar illness (OR =3, p <0.01)., Limitations: The transversal design prevents from drawing causal conclusions., Conclusion: Increased severity of BD with AUD compared to BD alone did not differ according to the sequence of onset. A few differences, though, could be used to better monitor the trajectory of patients showing either one of these disorders., (Copyright © 2021. Published by Elsevier B.V.)

Although effective in major depressive disorder (MDD), repetitive transcranial magnetic stimulation (rTMS) is costly and complex, limiting accessibility. To address this, we tested the feasibility of novel rTMS techniques with cost-saving opportunities, such as an open-room setting, large non-focal parabolic coils, and custom-built coil arms. We employed a low-frequency (LF) 1 Hz stimulation protocol (360 pulses per session), delivered on the most affordable FDA-approved device. MDD participants received an initial accelerated rTMS course (arTMS) of 6 sessions/day over 5 days (30 total), followed by a tapering course of daily sessions (up to 25) to decrease the odds of relapse. The self-reported Beck Depression Inventory II (BDI-II) was used to measure severity of depression. Forty-eight (48) patients completed the arTMS course. No serious adverse events occurred, and all patients reported manageable pain levels. Response and remission rates were 35.4% and 27.1% on the BDI-II, respectively, at the end of the tapering course. Repeated measures ANOVA showed significant changes of BDI-II scores over time. Even though our protocol will require further improvements, some of the concepts we introduced here could help guide the design of future trials aiming at increasing accessibility to rTMS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The neural network that regulates breathing shows a significant sexual dimorphism. Ovarian hormones contribute to this distinction as, in rats, ovariectomy reduces the ventilatory response to CO 2 . Microglia are neuroimmune cells that are sensitive to neuroendocrine changes in their environment. When reacting to challenging conditions, these cells show changes in their morphology that reflect an augmented capacity for producing pro- and anti-inflammatory cytokines. Based on evidence suggesting that microglia contribute to sex-based differences in reflexive responses to hypercapnia, we hypothesized that ovariectomy and hypercapnia promote microglial reactivity in selected brain areas that regulate breathing. We used ionized calcium-binding-adapter molecule-1 (Iba1) immunolabeling to compare the density and morphology of microglia in the locus coeruleus (LC), the caudal medullary raphe, the caudal part of the nucleus of the tractus solitarius (cNTS), and the paraventricular nucleus of the hypothalamus (PVN). Tissue was obtained from SHAM (metaestrus) female rats or following ovariectomy. Rats were exposed to normocapnia or hypercapnia (5% CO 2, 20 min). Ovariectomy and hypercapnia did not affect microglial density in any of the structures studied. Ovariectomy promoted a reactive phenotype in the cNTS and LC, as indicated by a larger morphological index. In these structures, hypercapnia had a relatively modest opposing effect; the medullary raphe or the PVN were not affected. We conclude that ovarian hormones attenuate microglial reactivity in CO 2 /H + sensing structures. These data suggest that microglia may contribute to neurological diseases in which anomalies of respiratory control are associated with cyclic fluctuations of ovarian hormones or menopause., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Actigraphy is commonly used in case-control studies to explore sleep-wake patterns and circadian rhythmicity in bipolar disorders (BD). However, there is limited ecological research regarding actigraphy parameters associated with response to lithium (Li&#95;Resp)., Methods: Outpatients with BD-I (n=70) and BD-II (n=20) who were all prescribed prophylactic Li undertook 21 consecutive days of actigraphy recording. The Retrospective Assessment of Response to Lithium Scale (also referred as the Alda scale) was rated on a 0-10 continuum. We used principal component analysis (PCA) to summarize interrelationships among clinical and actigraphic variables and Li&#95;Resp., Results: PCA demonstrated the existence of a Li&#95;Resp dimension (accounting for >20% explained variance) characterized by 5 markers of circadian timing and rhythmicity. Replication of the PCA, using the resampling procedure, confirmed this model was robust for the BD-I but not for BD-II (which showed weaker associations between Li&#95;Resp and sleep variables). These circadian rhythm markers identified by PCA correctly classified 64% (95% Confidence Intervals: 52-76%; p<0.03) of all BD cases as Li responders or non-responders., Limitations: Although we attempted to minimize risk of statistical error, the small BD-II subsample may have undermined the ability of PCA to identify a robust Li&#95;Resp dimension for this subtype., Conclusions: Our findings are compatible with circadian models of BD and with putative mechanisms of action of Li. If confirmed in prospective studies, the study offers support for use of actigraphy as a relevant method for real time objective monitoring of Li&#95;Resp, with few concerns regarding reliability and validity., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Bipolar disorder (BD) is a chronic and severe mental illness. It requires a non-discontinued pharmacological treatment to prevent mood recurrences but nonadherence to medication is frequent. To this date, medication adherence in BD has been mostly evaluated in cross-sectional studies and often considered as a stable trait. We aimed to study medication adherence using a prospective person-oriented approach., Methods: 1627 BD patients were followed on a 2 years period and assessed every 6 months. Medication adherence was evaluated at each visit with the Medication Adherence Rating Scale (MARS). A latent class mixed model (LCMM) was used to identify trajectory classes of adherence over time. Regression analyses and linear mixed model were used to search for predictors and covariables of the trajectories., Results: Three distinct and robust trajectories of medication adherence have been identified: one that starts poorly and keeps deteriorating (4.8%), one that starts poorly but improves (9%) and one that starts well and keeps improving (86.2%). A good tolerance to psychotropic medications, low depressive symptoms, the absence of comorbid eating disorders and anticonvulsant medication were associated to a better prognosis of adherence. Along the follow-up, the lower were the depressive symptoms, the better was the medication adherence (p < .001) LIMITATIONS: The use of a single measure of medication adherence although it is a validated instrument and a possible positive selection bias that might limit the generalization of our findings., Conclusions: This study demonstrates that medication adherence in BD patients is a heterogeneous and potentially variable phenomenon., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Electroconvulsive therapy is a highly effective treatment of several psychiatric disorders. The debate regarding which charge dosing method offers the most favorable risk-benefit ratio remains. Our objective was to review the comparative evidence regarding efficacy and tolerability of dose titration (DT) vs other charge dosing methods, such as the age-based method (ABM) and the fixed dose method. Our secondary objective was to examine which populations would most benefit from DT. We conducted a systematic review of the literature in March 2020. Studies comparing DT to another charge dosing method were included. Fourteen articles depicting hypothetical comparisons between DT and another dosing method were found and seven articles made hypothetical comparisons without measurement of clinical outcomes. Although there is a trend in favor of DT in these articles, no clear recommendations could be drawn regarding the clinical superiority of one method. Older patients could be at higher risk of overstimulation with ABM, especially older women. The lack of high-quality prospective trials was a limitation as well as the fact that many studies used suprathreshold stimulus intensity deemed insufficient according to recent guidelines. This review emphasizes that more studies are needed to establish the differential clinical relevance of each method., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Valproate is associated with teratogenic and neurodevelopmental effects. Several agencies have restricted the conditions of its prescription in bipolar disorders (BD). We aimed to assess the evolution of valproate prescription and the clinical profile of BD women of childbearing age receiving valproate., Methods: Based on a large national cohort, we included all BD women 16-50 years old. Sociodemographic, clinical and pharmacological data were recorded. Logistic regression analyses were used to describe variables associated with valproate prescription., Results: Of the 1018 included women 16-50 years old, 26.9% were treated with valproate with a mean daily dosage of 968 mg. The prevalence of BD women using valproate was 32.6% before May 2015 and 17.3% after May 2015 (p<0.001), the date of French regulatory publication of restriction of valproate prescription. The multivariate analysis revealed that the inclusion period after May 2015 (OR=0.54, CI 95% 0.37-0.78, p=0.001), the age lower than 40 years (OR=0.65, CI 95% 0.43-0.98, p=0.040) and the number of lifetime mood episodes (OR=0.98, CI 95% 0.95-0.99, p=0.040) were the variables negatively associated with the use of valproate., Limitations: Study could be underpowered to determine a clinical profile associated with valproate prescription., Conclusions: The regulatory change in BD women of childbearing age had a significant impact on valproate prescription, even if the prescription rate remains high. Important efforts are needed to help clinicians and patients to improve quality of care in BD women of childbearing age., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The aim of this study was to find the sociodemographic and clinical characteristics of major depressive episode (MDE) with (MDE-HPS+) and without a history of psychotic symptoms (MDE-HPS) in the general population., Methods: The Mental Health in the General Population survey interviewed 38,694 individuals in France by using the MINI. The prevalence and sociodemographic and clinical correlates of MDE-HPS+ were assessed., Results: Of the sample, 11.2% were diagnosed with current MDE and among them, 39.3% presented a history of at least one psychotic symptom (hallucination or delusion). Patients with MDE-HPS+ were younger with more severe social impairment than those with MDE-HPS-. We also found a higher proportion of three generations of migrants in the MDE-HPS+ group. Comorbid psychiatric disorders such as a history of a manic episode, alcohol use disorder, social anxiety, generalized anxiety disorder, and a personal history of a suicide attempt were more frequent in patients with MDE-HPS+ than in those with MDE-HPS-. Finally, we found a specific gradient of severity for psychiatric comorbid disorders depending on the number of psychotic symptoms lifetime in MDE., Limitations: The study also has an observational cross-sectional design that does not permit causal inferences, and it is difficult to eliminate recall bias and reporting errors., Conclusion: In the general population, patients with MDE-HPS+, when compared to MDE-HPS-, presented with a more severe clinical profile, with increased rates of psychiatric comorbidities, particularly a history of bipolar disorder and a history of a suicide attempt., Competing Interests: Conflict of interest The authors have declared that there are no conflicts of interest in relation to the subject of this study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: Bipolar Disorder (BD) is frequently comorbid with other psychiatric disorders. However, few studies systematically examine which disorders are more likely to occur pre- or post-BD onset. We examine the prevalence and Age At Onset (AAO) of psychiatric conditions in adults with BD., Methods: A structured clinical interview was used to assess lifetime history and AAO of alcohol and cannabis misuse, suicide attempts, anxiety and eating disorders in a French sample of euthymic patients with BD (n = 739). Regression analyses were used to test for statistically significant associations between rates and AAO of comorbidities in BD groups stratified by sex or subtype., Results: Prevalence of alcohol and cannabis misuse was associated with male sex and BD-I subtype; whilst most anxiety and eating disorders were associated with female sex. The AAO of most comorbid conditions preceded that of BD, except for panic disorder, agoraphobia and alcohol misuse. Few variations were observed in AAO of comorbidities according to groups., Limitations: All assessments were retrospective, so estimates of prevalence rates and especially exact AAO of some comorbidities are at risk of recall bias., Conclusions: Sex and BD subtype are associated with different rates of comorbid disorders. However, there were minimal between group differences in median AAO of comorbidities. By describing the chronological sequence of comorbidities in BD we were able to demonstrate that a minority of comorbidities typically occurred post-onset of BD. This is noteworthy as these disorders might be amenable to interventions aimed at early secondary prevention., Competing Interests: Declaration of Competing interest The authors declare no financial or other conflicts of interest in relation to this study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Bipolar disorders are complex disorders involving the interaction of multiple factors. Affective temperaments, insomnia, and chronobiological rhythms desynchronization may all contribute to bipolar disorder. Since there is a paucity of research examining this topic we aimed to study how they are interrelated and collectively associated with clinical features of bipolar disorder., Method: One-hundred patients with Bipolar Disorder type II depressive episode with and without mixed features were recruited and compared. Subjects were evaluated with SCID -5, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), the Insomnia Severity Index (ISI), and the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A) while evaluating depressive (Beck Depression Inventory-BDI-II) and manic (Young Mania Rating Scale-YMRS) symptoms. Logistic regression and mediation analyses were conducted., Results: Subjects with mixed features showed a higher scores in both insomnia and chronobiological rhythms scores. When considering affective temperaments not only depressive, cyclothymic and irritable temperaments predicted mood symptoms but also insomnia (depressive symptoms O.R. 4.17, p = 0.043) and chronobiological sleep de-synchronization (manic symptoms O.R. 8.69, p = 0.001). Insomnia symptoms and chronobiological alterations mediated the association between affective temperaments and mood symptoms., Limitations: the cross-sectional design limited any causal interpretation., Conclusion: Subjects with mixed features showed a greater severity of insomnia and chronobiological rhythm de-synchronization compared to subjects without. Insomnia and chronobiological alterations may contribute to mood disorders together with affective temperaments in a complex interplay also mediating their effect on mood. Preventive strategies for bipolars should also act on the dysregulation of sleep and circadian rhythms., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA., Method: The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed., Results: Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation., Conclusion: Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Unipolar mania is a putative subtype of bipolar disorder (BD) in which individuals experience recurrent manic but not major depressive episodes. Few studies of unipolar mania have been conducted in developed countries and none in the UK. This study aimed to identify and characterise people with unipolar mania in the UK and France., Methods: People with unipolar mania were ascertained using a South London UK electronic case register and a French BD case series. Each unipolar mania group was compared to a matched group of people with BD who have experienced depressive episodes., Results: 17 people with unipolar mania were identified in South London and 13 in France. The frequency of unipolar mania as a percentage of the BD clinical population was 1.2% for the South London cohort and 3.3% for the French cohort. In both cohorts, people with unipolar mania experienced more manic episodes than people with BD, and in the French cohort were more likely to experience a psychotic illness onset and more psychiatric admissions. Treatment and self-harm characteristics of people with unipolar mania were similar to people with BD., Limitations: The relatively small number of people with unipolar mania identified by this study limits its power to detect differences in clinical variables., Conclusions: People with unipolar mania can be identified in France and the UK, and they may experience a higher frequency of manic episodes but have similar treatment and self-harm characteristics as people with BD., Competing Interests: Declaration of Competing Interest Dr. Stokes reports grants from the National Institute for Health Research and the Medical Research Council UK during the conduct of the study; grants and non-financial support from Corcept Therapeutics, non-financial support from Janssen Research and Development LLC, grants from H. Lundbeck A/S outside the submitted work. Dr. Yalin reports being an investigator in clinical studies conducted together with Janssen-Cilag, Corcept Therapeutics and COMPASS Pathways during the last 36 months. Mr. Mantingh has nothing to disclose. Dr. Colasanti has nothing to disclose. Dr. Patel reports grants from MRC, grants from Academy of Medical Sciences, during the conduct of the study. Prof Bellivier reports personal fees from Sanofi, outside the submitted work. Prof Kahn reports personal fees from Janssen-Cilag and other from Lundbeck, outside the submitted work. Dr. Leboyer has nothing to disclose. Dr. Henry has nothing to disclose. Prof. Etain reports grants from INSERM, grants from Assistance Publique - Hôpitaux de Paris, grants from Labex Biopsy, personal fees from Fondation Fondamental, during the conduct of the study. Prof. Young reports grants from Janssen, grants from Compass, personal fees from Livanova, personal fees from Lundbeck, personal fees from Otsuka, personal fees from Sunovion, personal fees from Bionomics, outside the submitted work., (Copyright © 2019. Published by Elsevier B.V.)