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Background: Olfactory function is closely related to mood and the endocrine system. However, the role of olfactory function in bipolar disorder combined with metabolic syndrome remains unclear. The purpose of this study was to explore the associations among olfactory function, tumor necrosis factor alpha (TNF-α), and metabolic syndrome and its components in patients with bipolar disorder., Methods: Ninety-six bipolar disorder patients were divided into two groups with and without metabolic syndrome. We also included 46 healthy controls. Olfactory function was assessed using the Sniffin' Sticks test. Blood samples were collected to measure metabolic indicators and serum TNF-α levels., Results: Significant differences in olfactory function were found among the three groups. Compared with the healthy controls, the bipolar disorder without metabolic syndrome group showed poorer olfactory identification ability (P < 0.001) and the bipolar disorder with metabolic syndrome group showed impaired olfactory sensitivity (P = 0.003) and olfactory identification (P < 0.001). Moreover, the bipolar disorder with metabolic syndrome group had poorer olfactory identification ability than the bipolar disorder without metabolic syndrome group (P = 0.015). Both bipolar disorder groups showed lower TNF-α levels than healthy controls. However, there was no significant difference between the two patient groups. Correlation analysis showed that, in the bipolar disorder with metabolic syndrome group, olfactory identification was negatively correlated with systolic blood pressure (r = - 0.424, P = 0.031), and serum TNF-α level was negatively correlated with body mass index (BMI; r = - 0.398, P = 0.049), triglyceride (r = - 0.503, P = 0.010), total cholesterol (r = - 0.491, P = 0.013), low-density lipoprotein-cholesterol (r = - 0.491, P = 0.013), and high-density lipoprotein-cholesterol (r = - 0.454, P = 0.023)., Conclusions: The olfactory identification ability of patients with bipolar disorder is worse than that of healthy controls, and the occurrence of metabolic syndrome will further aggravate the olfactory identification impairment of those patients. Furthermore, there may be a stronger link between serum TNF-α level and multiple metabolic indicators in bipolar disorder patients with metabolic syndrome than in bipolar disorder patients without metabolic syndrome., (© 2024. The Author(s).)

Background: Cardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD., Methods: A total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission., Results: During the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte-lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01-1.05) and MLRs (95% CI, OR: 1.01-1.09) were significantly associated with CVD in patients with BD, respectively., Conclusions: Monocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD., (© 2024. The Author(s).)

Introduction: Bipolar I disorder (BD-I) is associated with an increased risk of obesity, but few studies have evaluated the real-world clinical, humanistic, and economic effects associated with obesity in people with BD-I., Methods: This was a retrospective, cross-sectional analysis of responses to the 2016 and 2020 National Health and Wellness surveys. Respondents (18-64 years) with a self-reported physician diagnosis of BD-I were matched to controls without BD-I based on demographic and health characteristics. Respondents were categorized by body mass index as underweight/normal weight (< 25 kg/m 2 ), overweight (25 to < 30 kg/m 2 ), or obese (≥ 30 kg/m 2 ). Multivariable regression models were used to compare obesity-related comorbidities, healthcare resource utilization (HCRU), health-related quality of life (HRQoL), work productivity, and indirect and direct costs., Results: Before matching, the BD-I cohort was younger than the non-BD-I cohort and included more female and white respondents and a greater proportion covered by Medicaid or Medicare. After matching, the BD-I and non-BD-I cohorts had similar characteristics. A total of 5418 respondents (BD-I, n = 1806; matched controls, n = 3612) were analyzed. Obese respondents with BD-I reported the highest adjusted prevalences of high blood pressure (50%), high cholesterol (35%), sleep apnea (27%), osteoarthritis (17%), type 2 diabetes (12%), and liver disease (4%). Obesity in respondents with BD-I was associated with the lowest HRQoL scores. Measures of work impairment were highest in respondents with BD-I and obesity, as was HCRU. Respondents with BD-I and obesity had the highest associated total indirect and direct medical costs ($25,849 and $44,482, respectively)., Conclusion: Obese respondents with BD-I had greater frequencies of obesity-related comorbidities, higher HCRU, lower HRQoL, greater work impairments, and higher indirect and direct medical costs. These findings highlight the real-world burden of obesity in people with BD-I and the importance of considering treatments that may reduce this burden., (© 2024. The Author(s).)

Verbal fluency (VF) has been proposed as a putative neurocognitive endophenotype in schizophrenia (SZ) and bipolar disorder (BD). However, this hypothesis has not been examined using a longitudinal family approach. We conducted a five-group, comparative study. The sample comprised 323 adult participants, including 81 BD patients, 47 unaffected relatives of BD BD-Rel), 76 SZ patients, 40 unaffected relatives of SZ (SZ-Rel), and 79 genetically unrelated healthy controls (HC). All subjects were assessed twice with semantic VF (sem-VF) and phonological VF (ph-VF) tests over a 2-year follow-up period. ANCOVAs controlling for age and years of education were used to compare performance across groups. Patients with SZ and BD and their unaffected relatives showed sem-VF and ph-VF deficits at baseline, which persisted over time (all, p < 0.05). Moreover, BD-Rel showed an intermediate performance between SZ and HC. A repeated-measures ANOVA revealed no significant differences in the between-group trajectories comparison (p > 0.05). Our findings support that VF may represent a neurocognitive endophenotype for SZ and BD. Further longitudinal, family studies are warranted to confirm this preliminary evidence., Competing Interests: Declaration of competing interest Dr. Vicent Balanzá-Martínez has been a consultant, advisor, or Continuing Medical Education (CME) speaker for Angelini. None of the remaining authors declare any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: To study the prevalence of fatigue and factors associated with fatigue in patients with major depressive disorder (MDD) or bipolar disorder (BD)., Methods: Two hundred fifty-three outpatients with MDD or BD at the initial assessment were used to study the prevalence of fatigue and relationship between fatigue and other clinical correlates. The severity of fatigue was measured with Iowa Fatigue Scale (IFS), and depression and anxiety symptom-severity were measured with the QIDS-16-SR (the 16-item Quick Inventory of Depressive Symptomatology - Self-Report) and Zung-SAS (Zung Self-Rating Anxiety Scale). Correlation between IFS and QIDS-16-SR total scores, QIDS-16-SR item scores or Zung-SAS total scores, and independent factors associated with fatigue was assessed with simple or multiple linear regression analysis., Results: Overall, 28.4 % of MDD and 29.8 % of BD patients did not have fatigue, but 41.2 % of MDD and 45.0 % of BD patients had fatigue, and 30.4 % of MDD and 25.2 % of BD patients had severe fatigue. Depression/anxiety severity was significantly correlated with fatigue. However, after controlling current psychiatric comorbidities, demographics, some social factors, and psychotropic use, only QIDS-16-SR scores were still significantly and positively correlated with IFS scores in both MDD and BD. Differential correlations between IFS scores and item scores of QIDS-16-SR in MDD and BD were observed., Limitation: Cross-sectional., Conclusions: In this outpatient sample, fatigue was highly prevalent in patients with MDD or BD. The independent association of depressive severity with the severity of fatigue highlights the importance of complete resolution of depressive symptoms in treating MDD and BD., Competing Interests: Declaration of competing interest Dr. Joseph R. Calabrese received federal funding from the Department of Defense, Health Resources Services Administration and National Institute of Mental Health as well as grant support from: Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc. (now Teva Pharmaceutical Industries Ltd.); Dainippon Sumitomo Pharma Co., Ltd.; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Eli Lilly and Company; Intra-Cellular Therapies, Inc.; Pfizer, Inc; H. Lundbeck A/S; Sunovion Pharmaceuticals Inc.; Takeda Pharmaceutical Company Limited. Dr. Calabrese has served as a consultant/advisory board member/speaker for: Abbott Laboratories; Allergan; AstraZeneca; Bristol-Myers Squibb Company; Cephalon, Inc. (now Teva Pharmaceutical Industries Ltd.); Dainippon Sumitomo Pharma Co., Ltd.; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; H. Lundbeck A/S,;Merck & Co., Inc.; Otsuka Pharmaceutical Co., Ltd.; Pfizer, Inc.; Repligen Corporation; Servier; Sunovion Pharmaceuticals Inc.; Solvay Pharmaceuticals, Inc.; Takeda Pharmaceutical Company Limited. Dr. Keming Gao was on a speakers bureau of AstraZeneca, Pfizer and Sunovion, and an advisory board of Sunovion and Otsuka, and received grant supports from AstraZeneca, Brain and Behavior Research Foundation, and Cleveland Foundation., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Patients with mood disorders commonly manifest comorbid psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). However, few studies have evaluated ADHD symptoms in this population. The current study aimed to explore the network structure of ADHD symptomology and identify central symptoms in patients with mood disorders. The Korean version of the Adult ADHD Self-Report Scale was used to assess the overall ADHD symptoms in 1,086 individuals diagnosed with mood disorders (major depressive disorder [n = 373], bipolar I disorder [n = 314], and bipolar II disorder [n = 399]). We used exploratory graph analysis to detect the number of communities, and the network structure was analyzed using regularized partial correlation models. We identified the central ADHD symptom using centrality indices. Network comparison tests were conducted with different subgroups of patients with mood disorders, including three mood diagnosis groups, between the patients who met the diagnostic criteria for ADHD [ADHD-suspected, n = 259] in their self-report and the others [ADHD-non-suspected, n = 827], and groups with high [n = 503] versus low [n = 252] levels of depressive state. The network analysis detected four communities: disorganization, agitation/restlessness, hyperactivity/impulsivity, and inattention. The centrality indices indicated that "feeling restless" was the core ADHD symptom. The result was replicated in the subgroup analyses within our clinically diverse population of mood disorders, encompassing three presentations: Patients with suspected ADHD, patients without suspected ADHD, and patients with a high depressive state. Our findings reveal that "feeling restless" is the central ADHD symptom. The treatment intervention for "feeling restless" may thus play a pivotal role in tackling ADHD symptoms in adult patients with mood disorders., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Hereditary angioedema (HAE) is a rare autosomal dominant disorder caused by the deficiency or dysfunction of C1 esterase inhibitors. We present a case of a female in her 50s with HAE and bipolar affective disorder (BPAD). She has experienced severe depressive and manic episodes with significant disruption to her life. She has also had potentially life-threatening episodes of recurrent angioedema with severe facial and body swelling and post-pharyngeal symptoms.She presented to us with a depressive episode with suicidal ideation. Her angioedema was flared by both psychological stressors and psychotropic medications. Choosing the correct mood stabiliser without triggering angioedema was a major challenge in her treatment. Also, psychosocial interventions and frequent liaison with her immunology team were necessary to provide her with optimum care in the community. Here, we discuss the challenges we faced and how we overcame them in managing this rare presentation of coexisting BPAD and HAE., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Childhood maltreatment, alexithymia and impulsivity are related to bipolar disorder (BD), but the role of potential underlying mechanisms of this link, such as extreme sensory processing, in BD are unclear. This study compared sensory processing patterns between individuals with BD-I or BD-II and between those with and without alexithymia and childhood maltreatment. Additionally, the study aimed to examine the role of extreme sensory processing in the relationship between childhood trauma, alexithymia and impulsivity with both depression and mania in a sample of hospitalized individuals with BD (n = 300). Participants completed self-report and clinician-rated scales. Patients with BD-II exceeded those with BD-I in low registration, sensory sensitivity and sensation avoidance, whereas patients with BD-I exhibited a more heightened sensation-seeking pattern. Patients with BD who had alexithymia and a history of childhood maltreatment exhibited more heightened sensory processing patterns, apart from sensory seeking, compared to those without alexithymia and childhood maltreatment. Additionally, the same pattern was more pronounced in individuals with BD who had both alexithymia and childhood maltreatment compared to those with either condition or neither of these conditions. The pathways from childhood maltreatment and alexithymia to depressive symptoms were mediated by low registration and sensation avoidance. Sensory seeking indirectly affected the link between alexithymia and manic symptoms. Childhood maltreatment and challenges in effectively processing emotional information, along with their related hypo- and hypersensitivity, may characterize BD individuals and its manifestation of depressive and manic symptoms., (© 2024 John Wiley & Sons Ltd.)

Background: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo., Methods: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures., Results: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups., Conclusions: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Anxiety comorbidity in bipolar disorder (BD) is important and thus significantly affects the course of BD and its outcomes. The treatment of generalized anxiety disorder comorbid with BD involves certain challenges, as antidepressant medications, which are standard in the treatment of anxiety disorder, have the risk of shifting to manic episodes and rapid cycling. In this case report, the response to agomelatine treatment in generalized anxiety disorder comorbid with bipolar 1 disorder was evaluated., Competing Interests: Conflicts of Interest and Source of Funding: The authors have no conflicts of interest to declare., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Psychiatric comorbidity is common in cancer patients, emphasizing the need for comprehensive care. While depressive symptoms in pancreatic cancer have been studied, there is limited attention given to manic symptoms. This case report aims to contribute to the knowledge of pancreatic cancer psychiatric comorbidities by describing a case of a patient with stage IV pancreatic cancer who presented a sudden onset manic episode. The patient, a 61-year-old male with stage IV pancreatic cancer, presented at the Emergency Room with abrupt behavioural changes suggestive of a manic episode of 2 weeks of evolution. The patient had been undergoing chemotherapy and short 3-day cycles of corticosteroids for the past 9 months but had been off this treatment for 20 days when the episode began. Acute organic causes were ruled out. The patient was admitted to the psychiatric unit, where organic screening was expanded and treatment with antipsychotics and a mood stabiliser was initiated with subsequent remission of symptoms after 2 weeks. This case shows a manic episode as a rare psychiatric complication in pancreatic cancer. In the literature reviewed, four other similar cases have been observed. Further research is needed to elucidate the underlying pathophysiology and explore possible treatment strategies., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The association between mood disorders, especially bipolar disorder (BD), and metabolic disorders, is long known. However, to which extent metabolic disorders affect the course of mood disorders in late life is still open to inquiring. To assess the impact of type 2 diabetes mellitus (T2DM) on late-life mood disorders a retrospective chart review was performed. Elderly depressive patients (≥ 65 years) diagnosed with Major Depressive Disorder (N = 57) or BD (N = 43) and followed up for at least 18 months were included and subdivided according to the presence of T2DM comorbidity. Vascular encephalopathy (39.1% vs. 15.6%, P  = 0.021) and neurocognitive disorders (21.7% vs. 5.2%, P  = 0.028), were more frequently reported in patients with T2DM than in those without. Patients with T2DM showed a greater percentage of follow-up time in manic episodes (r = -0.23, P  = 0.020) and a higher rate of manic episode(s) during follow-up (21.7% vs. 5.2%, P  = 0.028) than those without. When restricting longitudinal analyses to patients with bipolar spectrum disorders, results were confirmed. In line with the well-known connection between BD and metabolic disorders, our data support an association between T2DM and unfavorable course of illness in the elderly with BD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Fatigue is a multidimensional condition that may overlap with depression. Initial studies found that fatigue responds in only a limited way to standard monoaminergic antidepressants and mood stabilizers but does respond positively to intravenous (IV) racemic (R,S)-ketamine (ketamine). However, IV ketamine's use is limited by cost and access barriers. To date, no study has evaluated intranasal (IN) ketamine in individuals with fatigue. This study sought to evaluate the anti-fatigue effects of a single 50 mg dose of IN ketamine in individuals with major depressive disorder (MDD) or bipolar depression (BDep), both with and without comorbid alcohol use disorder (AUD)., Methods: Twenty-eight individuals with primary diagnoses of MDD or BDep I/II currently experiencing a depressive episode with active suicidality were enrolled; approximately 60 % had comorbid AUD. Changes in the NIH-Brief Fatigue Inventory (NIH-BFI) were assessed at baseline and at 4, 24, and 48 h post-treatment., Results: The group x time interaction for NIH-BFI score was significant (F = 3.44, p = 0.022), favoring IN ketamine over placebo. IN ketamine was well-tolerated with minimal adverse effects., Limitations: Limitations include the limited sample size, short duration, and single, fixed dose., Conclusions: IN ketamine appears to induce rapid anti-fatigue effects in individuals with severe MDD and BDep both with and without comorbid AUD. This suggests that IN ketamine holds potential as an alternative, rapid-acting, anti-fatigue option for different medical conditions., Competing Interests: Declaration of competing interest Dr. Machado-Vieira has received consulting fees from Eurofarma Pharmaceuticals, Abbott, and BioStrategies group; has research contracts with Boerhinger Ingelheim and Janssen Pharmaceuticals; has received speaker fees from Otsuka, EMS, and Cristalia; and is a member of the scientific boards of Symbinas Pharmaceuticals and Allergan. Dr. Machado-Vieira is also the PI for the following grants: NIH (R21HD106779 and R21MH129888), Milken Institute (BD-0000000081), Dr Machado-Vieira was PI for the Janssen 54135419TRD4005 study. Dr. Soares has served on the Advisory Board of Alkermes; as a Consultant for Boehringer, Johnson and Johnson, Livanova, and Sunovian; and received research grants from Compass Pathways, Mind Med, and Relmada. Dr. Zarate is listed as a co-inventor on a patent for the use of ketamine in major depression and suicidal ideation; as a co-inventor on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine, and other stereoisomeric dehydroxylated and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain; and as a co-inventor on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorder. He has assigned his patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. All other authors have no conflict of interest to disclose, financial or otherwise., (Copyright © 2024. Published by Elsevier B.V.)

Patients with cancer and pre-existing severe mental disorder, which include moderate to severe depression, bipolar disorder and schizophrenia, are known to have reduced life expectancy and are less likely to get recommended cancer treatment. Barriers at patient-, provider- and system level have been identified, e.g. lack of identification of psychiatric comorbidity, shortage of stabilising psychiatric symptoms and fragmentation of the healthcare system. Patient-centered, interdisciplinary and cross-sectorial healthcare interventions have shown a high potential to improve the cancer care, as argued in this review., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

Introduction: Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits., Methods: We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts., Results: Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05)., Conclusions: OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Miedlich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Sleep disturbance and impulsivity are key components of mood vulnerability in bipolar disorder (BD), but few studies have assessed the association between these two symptoms among patients with BD., Methods: Forty-seven euthymic patients with bipolar I disorder (BDI) or bipolar II disorder (BDII) and 58 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Trait impulsivity was measured using the Barratt Impulsiveness Scale Version 11 (BIS-11), which yielded 3 second-order factors: attention, motor, and non-planning. Subjective sleep quality was assessed using the self-reported Pittsburgh Sleep Quality Index (PSQI). General linear models (GLMs) were used to assess the associations between subjective poor sleep and trait impulsivity with multiple testing corrections., Results: Patients with BD scored higher in BIS-11 and PSQI than healthy controls. PSQI total scores positively correlated with BIS-11 total scores, while sleep disturbance and daytime dysfunction were associated with attentional impulsiveness after controlling for covariates. Participants with higher PSQI total scores (>10) had higher scores in BIS-11 total, attention, and non-planning than those with low PSQI scores (≤5)., Conclusion: These findings support the hypothesis that poor sleep quality might lead to impulsivity and add to the growing evidence that improving sleep quality may be a therapeutic target for patients with BD.

Psychosis can be considered a dimension that in its most severe extreme can be expressed with alterations in sensory perception, mainly hallucinations. Their presence is a fact that is frequently observed in severe psychiatric pathologies such as schizophrenia (EZQ) and bipolar disorder (BD) where they can be markers of severity. However, sensory-perceptual disturbances are not pathognomonic of these disorders, nor do they signal any of these illnesses as an isolated event. Such symptomatology can be described in a variety of situations both within and outside psychopathology. In this sense, proposing a direct line between hallucinations and diseases such as CZS or TB disregards their occurrence in other pathologies, as is the case of Borderline Personality Disorder (BPD). It is feasible that we may find the expression of pseudo hallucinations or hallucinations in patients with this disorder and their presence may have etiological, clinical and therapeutic connotations that should be reviewed and taken into account in our clinical practice., (CC BY NC ND)

Toxoplasma gondii is a neurotropic protozoan parasite that affects neuronal processing in the brain. This study aimed to investigate the prevalence of T. gondii infection in psychiatric disorder patients. We also investigated the potential association between sociodemographic, clinical manifestation, and behavior of Toxoplasma-seropositive patients with psychiatric disorders. Commercial ELISAs (IgG, IgM, and IgG avidity) using serum and PCR using buffy coat were performed on samples from 54 individuals in each of the following groups: patients diagnosed with depressive disorder, bipolar disorder, and schizophrenia, as well as psychiatrically healthy subjects (control group). They were recruited from the Hospital Universiti Sains Malaysia in Kelantan, Malaysia. Of 54 patients with depressive disorder, 24/54 (44.4 %) were seropositive for IgG, and four (16.7 %) were IgG+/IgM+. Among the latter, a high avidity index indicating a past infection was observed in half of the samples (50.0 %), and the other half (50.0 %) showed a low avidity index, indicating a possible recent infection. Meanwhile, 30/54 (55.6 %) patients with bipolar disorder were seropositive for IgG+, five (16.7 %) were IgG+/IgM+, and four of them had a high avidity index, and one had a low avidity index. Patients with schizophrenia showed 29/54 (53.7 %) seropositive for IgG, two of them (6.9 %) were IgG+/IgM+; one of latter had a high avidity index, and one had a low avidity index. Of 54 people in the control group, 37.0 % (20/54) were seropositive for T. gondii IgG antibodies. However, no significant difference was observed in seroprevalence between the control group and each patient group. No PCR-positive results were documented. A Chi-Square and multiple logistic regression showed that age (p = 0.031), close contact with cats/pets (p = 0.033) and contact with soil (p = 0.012) were significantly associated with Toxoplasma seropositivity in patients with psychiatric disorders. Additional research is needed to elucidate the causal relationships and underlying mechanisms., 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: Bipolar disorder (BD) is characterized by episodic mood dysregulation, although a significant portion of patients suffer persistent cognitive impairment during euthymia. Previous magnetic resonance imaging (MRI) research suggests BD patients may have accelerated brain aging, observed as lower grey matter volumes. How these neurostructural alterations are related to the cognitive profile of BD is unclear., Methods: We aim to explore this relationship in euthymic BD patients with multimodal structural neuroimaging. A sample of 27 euthymic BD patients and 24 healthy controls (HC) underwent structural grey matter MRI and diffusion-weighted imaging (DWI). BD patient's cognition was also assessed. FreeSurfer algorithms were used to obtain estimations of regional grey matter volumes. White matter pathways were reconstructed using TRACULA, and four diffusion metrics were extracted. ANCOVA models were performed to compare BD patients and HC values of regional grey matter volume and diffusion metrics. Global brain measures were also compared. Bivariate Pearson correlations were explored between significant brain results and five cognitive domains., Results: Euthymic BD patients showed higher ventricular volume (F(1, 46) = 6.04; p = 0.018) and regional grey matter volumes in the left fusiform (F(1, 46) = 15.03; pFDR = 0.015) and bilateral parahippocampal gyri compared to HC (L: F(1, 46) = 12.79, pFDR = 0.025/ R: F(1, 46) = 15.25, pFDR = 0.015). Higher grey matter volumes were correlated with greater executive function (r = 0.53, p = 0.008)., Limitations: We evaluated a modest sample size with concurrent pharmacological treatment., Conclusions: Higher medial temporal volumes in euthymic BD patients may be a potential signature of brain resilience and cognitive adaptation to a putative illness neuroprogression. This knowledge should be integrated into further efforts to implement imaging into BD clinical management., Competing Interests: Declaration of competing interest EV has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Angelini, Biogen, Boehringer-Ingelheim, Celon Pharma, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Janssen, Lundbeck, Merck, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work. Other authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Alcohol use disorder (AUD) is present in nearly half of individuals with bipolar disorder (BD) and is associated with markedly worsening outcomes. Yet, the concurrent treatment of BD and AUD remains neglected in both research and clinical care; characterizing their dynamic interplay is crucial in improving outcomes., Objective: To characterize the longitudinal alcohol use patterns in BD and examine the temporal associations among alcohol use, mood, anxiety, and functioning over time., Design, Setting, and Participants: This cohort study selected participants and analyzed data from the Prechter Longitudinal Study of Bipolar Disorder (PLS-BD), an ongoing cohort study that recruits through psychiatric clinics, mental health centers, and community outreach events across Michigan and collects repeated phenotypic data. Participants selected for the present study were those with a diagnosis of BD type I (BDI) or type II (BDII) who had been in the study for at least 5 years. Data used were extracted from February 2006 to April 2022, and follow-up ranged from 5 to 16 years., Main Outcomes and Measures: Alcohol use was measured using the Alcohol Use Disorders Identification Test. Depression, mania or hypomania, anxiety, and functioning were measured using the 9-Item Patient Health Questionnaire, the Altman Self-Rating Mania Scale, the 7-item Generalized Anxiety Disorder assessment scale, and the Life Functioning Questionnaire, respectively., Results: A total of 584 individuals (386 females (66.1%); mean [SD] age, 40 [13.6] years) were included. These participants had a BDI (445 [76.2%]) or BDII (139 [23.8%]) diagnosis, with or without a lifetime diagnosis of AUD, and a median (IQR) follow-up of 9 (0-16) years. More problematic alcohol use was associated with worse depressive (β = 0.04; 95% credibility interval [CrI], 0.01-0.07) and manic or hypomanic symptoms (β = 0.04; 95% CrI, 0.01-0.07) as well as lower workplace functioning (β = 0.03; 95% CrI, 0.00-0.06) over the next 6 months, but increased depressive and manic or hypomanic symptoms were not associated with greater subsequent alcohol use. These latter 2 associations were more pronounced in BDII than BDI (mania or hypomania: β = 0.16 [95% CrI, 0.02-0.30]; workplace functioning: β = 0.26 [95% CrI, 0.06-0.45]). Alcohol use was not associated with anxiety over time., Conclusions and Relevance: This study found that alcohol use, regardless of diagnostic status, was associated with mood instability and poorer work functioning in BD, but increased mood symptoms were not associated with subsequent alcohol use. Given its prevalence and repercussions, dimensional and longitudinal assessment and management of alcohol use are necessary and should be integrated into research and standard treatment of BD.

Competing Interests: All authors have disclosed no conflicts of interest.

Aims/hypothesis: The aim of this study was to compare cardiovascular risk management among people with type 2 diabetes according to severe mental illness (SMI) status., Methods: We used linked electronic data to perform a retrospective cohort study of adults diagnosed with type 2 diabetes in Scotland between 2004 and 2020, ascertaining their history of SMI from hospital admission records. We compared total cholesterol, systolic BP and HbA 1c target level achievement 1 year after diabetes diagnosis, and receipt of a statin prescription at diagnosis and 1 year thereafter, by SMI status using logistic regression, adjusting for sociodemographic factors and clinical history., Results: We included 291,644 individuals with type 2 diabetes, of whom 1.0% had schizophrenia, 0.5% had bipolar disorder and 3.3% had major depression. People with SMI were less likely to achieve cholesterol targets, although this difference did not reach statistical significance for all disorders. However, people with SMI were more likely to achieve systolic BP targets compared to those without SMI, with effect estimates being largest for schizophrenia (men: adjusted OR 1.72; 95% CI 1.49, 1.98; women: OR 1.64; 95% CI 1.38, 1.96). HbA 1c target achievement differed by SMI disorder and sex. Among people without previous CVD, statin prescribing was similar or better in those with vs those without SMI at diabetes diagnosis and 1 year later. In people with prior CVD, SMI was associated with lower odds of statin prescribing at diabetes diagnosis (schizophrenia: OR 0.54; 95% CI 0.43, 0.68, bipolar disorder: OR 0.75; 95% CI 0.56, 1.01, major depression: OR 0.92; 95% CI 0.83, 1.01), with this difference generally persisting 1 year later., Conclusions/interpretation: We found disparities in cholesterol target achievement and statin prescribing by SMI status. This reinforces the importance of clinical review of statin prescribing for secondary prevention of CVD, particularly among people with SMI., (© 2024. The Author(s).)

Objectives: Although free from characterized manic and depressive episodes, the euthymic period in bipolar disorder (BD) remains characterized by a whole host of difficulties, particularly relational. These difficulties are factors of vulnerabilities and relapses. People's perception of their own relationships has an impact on their symptomatology, their responses to treatment and on relapse rates. Young's early maladaptive schemas (EMS) approach proves to be relevant for understanding the construction of these perceptions and working on them. Nevertheless, to this date, few studies have investigated which EMS are related to relationship dysfunction in this particular population. Determining the link between EMS and relationship difficulties would be relevant to understand psychosocial impairment of people with BD in euthymic states. The present study aims to investigate the associations between the different domains of EMS and relationship dysfunction among patients with bipolar disorder in the euthymic phase., Methods: Data are extracted from the FACE-BD cohort, within the BD Expert Center in Versailles. Inclusion criteria were to be aged between 18 and 65 and to be an outpatient with a diagnosis of bipolar disorder (DSM-IV-TR). Patients had to be euthymic at the time of inclusion, according to DSM-IV-TR criteria with a cut-off score of 14 on the Montgomery-Asberg Depression Rating Scale and the Young Mania Rating Scale. Non-inclusion criteria were meeting at the time of the study the criteria for characteristic depressive episode, hypomania or mania according to the DSM-IV-TR. Sociodemographic data, clinical features associated with relationship dysfunction were assessed. EMS and EMS domains were assessed with the YSQ-R short form (Young Schema Questionnaire 3 Short Form) and current relationship dysfunction were assessed with the FAST (Functioning assessment short test subscale). Successive simple linear regression analyses were performed to investigate the association between the severity scores of each EMS and the intensity of relationship dysfunction. Furthermore, successive simple linear regression analyses investigated the association between EMS domain scores and intensity of relationship dysfunction. Multiple linear regression analyses were performed to test the association between EMS scores, then EMS domains, and the intensity of relationship dysfunction after adjusting for age as well as the intensity of residual depressive and manic symptoms., Results: Relationship dysfunction is partly associated with EMS activation in particular in the separation and rejection domain (P<0.0001), the other-directedness domain (P=0.031) and the over-vigilance and inhibition domain (P=0.005). Having residual depressive symptoms is also among the factors contributing to the relationship dysfunctions of people with bipolar disorder in the euthymic phase., Discussion: This is the first study demonstrating that the activation of several domains of EMS is a risk factor of relationships difficulties for people in euthymic phase of bipolar disorder. It is necessary to identify which EMS are specifically activated and their domains of belonging in order to prevent and reduce them. EMS are a lever for functional remission. It is therefore relevant to refer people reporting relationship problems to schema therapy consistent with a personalized care. Finally, future studies should focus on the mechanisms underlying the complex relationship between EMS domains and relationship dysfunction in people with bipolar disorder in the euthymic phase. It may also be relevant for future research to control for different types of relationship dysfunction. EMS may be differentially associated with several types of interpersonal problems. The relations between different adaptation styles and EMS should be further investigated to offer more personalized care, with the aim to improve functional remission., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Myelinolysis is a neurological condition that can display diverse psychiatric symptoms, with electrolyte imbalance, alcoholism and malnutrition being the frequent causes. Rapid correction of hyponatremia may trigger pontine and extra-pontine myelinolysis., Cases: This paper examines two cases: one of hyponatremia after antihypertensive use and the other of myelinolysis due to rapid correction of hyponatremia. Since myelinolysis appeared as a manic episode, the patients sought treatment at the psychiatry outpatient clinic. Further tests were conducted to rule out organic causes and the diagnosis was confirmed prior to referring the patients to the neurology clinic., Conclusion: Psychiatrists should be meticulous in excluding organic causes in first-episode mania and consider these possibilities in the differential diagnosis for the pertinent patient group., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patients with bipolar disorder (BD) show abnormalities in glucolipid metabolism and reproductive hormone levels, which are of concern in women with BD. This study was dedicated to investigating the glucolipid and reproductive hormone levels of female patients, and to preliminarily investigating their relationships with cognition., Methods: A total of 58 unmedicated female BD patients, 61 stable-medicated female BD patients, and 63 healthy controls (HC) were recruited in this study. Serum glycolipid indexes and reproductive hormones were measured. Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (Stroop test)., Results: Patients with BD showed significant cognitive impairment (p < 0.05), which was not affected by medication. Triglycerides (TG), luteinizing hormone (LH), and high-density lipoprotein cholesterol (HDL-c) were altered in stable-medicated BD patients. In addition, regression analysis showed that progesterone (PRGE) and prolactin (PRL) were negatively associated with cognitive performance in stable-medicated BD patients., Conclusions: Female BD patients may have cognitive deficits and abnormal levels of glycolipids and reproductive hormones. And abnormal levels of glycolipids and reproductive hormones may be associated with cognitive dysfunction in female BD patients., (© 2024. The Author(s).)

Background: Recent evidences have shown sex-differential cognitive deficits in bipolar disorder (BD) and differences in cognitions across BD subtypes. However, the sex-specific effect on cognitive impairment in BD subtype II (BD-II) remains obscure. The aim of the current study was to examine whether cognitive deficits differ by gender in youth with BD-II depression., Method: This cross-sectional study recruited 125 unmedicated youths with BD-II depression and 140 age-, sex-, and education-matched healthy controls (HCs). The Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess cognitive functions. Mood state was assessed using the 24-item Hamilton Depression Rating Scale (24-HDRS) and the Young Mania Rating Scale (YMRS). Multivariate analysis of covariance (MANCOVA) was conducted., Result: ​Compared with HCs, patients with BD-II depression had lower scores on MCCB composite and its seven cognitive domains (all p < 0.001). After controlling for age and education, MANCOVA revealed significant gender-by-group interaction on attention/vigilance (F = 6.224, df = 1, p = 0.013), verbal learning (F = 9.847, df = 1, p = 0.002), visual learning (F = 4.242, df = 1, p = 0.040), and composite (F = 8.819, df = 1, p = 0.003). Post hoc analyses suggested that males performed worse in the above-mentioned MCCB tests than females in BD-II depression., Conclusion: Our study demonstrated generalized cognitive deficits in unmedicated youths with BD-II depression. Male patients performed more serious cognitive impairment on attention/vigilance, verbal learning, and visual learning compared to female patients., (© 2024. The Author(s).)

Recent findings link cognitive impairment and inflammatory-immune dysregulation in schizophrenia (SZ) and bipolar (BD) spectrum disorders. However, heterogeneity and translation between the periphery and central (blood-to-brain) mechanisms remains a challenge. Starting with a large SZ, BD and healthy control cohort (n = 1235), we aimed to i) identify candidate peripheral markers (n = 25) associated with cognitive domains (n = 9) and elucidate heterogenous immune-cognitive patterns, ii) evaluate the regulation of candidate markers using human induced pluripotent stem cell (iPSC)-derived astrocytes and neural progenitor cells (n = 10), and iii) evaluate candidate marker messenger RNA expression in leukocytes using microarray in available data from a subsample of the main cohort (n = 776), and in available RNA-sequencing deconvolution analysis of postmortem brain samples (n = 474) from the CommonMind Consortium (CMC). We identified transdiagnostic subgroups based on covariance between cognitive domains (measures of speed and verbal learning) and peripheral markers reflecting inflammatory response (CRP, sTNFR1, YKL-40), innate immune activation (MIF) and extracellular matrix remodelling (YKL-40, CatS). Of the candidate markers there was considerable variance in secretion of YKL-40 in iPSC-derived astrocytes and neural progenitor cells in SZ compared to HC. Further, we provide evidence of dysregulated RNA expression of genes encoding YKL-40 and related signalling pathways in a high neuroinflammatory subgroup in the postmortem brain samples. Our findings suggest a relationship between peripheral inflammatory-immune activity and cognitive impairment, and highlight YKL-40 as a potential marker of cognitive functioning in a subgroup of individuals with severe mental illness., 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 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Although individuals with a family history of alcohol use disorder (AUD) have a superior antidepressant response to ketamine, outcomes in patients with current AUD remain unclear. This study sought to investigate whether intranasal (IN) racemic ( R,S )-ketamine had antisuicidal and antidepressant effects in unipolar and bipolar depression and whether comorbid AUD conferred superior antisuicidal outcomes for patients., Methods: This was a double-blind, randomized, placebo-controlled trial (May 2018 to January 2022) of single administration, fixed-dose (50 mg) IN ( R,S )-ketamine (or saline comparator) in unmedicated inpatients meeting Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition, Text Revision, criteria for a current major depressive episode (bipolar or unipolar), with current suicidal ideation (SI) and past attempt. Patients with and without comorbid AUD were enrolled. Change in Scale for Suicide Ideation score was the primary outcome measure, and change in Montgomery-Åsberg Depression Rating Scale score was the secondary outcome measure., Results: No significant group × time effect was noted for SI ( F = 1.1, P = .36). A statistical trend toward superior improvement in suicidality was observed in participants with comorbid AUD. The group × time interaction was significant for improvements in depression ( F = 3.06, P = .03) and largely unaffected by comorbid AUD or primary mood disorder type. Within the ketamine group, a significant correlation was observed between improvement in depressive symptoms and SI for patients without comorbid AUD ( r =0.927, P = .023) that was absent in patients with AUD ( r = 0.39, P = .44)., Conclusion: IN ketamine induced rapid antidepressant effects compared to placebo but did not significantly alter SI scores. The treatment was well tolerated. Continued investigation with IN ketamine as a practical alternative to current formulations is warranted., Trial Registration: ClinicalTrials.gov identifier: NCT03539887., (© Copyright 2024 Physicians Postgraduate Press, Inc.)

It has long been speculated that psychedelic use could provoke the onset of psychosis, but there is little evidence to support this conjecture. Using a longitudinal research design with samples representative of the US and UK adult populations with regard to sex, age, and ethnicity (n = 9732), we investigated associations between psychedelic use and change in the number of psychotic symptoms during the two-month study period. In covariate-adjusted regression models, psychedelic use during the study period was not associated with a change in the number of psychotic symptoms unless it interacted with a personal or family history of bipolar disorder, in which case the number of symptoms increased, or with a personal (but not family) history of psychotic disorders, in which case the number of symptoms decreased. Taken together, these findings indicate that psychedelic use may affect psychotic symptoms in individuals with a personal or family history of certain disorders characterized by psychotic symptomatology., Competing Interests: Declaration of competing interest PSH has been in paid advisory relationships with the following organizations regarding the development of psychedelics and related compounds: Bright Minds Biosciences Ltd., Eleusis Benefit Corporation, Journey Colab Corporation, Reset Pharmaceuticals Inc., and Silo Pharma. OS was a co-founder of Eudelics AB. Alexander Lebedev is a co-founder of Katharsis Journeys AB., (Copyright © 2024. Published by Elsevier B.V.)

Background: Insomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients., Methods: A total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected., Results: The results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea-hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects., Conclusion: This study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Major depressive disease (MDD), schizophrenia (SCZ), and bipolar disorder (BD) are common psychiatric disorders, and their relationship with thyroid cancer has been of great interest. This study aimed to investigate the potential causal effects of MDD, SCZ, BD, and thyroid cancer., Methods: We used publicly available summary statistics from large-scale genome-wide association studies to select genetic variant loci associated with MDD, SCZ, BD, and thyroid cancer as instrumental variables (IVs), which were quality controlled and clustered. Additionally, we used three Mendelian randomization (MR) methods, inverse variance weighted (IVW), MR-Egger regression and weighted median estimator (WME) methods, to estimate the bidirectional causal relationship between psychiatric disorders and thyroid cancer. In addition, we performed heterogeneity and multivariate tests to verify the validity of the IVs., Results: We used two-sample bidirectional MR analysis to determine whether there was a positive causal association between MDD and thyroid cancer risk. The results of the IVW analysis (OR = 3.956 95% CI = 1.177-13.299; P = 0.026) and the WME method (OR = 5.563 95% CI = 0.998-31.008; P = 0.050) confirmed that MDD may increase the risk of thyroid cancer. Additionally, our study revealed a correlation between genetic susceptibility to SCZ and thyroid cancer (OR = 1.532 95% CI = 1.123-2.088; P = 0.007). The results of the WME method analysis based on the median estimate (OR = 1.599 95% CI = 1.014-2.521; P = 0.043) also suggested that SCZ may increase the risk of thyroid cancer. Furthermore, our study did not find a causal relationship between BD and thyroid cancer incidence. In addition, the results of reverse MR analysis showed no significant causal relationships between thyroid cancer and MDD, SCZ, or BD (P > 0.05), ruling out the possibility of reverse causality., Conclusions: This MR method analysis provides new evidence that MDD and SCZ may be positively associated with thyroid cancer risk while also revealing a correlation between BD and thyroid cancer. These results may have important implications for public health policy and clinical practice. Future studies will help elucidate the biological mechanisms of these associations and potential confounders., (© 2024. The Author(s).)

Background: Bipolar disorder (BD) is a severe mental disorder with heavy disease burden. Females with BD are special populations who suffer a lot from childhood trauma, social support, cognitive deficits, and suicidality. In this study, the relationship among childhood trauma, social support, and clinical symptoms of BD was investigated and the risk factors for suicidality were explored in female patients with BD., Methods: This study included 57 drug-naive female BD patients, 64 female BD patients with long-term medication, and 50 age-matched female healthy controls. Childhood trauma, social support, clinical symptoms, cognition, and suicidality (suicide ideation, suicide plan, suicide attempt, suicide frequency) were measured with scales., Results: Compared with healthy controls, females with BD showed higher levels of childhood trauma and suicidality, and lower levels of social support and cognitive deficits. In the drug-naïve BD group, social support mediated the relationship between childhood trauma and insomnia symptoms (indirect effect: ab = 0.025). In the BD with long-term medication group, mania symptom was associated with suicide plan (OR = 1.127, p = 0.030), childhood trauma was associated with suicide attempt (OR = 1.088, p = 0.018), and years of education (OR = 0.773, p = 0.028), childhood trauma (OR = 1.059, p = 0.009), and delayed memory (OR= 1.091, p= 0.016) was associated with suicide frequency (OR = 1.091, p = 0.016)., Conclusions: This study provides initial evidence that social support partially explains the relationship between childhood trauma and clinical symptoms in females with BD. Additionally, mania symptoms, childhood trauma, and delayed memory were risk factors for suicidality. Interventions providing social support and improving cognitive function may be beneficial for females with BD who are exposed to childhood trauma and with high suicide risk., (© 2024. The Author(s).)

Objective: Drug addiction is a chronic mental disorder that significantly impacts all aspects of an individual's life, and substance use disorder in patients with bipolar disorder. The objective of this study is to assess the frequency of substance abuse among patients with bipolar spectrum disorder., Method: This cross-sectional study evaluated the frequency of bipolar spectrum disorder in patients taking methadone through various screening measures, including Mini Mental State Examination (MMSE), DSM IV criteria, Mood Disorders Questionnaire (MDQ), Goodwin and Ghaemi's criteria, and Akiskal classification for bipolar disorders., Results: Out of the total 197 participants in the study, 77 were identified as individuals engaging in poly-substance abuse. The investigation assessed the frequency of bipolar spectrum disorder based on various diagnostic criteria: 24% according to DSM-IV criteria, 29.9% using MDQ, 29.9% based on Ghaemi and Goodwin's criteria, and the highest rate at 48.2% when applying Akiskal's classification., Conclusions: This study highlights the high frequency of bipolar disorder among individuals with substance use disorder, especially those with concomitant depression. Therefore, it is crucial to pay special attention to individuals with substance use disorder with co-existing bipolar disorder.

Objective: Symptomatic overlap between dissociation and psychosis is well documented; however, the pathogenesis of these two phenomena might be distinct. Few studies have analyzed the relation of dissociative and psychotic symptoms transdiagnostically. The current study examines an emerging trauma-dissociation theoretical model that accounts for psychotic symptoms across affective disorders and schizophrenia (SCZ)., Method: Psychiatric inpatients with DSM-5 major depressive disorder (MDD), bipolar disorders (BD) currently in a major depressive episode, and SCZ, and healthy controls (HC) were recruited. Potentially traumatizing events in childhood, dissociative symptoms, and psychotic symptoms were assessed. In addition to participant's self-report, dissociative and psychotic symptoms were rated by psychiatrists blind to the hypothesis. Path analysis was conducted., Results: Dissociation was commonly experienced by clinical participants, particularly for those with MDD or BD. For the SCZ group, ratings of dissociation differed between patient and clinician; specifically, patient-reported dissociation scores, but not clinician-rated scores, were higher than that of the HC group. Importantly, the links between childhood trauma, dissociation, and psychotic symptoms were not homogenous across the diagnostic groups. Dissociation mediated the relationship between childhood trauma and psychotic symptoms in the MDD and BD groups, but not the SCZ group., Conclusion: Depending on the psychiatric condition, dissociation and psychosis have different clinical implications. Childhood trauma and dissociation provide an account for psychotic symptoms in patients diagnosed with MDD and BD, but not with SCZ. (PsycInfo Database Record (c) 2024 APA, 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.)

Background: Two established staging models outline the longitudinal progression in bipolar disorder (BD) based on episode recurrence or inter-episodic functioning. However, underlying neurobiological mechanisms and corresponding biomarkers remain unexplored. This study aimed to investigate if global and (sub)cortical brain structures, along with brain-predicted age difference (brain-PAD) reflect illness progression as conceptualized in these staging models, potentially identifying brain-PAD as a biomarker for BD staging., Methods: In total, 199 subjects with bipolar-I-disorder and 226 control subjects from the Dutch Bipolar Cohort with a high-quality T1-weighted magnetic resonance imaging scan were analyzed. Global and (sub)cortical brain measures and brain-PAD (the difference between biological and chronological age) were estimated. Associations between individual brain measures and the stages of both staging models were explored., Results: A higher brain-PAD (higher biological age than chronological age) correlated with an increased likelihood of being in a higher stage of the inter-episodic functioning model, but not in the model based on number of mood episodes. However, after correcting for the confounding factors lithium-use and comorbid anxiety, the association lost significance. Global and (sub)cortical brain measures showed no significant association with the stages., Conclusions: These results suggest that brain-PAD may be associated with illness progression as defined by impaired inter-episodic functioning. Nevertheless, the significance of this association changed after considering lithium-use and comorbid anxiety disorders. Further research is required to disentangle the intricate relationship between brain-PAD, illness stages, and lithium intake or anxiety disorders. This study provides a foundation for potentially using brain-PAD as a biomarker for illness progression.

Objectives: Identification of comorbid attention-deficit/hyperactivity disorder (ADHD) in patients with bipolar disorder (BD) is complicated by overlapping cognitive symptoms and methodological challenges. This cross-sectional study investigated whether virtual reality (VR)-based cognitive assessment that mimics daily life cognitive challenges can aid in the detection of sustained attention impairment in BD individuals with comorbid ADHD (BD + ADHD)., Methods: Forty-nine fully or partially remitted outpatients with BD, of whom 14 (24%) had BD + ADHD, were assessed with the Cognition Assessment in Virtual Reality (CAVIR) test, including a sustained attention test that involves distractions, and the Screen for Cognitive Impairment in Psychiatry (SCIP). Patients were also rated for mood symptoms and functioning and completed questionnaires assessing subjective cognition and quality of life. Patients' cognitive impairment on the SCIP was estimated with reference to n  = 100 demographically comparable healthy control participants., Results: BD + ADHD participants exhibited more pronounced performance deficits on the CAVIR sustained attention test ( t (48) = 2.15, p = .037, d = .66). Notably, deficits on this test were proportional to self-reported daily life concentration difficulties in BD + ADHD individuals. Exploratory analyses revealed that BD + ADHD participants also displayed greater impairment on the SCIP working memory- and delayed verbal learning subtests and greater subjective cognitive complaints than BD patients without this comorbidity (p-levels < .001), but only the difference in subjective cognition survived correction for multiple comparisons ( F (1,47) = 14.13, p = .005, np2  = 0.24)., Conclusion: Screening for deficits in sustained attention with an ecologically valid VR test involving distracting stimuli may be useful for identifying BD + ADHD individuals.

This study aims to investigate the relationship between different phases of bipolar disorder (depressive, manic, and euthymic) and myocardial deformation, assessed by echocardiography, compared to healthy controls. It seeks to elucidate whether these phases of bipolar disorder are associated with different myocardial strain patterns, thus contributing to the understanding of cardiovascular implications in bipolar disorder. A cross-sectional design was employed at Dursun Odabaş Medical Centre, Psychiatry Clinic of Van Yüzüncü Yl University. The study enrolled 200 participants, divided into 4 groups: 50 in a depressive phase, 50 in a manic phase, 50 in an euthymic phase of bipolar disorder, and 50 healthy volunteers. Participants underwent detailed electrocardiographic and ECG evaluations, focusing on myocardial strain patterns and cardiac function. Statistical analyses, including ANOVA and chi-square tests, were used to compare the groups. Significant differences in global longitudinal strain (GLS) values were observed between the groups. The manic phase group exhibited the highest GLS (21.51), followed by the euthymic (20.75), depressive (20.25), and healthy control groups (19.0). The E/A ratio of the mitral valve also varied, with the manic group displaying the highest ratio (1.21). Other echocardiographic parameters such as left atria size and Ejection Fraction also differed significantly between the groups. The study concluded that the phases of bipolar disorder are associated with distinct myocardial strain patterns, as evidenced by the variation in GLS values. The findings underscore the importance of cardiac monitoring in bipolar disorder, suggesting potential cardiac risks, particularly during the manic phase. This study advocates integrated care approaches, combining psychiatric and cardiac evaluations for patients with bipolar disorder., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hemorrhoids and psychiatric disorders exhibit high prevalence rates and a tendency for relapse in epidemiological studies. Despite this, limited research has explored their correlation, and these studies are often subject to reverse causality and residual confounding. We conducted a Mendelian randomization (MR) analysis to comprehensively investigate the association between several mental illnesses and hemorrhoidal disease., Methods: Genetic associations for four psychiatric disorders and hemorrhoidal disease were obtained from large consortia, the FinnGen study, and the UK Biobank. Genetic variants associated with depression, bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease at the genome-wide significance level were selected as instrumental variables. Screening for potential confounders in genetic instrumental variables using PhenoScanner V2. Bidirectional MR estimates were employed to assess the effects of four psychiatric disorders on hemorrhoidal disease., Results: Our analysis revealed a significant association between genetically predicted depression and the risk of hemorrhoidal disease (IVW, OR=1.20,95% CI=1.09 to 1.33, P <0.001). We found no evidence of associations between bipolar disorder, anxiety disorders, schizophrenia, and hemorrhoidal disease. Inverse MR analysis provided evidence for a significant association between genetically predicted hemorrhoidal disease and depression (IVW, OR=1.07,95% CI=1.04 to 1.11, P <0.001)., Conclusions: This study offers MR evidence supporting a bidirectional causal relationship between depression and hemorrhoidal disease., (© 2024. The Author(s).)

Bipolar disorder and borderline personality disorder commonly co-occur. Each disorder is associated with substantial morbidity and mortality, which are worsened by co-occurrence of the disorders. Emotional dysregulation, suicidality, and disrupted circadian rhythm are key aspects of psychopathology associated with both conditions. A novel psychotherapy combining elements of two evidence-based treatments (i.e., dialectical behavior therapy [DBT] for borderline personality disorder and social rhythm therapy [SRT] for bipolar disorder) is described. Unlike either treatment alone, the new therapy, called dialectical behavior and social rhythm therapy (DBSRT), targets all three disease-relevant processes and therefore may represent a promising new approach to treatment for individuals with these two conditions. DBSRT may also have utility for individuals with overlapping characteristics of bipolar disorder and borderline personality disorder or for those whose illness manifestation includes a mix of bipolar and borderline personality disorder traits. Strategies associated with DBSRT are described, and a brief case vignette illustrates its application., Competing Interests: Dr. Swartz is Editor of the journal; she reports receiving royalties from UpToDate (Wolters Kluwer) and the American Psychiatric Association and has served as a consultant to the Clinical Education Alliance, Intra-Cellular Therapies, Mediflix, Medscape (Internet Brands/WebMD), and Physicians Postgraduate Press. The other authors report no financial relationships with commercial interests. Lisa O’Donnell served as decision editor during peer review of the manuscript.

Objective: The aim of this study is to evaluate the discrepancy between objective cognitive measures and cognitive subjective complaints in a sample of euthymic patients with bipolar disorder (BD)., Methods: One hundred and sixteen participants (83 euthymic patients with BD and 33 healthy controls) were enrolled for this study. Patients were assessed with a comprehensive neuropsychological battery and they also reported their subjective cognitive complaints with the Cognitive Complaints in Bipolar Disorder Rating Scale (COBRA). The discrepancy between objective and subjective data was calculated using a novel methodology proposed in a previous study (Miskowiak, 2016). Statistical analyses included Pearson correlations and multiple linear regression., Results: Higher number of previous depressive episodes was identified as one variable associated with the global sensitivity composite score (Beta = 0.25; t = 2.1; p = 0.04) and with the verbal learning and memory sensitivity score (Beta = 0.26; t = 2.16; p = 0.03). That is, patients with more previous depressive episodes tend to over-report cognitive complaints. In contrast, higher number of previous hospitalizations was associated with stoicism in the global total score (Beta = -0.27; t = -2.24: p = 0.029) and in the domain of attention/processing speed (Beta = -0.34; t = -2.52; p = 0.016), indicating patients with more hospitalizations tend to report less cognitive complaints., Discussion: Our study identified some factors that might help to explain the discrepancy between objective and subjective cognitive measures in BD, including number of previous depressive episodes and number of previous hospitalizations. This highlights the need of the combined use of both types of cognitive measures to make an accurate assessment of cognitive dysfunctions and their effective treatment., Competing Interests: Declaration of competing interest EV has received grants and served as consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Angelini, Biogen, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, Idorsia, Janssen, Lundbeck, Medincell, Novartis, Orion Corporation, Organon, Otsuka, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, and Viatris, outside the submitted work; DHM has received CME-related honoraria and served as consultant for Abbott, Angelini, Ethypharm Digital Therapy and Janssen-Cilag, with no financial or other relationship relevant to the subject of this article. All authors report no financial or other relationship relevant to the subject of this article., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Treating depressive symptoms in patients with schizophrenia is challenging. While transcranical Dicrect Current Stimulation (tDCS) improved other core symptoms of schizophrenia, conflicting results have been obtained on depressive symptoms. Thus, we aimed to expand current evidence on tDCS efficacy to improve depressive symptoms in patients with schizophrenia., Methods: A double-blind RCT was performed with patients randomized to 2 mA active-tDCS or sham-tDCS (15 daily sessions) with a bilateral bipolar-nonbalanced prefrontal placement (anode: left Dorsolateral prefrontal cortex; cathode: right orbitofrontal region). Clinical outcomes included variations of Calgary Depression Scale for Schizophrenia total score (CDSS) and of Depression-hopelessness and Guilty idea of reference-pathological guilt factors. Analysis of covariance was performed evaluating between-group changes over time. The presence/absence of probable clinically significant depression was determined when CDSS > 6., Results: As 50 outpatients were included (both groups, n = 25), significant improvements following active-tDCS were observed for CDSS total score (p = 0.001), Depression-hopelessness (p = 0.001) and Guilty idea of reference-pathological guilt (p = 0.03). Considering patients with CDSS>6 (n = 23), compared to sham, active-tDCS significantly improved CDSS total score (p < 0.001), Depression-hopelessness (p = 0.001) but Guilty idea of reference-pathological guilt only marginally improved (p = 0.051). Considering response rates of clinically significant depression, important reductions of CDSS score were observed (78 % of the sample scored ≤6; active-tDCS, n = 23; sham-tDCS, n = 16; p = 0.017). Early wakening item did not significantly change in any group., Limitations: The study lacks a follow-up period and evaluation of tDCS effects on psychosocial functioning., Conclusions: Bilateral bipolar-nonbalanced prefrontal tDCS is a successful protocol for the treatment of depressive symptoms in patients with schizophrenia., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

More than 25 years after being diagnosed with bipolar disorder and receiving continuous treatment with lithium, a woman develops Takotsubo syndrome., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An increasing number of adults over 60 years old are presenting with requests for treatment of attention-deficit/hyperactivity disorder (ADHD). However, the prevalence of ADHD in older adults in geriatrics is unknown. Further, comorbid bipolar disorder and adult ADHD are likely underrecognized with many patients only receiving treatment for one of these conditions. The occurrence of bipolar disorder with geriatric onset ADHD is unknown., Case Presentation: A 64-year-old Hispanic woman with a psychiatric history of bipolar I disorder (diagnosed in early adulthood) was diagnosed with ADHD suspected of geriatric onset, and able to be successfully managed on concurrent mood stabilizers and psychostimulant medication., Conclusions: The findings of this case report emphasize the importance of appropriately recognizing and treating comorbid ADHD and bipolar disorder in any age group, including the geriatric population for which this occurrence appears to be very rare. Additionally, this case report demonstrates the safe utilization of psychostimulant medications in a geriatric patient with bipolar disorder without inducing a manic episode or other significant adverse reactions., (© 2024. The Author(s).)

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.)

Background: The goal of this study was to assess psychosocial functioning in older patients with bipolar I disorder compared with healthy subjects and to identify the psychopathological factors associated with poor functioning in patients., Methods: We recruited 68 euthymic patients with bipolar I disorder from the outpatient unit and 89 healthy controls who were older than 50 years of age. In addition to clinical variables, we used other standardized measures, including the Young Mania Rating Scale, the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, the Functional Assessment Short Test, and the Montreal Cognitive Assessment., Results: Older patients with bipolar I disorder had poorer psychosocial functioning in general and in the domains of occupation, autonomy, and cognition than the healthy controls on the basis of previously defined Functional Assessment Short Test cutoff scores. We found that 35.3% (95% CI: 23%-47%) of the patients did not have clinically significant functional impairment, 38.2% (95% CI: 26%-50%) had mild impairment, and 26.5% (95% CI: 16%-37%) had moderate impairment. Depressive symptoms and impaired cognition were associated with poor overall functioning., Conclusions: The level of psychosocial functioning was heterogeneous among the patients. Subsyndromal depressive symptoms, even at low levels, and impaired cognition predicted poor functioning in euthymic middle-aged and older patients with bipolar I disorder., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Major depressive disorder (MDD) and bipolar disorder (BD) are commonly comorbid with eating disorders (EDs). However, there is limited data about the clinical features of such patients, especially their association with traumatic histories and PTSD, which occur commonly in patients admitted to residential treatment., Methods: Adults (≥18 years, 91% female, n = 2155) admitted to residential ED treatment were evaluated upon admission for DSM-5 defined MDD and BD. Patients were divided into three groups based on an admission diagnosis of no mood disorder (NMD), MDD, and BD (types I and II) and compared on a number of demographic variables, clinical features and assessments., Results: Mood disorders occurred in 76.4% of participants. There were statistically significant differences across groups in most measures with the BD group showing higher rates and doses of traumatic events; higher current PTSD; higher BMIs; higher severity of ED, depression and state-trait anxiety symptoms; worse quality of life; and higher rates of substance use disorders. Similarly, the MDD group had higher rates than the NMD group on most measures., Conclusions: These findings have important implications for prevention, treatment and long-term follow-up and highlight the need for early trauma-focused treatment of ED patients with comorbid mood disorders and PTSD., (© 2023 Eating Disorders Association and John Wiley & Sons Ltd.)