Substance use disorders (SUD) frequently occur alongside bipolar disorder (BD), with some studies indicating a 29 % comorbidity rate in Western populations [1]. The relationship between BD and SUD is intricate and bidirectional - drug misuse can increase the risk of developing BD, and individuals with BD have a higher risk of developing SUD. This complex interplay often leads to earlier BD onset, more hospitalizations, and reduced effectiveness of pharmacological treatments, particularly mood stabilizers. This work aims to describe the impact of drugs in the risk of relapse in BD and to approach the differences in the evolution in substance users compared to non-users.

We conducted a prospective cohort study including the patients admitted to Hospital Clínic of Barcelona acute psychiatric unit with the diagnosis of manic or mixed episode during the period between 2015 and 2019. We established a follow-up of 3 years from the date of admission in which hospital readmissions are examined.

The study, which included 279 patients, concluded that only tobacco users showed significantly higher rates of emergency room (ER) visits and hospital readmissions in the period study, while cannabis was only associated with earlier onset of illness, current manic polarity, the presence of psychotic symptoms and a higher likelihood of discontinuing treatment. Alcohol, cocaine and stimulants did not appear to have an association with the variables studied.

Lack of follow-up information from people leaving the region or changing to private sector services, lack of detailed information around the pattern and history of consumption.

Tobacco seemed to have a clear negative association with the course of the illness. Cannabis, while its use was not associated with the relapse rate, was indirectly associated with variables suggesting a more severe symptomatology and a possible qualitatively different course of illness. More evidence is needed to define the mechanisms and patterns related to these effects.

Despite advances in psychiatric treatment, individuals with schizophrenia (SZ) and bipolar disorder (BD) continue to experience alarmingly high suicide rates. Clozapine, lithium, and valproate are medications that may potentially reduce suicide in these populations, but evidence is limited and often inconsistent. This study aimed to evaluate the anti-suicidal effectiveness of these medications using a nationwide health insurance database in South Korea. A retrospective cohort study was conducted using data from the National Health Information Database. This study included 102,540 patients with SZ and 96,336 patients with BD diagnosed between 2007 and 2010. We assessed the association between suicide mortality and recent prescriptions of clozapine, lithium, and valproate, as well as other psychotropic drugs. Suicide hazard ratios (HR) were calculated using a time-dependent Cox regression analysis. Suicide rates per 100,000 person-years were 308.0 for SZ and 285.1 for BD. After adjustment for confounders, lithium and valproate prescriptions were associated with significantly lower suicide hazard ratios in both SZ (HR of lithium: 0.58, 95 % CI: 0.46-0.72; HR of valproate: 0.61, 95 % CI: 0.52-0.71) and BD (HR of lithium: 0.54, 95 % CI: 0.44-0.65; HR of valproate: 0.66, 95 % CI: 0.57-0.76). Clozapine was associated with a lower suicide hazard in patients with SZ but remained statistically non-significant. Lithium and valproate have significant anti-suicidal effects in patients with SZ and BD, underscoring the potential role of mood stabilizers in suicide prevention among them.

Major depressive disorder (MDD), bipolar disorder, and schizophrenia involve disruptions in processing rewarding stimuli. In this review, we propose that distinct mechanistic pathways underlie these disruptions in mood disorders versus schizophrenia, and we highlight the importance of understanding these differences for developing personalized treatments. We summarize evidence suggesting that reward processing abnormalities in mood disorders are driven by dysregulated motivational systems; MDD is characterized by blunted responses to reward cues, and bipolar disorder is characterized by heightened responses. In contrast, we argue that reward processing disruptions in schizophrenia do not reflect abnormalities in motivation or hedonic experience; rather, they reflect impairments in the cognitive representation of past and future rewards as well as misdirected attention to irrelevant stimuli. To integrate these findings, we present a neurodevelopmental framework for the onset of mood and psychotic disorders and explore how disruptions in normative brain development contribute to their pathophysiology, timing, and onset. Additionally, we move beyond viewing these conditions as homogeneous disorders and discuss how reward processing profiles may align with specific symptom dimensions.

Obsessive-compulsive disorder (OCD) is characterized by obsessions and compulsions that significantly impair functioning. Obsessive-compulsive personality disorder (OCPD) co-occurs in 17-45% of OCD patients, worsening outcomes across multiple domains. Therefore, we aimed to study the impact of OCPD in more detail by analyzing selected comorbidities, emotional aspects, and sociodemographic data. This study assessed 78 OCD patients (average age 44.9 years, 34.61% OCPD), using Y-BOCS, BABS, BPAQ, BIS-11, YMRS, HDRS-17, and ASEX. Patients with comorbid OCPD had significantly worse outcomes in symptom severity (Y-BOCS = 0.0006), treatment duration (p = 0.0127), insight (BABS, p = 0.0185), aggression (p = 0.0266), impulsivity (p = 0.0469), depression (HDRS, p = 0.0178), mania (YMRS, p = 0.0003), and sexual dysfunction (ASEX, p = 0.008). OCPD was more prevalent in unemployed individuals (p = 0.046) and older patients (p = 0.009). No significant differences were found regarding gender, education, or relationship status. Obsessions and compulsions, such as contamination (p = 0.025), somatic (p = 0.018), ruminations (p = 0.003), and obsessional slowness (p = 0.007), were more common in the OCPD group. In the group with OCPD, aggression and OCD severity were correlated with increased levels of depression, which can be considered potential correlates of bipolarity in the relationship between OCD and OCPD. In conclusion, OCPD significantly worsens clinical outcomes in OCD across emotional, behavioral, and functional dimensions.

Bipolar disorder is a mental health problem that primarily affects mood. Symptoms of bipolar disorder are extreme irritability or agitation, a period of feeling empty, loss of interest in usual activities, sleep problems Etc. Symptomatic recovery is a dimensional measure that refers to improvement in the magnitude of symptoms. This investigation aims to determine the association between the burden of symptoms and time to symptomatic recovery of bipolar disorder that may increase more awareness about this disorder.

A Bayesian joint modeling of longitudinal and survival data was proposed to examine the association between the burden of symptoms and time to symptomatic recovery of bipolar disordered individuals at Jimma University Medical Center, Jimma, Ethiopia. The data in this investigation were retrospective longitudinal data and survival data from all the admitted follow-up of bipolar disorder patients from September 2018 to January 2020.

From the total of 257 bipolar disorders, about 116(45.1%) of them experienced an event of recovery. The time interval of follow up, age, the interaction between time interval of follow up and adolescent first onset of the disease, the interaction between time interval of follow up and event of relapse, the interaction between linear time interval of follow up and existence of other cofactors, and the interaction of substance abuse and chewing khat have significantly affected the log expected burden of bipolar symptoms. In survival sub-models, the covariates; divorced, event of relapse, mixed type of episodes significantly affect the time to symptomatic recovery at 95% confidence level. The association between burden of bipolar symptoms and time-to- symptomatic recovery is explained by α0 = - 8.403 with a [- 11.157,- 6.576]. It associates longitudinal count, the burden of symptoms, and time-to-symptomatic recovery of bipolar disorder using shared random effect parameters. There was a significant negative relationship between the subject-specific random intercept (baseline) of the burden of symptoms and the time to symptomatic recovery of bipolar disorder. Their 95% credible intervals exclude zero.

This study using the Bayesian joint modeling of longitudinal and survival has revealed a strong negative relationship between the event of recovery and the burden of bipolar symptoms at the baseline time. The study indicates that at the beginning, since the burden of bipolar symptoms is high, the chance of symptomatic recovery is low. And, we hypothesize that individuals with a higher initial symptom burden or a slower rate of symptom reduction (captured by bi) will experience a longer time to recovery. So, bipolar disorders at the initial follow-up need exceptional service and treatment.

Major depressive disorder (MDD) and bipolar disorder (BD) share various clinical behaviors and have confounded clinical diagnoses. Converging studies have suggested MDD and BD as disorders with abnormal communication among functional brain networks involved in mental activity and redirection. However, whether MDD and BD show disease-specific alterations in network information interaction remains unclear. This study collected resting-state functional MRI data of 98 patients with MDD, 55 patients with BD, and sex-, age-, and education-matched 95 healthy controls. Spectral dynamic causal model (spDCM) was used to investigate effective connectivities among three large-scale intrinsic functional networks including the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). Effective connectivities showing disease-specific changes were then used as input features of support vector models to predict clinical symptoms and classify individuals with MDD and BD. Compared with healthy controls, both the MDD and BD groups showed increased DAN → SN connectivity. However, within-network connectivities of DMN and DAN showed opposite effects on the diseases. Notably, MDD and BD also showed different alterations on a connectivity loop of SN → DAN → DMN → SN, which could be used to predict the clinical symptom severity of either MDD or BD. Individuals with MDD and BD could be further classified by using connectivities showing opposite disease effects. Our findings reveal common and unique alterations of network interactions in MDD and BD, and further suggest disease-specific neuroimaging markers for clinical diagnosis.

After decades of limited progress in depression treatment, recent advancements have sparked renewed interest in developing novel antidepressants, particularly rapid-acting antidepressants (RAADs). Despite these promising developments, there remains a significant gap in research on bipolar depression. While several antipsychotics have been investigated for their efficacy in bipolar depression due to the reduced risk of mania induction, research on RAADs, such as (es)ketamine, remains scarce despite their demonstrated safety and effectiveness. In this review, we give an overview of current developments in RAADs in the context of bipolar disorder. Both published studies as well as phase II, III, and IV studies on bipolar depression (based on ClinicalTrials.gov) are reviewed in this work. The following RAAD substance classes have been or are currently being investigated as possible treatments for bipolar depression: NMDA antagonists and indirect AMPA agonists (ketamine, esketamine, riluzole, felbamate), GABAA (gamma-aminobutyric acid A) activators or positive allosteric modulators (zuranolone, pregnenolone, PEA), psychedelics (psilocybin, 5-MeO-DMT), muscarine receptor antagonists (scopolamine), and kappa opioid receptor antagonists (navacaprant). Other than the well-established efficacy and safety of (es)ketamine in treating bipolar depression, there has been little research effort in the treatment of bipolar depression. Recent research into RAADs demonstrates the growing field of novel mechanisms of action in the pharmacological treatment of bipolar depression. However, there is an urgent need for well-controlled clinical studies on RAADs in bipolar depression to expand treatment options and improve outcomes for millions of affected individuals worldwide.

National surveys have suggested that obsessive-compulsive disorder (OCD) is a prevalent and impairing condition. However, there are few cross-national data on OCD, with data particularly scarce in low- and middle-income countries. Here we employ data from the World Mental Health surveys to characterize the onset, course, severity, and treatment of OCD across a range of countries in different geographic regions of the world.

Data came from general population surveys carried out in 10 countries using a consistent research protocol and interview. A total of 26,136 adults were assessed for OCD in face-to-face interviews and were included in the present analyses. We examined lifetime and 12-month prevalence as well as age of onset, persistence, severity, and treatment of DSM-IV OCD in six high-income countries (HICs) and four low- or middle-income countries (LMICs). We also investigated socio-demographic variables and temporally prior mental disorders as predictors of OCD onset, persistence, severity, and treatment.

Across the 10 countries surveyed, OCD has a combined lifetime prevalence of 4.1%. The 12-month prevalence (3.0%) is nearly as high, suggesting a highly persistent course of illness. Age of onset is early, with more than 80% of OCD cases beginning by early adulthood. Most OCD cases in the community are mild (47.0%) or very mild (27.5%), with a smaller percentage designated as moderate (22.9%) or severe (2.7%) by the Yale-Brown Obsessive-Compulsive Scale. Only 19.8% of respondents with OCD received any mental health treatment in the past year, with treatment rates much higher in HICs (40.5%) than LMICs (7.0%). Cross-nationally, OCD commonly emerges in adolescence or early adulthood against a backdrop of earlier-occurring mental disorders. With few exceptions (e.g., marital status, prior social phobia), the socio-demographic and psychopathological risk factors for OCD onset, persistence, severity, and treatment are distinct.

These cross-national data underscore clinical lessons regarding the importance of early diagnosis of OCD and comprehensive evaluation of comorbidity; draw attention to OCD as an undertreated disorder, particularly in LMIC contexts; and emphasize the public health significance of this often-overlooked condition.

Bipolar disorder (BD) presents with a wide range of symptoms that vary among relatives, casting doubt on categorical illness models. To address this uncertainty, we investigated the heritability and genetic relationships between categorical and dimensional models of BD in a family sample.

This retrospective study included participants (n = 397 Females, n = 329 Males, mean age 47 yr) in the Amish-Mennonite Bipolar Genetics (AMBiGen) study from North and South America that were assigned categorical mood disorder diagnoses ("narrow" or "broad") by structured psychiatric interview and completed the Mood Disorder Questionnaire (MDQ), which assesses lifetime history of manic symptoms and associated impairment. MDQ-dimensions were analyzed by Principal Component Analysis (PCA). Heritability and genetic overlaps between categorical diagnoses and MDQ-dimensions were estimated with SOLAR-ECLIPSE within 432 genotyped participants.

Individuals diagnosed with BD (n = 124) endorsed more MDQ items (61 %) than those with other mood disorders (26 %) or with no mood disorder (9 %), as expected. PCA suggested a three-component model for the MDQ, capturing 60 % of the variance. Heritability of the MDQ and its principal components was significant but modest (20-30 %, p < 0.001). Genetic correlations between MDQ measures and categorical diagnoses (ρG = 0.62-1.0; p < 0.001) were stronger than phenotypic correlations (ρP = 0.11-0.58; p < 0.001).

Recruitment through probands with BD resulted in increased prevalence of BD in this sample, limiting generalizability. Unavailable genetic data reduced sample size for some analyses.

Findings support a genetic continuity between dimensional and categorical models of BD and suggest that the MDQ is a useful phenotype measure for genetic studies of BD.

Bipolar disorder (BD) has a significant impact on functioning in the absence of acute mood episodes. This has been associated with subsyndromal symptoms, co-morbidities, and emotional dysregulation. The present study aims to evaluate the acceptability and preliminary efficacy of imagery-based cognitive therapy (ImCT) in a French community setting. We were particularly interested in the link between mental imagery and emotional dysregulation as this may clarify the mechanisms involved in the potential efficacy of the therapy and ultimately improve its relevance.

Ten participants underwent ImCT, with weekly assessments of mood fluctuations, anxiety, and emotional dysregulation conducted over 1 month (i.e. pre-therapy, post-therapy and 1-month follow-up). Recovery, post-traumatic stress symptoms and self-compassion were measured at baseline and post-therapy. Attrition rates and satisfaction were measured.

All participants who completed therapy (n=8) reported high levels of satisfaction. Five of them showed reliable individual improvement on emotion dysregulation scores. At the group level, a significant decrease in mood fluctuation with a large effect size was found post-therapy.

ImCT showed good acceptability among participants who completed the study. Importantly, our study is the first to provide an indication that ImCT may alleviate subsyndromal mood symptoms but also emotional dysregulation in individuals with BD. This latter finding is particularly relevant given the scarcity of validated psychosocial interventions targeting emotional dysregulation in BD.

Suicide attempts are more prevalent in people with bipolar I disorder (BD-I) than in the general population. Most prior studies of suicide in BD-I have focused on separate emotion-related assays or clinician-administered scales, whereas a single, brief, and multidimensional battery of self-report measures has not yet been explored. Here, we utilized the NIH Toolbox Emotion Battery (NIHTB-EB) to assess various emotional measures, determine which were cross-sectionally associated with prior suicide attempt in BD-I, evaluate whether the NIHTB-EB could be used to identify past suicide attempt in BD-I with machine learning, and compare model performance versus using clinical mood scales. The study included 39 participants with BD-I and history of suicide attempt, 48 with BD-I without history of suicide attempt, and 58 controls. We found that 9 of the 17 measures were associated with past suicide attempt in BD-I. The initial random forest model indicated that the most important distinguishing variables were perceived stress, emotional support, anger-hostility, anger-physical aggression, perceived rejection, loneliness, and self-efficacy. Overall, the models utilizing NIHTB-EB measures performed better (69.0 % to 70.1 % accuracy) than the model containing clinical mood scale information without the NIHTB-EB measures (57.5 % accuracy). These findings suggest the NIHTB-EB could be a useful and easy-to-deploy tool in understanding the role of emotion-related measures in suicide in BD-I. Furthermore, these results highlight specific emotional subdomains that could be promising targets for longitudinal studies or interventions aimed at reducing suicide in BD-I.

Bipolar disorder (BD) is a complex mental condition of which the mechanism of onset remains unclear. Mendelian randomization (MR) allows evaluation of the causal effects of biomarkers by minimizing the risks of reverse causation and confounding factors. In this study, MR was used to assess the causal relationships between neurodevelopment-related proteins and BD, thereby providing potential evidence for the neurodevelopmental hypothesis of this mental disorder.

Leveraging data from large-scale genome-wide association studies (GWASs), the associations between six neurodevelopment-related proteins and BD were analyzed using five MR approaches; namely, inverse-variance weighted, weighted median, MR-Egger, simple mode, and weighted mode methods. The neurodevelopment-related proteins were selected in the study with 5368 European descents. GWAS of BD come from the Psychiatric Genomics Consortium (NCase = 41,917, NControl = 371,549).

The analyses identified robust causal relationships between BD and the proteins inter-alpha-trypsin inhibitor heavy chain (ITIH)5 (OR = 1.08, 95% CI = 1.00-1.17, p = 0.04) and neurofascin (NFASC) (OR = 0.96, 95% CI = 0.92-1.00, p = 0.042). Initial findings for ITIH1 and ITIH3 were deemed unreliable due to pleiotropy (ITIH1: MR-Egger intercept p = 0.025) or heterogeneity (ITIH3: Cochran's Q p = 0.001). Furthermore, the MR analyses failed to yield evidence supporting a causal effect of liability to BD on neurodevelopment-related proteins.

The MR analysis indicated potential causal relationships between two neurodevelopment-related proteins (NFASC and ITIH5) and BD. Further studies are required to validate these results and elucidate the specific functions of these proteins in the development of this mental disorder.

Objective: Substance use disorders (SUD) still represent a huge worldwide health problem, as, despite withdrawal, medication, social support and psychotherapy, the relapse rate (around 80% at one year following treatment) remains tremendously high. Therefore, an important challenge consists in finding new complementary add-on tools to enhance quality of care. Methods and Results: In this report we focus on new insights reported through the use of three electrophysiological tools (quantitative electroencephalography (EEG), QEEG; cognitive event-related potentials, ERPs; and neurofeedback) suggesting that their use might be helpful at the clinical level in the management of various forms of SUDs. Empirical evidence were presented. Conclusion: In light of encouraging results obtained highlighting how these electrophysiological tools may be used in the treatment of SUDs, further studies are needed in order to facilitate the implementation of such procedures in clinical care units.

Little is known about the effect of ethnicity on drug treatment in patients with an acute manic episode. The aim of this study is to determine whether ethnicity moderates the response to drug treatment in patients with an acute manic episode, and whether this moderation is independent of potential confounders.

We analysed ten short-term placebo-controlled registration trials of atypical antipsychotics and anticonvulsive mood stabilizers in patients with an acute manic episode (n = 2199). A one-step random effects individual patient data meta-analysis (IPD) was applied to establish the moderating effect of ethnicity on symptom improvement on the Young Mania Rating Scale (Y)MRS and on response defined as 50% (Y)MRS symptom reduction. These analyses were corrected for baseline severity, age, and gender. A two-step IPD comparing these outcomes between White, Black and Asian patients. Additionally, a conventional meta-analysis was performed to determine the effect size of drug treatment separately for these ethnic groups.

In the complete dataset, 60.4% of the patients was White, 8.0% was Black, 12.7% was Asian, 33.7% was of other ethnicities. Ethnicity did not significantly moderate the efficacy of drug treatment: pooled beta-coefficient (β) for the interaction between treatment and the ethnicities White, Black and Asian, varying from 0.889 to 0.899 with overlapping confidence-intervals ranging from 2.356 to 2.430 in the main analysis. The drug treatment effects were significant in all three analysable ethnicity groups compared to placebo.

In White,Black, and Asian patients with an acute manic episode drug treatment is equally effective.

Little attention has been paid to the generalizability of cohort studies in bipolar disorder (BD) to patient with BD in everyday clinical practice.

A sample of patients with bipolar I disorder (BD-I) treated at a Dutch outpatient clinic for BD were compared with Dutch participants with BD-I of four clinical cohort studies, and participants with BD-I in a general population study in the Netherlands, on sociodemographic and clinical characteristics.

On many variables participants from the outpatient sample matched with those of the included studies. However, compared with participants of several of the clinical cohort studies, these outpatients were significantly younger, had an earlier age of onset of mood symptoms, and had a shorter duration of illness. Compared with participants in the general population study, outpatients had significant higher levels of education and less often lived together or were married. One cohort study reported much lower comorbidity rates of alcohol use disorders, drug use disorders, and anxiety disorders than in the outpatient sample. In contrast, comorbidity rates were higher in the population study.

Due to methodological differences between studies, comparisons between several variables was limited, and for some variables data was lacking.

Our findings suggest that many findings from cohort studies and general population study in BD-I are generalizable to everyday clinical practice, especially mood disorder outpatient centers. However, differences between samples indicate some selection and referral bias.

Background: Early and accurate diagnosis is crucial for effective prevention and treatment of severe mental illnesses, such as schizophrenia and bipolar disorder. However, identifying these conditions in their early stages remains a significant challenge. Our goal was to develop a method capable of detecting latent disease liability in healthy volunteers. Methods: Using questionnaires examining affective temperament and schizotypal traits among voluntary, healthy university students (N = 710), we created three groups. These were a group characterized by an emphasis on positive schizotypal traits (N = 20), a group showing cyclothymic temperament traits (N = 17), and a control group showing no susceptibility in either direction (N = 21). We performed a resting-state EEG examination as part of a complex psychological, electrophysiological, psychophysiological, and laboratory battery, and we developed feature-selection machine-learning methods to differentiate the low-risk groups. Results: Both low-risk groups could be reliably (with 90% accuracy) separated from the control group. Conclusions: Models applied to the data allowed us to differentiate between healthy university students with latent schizotypal or bipolar tendencies. Our research may improve the sensitivity and specificity of risk-state identification, leading to more effective and safer secondary prevention strategies for individuals in the prodromal phases of these disorders.

This study employed an experimental vignette design in Jewish communities in the United States (n = 243) to investigate whether public stigma toward target individuals with major depressive disorder or bipolar disorder presenting with either mania or depression was associated with their gender and symptomatology. The Mental Illness Stigma Scale (Day et al., in J Appl Soc Psychol 37(10):2191-2219, 2007) was used to measure the following dimensions of public stigma: (a) anxiety; (b) relationship disruption; (c) hygiene; (d) visibility; (e) treatability; (f) professional efficacy; and (g) recovery. The influence of characteristics of survey respondents on public stigma was also examined. In Jewish communities in the United States, mood disorder symptomatology was associated with the stigma dimensions of recovery, relationship disruption, and hygiene. Among respondents, younger and middle-aged males reported increased treatment efficacy stigma. Research implications include designing stigma reduction interventions tailored to specific diagnostic (e.g., bipolar disorder) and demographic (e.g., younger males) groups within the Jewish community.

Although scientific knowledge about bipolar disorder (BD) is readily available and accumulating, there is still a particular need to inform this inquiry with evidence generated in understudied cultures. This study was set up to fulfill this need, focusing on two objectives: ascertaining the levels of hypo(manic) and depressive symptoms ( i.e. , symptom profile) in Saudis with BD and looking at the psychopathological correlates of bipolarity. These objectives were addressed using data from 87 individuals with BD (M age = 30.95, ±9.58 years) and 86 nonclinical persons (M age = 22.20, ±1.29 years). Racing thoughts was the most common hypo(manic) symptom, whereas depressed mood was the most depressive symptom reported. Somatization and hostility psychopathological dimensions appeared to constitute significant independent predictors of bipolarity, independent of depression and hypo(mania). Findings partially replicate previous ones, indicating a cross-cultural resemblance for BD.

Bipolar disorder (BD) is a significant neuropsychiatric condition characterized by marked psychological mood disturbances. Despite extensive research on the symptomatology of BD, the mechanisms underlying its development and presentation remain unknown. Consequently, potential treatments are limited, and existing medications often cause significant side effects, leading to treatment discontinuation. Dopamine (DA) has been implicated in behavioral regulation, reward systems, and mood, highlighting the importance of the dopaminergic system in BD. Elevated levels of DA and tyrosine hydroxylase are associated with the onset of manic episodes, whereas reduced levels are linked to the depressive phase. Additionally, endogenous melatonin (MEL) levels are considerably lower in patients with BD. When administered as a treatment, exogenous MEL and MEL agonists improve behavioral characteristics and significantly modulate DA-related pathophysiological pathways in BD, with minimal adverse effects achieved through MEL receptor activation. Moreover, MEL and MEL agonists offer neuroprotection by promoting physiological homeostasis during disruption. The aim of this review is to investigate and propose MEL receptors as potential novel therapeutic targets for BD. This review seeks to analyze the role of MEL and its agonists in modulating dopamine-related pathophysiological pathways, improving behavioral outcomes, and providing neuroprotection with minimal side effects.

Distinguishing bipolar depression (BD) from unipolar depression (UD) remains a major clinical challenge, especially in drug-naïve patients. The present study aimed to investigate whether demographic, clinical, and biochemical parameters can help differentiate drug-naïve BD from UD.

Drug-naïve patients with UD and BD were recruited from Shandong Mental Health Center. Ninety-four inpatients (61 UD and 33 BD) were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17) and P300 latency. Fasting serum levels of free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), as well as fasting plasma glucose (FPG), lipid, C-reactive protein (CRP), and uric acid (UA) indicators were measured.

Patients with BD had longer illness duration and P300 latency and lower FT3 levels, but higher levels of TSH and FPG than patients with UD (all P<0.05). Binary logistic regression analysis indicated illness duration, TSH, FPG, and P300 latency were significantly associated with BD. Illness duration, TSH, FPG, and P300 latency achieved an area under the ROC curve of 0.777, 0.699, 0.646, and 0.635, respectively, in discriminating unipolar and bipolar depression.

Increased illness duration, serum TSH and FPG levels, and P300 latency were independent risk factors for BD. Demographic, clinical, biochemical, and electrophysiological markers identified may have the potential to distinguish BD from UD.

Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data. Because of the variability in how phenotypic data was collected by the various BD studies over the years, homogenizing this subphenotypic data is a challenging task, and so is replication. An alternative methodology, taken here, is to set aside the intricacies of subphenotype and allow the genetic data itself to determine which subjects define a homogeneous genetic subgroup (termed 'bicluster' below).

In this paper, we leverage recent advances in heterogeneity analysis to look for genetically-driven subgroups (i.e., biclusters) within the broad phenotype of Bipolar Disorder. We first apply this covariate-corrected biclustering algorithm to a cohort of 2524 BD cases and 4106 controls from the Bipolar Disease Research Network (BDRN) within the Psychiatric Genomics Consortium (PGC). We find evidence of genetic heterogeneity delineating a statistically significant bicluster comprising a subset of BD cases which exhibits a disease-specific pattern of differential-expression across a subset of SNPs. This disease-specific genetic pattern (i.e., 'genetic subgroup') replicates across the remaining data-sets collected by the PGC containing 5781/8289, 3581/7591, and 6825/9752 cases/controls, respectively. This genetic subgroup (discovered without using any BD subtype information) was more prevalent in Bipolar type-I than in Bipolar type-II.

Our methodology has successfully identified a replicable homogeneous genetic subgroup of bipolar disorder. This subgroup may represent a collection of correlated genetic risk-factors for BDI. By investigating the subgroup's bicluster-informed polygenic-risk-scoring (PRS), we find that the disease-specific pattern highlighted by the bicluster can be leveraged to eliminate noise from our GWAS analyses and improve risk prediction. This improvement is particularly notable when using only a relatively small subset of the available SNPs, implying improved SNP replication. Though our primary focus is only the analysis of disease-related signal, we also identify replicable control-related heterogeneity.

Time distortions characterise severe mental disorders, exhibiting different clinical and neurobiological manifestations. This systematic review aims to explore the existing literature encompassing experimental studies on time perception in patients with bipolar disorder (BD), considering psychopathological and cognitive correlates.

Studies using an experimental paradigm to objectively measure the capacity to judge time have been searched for. Selected studies have been described based on whether i) explicit or implicit time perception was investigated, ii) the temporal intervals involved were sub-second or supra-second, and iii) a perceptual or motor timing paradigm was used.

Only 11 met the criteria for inclusion in the review. The available literature shows that the performance of BD patients mostly aligns with controls within sub-second timeframes (six articles), while a different pattern emerges within supra-second intervals based on the clinical phase of the disease (seven articles). Specifically, for longer temporal spans, BD patients tend to overestimate the duration during manic states and underestimate it during depressive states. Notably, no studies have directly investigated the neurobiological mechanisms associated with time perception.

This review indicates that BD patients exhibit time perception similar to controls within sub-second intervals, but tend to overestimate time and underestimate it based on the clinical phase within supra-second intervals. Expanding the understanding of time perception in BD, particularly in relation to clinical phases and cognitive function, is of great importance. Such insights could deepen our understanding of the disorder, refine diagnostic processes, and guide the development of innovative therapeutic interventions.

While bipolar disorder is not uncommon in primary care, collaborative care models for bipolar depression treatment are underdeveloped. Our aim was to compare initial pharmacological treatment patterns for an episode of bipolar depression in different care models, namely primary care (PC), integrated behavioral health (IBH), and mood specialty clinic (SC).

A retrospective study of adults diagnosed with bipolar disorder who received outpatient care in 2020 was completed. Depressive episodes were captured based on DSM-5 criteria, ICD codes, or de novo emergent symptom burden (PHQ-9 ≥ 10). Pharmacological strategies were classified as 1) continuation of current regimen, 2) dose increase or 3) augmentation 4) switch to monotherapy or 5) a combination of more than two different strategies. Logistic regression was applied.

A total of 217 encounters (PC = 32, IBH = 53, SC = 132) representing 186 unique patients were identified. PC was significantly more likely to continue the current regimen, while combination strategies were significantly more likely recommended in IBH and SC. Mood stabilizers were significantly more utilized in IBH and SC. There were no significant group differences in antidepressant use.

Retrospective study design at a single site.

This study provides evidence of delays in depression care in bipolar disorder. This is the first study to compare treatment recommendations for bipolar depression in different clinical settings. Future studies are encouraged to better understand this gap and to guide future clinical practice, regardless of care model, emphasizing the potential benefits of decision support tools and collaborative care models tailored for bipolar depression.

Bipolar Disorder (BD) is an important psychiatric disease that progresses with attacks, can be chronic and causes serious mental problems. In this study, we aimed to identify the retinal vascular pathologies in BD patients by optical coherence tomography angiography (OCTA) imaging.

Retinal vascular analysis from 35 BD patients and 30 healthy controls (HCs) were scanned using the OCTA machine. In addition, psychometric tests such as the Young Mania Rating Scale (YMRS) and Clinical Global Impression Scale (CGI-S) were applied to BD patients to assess the severity of the disease and determine the patient's level of functionality.

As a result of OCTA scans, there were significant differences between the groups as following; Deep retinal vessel density (VD) in the total, parafoveal and perifoveal area, Macular thickness in the inner parafoveal area, VD of retinal capillary plexuses in the inside disk and the Choroidal thickness (p < 0.05). Furthermore, according to the results of Pearson correlation analysis between OCTA scans and YMRS and CGI-S scores, it was determined that there was no significant relationship in any measurement (p > 0.05).

In our study, it was determined that there were general differences in deep retinal vascular density and inner macular thickness in BD patients. These findings demonstrate that the deep and inner zone of the retina is affected in BD patients.

To develop a composite score for differential resilience to effects of combat-related stressors (CRS) on persistent DSM-IV post-traumatic stress disorder (PTSD) among US Army combat arms soldiers using survey data collected before deployment.

A sample of n = 2542 US Army combat arms soldiers completed a survey shortly before deployment to Afghanistan and then again two to three and 8-9 months after redeployment. Retrospective self-reports were obtained about CRS. Precision treatment methods were used to determine whether differential resilience to persistent PTSD in the follow-up surveys could be developed from pre-deployment survey data in a 60% training sample and validated in a 40% test sample.

40.8% of respondents experienced high CRS and 5.4% developed persistent PTSD. Significant test sample heterogeneity was found in resilience (t = 2.1, p = 0.032), with average treatment effect (ATE) of high CRS in the 20% least resilient soldiers of 17.1% (SE = 5.5%) compared to ATE = 3.8% (SE = 1.2%) in the remaining 80%. The most important predictors involved recent and lifetime pre-deployment distress disorders.

A reliable pre-deployment resilience score can be constructed to predict variation in the effects of high CRS on persistent PTSD among combat arms soldiers. Such a score could be used to target preventive interventions to reduce PTSD or other resilience-related outcomes.

Knowledge of clinical, treatment and life circumstances of individuals with bipolar I disorder (BP-I) in US households is informed by decades old epidemiological surveys.

The Mental and Substance Use Disorders Prevalence Study was conducted October 2020-October 2022. Clinicians administered the Structured Clinical Interview for the DSM-5 diagnosing 12-month prevalence of BP-I and other mental health disorders (MHD) among 4764 adults aged 18-65 years and collected sociodemographic information. We examined clinical characteristics, differences by sex and age among adults with BP-I, and compared adults with BP-I versus no MHD regarding sociodemographic characteristics, functioning, and substance use disorders (SUDs).

Prevalence of BP-I in the MDPS was 1.5 %. Among those with BP-I, 73.4 % had comorbid psychiatric disorders, and 43.4 % had comorbid SUDs. Alcohol use disorder was higher in those with BP-I versus no MHD (33.0 % vs. 6.3 %). Mean Global Assessment of Functioning scores were lower among those with BP-I versus no MHD (53.2 vs. 77.0). Of individuals with BP-I, 64.9 % had past-year outpatient, 5.4 % inpatient, and 18.7 % minimally adequate treatment (≥1 antimanic agent and ≥ 4 outpatient visits). Individuals with BP-I were less likely to be employed (37.3 % vs. 63.0 %) and have a family income ≥$20,000 (48.2 % vs. 81.9 %) versus no MDPS MHD.

The survey response rate was low.

In this sample, many individuals with BP-I had psychiatric and SUD comorbidities, lived in poverty and had functional impairment. Few received adequate treatment; women and younger individuals were particularly disadvantaged. Early detection and treatment represent substantial opportunities to improve outcomes.

Bipolar disorder is a mood illness that affects many people. It has a high recurrence frequency and will cause significant damage to the patient's social function. At present, the pathogenesis of BD is not clear. The National Center for Biotechnology Information (NCBI) established and maintained the Gene Expression Omnibus (GEO) database, a gene expression database. For bioinformatics analysis, researchers can obtain expression data from the internet. At present, the samples of the dataset used in the research of BD are mostly from brain tissue, and the data containing blood samples are rarely used. GEO databases (GSE46416, GSE5388, and GSE5389) were used to retrieve public data, and utilizing the online tool GEO2R, differentially expressed genes (DEGs) were retrieved. The common DEGs between the samples of patients with BD and the samples of the normal population were screened by Venn diagrams. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional annotation and pathway enrichment analysis of DEGs. A protein-protein interaction network (PPI) was built to investigate hub genes on this basis. There were 117 up-regulated DEGs and 38 down-regulated DEGs discovered, with two hub genes [SRC, CDKN1A] among the up-regulated DEGs. These two hub genes were also highly enriched in the oxytocin signaling pathway, proteoglycans in cancer and bladder cancer, according to KEGG analysis. The results of the receiver operating characteristic curve (ROC) of SRC and CDKN1A in the three datasets strongly suggested that SRC and CDKN1A were potential diagnostic markers of BD. The results strongly suggest that SRC and CDKN1A are related to the pathogenesis of BD.

To investigate the impact of circadian rhythm disruptions on mental health among college students and explore effective interventions for maintaining stable circadian rhythms.

A comprehensive review of literature was conducted, focusing on sleep patterns, circadian rhythms, and their effects on mental health. Studies were analyzed to identify common factors contributing to circadian misalignment in college students and effective treatments. Data from large-scale studies and specific clinical trials were utilized to understand the relationship between circadian rhythms and psychiatric disorders.

Disruptions in circadian rhythms were linked to increased prevalence of psychiatric disorders such as depression, anxiety, and bipolar disorder. Biological changes during adolescence, academic pressures, and extensive use of electronic devices were major contributing factors. Effective interventions included light therapy, chronotherapy, melatonin supplementation, and cognitive behavioral therapy for insomnia.

Stable circadian rhythms are crucial for mental health, particularly in college students who are vulnerable to disruptions due to lifestyle factors. Implementing interventions such as regular sleep schedules, light exposure management, and behavioral therapies can significantly improve mental health outcomes. Further research and targeted mental health programs are essential to address circadian misalignment and its associated psychiatric disorders in this population.

Bipolar Disorder (BD) is a complex disease. It is heterogeneous, both at the phenotypic and genetic level, although the extent and impact of this heterogeneity is not fully understood. One way to assess this heterogeneity is to look for patterns in the subphenotype data. Because of the variability in how phenotypic data was collected by the various BD studies over the years, homogenizing this subphenotypic data is a challenging task, and so is replication. An alternative methodology, taken here, is to set aside the intricacies of subphenotype and allow the genetic data itself to determine which subjects define a homogeneous genetic subgroup (termed 'bicluster' below).

In this paper, we leverage recent advances in heterogeneity analysis to look for genetically-driven subgroups (i.e., biclusters) within the broad phenotype of Bipolar Disorder. We first apply this covariate-corrected biclustering algorithm to a cohort of 2524 BD cases and 4106 controls from the Bipolar Disease Research Network (BDRN) within the Psychiatric Genomics Consortium (PGC). We find evidence of genetic heterogeneity delineating a statistically significant bicluster comprising a subset of BD cases which exhibits a disease-specific pattern of differential-expression across a subset of SNPs. This disease-specific genetic pattern (i.e., 'genetic subgroup') replicates across the remaining data-sets collected by the PGC containing 5781/8289, 3581/7591, and 6825/9752 cases/controls, respectively. This genetic subgroup (discovered without using any BD subtype information) was more prevalent in Bipolar type-I than in Bipolar type-II.

Our methodology has successfully identified a replicable homogeneous genetic subgroup of bipolar disorder. This subgroup may represent a collection of correlated genetic risk-factors for BDI. By investigating the subgroup's bicluster-informed polygenic-risk-scoring (PRS), we find that the disease-specific pattern highlighted by the bicluster can be leveraged to eliminate noise from our GWAS analyses and improve risk prediction. This improvement is particularly notable when using only a relatively small subset of the available SNPs, implying improved SNP replication. Though our primary focus is only the analysis of disease-related signal, we also identify replicable control-related heterogeneity.

Around the world, people living in objectively difficult circumstances who experience symptoms of generalized anxiety disorder (GAD) do not qualify for a diagnosis because their worry is not 'excessive' relative to the context. We carried out the first large-scale, cross-national study to explore the implications of removing this excessiveness requirement.

Data come from the World Health Organization World Mental Health Survey Initiative. A total of 133 614 adults from 12 surveys in Low- or Middle-Income Countries (LMICs) and 16 surveys in High-Income Countries (HICs) were assessed with the Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-5 criteria for GAD were compared to respondents meeting all criteria for GAD, and to respondents without GAD, on clinically-relevant correlates.

Removing the excessiveness requirement increases the global lifetime prevalence of GAD from 2.6% to 4.0%, with larger increases in LMICs than HICs. Non-excessive and excessive GAD cases worry about many of the same things, although non-excessive cases worry more about health/welfare of loved ones, and less about personal or non-specific concerns, than excessive cases. Non-excessive cases closely resemble excessive cases in socio-demographic characteristics, family history of GAD, and risk of temporally secondary comorbidity and suicidality. Although non-excessive cases are less severe on average, they report impairment comparable to excessive cases and often seek treatment for GAD symptoms.

Individuals with non-excessive worry who meet all other DSM-5 criteria for GAD are clinically significant cases. Eliminating the excessiveness requirement would lead to a more defensible GAD diagnosis.

Seasonality in depressive and bipolar disorders, are recognized in the ICD-10/11 and DSM-5 diagnostic systems. The existence of a seasonal pattern of hospital diagnosis of major depression, bipolar disorder and prescription of antidepressant medications has not been evaluated in the Danish population.

We retrieved date and year for all first-time hospital contacts with depression or bipolar disorder between 1999 and 2019, registered in the Danish National Patient Registry. Depression was defined using the ICD-10 F32-F33 codes, and for bipolar disorder the F30 or F31 codes. Date and year of all first-time purchases of antidepressant medications with ATC codes (N06A) between 1999 and 2021 were retrieved from the Danish National Prescription Registry, containing information on all prescribed drugs dispensed at pharmacies since 1995. Data on sunlight hours from 2012 to 2021 were retrieved from the Danish Metrological Institute.

Incidences of hospital diagnoses as well as purchases of medication varied with month and season. The monthly variations were larger for antidepressant medication and smallest for bipolar disorder. The multiple linear regression analysis showed that number of first-time diagnoses of depression or bipolar disorder did not correlate with season. For antidepressant medication the number of first-time prescriptions was significantly lower in summer compared to the winter season.

This study found a seasonal variation of first-time prescriptions of antidepressant medication. We did not find a seasonal variation in first-time hospital diagnoses. Further research looking into depression severity, polarity of bipolar illness episodes, lag-time for sunlight exposure, and specific parts of the yearly photoperiods should be conducted.

Introduction: Lithium remains a gold standard treatment for bipolar disorder including during peripartum. Historically, guidelines advised against breastfeeding while taking lithium though recent data suggest it is acceptable for a healthy infant. Lack of awareness of acceptability contributes to decreased patient and clinician comfort and low breastfeeding rates. We report current breastfeeding rates, monitoring practices, and infant outcomes with lithium exposure in breastmilk at our institution. Methods: A retrospective chart review was conducted at a single academic medical center using records from 2013 to 2023. Electronic medical records were queried to identify patients prescribed lithium postpartum. Data were collected on timing of lithium initiation, lithium dose and concentration, breastfeeding status, and infant outcomes. Results: A total of 18 cases of lithium use in the postpartum period were identified. A total of 39% (n = 7) of patients taking lithium postpartum breastfed. Most patients, 61% (n = 11), initiated lithium prior to pregnancy, 11% (n = 2) initiated during pregnancy and 27% (n = 5) started postpartum. Four infant charts were reviewed with no reports of adverse events. Of these infants, average maternal lithium dose was 750 mg daily, with an average maternal serum lithium concentration of 0.62 mmol/L and average infant serum lithium concentration of 0.16 mmol/L. Conclusion: Our data demonstrate most patients using lithium postpartum have been taking lithium long-term and are not breastfeeding. Lithium exposure in breastmilk appears to be tolerated by healthy infants. There is a need for ongoing research and education on acceptability and infant monitoring recommendations to support patients who would like to breastfeed while on lithium.

Bipolar disorder is a recurrent mental health disorder with a prevalence rate of 1.4%. On average, there can be a delay of 9.5 years from the initial presentation of symptoms to a confirmed diagnosis. Individuals living with bipolar disorder have a reduced life expectancy. There is limited evidence regarding the effectiveness of antidepressants in treating bipolar disorder. The ASCEnD clinical trial will test the clinical and cost-effectiveness of the aripiprazole/sertraline combination in comparison with quetiapine for the treatment of bipolar depression (individuals who suffer from depressive episodes in bipolar disorder) and will include a nested qualitative study.

The qualitative study will use semi-structured interviews to explore pilot trial participants' and clinicians' perspectives on recruitment procedures, the acceptability of the intervention, the management of bipolar disorder and attitudes to medication combinations.

Findings will inform recruitment strategies and optimise training for the participating sites in the ASCEnD full trial. They will also help to illuminate the lived experience of people with bipolar disorder and the clinicians who work with people with bipolar disorder. The discussion will explore perspectives on the delay in diagnosis, having a diagnosis, the impact of living with bipolar disorder and attitudes to treatment, including drug combinations.

A Lived Experience Advisory Panel (LEAP) has been convened with the support of the McPin Foundation, which will contribute to the ASCEnD trial and its nested qualitative study to provide input on the design and delivery of the trial and qualitative study, analysis of qualitative data and dissemination of findings.

Bipolar disorder (BD), a mood disorder with recurrent affective episodes and a strong genetic basis is frequently associated with significant comorbidities, both physical and psychiatric, yet its neurobiology remains unclear. Recent evidence underscores oxidative stress as a pivotal factor linking BD to its comorbidities, prompting an investigation into whether this is a sign of a genetic vulnerability or a consequence of the disease. In this study, we systematically reviewed oxidative stress studies conducted on individuals at risk for BD. We performed a meta-analysis on studies examining oxidative DNA damage in these individuals.

The literature was searched across the databases PubMed, Web of Science, Scopus, Ovid MEDLINE, and Cochrane to locate studies of oxidative stress markers in relatives of patients with BD compared with healthy controls (from 1946 to March 2024). Studies were considered for inclusion based on the following criteria: (i) involvement of first- or second-degree relatives of individuals diagnosed with BD, (ii) presence of a healthy control group, (iii) reporting of oxidative stress parameters for relatives, including mean and standard deviation or median and interquartile range (25-75%) values, and (iv) publication in the English language. Studies comparing the levels of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) or its tautomer 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in individuals at risk for BD with healthy controls were evaluated using a meta-analysis with the random-effects method. The risk of bias was evaluated using the Risk of Bias in Non-Randomized Studies of Exposure (ROBINS-E) tool.

Eleven studies were included in the systematic review and four studies for the meta-analysis. The meta-analysis included 543 individuals (first-degree relatives of individuals with BD = 238, control = 305). 8-OH-dG levels were found to be increased in first-degree relatives of individuals with BD compared to healthy controls (random effects: Hedges's g = 0.53, 95% CI = 0.36-0.71, p < 0.001). Findings of oxidative stress markers other than oxidative DNA damage in relatives of individuals with BD are limited and scarce.

In this meta-analysis, which consists of a limited number of studies, oxidative DNA damage seems to be a trait marker for BD. This finding could be associated with increased comorbidity and a higher risk of premature aging in individuals at risk for BD. However, further studies with larger sample sizes and longitudinal designs are warranted to confirm findings. Clarifying the changes in these markers from individuals at risk for the disorder throughout the course of the illness would help bridge the gap in understanding the role of oxidative pathways in the risk of BD.

Bipolar disorder (BPD) is a debilitating mood disorder with an unclear etiology. A better understanding of the underlying pathophysiological mechanisms will help to identify novel targets for improved treatment options and prevention strategies. In this metabolome-wide Mendelian randomization study, we screened for metabolites that may have a causal role in BPD.

We tested a total of 913 circulating metabolite exposures assessed in 14,296 Europeans using a mass spectrometry-based platform. For the BPD outcome, we used summary data from the largest and most recent genome-wide association study reported to date, including 41,917 BPD cases.

We identified 33 metabolites associated with BPD (padjusted < 5.48 × 10-5). Most of them were lipids, including arachidonic acid (β = -0.154, SE = 0.023, p = 3.30 × 10-11), a polyunsaturated omega-6 fatty acid, along with several complex lipids containing either an arachidonic or a linoleic fatty acid side chain. These associations did not extend to other closely related psychiatric disorders like schizophrenia or depression, although they may be involved in the regulation of lithium response. These lipid associations were driven by genetic variants within the FADS1/2/3 gene cluster, which is a robust BPD risk locus encoding a family of fatty acid desaturase enzymes that are responsible for catalyzing the conversion of linoleic acid into arachidonic acid. Statistical colocalization analyses indicated that 27 of the 33 metabolites shared the same genetic etiology with BPD at the FADS1/2/3 cluster, demonstrating that our findings are not confounded by linkage disequilibrium.

Overall, our findings support the notion that arachidonic acid and other polyunsaturated fatty acids may represent potential targets for BPD.