Family environmental factors are known to contribute to adolescent suicidal ideation (SI), but how these factors interact and relate to SI needs further investigation.

To examine how family factors interact with each other and are associated with adolescent SI in a psychiatric clinical setting, using network analysis with regularization methods.

Utilizing a quantitative research design, this study analyzed data from 293 adolescents aged 12 to 18 years seeking care in a psychiatric hospital. Data collection involved standardized interviews and self-report measures to assess SI, anxiety, depression, and various family environmental factors. Network analysis with regularization methods, including LASSO regression, was employed to elucidate the relationships among these variables.

Over 40% of adolescents reported SI, with positive relationship quality(RQ) significantly reducing SI. Network analysis indicated that family economic status did not directly relate to SI but through RQ. Additionally, anxiety was found to mediate the relationship between RQ and SI significantly, with a mediation effect of 53.34%. Parental marital status directly related to SI, whereas parental education level, particularly mothers', was not directly associated with SI or other mental health outcomes.

This study reveals the complex interplay between family environmental factors and psychiatric symptoms in adolescents, highlighting family relationship quality as a critical risk mechanism. These findings underscore the importance of family-centered interventions and public mental health policies to reduce suicidal ideation in adolescents.

Multiple genetic and environmental risk factors play a role in the development of both schizophrenia-spectrum disorders and affective psychoses. How they act in combination is yet to be clarified.

We analyzed 573 first episode psychosis cases and 1005 controls, of European ancestry. Firstly, we tested whether the association of polygenic risk scores for schizophrenia, bipolar disorder, and depression (PRS-SZ, PRS-BD, and PRS-D) with schizophrenia-spectrum disorder and affective psychosis differed when participants were stratified by exposure to specific environmental factors. Secondly, regression models including each PRS and polyenvironmental measures, including migration, paternal age, childhood adversity and frequent cannabis use, were run to test potential polygenic by polyenvironment interactions.

In schizophrenia-spectrum disorder vs controls comparison, PRS-SZ was the strongest genetic predictor, having a nominally larger effect in nonexposed to strong environmental factors such as frequent cannabis use (unexposed vs exposed OR 2.43 and 1.35, respectively) and childhood adversity (3.04 vs 1.74). In affective psychosis vs controls, the relative contribution of PRS-D appeared to be stronger in those exposed to environmental risk. No evidence of interaction was found between any PRS with polyenvironmental score.

Our study supports an independent role of genetic liability and polyenvironmental risk for psychosis, consistent with the liability threshold model. Whereas schizophrenia-spectrum disorders seem to be mostly associated with polygenic risk for schizophrenia, having an additive effect with well-replicated environmental factors, affective psychosis seems to be a product of cumulative environmental insults alongside a higher genetic liability for affective disorders.

Bipolar disorder (BD) hospitalization rates in children and adolescents vary greatly across place and over time. There are no population-based studies on youth BD hospitalizations in Spain.

We identified all patients aged 10-19 hospitalized due to BD in Spain between 2000 and 2021, examined their demographic and clinical characteristics, and assessed temporal trends in hospitalizations - overall and stratified by age and presence of additional psychiatric comorbidity. We used Joinpoint regressions to identify inflection points and quantify whole-period and annual percentage changes (APCs) in trends.

Of 4770 BD hospitalizations in 10-19-year-olds between 2000 and 2021 (average annual rate: 4.8 per 100,000), over half indicated an additional psychiatric comorbidity, most frequently substance abuse (62.2%), mostly due to cannabis (72.4%). During the study period, admissions increased twofold with an inflection point: Rates increased annually only between 2000 and 2008, for APCs 34.0% (95% confidence interval: 20.0%, 71.1%) among 10-14-year-olds, 10.3% (6.4%, 14.3%) among 15-19-year-olds, and 15.5% (11.5%, 22.7%) among patients with additional psychiatric comorbidity. Between 2009 and 2021, rates decreased moderately among 10-14-year-olds - APC: -8.3% (-14.1%, -4.4%) and slightly among 15-19-year-olds without additional psychiatric comorbidity - APC: -2.6(-5.7, -1.0), remaining largely stable among 15-19-year-olds overall.

Recent trends in hospitalization due to BD in 10-19-year-olds in Spain indicate salient increases in the early 2000s - especially among (i) patients aged 10-14 (decreasing moderately after 2009 among 10-14-year-olds and plateauing among 15-19-year-olds) and (ii) patients with additional psychiatric comorbidity (i.e., cannabis use disorder). These findings suggest links with recent changes in clinical practices for children and recent trends in substance use among Spanish youth.

To evaluate the possibility of suicide and related factors among individuals with schizophrenia and bipolar disorder (BD).

Data were collected for 270 individuals registered in a community mental health center using the Suicide Probability Scale (SPS). Subsequently, t test and multiple linear regression analyses were conducted on independent samples.

There was no statistically significant difference found between mean SPS scores of participants with schizophrenia and BD. However, hostility subscale mean scores of participants with schizophrenia were higher than those of participants with BD, and the difference was statistically significant. Sex, family history of mental illness, need for help with medication, suicidal ideation in the past 10 days, and number of suicide attempts were important predictors of suicide probability.

Individuals with schizophrenia and BD and in remission should be evaluated periodically for the possibility of suicide. [Journal of Psychosocial Nursing and Mental Health Services, 62(8), 37-45.].

This study aimed to explore the associations between homocysteine, rumination, affective temperaments, clinical features, and hopelessness in bipolar disorder-1 (BD-1).

In total, 57 euthymic patients with BD-1 and 57 healthy controls were included. The Beck Hopelessness Scale (BHS), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego-Autoquestionnaire (TEMPS-A), and Ruminative Responses Scale Short Form (RRS-SF) were administered. Homocysteine, folate, and vitamin B12 levels were measured.

The BHS total (p = 0.047), TEMPS-A irritable (p = 0.007), and TEMPS-A cyclothymic (p= 0.001) scores were significantly higher than the control group in the BD-1 group. Hyperhomocysteinemia (HHcy) was found in 33.3% of the patients (n = 19). In the HHcy group, age of onset of disease (p = 0.020) was significantly lower than the non-HHcy group in patients. Previous suicide attempt number was significantly correlated with scores of reflective pondering, brooding, and global rumination in BD-1 (p ˂ 0.05). Except for hyperthymic temperament, all types of affective temperaments were correlated with the scores of RRS-SF brooding (p ˂ 0.05) in the BD-1 group. The RRS-SF brooding scores significantly correlated with the BHS total scores (r = 0.263, p < 0.05); the TEMPS-A hyperthymic (β = -0.351, p = 0.001) and TEMPS-A irritable (β = 0.536, p < 0.001) scores significantly predicted the BHS total scores in the BD-1 group.

The findings may lead clinical efforts and future clinical trials to explore and intervene in related sources and presentations of BD-1's adverse consequences.

Bipolar Disorder is associated with high rates of suicidal thoughts, behaviors, and outcomes, yet the lived experience of suicidality and Bipolar Disorder is not particularly well understood. Understanding the role of psychosocial aetiologies in suicidality outcomes for those living with Bipolar Disorder is key for developing appropriately targeted interventions focusing on factors that are amenable to change. In line with PRISMA guidance, we conducted a scoping review to identify the types of psychosocial factors studied in relation to the experience of suicidality for people living with Bipolar Disorder diagnoses. Systematic literature searches identified a sample of 166 articles from which key study data were extracted and charted. A narrative synthesis of the reviewed literature is presented ordered by the factors investigated across studies, a frequency count of the types of psychological/social aetiologies studied, and a brief overview of the key findings for each aetiology. Most of the identified literature took the form of quantitative cross-sectional studies, with only one qualitative study and 18 quantitative prospective studies. The most studied aetiologies were trauma (specifically early adverse experiences and childhood traumas) and stressful life events, impulsivity (primarily subjective self-reported trait impulsivity), social support and functioning, and personality/temperament factors. Only six studies in the final sample reported basing their research questions and/or hypotheses on an explicit theoretical model of suicide. The literature was primarily focused on using self-report measurements of key aetiologies and on factors which lead to worsened suicidality rather than focusing on potentially protective or buffering factors. Future research needs to better justify the aetiologies investigated in relation to suicidality outcomes for people living with Bipolar Disorder, including a firmer basis in theory and hypothesis testing, more prospective designs, and the use of alternative assessments of psychosocial aetiologies in addition to self-report questionnaires.

Suicidal behavior is more prevalent in bipolar disorders than in other psychiatric illnesses. In the last thirty years evidence has emerged to indicate that long-term treatment of bipolar disorder patients with lithium may reduce risk of suicide and attempts, with possibly similar benefits in recurrent major depressive disorder. We review and update selected research literature on effects of lithium treatment in reducing suicidal behavior and consider proposals that higher levels of lithium in drinking water may be associated with lower suicide rates. We summarize results of a growing number of randomized, controlled studies of lithium treatment for suicide prevention including comparisons with placebos or alternative treatments, and comment on the severe challenges of such trials. The basis of a proposed protective effect of lithium against suicidal behaviors remains uncertain but may include protective effects against recurrences of depressive phases of mood disorders, especially with mixed features or agitation, and possibly through beneficial effects on impulsivity, agitation and dysphoric mood.

Suicidal behaviour among young people is a serious public health concern. Each suicide attempt is related to further suicide attempts and completed suicide. This study aims to explore risk factors associated with repeated suicide attempt among adolescents and young adults. The cohort included 510 patients aged 12-29 years residing in Piedmont Region in North-Western Italy, who had been admitted to hospital or emergency department with a diagnosis of suicide attempt between 2010 and 2020. Cox regression models were used to evaluate potential risk factors for repeated suicide attempt. During the 11-years follow-up, 20.6% of adolescents and young adults repeated suicide attempt, 24.8% of females and 12.3% of males. Nearly 90% of youth who attempted suicide had a diagnosis of psychiatric disorder. After adjustment, younger age of onset of suicidal behaviour, and diagnosis of schizophrenia, bipolar disorder, depressive disorder, anorexia nervosa and personality disorder were significantly associated with repeated suicide attempt. The early identification of patients at higher risk of repetition of suicidal behaviour is of crucial importance. Better understanding of risk factors and effective treatment of mental disorders could help suicide prevention to reduce the burden of the problem among young people. Special attention should be paid during the initial months following discharge from hospital or emergency department, when suicide reattempt risk is very high.

Suicide is nearly always associated with underlying mental disorders. Risk factors for suicide attempts (SAs) in patients with bipolar disorder (BD) misdiagnosed with major depressive disorder (MDD) remain unelucidated. This study was to evaluate the prevalence and clinical risk factors of SAs in Chinese patients with BD misdiagnosed with MDD.

A total of 1487 patients with MDD from 13 mental health institutions in China were enrolled. Mini International Neuropsychiatric Interview (MINI) was used to identify patients with BD who are misdiagnosed as MDD. The general sociodemographic and clinical data of the patients were collected and MINI suicide module was used to identify patients with SAs in these misdiagnosed patients.

In China, 20.6% of patients with BD were incorrectly diagnosed as having MDD. Among these misdiagnosed patients, 26.5% had attempted suicide. These patients tended to be older, had a higher number of hospitalizations, and were more likely to experience frequent and seasonal depressive episodes with atypical features, psychotic symptoms, and suicidal thoughts. Frequent depressive episodes and suicidal thoughts during depression were identified as independent risk factors for SAs. Additionally, significant sociodemographic and clinical differences were found between individuals misdiagnosed with MDD in BD and patients with MDD who have attempted suicide.

This study highlights the importance of accurate diagnosis in individuals with BD and provide valuable insights for the targeted identification and intervention of individuals with BD misdiagnosed as having MDD and those with genuine MDD, particularly in relation to suicidal behavior.

Data on trends in the epidemiological burden of bipolar disorder are scarce.

To provide an overview of trends in bipolar disorder burden from 1990 to 2019.

Revisiting the Global Burden of Disease Study 2019, we analysed the number of cases, calculated the age-standardised rate (per 100 000 population) and estimated annual percentage change (EAPC) of incidence, prevalence and years lived with disability (YLDs) for bipolar disorder from 1990 to 2019. The independent effects of age, period and cohort were estimated by the age-period-cohort modelling.

Globally, the bipolar disorder-related prevalent cases, incident cases and number of YLDs all increased from 1990 to 2019. Regionally, the World Health Organization Region of the Americas accounted for the highest estimated YLD number and rate, with the highest age-standardised prevalence rate in 1990 and 2019 and highest EAPC of prevalence. By sociodemographic index (SDI) quintiles, all five SDI regions saw an increase in estimated incident cases. Nationally, New Zealand reported the highest age-standardised rate of incidence, prevalence and YLDs in 1990 and 2019. The most prominent age effect on incidence rate was in those aged 15-19 years. Decreased effects of period on incidence, prevalence and YLD rates was observed overall and in females, not in males. The incidence, prevalence and YLD rates showed an unfavourable trend in the younger cohorts born after 1990, with males reporting a higher cohort risk than females.

From 1990 to 2019, the overall trend of bipolar disorder burden presents regional and national variations and differs by age, sex, period and cohort.

Bipolar Affective Disorder (BPAD) merits careful consideration within the medical and healthcare communities, researchers, and policymakers. This is due to its substantial disability burden, elevated prevalence of co-morbidities, heightened lifetime risk of suicidality, and a significant treatment gap. This article focuses on the lifetime and current prevalence, correlates, co-morbidities, associated disabilities, socio-economic impact, and treatment gap for BPAD in the adult population of the National Mental Health Survey (NMHS) 2016.

The NMHS 2016 was a nationally representative study conducted across 12 Indian states between 2014 and 2016. A multi-stage, stratified, random cluster sampling technique based on probability proportionate to size at each stage was used. The diagnosis of BPAD was based on Mini-International Neuropsychiatric Interview 6.0.0. Sheehan's Disability Scale was used to assess the disability.

A total of 34,802 adults were interviewed. The overall weighted prevalence of BPAD was 0.3% [95% confidence interval (CI): 0.29-0.31] for current and 0.5% (95% CI: 0.49-0.51) for lifetime diagnosis. Male gender [odds ratio (OR) 1.56] and residence in urban metropolitans (OR 2.43) had a significantly higher risk of a lifetime diagnosis of BPAD. Substantial cross-sectional co-morbidities were noted as per MINI 6.0.0 with the diagnosis of current BPAD such as tobacco use disorder (33.3%), other substance use disorders (14.6%), and anxiety disorders (10.4%). Two-thirds of persons with current BPAD reported disability of varying severity at work (63%), social (59.3%), and family life (63%). The treatment gap for current BPAD was 70.4%.

Most individuals with current BPAD reported moderate-severe disability. There were substantial co-morbidities and a large treatment gap. These warrant concentrated efforts from policymakers in devising effective strategies.

Chronic exposure to stress is a non-adaptive situation that is associated with mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS), especially superoxide anion (SA). This accumulation of ROS produces damage-associated molecular patterns (DAMPs), which activate chronic inflammatory states and behavioral changes found in several mood disorders. In a previous study, we observed that an imbalance of SA triggered by rotenone (Ro) exposure caused evolutionarily conserved oxi-inflammatory disturbances and behavioral changes in Eisenia fetida earthworms. These results supported our hypothesis that SA imbalance triggered by Ro exposure could be attenuated by lithium carbonate (LC), which has anti-inflammatory properties. The initial protocol exposed earthworms to Ro (30 nM) and four different LC concentrations. LC at a concentration of 12.85 mg/L decreased SA and nitric oxide (NO) levels and was chosen to perform complementary assays: (1) neuromuscular damage evaluated by optical and scanning electron microscopy (SEM), (2) innate immune inefficiency by analysis of Eisenia spp. extracellular neutrophil traps (eNETs), and (3) behavioral changes. Gene expression was also evaluated involving mitochondrial (COII, ND1), inflammatory (EaTLR, AMP), and neuronal transmission (nAchR α5). LC attenuated the high melanized deposits in the circular musculature, fiber disarrangement, destruction of secretory glands, immune inefficiency, and impulsive behavior pattern triggered by Ro exposure. However, the effects of LC and Ro on gene expression were more heterogeneous. In summary, SA imbalance, potentially associated with mitochondrial dysfunction, appears to be an evolutionary component triggering oxidative, inflammatory, and behavioral changes observed in psychiatric disorders that are inhibited by LC exposure.

Patients on acute psychiatric wards desire more psychosocial treatment than they receive, according to recent studies, but evidence-based interventions tailored to this setting are currently lacking. Metacognitive Training for psychosis (MCT) is a flexible, easy-to-administer group therapy that has been adapted to meet this demand (MCT-Acute). Thirty-seven patients with severe mental illness took part in MCT-Acute twice a week during their stay on a locked acute ward and were interviewed before, during, and after the intervention period regarding subjective utility, subjective adverse events, and symptom severity; attendance rates and reasons for absence were recorded. In addition, staff rated adverse events, symptom severity, and functioning (German Clinical Trial Register ID: DRKS00020551). Overall, most patients evaluated MCT-Acute positively and reported symptom stabilization. Staff also reported improvement in functioning. No clinician-rated adverse events related to participation in MCT-Acute were reported. Conducting MCT-Acute is feasible and safe and may contribute to meeting patients', practitioners', and researchers' demands for more evidence-based psychotherapeutic interventions for the acute psychiatric care setting.

ID: DRKS00020551, https://drks.de/search/de/trial/DRKS00020551.

Suicide is a serious global public health problem, with a worrying recent increase in suicide rates in both adolescent and adult populations. However, it is essential to recognize that suicide is preventable. A myriad of factors contributes to an individual's vulnerability to suicide. These factors include various potential causes, from psychiatric disorders to genetic and epigenetic alterations. These changes can induce dysfunctions in crucial systems such as the serotonergic, cannabinoid, and hypothalamic-pituitary-adrenal axes. In addition, early life experiences of abuse can profoundly impact an individual's ability to cope with stress, ultimately leading to changes in the inflammatory system, which is a significant risk factor for suicidal behavior. Thus, it is clear that suicidal behavior may result from a confluence of multiple factors. This review examines the primary risk factors associated with suicidal behavior, including psychiatric disorders, early life adversities, and epigenetic modifications. Our goal is to elucidate the molecular changes at the genetic, epigenetic, and molecular levels in the brains of individuals who have taken their own lives and in the plasma and peripheral mononuclear cells of suicide attempters and how these changes may serve as predisposing factors for suicidal tendencies.

Suicidal behavior is strongly associated with major affective disorders, but there is a need to quantify and compare specific risk and protective factors in bipolar disorder (BD) and major depressive disorder (MDD).

In 4307 extensively evaluated major affective-disorder participants with BD (n = 1425) or MDD (n = 2882) diagnosed by current international criteria, we compared characteristics among those with versus without suicidal acts from illness-onset through 8.24 years of follow-up.

Suicidal acts were identified in 11.4 % of participants; 25.9 % were violent and 6.92 % (0.79 % of all participants) were fatal. Associated risk factors included: diagnosis (BD > MDD), manic/psychotic features in first-episodes, family history of suicide or BD, separation/divorce, early abuse, young at illness-onset, female sex with BD, substance abuse, higher irritable, cyclothymic or dysthymic temperament ratings, greater long-term morbidity, and lower intake functional ratings. Protective factors included marriage, co-occurring anxiety disorder, higher ratings of hyperthymic temperament and depressive first episodes. Based on multivariable logistic regression, five factors remained significantly and independently associated with suicidal acts: BD diagnosis, more time depressed during prospective follow-up, younger at onset, lower functional status at intake, and women > men with BD.

Reported findings may or may not apply consistently in other cultures and locations.

Suicidal acts including violent acts and suicides were more prevalent with BD than MDD. Of identified risk (n = 31) and protective factors (n = 4), several differed with diagnosis. Their clinical recognition should contribute to improved prediction and prevention of suicide in major affective disorders.

Bipolar disorder is associated with a considerable risk of suicide, and this fact must be incorporated into management of all patients with the condition. This article highlights the importance of a more nuanced understanding of the factors associated with the increased risk of suicidal behavior in people diagnosed as having bipolar disorder and interventions that could mitigate it. Several sociodemographic, clinical, environmental, and other variables have been associated with suicide attempts or deaths in bipolar disorder. Youths with bipolar disorder are a particularly vulnerable group, and their trajectory of illness could be modified by early interventions. Several medications have been studied regarding their relationship to suicide risk in bipolar disorder, and interventional psychiatry is a newer area of research focus. Finally, community-based approaches can be incorporated into a comprehensive approach to suicide prevention. This article summarizes the current understanding of key variables that can help inform a clinical risk assessment of individuals and interventions that can be employed in suicide prevention in bipolar disorder.

Impulsivity is a transdiagnostic feature linked to severe clinical expression and a potential target for psychopharmacological strategies. Biological underpinnings are largely unknown, but involvement of immune dysregulation has been indicated, and the effects of psychopharmacological agents vary. We investigated if impulsivity was associated with circulating immune marker levels and with a range of psychopharmacological treatment regimens in severe mental disorders.

Impulsivity was assessed in a sample (N = 657) of patients with schizophrenia or schizophreniform disorder (SCZ) (N = 116) or bipolar disorder (BD) (N = 159) and healthy participants (N = 382) using the Barratt Impulsiveness Scale (BIS-11) questionnaire. Plasma levels of systemic immune markers (RANTES, IL-1RA, IL-18, IL-18BP, sTNFR-1) were measured by enzyme immunoassays. Patients underwent thorough clinical assessment, including evaluation of psychotropic medication. Associations were assessed using linear regressions.

Impulsivity  was positively associated with SCZ (p < 0.001) and BD (p < 0.001) diagnosis and negatively associated with age (p < 0.05), but not significantly associated with any of the circulating immune markers independently of diagnostic status. Among patients, impulsivity was negatively associated with lithium treatment (p = 0.003) and positively associated with antidepressant treatment (p = 0.011) after controlling for diagnosis, psychotropic co-medications, manic symptoms, and depressive symptoms.

We report elevated impulsivity across SCZ and BD but no associations to systemic immune dysregulation based on the current immune marker selection. The present study reveals associations between impulsivity in severe mental disorders and treatment with lithium and antidepressants, with opposite directions. Future studies are warranted to determine the causal directionality of the observed associations with psychopharmacotherapy.

The present study was aimed at investigating the clinical correlates of evening chronotype in a population of subjects suffering from bipolar disorders (BD).

We assessed chronotype using the Morningness-Eveningness Questionnaire. We administered the brief Temperament Evaluation of Memphis, Pisa, and San Diego, the Barratt Impulsiveness Scale, and the Alda Scale to evaluate affective temperaments, impulsiveness, and response to mood stabilisers. We performed bivariate analyses and ran a logistic regression model to analyse clinical variables associated with evening chronotype.

In our sample (n = 178), subjects with an evening chronotype (n = 56, 31.5%) more often suffered from BD type I and reported higher prevalence of seasonality, antidepressant-induced mood switches, psychotic, aggressive, mixed, and anxiety features, and substance use disorders. The number of lifetime suicide attempts and mood episodes was higher in this subgroup. Depressive, cyclothymic, irritable, and anxious temperament scores were higher among evening-chronotype subjects, who also displayed greater levels of impulsiveness and worse treatment response. At the logistic regression, evening chronotype was associated with depressive and irritable temperaments.

Subjects with evening chronotype display higher clinical severity and worse BD course. Clinicians should evaluate the presence of evening chronotype in BD subjects, especially in those with irritable or depressive temperament.Key pointsEvening chronotype is a frequent clinical feature in subjects suffering from bipolar disorders (BD);Affective temperaments, particularly depressive and irritable, are associated with evening chronotype in BD;Evening chronotype underpins higher severity of the clinical picture in BD, as well as a worse response to mood stabiliser treatment;Circadian preferences should be systematically assessed in subjects suffering from BD, with particular attention to evening preference.

Mounting evidence showed that insula contributed to the neurobiological mechanism of suicidal behaviors in bipolar disorder (BD). However, no studies have analyzed the dynamic functional connectivity (dFC) of insular Mubregions and its association with personality traits in BD with suicidal behaviors. Therefore, we investigated the alterations of dFC variability in insular subregions and personality characteristics in BD patients with a recent suicide attempt (SA).

Thirty unmedicated BD patients with SA, 38 patients without SA (NSA) and 35 demographically matched healthy controls (HCs) were included. The sliding-window analysis was used to evaluate whole-brain dFC for each insular subregion seed. We assessed between-group differences of psychological characteristics on the Minnesota Multiphasic Personality Inventory-2. Finally, a multivariate regression model was adopted to predict the severity of suicidality.

Compared to NSA and HCs, the SA group exhibited decreased dFC variability values between the left dorsal anterior insula and the left anterior cerebellum. These dFC variability values could also be utilized to predict the severity of suicidality (r = 0.456, p = 0.031), while static functional connectivity values were not appropriate for this prediction. Besides, the SA group scored significantly higher on the schizophrenia clinical scales (p < 0.001) compared with the NSA group.

Our findings indicated that the dysfunction of insula-cerebellum connectivity may underlie the neural basis of SA in BD patients, and highlighted the dFC variability values could be considered a neuromarker for predictive models of the severity of suicidality. Moreover, the psychiatric features may increase the vulnerability of suicidal behavior.

Suicide attempts in Bipolar Disorder are characterized by high levels of lethality and impulsivity. Reduced rates of amygdala and cortico-limbic habituation can identify a fMRI phenotype of suicidality in the disorder related to internal over-arousing states. Hence, we investigated if reduced amygdala and whole-brain habituation may differentiate bipolar suicide attempters (SA, n = 17) from non-suicide attempters (nSA, n = 57), and healthy controls (HC, n = 32). Habituation was assessed during a fMRI task including facial expressions of anger and fear and a control condition. Associations with suicidality and current depressive symptomatology were assessed, including machine learning procedure to estimate the potentiality of habituation as biomarker for suicidality. SA showed lower habituation compared to HC and nSA in several cortico-limbic areas, including amygdalae, cingulate and parietal cortex, insula, hippocampus, para-hippocampus, cerebellar vermis, thalamus, and striatum, while nSA displayed intermediate rates between SA and HC. Lower habituation rates in the amygdalae were also associated with higher depressive and suicidal current symptomatology. Machine learning on whole-brain and amygdala habituation differentiated SA vs. nSA with 94% and 69% of accuracy, respectively. Reduced habituation in cortico-limbic system can identify a candidate biomarker for attempting suicide, helping in detecting at-risk bipolar patients, and in developing new therapeutic interventions.

Bipolar disorder (BD) is associated with marked suicidal susceptibility, particularly during a major depressive episode. However, the evaluation of suicidal risk remains challenging since it relies mainly on self-reported information from patients. Hence, it is necessary to complement neuroimaging features with advanced machine learning techniques in order to predict suicidal behavior in BD patients. In this study, a total of 288 participants, including 75 BD suicide attempters, 101 BD nonattempters and 112 healthy controls, underwent a resting-state functional magnetic resonance imaging (rs-fMRI). Intrinsic brain activity was measured by amplitude of low-frequency fluctuation (ALFF). We trained and tested a two-level k-nearest neighbors (k-NN) model based on resting-state variability of ALFF with fivefold cross-validation. BD suicide attempters had increased dynamic ALFF values in the right anterior cingulate cortex, left thalamus and right precuneus. Compared to other machine learning methods, our proposed framework had a promising performance with 83.52% accuracy, 78.75% sensitivity and 87.50% specificity. The trained models could also replicate and validate the results in an independent cohort with 72.72% accuracy. These findings based on a relatively large data set, provide a promising way of combining fMRI data with machine learning technique to reliably predict suicide attempt at an individual level in bipolar depression. Overall, this work might enhance our understanding of the neurobiology of suicidal behavior by detecting clinically defined disruptions in the dynamics of instinct brain activity.

There is a critical need to better understand the factors underlying the increased suicide risk for youth with bipolar disorder (BD) in order to develop targeted prevention efforts. This study aimed to examine differences in characteristics of suicide ideation (SI) in youth with BD compared to youth with major depressive disorder (MDD) that may be associated with increased suicide risk.

One hundred and fifty-one participants (92 MDD and 59 BD), ages 13-21, completed a diagnostic interview and clinical assessments. Lifetime symptoms of SI and SA were assessed using the Columbia Suicide Severity Rating Scale. Ordinal logistic regression models were used to investigate whether the diagnostic group predicted the severity and intensity of the most severe or most common SI with the age of onset, age, and gender as covariates.

Compared to MDD youth, BD youth were more likely to report experiencing more severe SI, p = 0.039, experiencing the most severe SI more frequently, p = 0.002, having less control of the most severe SI, p = 0.012, and that deterrents were less likely to stop them from acting on the most severe SI, p = 0.006.

This study highlights differences in the severity and intensity of SI in youth with BD and suggests that youth with BD have greater difficulty inhibiting thoughts of SI which may lead to less resistance to suicide action. Findings underscore the need for a more detailed assessment of SI in youth with BD to better understand SI as a proximal risk factor for future SA and a potential target for intervention.

Response to lithium (Li) is highly variable in bipolar disorders (BD). Despite decades of research, no clinical predictor(s) of response to Li prophylaxis have been consistently identified. Recently, we developed epigenetic Methylation Specific High-Resolution Melting (MS-HRM) assays able to discriminate good responders (GR) from non-responders (NR) to Li in individuals with BD type 1 (BD-I). This study examined whether a combination of clinical and epigenetic markers can distinguish NR from other types of Li responders.

We recorded clinical variables that are potentially associated with Li response in 64 individuals with BD-I. MS-HRM assays were performed on DNA isolated from peripheral blood. We used backward stepwise logistic regression analyses, followed by receiver operating characteristic (ROC) curve analysis to estimate the performance of the clinical variables, alone then in combination with the epigenetic biomarkers, to identify GR and partial responders (PaR) vs NR.

Polarity at onset, psychotic symptoms at onset and family history of BD classified correctly 70% of individuals according to their Li response (PaR + GR = 86%; NR = 35%). When combined with the epigenetic biomarkers, these three clinical variables plus alcohol misuse (and one DMR: Differentially Methylated Region) correctly classified 86% of individuals, improving the prediction of PaR + GR (93%) and of NR (70%). The ROC analysis demonstrated an improvement in the area under the curve from 0.75 (clinical variables alone) to 0.87 (combination of clinical and epigenetic markers).

Combining clinical predictors and DNA methylation markers of Li response may have greater utility in clinical practice than relying on clinical characteristics alone.

Bipolar disorders (BDs) are recurrent and sometimes chronic disorders of mood that affect around 2% of the world's population and encompass a spectrum between severe elevated and excitable mood states (mania) to the dysphoria, low energy, and despondency of depressive episodes. The illness commonly starts in young adults and is a leading cause of disability and premature mortality. The clinical manifestations of bipolar disorder can be markedly varied between and within individuals across their lifespan. Early diagnosis is challenging and misdiagnoses are frequent, potentially resulting in missed early intervention and increasing the risk of iatrogenic harm. Over 15 approved treatments exist for the various phases of bipolar disorder, but outcomes are often suboptimal owing to insufficient efficacy, side effects, or lack of availability. Lithium, the first approved treatment for bipolar disorder, continues to be the most effective drug overall, although full remission is only seen in a subset of patients. Newer atypical antipsychotics are increasingly being found to be effective in the treatment of bipolar depression; however, their long term tolerability and safety are uncertain. For many with bipolar disorder, combination therapy and adjunctive psychotherapy might be necessary to treat symptoms across different phases of illness. Several classes of medications exist for treating bipolar disorder but predicting which medication is likely to be most effective or tolerable is not yet possible. As pathophysiological insights into the causes of bipolar disorders are revealed, a new era of targeted treatments aimed at causal mechanisms, be they pharmacological or psychosocial, will hopefully be developed. For the time being, however, clinical judgment, shared decision making, and empirical follow-up remain essential elements of clinical care. This review provides an overview of the clinical features, diagnostic subtypes, and major treatment modalities available to treat people with bipolar disorder, highlighting recent advances and ongoing therapeutic challenges.

Lithium is the standard treatment for bipolar disorders (BD) in adults. There is a dearth of data on its use in the pediatric age. This review aimed to investigate the use of lithium in pediatric bipolar disorder (BD) and other externalizing childhood-related disorders.

We applied the Preferred Reporting Items for Systematic Reviews and Meta-analyses criteria (PRISMA) to identify randomized controlled trials evaluating the use of lithium in pediatric (BD), conduct disorder (CD), attention deficit hyperactivity disorder, oppositional defiant disorder, and disruptive mood dysregulation disorder. The primary outcome of our study was to evaluate the efficacy of lithium compared to a placebo or other pharmacological agents. The secondary outcomes were acceptability and tolerability.

Twelve studies were eligible, 8 on BD and 4 on CD. Overall, 857 patients were treated with lithium. No studies for externalizing disorder diagnoses were identified. Regarding BD patients (n = 673), efficacy results suggested that lithium was superior to placebo in manic/mixed episodes but inferior to antipsychotics. Lithium efficacy ranged from 32% to 82.4%. Results on maintenance need to be expanded. Comorbidity rates with other externalizing disorders were extremely high, up to 98.6%. Results in CD patients (n= 184) suggested the efficacy of lithium, especially for aggressive behaviors. No severe adverse events directly related to lithium were reported in BD and CD; common side effects were similar to adults.

This systematic review supports the use of lithium in BD and CD as an efficacious and generally well-tolerated treatment in the pediatric age. However, evidence is limited due to the paucity of available data.

Lithium salts are widely used clinically, mainly for treatment of bipolar disorder, in which it is highly effective. Various preparations have been developed and tested, including older immediate-release (IR) forms of lithium carbonate and other salts and formulations with slow-release (SR) properties, developed in hopes of increasing the tolerability of lithium treatment, adherence to its use, and possibly its efficacy. Systematic reviews of head-to-head comparisons of pharmacological and clinical properties of such preparations are lacking. Accordingly, we systematically reviewed clinical studies of both IR and SR formulations of lithium salts, seeking to compare their pharmacokinetic properties, adverse effects, clinical tolerability, and clinical effectiveness. Very few such comparative studies were identified and they are highly heterogeneous in design and findings. In 11 included reports, SR formulations appeared to be better tolerated and possibly to be associated with greater adherence to treatment. Studies of comparative clinical efficacy are lacking. Despite decades of use of various lithium salts, systematic comparisons of the pharmacological and clinical properties of IR vs. SR preparations remain rare and to be deepened, though with suggestive superiority of SR salts.

Lithium treatment is considered the gold standard for the long-term management of bipolar disorder and recurrent unipolar depression. It is also extremely effective in other psychiatric conditions characterized by impulsivity and aggression, and for the prevention of suicidal behaviours.

This paper provides a scoping review and an expert commentary regarding the use of lithium in adult patients. Available information about efficacy, tolerability, dosing, and switching is analyzed, and the strategies that may be most useful in real-world clinical settings are highlighted.

Lithium is effective on different domains of bipolar disorder, including the long-term prevention of recurrences of affective episodes, management of acute mania as well as in the prophylaxis of all affective episodes. Lithium has been defined a 'forgotten drug,' since its use in routine clinical practice has been declined over the last 20 or 30 years. Reasons for this trend include lack of adequate training on the management of lithium side effects. Considering its efficacy, use of lithium in ordinary clinical practice should be promoted. Several strategies, such as using slow-release formulations, can be easily implemented in order to minimize lithium side effects and improve its tolerability profile.

Time to a new episode of bipolar disorder (BD) is shorter after discontinuing lithium rapidly. We now address this and other factors associated with the risk of early illness after discontinuing lithium.

We compared factors for association with recurrences of BD within 12 months of discontinuing long-term lithium treatment, using bivariate and multivariable analyses, as well as survival analysis to evaluate latency to new episodes versus rate of lithium-discontinuation and prior treatment duration.

Among 227 BD subjects who received lithium for 4.47 [CI: 3.89-5.04] years and then discontinued, rapid treatment-discontinuation, and stopping for medical reasons were strongly associated with new illness-episodes within 12 months, as were diagnosis (BD-I > BD-II), greater morbidity during lithium-treatment, and less education, but neither longer treatment nor serum lithium concentrations. Discontinuation rate was strongly associated with shorter median latency to a new episode (rapid: 3.50; gradual [≥2 weeks]: 10.6 months), even with very early recurrences excluded to avoid potential contributions of emerging illness to treatment-discontinuation. Early recurrence was not associated with treatment-duration of ≥2 or ≥5 years or less. In multivariable logistic regression, rapid discontinuation, stopping for medical reasons, and BD-I diagnosis remained significantly, independently associated with early illness after lithium-discontinuation, with no effect of treatment duration.

Early recurrence risk was again much greater after rapid discontinuation of lithium and discontinuing for medical reasons, somewhat greater with BD-I than BD-II, and following greater morbidity during lithium-treatment, but not related to dose or duration of preceding treatment exposure.

The evolution of cognitive performance throughout the lifespan in bipolar disorder (BD) is understudied. This cross-sectional study aims to describe the cognitive performance across age groups.

A sample of 654 participants was recruited for this study (BD = 432 and healthy controls -HC- =222). Three subgroups, divided according to age range (18 to 35, 36 to 49, and ≥50 years old) were analyzed after administering a comprehensive neuropsychological battery including six cognitive domains. Demographic, clinical, and psychosocial functioning data were also analyzed. Generalized linear models (GLM) with age, diagnostic group, and age × group as main effects were carried out to examine their potential association on cognitive domains. Subsequently, a GLM in the BD sample was conducted to analyze interactions of several clinical variables by age on each cognitive domain.

Main effects of diagnostic group and age were found in all cognitive domains. Significant group × age effect interaction was found for attention domain (p = 0.02) demonstrating a worse cognitive evolution across age in BD, driven by older age, but not in HC. Significant interaction effects of higher number of manic episodes and older age were also found in attention and verbal memory. Older age was also associated with a longer duration of illness, higher number of episodes, more somatic comorbidities, and poorer psychosocial functioning.

These results suggest that older age was associated with a selective cognitive decline in BD in the attentional domain. These findings highlight the importance of developing interventions targeting cognitive dysfunction throughout the BD adulthood lifespan.

Pharmacological treatments recommended for bipolar depression are inconsistent across guidelines. We compared the efficacy and safety of antipsychotics and mood stabilizers for bipolar depression.

A systemic review and meta-analysis of randomized controlled trials comparing antipsychotics and mood stabilizers for bipolar depression was conducted based on a literature search of major electronic databases.

Three studies comparing quetiapine with lithium were identified and analyzed; no other antipsychotic-mood stabilizer combinations were found. The meta-analysis revealed no significant differences between quetiapine and lithium for the following outcomes: (1) remission from depressive episodes (risk ratio [RR]: 1.80, 95% CI: 0.51-6.40, P = 0.36), (2) changes in depressive symptom (standardized mean difference: -0.22, 95% CI: -0.52-0.08, P = 0.15), (3) changes in social function (standardized mean difference: -0.00, 95% CI: -0.19-0.18, P = 0.98), (4) suicide-related events (odds ratio [OR]: 2.35, 95% CI: 0.40-13.65, P = 0.34), (5) severe adverse events (OR: 1.63, 95% CI: 0.51-5.20, P = 0.41), (6) dropouts due to adverse events (RR: 1.19, 95% CI: 0.76-1.87, P = 0.45, 7) dropout for any reasons (RR: 0.95, 95% CI: 0.74-1.22, P = 0.70).

Although this study found no differences in the efficacy and safety of quetiapine and lithium for bipolar depression, a comprehensive comparison of antipsychotics and mood stabilizers was not performed. Further studies are needed to clarify which of these, not just quetiapine and lithium, is more useful for bipolar depression.

This study aimed to identify predictors of emergency department (ED) use for suicide ideation or suicide attempt compared with other reasons among 14,158 patients with substance-related disorders (SRD) in Quebec (Canada).

Longitudinal data on clinical, sociodemographic, and service use variables for patients who used addiction treatment centers in 2012-13 were extracted from Quebec administrative databases. A multinomial logistic regression was produced, comparing predictors of suicide ideation or attempts to other reasons for ED use in 2015-16.

Patients using ED for both suicide ideation and attempt were more likely to have bipolar or personality disorders, problems related to the social environment, 4+ previous yearly outpatient consultations with their usual psychiatrist, high prior ED use, and dropout from SRD programs in addiction treatment centers in the previous 7 years, compared with those using ED for other reasons. Patients with alcohol- or drug-related disorders other than cannabis and living in the least materially deprived areas, urban territories, and university healthcare regions made more suicide attempts than those using ED for other reasons. Patients with common mental disorders, 1-3 previous yearly outpatient consultations with their usual psychiatrist, one previous treatment episode in addiction treatment centers, and those using at least one SRD program experienced more suicide ideation than patients using ED for other reasons.

Clinical variables most strongly predicted suicidal behaviors, whereas completion of SRD programs may help to reduce them. SRD services and outreach strategies should be reinforced, particularly for patients with complex issues living in more advantaged urban areas. HIGHLIGHTSOver 10% of ED visits were for suicidal behaviors among patients with SRD.ED use for suicidal behaviors was mainly associated with clinical variables.Addiction treatment centers may help reduce ED use for suicidal behaviors.

Bipolar disorder (BD) has a higher lifetime rate of suicide attempts (SA) than other psychiatric disorders. Furthermore, BD patients with SA (BD + S) are prone to a worse quality of life. However, the pathophysiology of BD + S is poorly understood. To further reveal the potential mechanisms of BD + S, abnormalities in peripheral plasma inflammatory cytokines and brain white matter (WM) in BD + S, as well as the correlation between them are investigated.

We tested the levels of TNF-α, IL-1β, and IL-6 in peripheral plasma and collected the diffusion tensor imaging (DTI) data from 14 BD + S, 24 BD patients without SA (BD-S), and 26 healthy controls (HCs). The three groups were matched by age and gender. The levels of TNF-α, IL-1β, and IL-6 were detected by Luminex multifactor detection technology, and the fractional anisotropy (FA) values were employed to depict the alterations of WM. Partial correlation analyses were conducted to detect correlations between levels of TNF-α, IL-1β, and IL-6 and changes of WM, and the relationships between severity of clinical symptoms, including scores of HAMD-17 and YMRS, and cytokine levels or FA values in all groups.

For plasma inflammatory cytokines, there was no significant difference in their levels except for IL-6 among the three groups. Post-hoc analyses revealed that increased IL-6 level was only detected in BD + S (p < 0.05, Bonferroni correction). For DTI, BD + S showed specifically decreased FA in the bilateral middle cerebellar peduncle and the left superior corona radiata compared to BD-S and HCs (p < 0.05, Bonferroni correction). Additionally, both BD + S and BD-S groups revealed decreased FA in the bilateral body and genu of corpus callosum (CC) compared to HCs (p < 0.05, Bonferroni correction). No significant correlation between plasma inflammatory cytokines and WM integrity was found. In the BD + S group, we found negative correlation between the scores of YMRS and FA values of the left middle cerebellar peduncle (r = -0.74, p = 0.035).

The inflammation and impaired WM integrity may provide a scientific basis to understand the potential mechanisms of BD + S.

The underlying pathologies of psychiatric disorders, which cause substantial personal and social losses, remain unknown, and their elucidation is an urgent issue. To clarify the core pathological mechanisms underlying psychiatric disorders, in addition to laboratory-based research that incorporates the latest findings, it is necessary to conduct large-sample-size research and verify reproducibility. For this purpose, it is critical to conduct multicenter collaborative research across various fields, such as psychiatry, neuroscience, molecular biology, genomics, neuroimaging, cognitive science, neurophysiology, psychology, and pharmacology. Moreover, collaborative research plays an important role in the development of young researchers. In this respect, the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium and Cognitive Genetics Collaborative Research Organization (COCORO) have played important roles. In this review, we first overview the importance of multicenter collaborative research and our target psychiatric disorders. Then, we introduce research findings on the pathophysiology of psychiatric disorders from neurocognitive, neurophysiological, neuroimaging, genetic, and basic neuroscience perspectives, focusing mainly on the findings obtained by COCORO. It is our hope that multicenter collaborative research will contribute to the elucidation of the pathological basis of psychiatric disorders.

Rural locations have been associated with suicidal risk; low population density may be a relevant factor. Accordingly, we investigated hypothesized associations between suicidal ideation and behavior with selected geographic and population-related measures and other factors.

Consenting adult patients at a mood disorder center in Cagliari, Sardinia, were assessed for the presence of suicidal ideation and acts and their association with selected demographic and clinical factors as well as indicators of urbanicity and rurality, including distance from the region's main metropolitan area, population density, altitude, and population growth trends.

Of 5,668 subjects, 27% had an indication of lifetime suicidal behavior or ideation; 8.6% had at least one suicidal act. Low population density, higher altitude and their interaction, distance from the metropolitan center of the main city (Cagliari), and population decline were associated with greater risk of suicidal ideation or behavior. In addition, and as expected, alcohol or substance abuse, diagnosis of mood disorders, higher depression ratings at intake, being younger at illness-onset, family history of suicide or other psychiatric disorder, being female, unmarried, separated or divorced, currently smoking cigarettes, being unemployed, and having experienced sexual abuse all were more likely in subjects with suicidal ideation or behavior.

Suicidal ideation and behavior were associated with indicators of social isolation as well as with previously reported clinical and demographic risk factors.

Mortality is increased in bipolar disorder due to both suicide and death by physical disorders, but it has never been investigated whether these mortalities translate into relatives to patients with bipolar disorder. The aim was to present the life expectancy and the overall mortality and mortality due to suicide and physical disorders among patients with bipolar disorder and their unaffected full siblings, respectively, compared with control individuals from the general population.

We used Danish nation-wide population-based longitudinal register linkage to identify 19.955 patients with bipolar disorder, their 13.923 siblings and 20 sex, age and calendar matched control individuals from the general population. Follow-up was from 1995 to 2017.

Bipolar disorder was associated with a decreased life expectancy of 7.7 (95% CI: 7.4-8.1) years and increased mortality overall (hazard ratio (HR): 2.11 (95% CI: 2.04-2.18)) and due to suicide (HR: 18.23 (95% CI: 15.81-21.02) and physical disorders (HR: 2.01 (95% CI: 1.94-2.08). In contrast, siblings to patients with bipolar disorder who were unaffected by bipolar disorder did not have decreased life expectancy (0.45 (95% CI: -6.62-2.46)) or increased mortality overall (HR: 1.00 (95% CI: 0.88-1.14) or due to suicide (HR: 1.50 (95% CI: 0.95-2.36) or physical disorders (HR: 0.99 (95% CI: 0.87-1.34).

Increased mortality in bipolar disorder is mainly due to the impact of bipolar psychopathology and to a lesser degree to familial transmitted factors, highlighting the urgent need for preventive intervention studies in relation to suicide and physical disorders following onset of bipolar disorder.