Syndrome métabolique et troubles bipolaires : le sommeil est-il le chaînon manquant ?

ObjectiveTo examine the pathophysiologic mechanisms that may link circadian disorder and metabolic syndrome in bipolar disorder (BP).MethodA systematic review of the literature was conducted from January 2013 to January 2015, using the Medline and Cochrane databases, using the keywords “metabolic syndrome”, “obesity”, “leptin” and “circadian disorders”, “sleeping disorders” and cross-referencing them with “bipolar disorder”. The following types of publications were candidates for review: (i) clinical trials; (ii) studies involving patients diagnosed with bipolar disorder; (iii) studies involving patients with sleeping disorder; or (iv) data about metabolic syndrome.ResultsForty articles were selected. The prevalence of metabolic syndrome in BP was significantly higher compared to the general population (from 36 to 49% in the USA [Vancampfort, 2013]), and could be explained by several factors including reduced exercise and poor diet, genetic vulnerability, frequent depressive episodes, psychiatric comorbidity and psychotropic treatment. This high frequency of metabolic syndrome worsens the prognosis of these patients, increasing morbidity and mortality. Secondly, patients with BP experienced circadian and sleep disturbance, including modification in melatonin secretion. These perturbations are known to persist in periods of mood stabilization and are found in patients’ relatives. Circadian disturbances are factors of relapse in bipolar patients, and they may also have a role in the metabolic comorbidities of these patients. Recent studies show that in populations of patients with bipolar disorder, a correlation between circadian disturbance and metabolic parameters are found. To identify the pathophysiological pathway connecting both could lead to a better comprehension of the disease and new therapeutics. In the overall population, mechanisms have been identified linking circadian and metabolic disorder involving hormones like leptin and ghrelin. These hormones are keys to regulation of energy balance in the organism, via their action on the hypothalamus, and are also regulated by sleep. We have hypothesized that these pathways could be implicated in the vulnerability of bipolar patients to metabolic syndrome. This hypothesis is supported by several studies showing dysregulation in leptin and ghrelin secretion in multiple psychiatric disorders, including bipolar disorder, as well as genetic variations of leptin and ghrelin genes in these diseases. We also assume that other mechanisms may be at stake to explain this link, such as melatonin dysregulation and inflammation.ConclusionsCircadian and sleeping disorder may have a role in the prevalence of metabolic syndrome in BP. Hormones like leptin and ghrelin could be the link between these perturbations. Prevention and treatment of circadian disorder in BP may greatly reduce the occurrence of MetS in these patients. Being aware of this statement and taking care of these troubles should be a big step forward for treatment of BP.     

Metabolic syndrome in subjects with bipolar disorder and major depressive disorder in a current depressive episode: Population-based study: Metabolic syndrome in current depressive episode

ObjectiveTo assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode.MethodsThis was a cross-sectional study with young adults aged 24–30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview – Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III).ResultsThe sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016).ConclusionMetabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis.     

Neither bipolar nor obsessive-compulsive disorder: compulsive buyers are impulsive acquirers

IntroductionCompulsive buying (CB) is currently classified as an impulse control disorder (ICD) not otherwise classified. Compulsive buying prevalence is estimated at around 5% of the general population. There is controversy about whether CB should be classified as an ICD, a subsyndromal bipolar disorder (BD), or an obsessive-compulsive disorder (OCD) akin to a hoarding syndrome. To further investigate the appropriate classification of CB, we compared patients with CB, BD, and OCD for impulsivity, affective instability, hoarding, and other OCD symptoms.MethodEighty outpatients (24 CB, 21 BD, and 35 OCD) who were neither manic nor hypomanic were asked to fill out self-report questionnaires.ResultsCompulsive buying patients scored significantly higher on all impulsivity measures and on acquisition but not on the hoarding subdimensions of clutter and “difficulty discarding.” Patients with BD scored higher on the mania dimension from the Structured Clinical Interview for Mood Spectrum scale. Patients with OCD scored higher on obsessive-compulsive symptoms and, particularly, higher on the contamination/washing and checking dimensions from the Padua Inventory; however, they did not score higher on any hoarding dimension. A discriminant model built with these variables correctly classified patients with CB (79%), BD (71%), and OCD (77%).ConclusionPatients with CB came out as impulsive acquirers, resembling ICD- rather than BD- or OCD-related disorders. Manic symptoms were distinctive of patients with BD. Hoarding symptoms other than acquisition were not particularly associated with any diagnostic group.     

Staging and Neuroprogression in Bipolar Disorder: A Systematic Review of the Literature

IntroductionThe use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term “neuroprogression” has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress.MethodA search in the PubMed database was performed with the following terms: “staging”, “neuroprogression”, “serum”, “plasma”, “blood”, “neuroimaging”, “PET scan”, “fMRI”, “neurotrophins”, “inflammatory markers” and “oxidative stress markers”, which were individually crossed with “cognition”, “functionality”, “response to treatments” and “bipolar disorder”. The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included.ResultsWe divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences.ConclusionThe challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.     

Factorial structure and familial aggregation of the Hypomania Checklist-32 (HCL-32): Results of the NIMH Family Study of Affective Spectrum Disorders

BackgroundThere is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people.PurposeThe aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD.ProceduresNinety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used.FindingsA four-factor (“Activity/Increased energy,” “Distractibility/Irritability”, “Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14–1.30). The “Distractibility/Irritability” score was transmitted within families (β = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors.ConclusionsOur findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses.     

Exploring the association between bipolar disorder and uric acid: A mediation analysis

ObjectiveRecent evidence shows that bipolar disorder might be associated with a purinergic system dysfunction. This study aimed at (i) testing the association between bipolar disorder and uric acid serum levels, and (ii) clarifying whether this relationship is mediated by metabolic syndrome and other relevant metabolic parameters.MethodsPatients consecutively admitted to a Mental Health Inpatient Unit, with a diagnosis of bipolar disorder or other severe mental disorders, and an appropriate healthy control sample, were included in this cross-sectional, exploratory study. We performed linear regression analyses, to explore factors associated with uric acid levels, and formal tests of mediation to assess mediating effect of candidate variables.Results176 individuals with mental disorders and 89 healthy controls met inclusion criteria. Bipolar disorder was the only diagnostic subgroup significantly associated with increased uric acid levels. Furthermore, male gender, metabolic syndrome, as well as abdominal circumference and triglycerides levels, had a significant effect on uric acid. Relevant mediation analyses showed that the estimated effect between bipolar disorder and uric acid levels was only partially mediated by metabolic abnormalities.ConclusionThis study suggests a direct association between bipolar disorder and uric acid levels, only partially mediated by metabolic abnormalities. It seems consistent with results of previous studies highlighting a purinergic dysfunction in bipolar disorder and the role that purinergic modulators, lowering uric acid levels, could have in clinical practice.     

Impact of comorbid migraine on the clinical course of bipolar disorder

BackgroundRecent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown.ObjectiveThis study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course.MethodsThree hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition–defined bipolar I or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews.ResultsPatients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction.ConclusionsComorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses.     

Different characteristics associated with suicide attempts among bipolar I versus bipolar II disorder patients

BackgroundSuicide attempts are common in patients with bipolar disorder (BD), and consistently associated with female gender and certain unfavorable BD illness characteristics. Findings vary, however, regarding effects of BD illness subtype and yet other illness characteristics upon prior suicide attempt rates. We explored the effects of demographics and BD illness characteristics upon prior suicide attempt rates in patients stratified by BD illness subtype (i.e., with bipolar I disorder (BDI) versus bipolar II disorder (BDII)).MethodsOutpatients referred to the Stanford BD Clinic during 2000–2011 were assessed with the Systematic Treatment Enhancement Program for BD Affective Disorders Evaluation. Rates of prior suicide attempt were compared in patients with and without diverse demographic and BD illness characteristics stratified by BD subtype.ResultsAmong 494 BD outpatients (mean ± SD age 35.6 ± 13.1 years; 58.3% female; 48.6% BDI, 51.4% BDII), overall prior suicide attempt rates in were similar in BDI versus BDII patients, but approximately twice as high in BDI (but not BDII) patients with compared to without lifetime eating disorder, and in BDII (but not BDI) patients with compared to without childhood BD onset. In contrast, current threshold-level suicidal ideation and lifetime alcohol use disorder robustly but less asymmetrically increased prior suicide attempt risk across BD subtypes.LimitationsAmerican tertiary bipolar disorder clinic referral sample, cross-sectional design.ConclusionsFurther studies are needed to assess the extent to which varying clinical characteristics of samples of patients with BDI and BDII could yield varying prior suicide attempt rates in patients with BDI versus BDII.     

未治疗的双相障碍患者共病代谢综合征的临床分析

目的:探讨未治疗的双相障碍(BD)患者共病代谢综合征(MS)的情况及相关因素分析。方法:收集125例未治疗的BD患者(BD组)的一般人口学资料及临床资料,检测其代谢指标,包括体质量指数(BMI)、收缩压(SBP)和舒张压(DBP)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、空腹血糖(FPG),并与201名健康体检者(对照组)比较,分析BD患者发生MS的危险因素。结果:BD组年龄明显低于对照组,校正年龄和性别后,BD组SBP及FPG异常率及MS发生率明显高于对照组(P均<0.01)。男性患者SBP、TG明显高于女性,HDL水平明显低于女性(P均<0.01);TG异常率及代谢指标异常≥2项的比率明显高于女性(P均<0.05)。Logistic回归分析显示,BD患者发生MS的危险因素是BMI、性别和年龄。结论:BD患者共病MS的风险较健康人更高,其中男性、年龄和BMI是MS的危险因素。     

Branched-chain amino acids are associated with metabolic parameters in bipolar disorder

Abstract

Objectives: An important aspect of bipolar disorder (BD) research is the identification of biomarkers pertaining to the somatic health state. The branched-chain essential amino acids (BCAAs), viz valine, leucine and isoleucine, have been proposed as biomarkers of an individual’s health state, given their influence on protein synthesis and gluconeogenesis inhibition.

Methods: BCAA levels of 141 euthymic/subsyndromal individuals with BD and 141 matched healthy controls (HC) were analysed by high-pressure lipid chromatography and correlated with clinical psychiatric, anthropometric and metabolic parameters.

Results: BD and HC did not differ in valine and isoleucine, whereas leucine was significantly lower in BD. Furthermore, correlations were found between BCAAs and anthropometric and glucose metabolism data. All BCAAs correlated with lipid metabolism parameters in females. There were no associations between BCAAs and long-term clinical parameters of BD. A negative correlation was found between valine and Hamilton Depression-Scale, and Beck Depression Inventory II, in male individuals

Conclusions: Our results indicate the utility of BCAAs as biomarkers for the current state of health, also in BD. As BD individuals have a high risk for overweight/obesity, in association with comorbid medical conditions (e.g. cardiovascular diseases or insulin resistance), health state markers are urgently required. However, no illness-specific associations were found in this euthymic/subsyndromal BD group.     

Heart rate variability in bipolar disorder: A systematic review and meta-analysis

BackgroundHeart rate variability (HRV) has been suggested reduced in bipolar disorder (BD) compared with healthy individuals (HC). This meta-analysis investigated: HRV differences in BD compared with HC, major depressive disorder or schizophrenia; HRV differences between affective states; HRV changes from mania/depression to euthymia; and HRV changes following interventions.MethodsA systematic review and meta-analysis reported according to the PRISMA guidelines was conducted. MEDLINE, Embase, PsycINFO, The Cochrane Library and Scopus were searched. A total of 15 articles comprising 2534 individuals were included.ResultsHRV was reduced in BD compared to HC (g = -1.77, 95% CI: −2.46; −1.09, P < 0.001, 10 comparisons, n = 1581). More recent publication year, larger study and higher study quality were associated with a smaller difference in HRV. Large between-study heterogeneity, low study quality, and lack of consideration of confounding factors in individual studies were observed.ConclusionsThis first meta-analysis of HRV in BD suggests that HRV is reduced in BD compared to HC. Heterogeneity and methodological issues limit the evidence. Future studies employing strict methodology are warranted.     

Understanding Aging in Bipolar Disorder by Integrating Archival Clinical Research Datasets

ObjectiveAlthough 25% of people with bipolar disorder (BD) are over age 60, there is a dearth of research on older age bipolar disorder (OABD). This report describes an initial effort to create an integrated OABD database using the U.S. National Institute of Mental Health Data Archive (NDA). Goals were to: 1) combine data from three BD studies in the United States that included overlapping data elements; 2) investigate research questions related to aims of the original studies; and 3) take an important first step toward combining existing datasets relevant to aging and BD.MethodsData were prepared and uploaded to the NDA, with a focus on data elements common to all studies. As appropriate, data were harmonized to select or collapse categories suitable for cross-walk analysis. Associations between age, BD symptoms, functioning, medication load, medication adherence, and medical comorbidities were assessed. The total sample comprised 451 individuals, mean age 57.7 (standard deviation: 13.1) years.ResultsMedical comorbidity was not significantly associated with either age or functioning and there did not appear to be an association between medication load, comorbidity, age, and adherence. Men and African-Americans were significantly more likely to have poor adherence. Both BD mania and depression symptoms were associated with functioning, but this differed across studies.ConclusionDespite limitations including heterogeneity in study design and samples and cross-sectional methodology, integrated datasets represent an opportunity to better understand how aging may impact the presentation and evolution of chronic mental health disorders across the lifespan.     

Intervenir précocement dans les stades débutants du trouble bipolaire : pourquoi,quand et comment

ObjectivesBipolar disorder (BD) is a chronic and severe psychiatric disease. There are often significant delays prior to diagnosis, and only 30 to 40 % of patients will experience complete remission. Since BD occurs most often at a young age, the disorder can seriously obstruct future socio-professional development and integration. Vulnerability-stress model of BD is considered to be the result of an interaction between vulnerability genes and environmental risk factors, which leads to the onset of the disorder most often in late adolescence or early adulthood. The clinical “staging” model of BD situates the subject in a clinical continuum of varying degrees of severity (at-risk status, first episode, full-blown BD). Given the demonstrated effectiveness of early intervention in the early stages of psychotic disorder, we posit that early intervention for early stages of BD (i.e. at-risk status and first episode mania or hypomania) would reduce the duration of untreated illness and optimize the chances of therapeutic response and recovery.MethodsWe conducted a narrative review of the literature to gather updated data on: (1) features of early stages: risk factors, at-risk symptoms, clinical specificities of the first manic episode; (2) early screening: targeted populations and psychometric tools; (3) early treatment: settings and therapeutic approaches for the early stages of BD.Results(1) Features of early stages: among genetic risk factors, we highlighted the diagnosis of BD in relatives and affective temperament including as cyclothymic, depressive, anxious and dysphoric. Regarding prenatal environmental risk, we identified peripartum factors such as maternal stress, smoking and viral infections, prematurity and cesarean delivery. Later in the neurodevelopmental course, stressful events and child psychiatric disorders are recognized as increasing the risk of developing BD in adolescence. At-risk symptoms could be classified as “distal” with early but aspecific expressions including anxiety, depression, sleep disturbance, decreased cognitive performance, and more specific “proximal” symptoms which correspond to subsyndromic hypomanic symptoms that increase in intensity as the first episode of BD approaches. Specific clinical expressions have been described to assess the risk of BD in individuals with depression. Irritability, mixed and psychotic features are often observed in the first manic episode. (2) Early screening: some individuals with higher risk need special attention for screening, such as children of people with BD. Indeed, it is shown that children with at least one parent with BD have around 50 % risk of developing BD during adolescence or early adulthood. Groups of individuals presenting other risk factors, experiencing an early stage of psychosis or depressive disorders should also be considered as targeted populations for BD screening. Three questionnaires have been validated to screen for the presence of at-risk symptoms of BD: the Hypomanic Personality Scale, the Child Behavior Checklist-Paediatric Bipolar Disorder, and the General Behavior Inventory. In parallel, ultra-high risk criteria for bipolar affective disorder (“bipolar at-risk”) distinguishing three categories of at-risk states for BD have been developed. (3) Early treatment: clinical overlap between first psychotic and manic episode and the various trajectories of the at-risk status have led early intervention services (EIS) for psychosis to reach out for people with an early stage of BD. EIS offers complete biopsychosocial evaluations involving a psychiatric examination, semi-structured interviews, neuropsychological assessments and complementary biological and neuroimaging investigations. Key components of EIS are a youth-friendly approach, specialized and intensive care and client-centered case management model. Pharmaceutical treatments for at-risk individuals are essentially symptomatic, while guidelines recommend the use of a non-antipsychotic mood stabilizer as first-line monotherapy for the first manic or hypomanic episode. Non-pharmacological approaches including psychoeducation, psychotherapy and rehabilitation have proven efficacy and should be considered for both at-risk and first episode of BD.ConclusionsEIS for psychosis might consider developing and implementing screening and treatment approaches for individuals experiencing an early stage of BD. Several opportunities for progress on early intervention in the early stages of BD can be drawn. Training first-line practitioners to identify at-risk subjects would be relevant to optimize screening of this population. Biomarkers including functional and structural imaging measures of specific cortical regions and inflammation proteins including IL-6 rates constitute promising leads for predicting the risk of transition to full-blown BD. From a therapeutic perspective, the use of neuroprotective agents such as folic acid has shown particularly encouraging results in delaying the emergence of BD. Large-scale studies and long-term follow-up are still needed to achieve consensus in the use of screening and treatment tools. The development of specific recommendations for the early stages of BD is warranted.     

Comment caractériser et traiter les plaintes de sommeil dans les troubles bipolaires ?

Objectives

Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD.

Subcortical Gray Matter Volume Abnormalities in Healthy Bipolar Offspring: Potential Neuroanatomical Risk Marker for Bipolar Disorder?

ObjectiveA growing number of structural neuroimaging studies have shown that bipolar disorder (BD) is associated with gray matter (GM) volume abnormalities in brain regions known to support affect regulation. The goal of this study was to examine whole-brain regional GM volume in healthy bipolar offspring (HBO) relative to age-matched controls to identify possible structural abnormalities that may be associated with risk for BD.MethodParticipants were 20 youths (8-17 years old) with at least one parent diagnosed with BD, and 22 age-matched healthy individuals. All of them were free of Axis I diagnoses. High-resolution magnetic resonance imaging structural images were acquired using a 3-T Siemens scanner. Voxel-based morphometric analyses were conducted using SPM5.ResultsRelative to controls, HBO had significantly increased GM volume in left parahippocampal/hippocampal gyrus (p <.05 corrected), following whole-brain analyses. This increase was correlated with puberty but not age in HBO. Region-of-interest analyses on the amygdala and orbitomedial prefrontal cortex did not yield any significant group differences after conducting small volume correction.ConclusionsThe pattern of increased GM volume in parahippocampal/hippocampal gyrus in HBO suggests a potential marker for risk for BD. It can also be considered as a potential neuroprotective marker for the disorder because HBO were free of current psychopathology. Prospective studies examining the relationship between changes in GM volume in these regions and subsequent development of BD in HBO will allow us to elucidate further the role of this region in either conferring risk for or protecting against the development of BD.     

Sleep and circadian alterations in people at risk for bipolar disorder: A systematic review

BackgroundSleep and circadian abnormalities have been mostly demonstrated in bipolar patients. However, it is not clear whether these alterations are present in population at high risk for bipolar disorder (BD), indicating a possible risk factor for this condition.ObjectiveThis systematic review aims to define current evidence about sleep and rhythm alterations in people at risk for BD and to evaluate sleep and circadian disorders as risk factor for BD.MethodsThe systematic review included all articles about the topic until February 2016. Two researchers performed an electronic search of PubMed and Cochrane Library. Keywords used were ‘sleep’ or ‘rhythm’ or ‘circadian’ AND ‘bipolar disorder’ or ‘mania’ or ‘bipolar depression’ AND ‘high-risk’ or ‘risk’.ResultsThirty articles were analyzed (7451 participants at risk for BD). Sleep disturbances are frequent in studies using both subjective measures and actigraphy. High-risk individuals reported irregularity of sleep/wake times, poor sleep and circadian rhythm disruption. Poor sleep quality, nighttime awakenings, and inadequate sleep are possible predictive factors for BD. A unique study suggested that irregular rhythms increase risk of conversion. People at risk for BD showed high cortisol levels in different times of day. Studies about anatomopathology, melatonin levels, inflammatory cytokines and oxidative stress were not identified. The most important limitations were differences in sleep and rhythm measures, heterogeneity of study designs, and lack of consistency in the definition of population at risk.ConclusionSleep and circadian disturbances are common in people at risk for BD. However, the pathophysiology of these alterations and the impact on BD onset are still unclear.     

The clinical implications of cognitive impairment and allostatic load in bipolar disorder

BackgroundAllostatic load (AL) relates to the neural and bodily “wear and tear” that emerge in the context of chronic stress. This paper aims to provide clinicians with a comprehensive overview of the role of AL in patophysiology of bipolar disorder (BD) and its practical implications.MethodsPubMed searches were conducted on English-language articles published from 1970 to June 2011 using the search terms allostatic load, oxidative stress, staging, and bipolar disorder cross-referenced with cognitive impairment, comorbidity, mediators, prevention.ResultsProgressive neural and physical dysfunction consequent to mood episodes in BD can be construed as a cumulative state of AL. The concept of AL can help to reconcile cognitive impairment and increased rates of clinical comorbidities that occur over the course of cumulative BD episodes.ConclusionsData on transduction of psychosocial stress into the neurobiology of mood episodes converges to the concept of AL. Mood episodes prevention would not only alleviate emotional suffering, but also arrest the cycle of AL, cognitive decline, physical morbidities and, eventually, related mortality. These objectives can be achieved by focusing on effective prophylaxis from the first stages of the disorder, providing mood-stabilizing agents and standardized psychoeducation and, potentially, addressing cognitive deficits by the means of specific medication and neuropsychological interventions.     

Debate: Bipolar disorder: extremely rare before puberty and antipsychotics cause serious harms – a commentary on Van Meter et al. (2019)

‘Paediatric bipolar disorder’ (PBD) remains controversial; because it is based on the hypothesis that bipolar disorder (BD) often begins in childhood with atypical forms of mania. A meta-analysis of 12 epidemiological surveys found a high prevalence of PBD among children and adolescents worldwide (1.8%), however, our study of the measurement issues (Child and Adolescent Mental Health, 23, 2018, 14) found that PBD rates were lower than claimed. Our findings are consistent with the developmental trajectory of BD, as described by most longitudinal studies of high-risk offspring. BD is extremely rare in childhood with nearly all index manic/hypomanic episodes being in midadolescence or later. Treatment for BD should not commence until the first well-defined manic/hypomanic episode, because children and younger adolescents are extremely sensitive to the side effects of second-generation antipsychotics including weight gain, metabolic syndrome, extrapyramidal side effects and the risk of cerebral atrophy, as observed in studies of juvenile animals.     

Characteristics of the gut microbiota in bipolar depressive disorder patients with distinct weight

Background

Preliminary studies have indicated metabolic dysfunction and gut dysbiosis in patients with bipolar disorder (BD). In this study, we aimed to clarify the impact of the gut microbial composition and function on metabolic dysfunction in BD patients with an acute depressive episode.

Methods

Fresh fecal samples were provided from 58 patients with BD depression, including 29 with normal weight (NW) and 29 with overweight/obesity (OW), and 31 healthy controls (HCs). The hypervariable region of 16 S rRNA gene (V3-V4) sequencing was performed using IonS5TMXL platform to evaluate the bacterial communities. Differences of microbial community and correlation to clinical parameters across different groups were analyzed.

Results

Compared to NW and HCs, the OW group showed a decreased tendency in alpha diversity index. Beta diversity was markedly different among these groups (PERMANOVA: R² = 0.034, p = 0.01) and was higher in patients versus HCs. A total number of 24 taxa displayed significantly different abundance among OW, NW, and HCs. At the family level, the abundance of three taxa was remarkably increased in NW, one in OW, and one in HCs. At the genus level, five taxa were enriched in OW, eight in NW, and two in HCs. The relative abundance of the genera Megamonas was positively associated with BMI, while Eggerthella was negatively correlated with BMI. Functional prediction analysis revealed the metabolism of cofactors and vitamins and amino acid were highly enriched in OW compared to HCs. In addition, microbial functions involved in “lipid metabolism” were depleted while the “fructose and mannose metabolism” was enriched in OW compared to NW group.

Conclusions

Specific bacterial taxa involved in pathways regulating the lipid, energy, and amino acid metabolisms may underlie the weight concerns in depressed BD patients. Potential targeting gut microbial therapy is provided for overweight/obesity patients with BD, which still need further studies in the future.     

Lithium and suicide prevention in bipolar disorder

IntroductionBipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations.MethodsWe conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: “lithium” AND “suicide” OR “suicidality” OR “suicide attempt”.ResultsAs confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The “impulsive-aggressive” endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/β (GSK3α and β; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations.ConclusionThe anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces “impulsive-aggressive” behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population.