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Objective: The aim of this study was to test the effects of repetitive active transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex (rDLPFC) associated with a hypocaloric diet on glucose homeostasis in people with excessive weight.Methods: Adults with overweight or obesity were selected in a randomized, double-blind pilot study to complete 4 weeks (20 sessions) of fixed-dose tDCS (2 mA, 20 minutes) delivered over the rDLPFC and associated with a standard hypocaloric diet. Participants were randomly assigned (1:1) and stratified by sex to the active tDCS group (active) or the sham tDCS group (sham). Changes in glucose homeostasis were assessed in a 4-hour liquid meal tolerance test, performed before and after the intervention.Results: Twenty-eight participants were randomized (79% with obesity; mean [SD] age 37.6 [5.8] years). After the intervention, fasting plasma glucose (mean [95% CI], -7.8 mg/dL [-14.0 to -1.6]) and insulin levels (-7.7 μIU/mL [-13.9 to -1.6]) decreased in the active compared with the sham. Similarly, the Matsuda insulin sensitivity index increase in the active (4.7 pmol-1  × mmol-1 [1.6 to 7.8]) compared with the sham (0.6 pmol-1  × mmol-1 [-1.4 to 3.2]).Conclusions: Repetitive, active tDCS over the rDLPFC could be a promising noninvasive technique to improve glucose homeostasis in individuals with overweight or obesity on a low-calorie diet, highlighting the importance of investigating this intervention modality in individuals with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: The clinical effects of smartphone‐based interventions for bipolar disorder (BD) have yet to be established. Objectives: To examine the efficacy of smartphone‐based interventions in BD and how the included studies reported user‐engagement indicators. Methods: We conducted a systematic search on January 24, 2022, in PubMed, Scopus, Embase, APA PsycINFO, and Web of Science. We used random‐effects meta‐analysis to calculate the standardized difference (Hedges' g) in pre‐post change scores between smartphone intervention and control conditions. The study was pre‐registered with PROSPERO (CRD42021226668). Results: The literature search identified 6034 studies. Thirteen articles fulfilled the selection criteria. We included seven RCTs and performed meta‐analyses comparing the pre‐post change in depressive and (hypo)manic symptom severity, functioning, quality of life, and perceived stress between smartphone interventions and control conditions. There was significant heterogeneity among studies and no meta‐analysis reached statistical significance. Results were also inconclusive regarding affective relapses and psychiatric readmissions. All studies reported positive user‐engagement indicators. Conclusion: We did not find evidence to support that smartphone interventions may reduce the severity of depressive or manic symptoms in BD. The high heterogeneity of studies supports the need for expert consensus to establish ideally how studies should be designed and the use of more sensitive outcomes, such as affective relapses and psychiatric hospitalizations, as well as the quantification of mood instability. The ISBD Big Data Task Force provides preliminary recommendations to reduce the heterogeneity and achieve more valid evidence in the field. [ABSTRACT FROM AUTHOR]

Objectives: Clinical staging is widely used in medicine to map disease progression, inform prognosis, and guide treatment decisions; in psychiatry, however, staging remains a hypothetical construct. To facilitate future research in bipolar disorders (BD), a well‐defined nomenclature is needed, especially since diagnosis is often imprecise with blurred boundaries, and a full understanding of pathophysiology is lacking. Methods: Under the auspices of the International Society of Bipolar Disorders, a Task Force of international experts was convened to review, discuss, and integrate findings from the scientific literature relevant to the development of a consensus staging model and standardize a terminology that could be used to advance future research including staging of BD and related disorders. Results: Consensus opinion and areas of uncertainty or difference were identified in regard to terms referring to staging as it may apply to BD, to at‐risk status and subthreshold stages, and to various clinical stages of BD as it is currently diagnosed. Conclusion: The use of a standardized nomenclature about the clinical stages of BD will facilitate communication about research on clinical and pathological components of this heterogeneous group of disorders. The concepts presented are based on current evidence, but the template provided allows for further refinements as etiological advances come to light. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter‐episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic dysregulation and functional impairment. Methods: Levels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper‐reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data‐driven biomarker selection. Results: BALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper‐reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper‐reactivity had significantly lower global and cognitive functioning than those without emotional hyper‐reactivity (P <.0001). Conclusions: A multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper‐reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic disturbances and functional impairment. [ABSTRACT FROM AUTHOR]

Objectives: Metabolically based distinctions for disturbances in glucose and insulin may provide meaningful insights both clinically and mechanistically. Methods: Data were derived from 352 subjects of previously completed clinical studies with a mood disorder (MD) (bipolar disorder: n = 179, major depressive disorder: n = 173) and 218 healthy controls from the Comprehensive Assessment of Long‐Term Effects of Reducing Intake of Energy. We conducted a factor analysis to replicate a priori dissociable factors informed by glucose and insulin levels and indices of insulin resistance and beta‐cell function: elevated insulin and insulin resistance ("insulin‐IR"), and increased fasting glucose and reduced insulin secretion ("glucotoxicity"). Cluster analyses were conducted, separately in men and women, to evaluate the clinical relevance of subtyping individuals with MDs using insulin‐IR and glucotoxicity (GT) factor scores. Results: Factors insulin‐IR and GT explained 92.64% and 92.09% of the variance in men and women respectively. Three clusters were replicated in men and women separately: metabolically healthy (MH), high GT, and insulin‐resistant (IR). After adjusting for age, gender, study cohort, MD diagnosis, and antipsychotics use, body mass index (BMI) and mean arterial pressure were higher in IR‐ vs GT‐ or MH‐clustered individuals; GT‐clustered individuals had more metabolic syndrome components and higher C‐reactive protein. Glucotoxic‐clustered subjects reported greater impairments in cognitive function and global functioning when compared to MH‐ or IR‐clustered subjects. Conclusions: Using simple, cost‐effective, and accessible measures, we identified stable, gender‐convergent, subgroups of individuals that significantly diverged on measures of cognitive dysfunction, self‐reported anhedonia, functional disability, BMI, and blood pressure. [ABSTRACT FROM AUTHOR]

Objectives: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. Method: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. Results: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data‐driven phenotypes, as well as by predicting transition to the disorder in high‐risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non‐stationary distribution of the data, and lack of appropriate funding. Conclusion: Machine learning‐based studies, including atheoretical data‐driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse‐relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings. [ABSTRACT FROM AUTHOR]

For instance, topiramate and gabapentin were considered and used as mood stabilizers in BD patients based on some preliminary data and the belief that all anticonvulsants would be effective for BD. Similarly, some atypical antipsychotics treat bipolar depression, so all atypical antipsychotics could be seen to work for bipolar depression. [Extracted from the article]

Background: Recent studies have demonstrated the existence of a distinct late‐onset attention deficit/hyperactivity disorder (ADHD) trajectory. Our objective is to test if there are distinct ADHD trajectories regarding age of onset from childhood to adolescence and to compare clinical manifestations, cognitive functions and genetic risk for ADHD among distinct longitudinal groups. Method: Nine hundred and twenty four children and adolescents from the community participated in the study. We compared clinical, cognitive features and genetic risk among four groups of participants: (a) childhood‐limited, (b) youth‐onset, (c) childhood‐onset with youth persistence, and (d) community comparisons without ADHD. Symptomatic and diagnostic assessments were performed using the Development and Well‐Being Behavior Assessment, the Strengths and Difficulties Questionnaire, and the Child Behavior Checklist. Cognitive functions were measured using a battery of standardized tests. Genetic risk for ADHD was calculating using summary statistics from the Psychiatric Genomics Consortium. Results: Half of the adolescents (52%) with ADHD had their symptom onset in adolescence. The impairment level of this group in adolescence is similar to the persistent group. Despite not having ADHD, the youth‐onset group already presented in childhood more symptoms from other domains of psychopathology, higher shared variance in psychiatric symptomatology (p‐factor), school impairment, and executive dysfunctions than community comparisons. Furthermore, the youth‐onset group presented lower levels of genetic risk for ADHD compared to other cases. Conclusions: A significant proportion of adolescents with ADHD were youth‐onset cases and presented similar impairment levels as those cases with early‐onset ADHD. The presence of cognitive impairments and higher levels of clinical symptoms in the youth‐onset group already at childhood speaks in favor of a heterotypic trajectory of psychopathology suggesting that youth‐onset ADHD might be an artificial consequence of categorizing dimensional psychopathology into discrete diagnostic groups. [ABSTRACT FROM AUTHOR]

Aim: We sought to compare alterations in serum bioenergetic markers within a well‐characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia. Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug‐naïve (i.e., first‐episode) participants and treatment non‐adherent participants. Pre‐ and post‐treatment serum samples were analyzed using liquid chromatography–tandem mass spectrometry. Results: Metabolites with the greatest change, when comparing pre‐ and post‐treatment levels, were identified revealing 14 water‐soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines – oleoylcarnitine, L‐palmitoylcarnitine, linoleyl carnitine, and L‐acetylcarnitine – were decreased post‐treatment. Of these metabolite biomarkers, six – oleoylcarnitine, linoleyl carnitine, L‐acetylcarnitine, LysoPC(15:0), D‐glutamic acid, and L‐arginine – were identified as having most consistently and predictably changed after 8 weeks of treatment. Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side‐effects (e.g., metabolic syndrome) of antipsychotics. [ABSTRACT FROM AUTHOR]

This study (registered with PROSPERO, CRD42018085967) compares the efficacy (i.e. pro‐cognitive effects) and acceptability of antidiabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials comparing antidiabetic agents with placebo and/or another active antidiabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4855) evaluating the effects of 6 different antidiabetic drugs (i.e. intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with antidiabetic agents compared with placebo. Pioglitazone 15 to 30 mg demonstrated the greatest efficacy compared to placebo in network meta‐analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro‐cognitive class effect of antidiabetic agents in AD/MCI. Other antidiabetic agents should also be investigated in future studies. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recent neurobiological evidences along with clinical observations justify the use of N-acetylcysteine (NAC) as a medication for craving. The objective of our study was to assess the evidence of efficacy of NAC for craving in substance use disorders in randomized clinical trials (RCTs).Methods: Systematic review of the RCTs literature (PROSPERO number 56698) until February, 2017, using MEDLINE, Cochrane Library and clinicaltrials.gov. We included seven RCTs (n = 245); most with small-to-moderate sample sizes. The main outcome was the Hedges' g for continuous scores in a random-effects model. Heterogeneity was evaluated with the I2 and the χ2 test. Publication bias was evaluated using the Begg's funnel plot and the Egger's test. Meta-regression was performed using the random-effects model.Results: Comparing NAC versus placebo, NAC was significantly superior for craving symptoms (Hedges' g = 0.94; 95%CI 0.55-1.33). The funnel plot showed the risk of publication bias was low and between-study heterogeneity was not significant (I2  = 44.4%, p = 0.07 for the χ2 test). A subgroup analysis performed using meta-regression showed no particular influence.Discussion and Conclusions: NAC was superior to placebo for craving reduction in SUDs. The relatively small number of trials and their heterogeneous methodology were possible limitations; however, these positive thrilling results stimulate further studies for clarifying the potential impact of NAC for craving symptoms in SUDs.Scientific Significance: The safety profile of NAC and favorable tolerability, in addition to being an over-the-counter medication, presents with an interesting potential clinical use for craving in SUDs.Scientific Significance: The safety profile of NAC and its favorable tolerability, in addition to being anover-the-counter medication, presents with an interesting potential clinical use for craving in SUDs. (Am J Addict 2017;26:660-666). [ABSTRACT FROM AUTHOR]

Aim This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. Methods We measured plasma levels of copeptin in individuals with BD ( n = 55) and healthy controls ( n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and β-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. Results Plasma copeptin levels were lower in individuals with BD, relative to healthy controls ( P < 0.001). There were significant interactions between BD and plasma copeptin on β-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between β-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. Conclusion Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population. [ABSTRACT FROM AUTHOR]

Objectives The objectives of the study were to determine if adjunctive minocycline mitigates depressive symptom severity and improves cognitive function in individuals with bipolar I/ II disorder ( BD). The study also aimed to determine if changes in depressive and/or cognitive symptoms over the course of treatment were associated with changes in circulating inflammatory cytokine levels. Methods A total of 29 (intention-to-treat: n=27) adults meeting DSM- IV- TR criteria for a major depressive episode as part of bipolar I or II disorder (i.e. Hamilton Depression Rating Scale 17-item [ HAMD-17] ≥20) were enrolled in an 8-week, open-label study with adjunctive minocycline (100 mg bid). The primary outcome measure was the Montgomery−Åsberg Depression Rating Scale ( MADRS). The HAMD-17, Clinical Global Impression-Severity ( CGI-S), cognitive test composite scores and plasma cytokines were secondary outcome measures. Plasma cytokines were measured with the 30 V-Plex Immunoassay from Meso Scale Discovery. Results Adjunctive minocycline was associated with a reduction in depressive symptom severity from baseline to week 8 on the MADRS ( P<.001, d=0.835), HAMD-17 ( P<.001, d=0.949) and CGI-S ( P<.001, d=1.09). Improvement in psychomotor speed, but not verbal memory or executive function, was observed only amongst individuals exhibiting a reduction in depression severity ( P=.007, d=0.826). Levels of interleukin ( IL)-12/23p40 ( P=.002) were increased, while levels of IL-12p70 ( P=.001) and C-C motif chemokine ligand 26 (CCL26) ( P<.001) were reduced from baseline to week 8. A reduction in CCL26 levels was associated with a less favourable treatment response ( P<.001). Conclusions Results from the pilot study suggest that adjunctive minocycline may exert antidepressant effects in individuals with bipolar depression, possibly by targeting inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Objectives Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. Methods We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. Results There were negative correlations between BDNF, GPx ( r=−.449, P≤.001) and GPx/SOD ratio ( r=−.503, P<.001), and a positive correlation between BDNF and SOD ( r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. Conclusions There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD. [ABSTRACT FROM AUTHOR]

Objectives The neurotrophin brain-derived neurotrophic factor ( BDNF) has been proposed as a potential biomarker in bipolar disorder ( BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism ( IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. Methods We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. Results Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM ( P=.046). There was no effect of IGM ( P=.860) and no interaction between BD diagnosis and IGM ( P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes ( P<.001), psychiatric hospitalizations ( P=.001) and suicide attempts ( P=.021). IGM moderated the association between BDNF and the number of previous mood episodes ( P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. Conclusions BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression. [ABSTRACT FROM AUTHOR]

Objective Inflammation has been implicated in the risk, pathophysiology, and progression of mood disorders and, as such, has become a target of interest in the treatment of bipolar disorder ( BD). Therefore, the objective of the current qualitative and quantitative review was to determine the overall antidepressant effect of adjunctive anti-inflammatory agents in the treatment of bipolar depression. Methods Completed and ongoing clinical trials of anti-inflammatory agents for BD published prior to 15 May 15 2015 were identified through searching the PubMed, Embase, Psych INFO, and Clinicaltrials.gov databases. Data from randomized controlled trials ( RCTs) assessing the antidepressant effect of adjunctive mechanistically diverse anti-inflammatory agents were pooled to determine standard mean differences ( SMDs) compared with standard therapy alone. Results Ten RCTs were identified for qualitative review. Eight RCTs (n = 312) assessing adjunctive nonsteroidal anti-inflammatory drugs (n = 53), omega-3 polyunsaturated fatty acids (n = 140), N-acetylcysteine (n = 76), and pioglitazone (n = 44) in the treatment of BD met the inclusion criteria for quantitative analysis. The overall effect size of adjunctive anti-inflammatory agents on depressive symptoms was −0.40 (95% confidence interval −0.14 to −0.65, p = 0.002), indicative of a moderate and statistically significant antidepressant effect. The heterogeneity of the pooled sample was low ( I² = 14%, p = 0.32). No manic/hypomanic induction or significant treatment-emergent adverse events were reported. Conclusions Overall, a moderate antidepressant effect was observed for adjunctive anti-inflammatory agents compared with conventional therapy alone in the treatment of bipolar depression. The small number of studies, diversity of agents, and small sample sizes limited interpretation of the current analysis. [ABSTRACT FROM AUTHOR]

However, as patients with BD share some characteristics, there are common themes that will be experienced by almost any physician, or health professional involved in the care of these patients. Key MessageThe treatment of individuals with Bipolar Disorder requires a strong therapeutic alliance (TA) which is related to the management of professionals' countertransference (CT). For example, it is not uncommon that practitioners at some point stop questioning the patient about ownership of weapons or ammunition.3 Suicidal ideation is highly prevalent in patients with BD and prevent suicides are a top priority for physicians. [Extracted from the article]

The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders . We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random =958; high risk =1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high-risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub-sample with 'high risk' for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective To provide a strategic framework for the prevention of bipolar disorder ( BD) that incorporates a 'Big Data' approach to risk assessment for BD. Methods Computerized databases (e.g., Pubmed, PsychInfo, and MedlinePlus) were used to access English-language articles published between 1966 and 2012 with the search terms bipolar disorder, prodrome, 'Big Data', and biomarkers cross-referenced with genomics/genetics, transcriptomics, proteomics, metabolomics, inflammation, oxidative stress, neurotrophic factors, cytokines, cognition, neurocognition, and neuroimaging. Papers were selected from the initial search if the primary outcome(s) of interest was (were) categorized in any of the following domains: (i) 'omics' (e.g., genomics), (ii) molecular, (iii) neuroimaging, and (iv) neurocognitive. Results The current strategic approach to identifying individuals at risk for BD, with an emphasis on phenotypic information and family history, has insufficient predictive validity and is clinically inadequate. The heterogeneous clinical presentation of BD, as well as its pathoetiological complexity, suggests that it is unlikely that a single biomarker (or an exclusive biomarker approach) will sufficiently augment currently inadequate phenotypic-centric prediction models. We propose a 'Big Data'- bioinformatics approach that integrates vast and complex phenotypic, anamnestic, behavioral, family, and personal 'omics' profiling. Bioinformatic processing approaches, utilizing cloud- and grid-enabled computing, are now capable of analyzing data on the order of tera-, peta-, and exabytes, providing hitherto unheard of opportunities to fundamentally revolutionize how psychiatric disorders are predicted, prevented, and treated. High-throughput networks dedicated to research on, and the treatment of, BD, integrating both adult and younger populations, will be essential to sufficiently enroll adequate samples of individuals across the neurodevelopmental trajectory in studies to enable the characterization and prevention of this heterogeneous disorder. Conclusions Advances in bioinformatics using a 'Big Data' approach provide an opportunity for novel insights regarding the pathoetiology of BD. The coordinated integration of research centers, inclusive of mixed-age populations, is a promising strategic direction for advancing this line of neuropsychiatric research. [ABSTRACT FROM AUTHOR]

Aims: In this paper, we review the literature on the efficacy of anti-inflammatory agents as neuroprotectors in clinical and preclinical stages of schizophrenia. Method: A synthetic and integrative approach was applied to review studies stemming from epidemiology, phenomenology, cognition, genetics and neuroimaging data. We provide conclusions and future directions of research on early-onset schizophrenia. Results: Abnormal inflammatory activation has been demonstrated in schizophrenia. Increases or imbalances in cytokines before birth or during childhood may impact neurodevelopment and produce vulnerability to schizophrenia. The specificity of inflammatory abnormalities in psychiatric disorders is controversial. Similar increases in pro-inflammatory cytokines have been described in other disorders, especially mood and anxiety disorders. One of the most important challenges at this point is the understanding of neurobiological correlates of prodromal stages of schizophrenia. Conclusion: Although future research should investigate the exact role of different cytokines in pathophysiology of schizophrenia, these mediators emerge as promising molecular targets to its prevention and treatment. [ABSTRACT FROM AUTHOR]

Aim: Several lines of evidence suggest that major depressive disorder is associated with an inflammatory status. Tumor necrosis factor-α has been investigated as a potential molecular target in mood disorders. Tumor necrosis factor-α exerts its activity through binding to specific cell membrane receptors named as TNFR1 and TNFR2. The aim of the present study was to investigate soluble plasma TNFR1 (sTNFR1) and TNFR2 levels (sTNFR2) in major depressive disorder patients. Methods: Female outpatients with major depressive disorder ( n = 30) were compared with a healthy control group ( n = 19). Severity of depressive symptoms was evaluated on Beck Depression Inventory; post-traumatic stress disorder (PTSD) symptoms were evaluated on PTSD Checklist–Civilian Version; and childhood abuse and neglect on the Childhood Trauma Questionnaire. Plasma tumor necrosis factor-α and its soluble receptors were measured by ELISA. Results: Patients had no changes in tumor necrosis factor-α concentrations but did have increased sTNFR1 ( P < 0.001) and sTNFR2 ( P < 0.001) levels compared to controls. Plasma level of sTNFR1 was positively predicted by age (B = 0.25, P = 0.05) and PTSD-like symptoms (B = 0.41, P = 0.002) and plasma levels of sTNFR2 by depression severity (B = 0.67, P < 0.001). Conclusions: Soluble tumor necrosis factor-α receptors could be reliable markers of inflammatory activity in major depression. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. Methods: Forty‐four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence‐related parameters were assessed: proportions of late‐differentiated cells (e.g., CD3+CD8+CD28‐CD27‐ and CD3‐CD19+IgD‐CD27‐), and the expression of CD69, CD71, and CD152 after stimulation. Confirmatory factor analysis was applied to generate an IA trait underling the 5 measures. Results: The best‐fit model was constituted by 4 parameters that were each related to an underlying IA trait, with 1 cell population positively correlated (CD3+CD8+CD28‐CD27‐ [λ = 0.544, where λ represents the loading of the parameter onto the IA trait] and 3 markers negatively correlated (CD69 [λ = −0.488], CD71 [λ = −0.833], and CD152 [λ = −0.674]). The IA trait was associated with chronological age (β = 0.360, p = .013) and the number of previous mood episodes (β = 0.426, p = .006). In a mediation model, 84% of the effect between manic episodes, and IA was mediated by body mass index. Conclusion: In bipolar disorder type I, premature aging of the immune system could be reliably measured using an index that validated against chronological age, which was related to adverse metabolic effects of the disease course. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Similar Immune Profile in Bipolar Disorder and Schizophrenia: Selective Increase in Soluble Tumor Necrosis Factor Receptor I and Von Willebrand Factor," by S. Hope and colleagues.

A letter to the editor is presented regarding the application of long-acting injectable risperidone to a 43-year-old woman who developed intolerance to mood stabilizers after she underwent bariatric surgery.