Identifying social cognition subgroups in euthymic patients with bipolar disorder: a cluster analytical approach.

BACKGROUND: Bipolar disorder (BD) is associated with social cognition (SC) impairments even during remission periods although a large heterogeneity has been described. Our aim was to explore the existence of different profiles on SC in euthymic patients with BD, and further explore the potential impact of distinct variables on SC. METHODS: Hierarchical cluster analysis was conducted using three SC domains [Theory of Mind (ToM), Emotional Intelligence (EI) and Attributional Bias (AB)]. The sample comprised of 131 individuals, 71 patients with BD and 60 healthy control subjects who were compared in terms of SC performance, demographic, clinical, and neurocognitive variables. A logistic regression model was used to estimate the effect of SC-associated risk factors. RESULTS: A two-cluster solution was identified with an adjusted-performance group (N = 48, 67.6%) and a low-performance group (N = 23, 32.4%) with mild deficits in ToM and AB domains and with moderate difficulties in EI. Patients with low SC performance were mostly males, showed lower estimated IQ, higher subthreshold depressive symptoms, longer illness duration, and poorer visual memory and attention. Low estimated IQ (OR 0.920, 95% CI 0.863-0.981), male gender (OR 5.661, 95% CI 1.473-21.762), and longer illness duration (OR 1.085, 95% CI 1.006-1.171) contributed the most to the patients clustering. The model explained up to 35% of the variance in SC performance. CONCLUSIONS: Our results confirmed the existence of two discrete profiles of SC among BD. Nearly two-thirds of patients exhibited adjusted social cognitive abilities. Longer illness duration, male gender, and lower estimated IQ were associated with low SC performance.

Suicide associated with COVID-19 infection: an immunological point of view.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide. MATERIALS AND METHODS: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients. RESULTS: Patients infected with COVID-19 have high amounts of IL-1ß, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed. CONCLUSIONS: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Empirical assessment of biases in cerebrospinal fluid biomarkers of Alzheimer's disease: an umbrella review and re-analysis of data from meta-analyses.

OBJECTIVE: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available. MATERIALS AND METHODS: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval. RESULTS: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers. CONCLUSIONS: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Increasing Nrf2 Activity as a Treatment Approach in Neuropsychiatry.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor encoded by NFE2L2. Under oxidative stress, Nrf2 does not undergo its normal cytoplasmic degradation but instead travels to the nucleus, where it binds to a DNA promoter and initiates transcription of anti-oxidative genes. Nrf2 upregulation is associated with increased cellular levels of glutathione disulfide, glutathione peroxidase, glutathione transferases, thioredoxin and thioredoxin reductase. Given its key role in governing the cellular antioxidant response, upregulation of Nrf2 has been suggested as a common therapeutic target in neuropsychiatric illnesses such as major depressive disorder, bipolar disorder and schizophrenia, which are associated with chronic oxidative and nitrosative stress, characterised by elevated levels of reactive oxygen species, nitric oxide and peroxynitrite. These processes lead to extensive lipid peroxidation, protein oxidation and carbonylation, and oxidative damage to nuclear and mitochondrial DNA. Intake of N-acetylcysteine, coenzyme Q10 and melatonin is accompanied by increased Nrf2 activity. N-acetylcysteine intake is associated with improved cerebral mitochondrial function, decreased central oxidative and nitrosative stress, reduced neuroinflammation, alleviation of endoplasmic reticular stress and suppression of the unfolded protein response. Coenzyme Q10, which acts as a superoxide scavenger in neuroglial mitochondria, instigates mitohormesis, ameliorates lipid peroxidation in the inner mitochondrial membrane, activates uncoupling proteins, promotes mitochondrial biogenesis and has positive effects on the plasma membrane redox system. Melatonin, which scavenges mitochondrial free radicals, inhibits mitochondrial nitric oxide synthase, restores mitochondrial calcium homeostasis, deacetylates and activates mitochondrial SIRT3, ameliorates increased permeability of the blood-brain barrier and intestine and counters neuroinflammation and glutamate excitotoxicity.

Feeding Habits and Behavior of a Bee Killer: Hololepta reichii (Coleoptera, Histeridae).

Hololepta (Leionota) reichii Marseul is a widespread but rarely encountered natural enemy of social bees, so we evaluated feeding habits and behavior of such a clown beetle regarding bees, beehive by-products, and other sources of food under a monitored environment. The experiments revealed that H. reichii preferentially predates larvae and pupae of social bees extracted from brood cells, but also feeds on dead adult stingless bees and on larvae and pupae inside cells. This note reports the first finding of clown beetles (Coleoptera, Histeridae) in a hive aggregation of stingless and honey bees in natural conditions and expands the known distribution of the species to the state of Espírito Santo, the second record in the Brazilian Atlantic Forest.

Uma análise histórico-crítica sobre o desenvolvimento das normas brasileiras relacionadas a queijos artesanais / [A critical-historical analysis of the continuous development of Brazilian legislation related to artisanal cheeses]

Diferentes tipos de queijos artesanais são produzidos, comercializados e consumidos no Brasil, o que impulsiona o constante desenvolvimento de normas por órgãos oficiais, como o Mapa. A criação do Suasa e do Sisbi-POA foi fundamental para esse setor, por permitir um sistema de equivalência na fiscalização e por ampliar a distribuição. Ainda, o Mapa passou a permitir que queijos artesanais produzidos com leite cru pudessem ser maturados em um período inferior a 60 dias, desde que comprovada sua inocuidade. A redução do tempo de maturação é um tema controverso e polêmico, já que não há critérios específicos que estudos científicos devem contemplar, o que permite múltiplas interpretações de dados. Com a criação e a regulamentação do selo Arte, a fiscalização dos produtos artesanais foi designada aos órgãos de agricultura, pecuária e de saúde pública, em complementação à atribuição já prevista pelo Mapa e pelo Sisbi-POA. Ainda, o selo Arte atribui aos órgãos de inspeção uma função orientadora, atividade que deveria ser prioritariamente executada por agências de extensão e associações. As normas que balizam a produção e comercialização de produtos artesanais devem ser frequentemente atualizadas, devido aos constantes avanços científicos na área e para assegurar a oferta de produtos com qualidade e inócuos aos consumidores.(AU)

Different artisanal cheeses are produced, commercialized and consumed in Brazil, leading to a constant development of related rules by the MAPA and other official agencies. The establishment of two national programs (SUASA and SISBI-POA) allowed an equivalence in inspection system and an expanded distribution. Also, MAPA allowed ripening time lower than 60 days for artisanal raw milk cheeses, based on scientific studies that assure their safety. However, lowering the ripening period is still controversial, once there are no proper established criteria for such scientific studies, leading to potential multiple interpretation of data. The newly established ARTE certification transferred the inspection responsibilities of artisanal products to secretaries of agriculture, livestock and health, in support of what was already predicated by MAPA and SISBI-POA. Based on ARTE certification, the inspection service must also provide orientation guidance to producers, which should be done specifically by extension organs and associations. The norms that guide the production and commercialization of these artisanal products often need to be updated, but based on well-established methodologies and procedures, to ensure the distribution of suitable products to consumers.(AU)

Lithium and suicide prevention in mood disorders and in the general population: A systematic review.

Suicide contributes to 1-4 % of deaths worldwide every year. We conducted a systematic review aimed at summarizing evidence on the use of lithium for the prevention of suicide risk both in mood disorders and in the general population. We followed the PRISMA methodology (keywords: "lithium", "suicide" AND "suicidal" on Pubmed, Cochrane CENTRAL, Clinicaltrial.gov, other databases). Inclusion criteria: lithium therapy in mood disorder or found in drinking water or scalp in the general population. Exclusion criteria: no lithium administration. From 918 screened references, 18 prospective (number of participants: 153786), 10 retrospective (number of participants: 61088) and 16 ecological studies (total sample: 2062) were included. Most of the observational studies reported a reduction in suicide in patients with mood disorders. All studies about lithium treatment's duration reported that long-term lithium give more benefits than short-term lithium in suicide risk The evidence seems to attribute an intrinsic anti-suicidal property of lithium, independent of its proven efficacy as a mood stabilizer.

Association between ideal cardiovascular health and depression incidence: a longitudinal analysis of ELSA-Brasil.

OBJECTIVE: We investigated whether ideal cardiovascular health (ICH), a metric proposed by the American Heart Association, predicts depression development. METHODS: Cohort analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Adults with no current depression and other common mental disorders, cardiovascular diseases, and antidepressant drug use at baseline had their ICH (composite score of smoking, dietary habits, body mass index, blood pressure, fasting glucose, cholesterol, and physical activity) assessed and classified into poor, intermediate, and optimal. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R). Poisson regression models, adjusted for sociodemographic factors and alcohol consumption, were employed. Stratified analyses were performed for age and sex. RESULTS: We included 9214 participants (mean age 52 ± 9 years, 48.6% women). Overall depression incidence at 3.8-year follow-up was 1.5%. Intermediate and poor ICH significantly increased the risk rate (RR) of developing depression (2.48 [95%CI 1.06-5.78] and 3 [1.28-7.03], respectively) at a 3.8-year follow-up. Higher ICH scores decreased the rate of depression development (RR = 0.84 [0.73-0.96] per metric). Stratified analyses were significant for women and adults < 55 years old. CONCLUSIONS: Poor cardiovascular health tripled depression risk at follow-up in otherwise healthy adults. Ameliorating cardiovascular health might decrease depression risk development.

Microbial safety status of Serro artisanal cheese produced in Brazil.

Considering the growing consumption of artisanal foods worldwide, we aimed to evaluate the microbial safety of Serro artisanal cheese (SAC), produced in Minas Gerais State, Brazil. This cheese is produced with raw milk using 1 of 2 natural starter cultures: "pingo" and "rala." A total of 53 SAC samples (pingo = 8; rala = 45) were obtained from different farmers and subjected to conventional and molecular assays to detect and enumerate Listeria monocytogenes, Salmonella spp., coagulase-positive staphylococci (CPS), diarrheagenic Escherichia coli, Mycobacterium tuberculosis, and Brucella abortus. The SAC samples were also subjected to an ELISA to detect classical staphylococcal enterotoxins (CSE: SEA, SEB, SEC, SED, SEE) and to PCR assays to detect staphylococcal enterotoxin-related genes (sea, seb, sec, sed, see). Coagulase-positive staphylococci isolates were obtained and tested by the same assays to detect their potential in CSE production and presence of CSE-related genes. None of the SAC samples showed any of the screened food-borne pathogens and zoonotic agents, and none showed the presence of CSE by phenotypic and genotypic approaches. Despite the absence of microbial hazards, mean counts of CPS in SAC samples were 5.2 log cfu/g (pingo starter) and 4.6 log cfu/g (rala starter), indicating poor hygiene practices during production. None of the tested CPS isolates (n = 116) produced CSE or presented CSE-related genes. Despite the relative microbial safety, hygienic conditions during SAC production must be improved to meet official guidelines established in Brazil.

Prevention of Postdental Procedure Bacteremia: A Network Meta-analysis.

Postdental procedure bacteremia is common and troublesome. The comparative efficacy of multiple prophylactic interventions is unclear. We compared the efficacy of interventions for the prevention of postdental procedure bacteremia. We conducted a review of ClinicalKey, Cochrane CENTRAL, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov from inception to December 4, 2018. Randomized controlled trials that evaluated prophylactic interventions for the prevention of postdental procedure bacteremia were eligible. The primary outcome was the incidence of postdental procedure bacteremia. A total of 24 trials were included with 2,147 participants. Our network meta-analysis demonstrated that intravenous administration of 1,000/200 mg of amoxicillin/clavulanate provided the least incidence of postdental procedure bacteremia among all the prophylactic interventions (odds ratio = 0.03, 95% CI = 0.00 to 0.63) as compared with the placebo/controls. Oral 3 g of amoxicillin had the least incidence of postdental procedure bacteremia among all oral or topical forms of prophylactic interventions (odds ratio = 0.10, 95% CI = 0.02 to 0.44) as compared with the placebo/controls. No serious adverse events, such as anaphylactic shock, mortality, and the development of antibiotic-resistant bacteria, were reported. None of the included subjects were of high risk of infectious endocarditis. Our network meta-analysis demonstrates that intravenous amoxicillin/clavulanate and oral amoxicillin might be the best prophylactic interventions in preventing postdental procedure bacteremia among all the oral/topical forms of interventions for the overall populations.

Short communication: Effect of lactose on the spray drying of Lactococcus lactis in dairy matrices.

The effects of unfavorable conditions responsible for the viability loss of Lactococcus cells during spray drying can be minimized by the application of dairy matrices as encapsulating materials. This study aimed to evaluate the use of dairy matrices with different lactose contents on the survival of Lactococcus lactis during drying and storage. The use of hydrolyzed-lactose milk resulted in notable loss of cell viability (3.90 log cycles). However, milk enriched with lactose or without fat showed better protection (viability loss between 0.26 and 1.41 log cfu/g) and greater cell survival during storage at room temperature. The enrichment of milk with lactose seems to be ideal for the drying of heat-sensitive bacteria.

Antipsychotic use and risk of life-threatening medical events: umbrella review of observational studies.

OBJECTIVE: To quantify the risk of hip fracture, thromboembolism, stroke, myocardial infarction, pneumonia and sudden cardiac death associated with exposure to antipsychotics. METHODS: Systematic searches were conducted in Medline, Embase and PsycINFO from inception until 30/07/2018 for systematic reviews of observational studies. AMSTAR-2 was used for the quality assessment of systematic reviews, while the strength of associations was measured using GRADE and quantitative umbrella review criteria (URC). RESULTS: Sixty-eight observational studies from six systematic reviews were included. The association between antipsychotic exposure and pneumonia was the strongest [URC = class I; GRADE = low quality; odds ratio (OR) = 1.84, 95% confidence interval (CI) = 1.62-2.09; participants = 28 726; age = 76.2 ± 12.3 years], followed by the association with hip fracture (URC = class II; GRADE = low quality; OR = 1.57, 95% CI = 1.42-1.74; participants = 5 288 118; age = 55.4 ± 12.5 years), and thromboembolism (URC = class II; GRADE = very low quality; OR = 1.55, 95% CI = 1.31-1.83; participants = 31 417 175; age = 55.5 ± 3.2 years). The association was weak for stroke (URC = class III; GRADE = very low quality; OR = 1.45, 95% CI = 1.24-1.70; participants = 65 700; age = 68.7 ± 13.8 years), sudden cardiac death (URC = class III; GRADE = very low quality; OR = 2.24, 95% CI = 1.45-3.46; participants = 77 488; age = 52.2 ± 6.2 years) and myocardial infarction (URC = class III; GRADE = very low quality; OR = 2.21, 95% CI = 1.41-3.46; participants = 399 868; age = 74.1 ± 9.3 years). CONCLUSION: The most robust results were found for the risk of pneumonia, followed by the risk of hip fracture and thromboembolism. For stroke, sudden cardiac death and myocardial infarction, the strength of association was weak. The observational nature of the primary studies may represent a source of bias.

Determination of ideal water activity and powder temperature after spray drying to reduce Lactococcus lactis cell viability loss.

Spray drying presents a promising technology for preserving bacteria despite a low survival rate of heat-sensitive cultures when subjected to the drying process. The aim of this study was to determine the ideal powder parameters [water activity (Aw) and temperature (T°Cpowder)] needed to produce dehydrated Lactococcus lactis ssp. lactis with a high viability after drying. Cell concentrates injected into a spray dryer using varying cell concentrate flow rates (Fconcentrate = 0.3 to 1.0 kg/h), inlet air temperatures (T°Cinlet air = 115 to 160°C), and outlet air temperatures (T°Coutlet air = 70 to 115°C) resulted in powders with different values of Aw and T°Cpowder, and levels of cell viability loss. Lower cell viability reduction (∼0.43 log cycles) was obtained in conditions of Aw = 0.198 and T°Cpowder = 52°C, which can be met by using T°Cinlet air ∼126°C and T°Coutlet air = 88.9°C regardless of Fconcentrate values. After 60 d of storage at room temperature, cell population varied from 7.0 × 105 to 1.1 × 108 cfu/g. The initial powder Aw had no influence on cell death rate, but T°Cpowder influence was observed. The approach adopted in this study can be applied to other bacteria or spray dryer equipment to determine optimal drying conditions.

A systematic review on sleep alterations anticipating the onset of bipolar disorder.

BACKGROUND: Sleep alterations are frequent occurrence in Bipolar Disorder (BD), both in acute and interepisodic phases. Sleep alterations have been also described both long before BD onset, as aspecific risk syndromes, or as immediate prodromes of BD onset. The aim of the present study is to systematically review the relationship between sleep alterations anticipating for the full-blown onset of BD, both in general and according to specific polarities of onset. METHODS: A systematic literature research according to PRISMA statement and considering: 1. prospective studies about BD patients' offspring with sleep alterations who later developed BD. 2. prospective studies assessing patients with sleep disorders who later developed BD. 3. retrospective studies on BD patients where sleep alterations before BD onset of the disease were reported. RESULTS: A total of 16 studies were included in this review. Sleep disturbances may frequently appear 1 year before the onset of BD or more, often during childhood or adolescence. A decreased need for sleep may precede the onset of the illness, specially a manic episode, while insomnia appears to anticipate either a manic or a depressive episode. Hypersomnia seems to precede bipolar depressive episodes. CONCLUSIONS: Sleep alterations frequently appear long before the onset of BD, and appear to be related specifically to the polarity of the index episode. The detection and treatment of sleep alterations in special high risk populations may help achieving an earlier detection of the illness.

Behavioral addictions in bipolar disorders: A systematic review.

Clinical and epidemiological research suggests that behavioral addictions (BA) are associated with a wide range of psychiatric disorders. However, the relationship between BA and bipolar disorders (BD) has not been thoroughly explored. The aim of this systematic review was to critically summarize and evaluate the current available evidence regarding a possible association between BA and BD. A systematic review of major electronic databases according to PRISMA guidelines was conducted from inception to 31st December 2017. We sought quantitative studies data concerning prevalence of comorbidity, features and treatment related to BA-BD comorbidity. Data were narratively synthesized. Of the 1250 studies returned from the search, a total of 28 articles were included in this review. BA may be overrepresented in BD samples, and the other way around. Pathological gambling and kleptomania were the most prevalent conditions followed by compulsive buying, compulsive sexual behavior and internet addiction. BA was also associated with other mood disorders, anxiety disorders and substance use disorder. BD-BA comorbidity was related with more severe course of illness. Studies on treatment strategies for BD-BA comorbidity are rather limited; only one randomized controlled trial that fulfilled inclusion criteria was identified. Methodological heterogeneity in terms of design and results among studies was found. BD-BA commonly co-occurs although there is a need for rigorous studies. Routine screening and adequate assessment may be helpful in BD patients to identify individuals at risk for BA and to effectively manage the complex consequences associated with BA-BD comorbidity.

The role of meta-analyses and umbrella reviews in assessing the harms of psychotropic medications: beyond qualitative synthesis.

á½ φελέειν, á¼¢ µá½´ ßλάπτειν (Primum non nocere) - Hιppocrates' principle should still guide daily medical prescribing. Therefore, assessing evidence of psychopharmacologic agents' safety and harms is essential. Randomised controlled trials (RCTs) and observational studies may provide complementary information about harms of psychopharmacologic medications from both experimental and real-world settings. It is considered that RCTs provide a better control of confounding variables, while observational studies provide evidence from larger samples, longer follow-ups, in more representative samples, which may be more reflective of real-life clinical scenarios. However, this may not always hold true. Moreover, in observational studies, safety data are poorly or inconsistently reported, precluding reliable quantitative synthesis in meta-analyses. Beyond individual studies, meta-analyses, which represent the highest level of 'evidence', can be misleading, redundant and of low methodological quality. Overlapping meta-analyses sometimes even reach different conclusions on the same topic. Meta-analyses should be assessed systematically. Descriptive reviews of reviews can be poorly informative. Conversely, 'umbrella reviews' can use a quantitative approach to grade evidence. In this editorial, we present the main factors involved in the assessment of psychopharmacologic agents' harms from individual studies, meta-analyses and umbrella reviews. Study design features, sample size, number of the events of interest, summary effect sizes, p-values, heterogeneity, 95% prediction intervals, confounding factor adjustment and tests of bias (e.g., small-study effects and excess significance) can be combined with other assessment tools, such as AMSTAR and GRADE to create a framework for assessing the credibility of evidence.

Mixed states in bipolar and major depressive disorders: systematic review and quality appraisal of guidelines.

OBJECTIVE: This systematic review provided a critical synthesis and a comprehensive overview of guidelines on the treatment of mixed states. METHOD: The MEDLINE/PubMed and EMBASE databases were systematically searched from inception to March 21st, 2018. International guidelines covering the treatment of mixed episodes, manic/hypomanic, or depressive episodes with mixed features were considered for inclusion. A methodological quality assessment was conducted with the Appraisal of Guidelines for Research and Evaluation-AGREE II. RESULTS: The final selection yielded six articles. Despite their heterogeneity, all guidelines agreed in interrupting an antidepressant monotherapy or adding mood-stabilizing medications. Olanzapine seemed to have the best evidence for acute mixed hypo/manic/depressive states and maintenance treatment. Aripiprazole and paliperidone were possible alternatives for acute hypo/manic mixed states. Lurasidone and ziprasidone were useful in acute mixed depression. Valproate was recommended for the prevention of new mixed episodes while lithium and quetiapine in preventing affective episodes of all polarities. Clozapine and electroconvulsive therapy were effective in refractory mixed episodes. The AGREE II overall assessment rate ranged between 42% and 92%, indicating different quality level of included guidelines. CONCLUSION: The unmet needs for the mixed symptoms treatment were associated with diagnostic issues and limitations of previous research, particularly for maintenance treatment.

Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications.

Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD. Major electronic databases were searched to identify preclinical and clinical studies that have investigated the effects of DBS on depression-related outcomes. Overall, 92 references met inclusion criteria, and have evaluated six unique DBS targets namely the subcallosal cingulate gyrus (SCG), nucleus accumbens (NAc), ventral capsule/ventral striatum or anterior limb of internal capsule (ALIC), medial forebrain bundle (MFB), lateral habenula (LHb) and inferior thalamic peduncle for the treatment of unrelenting TRD. Electrical stimulation of these pertinent brain regions displayed differential effects on mood transition in patients with TRD. In addition, 47 unique references provided preclinical evidence for putative neurobiological mechanisms underlying antidepressant effects of DBS applied to the ventromedial prefrontal cortex, NAc, MFB, LHb and subthalamic nucleus. Preclinical studies suggest that stimulation parameters and neuroanatomical locations could influence DBS-related antidepressant effects, and also pointed that modulatory effects on monoamine neurotransmitters in target regions or interconnected brain networks following DBS could have a role in the antidepressant effects of DBS. Among several neuromodulatory targets that have been investigated, DBS in the neuroanatomical framework of the SCG, ALIC and MFB yielded more consistent antidepressant response rates in samples with TRD. Nevertheless, more well-designed randomized double-blind, controlled trials are warranted to further assess the efficacy, safety and tolerability of these more promising DBS targets for the management of TRD as therapeutic effects have been inconsistent across some controlled studies.

Assessing and addressing cognitive impairment in bipolar disorder: the International Society for Bipolar Disorders Targeting Cognition Task Force recommendations for clinicians.

OBJECTIVES: Cognition is a new treatment target to aid functional recovery and enhance quality of life for patients with bipolar disorder. The International Society for Bipolar Disorders (ISBD) Targeting Cognition Task Force aimed to develop consensus-based clinical recommendations on whether, when and how to assess and address cognitive impairment. METHODS: The task force, consisting of 19 international experts from nine countries, discussed the challenges and recommendations in a face-to-face meeting, telephone conference call and email exchanges. Consensus-based recommendations were achieved through these exchanges with no need for formal consensus methods. RESULTS: The identified questions were: (I) Should cognitive screening assessments be routinely conducted in clinical settings? (II) What are the most feasible screening tools? (III) What are the implications if cognitive impairment is detected? (IV) What are the treatment perspectives? Key recommendations are that clinicians: (I) formally screen cognition in partially or fully remitted patients whenever possible, (II) use brief, easy-to-administer tools such as the Screen for Cognitive Impairment in Psychiatry and Cognitive Complaints in Bipolar Disorder Rating Assessment, and (III) evaluate the impact of medication and comorbidity, refer patients for comprehensive neuropsychological evaluation when clinically indicated, and encourage patients to build cognitive reserve. Regarding question (IV), there is limited evidence for current evidence-based treatments but intense research efforts are underway to identify new pharmacological and/or psychological cognition treatments. CONCLUSIONS: This task force paper provides the first consensus-based recommendations for clinicians on whether, when, and how to assess and address cognition, which may aid patients' functional recovery and improve their quality of life.