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Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes.The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included.There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations.Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.

Background : Clinical practice guidelines (CPG) are an important tool for implementation of evidence-based clinical care. Despite clinical trials showing lack of efficacy of some agents in bipolar disorder (BD), they are still frequently prescribed in clinical practice. The objective of this study was to systematically review the CPG recommendations on pharmacological interventions with evidence against their use due to lack of efficacy data and/or due to serious safety concerns. Methods : A systematic literature search identified 29 guidelines published by national and international organizations during the 1994-2020 period. Information was extracted regarding how the recommendations framed non-use of treatments in particular clinical situations as well as the actual recommendation in the guideline. Results : Twenty-three guidelines (79%) mentioned at least one non-recommended treatment. The terms used to qualify recommendations varied amongst guidelines and included: “not recommended” “no recommendation” and “negative evidence”. Lamotrigine, topiramate and gabapentin were commonly cited as non-recommended treatments for mania and most CPG did not recommend monotherapy with antidepressants, aripiprazole, risperidone, and ziprasidone for treatment of acute bipolar depression. Most guidelines made recommendations about lack of efficacy data or potential harm in treatments for BD but there is a significant variation in the way this information is conveyed to the reader. Limitations : Non-recommended treatments were based on their use for BD episodes or maintenance but specific medications may benefit patients when treating comorbid conditions. Conclusions : The absence of a uniform language and recommendations in current guidelines may be an additional complicating factor in the implementation of evidence-based treatments in BD.

Bipolar Disorder (BD) optimal care involves pharmacotherapy in conjunction with psychosocial interventions. Both treatment modalities require the establishment of a therapeutic alliance (TA), a cornerstone necessary for the successful treatment of any chronic illness regardless of the psychotherapeutic model1 . In mental disorders, TA has been considered a mediator of adherence and treatment success in a number of conditions, including but not being restricted to schizophrenia spectrum disorders; major depressive disorders, personality disorders; addictions, and also BD. It is well known that there are several obstacles to the establishment of a TA with individuals with BD, including those related to patient's characteristics (e.g. history of childhood maltreatment, comorbidities with personality disorders or substance abuse), to their illness (e.g. severity of symptoms, poor insight), patient characteristics, level of expertise and experience of the health care professional, and systemic factors (e.g. time available to provide care, models of remuneration, possibility to provide both pharmacological and psychotherapeutic care)1 . However, for psychiatrists and health professionals involved in the care of individuals with BD, countertransference (CT) factors could be especially challenging.

The emergence of ketamine as a rapid-action treatment for depression provided the impetus for the investigation of several new agents to address this unmet need. Pharmacologic targets from ketamine became a focus of interest. Strategies for development of new rapid-action agents include the manipulation of ketamine targets and also repurposing drugs that have been used for other conditions, similarly what happened with this medication. In this chapter, we bring to the reader the results of some recent research on new agents. Although most of them are still under investigation, they highlight the remarkable effort from the scientific community in the field of rapid-action antidepressive medications.

Background The bidirectional association between Major Depressive Disorder (MDD) and obesity suggests that body mass index (BMI) at the baseline could influence remission rates (RR) with pharmacological treatment. We evaluated the influence of baseline BMI on the chances of remission among patients with MDD administered antidepressants. Methods Based on the guidelines of the PRISMA statement, we conducted a systematic review on PubMed, Cochrane and Embase databases with subsequent meta-analysis and meta-regression. We included only randomized controlled trials evaluating the efficacy of antidepressants of different classes (monotherapy and combined therapies) that evidenced baseline BMI assessment. We created a model to describe the linear relationship between baseline BMI and RR. Results Our systematic review yielded 70 studies with a total of 9,779 patients in the active group and 7,136 patients in the placebo group. In placebo controlled studies, BMI influenced the RR of patients randomized to active treatment. The RR for antidepressants in monotherapy was higher in normal weight to overweight patients rather than obese patients (33% vs 12%, respectively). Also in monotherapy, the RR is higher when the study is conducted on patients with a lower baseline BMI (p=0.029). For combined therapies, the pooled RR was higher in obese patients rather than in normal weight to overweight patients (75% vs 17%, respectively). Limitations BMI provides no information about body composition and obesity can be related to several potential confounders that potentially influence RR. Conclusion The RR with antidepressant therapy seems to be associated with baseline BMI in patients with MDD, although this simple variable was insufficiently explored so far.

Background The considerable rise of mental health challenges during the COVID-19 pandemic has had detrimental effects on the public health sector and economy. To meet the overwhelming and growing demand for mental health care, innovative approaches must be employed to significantly expand mental health care delivery capacity. Although it is not feasible to increase the number of mental health care providers or hours they work in the short term, improving their time efficiency may be a viable solution. Virtually and digitally delivering psychotherapy, which has been shown to be efficient and clinically effective, might be a good method for addressing this growing demand. Objective This research protocol aims to evaluate the feasibility and efficacy of using an online, digital, asynchronous care model to treat mental health issues that are started or aggravated by stressors associated with the COVID-19 pandemic. Methods This nonrandomized controlled trial intervention will be delivered through the Online Psychotherapy Tool, a secure, cloud-based, digital mental health platform. Participants will be offered a 9-week electronically delivered cognitive behavioral therapy program that is tailored to address mental health problems in the context of the COVID-19 pandemic. This program will involve weekly self-guided educational material that provides an overview of behavioral skills and weekly homework. Participants (N=80) will receive personalized feedback from and weekly interaction with a therapist throughout the course of the program. The efficacy of the program will be evaluated using clinically validated symptomology questionnaires, which are to be completed by participants at baseline, week 5, and posttreatment. Inclusion criteria includes the capacity to consent; a primary diagnosis of generalized anxiety disorder or major depressive disorder, with symptoms that started or worsened during the COVID-19 pandemic; the ability to speak and read English; and consistent and reliable access to the internet. Exclusion criteria includes active psychosis, acute mania, severe alcohol or substance use disorder, and active suicidal or homicidal ideation. Results This study received funding in May 2020. Ethics approval was received in June 2020. The recruitment of participants began in June 2020. Participant recruitment is being conducted via social media, web-based communities, and physician referrals. To date, 58 participants have been recruited (intervention group: n=35; control group: n=23). Data collection is expected to conclude by the end of 2020. Analyses (ie, linear regression analysis for continuous outcomes and binomial regression analysis for categorical outcomes) are expected to be completed by February 2021. Conclusions If proven feasible, this care delivery method could increase care capacity by up to fourfold. The findings from this study can potentially influence clinical practices and policies and increase accessibility to care during the COVID-19 pandemic, without sacrificing the quality of care. Trial Registration ClinicalTrials.gov NCT04476667; https://clinicaltrials.gov/ct2/show/NCT04476667 International Registered Report Identifier (IRRID) DERR1-10.2196/24913

BACKGROUND The considerable rise of mental health challenges during the COVID-19 pandemic has had detrimental effects on the public health sector and economy. To meet the overwhelming and growing demand for mental health care, innovative approaches must be employed to significantly expand mental health care delivery capacity. Although it is not feasible to increase the number of mental health care providers or hours they work in the short term, improving their time efficiency may be a viable solution. Virtually and digitally delivering psychotherapy, which has been shown to be efficient and clinically effective, might be a good method for addressing this growing demand. OBJECTIVE This research protocol aims to evaluate the feasibility and efficacy of using an online, digital, asynchronous care model to treat mental health issues that are started or aggravated by stressors associated with the COVID-19 pandemic. METHODS This nonrandomized controlled trial intervention will be delivered through the Online Psychotherapy Tool, a secure, cloud-based, digital mental health platform. Participants will be offered a 9-week electronically delivered cognitive behavioral therapy program that is tailored to address mental health problems in the context of the COVID-19 pandemic. This program will involve weekly self-guided educational material that provides an overview of behavioral skills and weekly homework. Participants (N=80) will receive personalized feedback from and weekly interaction with a therapist throughout the course of the program. The efficacy of the program will be evaluated using clinically validated symptomology questionnaires, which are to be completed by participants at baseline, week 5, and posttreatment. Inclusion criteria includes the capacity to consent; a primary diagnosis of generalized anxiety disorder or major depressive disorder, with symptoms that started or worsened during the COVID-19 pandemic; the ability to speak and read English; and consistent and reliable access to the internet. Exclusion criteria includes active psychosis, acute mania, severe alcohol or substance use disorder, and active suicidal or homicidal ideation. RESULTS This study received funding in May 2020. Ethics approval was received in June 2020. The recruitment of participants began in June 2020. Participant recruitment is being conducted via social media, web-based communities, and physician referrals. To date, 58 participants have been recruited (intervention group: n=35; control group: n=23). Data collection is expected to conclude by the end of 2020. Analyses (ie, linear regression analysis for continuous outcomes and binomial regression analysis for categorical outcomes) are expected to be completed by February 2021. CONCLUSIONS If proven feasible, this care delivery method could increase care capacity by up to fourfold. The findings from this study can potentially influence clinical practices and policies and increase accessibility to care during the COVID-19 pandemic, without sacrificing the quality of care. CLINICALTRIAL ClinicalTrials.gov NCT04476667; https://clinicaltrials.gov/ct2/show/NCT04476667 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/24913

Background As the percentage of elderly people (aged over 65) is expected to rise, from 16.0% of the population in 2010 to 29.3% in 2060 in Europe, a quality long-term care system is of increasing priority for governments. The aim of this study is to analyse long-term care services (LTCS) in the geographical area of the group of primary healthcare centres of Loures-Odivelas. Methods A retrospective, observational, descriptive study comprising data from public health inspections to LTCS between 2015 and 2019. Variables included were the number of residents, nurses, orderly, cooks, kitchen helpers and medical doctors; licensing status, public health inspection results and the presence of air conditioning. Descriptive analysis was performed for all variables. Results Between 2015 and 2019, a total of 200 public health inspections were carried out in 106 LTCS. Only 41 (38.7%) LTCS were licensed. The total number of residents was 2,803, 168 (6.0%) of which were bedridden. Concerning the staff ratio, 79 (74.5%) LTCS fulfilled the ratio of nurse to resident of 1:40 and 67 (63.2%) the ratio of orderly to resident of 1:8. On the first inspection, 11 LTCS (10.4%) complied with the minimal requirements for health care, hygiene, food preparation and facilities conditions. After the implementation of corrective measures proposed by the Public Health Unit, the number of LTCS which had complied for the same criteria was 64 (60.4%). Conclusions Society needs to adapt to a growing ageing population. LCTS, while part of the solution, still have deficiencies. In this sample, the majority were illegal and lacked the appropriate conditions. Public Health interventions can contribute to improving these services. Key messages In an ageing society, long-term care services are essential but the majority lack the appropriate conditions. Public Health intervention is crucial in implementing corrective measures that will result in better conditions for the elderly.

Background Tuberculosis (TB), a communicable disease, is the leading cause of death from a single infectious agent and one of the top 10 causes of death worldwide. Its burden varies among different countries. In the 31 European Economic Area member states, in 2017, the TB notification rate was 10.7/100,000 population; in Portugal, this rate was 17.5/100,000 population and the majority of the notified cases occurred in two districts: Lisbon and Oporto. The aim of this study is to analyse TB's notifications in a group of primary healthcare centres of Loures-Odivelas (ACES LO), between 2015 and 2019. Methods An observational, descriptive, retrospective, quantitative study was performed. Data was collected in January 2020, from the National System of Epidemiological Surveillance Database. Variables included were: age, sex, TB's presentation, antimicrobial susceptibility testing, HIV testing. Descriptive analysis was performed for all variables. Results In ACES LO, notified cases of TB dropped 18.0% between 2015 and 2017, having since increased by 54.8% (n = 113), a notification rate of 32.3/100,000 population in 2019. The male to female ratio was 1.7 and the most affected age group was the 30-40 year old group (n = 25). Notified cases in children Conclusions Surveillance is the first step towards taking action to control and eliminate TB. ACES LO has a high notification rate of TB, therefore effort should be made in order to reduce TB's incidence. More investigation should be performed in order to evaluate the possibility of reintroduction of Bacille Calmette-Guérin (BCG) vaccine to the general population, instead of only risk groups, as it happens in ACES LO since 2016. Key messages Surveillance is one of the ten essential Public Health operations, allowing us to measure and analyse health problems in a certain population. Tuberculosis’ incidence is still high in some populations; it is a critical issue to raise awareness about.

Author(s): Goldstein, Benjamin I; Baune, Bernhard T; Bond, David J; Chen, Pao-Huan; Eyler, Lisa; Fagiolini, Andrea; Gomes, Fabiano; Hajek, Tomas; Hatch, Jessica; McElroy, Susan L; McIntyre, Roger S; Prieto, Miguel; Sylvia, Louisa G; Tsai, Shang-Ying; Kcomt, Andrew; Fiedorowicz, Jess G | Abstract: ObjectivesThe association of bipolar disorder with early and excessive cardiovascular disease was identified over a century ago. Nonetheless, the vascular-bipolar link remains underrecognized, particularly with regard to how this link can contribute to our understanding of pathogenesis and treatment.MethodsAn international group of experts completed a selective review of the literature, distilling core themes, identifying limitations and gaps in the literature, and highlighting future directions to bridge these gaps.ResultsThe association between bipolar disorder and vascular disease is large in magnitude, consistent across studies, and independent of confounding variables where assessed. The vascular-bipolar link is multifactorial and is difficult to study given the latency between the onset of bipolar disorder, often in adolescence or early adulthood, and subsequent vascular disease, which usually occurs decades later. As a result, studies have often focused on risk factors for vascular disease or intermediate phenotypes, such as structural and functional vascular imaging measures. There is interest in identifying the most relevant mediators of this relationship, including lifestyle (eg, smoking, diet, exercise), medications, and systemic biological mediators (eg, inflammation). Nonetheless, there is a paucity of treatment studies that deliberately engage these mediators, and thus far no treatment studies have focused on engaging vascular imaging targets.ConclusionsFurther research focused on the vascular-bipolar link holds promise for gleaning insights regarding the underlying causes of bipolar disorder, identifying novel treatment approaches, and mitigating disparities in cardiovascular outcomes for people with bipolar disorder.

In the recent months, the world was taken by surprise by the outbreak of a coronavirus (SARS-CoV-2) pandemic (COVID-19). The COVID-19 pandemic is a unique opportunity to advance the understanding of the association of respiratory viruses with mood disorders and suicide. In this editorial, we explore three insights to the neuropsychoneuroimmunology of mood disorders that could be taken from the COVID-19 pandemic.

O transtorno bipolar é associado a diversas condições médicas gerais, resultando em um aumento significativo da morbimortalidade. As doenças do sistema cardiovascular e endócrino são as mais comumente associadas ao transtorno, havendo evidências significativas do efeito deletério de algumas medicações na etiologia e curso das comorbidades clínicas. Além disso, existem evidências recentes de que a própria doença bipolar, assim como os episódios recorrentes da doença, podem estar associados a uma maior incidência de doenças físicas. A avaliação do paciente bipolar deve incluir a realização de anamnese relacionada aos fatores de risco pessoais e familiares, exame clínico, solicitação de exames complementares que foram pertinentes ao quadro e monitorização dos efeitos colaterais das medicações na saúde global do paciente.

Background Bipolar disorder is associated with an increased burden of general medical conditions that might be related to a more severe illness course. Methods This is a cross-sectional study that evaluated clinical correlates of general medical comorbidities in outpatients with bipolar disorder (BD) involving 203 adult patients with a DSM-IV diagnosis of BD, consecutively recruited from the Bipolar Research Program (PROTAHBI) in Porto Alegre, Brazil. Clinical, demographic and anthropometrical variables were systematically assessed, and general medical comorbidity was measured using the Cumulative Illness Rating Scale (CIRS). Results The prevalence of one or more medical comorbidities was 90.1%. The most common were those from endocrine/metabolic/breast, neurologic and vascular categories. A high burden of general medical comorbidities (defined as CIRS total score ≥ 4) was related to increasing age and body mass index and longer duration of illness after controlling for confounding factors. Limitations The cross-sectional design limits our ability to make causal conclusions. Also, our sample consisted of patients with longer illness duration from a tertiary clinic and may not generalize to the whole spectrum of bipolar disorder. Conclusions BD was associated with a high burden of general medical conditions related to age, obesity and longer duration of illness. Medical comorbidities must be incorporated as a core feature in the development of effective treatment strategies for bipolar disorder.

Objective: Bipolar disorder (BD) is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD) that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD. Methods: A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN) in São Paulo and the Bipolar Disorder Program (PROTAHBI) in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed. Results: High rates of smoking (27%), physical inactivity (64.9%), alcohol use disorders (20.8%), elevated fasting glucose (26.4%), diabetes (13.2%), hypertension (38.4%), hypertriglyceridemia (25.8%), low HDL-cholesterol (27.7%), general (38.4%) and abdominal obesity (59.1%) were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis. Conclusion: This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population.

BACKGROUND: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. OBJECTIVE: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. METHOD: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre , Brazil. IR was diagnosed by the homeostatic model assessment - insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. RESULTS: IR was present in 43.1% of the sample (women 40%, men 44.4%). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3%, NCEP-ATP III modified was 40% and IDF was 41.5%. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6%) and specificity (89.2%) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. DISCUSSION: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population. CONTEXTO: O transtorno bipolar (TB) está associado a uma significativa morbi-mortalidade por causas metabólicas. Existem poucos dados sobre a prevalência de resistência à insulina (RI) e sua relação com a síndrome metabólica (SM) em pacientes com TB. OBJETIVO: Avaliar a prevalência de RI e SM em pacientes bipolares ambulatoriais e identificar os parâmetros clínicos associados à RI. MÉTODO: Estudo transversal em 65 pacientes com TB diagnosticados pelos critérios do DSM-IV-TR, avaliados de forma consecutiva no Programa de Transtorno Bipolar do Hospital de Clínicas de Porto Alegre, Brasil. RI foi diagnosticada utilizando o homeostatic model assessment - insulin resistance (HOMA-IR) e a SM foi diagnosticada utilizando três definições diferentes: do National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); do NCEP-ATP III modificado e da International Diabetes Federation (IDF). RESULTADOS: A prevalência de RI foi 43,1% (mulheres 40%, homens 44,4%). A prevalência de SM definida pelo NCEP ATP III foi 32,3%, pelo NCEP ATP III foi 40% e pela IDF foi 41,5%. Os critérios do NCEP ATP III modificado demonstrou a melhor relação entre sensibilidade (78,6%) e especificidade (89,2%) na detecção de RI. A circunferência da cintura foi o parâmetro clínico mais associado à RI. CONCLUSÃO: As definições atuais de SM podem identificar, com razoável sensibilidade e especificidade, RI em pacientes com TB. A obesidade abdominal é bastante associada à RI nessa população de pacientes.

CONTEXTO: O transtorno bipolar (TB) está associado a uma significativa morbi-mortalidade por causas metabólicas. Existem poucos dados sobre a prevalência de resistência à insulina (RI) e sua relação com a síndrome metabólica (SM) em pacientes com TB. OBJETIVO: Avaliar a prevalência de RI e SM em pacientes bipolares ambulatoriais e identificar os parâmetros clínicos associados à RI. MÉTODO: Estudo transversal em 65 pacientes com TB diagnosticados pelos critérios do DSM-IV-TR, avaliados de forma consecutiva no Programa de Transtorno Bipolar do Hospital de Clínicas de Porto Alegre, Brasil. RI foi diagnosticada utilizando o homeostatic model assessment - insulin resistance (HOMA-IR) e a SM foi diagnosticada utilizando três definições diferentes: do National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); do NCEP-ATP III modificado e da International Diabetes Federation (IDF). RESULTADOS: A prevalência de RI foi 43,1% (mulheres 40%, homens 44,4%). A prevalência de SM definida pelo NCEP ATP III foi 32,3%, pelo NCEP ATP III foi 40% e pela IDF foi 41,5%. Os critérios do NCEP ATP III modificado demonstrou a melhor relação entre sensibilidade (78,6%) e especificidade (89,2%) na detecção de RI. A circunferência da cintura foi o parâmetro clínico mais associado à RI. CONCLUSÃO: As definições atuais de SM podem identificar, com razoável sensibilidade e especificidade, RI em pacientes com TB. A obesidade abdominal é bastante associada à RI nessa população de pacientes.BACKGROUND: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. OBJECTIVE: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. METHOD: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre , Brazil. IR was diagnosed by the homeostatic model assessment - insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. RESULTS: IR was present in 43.1% of the sample (women 40%, men 44.4%). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3%, NCEP-ATP III modified was 40% and IDF was 41.5%. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6%) and specificity (89.2%) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. DISCUSSION: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population.

Objective: Substance use disorders and birth-cohort have been associated with an earlier onset in bipolar disorder (BD). This study aimed at evaluating the inter-relations of these factors in age-at-onset in bipolar illness. Method: Two-hundred and thirty patients with bipolar I disorder were cross-sectionally evaluated. Patients were categorized into four age groups for analysis. Lifetime comorbidity and age-at-onset were derived from the Structured Clinical Interview for DSM-IV. Results: There was a strong linear association between age group and age-at-onset. Lifetime alcohol and drug use disorders were also associated with age-at-onset. Illicit drug and alcohol use disorders and age group remained significant in the multivariate model. No interactions appeared. Conclusion: Both age group and dual diagnoses had strong and independent impacts on age-at-onset in out-patients with BD. Substance abuse may be partly accountable for earlier symptom onset, but other features of BD in younger generations are still in need to be accounted for.

There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD). Methods We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N = 21), manic (N = 32) and euthymic (N = 31) bipolar patients, and in chronically medicated patients with schizophrenia (N = 97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N = 32). Results Serum SOD (U/mg protein) activity was significantly increased (p

Current literature on the effects of chronic stress in general health converges to the concept of allostatic load (AL). AL is the bodily 'wear and tear' that emerges with sustained allostatic states. In the field of bipolar disorder (BD), AL offers an important clue as to why patients who undergo recurrent mood episodes are clinically perceived as less resilient. In addition, AL helps explaining the cumulative disruptive health effects of intermittent episodes and stressors. Stress- and episode-induced changes in brain regions involved in the emotional circuitry may lead to dysfunctional processing of information, which would render BD patients more vulnerable to subsequent environmental stressors, episodes, and drugs of abuse. Mood stabilizing agents exert opposite effects than chronic stress in neurons, increasing neuroprotective factors what may help to quench the cycle of affective episode recurrence and neural and bodily deterioration. Therefore, AL provides an explanatory link to apparently unrelated findings such as cognitive impairment and higher rates of physical comorbidity and mortality that are observed in the course of BD and further highlight the importance of effective long-term prophylaxis.

Gomes FA, Kauer-Sant’Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder.Objective:There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder.Methods:Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese.Results:Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s).Conclusion:Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients.

Objective There is an emerging body of data suggesting that oxidative stress may be associated with the pathophysiology of bipolar disorder (BD). In the present study we investigated the oxidative stress profile in two monozygotic twins during a manic episode. Methods Two monozygotic twins diagnosed as currently manic by the Structured Clinical Interview for DSM-IV were studied. Serum thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD) and catalase (CAT) were measured as parameters of oxidative stress. DNA damage was assessed using the single cell gel electrophoresis technique (Comet Assay). All biochemical measures were conducted at baseline and after a 6-week treatment. Results Bipolar twins had higher TBARS, SOD and DNA damage, and lower CAT than the healthy control. TBARS and SOD were normalized after mood stabilization, whereas CAT and DNA damage remained altered at week 6. Conclusions These findings support that oxidative stress may play a role in the pathophysiology of BD and that pharmacological treatment may exert antioxidant effects. Studies with larger samples are warranted to further clarify this issue.

Brain-derived neurotrophic factor (BDNF) plays a central role in synaptic plasticity and neurogenesis. Bipolar disorder (BD) is among the most disabling of all psychiatric disorders and is associated with poor outcomes. Some studies suggest that BDNF levels decrease during mood states and remain normal during euthymia, but other studies have contradicted this paradigm. Therefore, the aim of this study was to perform a meta-analysis of all studies that measured peripheral BDNF levels in adults with BD. We conducted a systematic review using electronic databases. Inclusion criteria were studies that measured BDNF in plasma or serum in vivo in adult patients with BD. The resulting studies were compiled to measure the effect sizes (ESs) of the differences in BDNF levels between BD patients in different mood states and controls. Thirteen studies were included with a total of 1113 subjects. The BDNF levels were decreased in both mania and depression when compared to controls (ES � 0.81, 95% CI � 1.11 to � 0.52, p < 0.0001 and ES � 0.97, 95% CI � 1.79 to � 0.51, p ¼ 0.02, respectively). The BDNF levels were not different in euthymia when compared to controls (ES � 0.20, 95% CI � 0.61 to 0.21, p ¼ 0.33). Meta- regression analyses in euthymia showed that age (p < 0.0001) and length of illness (p ¼ 0.04) influenced the variation in ES. There was also an increase in BDNF levels following the treatment for acute mania (ES � 0.63, 95% CI � 1.11 to � 0.15, p ¼ 0.01). In conclusion, BDNF levels are consistently reduced during manic and depressive episodes and recover after treatment for acute mania. In euthymia, BDNF decreases with age and length of illness. These data suggest that peripheral BDNF could be used as a biomarker of mood states and disease progression for BD.

Glutamate deregulation may be involved in the neuropathology of schizophrenia, mainly through N-methyl-d-aspartate (NMDA) receptor dysfunction. Memantine, a drug approved by the FDA for the treatment of moderate to severe Alzheimer's disease, acts as a weak nonselective NMDA receptor antagonist. The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia.In this double-blind, placebo-controlled study, outpatients with refractory schizophrenia according to DSM-IV clinical criteria were randomly assigned, from March 2005 to February 2008, to receive either 20 mg/d memantine (n = 10) or placebo (n = 11), in addition to clozapine, for 12 weeks. The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale (BPRS) and BPRS subscales of positive and negative symptoms. Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale (CGI), cognition as assessed by the Mini-Mental State Examination (MMSE), and extrapyramidal symptoms as assessed by the Simpson-Angus Scale (SAS).Twenty-one participants completed the study and were used in the analysis. Significant improvement (P.01) on the total BPRS score, its subscales of positive (effect size [ES] = -1.38) and negative (ES = -3.33) symptoms, the CGI score (ES = 1.56), and the MMSE score was observed with memantine as compared with placebo. No significant changes in extrapyramidal symptoms were observed.Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients.clinicaltrials.gov Identifier: NCT00757978.

Objetivo: O objetivo do estudo foi avaliar os níveis séricos do fator neurotrófico derivado do cérebro em um paciente com transtorno de estresse pós-traumático e em um paciente com transtorno de estresse agudo antes e após o tratamento, comparando esses níveis aos de controles saudáveis. Método: Os níveis do fator neurotrófico derivado do cérebro, a Escala Davidson de Trauma, o Inventário de Depressão de Beck, a Avaliação do Funcionamento Global e a Impressão Clínica Global foram medidos antes e após seis semanas de tratamento. Resultados: Os níveis de fator neurotrófico derivado do cérebro foram maiores nos pacientes, quando comparados aos controles, antes do tratamento. Depois de seis semanas houve redução dos sintomas e melhora do funcionamento nos dois casos. Ao mesmo tempo, houve redução dos níveis de fator neurotrófico derivado do cérebro, mesmo no caso 2, tratado exclusivamente com psicoterapia. Conclusões: Esses resultados sugerem que o fator neurotrófico derivado do cérebro está aumentado tanto no transtorno de estresse pós-traumático quanto no transtorno de estresse agudo, de forma oposta às alterações até então descritas nos transtornos do humor. Objective: The aim of this study was to evaluate brain-derived neurotrophic factor levels in two patients, one with posttraumatic stress disorder and one with acute stress disorder, before and after treatment, and to compare those levels to those of healthy controls. Method: Brain-derived neurotrophic factor level, Davidson Trauma Scale, Beck Depression Inventory, Global Assessment of Functioning, and Clinical Global Impression were assessed before and after 6 weeks of treatment. Results: Brain-derived neurotrophic factor levels were higher in patients than in matched controls before treatment. After 6 weeks, there was a reduction in symptoms and an improvement in functioning in both cases. At the same time, brain-derived neurotrophic factor levels decreased after treatment, even in case 2, treated with psychotherapy only. Conclusions: These results suggest that serum levels of brain-derived neurotrophic factor, as opposed to what has been described in mood disorders, are increased in posttraumatic stress disorder as well as in acute stress disorder.

There has been an increasing interest in the role of the immune and inflammatory systems in mood disorders. Mood episodes are associated with changes in acute phase proteins such as high-sensitivity C-reactive protein (hsCRP). The present study investigated serum hsCRP in manic, depressed, and euthymic BD patients as compared to matched healthy controls. Serum hsCRP was assessed using an ultrasensitive assay of particle-enhanced immunoturbidimetric latex agglutination. Serum hsCRP levels were increased in manic BD patients, as compared to euthymic, depressed patients and healthy controls (P < 0.001). These findings add to the notion that changes in the inflammatory system take place during acute episodes of mania.

Background It has been reported that patients with bipolar disorder (BD) remain about 10 years symptomatic before the correct diagnosis is made. This fact is particularly important for patients with predominantly depressed polarity who tend to be diagnosed as suffering from unipolar major depressive disorder and treated with antidepressants. The present study was carried out to assess clinical differences between predominantly manic and depressed BD patients with a special focus on the time that patients remained undiagnosed. Methods Clinical and socio-demographic characteristics were obtained from a sample of 149 euthymic bipolar outpatients. Patients were divided into depressive or manic predominance of polarity. Clinical features, number of years undiagnosed (NYU) and occupational functioning were assessed in the two groups. Results Forty-five patients were classified as a “Depressive Polarity” whilst forty-seven were considered as “Manic Polarity”. Depressive Polarity was associated with a longer delay to be diagnosed (F = 14.43, df = 89, p = 0.001). The predominantly depressive patients tended to present a depressive onset of illness, earlier age of onset, longer duration of illness and higher number of suicide attempts than manic polarity patients. Conclusion There was a marked clinical difference between predominantly manic and depressive bipolar patients. Predominantly depressive polarity is associated with a longer delay in receiving a correct diagnosis and effective treatment which has an important impact on the management of the illness.

To verify and classify, according to the JNC 7, the blood pressure levels (BPL) of the employees of University of Brasilia, a public university in Brazil, who are older than 40 years of age, and to estimate the prevalence of cardiovascular risk factors in this population.A cross-sectional study was conducted at the University of Brasilia, with employees over 40 years of age. They answered a questionnaire and had their blood pressure, weight and height measured. The BPLs were classified according to the JNC 7 classification and the demographic data of the subjects in each category were analyzed. The percentage of risk factors was calculated. The statistical analysis was carried out using the ANOVA test and the chi-square test, where applicable.Seven hundred and four subjects participated in the study, 438 male and 266 female. The median age was 47. According to the JNC 7, 139 (19.8%) subjects were classified as normotensive; 298 (42.3%) as prehypertensive and 267 (37.9%) as hypertensive. The risk factors assessed were overweight/obesity (56.8%), smoking habit (19.5%), alcohol consumption (53.6%), sedentary lifestyle (48.4%) and hypertension (37.9%).The high frequency of elevated blood pressure levels and cardiovascular risk factors among the employees indicates the need for preventive and therapeutic measures for cardiovascular disease targeted at the university's employees.

OBJETIVO: Verificar e classificar, de acordo com o JNC 7, os níveis de pressão arterial dos servidores acima de quarenta anos da Universidade de Brasília, e estimar a prevalência de fatores de risco cardiovasculares presentes em tal população. MÉTODOS: Foi realizado um estudo transversal na Universidade de Brasília, onde os servidores acima de quarenta anos responderam a um questionário e tiveram pressão arterial, peso e altura medidos. Os níveis de pressão arterial foram classificados de acordo com o JNC 7 e os dados demográficos dos indivíduos de cada categoria foram analisados. A porcentagem dos fatores de risco foi calculada. A análise estatística foi feita através do teste ANOVA e do teste qui-quadrado, quando aplicável. RESULTADOS: Setecentos e quatro servidores participaram do estudo, incluindo 438 homens e 266 mulheres. A mediana de idade foi 47 anos. Segundo o JNC 7, 139 (19,8%) pessoas foram classificadas como normotensas; 298 (42,3%) como pré-hipertensas e 267 (37,9%) como hipertensas. Os fatores de risco avaliados foram sobrepeso/obesidade (56,8%), tabagismo (19,5%), consumo de bebidas alcoólicas (53,6%), sedentarismo (48,4%) e hipertensão (37,9%). CONCLUSÃO: A alta freqüência de níveis pressóricos elevados e fatores de risco cardiovasculares apontam para a necessidade de medidas preventivas e terapêuticas de doenças cardiovasculares direcionadas aos servidores da universidade. OBJECTIVE: To verify and classify, according to the JNC 7, the blood pressure levels (BPL) of the employees of University of Brasilia, a public university in Brazil, who are older than 40 years of age, and to estimate the prevalence of cardiovascular risk factors in this population. METHODS: A cross-sectional study was conducted at the University of Brasilia, with employees over 40 years of age. They answered a questionnaire and had their blood pressure, weight and height measured. The BPLs were classifi ed according to the JNC 7 classifi cation and the demographic data of the subjects in each category were analyzed. The percentage of risk factors was calculated. The statistical analysis was carried out using the ANOVA test and the chi-square test, where applicable. RESULTS: Seven hundred and four subjects participated in the study, 438 male and 266 female. The median age was 47. According to the JNC 7, 139 (19.8%) subjects were classified as normotensive; 298 (42.3%) as prehypertensive and 267 (37.9%) as hypertensive. The risk factors assessed were overweight/obesity (56.8%), smoking habit (19.5%), alcohol consumption (53.6%), sedentary lifestyle (48.4%) and hypertension (37.9%). CONCLUSION: The high frequency of elevated blood pressure levels and cardiovascular risk factors among the employees indicates the need for preventive and therapeutic measures for cardiovascular disease targeted at the university’s employees.