The management of cognitive impairment in bipolar disorder: current status and perspectives.

Bipolar disorder (BD) is associated with important cognitive deficits that persist during the periods of remission. Although these deficits seem to play an important role in the functional impairment experienced by bipolar patients, evidence regarding their clinical management is scant. We revised the databases PubMed, MEDLINE, and clinicaltrials.gov, searching for studies focusing on the pharmacological and nonpharmacological treatment of cognitive deficits among bipolar patients. In addition, a manual search of bibliographical cross-references was performed. Currently, there is no Food and Drug Administration-approved pharmacological agent for the management of cognitive deficits in BD. A number of agents have been tested in the treatment of cognitive deficits in BD, with mixed results. Nonpharmacological interventions, such as cognitive remediation and noninvasive brain stimulation techniques, seem promising, but their role has not yet been properly explored among bipolar patients. Additional studies, aiming at evaluating the efficacy of interventions combining cognitive rehabilitation and biological treatments, are highly desirable.

Esters flash point prediction using artificial neural networks.

In this article, an artificial neural network to predict the flash point of 95 esters was implemented. Four variables were used for its development. A neural network with 4-5-8-5-1 topology was encountered to gain the best agreement of the experimental results with those predicted (square correlation coefficient (R(2)) and root mean square error were 0.99 and 5.46 K for the training phase and 0.96 and 13.02 K for the testing set).

Modeling mania in preclinical settings: A comprehensive review.

The current pathophysiological understanding of mechanisms leading to onset and progression of bipolar manic episodes remains limited. At the same time, available animal models for mania have limited face, construct, and predictive validities. Additionally, these models fail to encompass recent pathophysiological frameworks of bipolar disorder (BD), e.g. neuroprogression. Therefore, there is a need to search for novel preclinical models for mania that could comprehensively address these limitations. Herein we review the history, validity, and caveats of currently available animal models for mania. We also review new genetic models for mania, namely knockout mice for genes involved in neurotransmission, synapse formation, and intracellular signaling pathways. Furthermore, we review recent trends in preclinical models for mania that may aid in the comprehension of mechanisms underlying the neuroprogressive and recurring nature of BD. In conclusion, the validity of animal models for mania remains limited. Nevertheless, novel (e.g. genetic) animal models as well as adaptation of existing paradigms hold promise.

Lifestyle interventions targeting dietary habits and exercise in bipolar disorder: A systematic review.

BACKGROUND: Bipolar disorder (BD) is a serious mental illness associated with a high risk of medical comorbidities, long-term disability and premature death. This systematic review examined the current literature on therapeutic interventions targeting nutrition, physical activity and wellness in BD and collecting health-related measures such as mood and course of illness. METHODS: Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to June 2015, for studies focusing on lifestyle interventions in BD. Search terms were related to bipolar disorder, nutrition, physical activity, wellbeing, psychosocial interventions and course of illness. We hand searched content pages of Bipolar Disorders and Journal of Affective Disorders and checked references of relevant reviews and dissertations to identify additional papers. RESULTS: After applying inclusion and exclusion criteria to identified hits, this literature search retrieved six papers. Overall findings point towards a beneficial role of lifestyle interventions on mood, weight, blood pressure, lipid profile, physical activity and overall wellbeing. Methodological limitations include small sample size, gender ratio imbalance, inconsistencies in terms of laboratory measures, and lack of randomized controlled trials and absence of follow-up and longitudinal studies to determine the benefits of these factors on clinical and functional outcomes over time CONCLUSIONS: Lifestyle interventions in BD targeting nutrition, exercise, wellbeing alongside beliefs, coping strategies and attitudes towards health show promise in reducing the risk of comorbid ailments in BD. There is still a strong need for studies a) developing interventions which are informed by the patient's input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials.

Premorbid obesity and metabolic disturbances as promising clinical targets for the prevention and early screening of bipolar disorder.

Recent evidence shows an important relationship between metabolic disturbances and bipolar disorder (BD). However, it is still unclear whether such metabolic disturbances are only a consequence or to some extent the precipitating factors for health problems and maladaptive behaviors observed in BD. Because both metabolic disturbances and BD are medical conditions sharing common alterations in multiple biomarkers, it is plausible to hypothesize that metabolic disturbances may be considered to some extent as a major vulnerability factor in the latent phase of BD for some young adults. In line with this hypothesis, obesity may be regarded as a major driving force for prevalent cardio-metabolic disorders encountered within the early stages of BD. Likewise, premorbid metabolic disturbances as a whole may be considered as a potential source for vulnerability to develop BD. In addition, a synergistic relationship between obesity and metabolic disturbances associated with a premorbid disruption of biological rhythms may also lead to BD. Therefore, we postulate that metabolic disturbances may serve as a specific marker of premorbid illness activity in some people at risk for BD. Future prospective studies should focus on validating metabolic disturbances as vulnerability factors within the staging model of BD.

The medial forebrain bundle as a deep brain stimulation target for treatment resistant depression: A review of published data.

INTRODUCTION: Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. OBJECTIVE: To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. RESULTS: The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. DISCUSSION: The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. CONCLUSION: There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection.

Shared clinical associations between obesity and impulsivity in rapid cycling bipolar disorder: a systematic review.

BACKGROUND: Obesity seems to show a two-way relationship with bipolar disorder (BD), representing not only a possible vulnerability factor but also a consequence of chronic mood dysregulation associated with an overall poor prognosis. Increased impulsivity has been described across all stages and phases of BD as being also associated with a worse prognosis. Although obesity and impulsivity are common features among rapid cycling bipolar disorder (RC-BD) patients, there is a lack of understanding about the clinical implications of these conditions combined in BD. METHODS: To explore and integrate available evidence on shared clinical associations between obesity and impulsivity in RC-BD a systematic search of the literature in the electronic database of the National Library of Medicine (PubMed) has been conducted. RESULTS: One hundred and fourteen articles were included in our systematic review. Among RC-BD patients, substance abuse disorders (SUDs), anxiety disorders (ADs), predominantly depressive polarity, chronic exposure to antidepressants, psychotic symptoms, suicidality, and comorbid medical conditions are strongly associated with both obesity and impulsivity. LIMITATIONS: Heterogeneity of published data, inconsistent measurements of both obesity and impulsivity in RC-BD and an absence of control for RC-BD in epidemiological surveys. Consequently, their combined impact on the severity of RC-BD is yet to be recognized and remains to be poorly understood. CONCLUSION: In RC-BD patients the co-occurrence of obesity and impulsivity is associated with an unfavorable course of illness, specific shared clinical correlates, negative psychosocial impact, and overall worse prognosis. There is a need to examine obesity and impulsivity as modulating factors and markers of severity in RC-BD.

Common biological mechanisms between bipolar disorder and type 2 diabetes: Focus on inflammation.

INTRODUCTION: Bipolar disorder (BD) patients present a 3-5 fold greater risk of developing type 2 diabetes (T2D) compared to general population. The underlying mechanisms for the increased prevalence of T2D in BD population are poorly understood. OBJECTIVES: The purpose of this review is to critically review evidence suggesting that inflammation may have an important role in the development of both BD and T2D. RESULTS: The literature covered in this review suggests that inflammatory dysregulation take place among many BD patients. Such dysregulated and low grade chronic inflammatory process may also increase the prevalence of T2D in BD population. Current evidence supports the hypothesis of dysregulated inflammatory processes as a critical upstream event in BD as well as in T2D. CONCLUSIONS: Inflammation may be a factor for the development of T2D in BD population. The identification of inflammatory markers common to these two medical conditions will enable researchers and clinicians to better understand the etiology of BD and develop treatments that simultaneously target all aspects of this multi-system condition.