Isabelle E. Bauer

Inflammatory mediators of cognitive impairment in bipolar disorder

OBJECTIVES Recent studies have pointed to neuroinflammation, oxidative stress and neurotrophic factors as key mediators in the pathophysiology of mood disorders. Little is however known about the cascade of biological episodes underlying the cognitive deficits observed during the acute and euthymic phases of bipolar disorder (BD). The aim of this review is to assess the potential association between cognitive impairment and biomarkers of inflammation, oxidative stress and neurotrophic activity in BD. METHODS Scopus (all databases), Pubmed and Ovid Medline were systematically searched with no language or year restrictions, up to November 2013, for human studies that collected both inflammatory markers and cognitive data in BD. Selected search terms were bipolar disorder, depression, mania, psychosis, inflammatory, cognitive and neurotrophic. RESULTS Ten human studies satisfied the criteria for consideration. The findings showed that high levels of peripheral inflammatory-cytokine, oxidative stress and reduced brain derived neurotrophic factor (BDNF) levels were associated with poor cognitive performance. The BDNF val66met polymorphism is a potential vulnerability factor for cognitive impairment in BD. CONCLUSIONS Current data provide preliminary evidence of a link between the cognitive decline observed in BD and mechanisms of neuroinflammation and neuroprotection. The identification of BD specific inflammatory markers and polymorphisms in inflammatory response genes may be of assistance for therapeutic intervention.

Neuroprogression and Cognitive Functioning in Bipolar Disorder: A Systematic Review

Bipolar disorder (BD) has been associated with impairments in a range of cognitive domains including attention, verbal learning, and mental flexibility. These deficits are increased during the acute phases of the illness and worsen over the course of BD. This review will examine the literature in relation to potential mechanisms associated with cognitive decline in BD. Scopus (all databases), Pubmed, and Ovid Medline were systematically searched with no language or year restrictions, up to January 2015, for human studies that collected cross-sectional and longitudinal cognitive data in adults with BD and matched healthy controls (HC). Selected search terms were “bipolar,” “cognitive,” “aging,” “illness duration,” “onset,” and “progression.” Thirty-nine studies satisfied the criteria for consideration. There is evidence that cognitive function in BD is negatively associated with features of illness progression such as number of mood episodes, illness duration, and hospitalizations. Aging does not appear to affect cognitive functioning to a greater extent than in HC. Furthermore, the small number of longitudinal studies in this field does not allow to reaching firm conclusion in terms of which sub-populations would be more prone to cognitive decline in BD. The decline in cognitive abilities over the course of the BD seems to be associated with the number of episodes and number of hospitalizations. No meaningful interaction of age and bipolar disorder has been found in terms of cognitive decline. Future large-scale longitudinal studies are necessary to confirm these findings and assist in the development of preventive interventions in vulnerable individuals.

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.

Acute effects of different multivitamin mineral preparations with and without guarana on mood, cognitive performance and functional brain activation

Previous work has identified the positive effects of the acute administration of a multivitamin-guaraná preparation during an effortful executive/working memory task. Here, we aimed to differentiate the effects of multivitamins with and without guaraná and to examine the neural substrates of such effects using functional magnetic resonance imaging (fMRI). Following a double-blind, placebo-controlled, randomised, balanced crossover design, 20 participants (mean age 29 ± 5.54 years) consumed multivitamin preparations with or without guaraná (Berocca® Performance and Boost, respectively) and a placebo. Thirty minutes post-treatment, they underwent neurocognitive assessment, consisting of a 10 min Cognitive Demand Battery, with mood ratings taken immediately before and after the battery. Five additional participants underwent post-treatment fMRI scanning during Rapid Visual Information Processing and Inspection Time activation tasks. The multivitamin with guaraná treatment was associated with significantly enhanced Serial Threes performance and self-rated contentment. fMRI revealed that both multivitamin treatments increased activation in areas associated with working memory and attentional processing, with the effect being greater in the multivitamin with guaraná condition. These data confirm the acute benefits of multivitamins with guaraná on mood and cognitive performance. Furthermore, they demonstrate for the first time increased brain activation from multivitamin preparations both with and without guaraná, as measured using fMRI.

Reduced hippocampus volume and memory performance in bipolar disorder patients carrying the BDNF val66met met allele

BACKGROUND Previous studies investigated the impact of brain-derived neurotrophic factor (BDNF) val66met (rs6265) on hippocampus volumes and neurocognition in bipolar disorders (BD), but the results were not consistent. This study aimed to investigate the effect of BDNF polymorphism on hippocampus volumes and memory performance in well-characterized adult populations diagnosed with type I BD (BD-I) and major depressive disorder (MDD) compared with healthy controls (HC). METHODS 48 BD-I patients, 33 MDD patients and 60 HC were genotyped for BDNF rs6265 using DNA isolated from white blood cells. Individuals with val/met and met/met genotypes were grouped as met carriers and compared to those with the val/val. Brain segmentations were obtained from structural magnetic resonance imaging (MRI) using the Freesurfer. Memory performance was assessed with the California Verbal Learning Task (CVLT). RESULTS We found a significant diagnosis effect and marginal interaction between diagnosis and BDNF genotype group for both hippocampus volumes and memory performance. BDNF met allele carrier BD patients had smaller hippocampus volumes and reduced performance on multiple CVLT scores compared to MDD patients and HC. CONCLUSIONS We provide strong evidence for the BDNF val66met polymorphism as a putative biological signature for the neuroanatomical and cognitive abnormalities commonly observed in BD patients.

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 patients input and b) examining the effectiveness of such interventions targeting general wellness using well-controlled trials.

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.

Addiction pharmacogenetics: a systematic review of the genetic variation of the dopaminergic system.

Substance use disorders have significant personal, familial, and societal consequences. Despite the serious consequences of substance use, only a few therapies are effective in treating substance use disorders, thus highlighting a need for improved treatment practices. Substance use treatment response depends on multiple factors such as genetic, biological, and social factors. It is essential that each component is represented in treatment plans. The dopaminergic system plays a critical role in the pharmacotherapy for addictions, and an understanding of the role of variation of genes involved in this system is essential for its success. This review adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement guidelines. A computerized literature search was conducted using PubMed and Scopus (all databases). Articles published up to April 2015 that examined the role of dopaminergic gene variation in the pharmacotherapy of alcohol, opioid, and cocaine use disorders were reviewed. Search terms were dopamine, gene, polymorphism, substance abuse, treatment, and response. Polymorphisms of the DRD2, ANKK1, DAT1, DBH, and DRD4 genes have been found to moderate the effects of pharmacotherapy of alcohol, opioid, and cocaine use disorders. The integration of genetic information with clinical data will inform health professionals of the most efficacious pharmacotherapeutic intervention for substance use disorders. More studies are needed to confirm and extend these findings.

Evaluation of cognitive function in bipolar disorder using the Brief Assessment of Cognition in Affective Disorders (BAC-A)

BACKGROUND Although cognitive impairment is a core feature of bipolar disorder (BD) there is no instrument of choice for the assessment of bipolar patients. The aim of this study is to assess cognitive performance using the Brief Assessment of Cognition in Affective Disorders (BAC-A), a comprehensive test battery developed specifically for BD, and determine its suitability to estimate global functioning. METHODS The BAC-A was administered to 93 BD patients (M ± S.E: 35.18 ± 1.39 years) and 56 healthy controls (HC - M ± S.E: 36.17 ± 1.91 years). The scores of the BAC-A were combined in eight summary scores: visuomotor, immediate affective and non-affective memory, verbal fluency, delayed affective and non-affective memory, inhibition, and problem solving. Post hoc analyses were performed on subtests of the summary scores found to be significantly different between BD patients and HC. Correlational analyses explored the association between the Global Assessment of Functioning (GAF) score and cognitive functioning. RESULTS Compared to HC, BD patients showed a significant impairment in short-term non-affective memory and verbal fluency. Poorer performance in verbal memory and verbal fluency summary scores correlated positively with reduced GAF. CONCLUSIONS Our results are consistent with previous reports of verbal memory and verbal fluency impairment in BD. The deficits in short-term memory and semantic fluency may indicate inefficient learning strategies and/or difficulties in retrieving information. The BAC-A could be used to estimate global functioning in BD patients.

Does a history of substance abuse and illness chronicity predict increased impulsivity in bipolar disorder

BACKGROUND Impulsivity is a common feature shared by bipolar disorder (BD) and substance use disorder (SUD). SUD and recurrent mood episodes are considered to be risk factors for poor outcome in BD. However, the association between impulsivity, illness chronicity and SUD in BD remains unexplored. METHODS 103 BD patients with and without a lifetime history of SUD (36.82±11.34 years, 40 males) were recruited. Participants completed the SCID interview and were administered measures of impulsivity including the Barratt Impulsivity Scale (BIS) and selected tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Hierarchical regression analyses explored the relationship between illness chronicity, SUD, and impulsivity. RESULTS Variance in the BIS, number of false alarms on the Rapid Visual Processing task and other impulsivity indicators of the Cambridge Gambling Task (CGT) was not explained by the chosen variables. Only an increased number of commission errors in the negative condition of the Affective Go/No Go task was significantly associated with illness chronicity. Furthermore there was a trend suggesting a relationship between a lifetime history of SUD and increased propensity to risk-taking during the CGT. LIMITATIONS Potential limitations include medication and patients׳ remission status from SUD. CONCLUSIONS Contrary to our expectations impulsivity was generally not predicted by indicators of illness chronicity or SUD. While impulsivity could still be a marker of BD that is present before the onset of the disorder, the link between the number of mood episodes and specific indicators of impulsivity may be related to mechanisms of neuroprogression.