A focus on valproate and cognitive deficits in Bipolar Disorders: A mini-review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

BACKGROUND: Cognitive deficits represent a core feature of Bipolar Disorder (BD), which seem to characterize this disorder regardless of the mood phase. However, the role of pharmacological treatment in determining cognitive alterations is still not clear. Indeed, although drugs improve cognition by targeting mood symptoms, they could also carry their own cognitive side effects. This is true especially for mood stabilizers as they are the most commonly prescribed drugs in patients affected by BD and they are usually administered also during euthymic phases. METHODS: In this context, the present review aimed at summarizing the results of the studies evaluating the impact of valproate on cognitive functions in patients suffering from BD, as primary or secondary results. The inclusion criteria were met by ten studies. Specifically, we included one double-blind quasi-randomized study and nine cross-sectional or naturalistic studies, which a) used healthy subjects as control group (N = 1), b) compared valproate treated patients with healthy individuals and other treatments (N = 5), and c) compared valproate treated patients just with other treatments, with a specific focus on lithium (N = 3). RESULTS: Overall the results suggested a negative effect of valproate on cognitive functions in chronically-treated patients affected by BD. Notably, it has been found that the working memory was the most affected cognitive domain. LIMITATIONS: Few studies directly explored the effect of valproate on cognition in BD. CONCLUSIONS: These findings seem to suggest that valproate might have a negative effect on cognitive functions, especially on working memory domain. However, the results should be taken cautiously since the limited number of available studies published so far. In conclusion, these evidences seem to point out that the possible cognitive side effects of pharmacological treatments should be carefully taken into account, especially in chronic patients.

Association between serum BDNF levels and maternal perinatal depression: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD.

INTRODUCTION: A large amount of studies demonstrated reduced serum Brain-Derived Neurotrophic Factor (BDNF) levels in stress-related and depressive disorders. However, it is still unclear if a similar deficit in BDNF concentrations might also characterize maternal perinatal depression. METHODS: We performed a bibliographic search on PUBMED of all the studies investigating the association between maternal BDNF levels and perinatal depression. The inclusion criteria were met by thirteen studies. RESULTS: Overall, the majority of the studies reported a significant reduction in serum BDNF levels among depressed mothers compared to healthy mothers either during pregnancy or in the postpartum period. Moreover, some studies also demonstrated that the BDNF reduction could be more evident in those depressed mothers with perinatal stressful life events and suicide risk. LIMITATIONS: BDNF were collected at different time points across the studies. Potential confounding factors, including the clinical characteristics of the samples employed by the original studies, might have influenced the results. CONCLUSIONS: So far, the evidences suggested the presence of decreased BDNF concentrations in perinatal depressive disorders. However, further studies are needed in order to confirm the role of BDNF in this disorder.

Intravenous valproate in the treatment of acute manic episode in bipolar disorder: A review.

BACKGROUND: Mania is a state of elated or irritable mood characterizing Bipolar Disorder type I (BD-I). Among the pharmacological treatments for the management of mania, mood stabilizers are regularly employed, with valproate being one of the most used because of its effectiveness. However, while the oral formulation is approved for acute mania, it is unclear whether the intravenous (IV) formulation could be a valid and safe alternative. METHODS: We performed a bibliographic research on PUBMED of all studies investigating the use of IV valproate as a treatment of acute mania in BD-I. A total of 13 studies met our inclusion criteria. RESULTS: Overall, the results suggest that IV valproate as a loading therapy is an efficacious, safe and well tolerated treatment for manic episodes, and it is comparable to the oral loading regimen. Interestingly, only a few patients experienced significant side effects due to the administration of the IV valproate. LIMITATIONS: Few open label clinical trials have explored the effect of IV valproate in manic patients. Moreover, the original studies employed different clinical assessments and included manic patients taking other drugs, which made it impossible to determine whether the resolution of symptoms was due to valproate therapy alone. Additionally, serum valproate levels were not assessed by all studies. CONCLUSIONS: IV valproate may represent a valid option for the management of acute mania, with comparable effects in terms of efficacy and safety to the oral valproate. However, larger and more homogeneous studies are warranted in order to collect more precise information on the beneficial effect of IV valproate.

The impact of BDNF Val66Met polymorphism on cognition in Bipolar Disorder: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Converging lines of evidence suggest that Brain-Derived Neurotrophic Factor (BDNF) may play a central role in the pathogenesis of Bipolar Disorder (BD), thus representing a valid biomarker of the disease. A common genetic variation in the BDNF gene, the Val66Met, is associated with reduced maturation and secretion of BDNF and therefore it has been related to specific mood, cognitive and neuroanatomical alterations in BD. However, so far, only a handful of studies have investigated the association between Val66Met polymorphism and cognitive functioning in BD. METHODS: We performed a bibliographic search on PUBMED of all genetic studies investigating Val66Met modulation on cognitive performances in BD subjects. The inclusion criteria were met by nine studies, including a total amount of 897 BD subjects and 803 healthy controls. RESULTS: From the analysis of the existing literature emerged that a) Val allele in BD adults, but not in BD adolescents, was associated with better performances in selective cognitive domains including executive functions, verbal learning and memory; b) Met allele may negatively modulate the association between childhood trauma and performances in memory, verbal ability and verbal fluency tasks; c) Met allele may also negatively regulate structural abnormalities in cognitive cerebral structures; d) Val/Met carriers showed greater improvements in cognitive functions compared to Val/Val and Met/Met carriers. LIMITATIONS: Few genetic studies exploring the impact of Val66Met on cognition in BD. CONCLUSIONS: Val66Met polymorphism likely modulates cognitive functions in BD patients with complex gene-environment interactions and through potential modulations of cerebral structures. Further and larger genetic studies are required in order to detect association between BDNF polymorphism, BDNF levels, brain abnormalities and cognition in BD.

The impact of COMT polymorphisms on cognition in Bipolar Disorder: A review: Special Section on "Translational and Neuroscience Studies in Affective Disorders" Section Editor, Maria Nobile MD, PhD. This Section of JAD focuses on the relevance of translational and neuroscience studies in providing a better understanding of the neural basis of affective disorders. The main aim is to briefly summaries relevant research findings in clinical neuroscience with particular regards to specific innovative topics in mood and anxiety disorders.

BACKGROUND: Cognitive deficits represent a core feature of Bipolar Disorder. The dopamine system is considered fundamental for cognitive functions relying on prefrontal cortex, such as attention and executive functions. A genetic regulation of prefrontal dopamine has been described and the catechol-O-methyltransferase (COMT) has been extensively studied in relation to numerous psychiatric phenotypes, especially because of the involvement of its polymorphisms in the regulation of cognitive functions. Specifically, the Val158Met polymorphism greatly alters COMT function and cognitive performance in both psychiatric disorders and healthy controls. However, only few studies assessed the association between COMT polymorphisms and cognitive functions in bipolar disorder (BD) subjects and this association might help in the comprehension of cognitive alterations in BD. METHODS: In this context, the present review summarizes results from genetic studies that investigated COMT genetic modulation on cognitive performance in patients affected by BD. RESULTS: Overall the results confirmed that (a) COMT Val158Met polymorphism is associated with altered cognitive functions in BD patients, especially in the domains of memory, executive functions and emotion detection; and (b) COMT genotype may interact with both mood episodes and pharmacologic treatments in determining the cognitive profile of these subjects. LIMITATIONS: Few genetic studies exploring COMT genetic effect on cognition in BD. CONCLUSIONS: These findings seem to indicate a role of COMT polymorphisms in regulating cognitive functioning in patients with BD. The genetically determined dopaminergic tone may be further affected by mood episodes and pharmacological treatments.

Pharmacological properties of cannabidiol in the treatment of psychiatric disorders: a critical overview.

Cannabidiol (CBD) represents a new promising drug due to a wide spectrum of pharmacological actions. In order to relate CBD clinical efficacy to its pharmacological mechanisms of action, we performed a bibliographic search on PUBMED about all clinical studies investigating the use of CBD as a treatment of psychiatric symptoms. Findings to date suggest that (a) CBD may exert antipsychotic effects in schizophrenia mainly through facilitation of endocannabinoid signalling and cannabinoid receptor type 1 antagonism; (b) CBD administration may exhibit acute anxiolytic effects in patients with generalised social anxiety disorder through modification of cerebral blood flow in specific brain sites and serotonin 1A receptor agonism; (c) CBD may reduce withdrawal symptoms and cannabis/tobacco dependence through modulation of endocannabinoid, serotoninergic and glutamatergic systems; (d) the preclinical pro-cognitive effects of CBD still lack significant results in psychiatric disorders. In conclusion, current evidences suggest that CBD has the ability to reduce psychotic, anxiety and withdrawal symptoms by means of several hypothesised pharmacological properties. However, further studies should include larger randomised controlled samples and investigate the impact of CBD on biological measures in order to correlate CBD's clinical effects to potential modifications of neurotransmitters signalling and structural and functional cerebral changes.