Decreased Levels of Vitamin D in Bipolar Patients.

Recently, vitamin D is considered a pleiotropic hormone, and as such, it has also become a topic of renewed interest in neuropsychiatry for its proposed role in the aetiology and pathophysiology of different psychiatric conditions, including mood disorders (MDs). This seems particularly crucial while considering the relatively high and often neglected prevalence of hypovitaminosis D in the general population and in specific groups, such as patients suffering from the most common type of MDs, which are major depression (MDD) and bipolar disorders (BDs). Therefore, in view of the controversial literature and findings on this topic and its potential therapeutic implications, the present study aimed at evaluating vitamin D levels in the plasma of a sample of inpatients fulfilling the DSM-5 criteria for mood episodes within BDs. The clinical picture was assessed by means of specific rating scales. The results showed that the vitamin D levels (mean ± SD, nM/L) of the bipolar patients of our sample were significantly lower (14.58 ± 11.27 nmol/L) than the normative values (>30 nmol/L). Eleven patients had sufficient values and only 4 had optimal, while 19 showed insufficient, 18 critical, and 17 severely critical levels. No differences emerged according to different socio-demographic or clinical features. In our opinion, the present findings strengthen previous research highlighting decreased vitamin D levels in bipolar patients and support the role of this pleiotropic hormone in BDs. Nevertheless, further studies should follow to corroborate the data of this preliminary study and to address the potential benefits of vitamin D supplementation in the treatment of MDs.

Vitamin B12, homocysteine, and folic acid in patients suffering from bipolar disorders: Relationship with suicide.

OBJECTIVES: Vitamin B12, folic acid, and homocysteine play a key role in 'one-carbon metabolism', involved in different brain processes. Altered levels have been reported in mood disorders (MDs), particularly in major depression (MDD), while the information in bipolar disorders (BDs) is limited. The present study aimed at assessing vitamin B12, homocysteine, and folic acid in 69 bipolar inpatients. METHODS: Twenty-seven patients were diagnosed with BDI, 15 BDII, 16 schizoaffective disorders, and 11 MDD, according to DSM-5 criteria. The clinical picture was assessed by the MINI, HRSD, YMRS, and CGI. The blood parameters were measured according to common clinical-chemical methods. RESULTS: Thirty-four patients had significantly lower vitamin B12, and 14 higher homocysteine levels than normative values. Folic acid levels were normal in the majority of the sample. Patients with a family history of suicide showed significantly lower levels of vitamin B12. CONCLUSIONS: Our results underline the utility of assessing vitamin B12, homocysteine, and folic acid in patients with BD. Although other studies are necessary, the present findings that lower levels of vitamin B12 seem typical of patients with a family history of suicide independently from the phase of illness suggest that they might constitute a possible predictor of suicide.

Inflammatory and metabolic markers in patients with mood disorders.

OBJECTIVES: An increasing bulk of data underlined that mood disorders show alterations that are not confined to the brain, but involve several other systems. The aim of this retrospective study was to explore metabolic/inflammatory profiles, blood pressure, and BMI in patients affected by bipolar disorders (BDs) to better understand the role of peripheral biomarkers in mood disorders. METHODS: Different metabolic/inflammatory parameters and clinical characteristics were evaluated in 97 BD inpatients from Sicily, a southern Italian region, and compared with normative values from the same area. RESULTS: No difference was detected between the assessed parameters and the normative values, or between treated and untreated patients. Interestingly, the mean acid uric levels were at the lowest extreme of the normative values, with men showing higher concentrations than women. CONCLUSIONS: No metabolic nor inflammatory alterations emerged in BD patients, even if when obese. A possible explanation might be due to their geographical origin, with culinary traditions based on the Mediterranean diet. Therefore, it would be interesting to ascertain whether such a diet might improve the metabolic impairment often associated with mood disorders. Again, the routine assessment of different clinical/chemistry parameters might be helpful to improve the diagnostic stratification and the personalised treatment.

State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders.

Mounting evidence highlights the involvement of inflammatory/immune systems and their relationships with neurotransmitters and different metabolic processes in mood disorders. Nevertheless, there is a general agreement that available findings are still inconclusive. Therefore, further investigations are required, aimed at deepening the role of possible alterations of biomarkers in the pathophysiology of mood disorders that might lead to more focused and tailored treatments. The present study is a comprehensive review on these topics that seem to represent intriguing avenues for the development of real innovative therapeutic strategies of mood disorders.

Effectiveness of clozapine, oxcarbazepine and rivastigmine combination in a bipolar disorder patient with initial cerebral atrophy.

This paper reports the case of a 46-year-old woman suffering from bipolar disorder of type I with mixed features with initial fronto-temporal atrophy. Although considered treatment-resistant to conventional strategies, she successfully responded to a combination of rivastigmine, clozapine, and oxcarbazepine.

Frequency and phenotypic spectrum of KMT2B dystonia in childhood: A single-center cohort study.

BACKGROUND: Childhood-onset dystonia is often genetically determined. Recently, KMT2B variants have been recognized as an important cause of childhood-onset dystonia. OBJECTIVE: To define the frequency of KMT2B mutations in a cohort of dystonic patients aged <18 years at onset, the associated clinical and radiological phenotype, and the natural history of disease. METHODS: Whole-exome sequencing or customized gene panels were used to screen a cohort of 65 patients who had previously tested negative for all other known dystonia-associated genes. RESULTS: We identified 14 patients (21.5%) carrying KMT2B variants, of which 1 was classified as a variant of unknown significance. We also identified 2 additional patients carrying pathogenic mutations in GNAO1 and ATM. Overall, we established a definitive genetic diagnosis in 23% of cases. We observed a spectrum of clinical manifestations in KMT2B variant carriers, ranging from generalized dystonia to short stature or intellectual disability alone, even within the same family. In 78.5% of cases, dystonia involved the lower limbs at onset, with later caudocranial generalization. Eight patients underwent pallidal DBS with a median decrease of Burke-Fahn-Marsden Dystonia Rating Scale-Motor score of 38.5% in the long term. We also report on 4 asymptomatic carriers, suggesting that some KMT2B mutations may be associated with incomplete disease penetrance. CONCLUSIONS: KMT2B mutations are frequent in childhood-onset dystonia and cause a complex neurodevelopmental syndrome, often featuring growth retardation and intellectual disability as additional phenotypic features. A dramatic and long-lasting response to DBS is characteristic of DYT-KMT2B dystonia. © 2019 International Parkinson and Movement Disorder Society.

Prevalence, chronicity, burden and borders of bipolar disorder.

Bipolar disorder (BD) has traditionally been thought of as an episodic condition, characterized by periods of hypomania/mania and depression. However, evidence is accumulating to suggest that this condition is associated with significant chronicity. For a large proportion of patients with BD, residual, sub-syndromal symptoms persist between major syndromal episodes, and studies have shown that many patients with bipolar disorder are symptomatic for approximately 50% of the time over follow-up periods of greater than 10 years. Moreover, while the prevalence of BD has been estimated to be around 1-2%, there is growing evidence that this may be a substantial underestimation. There are a number of reasons for this potential underestimation, including difficulties in diagnosis. Adding to the burden of BD is the issue of comorbidity, with an increased prevalence of many chronic conditions in those with a primary diagnosis of BD. Conversely, for many patients with chronic conditions, both medical and psychiatric, BD frequently exists as a comorbid secondary diagnosis. This issue of comorbidity complicates estimates of use of pharmaceutical agents for BD, such as mood stabilizers, which are known to be used off-label in conditions such as borderline personality or substance use disorder. We speculate that such off-label prescribing may not be truly off-label but may be instead fully justified by an overlooked secondary diagnosis of BD. Finally, we discuss the association of bipolar disorder with a significant economic burden, to the individual and to society, both due to the direct costs of medical expenditure and indirect costs such as loss of productivity and increased mortality.

Asenapine for the treatment of manic and mixed episodes associated with bipolar I disorder: from clinical research to clinical practice.

INTRODUCTION: Asenapine is a sublingually administered second-generation antipsychotic with proven efficacy for the treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Its relatively favorable weight and metabolic profile, as well as the lack of appreciable activity at muscarinic cholinergic receptors and the sublingual administration are of clinical interest. AREAS COVERED: This paper comprises a review and commentary regarding the use of sublingual asenapine in the treatment of acute manic and mixed episodes of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration with other medications are provided. EXPERT OPINION: Asenapine displays quick and reliable effects on manic symptoms, very low risk of depressive switches, efficacy on depressive symptoms during manic and mixed episodes, usually good tolerability and continued longer-term efficacy on residual and subthreshold symptoms. The fast-dissolving sublingual route of administration may favor those who have difficulties in swallowing medications. Also, the sublingual administration reduces the risk of overdose when more than the prescribed tablets are swallowed. The relatively low metabolic risk and the lack of anticholinergic side effects contribute to making this medication a useful tool for the treatment of patients with bipolar disorder.