MIBG cardiac imaging compared to ejection fraction in evaluation of cardiotoxicity: a systematic review.

BACKGROUND: Advances in diagnosis and treatment of cancer has improved survival but resulted in increased cardiotoxic effects. The decrease in left ventricular ejection fraction (EF), one of the pillars of diagnosis of cardiotoxicity, seems to be a late process in the evolution of the disease, so 123I-metaiodobenzylguanidine (MIBG) cardiac imaging has been proposed to detect early cardiac impairment. The aim of this systematic review was to evaluate the performance of MIBG cardiac scan in this scenario. METHODS AND RESULTS: A systematic search was conducted in five international databases comparing MIBG parameters with EF for evaluation of cardiotoxicity. Twelve studies were included and separated in three groups. First, studies evaluating patients with established cardiotoxicity, in which EF was reduced and MIBG parameters were abnormal. Second, studies analyzing patients during or after treatment compared to controls, with MIBG parameters significantly different between groups in most studies, even when EF remained normal. Finally, studies analyzing anthracycline (ATC) dose-related changes, with alteration in MIBG parameters occurring even when EF was preserved. CONCLUSION: Although studies had high methodological variability, cardiac sympathetic innervation imaging seems to be a promising tool for assessing early cardiotoxicity. Further studies are needed to analyze its diagnostic value in this scenario.

Telomere Length, Oxidative Stress, Inflammation and BDNF Levels in Siblings of Patients with Bipolar Disorder: Implications for Accelerated Cellular Aging.

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls. Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction. Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers. Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted.

Hypothalamic-pituitary-adrenal axis dysfunction and illness progression in bipolar disorder.

BACKGROUND: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients. METHODS: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR). RESULTS: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels. CONCLUSIONS: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness.

Association between childhood trauma, parental bonding and antisocial personality disorder in adulthood: A machine learning approach.

Childhood trauma (CT) and parental bonding (PB) have been correlated with later antisocial personality disorder (ASPD). Aiming to better understand this complex interaction we analyzed the data from a cross-sectional study that evaluated 346 male inpatient cocaine users, using both traditional statistical analysis and machine learning (ML) approaches. Childhood Trauma Questionnaire (CTQ), Parental Bonding Instrument (PBI), and Mini International Neuropsychiatric Interview (MINI) were applied. We found a markedly higher prevalence of mental illness in the ASPD group. The ML method and the traditional analysis showed that emotional and physical abuse were the factors with the strongest relationship with ASPD. Also, there were discrepancies between the findings of both methods regarding physical neglect and paternal care. Although this study does not allow definitive answers in this matter, we do propose that these two methods can aid in better comprehending how multiple variables interact with each other in the development of psychological disorders.

Bipolar disorder and 1513A>C P2RX7 polymorphism frequency.

Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls. Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls. In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder.

Peripheral adenosine levels in euthymic patients with bipolar disorder.

Recent evidence points to the involvement of the purinergic signaling in the pathophysiology of bipolar disorder. The aim of this study was to assess the serum levels of adenosine and to evaluate its relation to functioning in 24 euthymic patients with bipolar disorder type I and in 25 matched healthy controls. Subjects were evaluated using the functioning assessment short test. Serum purine levels were measured by high pressure liquid chromatography. Our results show a decrease in serum adenosine levels in bipolar disorder patients compared with controls (t= -4.8, df= 43.96, p<0.001). Moreover, a significant negative correlation was found between patient adenosine levels and depression scale scores (r= -0.642, p= 0.001). Higher functional impairment was linked to lower levels of adenosine in patients (rho= -0.551, p= 0.008). Taken together, our results provide evidence for a purinergic imbalance in bipolar disorder, specifically an adenosinergic dysfunction. Our results also indicate a relation between adenosine levels and the functional impairment caused by the disorder, which could demonstrate a potential relation of adenosine levels in worsening of symptoms.