Familial traits of bipolar disorder: A systematic review and meta-analysis

Background

Genetic studies of bipolar disorder (BD) have shown varied results, which is in part because of the heterogeneity of the disorder. Identifying clinical phenotypes of BD could reduce variability and benefit research. Since BD has a robust genetic component, studies can investigate clinical traits that cluster in families to identify phenotypes with a probable genetic basis.

Methods

We conducted a systematic review of the current literature on familial clinical traits of BD. Text screening and data extraction were performed independently by two reviewers, and random effects meta-analysis was used.

Results

Of 1117 unique records, 16 studies met inclusion criteria. These studies indicated 14 potentially familial traits of BD: age of onset (OR: 4.50; 95% CI: [3.25, 6.22]), bipolar type (OR: 2.05 [1.50, 2.79]), lithium response (OR: 3.71 [1.28, 10.82]), polarity at onset (OR: 1.17 [1.03, 1.34]), psychotic features (OR: 2.20 [1.51, 3.20]), mood-incongruent psychosis (OR: 2.52 [1.66, 3.83]), puerperal psychosis (OR: 6.54 [2.55, 16.77]), rapid cycling (OR: 4.95 [0.96, 25.40]), suicide attempt (OR: 1.04 [0.65, 1.67]), alcoholism (OR: 1.53 [1.09, 2.16]), obsessive–compulsive disorder (OR: 3.10 [1.31; 7.09]), panic disorder (OR: 2.69 [1.12; 6.48]), social anxiety disorder (OR: 1.00 [0.39, 2.55]), and specific phobia (OR: 1.94 [0.95; 3.96]). For most traits, tests of heterogeneity were significant and publication bias was likely.

Conclusion

The results of our review and meta-analysis highlight the lack of studies investigating familial clinical traits of BD, despite the need to address heterogeneity. The large degree of variability between studies must be reduced for future research.     

Inflammatory fibroid polyp: an immunohistochemical study

BACKGROUND: Inflammatory fibroid polyp is a localized lesion, which arises in the submucosa of the gastrointestinal tract, most often in the stomach.Although it is generally believed to represent a reactive, nonneoplastic condition, its histogenesis remains controversial. AIM: To study inflammatory fibroid polyp by immunohistochemistry in an attempt to further clarify their histogenesis. MATERIAL AND METHODS: Nine cases were studied by immunohistochemistry using a panel of antibodies against smooth-muscle actin, vimentin, S-100 protein, factor VIII- R.Ag and macrophage (HAM-56). RESULTS: There was a strong diffuse positive staining pattern in the spindle cells with vimentin antibody. A patchy staining for smooth-muscle actin was observed in these cells. Immunophenotyping revealed a heterogeneous reaction with HAM-56. In edematous areas, HAM-56-positive cells show voluminous cytoplasm and reniform nuclei. In cell-rich areas, the HAM-56-positive cells had fusiform cytoplasm. Stains for S-100 and factor VIII RAg were negative in the proliferating elements. CONCLUSIONS: The present immunohistochemical study refutes the suggested neural or vascular nature of the lesion. The strong positivity for vimentin in all cases suggests a major component of spindle cells best recognizable as fibroblasts. These results would favor the existence of a span of morphological and immunohistochemical patterns possibly indicating evolutive phases of an inflammatory reaction.     

Obstructive sleep apnea syndrome: effect of respiratory events and arousal on pulse wave amplitude measured by photoplethysmography in NREM sleep

The objective of the study is to evaluate changes in finger pulse wave amplitude (PWA), as measured by photoplethysmography, and heart rate (HR), related to obstructive respiratory events and associated arousals during sleep. We analyzed 1,431 respiratory events in NREM sleep from 12 patients according to (1) the type of event (apnea, hypopnea, upper airway resistance episode) and (2) the duration of the associated EEG arousal (>10, 3–10, <3 s). Obstructive respiratory events provoked a relative bradycardia and vasodilation followed by HR increase and vasoconstriction. Relative PWA changes were significantly greater than HR changes. These responses differed significantly according to EEG-arousal grades (time×arousal interaction, p<0.0001), with longer arousals producing greater responses, but not to the type of respiratory event (time×event interaction, p = ns). Obstructive respiratory events provoke HR and PWA changes, the magnitude seemingly related to the intensity of central nervous activation, with PWA changes greater than HR. PWA obtained from a simple pulse oxymeter might be a valuable method to evaluate sleep fragmentation in sleep breathing disorders.     

Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease

Impaired bone formation contributes to the lack of bone healing in multiple myeloma and there is a need for agents with bone anabolic properties to reverse the bone deficit in patients. Bortezomib, a proteasome inhibitor with antitumour efficacy in myeloma patients, enhanced new bone formation in mouse calvarial cultures; this effect was blocked by dickkopf 1(Dkk1), an antagonist of Wnt signalling implicated in myeloma bone disease. Bortezomib inhibited Dkk1 expression in calvariae and bone marrow-derived stromal cells, suggesting a novel mechanism by which bortezomib exerts its effects in bone. Clinical trials in patients with myeloma bone disease are needed to validate these results.     

Natural history of vertically acquired HCV infection and associated autoimmune phenomena

The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12 years, interquartile range 6.9–15.5) were studied. Genotype 1 was predominant (53.3 %). Spontaneous viral clearance was achieved by 12 patients (26.7 %) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2 years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3 %) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3 %): two had low C4 levels and persistent proteinuria. Conclusions: Vertically acquired HCV infection may result in spontaneous clearance in up to 27 % of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.     

Atypical lesions as a sign of cutaneous dissemination of visceral leishmaniasis in a human immunodeficiency virus-positive patient simultaneously infected by two viscerotropic Leishmania species

Leishmaniasis is considered an emerging opportunistic disease in human immunodeficiency virus (HIV)-infected patients who have considerably variable clinical presentation. We report a patient with visceral leishmaniasis who had unexpected clinical aspects (atypical cutaneous lesions appearing after long-term evidence of visceral parasites). The patient had hepatoesplenomegaly in the absence of fever, but was otherwise generally healthy. The HIV viral load was low despite severe immunossupression (low lymphocyte proliferation and low level of interferon-γ, concomitant with a high lymphocyte activation status). Surprisingly, two Leishmania strains were isolated from his bone marrow (typical L. infantum sequence MON-1, type A) and skin (L. donovani MON-2 sequence); this second strain had not been previously identified in Brazil. The association of visceral leishmaniasis and HIV/acquired immunodeficiency syndrome is a largely unknown disease, particularly in areas in which leishmaniasis is not endemic. Such atypical cases indicate that this disease can be undiagnosed in clinical settings.     

Parallel increase of circulating CXCL11 and CXCL10 in mixed cryoglobulinemia, while the proinflammatory cytokine IL-6 is associated with high serum Th2 chemokine CCL2

The aim was to investigate circulating levels of interelukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, chemokine (C–X–C motif) ligand (CXCL)10, CXCL11 and chemokine (C–C motif) ligand (CCL)2 in “mixed cryoglobulinemia and hepatitis C” (MC?+?HCV). Serum levels of CXCL11, IL-1β, TNF-α, IL-6, and CCL2 were evaluated in 52 MC?+?HCV vs 52 sex- and age-matched controls to correlate them to the clinical features of mixed cryoglobulinemia. CXCL11 was significantly higher in MC?+?HCV than in controls (264?±?279 vs 70?±?16 pg/mL, respectively; P?=?0.0002; univariate analysis of variance (ANOVA)), in particular in 23 MC?+?HCV with active vasculitis vs those without (293?±?221 vs 168?±?57 pg/mL, respectively; P?<?0.001; ANOVA). Significantly high IL-1β, IL-6, TNF-α, CXCL10, and CCL2 in MC?+?HCV vs healthy controls were confirmed. In a multiple linear regression model (CXCL11 or CCL2, vs age, alanine aminotransferase, IL-1β, IL-6, TNF-α, and CXCL10), CXCL11 was significantly associated with high CXCL10 (P?<?0.001), while CCL2 with high IL-6 (P?<?0.001). This study demonstrates in MC?+?HCV high serum levels of (a) T-helper 1 chemokines, CXCL11 and CXCL10 (related to each other) and (b) proinflammatory cytokines IL-6 and CCL2 (related to each other).