The role of BDNF methylation and Val66Met in amygdala reactivity during emotion processing

Epigenetic alterations of the brain‐derived neurotrophic factor (BDNF) gene have been associated with psychiatric disorders in humans and with differences in amygdala BDNF mRNA levels in rodents. This human study aimed to investigate the relationship between the functional BDNF‐Val⁶⁶Met polymorphism, its surrounding DNA methylation in BDNF exon IX, amygdala reactivity to emotional faces, and personality traits. Healthy controls (HC, n = 189) underwent functional MRI during an emotional face‐matching task. Harm avoidance, novelty seeking and reward dependence were measured using the Tridimensional Personality Questionnaire (TPQ). Individual BDNF methylation profiles were ascertained and associated with several BDNF single nucleotide polymorphisms surrounding the BDNF‐Val⁶⁶Met, amygdala reactivity, novelty seeking and harm avoidance. Higher BDNF methylation was associated with higher amygdala reactivity (x = 34, y = 0, z = ?26, t₍₁₆₆₎ = 3.00, TFCE = 42.39, p_(FWE) = .045), whereby the BDNF‐Val⁶⁶Met genotype per se did not show any significant association with brain function. Furthermore, novelty seeking was negatively associated with BDNF methylation (r = ?.19, p = .015) and amygdala reactivity (r = ?.17, p = .028), while harm avoidance showed a trend for a positive association with BDNF methylation (r = .14, p = .066). The study provides first insights into the relationship among BDNF methylation, BDNF genotype, amygdala reactivity and personality traits in humans, highlighting the multidimensional relations among genetics, epigenetics, and neuronal functions. The present study suggests a possible involvement of epigenetic BDNF modifications in psychiatric disorders and related brain functions, whereby high BDNF methylation might reduce BDNF mRNA expression and upregulate amygdala reactivity.     

European seroepidemiology network 2: Standardisation of assays for seroepidemiology of varicella zoster virus.

BACKGROUND: The aim of the European Sero-Epidemiology Network (ESEN2) is to harmonise the serological surveillance of vaccine-preventable diseases in Europe. OBJECTIVE: To allow comparison of antibody prevalence in different countries by standardising results into common units. STUDY DESIGN: For varicella zoster virus (VZV), a reference laboratory established a panel of 148 samples, characterised by indirect enzyme-immunoassay (ELISA), indirect immunofluorescence, and complement fixation test. Fifty-seven samples were also studied by the fluorescence antibody to membrane antigen test. The geometric mean of the antibody activity (GMAA) obtained from four ELISA determinations was used to characterise each sample of the panel as positive (GMAA: >100 mIU/ml), equivocal (GMAA: 50-100 mIU/ml) or negative (GMAA: <50 mIU/ml) for antibody to VZV (anti-VZV). Thirteen laboratories, using five different ELISA tests, tested the panel. RESULTS: Agreement with the reference laboratory was above 85% in all cases, and the R(2) values obtained from regression analysis of the quantitative results were always higher than 0.87. Finally, the regression equations could be used to convert national values into a common unitage. CONCLUSION: This study confirmed that results for anti-VZV obtained by different ELISA methods can be converted into common units, enabling the comparison of the seroprevalence profiles obtained in the participant countries.     

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The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders?

BACKGROUND: The present analyses were designed to compare the clinical characteristics and long-term episode course of Bipolar-I and Bipolar-II patients in order to help clarify the relationship between these disorders and to test the bipolar spectrum hypothesis. METHODS: The patient sample consisted of 135 definite RDC Bipolar-I (BP-I) and 71 definite RDC Bipolar-II patients who entered the NIMH Collaborative Depression Study (CDS) between 1978 and 1981; and were followed systematically for up to 20 years. Groups were compared on demographic and clinical characteristics at intake, and lifetime comorbidity of anxiety and substance use disorders. Subsets of patients were compared on the number and type of affective episodes and the duration of inter-episode well intervals observed during a 10-year period following their resolution of the intake affective episode. RESULTS: BP-I and BP-II had similar demographic characteristics and ages of onset of their first affective episode. Both disorders had more lifetime comorbid substance abuse disorders than the general population. BP-II had a significantly higher lifetime prevalence of anxiety disorders in general, and social and simple phobias in particular, compared to BP-I. Intake episodes of BP-I were significantly more acutely severe. BP-II patietns had a substantially more chronic course, with significantly more major and minor depressive episodes and shorter inter-episode well intervals. BP-II patients were prescribed somatic treatment a substantially lower percentage of time during and between affective episodes. LIMITATIONS: BP-I patients with severe manic course are less likely to be retained in long-term follow-up, whereas the reverse might be true for BP-II patients who are significantly more prone to depression (i.e., patients with less inclination to depression and with good prognosis may have dropped out in greater proportions); this could increase the gap in long term course characteristics between the two samples. The greater chronicity of BP-II may be due, in part, to the fact that the patients were prescribed somatic treatments substantially less often both during and between affective episodes. CONCLUSIONS: The variety in severity of the affective episodes shows that bipolar disorders, similar to unipolar disorders, are expressed longitudinally during their course as a dimensional illness. The similarities of the clinical phenotypes of BP-I and BP-II, suggest that BP-I and BP-II are likely to exist in a disease spectrum. They are, however, sufficiently distinct in terms of long-term course (i.e., BP-I with more severe episodes, and BP-II more chronic with a predominantly depressive course), that they are best classified as two separate subtypes in the official classification systems.     

Influence of acetylsalicylic acid on aListeria monocytogenes infection

The influence of acetylsalicylic acid (ASA, CAS 50-78-2) on theListeria monocytogenes infection in balb/c mice was investigated. One day prior to lethal or sublethal infection, balb/c mice were treated intravenously with therapeutic concentrations of ASA alone or ASA in combination with murine recombinant interferon , a lymphokine produced by T-helper cells. Three days post-infection, parasite burdens of spleen and liver were determined by the colony-forming unit assay. It was shown that the prophylactic application of ASA in a concentration of 5 mg/kg body weight resulted in a more than 10-fold reduction of viableListeria monocytogenes in spleen and liver of balb/c mice. In addition, the combination of a suboptimal dosage of interferon with ASA resulted in a significantly higher survival rate compared to the untreated controls.     

A brief assessment of psychosocial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal Interval Follow-up Evaluation-Range Impaired Functioning Tool

Those afflicted with bipolar disorder often suffer from substantial functional impairment both when in episode and when in remission. This study examined the psychometric properties of a brief assessment of psychosocial functioning, the Range of Impaired Functioning Tool (LIFE-RIFT), among subjects with bipolar I disorder. The study sample consisted of 163 subjects who presented with bipolar I disorder at intake into the NIMH Collaborative Depression Study (CDS). All LIFE-RIFT items come from the Longitudinal Interval Follow-up Evaluation (LIFE). Follow-up data that were used to examine the reliability and validity of the scale come from assessments of psychosocial functioning that were conducted 6, 12, 18, and 24 months after intake into the CDS. The results of factor analyses indicate that the scale items are measures of one construct, psychosocial functioning. The interrater agreement on the scale score was very good with an intraclass correlation coefficient was 0.94. The internal consistency reliability among the scale items was uniformly satisfactory over the four assessment periods, with coefficient alpha ranging from 0.78 to 0.84. Mixed-effect regression analyses showed that during mood episodes subjects were significantly more impaired than those in recovery. In conclusion, the psychometric properties of the LIFE-RIFT were examined in subjects with bipolar I disorder. The analyses from this longitudinal, observational study provide empirical support for the reliability and validity of the scale. The LIFE-RIFT provides a brief, inexpensive alternative to scales currently used to assess psychosocial functioning and can be easily added to semistructured assessments that are used in clinical and treatment outcome studies.     

Ophthalmic masquerades of the atherosclerotic carotids

Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome). These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient''s presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease.     

Expression and characterization of αvβ5 integrin on intestinal macrophages

Macrophages play a crucial role in maintaining homeostasis in the intestine, but the underlying mechanisms have not yet been elucidated fully. Here, we show for the first time that mature intestinal macrophages in mouse intestine express high levels of αvβ5 integrin, which acts as a receptor for the uptake of apoptotic cells and can activate molecules involved in several aspects of tissue homeostasis such as angiogenesis and remodeling of the ECM. αvβ5 is not expressed by other immune cells in the intestine, is already present on intestinal macrophages soon after birth, and its expression is not dependent on the microbiota. In adults, αvβ5 is induced during the differentiation of monocytes in response to the local environment and it confers intestinal macrophages with the ability to promote engulfment of apoptotic cells via engagement of the bridging molecule milk fat globule EGF‐like molecule 8. In the absence of αvβ5, there are fewer monocytes in the mucosa and mature intestinal macrophages have decreased expression of metalloproteases and IL 10. Mice lacking αvβ5 on haematopoietic cells show increased susceptibility to chemical colitis and we conclude that αvβ5 contributes to the tissue repair by regulating the homeostatic properties of intestinal macrophages.