Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study

Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N = 28; age- and gender-matched comparison group, N = 19) at baseline and 3-year follow-up (MDD group, N = 19; comparison group, N = 17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by highperformance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine–glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression

Assessing the presence of shared genetic architecture between Alzheimer's disease and major depressive disorder using genome-wide association data

We are grateful to the families and individuals who took part in the GS:SFHS and UKB studies, and to all those involved in participant recruitment, data collection, sample processing and QC, including academic researchers, clinical staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/ 14/Z. We acknowledge with gratitude the financial support received from the Dr Mortimer and Theresa Sackler Foundation. This research has been conducted using the GS:SFHS and UK Biobank (project #4844) resources. GS:SFHS received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. UKB was established using funding from the Wellcome Trust, Medical Research Council, the Scottish Government Department of Health, and the Northwest Regional Development Agency. DJP, IJD, TCR and AMM are members of the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). TCR is supported by Alzheimer's Scotland, through the Marjorie MacBeath bequest. Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. We are grateful for the use of summary data from the International Genomics of Alzheimer's Project and the Major Depressive Disorder working group of the Psychiatric Genomics Consortium.Peer reviewedPublisher PD

HIV patients stable on ART retain evidence of a high CMV load but changes to Natural Killer cell phenotypes reflect both HIV and CMV

Background: Whilst ART corrects many effects of HIV disease, T cell populations retain features of accelerated immunological aging. Methods: Here we analyse phenotypic changes to natural killer (NK) cells in HIV patients who began ART with <200 CD4 T-cells/µl and maintained virological control for 12-17 years, compared with CMV seropositive and seronegative healthy control donors. Results: Humoral responses to CMV antigens (lysate, gB, IE-1) remain elevated in the patients (P <0.0001) despite the long duration of ART. Patient's NK cells responded poorly to K562 cells when assessed by CD107a and IFNγ, but this could not be attributed to CMV as responses were low in CMV-seronegative controls. Moreover HIV (and not CMV) increased expression of CD57 on CD56lo cells. Conclusions: Comparisons with published studies suggest that CMV accelerates age-related increases in CD57 expression but levels plateau by 60-70 years of age, so the effect of CMV disappears. In HIV patients the plateau is higher and perhaps reached sooner

Behavioural and psychological symptoms in the older population without dementia - relationship with socio-demographics, health and cognition

<p>Abstract</p> <p>Background</p> <p>Behavioural and psychological symptoms are associated with dementia, but are also present in a significant number of the older population without dementia. Here we explore the distribution of behavioural and psychological symptoms in the population without dementia, and their relationship with domains and severity of health and cognitive impairment.</p> <p>Methods</p> <p>The Medical Research Council Cognitive Function and Ageing Study is a two-phase longitudinal study of ageing representative of the population aged 65 and over of England and Wales. A subsample of 1781 participants without a study diagnosis of dementia was included in this study. Information on symptoms including depression, apathy, anxiety, feelings of persecution, hallucination, agitated behaviour, elation, irritability, sleep problems, wandering, confabulation and misidentification, cognitive function, health related factors and socio-demographic information was extracted from interviews with participants and knowledgeable informants. Participants were classified according to the Mini-Mental State Examination and by criteria for subtypes of mild cognitive impairment (MCI). The prevalence of behavioural and psychological symptoms and associations with cognitive function, health and socio-demographics was examined. Co-occurrence of symptoms was tested using factor analysis.</p> <p>Results</p> <p>Most symptoms were reported more frequently in those with more severe cognitive impairment. Subjective memory complaints were the strongest independent predictor of reported symptoms, and most were reported more often in those classified as having MCI than in those with cognitive impairments that did not meet the MCI criteria. The pattern of co-occurrence of symptoms is similar to that seen in dementia.</p> <p>Conclusions</p> <p>Our results highlight that behavioural and psychological symptoms are prevalent in the cognitively impaired older population, and partly explain the variation observed in previous cohorts of individuals with MCI. Behavioural and psychological symptoms offer a target for intervention and so are an important consideration in the assessment of cognitively impaired older people.</p

Health Literacy and Cardiovascular Disease: Fundamental Relevance to Primary and Secondary Prevention: A Scientific Statement From the American Heart Association

Health literacy is the degree to which individuals are able to access and process basic health information and services and thereby participate in health-related decisions. Limited health literacy is highly prevalent in the United States and is strongly associated with patient morbidity, mortality, healthcare use, and costs. The objectives of this American Heart Association scientific statement are (1) to summarize the relevance of health literacy to cardiovascular health; (2) to present the adverse associations of health literacy with cardiovascular risk factors, conditions, and treatments; (3) to suggest strategies that address barriers imposed by limited health literacy on the management and prevention of cardiovascular disease; (4) to demonstrate the contributions of health literacy to health disparities, given its association with social determinants of health; and (5) to propose future directions for how health literacy can be integrated into the American Heart Association's mandate to advance cardiovascular treatment and research, thereby improving patient care and public health. Inadequate health literacy is a barrier to the American Heart Association meeting its 2020 Impact Goals, and this statement articulates the rationale to anticipate and address the adverse cardiovascular effects associated with health literacy

Health Literacy and Power.

Comment article

Psychoneuroimmunology: application to ocular diseases

Psychoneuroimmunology (PNI) is a relatively new discipline within the field of neuroscience which researches the relationship between emotional states, the central and peripheral nervous systems, and the endocrine and immune systems. Negative psychological states, such as stress, anxiety, and depression, may alter immune system regulation and modulation of peripheral cytokines. A plethora of PNI studies have shown that increased psychological stress and depression are associated with an alteration of immune functioning and worsened health outcomes for many conditions. To date, application of PNI methodology has not been reported for ocular diseases. This article provides an historical perspective on the origins of the rift between the emotional and spiritual from physical aspects of disease. A review of how stress is mediated through sympathetic adrenomedullary and hypothalamic pituitary axis activation with shifts in immunity is provided. The literature which supports spirituality in healing is presented. Finally, ocular diseases which would be most amenable to a PNI approach are discussed