Hippocampal volume and integrity as predictors of cognitive decline in intact elderly

Risk of Alzheimer’s disease (AD) can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus to a novel measure of hippocampal integrity derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 or older at baseline, and were tested twice, roughly three years apart. Participants had been recruited for a study on late-life major 34 depression (LLMD) and were evenly split between depressed and controls. Linear regression models were applied to the data with a cognitive composite score as outcome, and hippocampal integrity (HI) and volume (HV), together or separately, as predictors. Subsequent cognitive performance was predicted well by models that include an interaction between HI and LLMD-status, such that lower HI scores predicted more cognitive decline in depressed subjects. More research is needed, but tentative results from this study appear to suggest that the newly introduced measure HI is an effective tool for the purpose of predicting future changes in general cognitive ability, and especially so in individuals with LLMD

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Familial Longevity Is Marked by Lower Diurnal Salivary Cortisol Levels: The Leiden Longevity Study

BACKGROUND: Reported findings are inconsistent whether hypothalamic-pituitary-adrenal (HPA) signaling becomes hyperactive with increasing age, resulting in increasing levels of cortisol. Our previous research strongly suggests that offspring from long-lived families are biologically younger. In this study we assessed whether these offspring have a lower HPA axis activity, as measured by lower levels of cortisol and higher cortisol feedback sensitivity. METHODS: Salivary cortisol levels were measured at four time points within the first hour upon awakening and at two time points in the evening in a cohort comprising 149 offspring and 154 partners from the Leiden Longevity Study. A dexamethasone suppression test was performed as a measure of cortisol feedback sensitivity. Age, gender and body mass index, smoking and disease history (type 2 diabetes and hypertension) were considered as possible confounding factors. RESULTS: Salivary cortisol secretion was lower in offspring compared to partners in the morning (Area Under the Curve = 15.6 versus 17.1 nmol/L, respectively; p = 0.048) and in the evening (Area Under the Curve = 3.32 versus 3.82 nmol/L, respectively; p = 0.024). Salivary cortisol levels were not different after dexamethasone (0.5 mg) suppression between offspring and partners (4.82 versus 5.26 nmol/L, respectively; p = 0.28). CONCLUSION: Offspring of nonagenarian siblings are marked by a lower HPA axis activity (reflected by lower diurnal salivary cortisol levels), but not by a difference in cortisol feedback sensitivity. Further in-depth studies aimed at characterizing the HPA axis in offspring and partners are needed

Enhanced Auditory Brainstem Response and Parental Bonding Style in Children with Gastrointestinal Symptoms

The electrophysiological properties of the brain and influence of parental bonding in childhood irritable bowel syndrome (IBS) are unclear. We hypothesized that children with chronic gastrointestinal (GI) symptoms like IBS may show exaggerated brainstem auditory evoked potential (BAEP) responses and receive more inadequate parental bonding. = 0.024). Multiple regression analysis in females also supported these findings.It is suggested that children with chronic GI symptoms have exaggerated brainstem responses to environmental stimuli and inadequate parental behaviors aggravate these symptoms

Innate and adaptive immunity in the development of depression: : An update on current knowledge and technological advances

The inflammation theory of depression, proposed over 20years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced 'omics' technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account.Peer reviewe

Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

Contains fulltext : 91627.pdf (publisher's version ) (Open Access

Investigating anhedonia in a non-conventional species: Do some riding horses Equus caballus display symptoms of depression?

International audienceInvestigating depression-like conditions in animals is methodologically challenging, but potentially important for welfare. Some riding horses display ‘withdrawn’ states of inactivity and low responsiveness that resemble the reduced engagement with the environment shown by certain depressed patients. To assess whether these animals are experiencing a depression-like state, we investigated anhedonia – the loss of pleasure, a key symptom of human depression – in 20 withdrawn and non-withdrawn horses from the same stable. The time horses spent being withdrawn appeared unrelated to age or sex, but correlated with time devoted to stereotypic behaviour, a possible marker of lifetime stress. Comparison with data collected 5 years earlier also revealed that horses scored as withdrawn then remained significantly likely to display the behaviour. We measured sucrose intake, a classic measure of anhedonia never previously applied to horses. Flavoured sugar blocks, novel to these subjects, were mounted in each stall and weighed 3, 8, 24 and 30 h after provision. We predicted that if affected by depression-like states, the most withdrawn horses would consume the least sucrose. This prediction was met (F1,18 = 4.65, two tailed p = 0.04). This pattern could, however, potentially reflect general appetite levels and/or food neophobia. To control for these confounds, hay consumption was measured over 5 days, as were subjects’ latencies to eat a meal scented with a novel odour. Although low hay consumption and long latencies to eat scented food did predict low sucrose consumption, statistically controlling for these confounds did not eliminate the relationship between being withdrawn and consuming less sucrose (although reducing it to a strong trend): F1,15 = 4.28, two-tailed p = 0.056. These data thus suggest long-lasting depression-like states in certain riding horses, which correlate with stereotypic behaviour and are characterised by anhedonia and bouts of ‘withdrawn’ unresponsiveness

Pharmacological Treatment of Anxiety Disorders: The Role of the HPA Axis

Stress in general, and early life stress in particular, has been associated with the development of anxiety and mood disorders. The molecular, biological and psychological links between stress exposure and the pathogenesis of anxiety and mood disorders have been extensively studied, resulting in the search of novel psychopharmacological strategies aimed at targets of the hypothalamic-pituitary-adrenal (HPA) axis. Hyperactivity of the HPA axis has been observed in certain subgroups of patients with anxiety and mood disorders. In addition, the effects of different anti-anxiety agents on various components of the HPA axis has been investigated, including benzodiazepines, tricyclic antidepressants (TCAs), and selective serotonin reuptake inhibitors (SSRIs). For example, benzodiazepines, including clonazepam and alprazolam, have been demonstrated to reduce the activity of corticotrophin releasing factor (CRF) neurons in the hypothalamus. TCAs and SSRIs are also effective anti-anxiety agents and these may act, in part, by modulating the HPA axis. In this regard, the SSRI escitalopram inhibits CRF release in the central nucleus of the amygdala, while increasing glucocorticoid receptor (GRs) density in the hippocampus and hypothalamus. The molecular effects of these anti-anxiety agents in the regulation of the HPA axis, taken together with their clinical efficacy, may provide further understanding about the role of the HPA axis in the pathophysiology of mood and anxiety disorders, paving the way for the development of novel therapeutic strategies

Spatial Memory and Hippocampus in London Taxi Drivers

Introducción. El impacto de la actividad ocupacional y/o profesional sobre el cerebro encuentra sustento en la capacidad del sistema nervioso para modificar su estructura y función, fenómeno denominado plasticidad cerebral. Los taxistas londinenses han permitido examinar dicho suceso. Esto se debe a las exigencias neurocognitivas específicas de la mencionada profesión tanto en el proceso de formación como en la conducción posterior diaria a través de la compleja ciudad de Londres. Objetivo. Revisar estudios empíricos vinculados a taxistas londinenses abordando las variables memoria espacial y la estructura del hipocampo, permitiendo determinar los aportes y limitaciones de esta línea de investigación en el entendimiento de la plasticidad cerebral y en el ejercicio de la rehabilitación neuropsicológica. Desarrollo. Los trabajos revisados coinciden en señalar que las demandas mnésicas espaciales de la conducción en los taxistas londinenses afectan la estructura del hipocampo, con un aumento del volumen de materia gris en su porción posterior y una disminución en su porción anterior. También se reportaron modificaciones en el rendimiento de procesos mnésicos específicos, incrementando el recuerdo asociado a sitios londinenses y en detrimento de la formación de nuevas memorias espaciales. Conclusiones. Los estudios efectuados a taxistas londinenses constituyen un modelo paradigmático en neurociencias para la comprensión de la plasticidad cerebral, haciendo uso de diseños con validez ecológica. Por otro lado se plantean algunos interrogantes necesarios para una adecuada capitalización de sus resultados en el ámbito de la estimulación y rehabilitación neuropsicológica.Introduction. The impact of occupational and / or professional activity on the brain finds support in the nervous system's ability to change its structure and function, a phenomenon known as brain plasticity. London taxi drivers have allowed to discuss that event. This is due to the specific neurocognitive demands of the above mentioned profession both in the process of formation as in the subsequent daily driving through the complex city of London. Objective. Review of empirical studies linked to London taxi drivers by addressing the spatial memory variables and the structure of the hippocampus, to determine the contributions and limitations of this line of research in the understanding of brain plasticity and the exercise of the neuropsychological rehabilitation. Development. The revised studies have noted that spatial mnemonic demands of driving in london taxi drivers affect the structure of the hippocampus, with an increase in the volume of gray matter in their posterior portion and a decrease in its anterior portion. There were also reported changes in the performance of specific memory processes, increasing the memory associated with London sites, and at the expense of the formation of new spatial memories. Conclusions. The studies conducted to London taxi drivers are a paradigmatic model in neuroscience for the understanding of brain plasticity, using ecologically valid designs. On the other hand some necessary questions arise for an adequate capitalization of the results in the field of stimulation and neuropsychological rehabilitation.Fil: Martino, Pablo. Universidad Nacional de Rosario. Facultad de Psicología. Secretaria de Ciencia y Tecnología. Centro de Investigación En Neurociencias; ArgentinaFil: Cervigni, Mauricio Alejandro. Universidad Nacional de Rosario. Facultad de Psicología. Secretaria de Ciencia y Tecnología. Centro de Investigación En Neurociencias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stelzer, Florencia. Universidad Nacional de Mar del Plata. Facultad de Psicología. Centro De Investigación en Procesos Básicos, Metodologías y Educación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Tafet, Gustavo. Universidad Maimónides; Argentin