Javier Santabárbara

Depressive disorder and incident diabetes mellitus: the effect of characteristics of depression.

OBJECTIVE The purpose of this study was to test the hypothesis that clinically significant depression detected in a population sample increases the risk of diabetes mellitus. The authors examined the effect of characteristics of depression frequently found in the community on the risk of incident diabetes mellitus. METHOD A large community sample of adults aged > or = 55 years (N=4,803) was assessed at baseline in a longitudinal three-wave epidemiological enquiry using a psychiatric interview and the Geriatric Mental State Schedule. Cases of depression were diagnosed according to standardized criteria, and diabetes was assessed using a risk factors questionnaire. Follow-up evaluations, conducted 2.5 and 5 years later, were completed to determine the incidence of diabetes. RESULTS At baseline, 379 case subjects with depression were identified. The risk of incident diabetes mellitus was higher among subjects with depression when compared with nondepressed subjects, and the association remained significant after controlling for potential confounders, including diabetes risk factors. The estimated rate of diabetes mellitus attributable to depression was 6.87%. An increased risk of diabetes mellitus was also associated with the following characteristics of depression: nonsevere depression, persistent depression, and untreated depression. Treatment with antidepressants was not associated with an increased risk of diabetes mellitus. CONCLUSIONS Clinically significant depression is associated with a 65% increased risk of diabetes mellitus. Characteristics of depression frequently found in the community, namely nonsevere depression, persistent depression, and untreated depression, may play a role in the development of diabetes in a predominantly elderly adult population.

Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis: Toward an Integrative Inflammatory Hypothesis of Schizophrenia

BACKGROUND Schizophrenia is a chronic syndrome of unknown etiology, predominantly defined by signs of psychosis. The onset of the disorder occurs typically in late adolescence or early adulthood. Efforts to study pathophysiological mechanisms in early stages of the disease are crucial in order to prompt intervention. METHODS Case-control study of first-episode psychotic (FEP) patients and matched controls. We recruited 117 patients during the first year after their FEP according to the DSM-IV criteria and recruited 106 gender-, race-, and age-matched controls between September 2010 and June 2011. RESULTS Biochemical studies carried out in peripheral mononuclear blood cells (PMBC) and plasma evidence a significant increase in intracellular components of a main proinflammatory pathway, along with a significant decrease in the anti-inflammatory ones. Multivariate logistic regression analyses identified the expression of inducible isoforms of nitric oxide synthase and cyclooxygenase in PMBC and homocysteine plasma levels as the most reliable potential risk factors and the inhibitor of the inflammatory transcription factor NFκB, IκBα, and the anti-inflammatory prostaglandin 15d-PGJ2 as potential protection factors. DISCUSSION Taken as a whole, the results of this study indicate robust phenotypical differences at the cellular machinery level in PMBC of patients with FEP. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways including the activity of nuclear receptors has interesting potential as biological markers and potential risk/protective factors for FEP. Due to its soluble nature, a notable finding in this study is that the anti-inflammatory mediator 15d-PGJ2 might be used as plasmatic biomarker for first episodes of psychosis.

Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Retinal nerve fiber layer thickness (RNFL) measured by means of Optical Coherence Tomography (OCT) has been used as a marker not only of ophthalmologic diseases but also of neurodegenerative diseases such as Alzheimer’s disease (AD) and mild cognitive impairment (MCI). The purpose of this work was to demonstrate that patients with amnestic MCI show an intermediate RNFL thickness between normality and AD, and a macular volume and thickness as well. In a cross-sectional study we consecutively recruited 18 patients with AD, 21 with MCI, and 41 healthy controls. OCT was performed in all of them to measure circumpapillary RNFL thickness in µm, as well as macular volume and thickness. In the analysis of variance we saw that RNFL was thinner in MCI patients compared with controls, and it was also thinner in AD patients compared with MCI patients and controls. With regard to the macular measurements in mm3, MCI patients had the greatest macular volume in comparison with AD patients and controls. In turn the controls had greater macular volume than AD patients. The decreased RNFL thickness in MCI and AD patients suggests loss of retinal neurons and their axons. The increased thickness and macular volume have never been reported before in aMCI. This finding could be explained by inflammation and/or gliosis in early stages of AD. OCT could be a useful marker of AD for early detection and monitoring progression.

Mild cognitive impairment diagnosed with the new DSM-5 criteria: prevalence and associations with non-cognitive psychopathology.

To contrast the prevalence of mild cognitive impairment (MCI) as diagnosed using DSM‐5 criteria (DSM5‐MCI) with MCI as diagnosed using Petersens criteria (P‐MCI) and to explore the association of both with non‐cognitive psychopathological symptoms (NCPS).

The Prevalence of Mild Cognitive Impairment in Diverse Geographical and Ethnocultural Regions: The COSMIC Collaboration

Background Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). Methods Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. Results The published range of MCI prevalence estimates was 5.0%–36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%–10.8%); Clinical Dementia Rating of 0.5 (1.8%–14.9%); Mini-Mental State Examination score of 24–27 (2.1%–20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). Conclusion Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.

Depression and Incident Alzheimer Disease: The Impact of Disease Severity

OBJECTIVES To test the hypothesis that clinically significant depression (particularly severe depression) increases the risk of Alzheimers disease (AD). METHODS A longitudinal, three-wave epidemiologic study was implemented in a sample of individuals aged 55 years and older (n = 4,803) followed up at 2.5 years and 4.5 years. This was a population-based cohort drawn from the Zaragoza Dementia and Depression (ZARADEMP) Project, in Zaragoza, Spain. Participants included individuals cognitively intact at baseline (n = 3,864). The main outcome measures were depression as assessed by using the diagnostic interview Geriatric Mental State- Automated Geriatric Examination for Computer Assisted Taxonomy package; and AD diagnosed by a panel of research psychiatrists according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The Fine and Gray multivariate regression model was used in the analysis, accounting for mortality. RESULTS At baseline, clinically significant depression was diagnosed in 452 participants (11.7%); of these, 16.4% had severe depression. Seventy incident cases of AD were found at follow-up. Compared with nondepressed individuals, the incidence rate of AD was significantly higher in the severely depressed subjects (incidence rate ratio: 3.59 [95% confidence interval: 1.30-9.94]). A consistent, significant association was observed between severe depression at baseline and incident AD in the multivariate model (hazard ratio: 4.30 [95% CI: 1.39-13.33]). Untreated depression was associated with incident AD in the unadjusted model; however, in the final model, this association was attenuated and nonsignificant. CONCLUSIONS Severe depression increases the risk of AD, even after controlling for the competing risk of death.

Incidence and lifetime risk of dementia and Alzheimer’s disease in a Southern European population

Lobo A, Lopez‐Anton R, Santabárbara J, de‐la‐Cámara C, Ventura T, Quintanilla MA, Roy JF, Campayo AJ, Lobo E, Palomo T, Rodriguez‐Jimenez R, Saz P, Marcos G. Incidence and lifetime risk of dementia and Alzheimer’s disease in a Southern European population.

COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups

BackgroundA large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.Methods/DesignLongitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.DiscussionThe challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.

Retinal nerve fiber layer and macular thickness in patients with schizophrenia: Influence of recent illness episodes.

Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (n=10) or NRIE (n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder.

Conversion to dementia in mild cognitive impairment diagnosed with DSM‐5 criteria and with Petersen's criteria

In a background of revision of criteria for states of increased risk for progression to dementia, we compare the conversion rate to dementia and Alzheimers disease (AD) of mild cognitive impairment (MCI) as diagnosed using DSM‐5 (DSM‐5‐MCI) and Petersens (P‐MCI) criteria.