Diana De Ronchi

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients.

The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate, response rate and response rate within 4 weeks using the cochrane review manager. We observed a significant association of the s/s variant of 5-HTTLPR with remission rate (P<0.0001) and both s/s and s/l variants with response rate (P=0.0002). Response rate within 4 weeks was associated in both models (P=0.003–P<0.00001). This effect is quite robust to ethnic differences although a significant heterogeneity is present in Asian samples.

Worldwide Prevalence and Incidence of Dementia

Dementia is a common and disabling disorder in the elderly. Because of the worldwide aging phenomenon, existing in both developed and developing countries, dementia has a growing public health relevance. This article reviews the prevalence and incidence data for dementia reported in the international literature in the last 10 years. Results from 36 prevalence and 15 incidence studies have been examined. Prevalence is equal to 0.3 to 1.0 per 100 people in individuals aged 60 to 64 years, and increases to 42.3 to 68.3 per 100 people in individuals 95 years and older. The incidence varies from 0.8 to 4.0 per 1000 person years in people aged 60 to 64 years, and increases to 49.8 to 135.7 per 1000 person years when the population was older than 95 years. The international comparison allows the following conclusions: (i) both prevalence and incidence show little geographical variation, as differences between countries seem to reflect methodological rather than real differences [the low prevalence of dementia in Africa needs to be confirmed by incidence data]; (ii) both incidence and prevalence figures increase with age even in the advanced ages; (iii) regarding dementia types, most of the inconsistency in results from different studies is due to vascular dementia rather than to Alzheimer’s disease (AD); (iv) it is still unclear if the reported higher frequency of vascular dementia in Asian populations is due to differential distribution of genetic and/or environmental factors, or due to methodological differences; (v) different dementia types might have different age distributions.

The epidemiology of the dementias: an update.

Purpose of review The epidemiology of dementia is one of the priority fields in aging research. This review aims to highlight the most relevant findings over last years concerning occurrence, risk factors, and prevention of dementia and its major subtypes. Recent findings It is estimated that currently around 24 million people have dementia in the world, with the number being projected to double every 20 years, and that 60% of dementia patients live in developing countries, with the proportion being raised to more than 70% by 2040. Current evidence suggests that vascular factors, such as midlife hypertension, diabetes, and cerebrovascular disease, contribute significantly to the development of dementia and Alzheimers disease, and that active engagement in mental, physical, and social activities may postpone the onset of dementia by providing cognitive reserve. Summary Dementia represents a major public health challenge as a consequence of rapid increase in the aging population worldwide, especially in developing countries. This challenge can be partly confronted by successful development of preventive strategies. Evidence has emerged that proper control of vascular disorders and maintenance of active lifestyles may prevent or delay the onset and progression of dementia and Alzheimers disease. Intervention trials are warranted to determine, to what extent, such programs are effective against dementia.

Serotonin Transporter Gene Variants and Behavior: A Comprehensive Review

The serotonin system modulates affective, cognitive and behavioral processes. A key molecular structure of this system, the serotonin transporter (SERT) gene, has been associated with many human behaviors, both normal and pathological. This article aim is a comprehensive overview of the human behavioral features influenced by SERT gene variants and to suggest some comprehensive hypotheses. In particular, the SERTPR insertion/deletion polymorphism has been related to hippocampal volume and amygdala response and it has been found to influence anxiety-related personality traits and anxiety disorders; in mood disorders it showed some influences on age at onset, periodicity, illness recurrence, rapid cycling, antidepressants response and depressive reaction to stressful life events. Psychosomatic disorders, suicide, alcoholism, smoking, eating disorders, attention deficit hyperactivity disorders and autism have been also found to be related to SERTPR variants. SERT gene variants seem therefore to modulate a wide range of aspects in both normal and affected individuals, many of which are possibly due to indirect correlations between such human features.

Late-Life Body Mass Index and Dementia Incidence: Nine-Year Follow-Up Data from the Kungsholmen Project

OBJECTIVES: To describe the association between late‐life body mass index (BMI) and dementia development with a time perspective and to investigate the effect of weight changes on dementia incidence.

Depressive symptomatology is influenced by chronotypes

BACKGROUND Rhythm disturbances are a frequent clinical manifestation of depression. In recent years a possible relationship between depression and chronotypes has emerged. Specifically eveningness has been proposed as vulnerability factor. The aim of this study was to describe sleep features of depressed patients according to chronotypes and to explore possible associations with the clinical features of depressive episodes. METHODS 100 patients diagnosed with Major Depressive Disorder according to the Mini International Neuropsychiatric Interview (MINI) were included (age: 34+/-11.74, range: 18-60 years; female/male:79/21). At admission the Hamilton Rating Scale for Depression (HRSD) was administered. Patients were also administered the Morningness-Eveningness Questionnaire (MEQ), the Epworth Sleepiness Scale, the Athens Insomnia Scale and the Pittsburgh Sleep Quality Index. RESULTS According to MEQ scores patients were classified in three groups: a) eveningness (n=18), b) neither (n=61) and c) morningness type (n=21). The age was different among chronotypes, being morningness-type patients older. The eveningness-type group showed higher scores in suicidal thoughts, more impaired work and activities, higher paranoid symptoms, higher scores on the anxiety cluster (HRSD), while the morningness-type group showed lower proportion of melancholic symptoms (MINI). We did not find association between sleep parameters and specific chronotypes. LIMITATIONS The relatively small sample size and the concurrent assessment of chronotypes and depression may have biased our findings. CONCLUSIONS Our data suggest the idea that chronotypes have an impact on depressive episodes features, with higher severity for the eveningness-type.

HTR2A gene variants and psychiatric disorders: a review of current literature and selection of SNPs for future studies.

Variants at the gene encoding for the 5-hydrosytryptamine (serotonin) receptor 2A (HTR2A) have been associated with many psychiatric disorders such as schizophrenia, mood disorders, attention deficit hyperactivity disorder, suicide, anxiety disorders, obsessive-compulsive disorder, eating disorders, and Alzheimers disease. The studied SNPs differ across studies, in the present review we focused on available evidence with the aim of identifying the overall phenotypic profile of HTR2A variant carriers. We then extensively analyzed all SNPs of the HTR2A gene with criteria of frequency, haplotype blocks, previous evidence, functionality in order to obtain a list of suitable SNPs for future studies that properly cover all possible genetic control of the HTR2A gene. Genetic association studies report conflicting and generally negative results. Most replicated data suggest C allele of the 102 T/C and Tyr452 variants as risk factor for psychosis and antipsychotic response, but the number of not replicating studies does not allow to draw any definite conclusion. Moreover their impact as risk factors is very small. In the other investigated psychiatric fields, evidence shows no involvement or at least a small and not replicated role for HTR2A gene variants. Conflicting and negative results could be due to a real marginal role of this receptor gene variants, or it could be caused by a lack of gene coverage of investigated SNPs. We suggest a wider investigation of the HTR2A gene to better understand its role in psychiatric disorders, preferably complemented with the use of proteomic or metabolomic approaches.

The effect of education on dementia occurrence in an Italian population with middle to high socioeconomic status.

Objective: To explore the relation between education and dementia prevalence by computing the odds ratios (ORs) for different educational levels after adjustment for age, gender, occupational level, and life habits. Methods: A two-phase community study including 495 elderly subjects with middle to high socioeconomic status, aged more than 60 years and with a high percentage of noneducated subjects, was carried out in the province of Ravenna, Italy. Dementia and dementia type were clinically diagnosed using DSM-III-R diagnostic criteria. Results: A higher prevalence of dementia was observed among noneducated subjects of both genders. Comparing no education with any education, the OR (adjusted for age, gender, and occupation) was 4.7 (95% CI = 2.3 to 9.6). The association, although present in all age groups, was extraordinarily strong among the youngest subjects (61 to 69 years) (OR = 139.5, 95% CI = 6.4 to 3,024.6) and decreased with increasing age. Life habits, such as smoking and alcohol consumption as well as current or previous history of hypertension, did not change the results. There was no significant difference in dementia prevalence among less well-educated (up to 3 years of education) and better-educated subjects (more than 3 years of schooling) after age and gender were taken into account. Similar findings were found to Alzheimers disease and vascular dementia separately. Conclusions: Having no education is associated with dementia independent of gender, occupation, life habits, and hypertension. This association was stronger among younger old persons, and decreased with increasing age. The findings suggest that the first decade of life is a critical period for developing dementia later in life. The decrease in dementia risk may be due to schooling, according to the cerebral reserve hypothesis, or to other factors associated with a higher educational level during childhood.

The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Occurrence of Cognitive Impairment and Dementia after the Age of 60: A Population-Based Study from Northern Italy

Objective: To evaluate the age, gender and education distribution of both cognitive impairment and dementia in the whole old age range of the elderly (from 61 years of age and over). Subjects and Methods: The study population consisted of all subjects born in 1930 or before, living in the municipality of Faenza and Granarolo, Italy (n = 7,930). A two-phase study design was implemented, by using the Mini-Mental State Examination and Global Deterioration Scale as screening instruments. The DSM-III-R diagnostic criteria were used for the clinical diagnosis of dementia. A subject was classified as affected by cognitive impairment, no dementia (CIND) if he/she scored 2 or more standard deviations lower than the corrected mean MMSE score. Results: The prevalences of dementia and CIND were 6.5 per 100 (95% CI 5.9–7.0) and 5.1 per 100 (95% CI 4.6–5.6), respectively. The prevalence of CIND was higher than that of dementia in the youngest old groups (61–74 years), both in men and women, whereas the opposite pattern was present among the older old (75+). In the older age groups, dementia prevalence increased exponentially with age, while CIND prevalence was more stable. There was not a substantial gender difference in CIND prevalence in all ages. Only in the subpopulation of higher educated subjects, women had a higher prevalence of both dementia and CIND than men. Lower educated subjects had a higher prevalence of both dementia and CIND. When compared to higher educated persons, subjects without any schooling had odds ratios of 10.9 (CI 7.0–16.7) and 16.7 (CI 11.2–25.0) for dementia and CIND, respectively. Conclusions: Cognitive impairment is very common in the younger old ages (under 70 years of age), whereas dementia becomes predominant after 75 years of age. Both conditions are strongly related to the educational level.