Jorge A. Cervilla

The risk for depression conferred by stressful life events is modified by variation at the serotonin transporter 5HTTLPR genotype: evidence from the Spanish PREDICT-Gene cohort

We report results from the PREDICT-Gene case-control study nested in a prospective cohort designed to identify predictors of the onset of depression among adult primary-care attendees. We tested the potential gene-by-environment interaction between 5HTTLPR genotype at the serotonin transporter gene and previous exposure to threatening life events (TLEs) in depression. A total of 737 consecutively recruited participants were genotyped. Additional information was gathered on exposure to TLEs over a 6-month period, socio-demographic data and family history of psychological problems among first-degree relatives. Diagnoses of depression were ascertained using the Composite International Diagnostic Interview (CIDI) by trained interviewers. Two different depressive outcomes were used (ICD-10 depressive episode and ICD-10 severe depressive episode). Both the s/s genotype and exposure to increasing number of TLEs were significantly associated with depression. Moreover, the 5HTTLPR s/s genotype significantly modified the risk conferred by TLEs for both depressive outcomes. Thus, s/s homozygous participants required minimal exposure to TLE (1 TLE) to acquire a level of risk for depression that was only found among l/s or l/l individuals after significantly higher exposure to TLEs (two or more TLEs). The interaction was more apparent when applied to the diagnosis of ICD-10 severe depressive episode and after adjusting for gender, age and family history of psychological problems. Likelihood ratios tests for the interaction were statistically significant for both depressive outcomes (ICD-10 depressive episode: LR X2=4.7, P=0.09 (crude), LR-X2=6.4, P=0.04 (adjusted); ICD-10 severe depressive episode: LR X2=6.9, P=0.032 (crude), LR-X2=8.1, P=0.017 (adjusted)).

Infectious agents associated with schizophrenia: A meta-analysis

Schizophrenia is a highly disabling and limiting disorder for patients and the possibility that infections by some microorganisms may be associated to its development may allow prevention and recovery. In the current study we have done a meta-analysis of studies that have assessed the possible association between detection of different infectious agents and schizophrenia. We report results that support the idea that there is a statistically significant association between schizophrenia and infection by Human Herpesvirus 2 (OR=1.34; CI 95%: 1.09-1.70; p=0.05), Borna Disease Virus (OR=2.03; CI 95%: 1.35-3.06; p<0.01), Human Endogenous Retrovirus W (OR=19.31; CI 95%: 6.74-55.29; p<0.001), Chlamydophila pneumoniae (OR=6.34; CI 95%: 2.83-14.19; p<0.001), Chlamydophila psittaci (OR=29.05; CI 95%: 8.91-94.70; p<0.001) and Toxoplasma gondii (OR=2.70; CI 95%: 1.34-4.42; p=0.005). The implications of these findings are discussed and further research options are also explicated.

Smoking, drinking, and incident cognitive impairment: a cohort community based study included in the Gospel Oak project

OBJECTIVES Recent longitudinal studies have reported that smoking increases risk for cognitive impairment and that moderate alcohol intake could be preventive.The association between both cigarette smoking and alcohol drinking and incident cognitive impairment was studied in a representative population. METHODS This is a 1 year prospective population based cohort sudy of all residents aged 65 or over in the electoral ward of Gospel Oak in London, UK (n=889). Cognitive impairment was assessed at baseline and 1 year later using the organic brain syndrome (OBS) cognitive impairment scale from the short CARE structured assessment. Subjects who were cognitively impaired at baseline were excluded from this analysis. RESULTS The prevalence of OBS cognitive impairment was 10.4% at index assessment and the 1 year cumulative incidence of cognitive impairment was 5.7%. Cognitive impairment was not associated with use of alcohol, although there was a non-significant association in the direction of a protective effect against onset of cognitive impairment for moderate drinkers compared with non-drinkers and heavy drinkers. Current smoking status predicted cognitive impairment (risk ratio (RR) 3.7; (95% confidence interval (95% CI)=1.1–12.3) independently from sex, age, alcohol, occupational class, education, handicap, depression, and baseline cognitive function. CONCLUSIONS Smoking seems to be a prospective risk factor for incident cognitive impairment; thus encouragement of older people to stop smoking could be considered as part of a strategy to reduce the incidence of cognitive impairment.

The 5‐HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: The PREDICT‐gene study

Previous reports and meta‐analyses have yielded inconclusive results as to whether the s/s genotype at the 5‐HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD‐10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD‐10 depressive episode and ICD‐10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD‐10 depressive episode and for severe ICD‐10 depressive episode were 1.50 (95% CI: 1.0–2.2; P = 0.045) and 1.79 (95% CI: 1.1–2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (χ2 for linear association=6.1; P = 0.013) suggesting a dose‐dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5‐HTTLPR genotype increasing the risk for depression.

Neurocognitive performance and negative symptoms: Are they equal in explaining disability in schizophrenia outpatients?

OBJECTIVE The aim of this study is to assess if cognitive variables and symptom dimensions can predict disability in a sample of outpatients with schizophrenia. METHOD A cross-sectional sample of 113 individuals with a diagnosis of schizophrenia (DSM-IV criteria) was selected from a computerized register of five Community Mental Health Centers. Patients were assessed by two trained psychologists, with a neuropsychological battery comprising measures for verbal memory, attention, operative memory and abstraction and flexibility functions. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS); a socio-demographic and clinical questionnaire, comprising the Disability Assessment Scale (DAS), was also completed. Test scores were standardized (t scores) to performance of healthy controls. To assess the relationship between clinical and sociodemographic factors and disability and cognitive functioning Pearsons correlation coefficients were computed. In order to establish the predictive capacity of the cognitive, clinical and symptom variables on disability linear regression models were fitted. RESULTS Mean age of patients was 41.6 years and 68% were male. Higher ratings in the negative dimension were associated with more cognitive deficits. Association with the positive dimension was present but less strong. All disability areas, except for disability in occupational functioning, were partially explained by the negative dimension. Disability in family functioning was also partially explained by attention and number of admissions since onset. CONCLUSION Negative symptoms are the major source of disability of our sample and are also associated to cognitive functioning. The present findings suggest that further investigation on the mediators between clinical and social outcomes may help to design specific treatments to reduce disability.

The association between APOE and dementia does not seem to be mediated by vascular factors

Objective: The effect of APOE on dementia may be mediated through dyslipidemia and atherogenesis through its effect on cholesterol metabolism. The authors investigated this possibility among aged survivors from the UK Medical Research Council Trial of the Treatment of Hypertension in Older Adults. Design: A total of 370 of 657 survivors from an initial cohort of 1,088 recruited into the trial between 1983 and 1985 were traced in 1994 and agreed to be screened for dementia. Blood samples were analyzed for APOE genotype and serum fibrinogen. Cholesterol level, smoking behavior, blood pressure, body mass index, and EKG recordings had been measured at recruitment 10 to 12 years earlier. Odds ratios (ORs) for the association between APOE ε4/* and both AD and dementia were estimated and adjusted incrementally for the effect of age and premorbid intelligence, cholesterol, other risk factors for vascular disease, and EKG evidence of cardiovascular disease. Results: The authors diagnosed 24 cases of National Institute of Neurological and Communicative Disorders and Stroke AD from 41 cases of dementia. The crude OR for the association between APOE ε4/* and AD was 3.40 (95% CI 1.30 to 8.91). APOE genotype was associated with serum cholesterol level, and there was a nonsignificant trend for an association with smoking behavior. After adjusting for these and all other vascular risk factors and vascular disease variables listed earlier, the OR for the association between APOE ε4/* and AD increased to 4.81 (1.60 to 14.4). Conclusion: Presence of APOE ε4/* seems to increase the risk for dementia and AD independently of its effect on dyslipidemia and atherogenesis.

Does depression predict cognitive outcome 9 to 12 years later? Evidence from a prospective study of elderly hypertensives

BACKGROUND Previous longitudinal studies of the association between depression and cognitive dysfunction have had relatively short follow-up periods. This report presents a long-term study of the association between baseline syndromal depression and cognitive outcome measured 9 to 12 years later. METHODS Self-CARE (D) depression, cognitive function and pre-morbid intelligence were recorded on 1083 subjects on entry to the Medical Research Council trial of treatment of hypertension in older adults in 1983-5. In 1994-5, we aimed to re-interview all survivors to assess cognitive function using the MMSE. We used multivariate analysis to explore whether baseline depression predicted cognitive outcome after this long follow-up period. RESULTS Baseline depression was crudely associated with poorer cognitive outcome at time 2. However, this long-term prospective association was no longer apparent after adjusting for baseline cognitive performance, which was associated with baseline depression and robustly predicted cognitive outcome at time 2. We found that gender modified the association between depression and poorer cognitive outcome, so that the association was statistically significant only among men. CONCLUSION Propensity for depression and failing cognition may have common determinants that still need to be established by future neurobiological investigations in conjunction with further long-term prospective epidemiological research.

Pain as a symptom of depression: Prevalence and clinical correlates in patients attending psychiatric clinics

BACKGROUND The need to assess the prevalence and characteristics of painful symptoms among depressed patients attended by psychiatrists in their regular clinical practice. METHODS A multi-centre, cross-sectional study was carried out in a large sample (n=3566) of patients attending out-patient psychiatric facilities in Spain. All types of DSM-IV-TR depressive disorders were included. Data on the diagnosis, specific symptoms, intensity of depression and antidepressant and analgesic drug treatments were collected. The presence and characteristics of significant pain (visual analogue scale score>40) at the time of the study were also recorded. RESULTS The prevalence of pain in depressed patients was 59.1% (CI 95%: 57.7%; 60.7%). Factors associated independently with the existence of significant pain were: being female, presence of loss of energy and the diagnosis of dysthymia or depression induced by physical disorders. In addition, age and the intensity of depression were two risk factors, where each year of age and each point in the Hamilton scale increased the risk of having pain by 2% and 8% respectively. The presence of anhedonia and the diagnosis of depression induced by illegal drugs were factors inversely related to pain. LIMITATIONS The cross-sectional naturalistic characteristics of the study. CONCLUSION Our data show a high prevalence of pain among depressive patients attending psychiatric clinics. Painful symptoms are modulated differently depending on the type of depression and the presence of specific symptoms, such as loss of energy or anhedonia. Psychiatrists should ask their depressive patients for the presence of pain on a regular basis.

The development of the Quality Indicator for Rehabilitative Care (QuIRC): a measure of best practice for facilities for people with longer term mental health problems

BackgroundDespite the progress over recent decades in developing community mental health services internationally, many people still receive treatment and care in institutional settings. Those most likely to reside longest in these facilities have the most complex mental health problems and are at most risk of potential abuses of care and exploitation. This study aimed to develop an international, standardised toolkit to assess the quality of care in longer term hospital and community based mental health units, including the degree to which human rights, social inclusion and autonomy are promoted.MethodThe domains of care included in the toolkit were identified from a systematic literature review, international expert Delphi exercise, and review of care standards in ten European countries. The draft toolkit comprised 154 questions for unit managers. Inter-rater reliability was tested in 202 units across ten countries at different stages of deinstitutionalisation and development of community mental health services. Exploratory factor analysis was used to corroborate the allocation of items to domains. Feedback from those using the toolkit was collected about its usefulness and ease of completion.ResultsThe toolkit had excellent inter-rater reliability and few items with narrow spread of response. Unit managers found the content highly relevant and were able to complete it in around 90 minutes. Minimal refinement was required and the final version comprised 145 questions assessing seven domains of care.ConclusionsTriangulation of qualitative and quantitative evidence directed the development of a robust and comprehensive international quality assessment toolkit for units in highly variable socioeconomic and political contexts.

High-activity variants of the uMAOA polymorphism increase the risk for depression in a large primary care sample

Studies on the association between the functional uMAOA polymorphism and depression have yielded non‐conclusive results up till now. One thousand two hundred twenty eight consecutive Spanish primary care attendees, participating in the PREDICT study, agreed to take part in this genetic PREDICT‐Gene study. We explored the association between depression and either high‐activity uMAOA alleles or genotypes. Depression was diagnosed using the Composite International Diagnostic Interview (CIDI) to establish three different depressive outcomes (ICD‐10 Depressive Episode (DE), ICD‐10 Severe Depressive Episode (SDE) and DSM‐IV Major Depression (MD)). uMAOA genetic variation was determined by PCR amplification and subsequent electrophoresis. Crude and adjusted (gender and/or age) odds ratios, with 95% confidence intervals, were calculated for the associations between allele or genotype frequencies and all three depressive outcomes. We found associations between all three depressive phenotypes and either high‐activity alleles or high‐activity genotypes in both sexes. The associations were statistically significant for females but not for males. Testing the same associations on the entire sample (males and females) also yielded significant associations between depression and either high‐activity alleles or high‐activity genotype distribution that were independent of age and/or gender (ICD‐10 DE: OR = 1.98; 95% CI: 1.42–1.77; P = 0.00002; ICD‐10‐SDE: OR = 2.05; 95% CI: 1.38–3.05; P = 0.0002; DSM‐IV MD: OR = 1.91; 95% CI: (1.26–2.91); P = 0.0014). Our results provide fairly consistent evidence that high‐activity variants of the MAOA promoter polymorphism confer a modestly higher risk for depression.