Cesare Turrina

Religion as a cross-cultural determinant of depression in elderly Europeans: results from the EURODEP collaboration

BACKGROUND The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans. METHODS Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17,739). RESULTS In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries. CONCLUSIONS Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life.

Cerebrovascular Accidents in Elderly People Treated with Antipsychotic Drugs: A Systematic Review

After 2002, an association between stroke and antipsychotic use was reported in clinical trials and large database studies. This review considers previous quantitative reviews, newly published clinical trials, and recent observational cohort and case-control studies, and focuses on the clinical significance of the risk for stroke, the difference between typical and atypical antipsychotics, the possible at-risk patient profile and the timing of stroke after exposure. A search of MEDLINE covering the period from 1966 to June 2009 was carried out using selected keywords. Inclusion criteria were (i) quantitative reviews on stroke and antipsychotics; (ii) double-blind, placebo-controlled clinical trials involving patients with dementia treated with antipsychotics; and (iii) observational database cohort studies and observational case-control studies investigating the association between stroke and antipsychotics. Clinical trials were excluded if they were single-blind or if patients were affected by dementia and/or other neurological illnesses.Four reviews with aggregate data, 2 meta-analyses, 13 randomized, double-blind, controlled trials, 7 observational cohort studies and 4 observational case-control studies were selected and analysed. The incidence of cerebrovascular accidents (CVAs) was found to be very low in aggregate reviews and meta-analyses (2–4%). When the number collected was sufficiently high, or different drug treatments were grouped together, the higher rate in subjects exposed to antipsychotics was statistically significant. Inspection of other randomized controlled clinical trials, not included in aggregate reviews and meta-analyses, reported similar rates of CVAs. The majority of observational cohort studies compared typical and atypical antipsychotics and no significant class differences were found. A comparison with non-users was carried out in some cohort studies. In case-control studies, the probability of CVAs in users compared with non-users was in the range of 1.3- to 2-fold greater. Preliminary data also indicate that the highest risk of stroke is related to the first weeks of treatment, and a risk profile for stroke is emerging, such as older age, cognitive impairment and vascular illness. Different pathophysiological pathways may be involved, ranging from the facilitation of thrombosis, pre-existing cardiovascular factors, sedation and a common diathesis for stroke of dementia, schizophrenia and affective illness.Before prescribing an antipsychotic, clinicians should weigh all the risk factors for a given patient and consider not only the indications as provided by the regulatory agencies, but also the overall effectiveness of typical and atypical antipsychotics.

Risk of stroke with typical and atypical anti-psychotics: a retrospective cohort study including unexposed subjects

The purpose of the study was to investigate the risk of stroke with typical and atypical anti-psychotics in elderly subjects, weighting for a number of known risk factors, including dementia. Data were retrospectively drawn from the primary care setting from the Health Search Database, which stores information on about 1.5% of the total Italian population served by general practitioners. All elderly patients (65+ years) prescribed an anti-psychotic in monotherapy from January 2000 to June 2003 were selected for the study. A cohort of patients not exposed to anti-psychotics was taken from the same database. Subjects who had previously had a stroke were excluded. The main outcome measure was the incidence of first-ever stroke during exposure to an anti-psychotic.The sample included non-users (69,939), users of atypicals (599), butyrophenones (749), phenotiazines (907) and substituted benzamides (1,968). The crude incidence of stroke in subjects not exposed to anti-psychotics was 12.0/1000 person-years. Risk was significantly higher for those on butyrophenones (47.1/1000), phenotiazines (72.7/1000) and in the atypical anti-psychotic group (47.4/1000). Substituted benzamides had an almost significant higher risk (25.0/1000). Cox regression modelling, weighting for demographic and clinical variables with non-users as the reference group, showed that the risk for stroke was 5.79 times for phenotiazines, 3.55 times for butyrophenones, and 2.46 times for atypicals. Clinicians should be cautious in prescribing phenotiazines and butyrophenones in elderly patients, since the risk for stroke would seem comparable or even greater than with atypicals.

Incidence of diabetes in a general practice population: a database cohort study on the relationship with haloperidol, olanzapine, risperidone or quetiapine exposure.

The present study aimed to estimate the incidence of diabetes in general practice patients who were treated with haloperidol, olanzapine, risperidone or quetiapine monotherapy and in subjects who were not exposed to antipsychotics. The design was a retrospective, up to 2 years, cohort study, with age-, sex- and length of observation-matching between subjects who were exposed and not exposed to antipsychotic drugs. Data were taken from the Health Search database, which contains information from 550 Italian general practitioners. Participants comprised 2071 subjects taking haloperidol, 266 taking olanzapine, 567 taking risperidone and 109 taking quetiapine, in addition to 6026 age- and sex-matched subjects who were not using antipsychotic drugs during the period of observation. Inclusion was limited to initially non-diabetic and antipsychotic drug-free individuals. The main outcome measure was the incidence of drug-treated diabetes. After age and sex correction by Cox regression analysis, the four groups treated with antipsychotics significantly differed from untreated subjects in hazard ratios for diabetes. The ratios for the haloperidol, olanzapine, risperidone and quetiapine groups were 12.4 (95% confidence interval 6.3–24.5), 20.4 (6.9–60.3), 18.7 (8.2–42.8) and 33.7 (9.2–123.6), respectively, with no significant differences when compared to each other.

Depressive disorders and personality variables in HIV positive and negative intravenous drug-users

BACKGROUND Only a few reports investigated the prevalence of depression in intravenous drug-users with HIV infection, including both asymptomatic and symptomatic subjects. In the same group, the association of depression and personality diagnoses was also poorly researched. METHODS A consecutive sample of intravenous drug-users was collected from patients admitted to an infectious disease clinic, another random sample was taken from out-patients attending a methadone maintenance treatment program. Subjects were first screened with the Hospital Anxiety and Depression Scale, and then all positive subjects were evaluated with the Composite International Diagnostic Interview. Depression was diagnosed according to DSM-IIIR. In-patients were also given a structured personality inventory (Karolinska Psychodynamic Profile). RESULTS HIV-positive patients had a high rate of depression (major depression 36.2%, dysthymic disorder 7.1%) when compared to HIV-negatives (15.7 and 3.9%, respectively). In-patients had the highest rate of depression, irrespective of HIV clinical staging. A personality disorder was diagnosed in 36% of the sample, but these subjects were no more significantly depressed. LIMITATIONS Poor detection of depression by the admitting physician may have led to selective hospitalization of patients with both HIV and mood disorder. The composition of the sample may also be biased by the help-seeking behavior of HIV patients who are also depressed. CONCLUSION Physicians treating AIDS patients should be alerted to the high rate of depression in clinical HIV illness, in order to identify and properly treat depression.

Timing of stroke in elderly people exposed to typical and atypical antipsychotics: a replication cohort study after the paper of Kleijer, et al.

A large body of evidence has recently established that, with possible minor drug-specific differences, both firstand secondgeneration antipsychotics increase the risk of stroke and related cerebrovascular events in elderly patients, irrespective of the specific disorder they suffer from (Herrmann, et al., 2004; Gill, et al., 2005; Kleijer, et al., 2008; Sacchetti, et al., 2008). However, the temporal profile of this association has been only marginally addressed so far. In a recent, well-designed, pioneer case-control nested analysis on 26,157 communitydwelling patients, the incidence of stroke was clearly concentrated in the first weeks of treatment (Kleijer, et al., 2008). Given the theoretical and practical relevance of the result, a replication study appeared worthwhile. With this aim, we planned a post-hoc, dedicated re-analysis of the data taken from the Health Search Database selected for our retrospective cohort study (Sacchetti, et al., 2008) on the incidence of firstever stroke in elderly primary care people, exposed or not to antipsychotic medication in monotherapy. Briefly, the enrolment and outcome criteria fully coincided with those we adopted previously (Sacchetti, et al., 2008), apart from the minimum age which was lowered from 65 to 50 years as in the Dutch study (Kleijer, et al., 2008). Furthermore, different from our original article, the users of antipsychotics were grouped together irrespective of the specific compound they received; this choice derived from the contingent, exclusive interest in the time-course of the association between antipsychotics and stroke and the largely shared opinion that this relation expresses a generalized class effect (Herrmann, et al., 2004; Gill, et al., 2005; Kleijer, et al., 2008; Sacchetti, et al., 2008). On this basis, we retrieved information on a total of 134,448 subjects. Of these, 128,308 were unexposed to antipsychotics and 6,180 were antipsychotic users. This wider sample included 2,824 cases of new-onset stroke and 131,664 controls. Monthly time stratifications were made in order to investigate a possible time pattern. After life table analysis, the cumulative proportion surviving (free from stroke) at the end of the first month was 0.9921 (95% CI 0.9899–0.9943) in subjects exposed to antipsychotics and 0.9995 (95% CI 0.9993–0.9997) in unexposed subjects. During the third month, the proportions were 0.9898 (95% CI 0.9872–0.9924) in patients exposed to antipsychotics and 0.9981 (95% CI 0.9979–0.9983) in unexposed subjects, whereas at the sixth month, the figures were 0.9819 (95% CI 0.9761–0.9879) in exposed patients and 0.9964 (95% CI 0.9960–0.9968) in unexposed subjects. A logistic regression analysis was then separately applied for each month of exposure (Figure 1) and weighted for a number of possible confounding factors such as age, sex, hypertension, coronary heart disease, heart failure, arrhythmias, diabetes, dislipidaemia, pneumonia, dementia and Parkinson’s disease. These were the independent, predictive variables; having a stroke or not was the predicted variable. The risk for stroke was 12.4 times higher (95% CI 8.4–18.1, P < 0.0001) in the first month of treatment, and much lower (mostly insignificant) in the following months (Figure 1). Our results overlap closely with those of the unique, previous publication on the chronology of the relationship between use of antipsychotics and stroke (Kleijer, et al., 2008). Therefore, our

Functional impairment in patients with major depression in clinical remission: results from the VIVAL-D-Rem, a nationwide, naturalistic, cross-sectional survey.

In recent years, the standard for successful treatment of major depression has switched from response to remission; however, little is known about patients who have achieved remission, but still have some residual symptoms and whether they regain previous levels of functioning. In a large, nationwide, cross-sectional, naturalistic survey (VIVAL-D) of 907 patients with major depression treated with a new course of an antidepressant in 41 Italian community psychiatric centers, patients with a Hamilton Rating Scale for Depression, 17-item version (HAM-D17) score up to 14 were selected (n=499). Of these, 169 were considered to be in remission (HAM-D17⩽7) and the other 330 to be mildly depressed. Their level of functioning was evaluated using the SF-12. Only a few (3%) patients in remission were completely symptom free; most were affected by residual symptoms. Patients in remission had better SF-12 scores than those with mild depression, but their functioning was significantly worse than general population norms. In the logistic regression analysis, the HAM-D17 total score and individual items were predictive of poor functioning. Analysis of sensitivity and specificity values showed that a lower cut-off score (4/5) of the HAM-D17 scale was best for predicting poor performance so that a reconsideration of the usual cut-off for remission of 7/8 for HAM-D17 seems overdue.

Brain Morphological Abnormalities at the Onset of Schizophrenia and Other Psychotic Disorders: A Review of the Evidence

A number of structural brain imaging studies and meta-analytic reviews have shown that multiple subtle brain abnormalities are consistently found in schizophrenia. However, quantitative reviews published to date suggest that structural brain changes found at the onset of the disease may be at least partially different from those found in patients with chronic schizophrenia. Some abnormalities seem to characterize schizophrenia at all stages; others seem more specific to the initial phases of the disease. These findings support the hypothesis of different patterns of involvement of various cerebral areas over the time course of schizophrenia. This suggests a complex scenario in which late cerebral changes, possibly related to the disease course and treatment, may complicate other early abnormalities, probably predating the disease onset. The specificity of such brain abnormalities to schizophrenia or the possibility that they may also be relevant to other psychotic disorders is a matter of debate. In particular, there is evidence for the presence of brain abnormalities in bipolar disorder, partially overlapping those found in schizophrenia. In this case, however, different findings have been reported in first-episode and chronic cases, raising the issue of converging trajectories of brain pathomorphology in these disorders, from a more specific pattern of abnormalities at onset, to a higher degree of overlap in chronic cases. In this chapter, the nature and meaning of these components of brain abnormalities, and how they affect the neurodevelopmental versus neurodegenerative hypotheses of psychoses are discussed.

Late-Onset Schizophrenia: Epidemiology, Clinical Profile, Prognosis, and Treatment Considerations

Historically, the possibility that schizophrenia can arise in middle or old age was supported by Emil Kraepelin, Eugene Bleuler and Manfred Bleuler. For very late-onset cases the British school used a specific diagnosis like late paraphrenia. However, until DSM-IIIR, clinicians in the United States did not consider a diagnosis of schizophrenia in patients with more than 45 years of age. In 2000 a consensus was reached to give a specific definition to late-onset schizophrenia (LOS) for cases in the 40–60 year age range, and very late-onset schizophrenia-like psychosis (VLOSLP) for cases aged 60 years or more. There have been few community surveys of LOS, and few reported estimates for broadly defined psychotic symptoms, or, at best, for the overall prevalence of schizophrenia in the elderly. Analyses of the clinical surveys indicate that, among patients with schizophrenia, 20–30% had an onset of illness after age 40 years. The symptom profile was generally investigated through matching patients with LOS with those with early onset schizophrenia (EOS). Some studies outlined the similarities between LOS and EOS, but often LOS had fewer negative symptoms, less disorganization, and better social performance. These comparisons must be weighted for the deterioration and selective mortality of schizophrenia with early onset. Patients with LOS have a worse neuropsychological performance than healthy controls, but for some tests they show an intermediate performance between EOS and controls. Genetic studies are very few and often not specifically designed, but evidence from the larger studies indicates a lower rate of first-degree relatives affected by schizophrenia in LOS compared with EOS. Brain imaging has found that LOS has abnormalities similar to EOS, although not all studies are concordant. Indices of cerebrovascular illness did not seem to be specific. Brain imaging, EEG and neuropathological studies do not indicate that neurodegeneration or cerebrovascular illness play a major role in LOS. Evidence-based guidelines for the treatment of LOS do not exist, for these patients are too few in randomized clinical trials. The indications from experts are to treat these late-onset patients with at least half the doses used for elderly patients with EOS. After 2000 more follow-up studies on LOS were published on whether patients with schizophrenia progressed to a dementia illness. Most did not find such evidence, but some studies suggested that, for a subgroup of patients, this possibility must be considered. Theories on the etiopathology of LOS have generally hypothesized a cerebral neurodevelopmental damage, similar to EOS, that predisposes an individual to the later development of psychosis when other insults occur in later life. Future research should probably concentrate on middle-age patients with LOS, because it is difficult to find patients with VLOSLP, should correct comparisons with aged patients with EOS for factors such as selective mortality and cognitive deterioration, and clarify the paradox of good premorbid functioning of patients with LOS despite existing neurodevelopmental deficits.