Has ‘lifetime prevalence’ reached the end of its life? An examination of the concept

Many cross‐sectional surveys in psychiatric epidemiology report estimates of lifetime prevalence, and the results consistently show a declining trend with age for such disorders as depression and anxiety. In a closed cohort with no mortality, lifetime prevalence should increase or remain constant with age. For mortality to account for declining lifetime prevalence, mortality rates in those with a disorder must exceed those without a disorder by a sufficient extent that more cases would be removed from the prevalence pool than are added by new cases, and this is unlikely to occur across most of the age range. We argue that the decline in lifetime prevalence with age cannot be explained by period or cohort effects or be due to a survivor effect, and are likely due to a variety of other factors, such as study design, forgetting, or reframing. Further, because lifetime prevalence is insensitive to changes in treatment effectiveness or demand for services, it is a parameter that should be dropped from the lexicon of psychiatric epidemiology. Copyright © 2009 John Wiley & Sons, Ltd.     

How does the ‘environment’ come to the person? The ‘ecology of the person’ and addiction

Currently, psychiatry lacks a field that can be called “theoretical psychiatry”, which uses theoretical concepts and explanatory models: The main stream of research is to collect data of all kinds in the hope that the computational Big Data approach will shed a bright light on the black box of mental disorders. Accordingly, the biology-based Research Domain Criteria of the National Institute of Mental Health have been established. However, as philosophical analyses of concepts and methods have shown, several epistemological gaps stand in the way of a consistent multilevel understanding of mental disorders. Also, the implicit ontological problems in the biological reduction of the psychosocial level and in the integration of so-called hard and soft disciplines are mostly left out. As a consequence, a non-reductive psychological theory of mental disorders is sought that also integrates correlating biological and sociological issues. In this context, one example of promising nonreductive psychiatric research is the option of systems/network psychopathology. The possibilities for integrating different psychological perspectives are highlighted for the field of addiction research and treatment, where pragmatic behaviorist approaches dominate over the theory-based practice of psychoanalysis. In comparing the theoretical constructs of these two approaches, the relevance of the concept of “(social) environment” as the wealth of influential sociocultural factors is discussed at levels superior to the interpersonal micro-level, namely the organizational meso- and societal macro level, which is not sufficiently considered in current biopsychiatry. On this basis of argumentation, the usefulness of grounding and framing psychiatry through the field of ecological sciences, especially human ecology, is demonstrated. Finally, to this end, an outline of an ecological model of mental health and illness is presented.     

What features improve the accuracy of the clinical diagnosis of progressive supranuclear palsy‐parkinsonism (PSP‐P)?

Progressive supranuclear palsy‐parkinsonism (PSP‐P) is a primary tauopathy characterised by neurofibrillary degeneration, which is frequently mistaken for Parkinson's disease (PD), multiple system atrophy (MSA), and vascular parkinsonism (VP) at presentation. The aim of this study was to identify particular clinical features (green flags) that may be helpful in differentiating PSP‐P from these other disorders. We identified 37 patients with PSP‐P from 726 patients archived at the Queen Square Brain Bank. Using a retrospective case notes review the clinical features were compared between the PSP‐P group and Lewy body associated parkinsonism (PD, n = 444 and dementia with Lewy bodies (DLB), n = 46), MSA (n = 90), and VP (n = 19), using the χ²‐test for proportions for a two‐by‐two contingency table. The sensitivity, specificity, and positive predictive values (PPV) and negative predictive values (NPV) were calculated for individual clinical features. A specificity of >0.85 or a PPV of >0.85 were considered reliable discriminators. No clinical features were predictive of PSP‐P, but late drug induced dyskinesias (specificity 0.92, PPV 0.99), late autonomic dysfunction (specificity 0.94, PPV 0.99) and any visual hallucinations (specificity 0.94, PPV 0.99) were better in distinguishing PD and PSP‐P than predicted using operational diagnostic criteria for PD. PSP‐P shares many clinical features with PD and DLB, MSA and VP, but visual hallucinations, drug induced dyskinesias and autonomic dysfunction are very uncommon and may be helpful exclusion criteria. © 2010 Movement Disorder Society     

The Structures of the E22Δ Mutant-Type Amyloid-β Alloforms and the Impact of E22Δ Mutation on the Structures of the Wild-Type Amyloid-β Alloforms

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Structures of the E46K Mutant-Type α-Synuclein Protein and Impact of E46K Mutation on the Structures of the Wild-Type α-Synuclein Protein

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Is insight in schizophrenia multidimensional? Internal structure and associations of the Greek version of the Schedule for the Assessment of Insight—Expanded

Despite the general agreement that insight is a multidimensional phenomenon, the studies on the factorial structure of the scales for its assessment have yielded rather inconsistent results. The present study aimed to assess the internal structure of the Schedule for the Assessment of Insight (SAI-E). Seventy-two chronic patients with schizophrenia were assessed with SAI-E. Hierarchical cluster analysis and multidimensional scaling (MDS) were used to identify insight components and assess their inter-relationships. The associations of the extracted components with demographic, clinical and cognitive characteristics were also examined. The SAI-E demonstrated good psychometric properties. Three subscales of SAI-E were identified measuring awareness of illness, relabeling of symptoms, and treatment compliance. Moreover, the MDS disclosed two underlying dimensions – degree of ‘specificity’ and ‘spontaneity’ – within the insight construct. Treatment compliance was more strongly correlated with symptom relabeling than illness awareness. Excitement symptoms, global functioning and general intelligence were correlated with all the components of insight. Depressive symptoms were more strongly correlated with illness awareness. Impaired relabeling ability was linked to cognitive rigidity and greater severity of disorganization and positive symptoms. Education and severity of negative symptoms specifically affect treatment compliance. Our results support the hypothesis that insight is a multidimensional construct.     

Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?

PURPOSE: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation-related epilepsy associated with different underlying causes. METHODS: Five hundred and fifty adolescent and adult patients who had partial epilepsy treated with AEDs and who had undergone magnetic resonance imaging of brain were followed up prospectively from 1984 at a single centre. More than 70% were newly diagnosed. None had had epilepsy surgery. RESULTS: Three hundred and twelve (57%) patients had been seizure free at their last clinic visit for at least a year. Patients with mesial temporal sclerosis (MTS; n = 73, 42% seizure free) were less likely to be controlled (p < 0.01) than were those with arteriovenous malformation (AVM; n = 14, 78%), cerebral infarction (n = 46, 67%), primary tumour (n = 35, 63%), cortical gliosis (n = 81, 57%), cerebral atrophy (n = 49, 55%), and cortical dysplasia (CD; n = 63, 54%). Among the seizure-free patients, those with MTS were more likely to require more than one AED compared with those with other aetiologies (48 vs. 35%; p < 0.05). There was no difference in outcome between patients with symptomatic and cryptogenic epilepsy (n = 361, 58% vs. n = 189, 56% seizure free, respectively). Patients with MTS, CD, and cryptogenic epilepsy were more likely (p = 0.02) to have a family history of epilepsy than were the other groups. MTS patients also had a higher incidence of febrile convulsions (p < 0.001). CONCLUSIONS: The majority of patients with focal-onset epilepsy became seizure free on AED treatment. MTS-related seizures had the worst prognosis. Although many patients with this pathology may benefit from epilepsy surgery, a considerable number will be controlled with AED therapy.     

Blockage of the Action of the Proneurotoxin MPTP and Toxin MPP<Superscript>+</Superscript> by Extracts of Homogenates of <Emphasis Type="Italic">Alphitobius diaperinus</Emphasis> Litter Beetles in an Experimental Model of Parkinson’s Disease

Adult male mice C57BL/6 (n = 105) were divided into five groups. The first group served as a control. In the 2nd–5th groups, the animals were treated subcutaneously with 40 mg/kg of proneurotoxin MPTP (methylphenyltetrahydropyridine), which forms a state similar to the initial stage of Parkinson’s disease over a 2-week period. Mice of groups 3–5 daily received an additive along with their food: one of three extracts of the biomass of the litter beetle Alphitobius diaperinus. In 2 weeks, all animals were tested for motor disorders in the vertical bar test; they were then euthanized and histochemical analysis of the dopamine-containing brain regions was performed. In addition, the same extracts were tested for counteraction to MPP⁺ toxin in cultured neuroblastoma cells. It was found that the primary aqueous and, especially, secondary water–methanol extracts had a powerful protective effect against the neurotoxic effect judging by the results of both the behavioral test and morphological control. Arginine was found at substantial concentrations in both effective extracts. An in vitro study confirmed the protective effect of the primary aqueous extract.     

Targeting Selective Activation of M1 for the Treatment of Alzheimer’s Disease: Further Chemical Optimization and Pharmacological Characterization of the M1 Positive Allosteric Modulator ML169

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Postnatal euphoria: are ‘the highs’ an indicator of bipolarity?

Research into postnatal mood disorders to date has concentrated on depressive syndromes of varying severity and full-blown acute puerperal mania. However, clinical experience, backed up by a review of the literature, indicates that milder hypomanic symptoms also occur in the early puerperium. Although these symptoms may often be regarded as clinically insignificant, there is evidence that the experience of minor puerperal elation may be a predictor of later postpartum depression. In addition, studying mild puerperal high mood may provide insights into the pathophysiology of more severe puerperal mania and psychosis. This paper critically reviews the literature on milder forms of high mood occurring in the puerperium and discusses the potential clinical and research significance of 'the highs'.     

Bilateral Olfactory Mucosa Damage Induces the Disappearance of Olfactory Glomerulus and Reduces the Expression of Extrasynaptic α5GABA<Subscript>A</Subscript>Rs in the Hippocampus in Early Postnatal Sprague Dawley Rats

Chloroform-induced olfactory mucosal degeneration has been reported in adult rats following gavage. We used fixed-point chloroform infusions on different postnatal days (PNDs) to investigate the effects of early olfactory bilateral deprivation on the main olfactory bulbs in Sprague Dawley rats. The experimental groups included rats infused with chloroform (5 μl) or saline (sham, 5 μl) on PNDs 3 and 8, and rats not receiving infusions (control) (n?=?6 in all groups). Rats receiving chloroform on PND 3 showed significant hypoevolutism when compared to those in other groups (P?<?0.05). There was a complete disappearance and a significant reduction in the size of olfactory glomeruli in the PND 3 and 8 groups, respectively, when compared to the respective sham groups. Rats receiving chloroform on PND 3 had significant memory impairment (P?<?0.01) and increased levels of learned helplessness (P?<?0.05), as measured using the Morris water maze and tail suspension tests, respectively. GABA_A receptor alpha5 subunit (α5GABA_AR) expression in hippocampal neurons was significantly lower in rats receiving chloroform on PND 3 than in rats in other groups (P?<?0.01), as measured using immunohistochemistry and polymerase chain reaction. There was thus a critical period for the preservation of regenerative ability in olfactory receptor neurons, during which damage and olfactory deprivation led to altered rhinencephalon structure and disappearance of olfactory glomeruli, which induced hypoevolutism. Olfactory deprivation after the critical period had no significant effect on olfactory receptor neuron regeneration, leading to reduced developmental and behavioral effects in Sprague Dawley rats.     

Expression of α<Subscript>2</Subscript>-macroglobulin,neutrophil elastase,and interleukin-1α differs in early-stage and late-stage atherosclerotic lesions in the arteries of the circle of Willis

Different types of atherosclerotic (AS) lesions can be distinguished histologically and represent different stages of AS plaque development. Late-stage lesions more frequently develop complications such as plaque rupture and thrombosis with vessel occlusion than early AS lesions. To clarify whether protective, destructive, and inflammatory proteins are differentially expressed in early-stage and late-stage AS plaques we examined the proteinase inhibitor α₂-macroglobulin (A2M), the neutrophil elastase (NE)—an enzyme degrading elastin and collagen fibers—and the proinflammatory protein interleukin-1α (IL-1α) in all types of AS plaques in the arteries of the circle of Willis from 78 human autopsy cases of both genders (61–91 years of age). Paraffin sections of AS plaques were immunostained with antibodies directed against A2M, NE and IL-1α. In initial AS lesions A2M was found, whereas NE and IL-1α were absent. NE and IL-1α became detectable as soon as a significant number of macrophages occurred within AS lesions. With increasing histopathological type of AS lesions, a marked increase of the area of the plaque exhibiting NE and IL-1α was observed. The area which exhibits A2M in AS plaques, on the other hand, did not vary significantly between the different stages. Thus, our results indicate a disproportionately high increase of the destructive enzyme NE and the proinflammatory protein IL-1α in relation to A2M with the progression of the grade of AS lesions pointing to the transgression of the protective capacity of A2M by NE and IL-1α in late-stage plaques. Therefore, our findings support the hypothesis that NE-induced tissue damage in late-stage AS plaques contributes to the development of plaque rupture and subsequent thrombosis.     

Influence of the Physiochemical Properties of Superparamagnetic Iron Oxide Nanoparticles on Amyloid β Protein Fibrillation in Solution

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Validation of the Bech–Rafaelsen Melancholia Scale and the Hamilton Depression Scale in patients with major depression; is the total score a valid measure of illness severity?

OBJECTIVE: Evaluation of antidepressant drug efficacy requires adequate rating scales for measuring the severity of depression. However, to measure the illness severity by such a total score, the scale needs to fulfil criteria of unidimensionality. On this background, we aimed at comparing the unidimensionality of the Bech-Rafaelsen Melancholia Scale (MES) and the 17-item Hamilton Depression Rating Scale (HAM-D(17)). METHOD: A total of 1629 patients aged between 18 and 65 years with a major depressive episode were treated openly with sertraline at a fixed oral dose of 50 mg daily during 4 weeks. The HAM-D(17) and the MES were applied at baseline and at weeks 2 and 4. Unidimensionality was tested with Mokken and Rasch analysis. RESULTS: Unidimensionality of the HAM-D(17) could not be confirmed. However, the 6-item Hamilton Depression Subscale (HAM-D(6)), was accepted by the Rasch analysis both at baseline and after 2 and 4 weeks of therapy. For the MES (as well as for the HAM-D(6)), a Loevinger coefficient of homogeneity above 0.40 (suggesting acceptance) was found at week 4. CONCLUSION: The HAM-D(6) and the MES did fulfil criteria for unidimensionality while the HAM-D(17) did not. Therefore, the extended use of the HAM-D(17) in drug trials may be questioned.     

How broad is the phenotype of Hallervorden–Spatz disease?

Magnetic resonance imaging (MRI) has enabled ante mortem diagnosis of Hallervorden Spatz disease (HSD). Childhood-onset cases are the most common type and usually present with progressive dystonia and dementia. The duration of illness is 15 to 20 years, leading to death. Presentation in adulthood and infancy have also been reported, however again the progression is usually inexorable. We present a 30-year-old woman who developed cognitive and motor developmental delay from the age of 8 months. There was further cognitive decline in her late teenage years with seizures and then more recent motor decline with dystonia. The imaging appearance was of iron deposition in the globus pallidus and substantia nigra leading to a diagnosis of HSD. The increased availability of MRI has allowed more cases of HSD to be diagnosed in life but as our case illustrates classification of the disease may need to be further examined.     

Where is the “where” in the brain? A meta‐analysis of neuroimaging studies on spatial cognition

Spatial representations are processed in the service of several different cognitive functions. The present study capitalizes on the Activation Likelihood Estimation (ALE) method of meta‐analysis to identify: (a) the shared neural activations among spatial functions to reveal the “core” network of spatial processing; (b) the specific neural activations associated with each of these functions. Following PRISMA guidelines, a total of 133 fMRI and PET studies were included in the meta‐analysis. The overall analysis showed that the core network of spatial processing comprises regions that are symmetrically distributed on both hemispheres and that include dorsal frontoparietal regions, presupplementary motor area, anterior insula, and frontal operculum. The specific analyses revealed the brain regions that are selectively recruited for each spatial function, such as the right temporoparietal junction for shift of spatial attention, the right parahippocampal gyrus, and the retrosplenial cortex for navigation and spatial long‐term memory. The findings are integrated within a systematic review of the neuroimaging literature and a new neurocognitive model of spatial cognition is proposed.