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.     

Who was the man who discovered the “Lewy bodies”?

In 1912, Fritz Heinrich Lewy described neuronal inclusions in the brain of patients who had suffered from Paralysis agitans (i.e., Parkinson's disease). Later, these findings became the so‐called “Lewy bodies.” However, little is known about the man who made this discovery. Our aim was to investigate Lewy's private and professional life and to gather information for a detailed biography. We contacted over 100 archives, libraries, and museums in Germany, Poland, Switzerland, United Kingdom, and United States. Over 300 documents, publications, and photos were collected. Lewy was born in Berlin, Germany in 1885 and lived there until 1933. After his dismissal on racial grounds by the Nazis, Lewy emigrated to England in 1933 and to the United States of America in 1934, where he lived and worked until his death in 1950. This article gives a summary of Lewy's life and briefly presents his contribution to German and American neurology. © 2010 Movement Disorder Society     

vCJD – predicting the future?

The recent emergence of variant Creutzfeldt-Jakob disease (vCJD) in the UK, and demonstration that vCJD is caused by the same prion strain that causes bovine spongiform encephalopathy, have led to concerns about the possibility of a human epidemic. Although only 79 cases of vCJD have occurred to date, it is likely that hundreds of thousands of infected cattle entered the human food chain in the late 1980s and early 1990s, and the average incubation period of vCJD is unknown. Mathematical models have not yet been able to give useful predictions of future numbers of cases, and in the absence of a blood test for vCJD, current attempts to reduce uncertainties about future numbers of cases are based on the accumulation of PrPSc in lymphoreticular tissues. Extensive lymphoreticular PrPSc accumulation has been seen in all cases of symptomatic vCJD so far examined, and in one case 8 months prior to the onset of symptoms. Animal models of prion disease suggest that lymphoreticular involvement occurs early in the incubation period and reliably predicts future neurological disease. Based on these data, large scale anonymous studies looking for PrP accumulation in surgically removed tonsillectomy and appendicectomy specimens are underway. Examination of the first 3000 specimens has not revealed any positive samples, but at the moment the significance of negative findings is uncertain. It is anticipated that by the time these studies are complete more data will be available on how early PrP can be demonstrated in lymphoreticular tissue in vCJD, which together with the results from examination of further samples, will allow some comment as to the likelihood of a large human vCJD epidemic.     

Where is the blood–brain barrier … really?

Few terms in the biomedical lexicon are as widely recognized as the phrase blood-brain barrier (BBB). Indeed, it immediately conjures up a "barricade" between the blood and the brain, a feature often considered more obstacle than safeguard. In truth, the BBB performs in both capacities, and it is precisely this duality that imparts such a vital role to the BBB in influencing physiological and pathophysiological processes in the CNS. Although the concept is more than a century old, the BBB continues to remain enigmatic in both substance and idea, with seemingly resolved issues once again beckoning for clarification. In this regard, recent technological advancements, such as sequencing of the human genome and development of microarray analysis, have illuminated novel aspects of vascular gene expression and provoked reconsideration of the cellular and biochemical makeup of the BBB. In light of the critical impact of the BBB in the realms of science and medicine, this Mini-Review will revisit the topic of the composition of the BBB, specifically highlighting how recent developments in endothelial biology have prompted a reevaluation of its precise vascular location. We have intentionally avoided discussing generalized features of the BBB, as these have been skillfully described elsewhere as noted.     

The murine <Emphasis Type="Italic">Bis1</Emphasis> seizure gene and the <Emphasis Type="Italic">Kcnab2</Emphasis> gene encoding the β2-subunit of the K<Superscript>+</Superscript> channel are different

Received: April 22, 1999 / Accepted: August 30, 1999 / Published online: January 10, 2000     

Abstinence from cocaine‐self‐administration activates the nELAV/GAP ‐43 pathway in the hippocampus: A stress‐related effect?

We previously demonstrated that nELAV/GAP‐43 pathway is pivotal for learning and its hippocampal expression is up‐regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence‐induced stress may sustain nELAV/GAP‐43 pathway during early abstinence following 2 weeks of cocaine self‐administration. We found that contingent, but not non‐contingent, cocaine exposure selectively increases hippocampal nELAV, but not GAP‐43, expression immediately after the last self‐administration session, an effect that wanes after 24 h and that comes back 7 days later when nELAV activation becomes associated with increased expression of GAP‐43, an effect again observed only in animals self‐administering the psychostimulant. Such effect is specific for nELAV since the ubiquitous ELAV/HuR is unchanged. This nELAV profile suggests that its initial transient alteration is perhaps related to the daily administration of cocaine, while the increase in the nELAV/GAP‐43 pathway following a week of abstinence may reflect the activation of this cascade as a target of stressful conditions associated with drug‐related memories. © 2016 Wiley Periodicals, Inc.     

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.     

Are the MDS‐UPDRS–Based Composite Scores Clinically Applicable?

Background: The International Parkinson and Movement Disorder Society–sponsored UPDRS (MDS‐UPDRS) is a powerful clinical outcome measure. Objectives: To evaluate the feasibility of various MDS‐UPDRS‐based composite scores and determine their minimal clinically important difference threshold values. Methods: Overall, 1,113 paired investigations of 452 patients were reviewed implementing three different techniques simultaneously. Results: Based on the ordinal regression modeling, the MDS‐UPDRS II+III, MDS‐UPDRS I+II+III, and the total score of MDS‐UPDRS are clinically applicable outcome measures. Any improvement greater than 4.9 points or any worsening more than 4.2 points on MDS‐UPDRS II+III represent a minimal, yet clinically meaningful, change. In reference to MDS‐UPDRS I+II+III, the smallest changes considered clinically relevant were 6.7 and 5.2 points for improvement and deterioration, respectively. The thresholds for the total score of MDS‐UPDRS were 7.1 points for improvement and 6.3 points for worsening. Conclusions: Our findings support the application of various MDS‐UPDRS–based composite scores. © 2018 International Parkinson and Movement Disorder Society     

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.     

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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Broadening the phenotype of <Emphasis Type="Italic">TARDBP</Emphasis> mutations: the <Emphasis Type="Italic">TARDBP</Emphasis> Ala382Thr mutation and Parkinson’s disease in Sardinia

Mutations in the TARDBP gene are a cause of autosomal dominant amyotrophic lateral sclerosis (ALS) and of frontotemporal lobar degeneration (FTLD), but they have not been found so far in patients with Parkinson’s disease (PD). A founder TARDBP mutation (p.Ala382Thr) was recently identified as the cause of ~30% of ALS cases in Sardinia, a Mediterranean genetic isolate. We studied 327 consecutive Sardinian patients with clinically diagnosed PD (88 familial, 239 sporadic) and 578 Sardinian controls. One family with FTLD and parkinsonism was also included. The p.Ala382Thr heterozygous mutation was detected in eight unrelated PD patients (2.5%). The three patients from the FTLD/parkinsonism family also carried this mutation. Within the control group, there were three heterozygous mutation carriers. During follow-up, one of these individuals developed motoneuron disease and another, a rapidly progressive dementia; the third remains healthy at the age of 79 but two close relatives developed motoneuron disease and dementia. The eight PD patients carrying the p.Ala382Thr mutation had all sporadic disease presentation. Their average onset age was 70.0 years (SD 9.4, range 51–79), which is later but not significantly different from that of the patients who did not carry this mutation. In conclusion, we expand the clinical spectrum associated with TARDBP mutations to FTLD with parkinsonism without motoneuron disease and to clinically definite PD. The TDP-43 protein might be directly involved in a broader neurodegenerative spectrum, including not only motoneuron disease and FTLD but also PD.