Frailty and Risk of Falls in Community-Dwelling Older Adults Living in a Rural Setting. The Atahualpa Project.

BACKGROUND: Data supporting a link between frailty and risk of falls is mostly confined to individuals living in urban centers, where risk factors and lifestyles are different from that of rural settings. OBJECTIVE: To assess the association between frailty and risk of falls in older adults living in rural Ecuador. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Community-dwellers aged ≥60 years living in a rural Ecuadorian village, in whom frail status and risk of falls were assessed. MEASUREMENTS: Frailty was evaluated by the Edmonton Frailty Scale (EFS) and risk of falls by the Downton Fall Risk Index (DFRI). Multivariate models were fitted to evaluate whether frailty was associated with risk of falls (dependent variable), after adjusting for demographics, alcohol intake, cardiovascular risk factors, sleep quality, symptoms of depression, and history of an overt stroke. Correlation coefficients were constructed to assess confounders modifying this association. RESULTS: A total of 324 participants (mean age: 70.5±8 years) were included. The mean EFS score was 4.4±2.5 points, with 180 (56%) participants classified as robust, 76 (23%) as pre-frail and 68 (21%) as frail. The DFRI was positive in 87 (27%) participants. In univariate analysis, the EFS score was higher among participants with a positive DFRI (p<0.001). The number of frail individuals was higher (p<0.001), while that of robust individuals was lower (p<0.001) among those with a positive DFRI. Adjusted logistic regression models showed no association between frailty and the DFRI. Correlation coefficients showed that age, high glucose levels, and history of an overt stroke tempered the association between frailty and the risk of falls found in univariate analyses. CONCLUSIONS: Frailty is not independently associated with risk of falls in older adults living in a remote rural setting. Further studies are needed to assess the impact of frailty on the risk of falls in these populations.

Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.

OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.

OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.

Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers.

OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.

Olfaction and symptoms in the multiple chemical sensitivities syndrome.

Whereas most idiosyncratic environmental sensitivity complaints do not fit known diagnoses, the multiple chemical sensitivities syndrome (MCS) is an extreme presentation that has defined diagnostic criteria. MCS symptomatics claim that they acquired a sensitized state as the result of a chemical exposure, usually to a solvent or pesticide, but not to a fragrance. Before this exposure, they did not experience symptoms. Following sensitization, symptoms increasing in number and severity with time are attributed by the MCS symptomatic to various exposures that are innocuous to most individuals. Although phenomenological studies have provided no evidence that particular odors elicit MCS symptoms, low levels of fragrances and perfumes are frequently associated with the reporting of MCS symptoms. This evaluation examines proposed mechanisms by which odorants and fragrances might cause either sensitization or elicitation of MCS symptoms, including altered odor sensitivity, primary irritancy or irritancy-induced upper airway reactivity, neurogenic switching of trigeminal irritancy signals, time-dependent sensitization and limbic kindling, CNS toxicity, and various psychiatric conditions. In no case was there persuasive evidence that any olfactory mechanism involving fragrance underlies either induction of a sensitized state or the triggering of MCS symptoms. Fragrances and other odorants could, however, be associated with symptoms as claimed by MCS symptomatics, because they are recognizable stimuli, but fragrance has not been demonstrated to be causal in the usual sense.

Behavioral medicine, complementary medicine and integrated care. Economic implications.

Health care concepts and practices are changing dramatically because of demographic and economic factors. The routine integration of behavioral and biomedical care is completely compatible with these changes and such integration would provide clinical and economic benefits to patients and to society.

Understanding delusions.

Delusions traditionally have been considered as fixed, false beliefs, born of morbidity. Whereas this definition serves to orient the clinician to the phenomena at hand, each element breaks down under scrutiny. It has been shown that delusions are not necessarily false, although in some sense they are discordant with reality. When delusions coincide with actual events their judgements can be shown to be independent of this evidential basis; when they refer to disorders of experience, such as first rank symptoms, the experience usually contains a distorted meaning. The supposition that delusions are a variety of belief has itself been questioned. On the one hand, they do not always refer in a meaningful way to anything, or when they do they fail to function as evaluative judgments; instead, delusions are experienced subjectively in ways that are characteristic of knowing rather than believing. On the other hand, delusions are not ascertained clinically by surveying the patient's belief system; rather their failure to achieve the status of objective knowledge leads to the post hoc relegation of delusions to the epistemologic waste basket of beliefs. To treat delusions as necessarily the product of morbidity is essentially tautologous insofar as delusions are, by definition, pathologic; that is, as defective judgments delusions are not simply erroneous, they are disordered. Finally, the fixity of delusions is an empirical matter and varies widely. Underlying this perceived intractability, however, are the subjective certainty and incorrigibility that Jaspers identified and which Spitzer has recast in the form of "epistemological asymmetry" misapplied to external reality. Although delusions typically have been recognized and categorized according to their manifest content, these formal considerations are crucial to understanding the nature of delusions.

Foundations of the new nosology.

DSM-III and its revisions have provided little in the way of explicit historical or philosophical foundations. The logical empiricism embedded in its operational criteria and its external approach to validation are inadequate to account for the presumption of nosological regularities or the specific categories endorsed by the taxonomy. The nosologic operation that Jaspers referred to as the "synthesis of disease entities" is explored in connection with the central distinction in DSM-IV between mood disorders and schizophrenic disorders. This synthetic operation is analyzed in terms of the paradigmatic shift from the mania-melancholia matrix of pre-modern psychiatry to the manic-depression/dementia praecox model defined by the work of Kraepelin. In the context of this analysis the self-evidence of these regularities is questioned.

Aprosodia in eight schizophrenic patients.

Research interest in the "negative" symptoms of schizophrenia has increased in recent years. Given the clinical similarity between affective deficits in schizophrenic patients and aprosodic deficits in stroke victims, the authors conducted a study testing for aprosodia in eight schizophrenic patients. Seven were found to have aprosodia with motor components. Further study of the aprosodias may provide some insight into affective disturbance in schizophrenia.

The legacy of Ewald Hecker: a new translation of "Die Hebephrenie". Translated by Marie-Louise Schoelly.

Early descriptions of schizophrenia may be found in the writings of Haslam and Morel, but the turning point in the development of the modern concept was Ewald Hecker's classic paper on hebephrenia in 1871. The syndrome he described--a psychosis of early onset with a deteriorating course characterized by a "silly" affect, behavioral peculiarities, and formal thought disorder--not only adumbrated Kraepelin's generic category of dementia praecox but quite specifically defined the later subtype of hebephrenic, or disorganized, schizophrenia as well. The present translation into English of Hecker's "Die Hebephrenie" makes accessible a crucial milestone in the history of modern psychiatry.

Falret's discovery: the origin of the concept of bipolar affective illness. Translated by M. J. Sedler and Eric C. Dessain.

Jean Pierre Falret's once celebrated but now neglected 1854 description of "circular insanity" has not been translated into English until now. This seminal essay clearly articulated for the first time the rudimentary elements of our present diagnosis of bipolar affective disorder. It contains lucid descriptions of manic excitement and depression and the "switch" from one to the other; moreover, it emphasizes the importance of course and prognosis, as well as hereditary and epidemiologic factors. Although American psychiatry instinctively looks to the German literature for its foundations in Kraepelin, Bleuler, and Freud, the translation of Falret's essay represents an effort to trace contemporary psychiatric concepts to their origins in nineteenth-century France.

Freud's concept of working through.

Of all Freud's concepts, working through most completely characterizes the role of the patient in analysis. Conceived as the labor of the patient, rather than as an analytic technique, working through consists of two phases: recognizing resistances (insight) and overcoming resistances (change). In this paper these achievements are explicated in terms of the collaborative, yet conflicting, functions of remembering and repeating. A metapsychological consideration of the resistances in question leads to the system of concepts defined by id-resistance, the compulsion to repeat, and the death instinct. Finally, the concept of working through gives evidence for the idea of a will to recovery which, in the psychoanalytic situation, becomes a will to remember.