Progress in neuro-psychopharmacology & biological psychiatry
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewAnesthesia, surgery, illness and Alzheimer's disease.
Patients and their families have, for many decades, detected subtle changes in cognition subsequent to surgery, and only recently has this been subjected to scientific scrutiny. Through a combination of retrospective human studies, small prospective biomarker studies, and experiments in animals, it is now clear that durable consequences of both anesthesia and surgery occur, and that these intersect with the normal processes of aging, and the abnormal processes of chronic neurodegeneration. It is highly likely that inflammatory cascades are at the heart of this intersection, and if confirmed, this suggests a therapeutic strategy to mitigate enhanced neuropathology in vulnerable surgical patients.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewHereditary vulnerabilities to post-operative cognitive dysfunction and dementia.
In view of multiple prospective investigations reporting an incidence of 10% or greater in elderly patients after cardiac and non-cardiac procedures, it is surprising that no families, twins or even individual cases have been reported with persistent post-operative cognitive dysfunction (POCD) or post-operative dementia (POD) that is otherwise unexplained. As POCD and POD research has shifted in recent years from surgical and anesthetic variables to predictors of intrinsic, patient-specific susceptibility, a number of markers based on DNA sequence variation have been investigated. Nevertheless, no heritable, genomic indices of persistent POCD or post-operative dementia lasting 3 months or longer after surgery have been identified to date. The present manuscript surveys challenges confronting the search for markers of heritable vulnerability to POCD and POD, and proposes steps forward to be taken now, including the addition of surgical and anesthetic descriptors to ongoing longitudinal dementia protocols and randomized clinical trials (RCTs) comprising serial psychometric testing, and a fresh focus on phenotypes and genotypes shared between outliers with "extreme" POCD and POD traits.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
Clozapine pre-treatment has a protracted hypolocomotor effect on the induction and expression of amphetamine sensitization.
Amphetamine locomotor sensitization is an animal model for the study of addiction and schizophrenia. The antipsychotic clozapine blocks the hyperlocomotion induced by an acute injection of amphetamine, but its effect on locomotor sensitization after repeated amphetamine administration remains unknown. In the present study we investigate the effect of repeated administration of clozapine on the induction and expression of amphetamine locomotor sensitization. ⋯ On the other hand, clozapine treatment had no effect over locomotor response on the expression of amphetamine sensitization in either LRS or HRS rats. These data suggest that clozapine effect on amphetamine locomotor response depends on individual differences. Also, our results suggest that clozapine pre-treatment attenuates the neuroplasticity underlying amphetamine sensitization, but clozapine treatment is unable to reverse these changes once amphetamine sensitization has been induced.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
ReviewA review of epidemiological evidence for general anesthesia as a risk factor for Alzheimer's disease.
Exposure to surgery and general anesthesia (GA) has been hypothesized to be a potential risk factor for the development of Alzheimer's disease (AD). Some basic science research studies have demonstrated AD pathology in animals following exposure to inhalational anesthetics. However, controversy exists as to whether GA is associated with an elevated risk of developing AD in human populations. ⋯ A limited number of retrospective cohort studies have likewise not provided definitive information supporting an association. Therefore, at the present time there is limited information to support the hypothesis of AD developing as a consequence of GA, although there are few high quality studies in this area. Given the high prevalence and impact of AD, and the relatively frequent exposure of large populations to surgical procedures, the association between AD and GA requires further study.
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Prog. Neuropsychopharmacol. Biol. Psychiatry · Dec 2013
Neural correlates of obsessive-compulsive related dysfunctional beliefs.
There have been few attempts to integrate neurobiological and cognitive models of obsessive-compulsive disorder (OCD), although this might constitute a key approach to clarify the complex etiology of the disorder. Our study aimed to explore the neural correlates underlying dysfunctional beliefs hypothesized by cognitive models to be involved in the development and maintenance of OCD. We obtained a high-resolution magnetic resonance image from fifty OCD patients and 30 healthy controls, and correlated them, voxel-wise, with the severity of OC-related dysfunctional beliefs assessed by the Obsessive Beliefs Questionnaire-44. ⋯ On splitting subjects into high- and low-belief subgroups, we observed that such brain structural differences between OCD patients and healthy controls were explained by significantly larger ATL volumes among healthy subjects from the low-belief subgroup. Our results suggest a significant correlation between OC-related dysfunctional beliefs and morphometric variability in the anterior temporal lobe, a brain structure related to socio-emotional processing. Future studies should address the interaction of these correlations with environmental factors to fully characterize the bases of OC-related dysfunctional beliefs and to advance in the integration of biological and cognitive models of OCD.