Orexin Receptors: Multi-Functional Therapeutic Targets for Sleeping Disorders, Eating Disorders, Drug Addiction, Cancers and Other Physiological Disorders.

Orexin receptors: Multi-functional therapeutic targets for sleeping disorders, eating disorders, drug addiction, cancers and other physiological disorders.

Cell Signal. 2013 Jul 31;
Xu TR, Yang Y, Ward R, Gao L, Liu Y

The orexin peptides (orexin A, orexin B) and their receptors (orexin receptor type 1, orexin receptor type 2) are involved in multiple physiological processes such as the regulation of sleep/wakefulness state, energy homeostasis and reward seeking. A result of this has been the development of small-molecule orexin receptor antagonists as novel therapies for the treatment of insomnia and drug addiction. Increased levels of signalling via the orexin peptide/receptor system may protect against obesity, whilst somewhat unexpectedly, orexins acting at orexin receptors induce dramatic apoptosis resulting in the significant reduction of cell growth in various cancer cell lines. Meanwhile, the orexin peptide/receptor system is also involved in cardiovascular modulation, neuroendocrine and reproduction regulation. This review summarizes the latest developments in deciphering the biology of orexin signalling as well as efforts to manipulate orexin signalling pharmacologically. HubMed – addiction

“I’m Not Abusing or Anything”: Patient-physician communication about opioid treatment in chronic pain.

Patient Educ Couns. 2013 Aug 2;
Matthias MS, Krebs EE, Collins LA, Bergman AA, Coffing J, Bair MJ

To characterize clinical communication about opioids through direct analysis of clinic visits and in-depth interviews with patients.This was a pilot study of 30 patients with chronic pain, who were audio-recorded in their primary care visits and interviewed after the visit about their pain care and relationship with their physicians. Emergent thematic analysis guided data interpretation.Uncertainties about opioid treatment for chronic pain, particularly addiction and misuse, play an important role in communicating about pain treatment. Three patterns of responding to uncertainty emerged in conversations between patients and physicians: reassurance, avoiding opioids, and gathering additional information. Results are interpreted within the framework of Problematic Integration theory.Although it is well-established that opioid treatment for chronic pain poses numerous uncertainties, little is known about how patients and their physicians navigate these uncertainties. This study illuminates ways in which patients and physicians face uncertainty communicatively and collaboratively.Acknowledging and confronting the uncertainties inherent in chronic opioid treatment are critical communication skills for patients taking opioids and their physicians. Many of the communication behaviors documented in this study may serve as a model for training patients and physicians to communicate effectively about opioids. HubMed – addiction

Shape Abnormalities of the Caudate Nucleus Correlate with Poorer Gait and Balance: Results from a Subset of the LADIS Study.

Am J Geriatr Psychiatry. 2013 Jul 31;
Macfarlane MD, Looi JC, Walterfang M, Spulber G, Velakoulis D, Styner M, Crisby M, Orndahl E, Erkinjuntti T, Waldemar G, Garde E, Hennerici MG, Bäzner H, Blahak C, Wallin A, Wahlund LO,

Functional deficits seen in several neurodegenerative disorders have been linked with dysfunction in frontostriatal circuits and with associated shape alterations in striatal structures. The severity of visible white matter hyperintensities (WMHs) on magnetic resonance imaging has been found to correlate with poorer performance on measures of gait and balance. This study aimed to determine whether striatal volume and shape changes were correlated with gait dysfunction.Magnetic resonance imaging scans and clinical gait/balance data (scores from the Short Physical Performance Battery [SPPB]) were sourced from 66 subjects in the previously published LADIS trial, performed in nondisabled individuals older than age 65 years with WMHs at study entry. Data were obtained at study entry and at 3-year follow-up. Caudate nuclei and putamina were manually traced using a previously published method and volumes calculated. The relationships between volume and physical performance on the SPPB were investigated with shape analysis using the spherical harmonic shape description toolkit.There was no correlation between the severity of WMHs and striatal volumes. Caudate nuclei volume correlated with performance on the SPPB at baseline but not at follow-up, with subsequent shape analysis showing left caudate changes occurred in areas corresponding to inputs of the dorsolateral prefrontal, premotor, and motor cortex. There was no correlation between putamen volumes and performance on the SPPB.Disruption in frontostriatal circuits may play a role in mediating poorer physical performance in individuals with WMHs. Striatal volume and shape changes may be suitable biomarkers for functional changes in this population. HubMed – addiction

Executive dysfunction correlates with caudate nucleus atrophy in patients with white matter changes on MRI: A subset of LADIS.

Psychiatry Res. 2013 Aug 2;
Macfarlane MD, Looi JC, Walterfang M, Spulber G, Velakoulis D, Crisby M, Orndahl E, Erkinjuntti T, Garde E, Waldemar G, Wallin A, Wahlund LO,

White matter changes (WMC) are common magnetic resonance imaging (MRI) findings, particularly in the elderly. Recent studies such as the Leukoaraiosis and Disability Study (LADIS) have found that WMC relate to adverse outcomes including cognitive impairment, depression, disability, unsteadiness and falls in cross-sectional and follow-up studies. Frontostriatal (or frontosubcortical) brain circuits may serve many of these functions, with the caudate nuclei playing a role in convergence of cognitive functions. This study aimed to determine whether reduced caudate volume relates to cognitive functions (executive functions, memory functions and speed of processing) and WMC. We determined caudate nuclei volumes, through manual tracing, on a subgroup of the LADIS study (n=66) from four centres with baseline and 3-year follow-up MRI scans. Regression analysis was used to assess relationships between caudate volume, cognitive function and WMC. Severity of WMC did not relate to caudate volume. Smaller caudate volumes were significantly associated with poorer executive functioning at baseline and at 3 years, but were not associated with scores of memory or speed of processing. Thus, in patients with WMC, a surrogate of small vessel disease, caudate atrophy relates to the dysexecutive syndrome, supporting the role of caudate as an important part of the frontostriatal circuit. HubMed – addiction