Friday, November 1, 2013

Neuropsychopharmacology and Neuroscience, November 1, 2013

Lanicemine: a low-trapping NMDA channel blocker produces sustained antidepressant efficacy with minimal psychotomimetic adverse effects 

Molecular Psychiatry
Ketamine, an N-methyl-d-aspartate receptor (NMDAR) channel blocker, has been found to induce rapid and robust antidepressant-like effects in rodent models and in treatment-refractory depressed patients. However, the marked acute psychological side effects of ketamine complicate the interpretation of both preclinical and clinical data. Moreover, the lack of controlled data demonstrating the ability of ketamine to sustain the antidepressant response with repeated administration leaves the potential clinical utility of this class of drugs in question. Using quantitative electroencephalography (qEEG) to objectively align doses of a low-trapping NMDA channel blocker, AZD6765 (lanicemine), to that of ketamine, we demonstrate the potential for NMDA channel blockers to produce antidepressant efficacy without psychotomimetic and dissociative side effects. Furthermore, using placebo-controlled data, we show that the antidepressant response to NMDA channel blockers can be maintained with repeated and intermittent drug administration. Together, these data provide a path for the development of novel glutamatergic-based therapeutics for treatment-refractory mood disorders.

FDA approves second brain imaging drug to help evaluate patients for Alzheimer’s disease, dementia

The Food and Drug Administration (FDA) approved Vizamyl (flutemetamol) for use with positron emission tomography (PET) brain imaging in adults being evaluated for Alzheimer's disease (AD) and dementia. The approval was the FDA's second approval for a radioactive diagnostic drug used to detect images of beta-amyloid—a major mechanism in progression of AD. Amyvid was the first such drug approved.

FDA Approves Long-Acting Extended-Release Hydrocodone Formulation

FDA has approved Zohydro ER, the first extended-release, single-entity hydrocodone-containing drug product. To enhance safe and appropriate use, Zohydro ER’s labeling reflects the newly required ER/LA opioid analgesic class safety labeling changes and will be subject to the recently announced class postmarket study requirements.

Sleep Duration May Be Associated With Brain Deposits Linked to Alzheimer's

JAMA Neurology
Results: After adjustment for potential confounders, reports of shorter sleep duration were associated with greater Aβ burden, measured by mean cortical DVR (B = 0.08 [95% CI, 0.03-0.14]; P = .005) and precuneus DVR (B = 0.11 [0.03-0.18]; P = .007). Reports of lower sleep quality were associated with greater Aβ burden measured by precuneus DVR (B = 0.08 [0.01-0.15]; P = .03).
Conclusions and Relevance: Among community-dwelling older adults, reports of shorter sleep duration and poorer sleep quality are associated with greater Aβ burden. Additional studies with objective sleep measures are needed to determine whether sleep disturbance causes or accelerates Alzheimer disease. 

Topiramate for the Treatment of Cocaine Addiction

JAMA Psychiatry
Results: Using an intent-to-treat analysis, topiramate was more efficacious than placebo at increasing the weekly proportion of cocaine nonuse days, irrespective of whether missing data were not or were imputed conservatively to the baseline value (13.3% vs 5.3%, 95% CI for the estimated mean difference, 1.4%-14.6%, P = .02 or 8.9% vs 3.7%, 95% CI for the estimated mean difference, 0.2%-10.1%, P = .04, respectively). Topiramate also was associated, significantly more than placebo, with increasing the likelihood of urinary cocaine-free weeks (16.6% vs 5.8%; odds ratio, 3.21; 95% CI, 1.24-8.32; P = .02), as well as decreasing craving and improving observer-rated global functioning (all P < .05).
Conclusions and Relevance: Topiramate is more efficacious than placebo at increasing the mean weekly proportion of cocaine nonuse days and associated measures of clinical improvement among cocaine-dependent individuals.

Video game training enhances cognitive control in older adults

Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal-directed manner. Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals (multitasking), generating interference as the result of fundamental information processing limitations. It is clear that multitasking behaviour has become ubiquitous in today’s technologically dense world, and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population. Here we show that multitasking performance, as assessed with a custom-designed three-dimensional video game (NeuroRacer), exhibits a linear age-related decline from 20 to 79 years of age. By playing an adaptive version of NeuroRacer in multitasking training mode, older adults (60 to 85 years old) reduced multitasking costs compared to both an active control group and a no-contact control group, attaining levels beyond those achieved by untrained 20-year-old participants, with gains persisting for 6 months. Furthermore, age-related deficits in neural signatures of cognitive control, as measured with electroencephalography, were remediated by multitasking training (enhanced midline frontal theta power and frontal–posterior theta coherence). Critically, this training resulted in performance benefits that extended to untrained cognitive control abilities (enhanced sustained attention and working memory), with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later. These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain, and provide the first evidence, to our knowledge, of how a custom-designed video game can be used to assess cognitive abilities across the lifespan, evaluate underlying neural mechanisms, and serve as a powerful tool for cognitive enhancement.

Study Finds Link Between Schizophrenia and Autoimmune Diseases

The American Journal of Psychiatry
Results: Individuals with schizophrenia had an elevated risk of subsequent autoimmune diseases, with an incidence rate ratio of 1.53 (95% CI=1.46–1.62). Among persons without hospital contacts for infections, the effect of having schizophrenia was smaller, with an increased incidence rate ratio of 1.32 (95% CI=1.22–1.43) for autoimmune diseases. For individuals with schizophrenia as well as hospital contacts for infections, the combined risk of autoimmune diseases was 2.70 (95% CI=2.51–2.89). A family history of schizophrenia slightly increased the overall risk of developing autoimmune diseases (incidence rate ratio=1.06, 95% CI=1.02–1.09). Autoimmune diseases developed subsequently in 3.6% of people with schizophrenia, and 3.1% of people with autoimmune diseases had a family history of schizophrenia.
Conclusions: The increased risk of subsequent autoimmune diseases in individuals with schizophrenia may involve neuropsychiatric manifestations from the undiagnosed autoimmune disease, medical treatment or lifestyle associated with schizophrenia, or common etiological mechanisms, such as infections and shared genetic factors.

Ondansetron May Be Effective in Treating Alcoholism in Certain Populations, Study Finds

The American Journal of Psychiatry 
Results: Individuals carrying one or more of genotypes rs1150226-AG and rs1176713-GG in HTR3A and rs17614942-AC in HTR3B showed a significant overall mean difference between ondansetron and placebo in drinks per drinking day (−2.50; effect size=0.867), percentage of heavy drinking days (−20.58%; effect size=0.780), and percentage of days abstinent (18.18%; effect size=0.683). Combining these HTR3A/HTR3B and SLC6A4-LL/TT genotypes increased the target cohort from approaching 20% (identified in the previous study) to 34%.
Conclusions: The authors present initial evidence suggesting that a combined five-marker genotype panel can be used to predict the outcome of treatment of alcohol dependence with ondansetron. Additional, larger pharmacogenetic studies would help to validate these results.


Psychopharmacology - November 2013

Nature Neuroscience - November 2013, Vol 16 N° 11

Journal of Psychopharmacology - November 2013; 27 (11)

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