Understanding the genetic architectonics of complex CNS traits: Lost by the association, but found in the interaction?
Recent evidence supports the value of endophenotypes and genome-wide association studies in psychiatric genetics, and their importance for dissecting the neural pathways and molecular mechanisms of complex neuropsychiatric disorders. Continuing this important discussion, here we outline three new mechanisms by which novel classes of genes may facilitate CNS pathogenesis without directly worsening its individual ‘established’ endophenotypes. These putative genetic mechanisms can apply to other human disorders in general, and may also be used for designing novel effective CNS drug treatments. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - July 20, 2015 Category: Psychiatry Authors: Stewart, A. M., Nguyen, M., Song, C., Kalueff, A. V. Tags: Perspectives Source Type: research
Polygenic risk scores in imaging genetics: Usefulness and applications
Genetic factors account for up to 80% of the liability for schizophrenia and bipolar disorder. Genome-wide association studies (GWAS) have successfully identified several single nucleotide polymorphisms (SNPs) and genes associated with increased risk for both disorders. Single SNP analyses alone do not address the overall genomic or polygenic architecture of psychiatric disorders as the amount of phenotypic variation explained by each GWAS-supported SNP is small whereas the number of SNPs/regions underlying risk for illness is thought to be very large. The polygenic risk score models the aggregate effect of alleles associa...
Source: Journal of Psychopharmacology - July 20, 2015 Category: Psychiatry Authors: Dima, D., Breen, G. Tags: Perspectives Source Type: research
Rating scales to measure side effects of antipsychotic medication: A systematic review
Conclusion:
This review will help researchers and clinicians make a purpose-oriented choice of which scale to use.
Systematic review registration number:
CRD42014013010. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - July 20, 2015 Category: Psychiatry Authors: van Strien, A. M., Keijsers, C. J., Derijks, H. J., van Marum, R. J. Tags: Review Source Type: research
Thank you to our Reviewers
(Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Tags: Thank you to our Reviewers Source Type: research
Midbrain raphe 5-HT1A receptor activation alters the effects of ghrelin on appetite and performance in the elevated plus maze
Prior research suggests that midbrain serotonergic signaling and hypothalamic ghrelinergic signaling both play critical roles in appetitive and emotional behaviors. In the present study, we investigated the effects of median raphe nucleus (MRN) somatodentritic 5-HT1A receptor activation on the feeding-stimulant and anxiogenic action of paraventricular nucleus (PVN) ghrelin. In an initial experiment, adult male Sprague-Dawley rats were injected with either ghrelin (200–800 pmol) into the PVN or 8-OH-DPAT (2.5–10 nmol), a 5-HT1A receptor agonist, into the MRN. Performance on the elevated plus maze (EPM) was then ...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Wauson, S. E., Sarkodie, K., Schuette, L. M., Currie, P. J. Tags: Original Papers Source Type: research
Learning ability is a key outcome determinant of GSK-3 inhibition on visuospatial memory in rats
Learning aptitude has never been a focus of visuospatial performance studies, particularly on memory consolidation and reconsolidation. The aim of this study was to determine the consequences of learning ability on memory consolidation/reconsolidation following inhibition of glucose synthase kinase-3 (GSK-3) by 4-benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8). The anxiety-like nature of rats was characterized in the elevated plus maze. The rats were then trained for four days in the Morris water maze (MWM) and classified as ‘superior’, ‘intermediate’ or ‘inferior’ learners. The...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Storozheva, Z. I., Gruden, M. A., Proshin, A. T., Sewell, R. D. Tags: Original Papers Source Type: research
Combined administration of buprenorphine and naltrexone produces antidepressant-like effects in mice
Opiates have been used historically for the treatment of depression. Renewed interest in the use of opiates as antidepressants has focused on the development of kappa opioid receptor (-receptor) antagonists. Buprenorphine acts as a partial µ-opioid receptor agonist and a -receptor antagonist. By combining buprenorphine with the opioid antagonist naltrexone, the activation of µ-opioid receptors will be reduced and the -antagonist properties enhanced. We have established that a combination dose of buprenorphine (1 mg/kg) with naltrexone (1 mg/kg) functions as a short-acting -antagonist in the mouse tail withdrawa...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Almatroudi, A., Husbands, S. M., Bailey, C. P., Bailey, S. J. Tags: Original Papers Source Type: research
Effects of ST1936, a selective serotonin-6 agonist, on electrical activity of putative mesencephalic dopaminergic neurons in the rat brain
The serotonin-6 (5-HT6) receptor is the most recently discovered serotonin receptor, and it represents an increasingly promising target for improving cognition in both normal and disease states. Recently, a new selective 5-HT6 receptor agonist, 2-(5 chloro-2-methyl-1H-indol-3-yl)-N,N-dimethylethanamine (ST1936), with nanomolar affinity for 5-HT6 receptors was described. We performed in-vivo electrophysiological studies to investigate the physiological role of 5-HT6 receptors in the control of the function of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Extracellular single-unit recordings were...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Borsini, F., Bordi, F., Poggi, A., Di Matteo, V. Tags: Original Papers Source Type: research
Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons
The rapid antidepressant action of a subanesthetic dose of ketamine in treatment-resistant patients represents the most striking recent breakthrough in the understanding of the antidepressant response. Evidence demonstrates tight interactions between the glutamatergic and monoaminergic systems. It is thus hypothesized that monoamine systems may play a role in the immediate/rapid effects of ketamine. In vivo electrophysiological recordings were carried in male rats following ketamine administration (10 and 25 mg/kg, i.p.) to first assess its effects on monoaminergic neuron firing. In a second series of experiments, the effe...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: El Iskandrani, K. S., Oosterhof, C. A., El Mansari, M., Blier, P. Tags: Original Papers Source Type: research
The role of distress intolerance for panic and nicotine withdrawal symptoms during a biological challenge
Conclusions:
Anxious responding in response to stressful experiences may explain the impact of perceived distress intolerance on panic and nicotine withdrawal symptom expression. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Farris, S. G., Zvolensky, M. J., Otto, M. W., Leyro, T. M. Tags: Original Papers Source Type: research
Effects of glucose administration on category exclusion recognition
Previous research has produced discrepant findings as to whether glucose administration effects lead to enhanced recollection or arise only under dual-task conditions. The aim of the present research was to address these issues by firstly employing an alternative cognitively demanding paradigm that has been linked to hippocampal function, i.e. the Process Dissociation Procedure (PDP). A second aim was to use this paradigm to explore whether glucose affects qualitative aspects of memory function. To achieve these aims, the PDP task was administered to participants who had either consumed a glucose (25 g) or aspartame-sweete...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Brandt, K. R. Tags: Original Papers Source Type: research
Randomised clinical trial of the effects of prolonged-release melatonin, temazepam and zolpidem on slow-wave activity during sleep in healthy people
Current pharmacological treatments for insomnia include benzodiazepine and non-benzodiazepine hypnotics targeting -aminobutyric acid (GABA)A receptors, as well as agonists of the melatonin receptors MT1 and MT2. Melatonin, temazepam and zolpidem are thought to exert their effect through different mechanisms of action, but whether this leads to differential effects on electroencephalogram (EEG) power spectra during sleep in middle-aged people is currently not known. To establish whether the effects of prolonged-release melatonin (2 mg) on the nocturnal sleep EEG are different to those of temazepam (20 mg) and zolpidem (10 m...
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Arbon, E. L., Knurowska, M., Dijk, D.-J. Tags: Original Papers Source Type: research
Omega-3 polyunsaturated fatty acid supplementation and cognition: A systematic review and meta-analysis
Conclusions:
There is marginal evidence that n-3 PUFA supplementation effects cognition in those who are n-3 PUFA deficient. However, there is no evidence of an effect in the general population or those with neurodevelopmental disorders. This has important implications given the widespread advertisement and consumption of n-3 PUFA; claims of cognitive benefit should be narrowed. (Source: Journal of Psychopharmacology)
Source: Journal of Psychopharmacology - June 15, 2015 Category: Psychiatry Authors: Cooper, R. E., Tye, C., Kuntsi, J., Vassos, E., Asherson, P. Tags: Review Source Type: research
GHB for cataplexy: Possible mode of action
The sleep disorder narcolepsy is caused by the loss of orexinergic neurones in the lateral hypothalamus. A troublesome symptom of narcolepsy is cataplexy, the sudden loss of muscle tone in response to strong emotions. It can be alleviated by antidepressants and sodium oxybate (-hydroxybutyric acid (GHB)). It is likely that the noradrenergic nucleus locus coeruleus (LC) is involved since it is essential for the maintenance of muscle tone, and ceases to fire during cataplectic attacks. Furthermore, alpha-2 adrenoceptors proliferate in the LC in cataplexy, probably due to ‘heterologous denervation supersensitivity&rsquo...
Source: Journal of Psychopharmacology - June 4, 2015 Category: Psychiatry Authors: Szabadi, E. Tags: Perspectives Source Type: research
3-Methyl-methcathinone: Pharmacokinetic profile evaluation in pigs in relation to pharmacodynamics
3-Methyl-methcathinone (3-MMC) is a novel, synthetic cathinone analog, recently linked to poisoning events among recreational users. The lack of pharmacological data on 3-MMC, prompted us to explore its pharmacokinetic profile as well as its effect on feeding behavior, weight gain, and serum biochemistry. 3-MMC was administered to male pigs (n=3, three months old) as a single intravenous dose (0.3 mg/kg), followed by a multiple oral dose administration (3 mg/kg) for five days and plasma and tissue concentrations determined. Concomitantly a control group consisting of two healthy male pigs received saline solution instead o...
Source: Journal of Psychopharmacology - June 4, 2015 Category: Psychiatry Authors: Shimshoni, J. A., Britzi, M., Sobol, E., Willenz, U., Nutt, D., Edery, N. Tags: Original Papers Source Type: research
