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Psychiatry pharmacology

J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
X Jégouzo, M Desbordes, S Delègue, G Le Vacon, M Patrick, S Mouchabac
OBJECTIVES: Behavioral and psychological symptoms have a high prevalence in dementia. They include mood disorders, psychotic disorders and behavioral disorders such as aggression or screaming. Despite a number of side effects and an increased mortality, antipsychotic drugs are widely prescribed for treatment of this disorder. In France, this increased risk of mortality led in 2009 to the adoption of guidelines concerning all antipsychotics. The guidelines propose a sensible use of antipsychotics after the establishment of non-pharmacological measures...
October 12, 2016: L'Encéphale
Agustín Ibáñez, Adolfo M García, Sol Esteves, Adrián Yoris, Edinson Muñoz, Lucila Reynaldo, Marcos Luis Pietto, Federico Adolfi, Facundo Manes
Multiple disorders once jointly conceived as 'nervous diseases' became segregated by the distinct institutional traditions forged in neurology and psychiatry. As a result, each field specialized in the study and treatment of a subset of such conditions. Here we propose new avenues for interdisciplinary interaction through a triangulation of both fields with social neuroscience. To this end, we review evidence from five relevant domains (facial emotion recognition, empathy, theory of mind, moral cognition, social context assessment), highlighting their common disturbances across neurological and psychiatric conditions and discussing their multiple pathophysiological mechanisms...
October 6, 2016: Social Neuroscience
F Razoux, H Russig, T Mueggler, C Baltes, K Dikaiou, M Rudin, I M Mansuy
Traumatic stress in early life is a strong risk factor for psychiatric disorders that can affect individuals across several generations. Although the underlying mechanisms have been proposed to implicate serotonergic transmission in the brain, the neural circuits involved remain poorly delineated. Using pharmacological functional magnetic resonance imaging in mice, we demonstrate that traumatic stress in postnatal life alters 5-HT1A receptor-evoked local and global functions in both, the exposed animals and their progeny when adult...
September 27, 2016: Molecular Psychiatry
Matteo F Olivieri, Francesca Marzari, Andreas J Kesel, Laura Bonalume, Francesco Saettini
Melampus is a seer-healer of Greek myth attributed with having healed the young princesses of Argos of madness. Analysis of this legend and its sources sheds light on the early stages of the "medicalizing" shift in the history of ancient Greek medicine. Retrospective psychological diagnosis suggests that the descriptions of the youths' madness rose from actual observation of behavioral and mental disorders. Melampus is credited with having healed them by administering hellebore. Pharmacological analysis of botanical specimens proves that Helleborus niger features actual neurological properties effective in the treatment of mental disorders...
September 13, 2016: Journal of the History of the Neurosciences
C D Pandya, N Hoda, A Crider, D Peter, A Kutiyanawalla, S Kumar, A O Ahmed, G Turecki, C M Hernandez, A V Terry, A Pillai
Serotonin (5-hydroxytryptamine, 5-HT) and brain-derived neurotrophic factor (BDNF) are two signaling molecules that have important regulatory roles in the development and plasticity of neural circuits that are known to be altered in depression. However, the mechanism by which 5-HT regulates BDNF signaling is unknown. In the present study, we found that 5-HT treatment increases BDNF receptor, TrkB (tropomyosin related kinase B), levels in mouse primary cortical neurons via a Rac1 (RAS-related C3 botulinum toxin substrate 1)-dependent mechanism...
September 13, 2016: Molecular Psychiatry
A Pérez-Cañamás, S Benvegnù, C B Rueda, A Rábano, J Satrústegui, M D Ledesma
Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient...
September 13, 2016: Molecular Psychiatry
R Zhang, M Asai, C E Mahoney, M Joachim, Y Shen, G Gunner, J A Majzoub
A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, whereas extra-hypothalamic CRH has a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex...
September 6, 2016: Molecular Psychiatry
E Lax, A Friedman, R Massart, R Barnea, L Abraham, D Cheishvili, M Zada, H Ahdoot, T Bareli, G Warhaftig, L Visochek, M Suderman, M Cohen-Armon, M Szyf, G Yadid
Reward-related memory is an important factor in cocaine seeking. One necessary signaling mechanism for long-term memory formation is the activation of poly(ADP-ribose) polymerase-1 (PARP-1), via poly(ADP-ribosyl)ation. We demonstrate herein that auto-poly(ADP-ribosyl)ation of activated PARP-1 was significantly pronounced during retrieval of cocaine-associated contextual memory, in the central amygdala (CeA) of rats expressing cocaine-conditioned place preference (CPP). Intra-CeA pharmacological and short hairpin RNA depletion of PARP-1 activity during cocaine-associated memory retrieval abolished CPP...
September 6, 2016: Molecular Psychiatry
K Radenbach, J Retzlik, S H Meyer-Rötz, C Wolff-Menzler, J Wolff, H Esselmann, F Godemann, M Riemenschneider, J Wiltfang, F Jessen
BACKGROUND: Dementia is of increasing medical and societal relevance. Hospitalization of dementia patients is mostly due to behavioral and psychological symptoms of dementia (BPSD). There is a need for sufficient qualified personnel in hospitals in order to be able to effectively treat these symptoms. OBJECTIVES: This study aims at identifying the personnel requirements for guideline-conform, evidence-based inpatient treatment concepts for patients with BPSD and to compare these with the resources defined by the German psychiatric personnel regulations (Psych-PV)...
August 31, 2016: Der Nervenarzt
A Caccamo, E Ferreira, C Branca, S Oddo
The multifunctional protein p62 is associated with neuropathological inclusions in several neurodegenerative disorders, including frontotemporal lobar degeneration, amyotrophic lateral sclerosis and Alzheimer's disease (AD). Strong evidence shows that in AD, p62 immunoreactivity is associated with neurofibrillary tangles and is involved in tau degradation. However, it remains to be determined whether p62 also plays a role in regulating amyloid-β (Aβ) aggregation and degradation. Using a gene therapy approach, here we show that increasing brain p62 expression rescues cognitive deficits in APP/PS1 mice, a widely used animal model of AD...
August 30, 2016: Molecular Psychiatry
Soumya P Thomas, A Nisha, P Joseph Varghese
BACKGROUND: Despite significant advances in pharmacological and psychological therapies for bipolar disorder, many people continue to have less than optimal outcomes, which are associated with significant disability and poor quality of life (QOL). This study aimed to assess the disability and QOL and factors associated with such suboptimal outcomes in subjects with bipolar disorder in remission. METHODS: Consecutive patients diagnosed to have bipolar disorder in remission attending the Department of Psychiatry, MOSC Medical College, Kerala, India were recruited for the study...
July 2016: Indian Journal of Psychological Medicine
Himanshu Sharma
Background-The Placebo is defined as an inert substance with a potent therapeutic effect. Its effect is attributed to its psychological and neurobiological effect. Its use in Psychiatric drug practice in drug trials and clinical practice is common, especially in India .Currently there is a debate whether to use it or not as there are ethical, moral and legal issues. Also, its mechanism of action is not known. Discussion-The Indian Psychiatry scenario is muddled in relation to use of placebo in Randomized Controlled Trials or Psychiatric clinical practice...
August 10, 2016: Central Nervous System Agents in Medicinal Chemistry
Rif S El-Mallakh, R Jeannie Roberts, Peggy L El-Mallakh, Lillian Jan Findlay, Kristen K Reynolds
Pharmacogenomic testing in psychiatry is becoming an established clinical procedure. Several vendors provide clinical interpretation of combinatorial pharmacogenomic testing of gene variants that have documented predictive implications regarding either pharmacologic response or adverse effects in depression and other psychiatric conditions. Such gene profiles have demonstrated improvements in outcome in depression, and reduction of cost of care of patients with inadequate clinical response. Additionally, several new gene variants are being studied to predict specific response in individuals...
September 2016: Clinics in Laboratory Medicine
Patrick A Forcelli, Jacqueline T DesJardin, Elizabeth A West, Angela L Holmes, Catherine Elorette, Laurie L Wellman, Ludise Malkova
Brain circuitry underlying defensive behaviors includes forebrain modulatory sites, e.g., the amygdala and hypothalamus, and midbrain effector regions, such as the deep/intermediate layers of the superior colliculus (DLSC). When disinhibited, this network biases behavior towards reflexive defense reactions. While well characterized in rodent models, little is known about this system in the primate brain. Employing focal pharmacological manipulations, we have previously shown that activation of the DLSC triggers reflexive defensive responses, including cowering, escape behaviors, and defensive vocalizations...
August 10, 2016: Social Cognitive and Affective Neuroscience
B Wang, Y Liu, L Huang, J Chen, J J Li, R Wang, E Kim, Y Chen, C Justicia, K Sakata, H Chen, A Planas, R S Ostrom, W Li, G Yang, M P McDonald, R Chen, D H Heck, F-F Liao
Induction of neuroprotective heat-shock proteins via pharmacological Hsp90 inhibitors is currently being investigated as a potential treatment for neurodegenerative diseases. Two major hurdles for therapeutic use of Hsp90 inhibitors are systemic toxicity and limited central nervous system permeability. We demonstrate here that chronic treatment with a proprietary Hsp90 inhibitor compound (OS47720) not only elicits a heat-shock-like response but also offers synaptic protection in symptomatic Tg2576 mice, a model of Alzheimer's disease, without noticeable systemic toxicity...
July 26, 2016: Molecular Psychiatry
E P Bello, R Casas-Cordero, G L Galiñanes, E Casey, M A Belluscio, V Rodríguez, D Noaín, M G Murer, M Rubinstein
Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function...
July 19, 2016: Molecular Psychiatry
Julien Dupouey, Natalia Doudka, Séphora Belo, Olivier Blin, Romain Guilhaumou
Therapeutic drug monitoring of antiepileptic drugs is widely practiced to achieve optimal efficacy and avoid adverse side effects. We describe an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC/MS/MS) method developed for the monitoring of 4 frequently prescribed antiepileptic drugs including lamotrigine, levetiracetam, oxcarbazepine and topiramate. Main pharmacologically active metabolite of oxcarbazepine (mono-hydroxy-derivative metabolite, MHD) was also quantified. After addition of internal standards and a simple stage of protein precipitation, plasmatic samples were analyzed on a C18 column...
July 15, 2016: Biomedical Chromatography: BMC
Y Han, R J Heuermann, K A Lyman, D Fisher, Q-A Ismail, D M Chetkovich
Major depressive disorder (MDD) is a prevalent psychiatric condition with limited therapeutic options beyond monoaminergic therapies. Although effective in some individuals, many patients fail to respond adequately to existing treatments, and new pharmacologic targets are needed. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate excitability in neurons, and blocking HCN channel function has been proposed as a novel antidepressant strategy. However, systemic blockade of HCN channels produces cardiac effects that limit this approach...
July 12, 2016: Molecular Psychiatry
Juliane Mielau, Jasmin Altunbay, Andreas Heinz, Benedikt Reuter, Felix Bermpohl, Johannes Rentzsch, Anja Lehmann, Christiane Montag
Objective: This study explores patients' preferences and measures of prevention of coercive methods in psychiatric treatment. Methods: Structured interviews of 90 patients with psychotic disorders were undertaken, most of whom had previously experienced coercive methods. Results: Participants saw preventive potential in a wider availability of individual non-pharmacological therapy, improvement of staff professional competence and communication skills, high staff-to-patient ratios and retreat facilities. The majority of participants preferred forced medication and manual restraint in case of self-endangerment, and forced medication and mechanical restraint in the event of endangerment of others...
July 11, 2016: Psychiatrische Praxis
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