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Psychiatry and transport

Andrew Kl Goey, Tristan M Sissung, Cody J Peer, William D Figg
The histone deacetylase inhibitor valproic acid (VPA) has been used for many decades in neurology and psychiatry. The more recent introduction of the histone deacetylase inhibitors (HDIs) belinostat, romidepsin and vorinostat for treatment of hematological malignancies indicates the increasing popularity of these agents. Belinostat, romidepsin and vorinostat are metabolized or transported by polymorphic enzymes or drug transporters. Thus, genotype-directed dosing could improve pharmacotherapy by reducing the risk of toxicities or preventing suboptimal treatment...
October 21, 2016: Pharmacogenomics
Dilip V Jeste, Dan G Blazer, Kathleen C Buckwalter, Keri-Leigh K Cassidy, Len Fishman, Lisa P Gwyther, Saul M Levin, Christopher Phillipson, Ramesh R Rao, Ellen Schmeding, William A Vega, Julie A Avanzino, Danielle K Glorioso, John Feather
Older adults consistently prefer aging in place, which requires a high level of community support and services that are currently lacking. With a rapidly aging population, the present infrastructure for healthcare will prove even more inadequate to meet seniors' physical and mental health needs. A paradigm shift away from the sole focus on delivery of interventions at an individual level to more prevention-focused, community-based approaches will become essential. Recent initiatives have been proposed to promote healthy lifestyles and preventive care to enable older adults to age in place...
July 28, 2016: American Journal of Geriatric Psychiatry
Soumaya Boudokhane, Amine Kalai, Aymen Haj Salah, Houda Migaou, Sana Salah, Anis Jellad, Mourad Gahbiche, Zohra Ben Salah Frih
OBJECTIVE: The aim of our study was to determine the demographic characteristics and the pathway of severe traumatic brain injury (STBI) victims in the Tunisian population. MATERIAL/PATIENTS AND METHODS: Our study included 26 patients victims of STBI hospitalized in intensive care unit, among 450 traumatic head injuries admitted to the Teaching Hospital of Fattouma Bourguiba in Monastir during the year 2014. The studied parameters were: demographic characteristics of the population, circumstances of the accident, transport modalities to the hospital, assessments of the injury types, duration of coma, length of hospitalization in the Intensive Care Unit (ICU) and finally the discharge mode after the ICU stay (transfer to neurosurgery ward, to rehabilitation unit, or home discharged)...
September 2016: Annals of Physical and Rehabilitation Medicine
A Desai, J M Sequeira, E V Quadros
Folate receptor alpha (FRα) autoantibodies have been associated with fetal abnormalities and cerebral folate deficiency-related developmental disorders. Over 70% of the children with autism spectrum disorders (ASD) are positive for these autoantibodies and high-dose folinic acid is beneficial in treating these children. Here we show that antibodies (Abs) to the rat FRα administered during gestation produce communication, learning and cognitive deficits in a rat model that can be prevented by folinic acid and dexamethasone...
September 20, 2016: Molecular Psychiatry
S E Legge, M L Hamshere, S Ripke, A F Pardinas, J I Goldstein, E Rees, A L Richards, G Leonenko, L F Jorskog, K D Chambert, D A Collier, G Genovese, I Giegling, P Holmans, A Jonasdottir, G Kirov, S A McCarroll, J H MacCabe, K Mantripragada, J L Moran, B M Neale, H Stefansson, D Rujescu, M J Daly, P F Sullivan, M J Owen, M C O'Donovan, J T R Walters
The antipsychotic clozapine is uniquely effective in the management of schizophrenia; however, its use is limited by its potential to induce agranulocytosis. The causes of this, and of its precursor neutropenia, are largely unknown, although genetic factors have an important role. We sought risk alleles for clozapine-associated neutropenia in a sample of 66 cases and 5583 clozapine-treated controls, through a genome-wide association study (GWAS), imputed human leukocyte antigen (HLA) alleles, exome array and copy-number variation (CNV) analyses...
July 12, 2016: Molecular Psychiatry
C Bonvicini, S V Faraone, C Scassellati
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug...
July 2016: Molecular Psychiatry
J R Swartz, A R Hariri, D E Williamson
Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness...
May 24, 2016: Molecular Psychiatry
Andreas Heinz, Florian Schlagenhauf, Anne Beck, Carolin Wackerhagen
It has been questioned that the more than 300 mental disorders currently listed in international disease classification systems all have a distinct neurobiological correlate. Here, we support the idea that basic dimensions of mental dysfunctions, such as alterations in reinforcement learning, can be identified, which interact with individual vulnerability and psychosocial stress factors and, thus, contribute to syndromes of distress across traditional nosological boundaries. We further suggest that computational modeling of learning behavior can help to identify specific alterations in reinforcement-based decision-making and their associated neurobiological correlates...
August 2016: Journal of Neural Transmission
F Z Marques, N Eikelis, R G Bayles, E A Lambert, N E Straznicky, D Hering, M D Esler, G A Head, D A Barton, M P Schlaich, G W Lambert
Norepinephrine released from sympathetic nerves is removed from the neuroeffector junction via the action of the norepinephrine transporter (NET). NET impairment is evident in several clinically important conditions including major depressive disorder (MDD), panic disorder (PD), essential hypertension and the postural orthostatic tachycardia syndrome (POTS). We aimed to determine whether a single nucleotide polymorphism (SNP) in the 3' untranslated region (UTR) of the NET gene is associated with NET impairment and to elucidate the mechanisms involved...
April 5, 2016: Molecular Psychiatry
A Elif Anıl Yağcioğlu, Gökhan Yoca, Yavuz Ayhan, R Özgür Karaca, Lokman Çevik, Ahmet Müderrisoğlu, Mustafa T Göktaş, Nurhayat Eni, M Kâzım Yazıcı, Atilla Bozkurt, Melih O Babaoğlu
Clozapine use is associated with leukopenia and more rarely agranulocytosis, which may be lethal. The drug and its metabolites are proposed to interact with the multidrug resistance transporter (ABCB1/MDR1) gene product, P-glycoprotein (P-gp). Among various P-glycoprotein genetic polymorphisms, nucleotide changes in exons 26 (C3435T), 21 (G2677T), and 12 (C1236T) have been implicated for changes in pharmacokinetics and pharmacodynamics of many substrate drugs. In this study, we aimed to investigate the association between these specific ABCB1 polymorphisms and clozapine-associated agranulocytosis (CAA)...
June 2016: Journal of Clinical Psychopharmacology
A C Pereira, J D Gray, J F Kogan, R L Davidson, T G Rubin, M Okamoto, J H Morrison, B S McEwen
Alzheimer's disease (AD) and age-related cognitive decline represent a growing health burden and involve the hippocampus, a vulnerable brain region implicated in learning and memory. To understand the molecular effects of aging on the hippocampus, this study characterized the gene expression changes associated with aging in rodents using RNA-sequencing (RNA-seq). The glutamate modulator, riluzole, which was recently shown to improve memory performance in aged rats, prevented many of the hippocampal age-related gene expression changes...
March 29, 2016: Molecular Psychiatry
H Wesseling, B Xu, E J Want, E Holmes, P C Guest, M Karayiorgou, J A Gogos, S Bahn
Deletions on chromosome 22q11.2 are a strong genetic risk factor for development of schizophrenia and cognitive dysfunction. We employed shotgun liquid chromatography-mass spectrometry (LC-MS) proteomic and metabonomic profiling approaches on prefrontal cortex (PFC) and hippocampal (HPC) tissue from Df(16)A(+/-) mice, a model of the 22q11.2 deletion syndrome. Proteomic results were compared with previous transcriptomic profiling studies of the same brain regions. The aim was to investigate how the combined effect of the 22q11...
March 22, 2016: Molecular Psychiatry
Shannon Reidt, Haley Holtan, Jennifer Stender, Toni Salvatore, Bruce Thompson
OBJECTIVES: To describe the integration of home-based Medication Therapy Management (MTM) into the ambulatory care infrastructure of a large urban health system and to discuss the outcomes of this service. SETTING: Minnesota from September 2012 to December 2013. The health system has more than 50 primary care and specialty clinics. Eighteen credentialed MTM pharmacists are located in 16 different primary care and specialty settings, with the greatest number of pharmacists providing services in the internal medicine clinic...
March 2016: Journal of the American Pharmacists Association: JAPhA
Sharon Stephan, Nancy Lever, Larraine Bernstein, Sarah Edwards, David Pruitt
OBJECTIVE: The purpose of this study was to describe the potential and limits of school telemental health (TMH) to support a full continuum from mental health promotion to intervention, particularly for students less likely to access community care. METHODS: A review of school TMH literature and model programs, and of data from focus groups with child psychiatry fellows, was undertaken to inform best practices and future directions for TMH in schools. RESULTS: Existing data suggest that TMH with children and adolescents is promising and well received...
April 2016: Journal of Child and Adolescent Psychopharmacology
M A Lebow, A Chen
The bed nucleus of the stria terminalis (BNST) is a center of integration for limbic information and valence monitoring. The BNST, sometimes referred to as the extended amygdala, is located in the basal forebrain and is a sexually dimorphic structure made up of between 12 and 18 sub-nuclei. These sub-nuclei are rich with distinct neuronal subpopulations of receptors, neurotransmitters, transporters and proteins. The BNST is important in a range of behaviors such as: the stress response, extended duration fear states and social behavior, all crucial determinants of dysfunction in human psychiatric diseases...
April 2016: Molecular Psychiatry
S Ozcelik, F Sprenger, Z Skachokova, G Fraser, D Abramowski, F Clavaguera, A Probst, S Frank, M Müller, M Staufenbiel, M Goedert, M Tolnay, D T Winkler
Abundant tau inclusions are a defining hallmark of several human neurodegenerative diseases, including Alzheimer's disease. Protein fragmentation is a widely observed event in neurodegenerative proteinopathies. The relevance of tau fragmentation for the neurodegenerative process in tauopathies has yet remained unclear. Here we found that co-expression of truncated and full-length human tau in mice provoked the formation of soluble high-molecular-weight tau, the failure of axonal transport, clumping of mitochondria, disruption of the Golgi apparatus and missorting of synaptic proteins...
February 2, 2016: Molecular Psychiatry
J Borg, S Cervenka, R Kuja-Halkola, G J Matheson, E G Jönsson, P Lichtenstein, S Henningsson, T Ichimiya, H Larsson, P Stenkrona, C Halldin, L Farde
The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about the regulation of receptor and transporter density levels. This lack of knowledge obscures interpretation of differences in protein availability reported in psychiatric patients. In this study, we used positron emission tomography (PET) in a twin design to estimate the relative contribution of genetic and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain...
August 2016: Molecular Psychiatry
C Garcia-Keller, Y M Kupchik, C D Gipson, R M Brown, S Spencer, F Bollati, M A Esparza, D J Roberts-Wolfe, J A Heinsbroek, A-C Bobadilla, L M Cancela, P W Kalivas
There is substantial comorbidity between stress disorders and substance use disorders (SUDs), and acute stress augments the locomotor stimulant effect of cocaine in animal models. Here we endeavor to understand the neural underpinnings of comorbid stress disorders and drug use by determining whether the glutamatergic neuroadaptations that characterize cocaine self-administration are induced by acute stress. Rats were exposed to acute (2 h) immobilization stress, and 3 weeks later the nucleus accumbens core was examined for changes in glutamate transport, glutamate-mediated synaptic currents and dendritic spine morphology...
August 2016: Molecular Psychiatry
I Loryan, E Melander, M Svensson, M Payan, F König, B Jansson, M Hammarlund-Udenaes
The current study provides a novel in-depth assessment of the extent of antipsychotic drugs transport across the blood-brain barrier (BBB) into various brain regions, as well as across the blood-spinal cord barrier (BSCB) and the blood-cerebrospinal fluid barrier (BCSFB). This is combined with an estimation of cellular barrier transport and a systematic evaluation of nonspecific brain tissue binding. The study is based on the new Combinatory Mapping Approach (CMA), here further developed for the assessment of unbound drug neuropharmacokinetics in regions of interest (ROI), referred as CMA-ROI...
January 26, 2016: Molecular Psychiatry
N Amram, G Hacohen-Kleiman, S Sragovich, A Malishkevich, J Katz, O Touloumi, R Lagoudaki, N C Grigoriadis, E Giladi, A Yeheskel, M Pasmanik-Chor, Y Jouroukhin, I Gozes
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences...
October 2016: Molecular Psychiatry
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