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Translational Psychiatry

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https://www.readbyqxmd.com/read/28323288/citalopram-amplifies-the-influence-of-living-conditions-on-mood-in-depressed-patients-enrolled-in-the-star-d-study
#1
F Chiarotti, A Viglione, A Giuliani, I Branchi
Selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed antidepressant drugs, have a variable and incomplete efficacy. In order to better understand SSRI action, we explored the hypothesis that SSRIs do not affect mood per se but amplify the influence of the living conditions on mood. To this aim, we exploited the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) data set, selected a subpopulation of 591 patients with an overlapping clinical history and analyzed treatment outcome according to dosage -20 or 40 mg per day of citalopram...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323287/experimental-medication-treatment-approaches-for-depression
#2
REVIEW
D F Ionescu, G I Papakostas
Depression is one of the most common psychiatric conditions. Symptoms can lead to significant disability, which result in impairments in overall quality of life. Though there are many approved antidepressant treatments for depression-including selective serotonin reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors-about a third of patients do not respond to these medications. Therefore, it is imperative for drug discovery to continue towards the development of novel and rapidly acting compounds, especially for patients with treatment-resistant depression...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323286/erythrocyte-glutathione-levels-as-long-term-predictor-of-transition-to-psychosis
#3
S Lavoie, M Berger, M Schlögelhofer, M R Schäfer, S Rice, S-W Kim, J Hesse, P D McGorry, S Smesny, G P Amminger
A high proportion of individuals deemed at elevated risk for psychosis will actually never progress to develop the illness. Pharmaceutical intervention may not be necessary in these cases, and may in fact be damaging depending on the invasiveness of the treatment strategy. This highlights the need for biomarkers that are better able to reliably differentiate between at-risk individuals who will subsequently transition to psychosis and those who will not. Low glutathione (GSH) levels have been observed in schizophrenia and in patients with first-episode psychosis...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323285/utilization-of-machine-learning-for-prediction-of-post-traumatic-stress-a-re-examination-of-cortisol-in-the-prediction-and-pathways-to-non-remitting-ptsd
#4
I R Galatzer-Levy, S Ma, A Statnikov, R Yehuda, A Y Shalev
To date, studies of biological risk factors have revealed inconsistent relationships with subsequent post-traumatic stress disorder (PTSD). The inconsistent signal may reflect the use of data analytic tools that are ill equipped for modeling the complex interactions between biological and environmental factors that underlay post-traumatic psychopathology. Further, using symptom-based diagnostic status as the group outcome overlooks the inherent heterogeneity of PTSD, potentially contributing to failures to replicate...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323284/altered-peripheral-immune-profiles-in-treatment-resistant-depression-response-to-ketamine-and-prediction-of-treatment-outcome
#5
D D Kiraly, S R Horn, N T Van Dam, S Costi, J Schwartz, S Kim-Schulze, M Patel, G E Hodes, S J Russo, M Merad, D V Iosifescu, D S Charney, J W Murrough
A subset of patients with depression have elevated levels of inflammatory cytokines, and some studies demonstrate interaction between inflammatory factors and treatment outcome. However, most studies focus on only a narrow subset of factors in a patient sample. In the current study, we analyzed broad immune profiles in blood from patients with treatment-resistant depression (TRD) at baseline and following treatment with the glutamate modulator ketamine. Serum was analyzed from 26 healthy control and 33 actively depressed TRD patients free of antidepressant medication, and matched for age, sex and body mass index...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323283/treadmill-exercise-suppressed-stress-induced-dendritic-spine-elimination-in-mouse-barrel-cortex-and-improved-working-memory-via-bdnf-trkb-pathway
#6
K Chen, L Zhang, M Tan, C S W Lai, A Li, C Ren, K-F So
Stress-related memory deficit is correlated with dendritic spine loss. Physical exercise improves memory function and promotes spinogenesis. However, no studies have been performed to directly observe exercise-related effects on spine dynamics, in association with memory function. This study utilized transcranial two-photon in vivo microscopy to investigate dendritic spine formation and elimination in barrel cortex of mice under physical constrain or naive conditions, followed by memory performance in a whisker-dependent novel texture discrimination task...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28323282/an-autism-associated-serotonin-transporter-variant-disrupts-multisensory-processing
#7
J K Siemann, C L Muller, C G Forsberg, R D Blakely, J Veenstra-VanderWeele, M T Wallace
Altered sensory processing is observed in many children with autism spectrum disorder (ASD), with growing evidence that these impairments extend to the integration of information across the different senses (that is, multisensory function). The serotonin system has an important role in sensory development and function, and alterations of serotonergic signaling have been suggested to have a role in ASD. A gain-of-function coding variant in the serotonin transporter (SERT) associates with sensory aversion in humans, and when expressed in mice produces traits associated with ASD, including disruptions in social and communicative function and repetitive behaviors...
March 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291264/abnormal-white-matter-structural-connectivity-in-adults-with-obsessive-compulsive-disorder
#8
J Gan, M Zhong, J Fan, W Liu, C Niu, S Cai, L Zou, Ya Wang, Yi Wang, C Tan, R C K Chan, X Zhu
Obsessive-compulsive disorder (OCD) is a complex and severe psychiatric disorder whose pathogenesis is not fully understood. Recent studies have shown white matter (WM) alterations in adults with OCD, but the results have been inconsistent. The present study investigated WM structure in OCD patients with the hypothesis that large-scale brain networks may be disrupted in OCD. A total of 24 patients with OCD and 23 healthy controls (HCs) were scanned with diffusion tensor imaging. A tract-based spatial statistics (TBSS) approach was used to detect differences across the whole brain in patients with OCD vs HCs; post hoc fiber tractography was applied to characterize developmental differences between the two groups...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291263/circumcision-does-not-alter-long-term-glucocorticoids-accumulation-or-psychological-effects-associated-with-trauma-and-stressor-related-disorders
#9
E Ullmann, J Licinio, A Barthel, K Petrowski, B Oratovski, T Stalder, C Kirschbaum, S R Bornstein
Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291262/effects-of-bumetanide-on-neurobehavioral-function-in-children-and-adolescents-with-autism-spectrum-disorders
#10
E Lemonnier, N Villeneuve, S Sonie, S Serret, A Rosier, M Roue, P Brosset, M Viellard, D Bernoux, S Rondeau, S Thummler, D Ravel, Y Ben-Ari
In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl(-))i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3-11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291261/modeling-anorexia-nervosa-transcriptional-insights-from-human-ipsc-derived-neurons
#11
P D Negraes, F R Cugola, R H Herai, C A Trujillo, A S Cristino, T Chailangkarn, A R Muotri, V Duvvuri
Anorexia nervosa (AN) is a complex and multifactorial disorder occurring predominantly in women. Despite having the highest mortality among psychiatric conditions, it still lacks robust and effective treatment. Disorders such as AN are most likely syndromes with multiple genetic contributions, however, genome-wide studies have been underpowered to reveal associations with this uncommon illness. Here, we generated induced pluripotent stem cells (iPSCs) from adolescent females with AN and unaffected controls...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291260/gene-expression-and-proliferation-biomarkers-for-antidepressant-treatment-resistance
#12
J Breitfeld, C Scholl, M Steffens, G Laje, J C Stingl
The neurotrophic hypothesis of depression suggests an association between effects on neuroplasticity and clinical response to antidepressant drug therapy. We studied individual variability in antidepressant drug effects on cell proliferation in lymphoblastoid cell lines (LCLs) from n=25 therapy-resistant patients versus n=25 first-line therapy responders from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Furthermore, the variability in gene expression of genes associated with cell proliferation was analyzed for tentative candidate genes for prediction of individual LCL donor's treatment response...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291259/infant-frontal-eeg-asymmetry-in-relation-with-postnatal-maternal-depression-and-parenting-behavior
#13
D J Wen, N N Soe, L W Sim, S Sanmugam, K Kwek, Y-S Chong, P D Gluckman, M J Meaney, A Rifkin-Graboi, A Qiu
Right frontal electroencephalogram (EEG) asymmetry associates with negative affect and depressed mood, which, among children, are predicted by maternal depression and poor parenting. This study examined associations of maternal depression and maternal sensitivity with infant frontal EEG asymmetry based on 111 mother-6-month-infant dyads. There were no significant effects of postnatal maternal depression or maternal sensitivity, or their interaction, on infant EEG frontal asymmetry. However, in a subsample for which the infant spent at least 50% of his/her day time hours with his/her mother, both lower maternal sensitivity and higher maternal depression predicted greater relative right frontal EEG asymmetry...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291258/adult-hippocampal-neuroplasticity-triggers-susceptibility-to-recurrent-depression
#14
N D Alves, J S Correia, P Patrício, A Mateus-Pinheiro, A R Machado-Santos, E Loureiro-Campos, M Morais, J M Bessa, N Sousa, L Pinto
Depression is a highly prevalent and recurrent neuropsychiatric disorder associated with alterations in emotional and cognitive domains. Neuroplastic phenomena are increasingly considered central to the etiopathogenesis of and recovery from depression. Nevertheless, a high number of remitted patients experience recurrent episodes of depression, remaining unclear how previous episodes impact on behavior and neuroplasticity and/or whether modulation of neuroplasticity is important to prevent recurrent depression...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28291257/integrated-transcriptome-and-methylome-analysis-in-youth-at-high-risk-for-bipolar-disorder-a-preliminary-analysis
#15
G R Fries, J Quevedo, C P Zeni, I F Kazimi, G Zunta-Soares, D E Spiker, C L Bowden, C Walss-Bass, J C Soares
First-degree relatives of patients with bipolar disorder (BD), particularly their offspring, have a higher risk of developing BD and other mental illnesses than the general population. However, the biological mechanisms underlying this increased risk are still unknown, particularly because most of the studies so far have been conducted in chronically ill adults and not in unaffected youth at high risk. In this preliminary study we analyzed genome-wide expression and methylation levels in peripheral blood mononuclear cells from children and adolescents from three matched groups: BD patients, unaffected offspring of bipolar parents (high risk) and controls (low risk)...
March 14, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28267152/effects-of-naltrexone-are-influenced-by-childhood-adversity-during-negative-emotional-processing-in-addiction-recovery
#16
G Savulich, R Riccelli, L Passamonti, M Correia, J F W Deakin, R Elliott, R S A Flechais, A R Lingford-Hughes, J McGonigle, A Murphy, D J Nutt, C Orban, L M Paterson, L J Reed, D G Smith, J Suckling, R Tait, E M Taylor, B J Sahakian, T W Robbins, K D Ersche
Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28267151/regulation-of-striatal-dopamine-responsiveness-by-notch-rbp-j-signaling
#17
M Toritsuka, S Kimoto, K Muraki, M Kitagawa, T Kishimoto, A Sawa, K Tanigaki
Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28267150/ablation-of-neuropsin-neuregulin-1-signaling-imbalances-erbb4-inhibitory-networks-and-disrupts-hippocampal-gamma-oscillation
#18
M Kawata, S Morikawa, S Shiosaka, H Tamura
Parvalbumin-expressing interneurons are pivotal for the processing of information in healthy brain, whereas the coordination of these functions is seriously disrupted in diseased brain. How these interneurons in the hippocampus participate in pathological functions remains unclear. We previously reported that neuregulin 1 (NRG1)-ErbB4 signaling, which is actuated by neuropsin, is important for coordinating brain plasticity. Neuropsin cleaves mature NRG1 (bound to extracellular glycosaminoglycans) in response to long-term potentiation or depression, liberating a soluble ligand that activates its receptor, ErbB4...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28267149/striatal-phosphodiesterase-10a-and-medial-prefrontal-cortical-thickness-in-patients-with-schizophrenia-a-pet-and-mri-study
#19
R Bodén, J Persson, A Wall, M Lubberink, L Ekselius, E-M Larsson, G Antoni
The enzyme phosphodiesterase 10A (PDE10A) is abundant in striatal medium spiny neurons and has been implicated in the pathophysiology of schizophrenia in animal models and is investigated as a possible new pharmacological treatment target. A reduction of prefrontal cortical thickness is common in schizophrenia, but how this relates to PDE10A expression is unknown. Our study aim was to compare, we believe for the first time, the striatal non-displaceable binding potential (BPND) of the new validated PDE10A ligand [(11)C]Lu AE92686 between patients with schizophrenia and healthy controls...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28267148/elevated-hair-cortisol-concentrations-in-recently-fled-asylum-seekers-in-comparison-to-permanently-settled-immigrants-and-non-immigrants
#20
R Mewes, H Reich, N Skoluda, F Seele, U M Nater
Recently fled asylum seekers generally live in stressful conditions. Their residency status is mostly insecure and, similar to other immigrants, they experience stress due to acculturation. Moreover, they often suffer from traumatization and posttraumatic stress disorder (PTSD). All of these factors can result in chronic maladaptive biological stress responses in terms of hyper- or hypocortisolism and, ultimately, illness. We believe the current study is the first to compare hair cortisol concentration (HCC) of recently fled asylum seekers with PTSD to those without PTSD, and to compare HCC of asylum seekers to HCC of permanently settled immigrants and non-immigrant individuals...
March 7, 2017: Translational Psychiatry
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