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Biological Psychiatry

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https://www.readbyqxmd.com/read/29275840/brain-stimulation-over-the-frontopolar-cortex-enhances-motivation-to-exert-effort-for-reward
#1
Alexander Soutschek, Pyungwon Kang, Christian C Ruff, Todd A Hare, Philippe N Tobler
BACKGROUND: Loss of motivation is a characteristic feature of several psychiatric and neurological disorders. However, the neural mechanisms underlying human motivation are far from being understood. Here, we investigate the role that the frontopolar cortex (FPC) plays in motivating cognitive and physical effort exertion by computing subjective effort equivalents. METHODS: We manipulated neural processing with transcranial direct current stimulation targeting the FPC while 141 healthy participants decided whether or not to engage in cognitive or physical effort to obtain rewards...
December 22, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29325847/amphetamine-induced-striatal-dopamine-release-measured-with-an-agonist-radiotracer-in%C3%A2-schizophrenia
#2
W Gordon Frankle, Jennifer Paris, Michael Himes, N Scott Mason, Chester A Mathis, Rajesh Narendran
BACKGROUND: Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH...
December 7, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29279202/the-emerging-relationship-between-interstitial-fluid-cerebrospinal-fluid-exchange-amyloid-%C3%AE-and-sleep
#3
REVIEW
Erin L Boespflug, Jeffrey J Iliff
Amyloid-β (Aβ) plaques are a key histopathological hallmark of Alzheimer's disease (AD), and soluble Aβ species are believed to play an important role in the clinical development of this disease. Emerging biomarker data demonstrate that Aβ plaque deposition begins decades before the onset of clinical symptoms, suggesting that understanding the biological determinants of the earliest steps in the development of AD pathology may provide key opportunities for AD treatment and prevention. Although a clinical association between sleep disruption and AD has long been appreciated, emerging clinical studies and insights from the basic neurosciences have shed important new light on how sleep and Aβ homeostasis may be connected in the setting of AD...
December 7, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29325848/a-genetic-investigation-of-sex-bias-in-the-prevalence-of-attention-deficit-hyperactivity-disorder
#4
Joanna Martin, Raymond K Walters, Ditte Demontis, Manuel Mattheisen, S Hong Lee, Elise Robinson, Isabell Brikell, Laura Ghirardi, Henrik Larsson, Paul Lichtenstein, Nicholas Eriksson, Thomas Werge, Preben Bo Mortensen, Marianne Giørtz Pedersen, Ole Mors, Merete Nordentoft, David M Hougaard, Jonas Bybjerg-Grauholm, Naomi R Wray, Barbara Franke, Stephen V Faraone, Michael C O'Donovan, Anita Thapar, Anders D Børglum, Benjamin M Neale
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is two to seven times more common in male individuals than in female individuals. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. METHODS: We analyzed genome-wide autosomal common variants from the Psychiatric Genomics Consortium and iPSYCH Project (n = 20,183 cases, n = 35,191 controls) and Swedish population register data (n = 77,905 cases, n = 1,874,637 population controls)...
December 2, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29198469/novel-small-molecule-inhibitors-of-protein-kinase%C3%A2-c-epsilon-reduce-ethanol-consumption-in%C3%A2-mice
#5
Angelo Blasio, Jingyi Wang, Dan Wang, Florence P Varodayan, Matthew B Pomrenze, Jacklyn Miller, Anna M Lee, Thomas McMahon, Sandeep Gyawali, Hua-Yu Wang, Marisa Roberto, Stanton McHardy, Michael A Pleiss, Robert O Messing
BACKGROUND: Despite the high cost and widespread prevalence of alcohol use disorders, treatment options are limited, underscoring the need for new, effective medications. Previous results using protein kinase C epsilon (PKCε) knockout mice, RNA interference against PKCε, and peptide inhibitors of PKCε predict that small-molecule inhibitors of PKCε should reduce alcohol consumption in humans. METHODS: We designed a new class of PKCε inhibitors based on the Rho-associated protein kinase (ROCK) inhibitor Y-27632...
December 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29279203/response-to-the-consensus-statement-of-the-ptsd-psychopharmacology-working-group
#6
LETTER
Allison A Feduccia, Michael C Mithoefer, Lisa Jerome, Julie Holland, Amy Emerson, Rick Doblin
No abstract text is available yet for this article.
November 23, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29331353/mechanisms-of-sex-differences-in-fear-and-posttraumatic-stress-disorder
#7
REVIEW
Teniel Sonya Ramikie, Kerry James Ressler
Following sexual maturity, females disproportionately have higher rates of posttraumatic stress disorder (PTSD) and experience greater symptom severity and chronicity as compared with males. This observation has led many to examine sex differences in PTSD risk factors. Though relatively few, these studies reveal that the root causes of PTSD sex differences are complex, and partly represent interactions between sex-specific nonbiological and biological risk factors, which differentially shape PTSD vulnerability...
November 21, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29305086/the-candidate-schizophrenia-risk-gene-dgcr2-regulates-early-steps-of-corticogenesis
#8
Aude Molinard-Chenu, Alexandre Dayer
BACKGROUND: Alterations in early steps of cortical circuit assembly are thought to play a critical role in vulnerability to schizophrenia (SZ), but the pathogenic impact of SZ-risk mutations on corticogenesis remains to be determined. DiGeorge syndrome critical region 2 (DGCR2) is located in the 22q11.2 locus, whose deletion is a major risk factor for SZ. Moreover, exome sequencing of individuals with idiopathic SZ identified a rare missense mutation in DGCR2, further suggesting that DGCR2 is involved in SZ...
November 21, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29301614/metabotropic-glutamate-receptors-2-and-3-as-targets-for-treating-nicotine-addiction
#9
REVIEW
Alan J Cross, Robert Anthenelli, Xia Li
Tobacco smoking, driven by the addictive properties of nicotine, continues to be a worldwide health problem. Based on the well-established role of glutamatergic neurotransmission in drug addiction, novel medication development strategies seek to halt nicotine consumption and prevent relapse to tobacco smoking by modulating glutamate transmission. The presynaptic inhibitory metabotropic glutamate receptors 2 and 3 (mGluR2/3) are key autoreceptors on glutamatergic terminals that maintain glutamate homeostasis...
November 21, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29331354/specificity-in-etiology-of-subtypes-of-bipolar-disorder-evidence-from-a-swedish-population-based-family-study
#10
Jie Song, Ralf Kuja-Halkola, Arvid Sjölander, Sarah E Bergen, Henrik Larsson, Mikael Landén, Paul Lichtenstein
BACKGROUND: Uncertainty remains whether bipolar I disorder (BDI) and bipolar II disorder (BDII) differ etiologically. We used a population-based family sample to examine the etiological boundaries between BDI and BDII by assessing their familial aggregation/coaggregation and by assessing the coaggregation between them and schizophrenia, depression, attention-deficit/hyperactivity disorder, eating disorders, autism spectrum disorder, substance use disorders, anxiety disorders, and personality disorders...
November 20, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29290371/mitochondrial-etiology-of-neuropsychiatric-disorders
#11
REVIEW
Liming Pei, Douglas C Wallace
The brain has the highest mitochondrial energy demand of any organ. Therefore, subtle changes in mitochondrial energy production will preferentially affect the brain. Considerable biochemical evidence has accumulated revealing mitochondrial defects associated with neuropsychiatric diseases. Moreover, the mitochondrial genome encompasses over a thousand nuclear DNA genes plus hundreds to thousands of copies of the maternally inherited mitochondrial DNA (mtDNA). Therefore, partial defects in either the nuclear DNA or mtDNA genes or combinations of the two can be sufficient to cause neuropsychiatric disorders...
November 20, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29275839/the-multifaceted-role-of-the-ventromedial-prefrontal-cortex-in-emotion-decision-making-social-cognition-and-psychopathology
#12
REVIEW
Jaryd Hiser, Michael Koenigs
The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala...
November 20, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29295738/psychiatry-in-a-dish-stem-cells-and-brain-organoids-modeling-autism-spectrum-disorders
#13
REVIEW
Mirolyba Ilieva, Åsa Fex Svenningsen, Morten Thorsen, Tanja Maria Michel
Autism spectrum disorders are a group of pervasive neurodevelopmental conditions with heterogeneous etiology, characterized by deficits in social cognition, communication, and behavioral flexibility. Despite an increasing scientific effort to find the pathophysiological explanations for the disease, the neurobiological links remain unclear. A large amount of evidence suggests that pathological processes taking place in early embryonic neurodevelopment might be responsible for later manifestation of autistic symptoms...
November 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29279201/replication-in-imaging-genetics-the-case-of-threat-related-amygdala-reactivity
#14
Reut Avinun, Adam Nevo, Annchen R Knodt, Maxwell L Elliott, Ahmad R Hariri
BACKGROUND: Low replication rates are a concern in most, if not all, scientific disciplines. In psychiatric genetics specifically, targeting intermediate brain phenotypes, which are more closely associated with putative genetic effects, was touted as a strategy leading to increased power and replicability. In the current study, we attempted to replicate previously published associations between single nucleotide polymorphisms and threat-related amygdala reactivity, which represents a robust brain phenotype not only implicated in the pathophysiology of multiple disorders, but also used as a biomarker of future risk...
November 16, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29275841/the-mediodorsal-thalamus-an-essential-partner-of-the-prefrontal-cortex-for-cognition
#15
REVIEW
Sébastien Parnaudeau, Scott S Bolkan, Christoph Kellendonk
Deficits in cognition are a core feature of many psychiatric conditions, including schizophrenia, where the severity of such deficits is a strong predictor of long-term outcome. Impairment in cognitive domains such as working memory and behavioral flexibility has typically been associated with prefrontal cortex (PFC) dysfunction. However, there is increasing evidence that the PFC cannot be dissociated from its main thalamic counterpart, the mediodorsal thalamus (MD). Since the causal relationships between MD-PFC abnormalities and cognitive impairment, as well as the neuronal mechanisms underlying them, are difficult to address in humans, animal models have been employed for mechanistic insight...
November 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29289333/understanding-neurodevelopmental-disorders-the-promise-of-regulatory-variation-in-the-3-utrome
#16
REVIEW
Kai A Wanke, Paolo Devanna, Sonja C Vernes
Neurodevelopmental disorders have a strong genetic component, but despite widespread efforts, the specific genetic factors underlying these disorders remain undefined for a large proportion of affected individuals. Given the accessibility of exome sequencing, this problem has thus far been addressed from a protein-centric standpoint; however, protein-coding regions only make up ∼1% to 2% of the human genome. With the advent of whole genome sequencing we are in the midst of a paradigm shift as it is now possible to interrogate the entire sequence of the human genome (coding and noncoding) to fill in the missing heritability of complex disorders...
November 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29146047/maternal-immune-activation-delays-excitatory-to-inhibitory-gamma-aminobutyric-acid-switch-in-offspring
#17
Irene Corradini, Elisa Focchi, Marco Rasile, Raffaella Morini, Genni Desiato, Romana Tomasoni, Michela Lizier, Elsa Ghirardini, Riccardo Fesce, Diego Morone, Isabella Barajon, Flavia Antonucci, Davide Pozzi, Michela Matteoli
BACKGROUND: The association between maternal infection and neurodevelopmental defects in progeny is well established, although the biological mechanisms and the pathogenic trajectories involved have not been defined. METHODS: Pregnant dams were injected intraperitoneally at gestational day 9 with polyinosinic:polycytidylic acid. Neuronal development was assessed by means of electrophysiological, optical, and biochemical analyses. RESULTS: Prenatal exposure to polyinosinic:polycytidylic acid causes an imbalanced expression of the Na+-K+-2Cl- cotransporter 1 and the K+-Cl- cotransporter 2 (KCC2)...
November 14, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29258653/exploring-the-role-of-astroglial-glutamate-release-and-association-with-synapses-in-neuronal-function-and-behavior
#18
REVIEW
Michael D Scofield
Astrocytes are stellate cells whose appearance can resemble a pointed star, especially when visualizing glial fibrillary acidic protein, a canonical marker for astrocytes. Accordingly, there is a commonly made connection between the points of light that shine in the night sky and the diffuse and abundant cells that buffer ions and provide support for neurons. An exceptional amount of function has been attributed to, negated for, and potentially reaffirmed for these cells, especially regarding their ability to release neuroactive molecules and influence synaptic plasticity...
November 11, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29274805/prospective-validation-that-subgenual-connectivity-predicts-antidepressant-efficacy-of-transcranial-magnetic-stimulation-sites
#19
Anne Weigand, Andreas Horn, Ruth Caballero, Danielle Cooke, Adam P Stern, Stephan F Taylor, Daniel Press, Alvaro Pascual-Leone, Michael D Fox
BACKGROUND: The optimal target in the dorsolateral prefrontal cortex for treating depression with repetitive transcranial magnetic stimulation (rTMS) remains unknown. Better efficacy has been associated with stimulation sites that are 1) more anterior and lateral and 2) more functionally connected to the subgenual cingulate. Here we prospectively test whether these factors predict response in individual patients. METHODS: A primary cohort (Boston, n = 25) with medication-refractory depression underwent conventional open-label rTMS to the left dorsolateral prefrontal cortex...
November 10, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29241584/a-schizophrenia-linked-kalrn-coding-variant-alters-neuron-morphology-protein-function-and-transcript-stability
#20
Theron A Russell, Melanie J Grubisha, Christine L Remmers, Seok Kyu Kang, Marc P Forrest, Katharine R Smith, Katherine J Kopeikina, Ruoqi Gao, Robert A Sweet, Peter Penzes
BACKGROUND: Large-scale genetic studies have revealed that rare sequence variants, including single nucleotide variants (SNVs), in glutamatergic synaptic genes are enriched in schizophrenia patients. However, the majority are too rare to show any association with disease and have not been examined functionally. One such SNV, KALRN-P2255T, displays a penetrance that greatly exceeds that of previously identified schizophrenia-associated SNVs. Therefore, we sought to characterize its effects on the function of kalirin (Kal)-9, a dual Ras-related C3 botulinum toxin substrate 1 and Ras homologue gene family, member A (RhoA) guanine nucleotide exchange factor, upregulated in human schizophrenia brain tissue...
November 7, 2017: Biological Psychiatry
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