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Psychosis Hippocampus

Rick P F Wolthusen, Garth Coombs, Emily A Boeke, Stefan Ehrlich, Stephanie N DeCross, Shahin Nasr, Daphne J Holt
BACKGROUND: Delusions are a defining and common symptom of psychotic disorders. Recent evidence suggests that subclinical and clinical delusions may represent distinct stages on a phenomenological and biological continuum. However, few studies have tested whether subclinical psychotic experiences are associated with neural changes that are similar to those observed in clinical psychosis. For example, it is unclear if overactivity of the hippocampus, a replicated finding of neuroimaging studies of schizophrenia, is also present in individuals with subclinical psychotic symptoms...
February 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Sagnik Bhattacharyya, Thomas Sainsbury, Paul Allen, Chiara Nosarti, Zerrin Atakan, Vincent Giampietro, Michael Brammer, P K McGuire
BACKGROUND: Cannabis and its main psychoactive ingredient δ-9-tetrahydrocannibidiol (THC) can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experience these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear. METHODS: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared with those who are not (NP)...
March 5, 2018: Psychological Medicine
O Giotakos
A variety of phenomena might be considered as reflecting impaired insight in psychosis, like failure to recognize signs, symptoms or disease, failure to derive appropriate cognitive representations, despite recognition of the disease, and misattribution of the source or cause of the disease. The unawareness of tardive dyskinesia symptoms in schizophrenic patients points that self-awareness deficits in schizophrenia may be domain specific. Poor insight is an independent phenomenological and a prevalent feature in psychotic disorders in general, and in schizophrenia in particular, but we don't know yet if delusions in schizophrenia are the result of an entirely normal attempt to account for abnormal perceptual experiences or a product of abnormal experience but of normal reasoning...
October 2017: Psychiatrikē, Psychiatriki
Peter Manza, Dardo Tomasi, Nora D Volkow
BACKGROUND: Cannabis abuse (CA) has been associated with psychopathology, including negative emotionality and higher risk of psychosis, particularly with early age of initiation. However, the mechanisms underlying this association are poorly understood. Because aberrant dopamine signaling is implicated in cannabis-associated psychopathology, we hypothesized that regular CA would be associated with altered resting-state functional connectivity in dopamine midbrain-striatal circuits. METHODS: We examined resting-state brain activity of subcortical regions in 441 young adults from the Human Connectome Project, including 30 subjects with CA meeting DSM-IV criteria for dependence and 30 control subjects matched on age, sex, education, body mass index, anxiety, depression, and alcohol and tobacco usage...
March 2018: Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Alfonso González, Loreto Massardo
PURPOSE OF REVIEW: Analysis of antiribosomal P protein autoantibodies (anti-P) pathogenicity in diffuse brain manifestations of neuropsychiatric lupus, emphasizing cognitive dysfunction and the recently emerged role of cross-reacting neuronal surface P antigen (NSPA) in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-Methyl-D-Aspartate receptor glutamatergic transmission. RECENT FINDINGS: Circulating anti-P antibodies associate with executive planning dysfunction and attention impairments in lupus patients and perturb glutamatergic transmission through NSPA in mice hippocampus, translating into impaired synaptic plasticity and spatial memory...
February 15, 2018: Current Opinion in Neurology
Gemma Modinos, Fatma Şimşek, Matilda Azis, Matthijs Bossong, Ilaria Bonoldi, Carly Samson, Beverly Quinn, Jesus Perez, Matthew R Broome, Fernando Zelaya, David J Lythgoe, Oliver D Howes, James M Stone, Anthony A Grace, Paul Allen, Philip McGuire
Preclinical models propose that the onset of psychosis is associated with hippocampal hyperactivity, thought to be driven by cortical GABAergic interneuron dysfunction and disinhibition of pyramidal neurons. Recent neuroimaging studies suggest that resting hippocampal perfusion is increased in subjects at ultra-high risk (UHR) for psychosis, but how this may be related to GABA concentrations is unknown. The present study used a multimodal neuroimaging approach to address this issue in UHR subjects. Proton magnetic resonance spectroscopy and pulsed-continuous arterial spin labeling imaging were acquired to investigate the relationship between medial prefrontal (MPFC) GABA+ levels (including some contribution from macromolecules) and hippocampal regional cerebral blood flow (rCBF) in 36 individuals at UHR of psychosis, based on preclinical evidence that MPFC dysfunction is involved in hippocampal hyperactivity...
January 30, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Hong Pan, Bárbara Oliveira, Gesine Saher, Ekrem Dere, Daniel Tapken, Marina Mitjans, Jan Seidel, Janina Wesolowski, Debia Wakhloo, Christina Klein-Schmidt, Anja Ronnenberg, Kerstin Schwabe, Ralf Trippe, Kerstin Mätz-Rensing, Stefan Berghoff, Yazeed Al-Krinawe, Henrik Martens, Martin Begemann, Winfried Stöcker, Franz-Josef Kaup, Reinhard Mischke, Susann Boretius, Klaus-Armin Nave, Joachim K Krauss, Michael Hollmann, Fred Lühder, Hannelore Ehrenreich
Autoantibodies of the IgG class against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB) were considered pathognomonic for anti-NMDAR encephalitis. This view has been challenged by the age-dependent seroprevalence (up to >20%) of functional NMDAR1-AB of all immunoglobulin classes found in >5000 individuals, healthy or affected by different diseases. These findings question a merely encephalitogenic role of NMDAR1-AB. Here, we show that NMDAR1-AB belong to the normal autoimmune repertoire of dogs, cats, rats, mice, baboons, and rhesus macaques, and are functional in the NMDAR1 internalization assay based on human IPSC-derived cortical neurons...
February 9, 2018: Molecular Psychiatry
Akiko Matsuura, Tamaki Ishima, Yuko Fujita, Yoshimi Iwayama, Shunsuke Hasegawa, Ryouka Kawahara-Miki, Motoko Maekawa, Manabu Toyoshima, Yusuke Ushida, Hiroyuki Suganuma, Satoshi Kida, Takeo Yoshikawa, Masaomi Iyo, Kenji Hashimoto
Maternal immune activation (MIA) contributes to behavioral abnormalities relevant to schizophrenia in adult offspring, although the molecular mechanisms underlying MIA-induced behavioral changes remain unclear. Here we demonstrated that dietary intake of glucoraphanin (GF), the precursor of a natural antioxidant sulforaphane, during juvenile and adolescent stages prevented cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial prefrontal cortex (mPFC) of adult offspring after MIA. Gene set enrichment analysis by RNA sequencing showed that MIA caused abnormal expression of centrosome-related genes in the PFC and hippocampus of adult offspring, and that dietary intake of GF improved these abnormal gene expressions...
February 1, 2018: Scientific Reports
David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Background: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. Method: We have recently developed a novel rodent model of schizophrenia susceptibility, the F2 MAM rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype...
January 10, 2018: International Journal of Neuropsychopharmacology
Julie Ottoy, Livia De Picker, Jeroen Verhaeghe, Steven Deleye, Leonie Wyffels, Lauren Kosten, Bernard Sabbe, Violette Coppens, Maarten Timmers, Luc Van Nueten, Sarah Ceyssens, Sigrid Stroobants, Manuel Morrens, Steven Staelens
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation positron emission tomography (PET) ligand that specifically binds the TSPO, allowing in-vivo visualization and quantification of neuroinflammation. The aim of this study is to evaluate if the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HC) and 11 male schizophrenia patients during a psychotic episode (SP)...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
J A Lieberman, R R Girgis, G Brucato, H Moore, F Provenzano, L Kegeles, D Javitt, J Kantrowitz, M M Wall, C M Corcoran, S A Schobel, S A Small
Scientists have long sought to characterize the pathophysiologic basis of schizophrenia and develop biomarkers that could identify the illness. Extensive postmortem and in vivo neuroimaging research has described the early involvement of the hippocampus in the pathophysiology of schizophrenia. In this context, we have developed a hypothesis that describes the evolution of schizophrenia-from the premorbid through the prodromal stages to syndromal psychosis-and posits dysregulation of glutamate neurotransmission beginning in the CA1 region of the hippocampus as inducing attenuated psychotic symptoms and initiating the transition to syndromal psychosis...
January 9, 2018: Molecular Psychiatry
James Allebone, Richard Kanaan, Sarah J Wilson
This systematic review critically assesses structural and functional neuroimaging studies of psychosis of epilepsy (POE). We integrate findings from 18 studies of adults with POE to examine the prevailing view that there is a specific relationship between temporal lobe epilepsy (TLE) and POE, and that mesial temporal lobe pathology is a biomarker for POE. Our results show: (1) conflicting evidence of volumetric change in the hippocampus and amygdala; (2) distributed structural pathology beyond the mesial temporal lobe; and (3) changes in frontotemporal functional network activation...
December 23, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
Mohamed A Sherif, Jose A Cortes-Briones, Mohini Ranganathan, Patrick D Skosnik
Preclinical and clinical data suggest that the cannabinoid and glutamatergic systems are implicated in the pathophysiology of schizophrenia (SZ), the prototypical psychotic disorder. This has led to distinct "cannabis" and "ketamine" models of SZ, respectively. However, these two models need not be mutually exclusive. Indeed, in several brain regions implicated in the putative neural circuitry of SZ (e.g., hippocampus, frontal cortex, cerebellum), cannabinoid receptors type 1 (CB1Rs) and glutamate N-methyl-D-aspartate receptors (NMDARs) have direct and indirect interactions...
December 15, 2017: European Journal of Neuroscience
Derek J Dean, Angela D Bryan, Raeana Newberry, Tina Gupta, Emily Carol, Vijay A Mittal
OBJECTIVE: A rapidly accumulating body of research suggests that exercise can improve symptoms and well-being in patients suffering from psychosis. Exercise may also promote neurogenesis in the hippocampus, a structure that plays an important role in the pathophysiology of psychosis. To date, there has not been an intervention focused on exercise prior to the onset of psychosis, a critical time for prevention of more serious illness. METHODS: In this pilot study, 12 young adults at ultrahigh risk (UHR) for psychosis were enrolled in a 12-week open-label exercise intervention...
November 2017: Journal of Clinical Psychiatry
Yadi Li, Wenhua Zhou, Haibo Dong, Wenwen Shen, Jianbing Zhang, Feng Li, Lingjun Zhang
The basolateral amygdala (BLA), hippocampal ventral subiculum, and nucleus accumbens (NAc) comprise the amygdala-hippocampus-NAc (AHN) circuit, which is implicated in drug seeking and reward. The goal of this study was to evaluate microstructural changes and relevant clinical features of the AHN circuit gray matter (GM) in methamphetamine (MA) users using diffusion tensor imaging (DTI). Thirty MA users and 30 age-matched normal volunteers underwent 3-T MR imaging to obtain structural T1-weighted images and DTI data...
October 16, 2017: Neurotoxicity Research
Jingyi Ma, L Stan Leung
The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABAA receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s...
October 7, 2017: Behavioural Brain Research
T Winton-Brown, A Schmidt, J P Roiser, O D Howes, A Egerton, P Fusar-Poli, N Bunzeck, A A Grace, E Duzel, S Kapur, P McGuire
Animal models of psychosis propose that abnormal hippocampal activity drives increased subcortical dopamine function, which is thought to contribute to aberrant salience processing and psychotic symptoms. These effects appear to be mediated through connections between the hippocampus, ventral striatum/pallidum and the midbrain. The aim of the present study was to examine the activity and connectivity in this pathway in people at ultra high risk (UHR) for psychosis. Functional magnetic resonance imaging was used to compare neural responses in a hippocampal-basal ganglia-midbrain network during reward, novelty and aversion processing between 29 UHR subjects and 32 healthy controls...
October 3, 2017: Translational Psychiatry
Wookbong Kwon, Hyeng-Soo Kim, Jain Jeong, Yonghun Sung, Minjee Choi, Song Park, Jinhee Lee, Soyoung Jang, Sung Hyun Kim, Sanggyu Lee, Myoung Ok Kim, Zae Young Ryoo
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) initiates DNA demethylation by converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) at CpG-rich regions of genes, which have key roles in adult neurogenesis and memory. In addition, the overexpression of Tet1 with 5-hmC alteration in patients with psychosis has also been reported, for instance in schizophrenia and bipolar disorders. The mechanism underlying Tet1 overexpression in the brain; however, is still elusive. In the present study, we found that Tet1-transgenic (Tet1-TG) mice displayed abnormal behaviors involving elevated anxiety and enhanced fear memories...
September 12, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Keiji Nishiyama, Hirobumi Suzuki, Toshiya Harasawa, Noriko Suzuki, Emi Kurimoto, Takayuki Kawai, Minoru Maruyama, Hidetoshi Komatsu, Kensuke Sakuma, Yuji Shimizu, Masato Shimojo
GPR52 is a Gs-coupled G protein-coupled receptor that is predominantly expressed in the striatum and nucleus accumbens (NAc) and was recently proposed as a potential therapeutic target for schizophrenia. In the current study, we investigated the in vitro and in vivo pharmacologic activities of a novel GPR52 agonist, 4-(3-(3-fluoro-5-(trifluoromethyl)benzyl)-5-methyl-1H-1,2,4-triazol-1-yl)-2-methylbenzamide (FTBMT). FTBMT functioned as a selective GPR52 agonist in vitro and in vivo, as demonstrated by the activation of Camp signaling in striatal neurons...
November 2017: Journal of Pharmacology and Experimental Therapeutics
Jun Konishi, Elisabetta C Del Re, Sylvain Bouix, Gabriëlla A M Blokland, Raquelle Mesholam-Gately, Kristen Woodberry, Margaret Niznikiewicz, Jill Goldstein, Yoshio Hirayasu, Tracey L Petryshen, Larry J Seidman, Martha E Shenton, Robert W McCarley
We examined whether abnormal volumes of several brain regions as well as their mutual associations that have been observed in patients with schizophrenia, are also present in individuals at clinical high-risk (CHR) for developing psychosis. 3T magnetic resonance imaging was acquired in 19 CHR and 20 age- and handedness-matched controls. Volumes were measured for the body and temporal horns of the lateral ventricles, hippocampus and amygdala as well as total brain, cortical gray matter, white matter, and subcortical gray matter volumes...
August 16, 2017: Brain Imaging and Behavior
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