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Molecular Psychiatry

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https://www.readbyqxmd.com/read/28220082/synaptic-and-neuronal-autoantibody-associated-psychiatric-syndromes-controversies-and-hypotheses
#1
Adam Al-Diwani, Thomas A Pollak, Alexander E Langford, Belinda R Lennox
Autoimmune encephalitis (AE) mediated by antibodies against synaptic and neuronal surface targets frequently presents with a psychiatric syndrome. In these patients, removal of autoantibodies treats the disease and outcomes are closely linked to early intervention. The discovery of these autoantibodies in isolated psychiatric syndromes has raised the possibility that these patients may derive similar benefits from immunotherapy, a potentially transformational approach to the treatment of mental illness. Although open-label case series suggest impressive therapeutic outcomes, the pathological relevance of these autoantibodies outside of canonical presentations is debated...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28220045/paternal-cocaine-taking-elicits-epigenetic-remodeling-and-memory-deficits-in-male-progeny
#2
M E Wimmer, L A Briand, B Fant, L A Guercio, A C Arreola, H D Schmidt, S Sidoli, Y Han, B A Garcia, R C Pierce
Paternal environmental perturbations including exposure to drugs of abuse can produce profound effects on the physiology and behavior of offspring via epigenetic modifications. Here we show that adult drug-naive male offspring of cocaine-exposed sires have memory formation deficits and associated reductions in NMDA receptor-mediated hippocampal synaptic plasticity. Reduced levels of the endogenous NMDA receptor co-agonist d-serine were accompanied by increased expression of the d-serine degrading enzyme d-amino acid oxidase (Dao1) in the hippocampus of cocaine-sired male progeny...
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28220044/pregnenolone-blocks-cannabinoid-induced-acute-psychotic-like-states-in-mice
#3
A Busquets-Garcia, E Soria-Gómez, B Redon, Y Mackenbach, M Vallée, F Chaouloff, M Varilh, G Ferreira, P-V Piazza, G Marsicano
Cannabis-induced acute psychotic-like states (CIAPS) represent a growing health issue, but their underlying neurobiological mechanisms are poorly understood. The use of antipsychotics and benzodiazepines against CIAPS is limited by side effects and/or by their ability to tackle only certain aspects of psychosis. Thus, safer wide-spectrum treatments are currently needed. Although the blockade of cannabinoid type-1 receptor (CB1) had been suggested as a therapeutical means against CIAPS, the use of orthosteric CB1 receptor full antagonists is strongly limited by undesired side effects and low efficacy...
February 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194008/genetic-otx2-mis-localization-delays-critical-period-plasticity-across-brain-regions
#4
H H C Lee, C Bernard, Z Ye, D Acampora, A Simeone, A Prochiantz, A A Di Nardo, T K Hensch
Accumulation of non-cell autonomous Otx2 homeoprotein in postnatal mouse visual cortex (V1) has been implicated in both the onset and closure of critical period (CP) plasticity. Here, we show that a genetic point mutation in the glycosaminoglycan recognition motif of Otx2 broadly delays the maturation of pivotal parvalbumin-positive (PV+) interneurons not only in V1 but also in the primary auditory (A1) and medial prefrontal cortex (mPFC). Consequently, not only visual, but also auditory plasticity is delayed, including the experience-dependent expansion of tonotopic maps in A1 and the acquisition of acoustic preferences in mPFC, which mitigates anxious behavior...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194005/genetic-inhibition-of-neurotransmission-reveals-role-of-glutamatergic-input-to-dopamine-neurons-in-high-effort-behavior
#5
M A Hutchison, X Gu, M F Adrover, M R Lee, T S Hnasko, V A Alvarez, W Lu
Midbrain dopamine neurons are crucial for many behavioral and cognitive functions. As the major excitatory input, glutamatergic afferents are important for control of the activity and plasticity of dopamine neurons. However, the role of glutamatergic input as a whole onto dopamine neurons remains unclear. Here we developed a mouse line in which glutamatergic inputs onto dopamine neurons are specifically impaired, and utilized this genetic model to directly test the role of glutamatergic inputs in dopamine-related functions...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194004/genetic-contributions-to-self-reported-tiredness
#6
V Deary, S P Hagenaars, S E Harris, W D Hill, G Davies, D C M Liewald, A M McIntosh, C R Gale, I J Deary
Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194003/lower-levels-of-the-glial-cell-marker-tspo-in-drug-naive-first-episode-psychosis-patients-as-measured-using-pet-and-11-c-pbr28
#7
K Collste, P Plavén-Sigray, H Fatouros-Bergman, P Victorsson, M Schain, A Forsberg, N Amini, S Aeinehband, S Erhardt, C Halldin, L Flyckt, L Farde, S Cervenka
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28194001/enhancing-vta-cav1-3-l-type-ca-2-channel-activity-promotes-cocaine-and-mood-related-behaviors-via-overlapping-ampa-receptor-mechanisms-in-the-nucleus-accumbens
#8
A Martínez-Rivera, J Hao, T F Tropea, T P Giordano, M Kosovsky, R C Rice, A Lee, R L Huganir, J Striessnig, N A Addy, S Han, A M Rajadhyaksha
Genetic factors significantly influence susceptibility for substance abuse and mood disorders. Rodent studies have begun to elucidate a role of Cav1.3 L-type Ca(2+) channels in neuropsychiatric-related behaviors, such as addictive and depressive-like behaviors. Human studies have also linked the CACNA1D gene, which codes for the Cav1.3 protein, with bipolar disorder. However, the neurocircuitry and the molecular mechanisms underlying the role of Cav1.3 in neuropsychiatric phenotypes are not well established...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167838/glrb-allelic-variation-associated-with-agoraphobic-cognitions-increased-startle-response-and-fear-network-activation-a-potential-neurogenetic-pathway-to-panic-disorder
#9
J Deckert, H Weber, C Villmann, T B Lonsdorf, J Richter, M Andreatta, A Arias-Vasquez, L Hommers, L Kent, C Schartner, S Cichon, C Wolf, N Schaefer, C R von Collenberg, B Wachter, R Blum, D Schümann, R Scharfenort, J Schumacher, A J Forstner, C Baumann, M A Schiele, S Notzon, P Zwanzger, J G E Janzing, T Galesloot, L A Kiemeney, A Gajewska, E Glotzbach-Schoon, A Mühlberger, G Alpers, T Fydrich, L Fehm, A L Gerlach, T Kircher, T Lang, A Ströhle, V Arolt, H-U Wittchen, R Kalisch, C Büchel, A Hamm, M M Nöthen, M Romanos, K Domschke, P Pauli, A Reif
The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3...
February 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167837/neural-mechanisms-of-mismatch-negativity-dysfunction-in-schizophrenia
#10
M Lee, P Sehatpour, M J Hoptman, P Lakatos, E C Dias, J T Kantrowitz, A M Martinez, D C Javitt
Schizophrenia is associated with cognitive deficits that reflect impaired cortical information processing. Mismatch negativity (MMN) indexes pre-attentive information processing dysfunction at the level of primary auditory cortex. This study investigates mechanisms underlying MMN impairments in schizophrenia using event-related potential, event-related spectral decomposition (ERSP) and resting state functional connectivity (rsfcMRI) approaches. For this study, MMN data to frequency, intensity and duration-deviants were analyzed from 69 schizophrenia patients and 38 healthy controls...
February 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167836/autism-associated-dyrk1a-truncation-mutants-impair-neuronal-dendritic-and-spine-growth-and-interfere-with-postnatal-cortical-development
#11
T Dang, W Y Duan, B Yu, D L Tong, C Cheng, Y F Zhang, W Wu, K Ye, W X Zhang, M Wu, B B Wu, Y An, Z L Qiu, B L Wu
Autism is a prevailing neurodevelopmental disorder with a large genetic/genomic component. Recently, the dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A) gene was implicated as a risk factor for autism spectrum disorder (ASD). We identified five DYRK1A variants in ASD patients and found that the dose of DYRK1A protein has a crucial role in various aspects of postnatal neural development. Dyrk1a loss of function and gain of function led to defects in dendritic growth, dendritic spine development and radial migration during cortical development...
February 7, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28162776/the-future-of-psychiatry-brain-devices
#12
Jorge Alberto Costa E Silva, Ricardo Ewbank Steffen
Recent advances in deep brain stimulators and brain-machine interfaces have greatly expanded the possibilities of neuroprosthetics and neuromodulation. Together with advances in neuroengineering, nanotechnology, molecular biology and material sciences, it is now possible to address fundamental questions in neuroscience in new, more powerful ways. It is now possible to apply these new technologies in ways that range from augmenting and restoring function to neuromodulation modalities that treat neuropsychiatric disorders...
January 11, 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28138159/caspase-3-dependent-cleavage-of-akt-modulates-tau-phosphorylation-via-gsk3%C3%AE-kinase-implications-for-alzheimer-s-disease
#13
J Chu, E Lauretti, D Praticò
The pathological hallmark of Alzheimer's disease (AD) is accumulation of misfolded amyloid-β peptides and hyperphosphorylated tau protein in the brain. Increasing evidence suggests that serine-aspartyl proteases-caspases are activated in the AD brain. Previous studies identified a caspase-3 cleavage site within the amyloid-β precursor protein, and a caspase-3 cleavage of tau as the mechanisms involved in the development of Aβ and tau neuropathology, respectively. However, the potential role that caspase-3 could have on tau metabolism remains unknown...
January 31, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28138158/selective-increase-of-cerebrospinal-fluid-il-6-during-experimental-systemic-inflammation-in-humans-association-with-depressive-symptoms
#14
H Engler, P Brendt, J Wischermann, A Wegner, R Röhling, T Schoemberg, U Meyer, R Gold, J Peters, S Benson, M Schedlowski
Systemic inflammation is accompanied by profound behavioral and mood changes that resemble symptoms of depression. Findings in animals suggest that pro-inflammatory cytokines released by activated immune cells in the periphery evoke these behavioral symptoms by driving inflammatory changes in the brain. However, experimental data in humans are lacking. Here we demonstrate in healthy male volunteers (10 endotoxin treated, 8 placebo treated) that intravenous administration of low-dose endotoxin (0.8 ng/kg body weight), a prototypical pathogen-associated molecular pattern that activates the innate immune system, not only induces a significant increase in peripheral blood cytokine concentrations (that is, tumor necrosis factor-α, interleukin (IL)-6, IL-10) but also results, with some latency, in a robust and selective increase of IL-6 in the cerebrospinal fluid (CSF)...
January 31, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28138157/forebrain-specific-ablation-of-phospholipase-c%C3%AE-1-causes-manic-like-behavior
#15
Y R Yang, J H Jung, S-J Kim, K Hamada, A Suzuki, H J Kim, J H Lee, O-B Kwon, Y K Lee, J Kim, E-K Kim, H-J Jang, D-S Kang, J-S Choi, C J Lee, J Marshall, H-Y Koh, C-J Kim, H Seok, S H Kim, J H Choi, Y-B Choi, L Cocco, S H Ryu, J-H Kim, P-G Suh
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1(f/f); CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses...
January 31, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115744/a-genome-wide-association-study-identifies-two-novel-susceptibility-loci-and-trans-population-polygenicity-associated-with-bipolar-disorder
#16
M Ikeda, A Takahashi, Y Kamatani, Y Okahisa, H Kunugi, N Mori, T Sasaki, T Ohmori, Y Okamoto, H Kawasaki, S Shimodera, T Kato, H Yoneda, R Yoshimura, M Iyo, K Matsuda, M Akiyama, K Ashikawa, K Kashiwase, K Tokunaga, K Kondo, T Saito, A Shimasaki, K Kawase, T Kitajima, K Matsuo, M Itokawa, T Someya, T Inada, R Hashimoto, T Inoue, K Akiyama, H Tanii, H Arai, S Kanba, N Ozaki, I Kusumi, T Yoshikawa, M Kubo, N Iwata
Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10(-9)), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (Pbest=5...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115743/adnp-nap-dramatically-increase-microtubule-end-binding-protein-tau-interaction-a-novel-avenue-for-protection-against-tauopathy
#17
Y Ivashko-Pachima, C Laura Sayas, A Malishkevich, I Gozes
Activity-dependent neuroprotective protein (ADNP), vital for brain formation and cognitive function, is mutated in autism and linked to neurodegenerative/psychiatric diseases. An eight-amino-acid peptide snippet of ADNP, NAP (NAPVSIPQ), identified as a smallest active fragment, includes the SxIP microtubule (MT) end-binding protein (EB) association motif, and enhances ADNP-EB3 interaction. Depletion of EB1 or EB3 abolishes NAP protection against zinc intoxication. Furthermore, NAP enhances Tau-MT interaction, and Tau regulates the localization and function of EB1 and EB3 in developing neuronal cells...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115742/mef2c-transcription-factor-is-associated-with-the-genetic-and-epigenetic-risk-architecture-of-schizophrenia-and-improves-cognition-in-mice
#18
A C Mitchell, B Javidfar, V Pothula, D Ibi, E Y Shen, C J Peter, L K Bicks, T Fehr, Y Jiang, K J Brennand, R L Neve, J Gonzalez-Maeso, S Akbarian
Large-scale consortia mapping the genomic risk architectures of schizophrenia provide vast amounts of molecular information, with largely unexplored therapeutic potential. We harnessed publically available information from the Psychiatric Genomics Consortium, and report myocyte enhancer factor 2C (MEF2C) motif enrichment in sequences surrounding the top scoring single-nucleotide polymorphisms within risk loci contributing by individual small effect to disease heritability. Chromatin profiling at base-pair resolution in neuronal nucleosomes extracted from prefrontal cortex of 34 subjects, including 17 cases diagnosed with schizophrenia, revealed MEF2C motif enrichment within cis-regulatory sequences, including neuron-specific promoters and superenhancers, affected by histone H3K4 hypermethylation in disease cases...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115741/bipolar-mood-cycles-and-lunar-tidal-cycles
#19
T A Wehr
In 17 patients with rapid cycling bipolar disorder, time-series analyses detected synchronies between mood cycles and three lunar cycles that modulate the amplitude of the moon's semi-diurnal gravimetric tides: the 14.8-day spring-neap cycle, the 13.7-day declination cycle and the 206-day cycle of perigee-syzygies ('supermoons'). The analyses also revealed shifts among 1:2, 1:3, 2:3 and other modes of coupling of mood cycles to the two bi-weekly lunar cycles. These shifts appear to be responses to the conflicting demands of the mood cycles' being entrained simultaneously to two different bi-weekly lunar cycles with slightly different periods...
January 24, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28115740/hippocampal-subfield-volumes-in-mood-disorders
#20
B Cao, I C Passos, B Mwangi, H Amaral-Silva, J Tannous, M-J Wu, G B Zunta-Soares, J C Soares
Volume reduction and shape abnormality of the hippocampus have been associated with mood disorders. However, the hippocampus is not a uniform structure and consists of several subfields, such as the cornu ammonis (CA) subfields CA1-4, the dentate gyrus (DG) including a granule cell layer (GCL) and a molecular layer (ML) that continuously crosses adjacent subiculum (Sub) and CA fields. It is known that cellular and molecular mechanisms associated with mood disorders may be localized to specific hippocampal subfields...
January 24, 2017: Molecular Psychiatry
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